Filed Pursuant to Rule 424(b)(5)
Registration No. 333-216748
Prospectus Supplement
(To Prospectus Dated October 12, 2017)
55,653,846 Shares Common Stock
Pre-Funded Warrants to Purchase up to 21,269,231 Shares
of Common Stock
We are offering 55,653,846 shares of our common
stock, par value $0.001 per share.
We are also offering pre-funded warrants
to purchase up to an aggregate of 21,269,231 shares
of common stock, which we refer to herein as the pre-funded warrants, to each investor whose purchase of shares of common stock
in this offering would otherwise result in such purchaser, together with its affiliates and certain related parties, beneficially
owning more than 4.99% (or, at the election of the purchaser, 9.99%) of our outstanding shares of common stock immediately following
the closing of this offering, in lieu of shares of common stock. Each pre-funded warrant will be exercisable for one share of
common stock. A holder of pre-funded warrants will not have the right to exercise any portion of its pre-funded warrants if the
holder, together with its affiliates, would beneficially own in excess of 4.99% (or, at the election of the holder, 9.99%) of
the number of shares of common stock outstanding immediately after giving effect to such exercise. This offering also relates
to the shares of common stock issuable upon exercise of any pre-funded warrants sold in this offering. Each pre-funded warrant
is being sold at a public offering price of $0.3249 per
pre-funded warrant.
Each pre-funded warrant will have an exercise
price per share of common stock equal to $0.0001 and is exercisable at any time after its original issuance until exercised in
full.
Our common stock is listed on the NYSE American
under the symbol “ATNM.” On June 15, 2020, the last reported sale price of our common stock was $0.4065 per share.
The final public offering price will be determined through negotiation between us and the investors in the offering and may be
at a discount to the current market price. There is no established trading market for the pre-funded warrants, and we do not
expect a market to develop. We do not intend to apply for a listing for the pre-funded warrants on any securities exchange or other
nationally recognized trading system. Without an active trading market, the liquidity of the pre-funded warrants will be limited.
Investing in our securities involves
a high degree of risk. See “Risk Factors” beginning on page S-11 of this prospectus supplement and page 8 of the accompanying
prospectus.
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Per Share
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Per Pre-Funded Warrant
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|
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Total
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Public offering price
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|
$
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0.32500
|
|
|
$
|
0.32490
|
|
|
$
|
24,997,873.10
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|
Placement
agent fees(1)
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$
|
0.02275
|
|
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$
|
0.02275
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|
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$
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1,750,000.00
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Proceeds, before expenses, to Actinium Pharmaceuticals, Inc.
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$
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0.30225
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|
|
$
|
0.30215
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|
|
$
|
23,247,873.10
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|
|
(1)
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We
have agreed to pay the placement agents a cash fee equal to 7.0% of the gross proceeds raised in this offering and to reimburse
the exclusive lead placement agent for certain expenses. See “Plan of Distribution.”
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Neither the U.S. Securities and
Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the
adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense.
We have retained H.C. Wainwright &
Co., LLC to act as our exclusive lead placement agent, or the exclusive lead placement agent, in connection with the
securities offered by this prospectus supplement. The exclusive lead placement agent is not purchasing or selling the
securities offered by us, and is not required to sell any specific number or dollar amount of securities, but will use its
reasonable best efforts to arrange for the sale of the securities offered by this prospectus supplement.
Delivery of the securities offered hereby is
expected to be made on or about June 19, 2020, subject to closing conditions.
Exclusive Lead Placement Agent
H.C. Wainwright & Co.
Co-Placement Agents
Maxim Group LLC
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JonesTrading
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The date of this prospectus supplement
is June 16, 2020
TABLE OF CONTENTS
About
this Prospectus Supplement
This prospectus supplement and the accompanying prospectus form
a part of a registration statement on Form S-3 that we filed with the U.S. Securities and Exchange Commission utilizing a “shelf”
registration process. This document is in two parts. The first part is the prospectus supplement, which describes the specific
terms of this offering. The second part, the accompanying prospectus, provides more general information about the securities we
may offer from time to time, some of which may not apply to the securities offered by this prospectus supplement. Generally, when
we refer to this prospectus, we are referring to both parts of this document combined. Before you invest, you should carefully
read this prospectus supplement, the accompanying prospectus, all information incorporated by reference herein and therein, and
the additional information described under “Where You Can Find More Information” in this prospectus supplement. These
documents contain information you should consider when making your investment decision. This prospectus supplement may add, update
or change information contained in the accompanying prospectus. To the extent that any statement that we make in this prospectus
supplement is inconsistent with statements made in the accompanying prospectus or any documents incorporated by reference therein,
the statements made in this prospectus supplement will be deemed to modify or supersede those made in the accompanying prospectus
and such documents incorporated by reference therein.
You should rely only on the information
contained in this prospectus supplement or the accompanying prospectus, or incorporated by reference herein. Neither we nor
the placement agents have authorized any other person to provide you with any information that is different. The information contained
in this prospectus supplement or the accompanying prospectus, or incorporated by reference herein or therein is accurate only as
of the respective dates thereof, regardless of the time of delivery of this prospectus supplement and the accompanying prospectus
or of any sale of our securities.
We are offering to sell, and seeking offers
to buy, our securities only in jurisdictions where offers and sales are permitted. The distribution of this prospectus supplement
and the accompanying prospectus and the offering of the securities in certain jurisdictions may be restricted by law. Persons
outside the United States who come into possession of this prospectus supplement and/or the accompanying prospectus must inform
themselves about, and observe any restrictions relating to, the offering of the securities and the distribution of this prospectus
supplement and/or the accompanying prospectus outside the United States. This prospectus supplement and the accompanying prospectus
do not constitute, and may not be used in connection with, an offer to sell, or a solicitation of an offer to buy, any securities
offered by this prospectus supplement and the accompanying prospectus by any person in any jurisdiction in which it is unlawful
for such person to make such an offer or solicitation.
We have suspended, and during the duration of this offering
we are no longer offering, any securities pursuant to (i) the prospectus supplement filed with the Securities and Exchange Commission
on October 18, 2018, relating to the offer and sale of shares of our common stock pursuant to a purchase agreement, dated October
18, 2018, with Lincoln Park Capital Fund, LLC, which we refer to as the Lincoln Park Agreement, and (ii) the prospectus supplement
filed with the Securities and Exchange Commission on December 28, 2018, relating to the offer and sale of shares of our common
stock pursuant to the Amended and Restated At Market Issuance Sales Agreement, dated December 28, 2018, with B. Riley FBR, Inc.
and JonesTrading Institutional Services LLC, which we refer to as the ATM Sales Agreement.
We further note that the representations,
warranties and covenants made by us in any agreement that is filed as an exhibit to any document that is incorporated by reference
in the accompanying prospectus were made solely for the benefit of the parties to such agreement, including, in some cases, for
the purpose of allocating risk among the parties to such agreements, and should not be deemed to be a representation, warranty
or covenant to you. Moreover, such representations, warranties or covenants were accurate only as of the date when made. Accordingly,
such representations, warranties and covenants should not be relied on as accurately representing the current state of our affairs.
Unless the context otherwise requires,
references in this prospectus supplement to “we”, “us” and “our” refer to Actinium Pharmaceuticals,
Inc.
Prospectus
Supplement Summary
This summary highlights selected information
about our company, this offering and information appearing elsewhere in this prospectus supplement, in the accompanying prospectus,
in the documents we incorporate by reference and in any free writing prospectus that we have authorized for use in connection
with this offering. This summary is not complete and does not contain all the information that you should consider before investing
in our securities. You should read this entire prospectus supplement and the accompanying prospectus carefully, including the
“Risk Factors” contained in this prospectus supplement, the accompanying prospectus and the financial statements and
the notes thereto incorporated by reference in this prospectus supplement and the accompanying prospectus and any free writing
prospectus that we have authorized for use in connection with this offering, before making an investment decision. This prospectus
supplement may add to, update or change information in the accompanying prospectus.
Business
Overview
Actinium Pharmaceuticals, Inc. is a clinical-stage,
biopharmaceutical company applying its proprietary platform technology and deep understanding of radiobiology to the development
of novel targeted therapies known as ARCs or Antibody Radiation-Conjugates. Radiation is an effective therapeutic modality that
is used in the treatment of over fifty percent of all cancer patients and often combined with chemotherapy and immunotherapy for
greater therapeutic effect. Radiation is typically administered from outside the body, which constrains the amount that can be
administered to patients due to dose-limiting toxicities. In addition, due to the diffuse nature of the external radiation beam,
its usage is limited to solid tumors and cannot be used in blood cancers, which are diffuse. ARCs combine the cell-killing ability
of a radioisotope payload with a targeting agent, such as a monoclonal antibody, or mAb, to deliver radiation inside the body
to specific cells, to potentially generate greater efficacy and less toxicity. ARCs usage is broader than external delivered radiation
as they can be used for both solid tumors and blood cancers. Blood or hematologic cancers are highly sensitive to radiation and
our clinical pipeline is focused on ARCs targeting the antigens CD45 and CD33, both of which are expressed in multiple hematologic
cancers. Our clinical programs are focused on two primary areas: targeted conditioning prior to a cell or gene therapy procedure
and therapeutics, either in combination with other agents or as a monotherapy. Our product development strategy is actively informed
by clinical data with our ARCs in over 500 patients, including the ongoing SIERRA trial. Our clinical pipeline has emanated from
our AWE, or Antibody Warhead Enabling technology platform, which is protected by over 110 issued and pending patents, trade secrets
and know-how.
Targeted Conditioning
We are advancing the only multi-target, multi-indication clinical-stage
pipeline for targeted conditioning and the only ARC-based targeted conditioning regimens in development. Our ARCs for targeted
conditioning are intended to potentially enable improved access to cell-based therapies with curative potential, including BMT,
or bone marrow transplant, ACT, or adoptive cell therapy such as CAR-T, and Gene Therapy, as well as improved outcomes. Conditioning
in the context of BMT, ACT or Gene Therapy is the act of depleting certain blood and immune-forming cells, including bone marrow
stem cells and, in some cases, diseased cells prior to transplanting new cells into a patient. Currently, conditioning is accomplished
using a combination of chemotherapeutic agents and external radiation. These non-targeted conditioning regimens may prevent a patient
from receiving a potentially curative therapy and hinder outcomes due to their toxicities. ARCs have the potential to increase
patient access and outcomes by way of their ability to selectively deplete targeted cells while sparing normal healthy cells. We
use our ARCs at high isotope dose levels to achieve myeloablation, which fully depletes bone marrow stem cells and at lower isotope
dose levels to achieve lymphodepletion, which spares bone marrow stem cells from depletion. In addition, dosing may be titrated
downward from myeloablative doses to achieve partial myeloablation, which may be appropriate for certain gene therapy programs.
CD45 Targeted Conditioning Program
Our CD45 ARC is comprised of the anti-CD45
monoclonal antibody known as apamistamab (formerly BC8) and the radioisotope I-131 or Iodine-131. CD45 is an antigen expressed
on leukemia, lymphoma and myeloma cancer cells, as well as nucleated immune cells, but is not expressed outside of the hematopoietic,
or blood, system. This unique expression on blood cancer and immune cells enables simultaneous depletion of both cell types, making
CD45 an optimal antigen for targeted conditioning applications. CD45 is a cell surface antigen with an average expression of 200,000
copies per cell, however, it only internalizes at a rate of 10-15%. We believe our ARC approach is the most effective method to
target CD45 positive cells, as the radioisotope payload linear energy transfer can readily ablate a targeted cell without requiring
payload internalization like an antibody drug conjugate or rely on biological effector function processes like a naked antibody.
Furthermore, since CD45 expression level varies from low to high antigen density as the immune cells become more terminally differentiated,
we can selectively condition depending on the therapeutic application, from full myeloablation to transient lymphodepletion, by
adjusting the dose or intensity of the I-131 isotope payload. Full myeloablation can be achieved with high doses of I-131, as
its energy pathlength and crossfire effect can penetrate into bone marrow niches to target and deplete blood and immune system
forming bone marrow stem cells. Myeloablation is applicable to autologous or allogeneic BMT and to autologous gene-edited or modified
therapies that can reconstitute a patient’s blood and immune systems. Alternatively, low doses of I-131 can be transiently
lymphodepleting and spare a patient’s bone marrow stem cells, which we believe is ideal for ACT applications such as CAR-T.
We intend to develop our CD45 targeted conditioning program for BMT, ACT and Gene Therapy applications for malignant and non-malignant
diseases.
Our lead CD45 targeted conditioning product
candidate is Iomab-B, which uses high doses of I-131 to achieve myeloablative conditioning prior to a BMT. Iomab-B is currently
being studied in the pivotal Phase 3 Study of Iomab-B in Elderly Relapsed or Refractory AML, or SIERRA, clinical trial for targeted
conditioning prior to an allogeneic BMT for patients with active, relapsed or refractory (r/r) Acute Myeloid Leukemia, or AML,
who are age 55 or older. Patients with active, r/r AML are not normally considered eligible for BMT and the SIERRA trial is the
only randomized Phase 3 trial to offer BMT as a treatment option for this patient population. The SIERRA trial compares outcomes
of patients randomized to receive Iomab-B and a BMT (the study arm) to those patients randomized to receive physician’s
choice of salvage chemotherapy (the control arm). Salvage chemotherapy is also defined as conventional care, as no standard of
care exists for this patient population. Patients who fail to achieve a CR or Complete Response on the control arm are ineligible
to proceed to a BMT, but the trial design permits these patients to “cross over” to receive the study arm treatment
if they meet the eligibility criteria. The primary endpoint of the SIERRA trial is durable Complete Remission, or dCR, of six
months and the secondary endpoint is one-year Overall Survival, or OS. When the crossover patients receive Iomab-B and BMT, they
have not achieved remission with their salvage therapy and are considered to be failures for the primary endpoint of the study.
The SIERRA trial is currently active at 20 sites in the United States and Canada, which includes many of the leading BMT sites
based on volume. We expect to complete enrollment of the SIERRA trial and have topline data that we believe will support the submission
of a Biologics License Application, or BLA, with the U.S. Food and Drug Administration, or FDA, in 2021. If approved, we expect
our initial commercial launch would target the leading 50-100 BMT and medical centers that perform the vast majority of BMT’s
in the United States. In the European Union or EU, we received favorable feedback from the European Medicines Agency or EMA via
their scientific advice program that the trial design, primary endpoint and planned statistical analysis from the SIERRA trial
are acceptable as the basis for a Marketing Authorization Application or MAA. Additionally, the EMA commented that it does not
anticipate the need for further standalone preclinical toxicology or safety studies. Overall, transplant procedures in the EU
are approximately fifty percent higher than in the United States with a similar market dynamic with a majority of BMT volume being
conducted in a concentrated number of leading medical centers. We intend to secure a partner for Iomab-B in the EU.
Safety and feasibility data from the first
75 patients enrolled on the SIERRA trial, which represents 50% of the total of 150 patients to be enrolled in the trial, was presented
in an oral presentation at the Transplantation & Cellular Therapy Meetings of the American Society for Transplantation and
Cellular Therapy (ASTCT) and Center for International Bone & Marrow Transplant Research (CIBMTER) in February 2020. It was
reported that 100% of patients (31/31) on the study arm that received a therapeutic dose of Iomab-B received a BMT, with a median
time to BMT of 30 days, and all patients achieved neutrophil and platelet engraftment in a median time of 20 days despite a high
median blast count of 30%. On the control arm, only 18% of patients (7/38) achieved remission after salvage therapy, and then
received a BMT with a median time to BMT of 67 days and median blast count of 26%. Of the 82% of patients failing to achieve a
CR with conventional care (31/38), 20 patients were eligible to cross over to the study arm. These patients are considered as
having failed the primary endpoint of the study. All crossover patients who received the therapeutic dose of Iomab-B (20/20) received
a BMT, with a median time to BMT of 64 days and all patients achieved engraftment in a median time of 19 days despite high median
blast count of 35% at time of crossover. It was also reported that 100-day non-relapse transplant-related mortality (100-day TRM)
of the study or Iomab-B arm was 6% (2/31) of patients that received a BMT compared to 29% of patients (2/7) who received a BMT
after salvage therapy on the control arm. The universal engraftment rate and low 100-day TRM rate of the Iomab-B arm resulted
in 29 patients potentially evaluable for the primary endpoint compared to 5 patients in the control arm, a nearly six times difference.
The SIERRA trial is powered for up to two
interim analyses of the primary endpoint exercisable at our discretion and triggered by an enrollment range of 70 to 110 patients
to evaluate, the primary endpoint of dCR of 180 days. We intend to exercise an ad-hoc analysis, basing our decision to do so on
the data reported from SIERRA thus far and comfort with the pace and current status of enrollment as of April 2020, which could
generate topline data for the primary endpoint in late 2020 and early termination of the trial if positive. Based on the statistical
plan of the study, a single ad-hoc analysis would result in a minimal alpha spend of no more than 0.00925, depending on the number
of patients included in the ad-hoc analysis.
Our Iomab-ACT program is intended for targeted
conditioning prior to ACT or Gene Therapy and uses the same 131I-apamistamab ARC construct as Iomab-B at varying
doses. At lower doses of one-eighth to one-sixth of the myeloablative dose, it is applicable for lymphodepletion prior to CAR-T
or certain Gene Therapy applications where stem cell myeloablation is not necessary. At higher doses it is applicable for Gene
Therapy applications where stem cell myeloablation is necessary.
In January 2020, we announced a collaboration
with University of California Davis to utilize Iomab-ACT conditioning in an ongoing Phase 1/2 trial with a novel anti-HIV autologous
stem cell gene therapy for patients with HIV-related lymphoma. We believe this to be the first Gene Therapy trial to use an ARC-based
conditioning regimen. 131I-Apamistamab has clinical proof of concept as a targeted conditioning regimen for patients
with high-risk, relapsed or refractory lymphoma prior to an autologous stem cell transplant from a previous study, where a favorable
safety profile with no dose-limiting toxicities and minimal non-hematologic toxicities were observed and promising efficacy with
median overall survival not reached (range: 29 months to not reached) and 31% of patients in prolonged remission at a median of
36 months follow up (range: 25 – 41 months). In this study, Iomab-ACT is intended to replace the chemotherapy-based condition
regimen known as BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) to simultaneously kill the patient’s lymphoma
cells and deplete the patient’s stem cells to make room for the transplant. Upon engraftment, the transplanted gene-modified
autologous stem cells containing three anti-HIV genes are intended to equip the patient with a new immune system that is resistant
to the HIV virus. Iomab-ACT will be substituted for BEAM in the ongoing Phase 1/2 trial and we expect to have clinical proof of
concept data in 2021.
We believe our Iomab-ACT program is highly
differentiated when compared to Fludarabine and Cyclophosphamide or Flu/Cy or other chemotherapy-based regimens that are used
as the standard of practice today for lymphodepletion prior to CAR-T. CD45 is an antigen expressed on certain immune cell types
that are relevant to the mechanism of CAR-T therapies including lymphocytes, regulatory T cells and macrophages that have been
associated with clinical responses that may limit the safety, efficacy and durability of response of these CAR-T therapies including
Cytokine Release Syndrome, or CRS, and neurotoxicity. Some of these limitations may be attributable to the chemotherapy-based
conditioning agents that are being used prior to CAR-T therapies. Preclinical data supporting the rational for our Iomab-ACT program
was presented at multiple medical conferences in 2019. Unlike chemotherapy, preclinical data suggests Iomab-ACT is targeted in
nature and, due to this targeted effect, we expect we can improve CAR-T cell expansion more efficiently, potentially resulting
in responses that are more durable, but also resulting in reduced CAR-T related toxicities. Importantly, we expect the Iomab-ACT
program construct to enable lymphodepletion through a single-dose, outpatient administration versus Flu/Cy or other chemotherapy-based
lymphodepletion regimens that can require multiple infusion cycles over several days. Because of this potentially superior profile,
the Iomab-ACT construct could result in improved access to CAR-T therapy and better outcomes. We intend to begin a clinical trial
with 131I-apamistamab as a targeted conditioning agent prior to CAR-T, subject to identifying a suitable partner
and we expect to have Phase 1 clinical proof of concept data in 2021.
CD33 Program: Targeted Conditioning, Combinations and Therapeutics
Our CD33 program is evaluating the clinical utility of an ARC
comprised of the anti-CD33 mAb lintuzumab linked to the potent alpha-emitting radioisotope Actinium-225 or Ac-225. CD33 is expressed
in the majority of patients with AML and myelodysplastic syndrome, or MDS, as well as approximately one third of patients with
multiple myeloma. Our CD33 development program is driven by data obtained from over one hundred treated patients, including results
from a Phase 1/2 trial that was conducted in 58 patients with newly diagnosed AML, which was completed in 2018. This clinical data,
as well as our experience with Iomab-B, is shaping a two-pronged approach with our CD33 program, where at high doses we are exploring
its use for targeted conditioning and at low doses we are exploring its use for therapeutic purposes in combination with other
modalities, such as chemotherapy, targeted agents or immunotherapy.
Actimab-MDS is our second clinical trial focused on targeted
conditioning, in this case for patients with high-risk MDS and is our second pivotal program. Actimab-MDS is informed by prior
experience with our CD33 ARC in multiple trials for patients with AML, MDS and for patients that have progressed from MDS to AML,
which is also known as secondary AML. Data from these trials showed that our CD33 ARC had single-agent activity capable of producing
complete remissions (CRs) in certain patients at varying dose levels with minimal non-hematologic extramedullary toxicities. However,
dose-dependent myelosuppression, a class effect of CD33 directed therapies, was seen in many of these patients. Given that myelosuppression
is necessary prior to a BMT and that a BMT can rescue patients with myelosuppression, we decided to pursue a trial in targeted
conditioning in high-risk MDS patients with this ARC in combination with Reduced Intensity Conditioning, or RIC, regimens. RIC
regimens are comprised of low doses of chemotherapies such as fludarabine, cytarabine, busulfan or melphalan. A BMT is the only
curative treatment option for these patients with high-risk MDS who have poor, or very poor cytogenetics. However, these patients
have poor outcomes due to high relapse rates following a BMT. Based on our interactions with FDA to date, we will conduct a Phase
1 dose-finding clinical trial that will be followed by a randomized trial that, depending on the results observed, may potentially
serve as a pivotal trial to support the submission of a BLA. We are currently finalizing discussions with the FDA.
We are also studying our CD33 ARC
construct at various dose levels and dosing regimens in combination with other therapeutic modalities such as chemotherapy,
targeted agents or immunotherapy in CD33 expressing hematologic disease indications. We believe that radiation can be
synergistic when used in combination with these modalities based on mechanistic rationale supported by our own clinical data,
preclinical research and scientific and clinical evidence in the literature. We have prioritized our efforts and resources in
favor of combination trials for our CD33 program development strategy rather than single agent trials, which we are no longer
advancing at this time. Our CD33 ARC development program encompasses the following ongoing and planned trials:
Combination Trials:
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Phase 1 investigator initiated Actimab-A
+ CLAG-M combination trial with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim and mitoxantrone)
for patients with relapsed or refractory AML at the Medical College of Wisconsin. At the 2019 American Society of Hematology
Annual Meeting, it was reported that 86% of patients (6/7) receiving 0.50 µCi/kg of Actimab-A, and CLAG-M achieved a
complete remission after receiving Actimab-A + CLAG-M, which is nearly 60% greater than the 55% remission rate observed in
a study of CLAG-M alone conducted at MCW in the same r/r AML patient population. In addition, 71% of these patients (5/7)
achieved negative minimal residual disease status, indicating that these are deep remissions. The 0.50 µCi/kg dose of
Actimab-A was shown to be subtherapeutic as a single agent. Since the combination to date has been well tolerated, the study
progressed to the third and final cohort for the study of Actimab-A at a dose of 0.75 µCi/kg in March 2020, and we expect
to complete this trial by the end of 2020. Upon completion, we intend to explore a regulatory pathway for a pivotal trial
that could potentially support a registration. The combination of Actimab-A + CLAG-M is supported by mechanistic rationale
for combining inhibitors of DNA replication and/or repair processes such as mitoxantrone, a topoisomerase-II inhibitor, and
radiation, as imparted by tumor targeting of Ac-225 with Actimab-A. The Actimab-A + CLAG-M combination study has provided
proof of principle that the addition of subtherapeutic doses of Actimab-A to other AML therapies can lead to well tolerated
regimens with improved responses.
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Phase 1 Actimab-A + Ven combination trial with
the BCL-2 inhibitor Venetoclax (Ven) for patients with relapsed or refractory AML. This trial will be led by UCLA Medical
Center and will be conducted at three additional trial sites. This combination is supported by mechanistic evidence in preclinical
studies using Ven-resistant AML tumor cell lines. In these models, we have demonstrated that Actimab-A can deplete Mcl-1 and
Bcl-XL, two proteins implicated in mediating resistance to venetoclax, in addition to causing potentially lethal double-stranded
DNA breaks in these CD33 targeted cells. Furthermore, in vivo studies in animal models of Ven-resistant AML demonstrated robust
tumor regression and improved survival in cohorts receiving the Actimab-A Ven combination compared to Ven alone. The rationale
for this clinical study is that the addition of Actimab-A will; 1) have a direct anti-tumor effect via double-stranded DNA
breaks and 2) deplete Mcl-1 and BCL-XL making the AML cells more susceptible to Ven. We expect to initiate the trial and have
preliminary proof of concept clinical data from this combination study by the end of 2020.
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Phase 1 Actimab-A + 7+3 combination trial in
patients with newly diagnosed AML with intermediate or high-risk cytogenetics or molecular markers. In February 2020, we announced
plans to initiate this combination trial to add Actimab-A to 7+3, which is the standard of care chemotherapy regimen comprised
of cytarabine and daunorubicin for patients with newly diagnosed AML who are fit for intensive therapy. As we have seen with
the combination of Actimab-A + CLAG-M chemotherapy, we believe that Actimab-A will have synergistic and potentiating properties
when added to 7+3, which causes DNA damage and has radiation sensitizing properties since daunorubicin is an anthracycline
antibiotic that cytotoxically inhibits DNA replication and repair and RNA synthesis through inhibition of topoisomerase II.
The rationale for studying Actimab-A in combination with 7+3 is the potential for both additive and synergistic effects due
to the interplay of various mechanisms including DNA damage from alpha radiation and the chemotherapy combination, radiation
sensitization, and prevention of DNA damage repair. We expect to initiate this Phase 1 trial by the end of 2020 and have proof
of concept data in 2021.
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Antibody Warhead Enabling Technology Platform
Our proprietary Antibody Warhead
Enabling, or AWE, Technology Platform is supported by intellectual property, know-how and trade secrets that cover the generation,
development, methods of use and manufacture of ARCs and certain of their components. Our AWE technology patent portfolio includes
28 patent families comprised of over 110 issued and pending patent applications, of which 9 are issued and 23 pending in the United
States, and 81 are issued and pending internationally. The effective life of the patents in our portfolio range from expirations
between 2020 to 2039. Our technology enables the direct labeling, or conjugation and labeling, of a biomolecular targeting agent
to a radionuclide warhead and its development and use as a therapeutic regimen for the treatment of diseases such as cancer. Our
AWE intellectual property covers various methods of use for ARCs in multiple diseases, including indication, dose and scheduling,
radionuclide warhead, and therapeutic combinations.
Recent Developments
Impact of COVID–19 Pandemic
In December 2019,
a novel strain of COVID-19 was reported in China. Since then, COVID-19 has spread globally. The spread of COVID-19 from China
to other countries has resulted in the World Health Organization (WHO) declaring the outbreak of COVID-19 as a “pandemic,”
or a worldwide spread of a new disease, on March 11, 2020. Many countries around the world have imposed quarantines and restrictions
on travel and mass gatherings to slow the spread of the virus and have closed non-essential businesses, and as of the date of
this prospectus, many local jurisdictions continue to have such restrictions in place.
As many local jurisdictions
continue to have such restrictions in place, our ability to continue to operate our business may also be limited. Such events
may result in a period of business, supply and drug product manufacturing disruption, and in reduced operations, any of which
could materially affect our business, financial condition and results of operations. In response to COVID-19, we implemented remote
working and thus far have not experienced a significant disruption or delay in our operations as it relates to the clinical development
of our drug candidates.
The spread of COVID-19, which has caused
a broad impact globally, may materially affect us economically. While the ultimate economic impact brought by, and the duration
of, the COVID-19 pandemic may be difficult to assess or predict, the pandemic has resulted significant disruptions in the general
commercial activity and the global economy and caused financial market volatility and uncertainty in significant and unforeseen
ways in the recent months. A continuation or worsening of the levels of market disruption and volatility seen in the recent past
could have an adverse effect on our ability to access capital, which could in the future negatively affect our liquidity. In addition,
a recession or market correction resulting from the spread of COVID-19 could materially affect our business and the value of our
common stock.
Currently, the Phase 3 SIERRA trial for our lead program, Iomab-B,
continues to remain active at a majority of our clinical trial sites, with investigators providing feedback that recruitment and
enrollment will remain active because of the acute nature of the disease, the high unmet needs of patients with relapsed or refractory
AML, the potentially curative nature of BMT and the differentiated profile of Iomab-B. Certain sites that had not been actively
enrolling due to COVID-19 have resumed recruitment and enrollment, and we currently anticipate that other sites that have not been
actively enrolling due to COVID-19 will likely resume recruitment and enrollment in the summer timeframe. We also believe our earlier
stage clinical trials for our CD33 program will also continue to recruit and enroll patients given the acute nature of relapsed
or refractory AML. The continuation of the pandemic could adversely affect our planned clinical trial operations, including our
ability to conduct the trials on the expected timelines and recruit and retain patients and principal investigators and site staff
who, as healthcare providers, may have heightened exposure to COVID-19 if their geography is impacted by the pandemic. Further,
the COVID-19 pandemic could result in delays in our clinical trials due to prioritization of hospital resources toward the pandemic,
restrictions in travel, potential unwillingness of patients to enroll in trials at this time, or the inability of patients to comply
with clinical trial protocols if quarantines or travel restrictions impede patient movement or interrupt healthcare services. In
addition, we rely on independent clinical investigators, contract research organizations and other third-party service providers
to assist us in managing, monitoring and otherwise carrying out our preclinical studies and clinical trials, and the pandemic may
affect their ability to devote sufficient time and resources to our programs or to travel to sites to perform work for us.
Additionally, COVID-19
may also result in delays in receiving approvals from local and foreign regulatory authorities, delays in necessary interactions
with IRB’s or Institutional Review Boards, local and foreign regulators, ethics committees and other important agencies
and contractors due to limitations in employee resources or forced furlough of government employees.
To date, COVID-19
has not had a financial impact on our company. However, COVID-19 has caused severe disruptions in transportation and limited access
to our facility, resulting in limited support from our staff and professional advisors. The small size of our accounting staff
and the additional responsibilities emanating from COVID-19 have presented difficulties to our ability to complete our Annual
Report on Form 10-K and our Quarterly Report on Form 10-Q for the quarter ended March 31, 2020, resulting in its delay, and may
continue to cause a delay in our ability to complete subsequent reports in a timely manner. We expect to file our Quarterly Report
on Form 10-Q for the quarter ended March 31, 2020, no later than June 29, 2020.
The ultimate impact from COVID-19 on our
business operations and financial results during 2020 will depend on, among other things, the ultimate severity and scope of the
pandemic, the pace at which governmental and private travel restrictions and public concerns about public gatherings will ease,
the rate at which historically large increases in unemployment rates will decrease, if at all, and whether, and the speed with
which the economy recovers. We are not able to fully quantify the impact that these factors will have on our financial results
during 2020 and beyond, but developments related to COVID-19 may materially affect us in 2020.
NYSE American Notification and Reverse Stock Split
On April 29, 2020, we received a deficiency
letter from the NYSE American LLC, or the NYSE American, indicating that we are not in compliance with certain NYSE American continued
listing standards. The deficiency letter states that our shares of common stock have been selling for a low price per share for
a substantial period of time. Pursuant to Section 1003(f)(v) of the Company Guide, the NYSE American staff determined that our
continued listing is predicated on us effecting a reverse stock split of our common stock or otherwise demonstrating sustained
price improvement within a reasonable period of time, which the staff determined to be until October 29, 2020.
The letter further stated that as a result
of the foregoing, we have become subject to the procedures and requirements of Section 1009 of the NYSE American Company Guide,
which could, among other things, result in the initiation of delisting proceedings, unless we cure the deficiency in a timely
manner. Our common stock will continue to be listed on the NYSE American while we attempt to regain compliance with the listing
standards, subject to our compliance with other continued listing requirements.
In addition, the NYSE American has advised
us that its policy is to immediately suspend trading in shares of, and commence delisting procedures with respect to, a listed
company if the market price of its shares falls below $0.06 per share at any time during the trading day.
We intend to regain compliance with the
NYSE American’s continued listing standards by undertaking a measure or measures that are for the best interests of the
Company and our stockholders. On October 18, 2019, our board of directors unanimously approved, subject to stockholder approval,
an amendment to our certificate of incorporation to effect a reverse stock split of our outstanding common stock by combining
outstanding shares of common stock into a lesser number of outstanding shares of common stock by a ratio of not more than 1-for-75
prior to December 18, 2020, with the exact ratio to be set within this range by our board of directors at its sole discretion.
On December 18, 2019, at our 2019 Annual Meeting of Stockholders, our stockholders approved such proposed amendment to our certificate
of incorporation. The primary intent of effecting the reverse stock split, if our board of directors determines to do so, would
be to ensure that we are able to maintain compliance with the listing standards of the NYSE American. The board of directors may
alternatively elect to abandon such proposed amendment and not effect the reverse stock split authorized by stockholders, in its
sole discretion.
Although we expect that a reverse stock split will result in
an increase in the market price of our common stock, such reverse stock split may not result in a permanent increase in the market
price of our common stock, which is dependent on many factors, including general economic, market and industry conditions and other
factors detailed from time to time in the reports we file with the Securities and Exchange Commission.
If we implement the reverse stock split,
the reverse stock split would affect all of our stockholders uniformly and will not affect any stockholder’s percentage
ownership interest in our company, except to the extent that the reverse stock split results in any of our stockholders owning
a fractional share. The reverse stock split would not change the terms of our common stock. After a reverse stock split, all shares
of common stock would have the same voting rights and rights to dividends and distributions and will be identical in all other
respects to the common stock now authorized, which is not entitled to preemptive or subscription rights, and is not subject to
conversion, redemption or sinking fund provisions.
As of the effective time of the reverse
stock split, if any, we would adjust and proportionately decrease the number of shares of our common stock reserved for issuance
upon exercise of, and adjust and proportionately increase the exercise price of, all options and warrants and other rights to
acquire our common stock. In addition, as of the effective time of a reverse stock split, we would adjust and proportionately
decrease the total number of shares of our common stock that may be the subject of the future grants under our stock plans.
The April 2020 Offering
On April 24, 2020, we issued and sold 128,333,333 shares of
common stock and pre-funded warrants to purchase 82,500,001 shares of common stock (the “April 2020 Offering”). The
price to the public for each share of common stock sold in the offering was $0.15, and the price to the public for each pre-funded
warrant sold in the offering was $0.1499. The pre-funded warrants are exercisable immediately upon issuance until all of the pre-funded
warrants are exercised in full, at an exercise price of $0.0001 per share. The pre-funded warrants are subject to certain limitations
on beneficial ownership. Gross proceeds from the April 2020 Offering to us were $31.6 million, before deducting underwriting discounts
and commissions and other offering expenses payable by us. Net proceeds from the April 2020 Offering were $29.1 million. In June
2020, holders of 36.0 million pre-funded warrants exercised their warrants and received shares of common stock.
Financial Update
Complete unaudited
financial information and operating data for quarter ended March 31, 2020, will not be available until after this offering is
complete. Based on the information and data currently available, as of March 31, 2020, we had approximately $5.9 million of cash
and cash equivalents. Subsequently, we closed the April 2020 Offering and received the net proceeds of $29.1 million. Additional
information and disclosures would be required for a more complete understanding of our financial position and results of operations
as of March 31, 2020.
Consultant Share Issuance
On June 1, 2020, we issued an aggregate of 157,181
shares of common stock to a consultant as part of an engagement fee pursuant to that certain letter agreement dated April 8, 2020.
Corporate and
Other Information
We were organized as a corporation in the
State of Nevada in October 1997 and reorganized as a corporation in the State of Delaware in March 2013. Our principal executive
offices are located at 275 Madison Avenue, 7th Floor, New York, New York 10016. Our telephone number is (646) 677-3870. Our website
address is www.actiniumpharma.com. Information accessed through our website is not incorporated into this prospectus supplement
and is not a part of this prospectus supplement or the accompanying prospectus.
The
Offering
Issuer
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Actinium Pharmaceuticals,
Inc.
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Common Stock Offered by Us
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55,653,846 shares
of common stock.
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Pre-funded warrants offered by us
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Pre-funded warrants to purchase up to an aggregate of 21,269,231 shares
of common stock. We are offering pre-funded warrants to each investor whose purchase of shares of common stock in this offering
would otherwise result in such purchaser, together with its affiliates and certain related parties, beneficially owning more than
4.99% (or, at the election of the purchasers, 9.99%) of our outstanding shares of common stock immediately following the closing
of this offering, in lieu of shares of common stock. Each pre-funded warrant is exercisable for one share of common stock. Each
pre-funded warrant is being sold at a public offering price of $0.3249. Each pre-funded warrant will have an exercise price per
share of common stock of $0.0001, and will be immediately exercisable and may be exercised at any time until exercised in full.
This prospectus supplement also relates to the offering of the shares of common stock issuable upon exercise of the pre-funded
warrants. The exercise price and number of shares of common stock issuable upon exercise will be subject to certain further adjustments
as described herein.
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Common Stock to be Outstanding Immediately After
this Offering (1)
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416,423,957 shares,
assuming all of the pre-funded warrants issued in this offering are exercised.
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Use of Proceeds
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We estimate that our net proceeds from our issuance and sale
of shares of our common stock and pre-funded warrants to purchase shares of common stock in this offering will be approximately
$22.8 million, after deducting placement
agent fees and estimated offering expenses payable by us.
We currently intend to use the net proceeds from the sale of
securities offered by this prospectus supplement to complete our ongoing pivotal, Phase 3 SIERRA trial for our lead product candidate
Iomab-B, prepare and submit a BLA to the FDA and MAA to the EMA, as well as commercialization activities for Iomab-B in the United
States. We will also use the net proceeds to progress Phase 1 trials for our refocused CD33 program to the proof of concept stage,
to support our AWE Technology Platform, Iomab-ACT program and research and development and for general working capital needs. See
the section entitled “Use of Proceeds” below.
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Risk Factors
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Investing in our securities involves a high degree of risk. For a discussion of factors that you should consider before buying our securities, see the information under “Risk Factors” in this prospectus supplement and under similar headings in the documents incorporated by reference into this prospectus supplement.
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NYSE American symbol
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“ATNM.”
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(1) The number of shares of our common stock that will be outstanding
immediately after the offering is based on 339,500,880 shares outstanding as of June 11, 2020. Unless we specifically state otherwise,
the share information in this prospectus supplement excludes, as of June 11, 2020:
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10,936,421 shares of common stock issuable upon the exercise of stock options outstanding under our equity incentive plans, with a weighted average exercise price of $1.20 per share;
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22,250,949 shares of common stock available for future grants under our equity incentive plans;
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86,140,575 shares of common stock issuable upon the exercise
of warrants with a weighted average exercise price of $0.69 per share; and
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46,500,001 shares of common stock issuable upon the exercise of pre-funded warrants with an exercise price of $0.0001 per share issued in the April 2020 Offering.
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In addition, the number of shares of
our common stock to be outstanding immediately after this offering as shown above does not include (i) up to approximately
$29.2 million of shares of our common stock that remained available for sale at June 12, 2020 under the Lincoln Park
Agreement, and (ii) up to approximately $67.6 million of shares of our common stock that remained available for sale at June
12, 2020 under the ATM Sales Agreement. In connection with this offering, we have suspended, and during the duration of this
offering we are no longer offering, any securities pursuant to the Lincoln Park Agreement or the ATM Sales Agreement.
Risk
Factors
An investment in our securities involves
a high degree of risk. Prior to making a decision about investing in our securities, you should carefully consider the specific
factors discussed below, together with all of the other information contained or incorporated by reference in this prospectus supplement
and the accompanying prospectus, including in our Annual Report on Form 10-K, as amended, and any updates described in our Quarterly
Reports on Form 10-Q or other documents filed by us with the Securities and Exchange Commission. If any of these risks actually
occurs, our business, financial condition, results of operations or cash flow could be seriously harmed. This could cause the trading
price of our common stock to decline, resulting in a loss of all or part of your investment. The risks and uncertainties described
below are not the only ones facing us. Additional risks and uncertainties not presently known to us, or that we currently see as
immaterial, may also harm our business. Please also read carefully the section above entitled “Special Note Regarding Forward-Looking
Statements.”
Risks Related to Our Business
We are a clinical-stage company and have generated no
revenue from commercial sales to date.
We are a clinical-stage biopharmaceutical
company with a limited operating history. We have no products approved for commercial sale and have not generated any revenue from
product sales to date. We will encounter risks and difficulties frequently experienced by early-stage companies in rapidly evolving
fields. If we do not address these risks successfully, our business will suffer.
We have incurred net losses in every year since our inception
and anticipate that we will continue to incur net losses in the future.
We are not profitable and have
incurred losses in each period since our inception. As of December 31, 2019 and December 31, 2018, we had an accumulated
deficit of $208.8 million and $186.9 million, respectively. We reported a net loss of $21.9 million and $23.7 million for the
years ended December 31, 2019 and 2018, respectively. We expect to continue to operate at a net loss as we continue our
research and development efforts, continue to conduct clinical trials and develop manufacturing, sales, marketing and
distribution capabilities. There can be no assurance that the products under development by us will be approved for sale in
the United States or elsewhere. Furthermore, there can be no assurance that if such products are approved, they will be
successfully commercialized, which would have an adverse effect on our business prospects, financial condition and results of
operation.
If we fail to obtain additional financing, we will be
unable to continue or complete our product development and you will likely lose your entire investment.
On
April 24, 2020, we issued and sold 210.8 million shares of common stock (or pre-funded warrants to purchase shares of common stock
in lieu thereof). Gross proceeds from this offering to us were $31.6 million, before deducting underwriting discounts and commissions
and other offering expenses payable by us. As of the date
of filing of this prospectus, we expect that our existing resources will be sufficient to fund our planned operations for more
than 12 months following the date of this prospectus.
Our business or operations may change in
a manner that would consume available funds more rapidly than anticipated and substantial additional funding may be required to
maintain operations, fund expansion, develop new or enhanced products, acquire complementary products, business or technologies
or otherwise respond to competitive pressures and opportunities, such as a change in the regulatory environment or a change in
preferred cancer treatment modalities. However, we may not be able to secure funding when we need it or on favorable terms or indeed
on any terms. In addition, from time to time, we may not be able to secure enough capital in a timely enough manner which may cause
the generation of a going-concern opinion from our auditors which can and may impair our stock market valuation and also our ability
to finance on favorable terms or indeed on any terms.
To raise additional capital, we may in the
future offer additional shares of our common stock or other securities convertible into or exchangeable for our common stock. We
cannot assure you that we will be able to sell shares or other securities in any other offering at a price per share that is equal
to or greater than the price per share paid by investors, and investors purchasing shares or other securities in the future could
have rights superior to existing stockholders.
If we cannot raise adequate funds to satisfy
our capital requirements, we will have to delay, scale back or eliminate our research and development activities, clinical studies
or future operations. We may also be required to obtain funds through arrangements with collaborators, which arrangements may require
us to relinquish rights to certain technologies or products that we otherwise would not consider relinquishing, including rights
to future product candidates or certain major geographic markets. We may further have to license our technology to others. This
could result in sharing revenues which we might otherwise have retained for ourselves. Any of these actions may harm our business,
financial condition and results of operations.
The amount of funding we will need depends
on many factors, including the progress, timing and scope of our product development programs; the progress, timing and scope of
our preclinical studies and clinical trials; the time and cost necessary to obtain regulatory approvals; the time and cost necessary
to further develop manufacturing processes and arrange for contract manufacturing; our ability to enter into and maintain collaborative,
licensing and other commercial relationships; and our partners’ commitment of time and resources to the development and commercialization
of our products.
We have limited access to the capital markets and even
if we can raise additional funding, we may be required to do so on terms that are dilutive to you.
We have limited access to the capital markets
to raise funds. The capital markets have been unpredictable in the recent past for radioisotope and other oncology companies and
unprofitable companies such as ours. Furthermore, the COVID-19 pandemic has created significant economic uncertainty and volatility
in the credit and capital markets. A continuation or worsening of the levels of market disruption and volatility seen in the recent
past could have an adverse effect on our ability to access capital. In addition, it is generally difficult for development-stage
companies to raise capital under current market conditions. The amount of capital that a company such as ours is able to raise
often depends on variables that are beyond our control. As a result, we may not be able to secure financing on terms attractive
to us, or at all. If we are able to consummate a financing arrangement, the amount raised may not be sufficient to meet our future
needs. If adequate funds are not available on acceptable terms, or at all, our business, including our technology licenses, results
of operations, financial condition and our continued viability will be materially adversely affected.
We are highly dependent on the success of Iomab-B and
the SIERRA trial and we many not able to complete the necessary clinical development or our development efforts may not result
in the data necessary to receive regulatory approval
Iomab-B, which we licensed from the Fred
Hutchinson Cancer Research Center in June 2012, is our lead program to which we allocate a significant portion of our resources.
We are currently enrolling patients in the pivotal Phase 3 SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML),
a 150-patient multi-center randomized trial that will compare outcomes of patients who receive Iomab-B and a BMT to those patients
receiving physician’s choice of salvage chemotherapy, defined as conventional care, as no standard of care exists for this
patient population. The SIERRA trial may be unsuccessful and fail to demonstrate a safety and efficacy profile that is necessary
to receive favorable regulatory approval. The trials DMC or Data Monitoring Committee may recommend that the trial be stopped early
for safety or efficacy concerns, which could prevent us from completing the SIERRA trial. Even if Iomab-B receives favorable regulatory
approval, we may not be successful in securing adequate reimbursement or establishing successful commercial operations. Any or
all of these factors could have a material adverse impact on our business and ability to continue operations.
We may be unable to establish sales, marketing and commercial
supply capabilities
We do not currently have, nor have we ever
had, commercial sales and marketing capabilities. If any of our product candidates become approved, we would have to build and
establish these capabilities in order to commercialize our approved product candidates. The process of establishing commercial
capabilities will be expensive and time consuming. Even if we are successful in building sales and marketing capabilities, we may
not be successful in commercializing any of our product candidates. Any delays in commercialization or failure to successfully
commercialize any product candidate may have material adverse impacts on our business and ability to continue operations.
Our business could be adversely
affected by the effects of health epidemics, including the global COVID-19 pandemic.
In December 2019,
a novel strain of COVID-19 was reported in China. Since then, COVID-19 has spread globally. The spread of COVID-19 from China
to other countries has resulted in the World Health Organization (WHO) declaring the outbreak of COVID-19 as a “pandemic,”
or a worldwide spread of a new disease, on March 11, 2020. Many countries around the world have imposed quarantines and restrictions
on travel and mass gatherings to slow the spread of the virus and have closed non-essential businesses, and as of the date of
this prospectus, many local jurisdictions continue to have such restrictions in place.
As many local jurisdictions
continue to have such restrictions in place, our ability to continue to operate our business may also be limited. Such events
may result in a period of business, supply and drug product manufacturing disruption, and in reduced operations, any of which
could materially affect our business, financial condition and results of operations. In response to COVID-19, we implemented remote
working and thus far have not experienced a significant disruption or delay in our operations as it relates to the clinical development
of our drug candidates.
The spread of COVID-19,
which has caused a broad impact globally, may materially affect us economically. While the ultimate economic impact brought by,
and the duration of, the COVID-19 pandemic may be difficult to assess or predict, the pandemic has resulted significant disruptions
in the general commercial activity and the global economy and caused financial market volatility and uncertainty in significant
and unforeseen ways in the recent months. A continuation or worsening of the levels of market disruption and volatility seen in
the recent past could have an adverse effect on our ability to access capital, which could in the future negatively affect our
liquidity. In addition, a recession or market correction resulting from the spread of COVID-19 could materially affect our business
and the value of our common stock.
Currently, the Phase
3 SIERRA trial for our lead program, Iomab-B, continues to remain active at a majority of our clinical trial sites, with investigators
providing feedback that recruitment and enrollment will remain active because of the acute nature of the disease, the high unmet
needs of patients with relapsed or refractory AML, the potentially curative nature of BMT and the differentiated profile of Iomab-B.
Certain sites that had not been actively enrolling due to COVID-19 have resumed recruitment and enrollment, and we currently anticipate
that other sites that have not been actively enrolling due to COVID-19 will likely resume recruitment and enrollment in the summer
timeframe. We also believe our earlier stage clinical trials for our CD33 program will also continue to recruit and enroll patients
given the acute nature of relapsed or refractory AML. The continuation of the pandemic could adversely affect our planned clinical
trial operations, including our ability to conduct the trials on the expected timelines and recruit and retain patients and principal
investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19 if their geography is impacted
by the pandemic. Further, the COVID-19 pandemic could result in delays in our clinical trials due to prioritization of hospital
resources toward the pandemic, restrictions in travel, potential unwillingness of patients to enroll in trials at this time, or
the inability of patients to comply with clinical trial protocols if quarantines or travel restrictions impede patient movement
or interrupt healthcare services. In addition, we rely on independent clinical investigators, contract research organizations
and other third-party service providers to assist us in managing, monitoring and otherwise carrying out our preclinical studies
and clinical trials, and the pandemic may affect their ability to devote sufficient time and resources to our programs or to travel
to sites to perform work for us.
Additionally, COVID-19
may also result in delays in receiving approvals from local and foreign regulatory authorities, delays in necessary interactions
with IRB’s or Institutional Review Boards, local and foreign regulators, ethics committees and other important agencies
and contractors due to limitations in employee resources or forced furlough of government employees.
COVID-19 has caused
severe disruptions in transportation and limited access to our facility, resulting in limited support from our staff and professional
advisors. The small size of our accounting staff and the additional responsibilities emanating from COVID-19 have presented difficulties
to our ability to complete our Annual Report on Form 10-K and our Quarterly Report on Form 10-Q for the quarter ended March 31,
2020, resulting in its delay, and may continue to cause a delay in our ability to complete subsequent reports in a timely manner.
The ultimate impact
from COVID-19 on our business operations and financial results during 2020 will depend on, among other things, the ultimate severity
and scope of the pandemic, the pace at which governmental and private travel restrictions and public concerns about public gatherings
will ease, the rate at which historically large increases in unemployment rates will decrease, if at all, and whether, and the
speed with which the economy recovers. We are not able to fully quantify the impact that these factors will have on our financial
results during 2020 and beyond, but developments related to COVID-19 may materially affect us in 2020.
Our business is subject to cybersecurity
risks.
Our operations are
increasingly dependent on information technologies and services. Threats to information technology systems associated with cybersecurity
risks and cyber incidents or attacks continue to grow, and include, among other things, storms and natural disasters, terrorist
attacks, utility outages, theft, viruses, phishing, malware, design defects, human error, and complications encountered as existing
systems are maintained, repaired, replaced, or upgraded. Risks associated with these threats include, among other things:
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theft
or misappropriation of funds;
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loss,
corruption, or misappropriation of intellectual property, or other proprietary, confidential
or personally identifiable information (including supplier, clinical data or employee
data);
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disruption
or impairment of our and our business operations and safety procedures;
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damage
to our reputation with our potential partners, patients and the market;
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exposure
to litigation;
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increased
costs to prevent, respond to or mitigate cybersecurity events.
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Although we utilize
various procedures and controls to mitigate our exposure to such risk, cybersecurity attacks and other cyber events are evolving
and unpredictable. Moreover, we have no control over the information technology systems of third parties conducting our clinical
trials, our suppliers, and others with which our systems may connect and communicate. As a result, the occurrence of a cyber incident
could go unnoticed for a period time.
We do not presently
maintain insurance coverage to protect against cybersecurity risks. If we procure such coverage in the future, we cannot ensure
that it will be sufficient to cover any particular losses we may experience as a result of such cyberattacks. Any cyber incident
could have a material adverse effect on our business, financial condition and results of operations.
Risks Related to Regulation
The FDA or comparable foreign regulatory authorities may
disagree with our regulatory plans and we may fail to obtain regulatory approval of our product candidates.
Our products are subject to rigorous regulation
by the FDA and numerous other federal, state and foreign governmental authorities. The process of seeking regulatory approval to
market an antibody radiation-conjugate product is expensive and time-consuming, and, notwithstanding the effort and expense incurred,
approval is never guaranteed. If we are not successful in obtaining timely approval of our products from the FDA, we may never
be able to generate significant revenue and may be forced to cease operations. In particular, the FDA permits commercial distribution
of a new antibody radiation-conjugate product only after a BLA for the product has received FDA approval. The BLA process is costly,
lengthy and inherently uncertain. Any BLA filed by us will have to be supported by extensive data, including, but not limited to,
technical, preclinical, clinical trial, manufacturing and labeling data, to demonstrate to the FDA’s satisfaction the safety
and efficacy of the product for its intended use. The lengthy approval process as well as the unpredictability of future clinical
trial results may result in our failing to obtain regulatory approval to market our product candidates, which would significantly
harm our business, results of operations and prospects. In addition, even if we were to obtain approval, regulatory authorities
may approve any of our product candidates for fewer or more limited indications than we request, may not approve the price we intend
to charge for our products, may grant approval contingent on the performance of costly post-marketing clinical trials, or may approve
a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization
of that product candidate. Any of the foregoing scenarios could materially harm the commercial prospects for our product candidates.
The approval process in the United States
and in other countries could result in unexpected and significant costs for us and consume management’s time and other resources.
The FDA and other foreign regulatory agencies could ask us to supplement our submissions, collect non-clinical data, conduct additional
clinical trials or engage in other time-consuming actions, or it could simply deny our applications. In addition, even if we obtain
approval to market our products in the United States or in other countries, the approval could be revoked, or other restrictions
imposed if post-market data demonstrates safety issues or lack of effectiveness. We cannot predict with certainty how, or when,
the FDA or other regulatory authorities will act. If we are unable to obtain the necessary regulatory approvals, our financial
condition and cash flow may be materially adversely affected, and our ability to grow domestically and internationally may be limited.
Additionally, even if we obtain approval, regulatory authorities may approve any of our product candidates for fewer or more limited
indications that we request. The Company’s products may not be approved for the specific indications that are most necessary
or desirable for successful commercialization or profitability.
We have not demonstrated that any
of our products are safe and effective for any indication and will continue to expend substantial time and resources on clinical
development before any of our current or future product candidates will be eligible for FDA approval, if ever.
We expect that a substantial
portion of our efforts and expenditures over the next few years will be devoted to development of our existing and contemplated
biological product candidates. Accordingly, our business currently depends heavily on the successful development, FDA approval,
and commercialization of such candidates, which may never receive FDA approval or be successfully commercialized even if FDA approval
is received. The research, testing, manufacturing, labeling, approval, sale, marketing, and distribution of our biological product
candidates are, and will remain, subject to extensive regulation by the FDA and other regulatory authorities in the United States
and other countries, as applicable. We are currently not permitted to market any of our current or future product candidates in
the United States until we receive FDA approval (of each) via the BLA process. To date, we have two product candidates in
clinical development and have not-yet submitted a BLA for any of our candidates and, for many such candidates, do not expect to
be in a position to do so for the foreseeable future, as there are numerous developmental steps that must be completed before we
can prepare and submit a BLA.
In the United States,
the FDA regulates pharmaceutical and biological product candidates under the Federal Food, Drug and Cosmetic Act (“FDCA”)
and the Public Health Service Act (“PHSA”), as well as their respective implementing regulations. Such products and
product candidates are also subject to other federal, state, and local statutes and regulations. The process of obtaining regulatory
approvals and the subsequent compliance with appropriate federal, state, local, and foreign statutes and regulations requires the
expenditure of substantial time and financial resources. The process required by the FDA before a drug or biological product may
be marketed in the United States generally involves the following:
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completion of preclinical laboratory tests and animal studies
in accordance with FDA’s good laboratory practices (“GLPs”) and applicable requirements for the humane use of
laboratory animals or other applicable regulations;
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submission to the FDA of an IND, which must become effective
before human clinical trials in the United States may begin;
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performance of adequate and well-controlled human clinical
trials in accordance with FDA’s IND regulations, good clinical practices (“GCPs”), and any additional requirements
for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed
biological product for its intended use;
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submission to the FDA of a BLA for marketing approval that
meets applicable requirements to ensure the continued safety, purity, and potency of the product that is the subject of the BLA
based on results of preclinical testing and clinical trials;
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satisfactory completion of an FDA inspection of the manufacturing
facility or facilities where the biological product is produced, to assess compliance with current good manufacturing processes
(“cGMPs”) and assure that the facilities, methods and controls are adequate to preserve the biological product’s
identity, strength, quality and purity;
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potential FDA audit of the nonclinical study and clinical
trial sites that generated the data in support of the BLA; and
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FDA review and approval, or denial, of the BLA.
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Before testing any
biological product candidate in humans, the product candidate enters the preclinical testing stage. Preclinical tests include laboratory
evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity
of the product candidate. The conduct of the preclinical tests must comply with federal regulations and requirements including
GLPs. The clinical trial sponsor must submit the results of the preclinical tests, together with manufacturing information, analytical
data, any available clinical data or literature and a proposed clinical protocol, to the FDA as part of the IND. Some preclinical
testing may continue even after the IND is submitted. The IND automatically becomes effective 30 days after receipt by the FDA,
unless the FDA raises concerns or questions regarding the proposed clinical trials and places the trial on a clinical hold within
that 30-day time period. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical
trial can begin. The FDA may also impose clinical holds on a biological product candidate at any time before or during clinical
trials due to safety concerns or non-compliance. If the FDA imposes a clinical hold, trials may not recommence without FDA authorization
and then only under terms authorized by the FDA. Accordingly, we cannot be sure that submission of an IND will result in the FDA
allowing clinical trials to begin or that, for those that have already commenced under an active IND, that issues will not arise
that suspend or terminate such trials.
Clinical trials involve
the administration of the biological product candidate to healthy volunteers or patients under the supervision of qualified investigators,
generally physicians not employed by or under the trial sponsor’s control. Clinical trials are conducted under protocols
detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria,
and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped
if certain adverse events should occur. Each protocol and any amendments to the protocol must be submitted to the FDA as part of
the IND. Clinical trials must be conducted and monitored in accordance with the FDA’s regulations composing the GCP requirements,
including the requirement that all research subjects provide informed consent. Further, each clinical trial must be reviewed and
approved by an independent institutional review board, or IRB, at or servicing each institution at which the clinical trial will
be conducted. An IRB is charged with protecting the welfare and rights of trial participants and considers such items as whether
the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits.
The IRB also approves the form and content of the informed consent that must be signed by each clinical trial subject or his or
her legal representative and must monitor the clinical trial until completed. Human clinical trials are typically conducted in
three sequential phases that may overlap or be combined:
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Phase 1. The biological product is initially introduced
into healthy human subjects and tested for safety. In the case of some products for severe or life-threatening diseases, especially
when the product may be too inherently toxic to ethically administer to healthy volunteers, the initial human testing is often
conducted in subjects.
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Phase 2. The biological product is evaluated in a limited
patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product
for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule.
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Phase 3. Clinical trials are undertaken to further evaluate
dosage, clinical efficacy, potency, and safety in an expanded patient population at geographically dispersed clinical trial sites.
These clinical trials are intended to establish the overall risk to benefit ratio of the product and provide an adequate basis
for product labeling.
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Post-approval clinical
trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval. These clinical trials
are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for
long-term safety follow-up.
After the completion
of clinical trials of a biological product, FDA approval of a BLA must be obtained before commercial marketing of the biological
product. The BLA must include results of product development, laboratory and animal studies, human trials, information on the manufacture
and composition of the product, proposed labeling and other relevant information. The FDA may grant deferrals for submission of
data, or full or partial waivers. The testing and approval processes require substantial time and effort and there can be no assurance
that the FDA will accept the BLA for filing and, even if filed, that any approval will be granted on a timely basis, if at all.
Before approving a BLA, the FDA will inspect the facilities at which the product is manufactured. The FDA will not approve the
product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate
to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will
typically inspect one or more clinical sites to assure that the clinical trials were conducted in compliance with IND trial requirements
and GCP requirements. To assure cGMP and GCP compliance, an applicant must incur significant expenditure of time, money and effort
in the areas of training, record keeping, production, and quality control.
Notwithstanding the
submission of relevant data and information, the FDA may ultimately decide that the BLA does not satisfy its regulatory criteria
for approval and deny approval. Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently
than we interpret the same data. Our product candidates are in the earliest stages of clinical development and, therefore, a long
way from BLA submission. We cannot predict with any certainty if or when we might submit a BLA for regulatory approval for our
product candidates or whether any such BLA will be approved by the FDA. Human clinical trials are very expensive and difficult
to design and implement, in part because they are subject to rigorous regulatory requirements. For example, the FDA may not agree
with our proposed endpoints for any clinical trial we propose, which may delay the commencement of our clinical trials. The clinical
trial process is also lengthy and requires substantial time and effort.
In December 2015, the
FDA cleared our IND filing for Iomab-B (for acute myeloid leukemia or AML), and we are currently enrolling patients in a randomized,
controlled, pivotal Phase 3 clinical trial under such IND to study Iomab-B in patients 55 years of age or older with relapsed or
refractory AML. Assuming the Phase 3 trial meets its endpoints and there are no unexpected issues or delays, it will form the basis
for a BLA in the reasonably near future for Iomab-B for use in preparing and conditioning AML patients for bone marrow transplants
(BMTs). Additionally, there are physician IND trials at the Fred Hutchinson Cancer Research Center (FHCRC) that have been conducted
or are currently ongoing at FHCRC with Iomab-B (for other target indications) and the BC8 antibody we licensed. And, we have multiple
Phase 1 and Phase 2 clinical trials ongoing and others that we have planned but not-yet commenced, for our other drug candidates
under our own sponsorship and multiple investigator-initiated trials ongoing. Except for Iomab-B (for patients with AML), we expect
that the clinical trials we need to conduct to be in a position to submit BLAs for our product candidates currently in-development
will take, at least, several years to complete. Moreover, failure can occur at any stage of the trials, and we could encounter
problems that cause us to abandon or repeat clinical trials. Also, the results of early preclinical and clinical testing may not
be predictive of the results of subsequent clinical trials. A number of companies in the biopharmaceutical industry have suffered
significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising
results in earlier studies. And, preclinical and clinical data are often susceptible to multiple interpretations and analyses.
Many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials
have, nonetheless, failed to obtain marketing approval of their products. Success in preclinical testing and early clinical trials
does not ensure that later clinical trials, which involve many more subjects, and the results of later clinical trials may not
replicate the results of prior clinical trials and preclinical testing. Any failure or substantial delay in our product development
plans may have a material adverse effect on our business.
We may encounter substantial delays in our clinical trials
or may not be able to conduct our trials on the timelines we expect.
We cannot predict whether we will encounter
problems with any of our ongoing or planned clinical trials that will cause us or regulatory authorities to delay, suspend, or
discontinue clinical trials or to delay the analysis of data from ongoing clinical trials. Any of the following could delay or
disrupt the clinical development of our product candidates and potentially cause our product candidates to fail to receive regulatory
approval:
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conditions imposed on us by the FDA or comparable foreign authorities regarding the scope or design of our clinical trials;
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delays in receiving, or the inability to obtain, required approvals from institutional review boards (IRBs) or other reviewing entities at clinical sites selected for participation in our clinical trials;
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delays in enrolling patients into clinical trials;
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a lower than anticipated retention rate of patients in clinical trials;
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the need to repeat or discontinue clinical trials as a result of inconclusive or negative results or unforeseen complications in testing or because the results of later trials may not confirm positive results from earlier preclinical studies or clinical trials;
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inadequate supply, delays in distribution, deficient quality of, or inability to purchase or manufacture drug product, comparator drugs or other materials necessary to conduct our clinical trials;
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unfavorable FDA or other foreign regulatory inspection and review of a clinical trial site or records of any clinical or preclinical investigation;
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serious and unexpected drug-related side effects experienced by participants in our clinical trials, which may occur even if they were not observed in earlier trials or only observed in a limited number of participants;
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a finding that the trial participants are being exposed to unacceptable health risks;
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the placement by the FDA or a foreign regulatory authority of a clinical hold on a trial; or
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delays in obtaining regulatory agency authorization for the conduct of our clinical trials.
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We may suspend, or the FDA or other applicable
regulatory authorities may require us to suspend, clinical trials of a product candidate at any time if we or they believe the
patients participating in such clinical trials, or in independent third-party clinical trials for drugs based on similar technologies,
are being exposed to unacceptable health risks or for other reasons.
Further, individuals involved with our clinical
trials may serve as consultants to us from time to time and receive stock options or cash compensation in connection with such
services. If these relationships and any related compensation to the clinical investigator carrying out the study result in perceived
or actual conflicts of interest, or the FDA concludes that the financial relationship may have affected interpretation of the study,
the integrity of the data generated at the applicable clinical trial site may be questioned and the utility of the clinical trial
itself may be jeopardized. The delay, suspension or discontinuation of any of our clinical trials, or a delay in the analysis of
clinical data for our product candidates, for any of the foregoing reasons, could adversely affect our efforts to obtain regulatory
approval for and to commercialize our product candidates, increase our operating expenses and have a material adverse effect on
our financial results.
Clinical trials may also be delayed or terminated
as a result of ambiguous or negative interim results. In addition, a clinical trial may be suspended or terminated by us, the FDA,
the IRBs at the sites where the IRBs are overseeing a trial, or a data safety monitoring board, or DSMB (Data Safety Monitoring
Board)/DMC (Data Monitoring Committee), overseeing the clinical trial at issue, or other regulatory authorities due to a number
of factors, including:
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failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols;
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inspection
of the clinical trial operations or trial sites by the FDA or other regulatory authorities resulting in the imposition of a clinical
hold;
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varying interpretation of data by the FDA or similar foreign regulatory authorities;
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failure to achieve primary or secondary endpoints or other failure to demonstrate efficacy;
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unforeseen safety issues; or
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lack of adequate funding to continue the clinical trial.
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Modifications to our product candidates may require federal
approvals.
The BLA application is the vehicle through
which the company may formally propose that the FDA approve a new pharmaceutical for sale and marketing in the United States. Once
a particular product candidate receives FDA approval, expanded uses or uses in new indications of our products may require additional
human clinical trials and new regulatory approvals, including additional IND and BLA submissions and premarket approvals before
we can begin clinical development, and/or prior to marketing and sales. If the FDA requires new approvals for a particular use
or indication, we may be required to conduct additional clinical studies, which would require additional expenditures and harm
our operating results. If the products are already being used for these new indications, we may also be subject to significant
enforcement actions.
Conducting clinical trials and obtaining
approvals is a time-consuming process, and delays in obtaining required future approvals could adversely affect our ability to
introduce new or enhanced products in a timely manner, which in turn would have an adverse effect on our business prospects, financial
condition and results of operation.
The FDA or comparable foreign regulatory authorities may
disagree with our regulatory plans, and we may fail to obtain regulatory approval of our product candidates.
In June 2012, we acquired rights to BC8
(Iomab), a clinical stage monoclonal antibody with safety and efficacy data in more than 300 patients in need of a BMT. Iomab-B
is our product candidate that links I-131 to the BC8 antibody that is being studied in an ongoing Phase 3 pivotal trial. Product
candidates utilizing this antibody would require BLA approval before they can be marketed in the United States. We are also evaluating
a lower dose of the BC8 antibody and I-131 for lymphodepletion prior to CAR-T or adoptive cell therapy. We are currently evaluating
clinical trials that would use our construct for lymphodepletion. Our lintuzumab-Ac-225 product candidate is also being studied
in several Phase 1 trials under our sponsorship and investigator-initiated trials in patients with AML, myelodysplastic syndrome
and multiple myeloma. Product candidates utilizing the lintuzumab antibody would require BLA approval before they can be marketed
in the United States. We are in the early stages of evaluating other product candidates consisting of conjugates of Ac-225 with
human or humanized antibodies for pre-clinical and clinical development in other types of cancer. The FDA may not approve these
products for the indications that are necessary or desirable for successful commercialization. The FDA may fail to approve any
BLA we submit for new product candidates or for new intended uses or indications for approved products or future product candidates.
Failure to obtain FDA approval for our products in the proposed indications would have a material adverse effect on our business
prospects, financial condition and results of operations.
Clinical trials necessary to support approval of our product
candidates are time-consuming and expensive.
Initiating and completing clinical trials
necessary to support FDA approval of a BLA for Iomab-B, CD33 program candidates, and other product candidates, is a time-consuming
and expensive process, and the outcome is inherently uncertain. Moreover, the results of early clinical trials are not necessarily
predictive of future results, and any product candidate we advance into clinical trials may not have favorable results in later
clinical trials. We have worked with the FDA to develop a clinical trial designed to test the safety and efficacy of Iomab-B in
patients with relapsed or refractory AML who are age 55 and above prior to a BMT. This trial is designed to support a BLA filing
for marketing approval by the FDA, pending results from the trial. We have also worked with the FDA to develop a regulatory pathway
for our Actimab-MDS trial that consists of a dose-confirming Phase 1 trial that can be followed by a randomized, controlled pivotal
trial that could support a BLA filing. There can be no assurance that the data generated during the trial will meet our chosen
safety and effectiveness endpoints or otherwise produce results that will eventually support the filing or approval of a BLA. Even
if the data from this trial are favorable, the data may not be predictive of the results of any future clinical trials.
Our clinical trials may fail to demonstrate adequately
the efficacy and safety of our product candidates, which would prevent or delay regulatory approval and commercialization.
Even if our clinical trials are completed
as planned, we cannot be certain that their results will support our product candidate claims or that the FDA or foreign authorities
will agree with our conclusions regarding them. Success in pre-clinical studies and early clinical trials does not ensure that
later clinical trials will be successful, and we cannot be sure that the later trials will replicate the results of prior trials
and pre-clinical studies. The clinical trial process may fail to demonstrate that our product candidates are safe and effective
for the proposed indicated uses. If FDA concludes that the clinical trials for Iomab-B, lintzumab-Ac-225, or any other product
candidate for which we might seek approval, have failed to demonstrate safety and effectiveness, we would not receive FDA approval
to market that product candidate in the United States for the indications sought. In addition, such an outcome could cause us to
abandon the product candidate and might delay development of others. Any delay or termination of our clinical trials will delay
or preclude the filing of any submissions with the FDA and, ultimately, our ability to commercialize our product candidates and
generate revenues. It is also possible that patients enrolled in clinical trials will experience adverse side effects that are
not currently part of a product candidate’s profile.
The intellectual property related to antibodies we have
licensed has expired or likely expired
The key patents related to the humanized
antibody, lintuzumab, which we use in our CD33 program product candidates have expired. It is generally possible that others may
be eventually able to use an antibody with the same sequence, and we will then need to rely on additional patent protection covering
alpha particle drug products comprising Ac-225. Our final drug construct consists of the lintuzumab antibody labeled with the isotope
Ac-225. We have licensed issued patents that relate to the linker technology we use to conjugate the isotope to the antibody. Further,
we own issued and pending patents related to methods for drug conjugation and isotope labeling and for methods of isotope production.
In addition, we possess trade secrets and know how related to the manufacturing and use of isotopes. Any competing product based
on the lintuzumab antibody is likely to require several years of development before achieving our product candidate’s current
status and may be subject to significant regulatory hurdles but is nevertheless a possibility that could negatively impact our
business in the future. We own an issued patent in the US relating to composition of the Iomab-B product candidate. Five related
patents are also pending in the US and internationally. We have and may continue to file patents related to Iomab-B that can provide
barriers to entry but there is no certainty that these patents will be granted or such granting thereof will adequately prevent
others from seeking to replicate and use the BC8 antibody or the construct. We have pending patents related to radioimmunoconjugate
composition, formulation administration, and methods of use in solid or liquid cancers. This matter includes composition, administration,
and methods of treatment for our products Actimab-A and Iomab-B. Any competing product based on the antibody used in Iomab-B is
likely to require several years of development before achieving our product candidate’s current status and may be subject
to significant regulatory hurdles but is nevertheless a possibility that could negatively impact our business in the future.
Our CD33 program clinical trials are testing the same
drug construct
Our CD33 program is comprised of several
clinical trials including several investigator-initiated trials including AML, MDS and Multiple Myeloma that are studying the same
drug construct consisting of lintuzumab-Ac-225. Negative results from any of these trials could negatively impact our ability to
enroll or complete our other trials studying lintzumab-Ac-225. Additionally, negative outcomes including safety concerns, may result
in the FDA discontinuing other trials utilizing lintuzumab-Ac-225.
We may be unable to obtain a sufficient supply of isotopes
to support clinical development or at commercial scale.
Iodine-131 is a key component of our Iomab-B
drug candidate. We currently source medical grade I-131 from three suppliers including two leading global manufacturers. Currently,
there is sufficient supply of I-131 to advance our ongoing SIERRA clinical trial, support additional trials we may undertake utilizing
I-131 and for commercialization of Iomab-B. We continually evaluate I-131 manufacturers and suppliers and intend to have multiple
qualified suppliers prior to the commercial launch of Iomab-B. While we consider I-131 to be commoditized and obtainable through
several suppliers, there can be no guarantee that we will be able to secure I-131 or obtain I-131 on terms that are acceptable
to us.
Actinium-225 is a key component of our CD33
ARC program, AWE platform and other drug candidates that we might consider for development with the Ac-225 payload. There are adequate
quantities of Ac-225 available today to meet our current needs via our present supplier, the Department of Energy, or DOE. The
current Ac-225 currently supplied to Actinium’s clinical trials from the DOE is derived from the natural decay of thorium-229
from so-called ‘thorium-cows’ and is able to produce sufficient quantities that are several multiples of the amount
of Ac-225 we require to supply our clinical programs through to early commercialization phase. The DOE is also producing Ac-225
from a recently developed alternative route for Ac-225 production via a linear accelerator that is currently being evaluated by
Actinium. Initial preclinical and modelling results have indicated that the linear accelerator sourced Ac-225 does not impact labelling
efficiency and expected distribution. Per representations made by the Department of Energy, the capacity of Ac-225 from this route
is expected to be sufficient to supply all of Actinium’s pipeline and commercial Ac-225 needs and support new program expansion
by not just Actinium but also other companies that are developing Ac-225 based products. Additional routes of Ac-225 production
are being pursued by the DOE including the generation of new thorium cows and production via a cyclotron. The cyclotron production
method for Ac-225 production leverages Actinium’s proprietary technology and know-how and presents an additional path towards
production of high-quality Ac-225 that would be able to satisfy commercial needs. In addition, we are aware of at least six other
government and non-government entities globally including the U.S., Canada, Russia, Belgium, France and Japan that have, or expect
to have ability to supply Ac-225 or equipment for its production within the timeframes relevant to first commercial approval of
our Ac-225 ARC.
Our contract for supply of this isotope
from the DOE must be renewed yearly, and the current contract extends through the end of 2020. While we expect this contract will
be renewed at the end of its term as it has since 2009, there can be no assurance that the DOE will renew the contract or that
change its policies that allow for the sale of isotope to us. Failure to acquire sufficient quantities of medical grade Ac-225
would make it impossible to effectively complete clinical trials and to commercialize any Ac-225 based drug candidates that we
may develop and would materially harm our business.
Our ability to conduct clinical trials to
advance our ARC drug candidates is dependent on our ability to obtain the radioisotopes I-131, Ac-225 and other isotopes we may
choose to utilize in the future. Currently, we are dependent on third party manufacturers and suppliers for our isotopes. These
suppliers may not perform their contracted services or may breach or terminate their agreements with us. Our suppliers are subject
to regulations and standards that are overseen by regulatory and government agencies and we have no control over our suppliers’
compliance to these standards. Failure to comply with regulations and standards may result in their inability to supply isotope
could result in delays in our clinical trials, which could have a negative impact on our business. We have developed intellectual
property, know-how and trade secrets related to the manufacturing process of Ac-225. While we have manufactured medical grade Ac-225
of a purity compared to the cyclotron sourced material in the past, this activity was terminated due to operating cost reasons
and we currently do not have experience in manufacturing medical grade Ac-225 and may not obtain the resources necessary to establish
our own manufacturing capabilities in future. Our inability to build out and establish our own manufacturing facilities would require
us to continue to rely on third party suppliers as we currently do. However, based on our current third-party suppliers and potential
future suppliers of Ac-225 we expect to have adequate isotope supply to support our current ongoing clinical trials, current AWE
program activities and commercialization should our drug candidates receive approval.
If we encounter difficulties enrolling patients in our
clinical trials, our clinical development activities could be delayed or otherwise adversely affected.
The timely completion of clinical trials
in accordance with their protocols depends on our ability to enroll a sufficient number of patients who remain in the trial until
its conclusion. We may experience difficulties in patient enrollment in our clinical trials for a variety of reasons, including:
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the size and nature of the patient population;
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the patient eligibility criteria defined in the protocol;
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the size of the study population required for analysis of the trial’s primary endpoints;
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the proximity of patients to trial sites;
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the design of the trial;
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our ability to recruit clinical trial investigators with the appropriate competencies and expertise;
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competing clinical trials for similar or alternate therapeutic treatments;
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clinician’s
and patients’ perceptions as to the potential advantages and side effects of the product candidate being studied in relation
to other available therapies;
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our ability to obtain and maintain patient consents; and
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the risk that patients enrolled in clinical trials will not complete a clinical trial.
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In addition, refractory patients, which
several of our trials are enrolling, participating in clinical trials are seriously and often terminally ill and therefore may
not complete the clinical trial due to reasons including comorbid conditions or occurrence of adverse medical events related or
unrelated to the investigational products, or death. Even if we are able to enroll a sufficient number of patients in our clinical
trials, delays in patient enrollment will result in increased costs or affect the timing of our planned trials, which could adversely
affect our ability to advance the development of our product candidates.
FDA may take actions that would prolong, delay, suspend,
or terminate clinical trials of our product candidates, which may delay or prevent us from commercializing our product candidates
on a timely basis.
There can be no assurance that the data
generated in our clinical trials will be acceptable to FDA or that if future modifications during the trial are necessary, that
any such modifications will be acceptable to FDA. Certain modifications to a clinical trial protocol made during the course of
the clinical trial have to be submitted to the FDA. This could result in the delay or halt of a clinical trial while the modification
is evaluated. In addition, depending on the quantity and nature of the changes made, FDA could take the position that some or all
of the data generated by the clinical trial is not usable because the same protocol was not used throughout the trial. This might
require the enrollment of additional subjects, which could result in the extension of the clinical trial and the FDA delaying approval
of a product candidate. If the FDA believes that its prior approval is required for a particular modification, it can delay or
halt a clinical trial while it evaluates additional information regarding the change.
Any delay or termination of our current
or future clinical trials as a result of the risks summarized above, including delays in obtaining or maintaining required approvals
from IRBs, delays in patient enrollment, the failure of patients to continue to participate in a clinical trial, and delays or
termination of clinical trials as a result of protocol modifications or adverse events during the trials, may cause an increase
in costs and delays in the filing of any submissions with the FDA, delay the approval and commercialization of our product candidates
or result in the failure of the clinical trial, which could adversely affect our business, operating results and prospects. Lengthy
delays in the completion of our Actimab-A clinical trials would adversely affect our business and prospects and could cause us
to cease operations.
We have obtained orphan drug designation
from FDA for two of our current product candidates and intend to pursue such designation for other candidates and indications in
the future, but we may be unable to obtain such designations or to maintain the benefits associated with any orphan drug designations
we have received or may receive in the future.
We have received orphan
drug designation for Iomab-B and lintuzumab-CD33 ARC for treatment of AML in both the United States and the EU. Under the Orphan
Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, which is a
disease or condition that affects fewer than 200,000 individuals in the United States, or if it affects more than 200,000 individuals
in the United States, there is no reasonable expectation that the cost of developing and making available a drug or biologic for
this type of disease or condition will be recovered from sales in the United States for that drug or biologic. Similarly, the EMA
grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention, or treatment
of a life-threatening or chronically debilitating condition affecting not more than five in 10,000 persons in the EU.
Orphan drug designation
neither shortens the development time or regulatory review time of a drug or biologic nor gives the drug or biologic any advantage
in the regulatory review or approval process. In the United States, orphan drug designation entitles a party to financial incentives,
such as opportunities for grant funding towards clinical trial costs, tax advantages, and application fee waivers. In addition,
if a product candidate receives the first FDA approval for the indication for which it has orphan designation, such product is
entitled, upon approval, to seven years of orphan-drug exclusivity, during which the FDA may not approve any other application
to market the same drug for the same indication, unless a subsequently approved product is clinically superior to orphan drug or
where the manufacturer is unable to assure sufficient product quantity in the applicable patient population. In the EU, orphan
drug designation entitles a party to financial incentives such as reduction of fees or fee waivers and ten years of market exclusivity
following drug or biological product approval. This period may be reduced to six years if the orphan drug designation criteria
are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market
exclusivity.
Even if we obtain (or
have obtained) orphan drug designation for certain product candidates, we may not be the first to obtain marketing approval for
such candidates for the applicable indications due to the uncertainties inherent in the development of novel biologic products.
And, an orphan drug candidate may not receive orphan-drug exclusivity upon approval if such candidate is approved for a use that
is broader than the indication for which it received orphan designation. In addition, exclusive marketing rights in the United
States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer
is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.
Finally, even if we
successfully obtain orphan-drug exclusivity for an orphan drug candidate upon approval, such exclusivity may not effectively protect
the product from competition because (i) different drugs with different active moieties can be approved for the same condition;
and (ii) the FDA or EMA can also subsequently approve a subsequent product with the same active moiety and for the same indication
as the orphan drug if the later-approved drug if deemed clinically superior to the orphan drug.
Even if we receive regulatory approval of our product
candidates, we will be subject to ongoing regulatory obligations and continued regulatory review.
Any regulatory approvals that we receive
for our product candidates will require surveillance to monitor the safety and efficacy of the product candidate. The FDA may also
require a risk evaluation and mitigation strategy in order to approve our product candidates, which could entail requirements for
a medication guide, physician communication plans or additional elements to ensure safe use, such as restricted distribution methods,
patient registries and other risk minimization tools. In addition, if the FDA or a comparable foreign regulatory authority approves
our product candidates, the manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising,
promotion, import, export and recordkeeping for our product candidates will be subject to extensive and ongoing regulatory requirements.
These requirements include submissions of safety and other post-marketing information and reports, registration, as well as continued
compliance with cGMPs and GCPs for any clinical trials that we conduct post-approval. In addition, the FDA could require us to
conduct another study to obtain additional safety or biomarker information. Later discovery of previously unknown problems with
our product candidates, including adverse events of unanticipated severity or frequency, or with our third-party suppliers or manufacturing
processes, or failure to comply with regulatory requirements, may result in, among other things:
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restrictions
on the marketing or manufacturing of our product candidates, withdrawal of the product from the market, or voluntary or mandatory
product recalls;
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fines,
warning letters or holds on clinical trials;
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refusal
by the FDA to approve pending applications or supplements to approved applications filed by us or suspension or revocation of
license approvals;
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product
seizure or detention, or refusal to permit the import or export of our product candidates; and
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injunctions
or the imposition of civil or criminal penalties.
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The FDA’s and other regulatory authorities’
policies may change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval
of our product candidates. We cannot predict the likelihood, nature or extent of government regulation that may arise from future
legislation or administrative action, either in the United States or abroad. If we are slow or unable to adapt to changes in existing
requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose
any marketing approval that we may have obtained, and we may not achieve or sustain profitability.
Coverage and reimbursement may be limited or unavailable
in certain market segments for our product candidates which could limit our sales of our product candidates, if approved.
The commercial success of our product candidates
in both domestic and international markets will be substantially dependent on whether third-party coverage and reimbursement is
available for patients that use our products. However, the availability of insurance coverage and reimbursement for newly approved
cancer therapies is uncertain, and therefore, third-party coverage may be particularly difficult to obtain even if our products
are approved by the FDA as safe and efficacious. Patients using existing approved therapies are generally reimbursed all or part
of the product cost by Medicare or other third-party payors. Medicare, Medicaid, health maintenance organizations and other third-party
payors are increasingly attempting to contain healthcare costs by limiting both coverage and the level of reimbursement of new
drugs, and, as a result, they may not cover or provide adequate payment for these products. Submission of applications for reimbursement
approval generally does not occur prior to the filing of a BLA for that product and may not be granted until many months after
BLA approval. In order to obtain coverage and reimbursement for these products, we or our commercialization partners may have to
agree to a net sales price lower than the net sales price we might charge in other sales channels. The continuing efforts of government
and third-party payors to contain or reduce the costs of healthcare may limit our revenue. Initial dependence on the commercial
success of our products may make our revenues particularly susceptible to any cost containment or reduction efforts.
Healthcare legislative reform measures
intended to increase pressure to reduce prices of pharmaceutical products paid for by Medicare or, otherwise, affect the federal
regulation of the U.S. healthcare system could have a material adverse effect our business, future revenue, if any, and results
of operations.
In the United States,
the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, also called the MMA, changed the way Medicare covers
and pays for pharmaceutical products. The legislation expanded Medicare coverage for drug purchases by the elderly and introduced
a new reimbursement methodology based on average sales prices for physician-administered drugs. In addition, this legislation provided
authority for limiting the number of drugs that will be covered in any therapeutic class. As a result of this legislation and the
expansion of federal coverage of drug products, we expect that there will be additional pressure to reduce costs. These cost reduction
initiatives and other provisions of this legislation could decrease the scope of coverage and the price that we receive for any
approved products and could harm our business. While the MMA applies only to drug benefits for Medicare beneficiaries, private
payors often follow Medicare coverage policies and payment limitations in setting their own reimbursement rates, and any reduction
in reimbursement that results from the MMA may cause a similar reduction in payments from private payors. This legislation may
pose an even greater risk to our drug candidates as a significant portion of the target patient population for our drug candidates
would likely be over 65 years of age and, therefore, many such patients will be covered by Medicare.
On March 23, 2010,
President Obama signed the “Patient Protection and Affordable Care Act” (P.L. 111-148) and on March 30, 2010, the signed
the “Health Care and Education Reconciliation Act” (P.L. 111-152) (collectively, the “Healthcare Reform Law”).
The Healthcare Reform Law included a number of new rules regarding health insurance, the provision of healthcare, conditions to
reimbursement for healthcare services provided to Medicare and Medicaid patients, and other healthcare policy reforms. Through
the law-making process, substantial changes have been and continue to be made to the current system for paying for healthcare in
the U.S., including changes made to extend medical benefits to certain Americans who lacked insurance coverage and to contain or
reduce healthcare costs (such as by reducing or conditioning reimbursement amounts for healthcare services and drugs, and imposing
additional taxes, fees, and rebate obligations on pharmaceutical and medical device companies). This legislation was one of the
most comprehensive and significant reforms ever experienced by the U.S. in the healthcare industry and has significantly changed
the way healthcare is financed by both governmental and private insurers. This legislation has impacted the scope of healthcare
insurance and incentives for consumers and insurance companies, among others. Additionally, the Healthcare Reform Law’s
provisions were designed to encourage providers to find cost savings in their clinical operations. Pharmaceuticals represent a
significant portion of the cost of providing care. This environment has caused changes in the purchasing habits of consumers and
providers and resulted in specific attention to the pricing negotiation, product selection and utilization review surrounding pharmaceuticals.
This attention may result in our current commercial products, products we may commercialize or promote in the future, and our therapeutic
candidates, being chosen less frequently or the pricing being substantially lowered. At this stage, it is difficult to estimate
the full extent of the direct or indirect impact of the Healthcare Reform Law on us.
These structural changes
could entail further modifications to the existing system of private payors and government programs (such as Medicare, Medicaid,
and the State Children’s Health Insurance Program), creation of government-sponsored healthcare insurance sources, or some
combination of both, as well as other changes. Restructuring the coverage of medical care in the U.S. could impact the reimbursement
for prescribed drugs and pharmaceuticals, including our current commercial products, those we and our development or commercialization
partners are currently developing or those that we may commercialize or promote in the future. If reimbursement for the products
we currently commercialize or promote, any product we may commercialize or promote, or approved therapeutic candidates is substantially
reduced or otherwise adversely affected in the future, or rebate obligations associated with them are substantially increased,
it could have a material adverse effect on our reputation, business, financial condition or results of operations.
Extending medical benefits
to those who currently lack coverage will likely result in substantial costs to the U.S. federal government, which may force significant
additional changes to the healthcare system in the U.S. Much of the funding for expanded healthcare coverage may be sought through
cost savings. While some of these savings may come from realizing greater efficiencies in delivering care, improving the effectiveness
of preventive care and enhancing the overall quality of care, much of the cost savings may come from reducing the cost of care
and increased enforcement activities. Cost of care could be reduced further by decreasing the level of reimbursement for medical
services or products (including our current commercial products, our development or commercialization partners or any product we
may commercialize or promote, or those therapeutic candidates currently being developed by us), or by restricting coverage (and,
thereby, utilization) of medical services or products. In either case, a reduction in the utilization of, or reimbursement for
our current commercial products, any product we may commercialize or promote, or any therapeutic candidate, or for which we receive
marketing approval in the future, could have a material adverse effect on our reputation, business, financial condition or results
of operations.
Several states and
private entities initially mounted legal challenges to the Healthcare Reform Law, and they continue to litigate various aspects
of the legislation. On July 26, 2012, the U.S. Supreme Court generally upheld the provisions of the Healthcare Reform Law at issue
as constitutional. However, the U.S. Supreme Court held that the legislation improperly required the states to expand their Medicaid
programs to cover more individuals. As a result, the states have a choice as to whether they will expand the number of individuals
covered by their respective state Medicaid programs. Some states have not expanded their Medicaid programs and have chosen to develop
other cost-saving and coverage measures to provide care to currently uninsured individuals. Many of these efforts to date have
included the institution of Medicaid-managed care programs. The manner in which these cost-saving and coverage measures are implemented
could have a material adverse effect on our reputation, business, financial condition or results of operations.
Further, the healthcare
regulatory environment has seen significant changes in recent years and is still in flux. Legislative initiatives to modify,
limit, replace, or repeal the Healthcare Reform Law and judicial challenges continue, and may increase in light of the current
administration and legislative environment. We cannot predict the impact on our business of future legislative and legal challenges
to the Healthcare Reform Law or other changes to the current laws and regulations. The financial impact of U.S. healthcare reform
legislation over the next few years will depend on a number of factors, including the policies reflected in implementing regulations
and guidance and changes in sales volumes for therapeutics affected by the legislation. From time to time, legislation is drafted,
introduced and passed in the U.S. Congress that could significantly change the statutory provisions governing coverage, reimbursement,
and marketing of pharmaceutical products. In addition, third-party payor coverage and reimbursement policies are often revised
or interpreted in ways that may significantly affect our business and our products.
Since taking office,
President Trump has continued to support the repeal of all or portions of the Healthcare Reform Law. President Trump has also issued
an executive order in which he stated that it is his administration’s policy to seek the prompt repeal of the Healthcare
Reform Law and in which he directed executive departments and federal agencies to waive, defer, grant exemptions from, or delay
the implementation of the provisions of the Healthcare Reform Law to the maximum extent permitted by law. Congress has enacted
legislation that repeals certain portions of the Healthcare Reform Law, including but not limited to the Tax Cuts and Jobs Act,
passed in December 2017, which included a provision that eliminates the penalty under the Healthcare Reform Law’s individual
mandate, effective January 1, 2019, as well as the Bipartisan Budget Act of 2018, passed in February 2018, which, among other things,
repealed the Independent Payment Advisory Board (which was established by the Healthcare Reform Law and was intended to reduce
the rate of growth in Medicare spending).
Additionally, in December
2018, a district court in Texas held that the individual mandate is unconstitutional and that the rest of the Affordable Care
Act is, therefore, invalid. On appeal, the Fifth Circuit Court of Appeals affirmed the holding on the individual mandate but remanded
the case back to the lower court to reassess whether and how such holding affects the validity of the rest of the Affordable Care
Act. Substantial uncertainty remains as to the future of the Affordable Care Act after the U.S. Supreme Court declined to expedite
its review of the Fifth Circuit’s holding on January 21, 2020. It is, thus, unlikely that these issues will be resolved
before the next presidential election in November 2020. The current administration may seek to pass additional reform measures
before the upcoming election. We cannot predict the outcome of the election, nor can we predict the healthcare-reform-related
initiatives that the newly elected (or re-elected, as applicable) administration will put forth thereafter. There is no way to
know whether, and to what extent, if any, the Affordable Care Act will remain in-effect in the future, and it is unclear how judicial
decisions, subsequent appeals, election-related measures, or other efforts to repeal and replace or, possibly, to restore the
Affordable Care Act will impact the U.S. healthcare industry or our business.
Risks
Related to Third Parties
We
rely on third parties to conduct our clinical trials. If these third parties do not successfully carry out their contractual duties
or meet expected deadlines or comply with regulatory requirements, we may not be able to obtain regulatory approval for or commercialize
our product candidates.
We
do not have the ability to independently conduct our pre-clinical and clinical trials for our product candidates and we must rely
on third parties, such as contract research organizations, medical institutions, clinical investigators and contract laboratories
to conduct such trials. Our reliance on these third parties for clinical development activities results in reduced control over
these activities. Moreover, the FDA requires us to comply with regulations and standards, commonly referred to as GCPs (good clinical
practices), for conducting, recording and reporting the results of clinical trials to assure that data and reported results are
credible and accurate and that the trial participants are adequately protected. Our reliance on third parties does not relieve
us of these responsibilities and requirements. If we or any of our third-party contractors fail to comply with applicable GCPs,
the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities
may require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that upon
inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical trials complies
with GCP regulations. In addition, our clinical trials must be conducted with product produced under current good manufacturing
practice, or cGMP, regulations. Our failure to comply with these regulations may require us to repeat clinical trials, which would
delay the regulatory approval process.
If
our consultants, contract research organizations and other similar entities with which we are working do not successfully carry
out their contractual duties, meet expected deadlines, or comply with applicable regulations, we may be required to replace them.
Although we believe that there are a number of other third-party contractors, we could engage to continue these activities, we
may not be able to enter into arrangements with alternative third-party contractors or to do so on commercially reasonable terms,
which may result in a delay of our planned clinical trials and delayed development of our product candidates.
In
addition, our third-party contractors are not our employees, and except for remedies available to us under our agreements with
such third-party contractors, we cannot control whether or not they devote sufficient time and resources to our programs. If these
third parties do not successfully carry out their contractual duties or regulatory obligations or meet expected deadlines, or
if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory
requirements or for other reasons, our pre-clinical development activities or clinical trials may be extended, delayed, suspended
or terminated, and we may not be able to obtain regulatory approval for, or successfully commercialize, our product candidates
on a timely basis, if at all, and our business, operating results and prospects would be adversely affected.
The
antibodies we use in our antibody radiation-conjugate product candidates may be subject to generic competition.
We
are not aware of any existing or pending regulations or legislation that pertains to generic radiopharmaceutical products such
as our antibody radiation-conjugate product candidates. Our product candidates are regulated by the FDA as biologic products and
we intend to seek approval for these products pursuant to the BLA pathway. The Biologics Price Competition and Innovation Act
of 2009, or BPCIA, created an abbreviated pathway for the approval of biosimilar and interchangeable biologic products. The abbreviated
regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible
designation of a biosimilar as “interchangeable” based on its similarity to an existing brand product. Under the BPCIA,
an application for a biosimilar product cannot be approved by the FDA until 12 years after the original branded product was approved
under a BLA. The law is complex and is still being interpreted and implemented by the FDA. As a result, its ultimate impact, implementation,
and meaning are subject to uncertainty. Even if a biosimilar gets approved for one of the antibodies that we use, the final constructs
of our drug candidates consist of an antibody, radioisotope and in some cases a linker. Therefore, we do not believe that the
final drug product of our candidates can be subject to competition from a biosimilar as outlined in BPCIA.
Our
product candidates may never achieve market acceptance.
Iomab-B,
CD33 ARC program candidates and future product candidates that we may develop may never gain market acceptance among physicians,
patients and the medical community. The degree of market acceptance of any of our products will depend on a number of factors,
including the actual and perceived effectiveness and reliability of the product; the results of any long-term clinical trials
relating to use of the product; the availability, relative cost and perceived advantages and disadvantages of alternative technologies;
the degree to which treatments using the product are approved for reimbursement by public and private insurers; the strength of
our marketing and distribution infrastructure; and the level of education and awareness among physicians and hospitals concerning
the product.
We
believe that oncologists and other physicians will not widely adopt a product candidate unless they determine, based on experience,
clinical data, and published peer-reviewed journal articles, that the use of that product candidate provides an effective alternative
to other means of treating specific cancers. Patient studies or clinical experience may indicate that treatment with our product
candidates does not provide patients with sufficient benefits in extension of life or quality of life. We believe that recommendations
and support for the use of each product candidate from influential physicians will be essential for widespread market acceptance.
Our product candidates are still in the development stage and it is premature to attempt to gain support from physicians at this
time. We can provide no assurance that such support will ever be obtained. If our product candidates do not receive such support
from these physicians and from long-term data, physicians may not use or continue to use, and hospitals may not purchase or continue
to purchase, them.
Failure
of Iomab-B, CD33 ARC program candidates or any of our other product candidates to significantly penetrate current or new markets
would negatively impact our business financial condition and results of operations.
We
may be subject to claims that our third-party service providers, consultants or current or former employees have wrongfully used
or disclosed confidential information of third parties.
We
have received confidential and proprietary information from third parties. In addition, we employ individuals who were previously
employed at other biotechnology or pharmaceutical companies. We may be subject to claims that we or our employees, consultants
or independent contractors have inadvertently or otherwise used or disclosed confidential information of these third parties or
our employees’ former employers. Litigation may be necessary to defend against these claims. Even if we are successful in
defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees.
We
currently depend on a single third-party manufacturer to produce our pre-clinical and clinical trial drug supplies. Any disruption
in the operations of our current third-party manufacturer, or other third-party manufacturers we may engage in the future, could
adversely affect our business and results of operations.
We
do not currently operate manufacturing facilities for pre-clinical or clinical production of any of our product candidates. We
rely on third-party manufacturers to supply, store, and distribute pre-clinical and clinical supply of the components of our drug
product candidates including monoclonal antibodies, linkers and radioisotopes, as well as the final construct which comprises
our drug product candidates. We expect to continue to depend on third-party manufacturers for the foreseeable future. Any performance
failure on the part of our existing or future manufacturers could delay clinical development, cause us to suspend or terminate
development or delay or prohibit regulatory approval of our product candidates or commercialization of any approved products.
Further avenues of disruption to our clinical or eventual commercial supply may also occur due to the sale, acquisition, business
reprioritization, bankruptcy or other unforeseen circumstances that might occur at any of our suppliers or contract manufacturing
partners including an inability to come to terms on renewal of existing contracts or new contracts.
We currently rely on single manufacturers to
manufacture our pre-clinical and clinical trial drug supplies. With a view to maintaining business continuity we are evaluating
alternatives and second and even third sources of supply or manufacturing for our core suppliers and manufacturing partners, however
there can be no assurances that we will be able to identify such suppliers or partners and assuming we did, that we would be able
to enter into contracts that are on favorable terms or on terms that will enable sufficient supply to ensure business continuity
and support our growth plans.
Our
product candidates require precise, high-quality manufacturing. Failure by our current contract manufacturer or other third-party
manufacturers we may engage in the future to achieve and maintain high manufacturing standards could result in patient injury
or death, product recalls or withdrawals, delays or failures in testing or delivery, cost overruns, or other problems that could
seriously hurt our business. Contract manufacturers may encounter difficulties involving production yields, quality control, and
quality assurance. These manufacturers are subject to ongoing periodic and unannounced inspections by the FDA and corresponding
state and foreign agencies to ensure strict compliance with cGMPs and other applicable government regulations and corresponding
foreign standards; we do not have control over third-party manufacturers’ compliance with these regulations and standards.
We
depend on vendors with specialized operations, equipment and know-how to manufacture the respective components of our drug candidates.
We have entered into manufacturing and supply agreements with these third-parties, and in some instances, we have agreed that
such vendor be the exclusive manufacturer and supplier. If any of the third-parties we depend on encounter difficulties in their
operations, fail to comply with required regulations or breach their contractual obligations it may be difficult, or we may be
unable to identify suitable alternative third-party manufacturers. While we identify and evaluate third-party manufacturers from
time to time, even if we do identify suitable alternative third-parties, we may fail to reach agreement on contractual terms,
it may be prohibitively expensive and there can be no assurance that we can successfully complete technology transfer and development
work necessary or complete the necessary work in a timely manner. Any of which could prevent us from commencing manufacturing
with third-parties. which could cause delays or suspension of our clinical trials and pre-clinical work that may have a negative
impact on our business.
Furthermore,
these third-party contractors, whether foreign or domestic, may experience regulatory compliance difficulty, mechanical shut downs,
employee strikes, or any other unforeseeable acts that may delay or limit production. Our inability to adequately establish, supervise
and conduct (either ourselves or through third parties) all aspects of the formulation and manufacturing processes, and the inability
of third-party manufacturers to consistently supply quality product when required would have a material adverse effect on our
ability to develop or commercialize our products. We have faced delays and risks associated with reliance on key third party manufacturers
in the past and may be faced with such delays and risks in the future. Any future manufacturing interruptions or related supply
issues could have an adverse effect on our company, including delays in clinical trials.
If
we are successful in obtaining marketing approval from the FDA and/or other regulatory agencies for any of our product candidates,
we anticipate continued reliance on third-party manufacturers.
To
date, our product candidates have been manufactured in small quantities for preclinical and clinical testing by third-party manufacturers.
If the FDA or other regulatory agencies approve any of our product candidates for commercial sale, we expect that we would continue
to rely, at least initially, on third-party specialized manufacturers to produce commercial quantities of approved products. These
manufacturers may not be able to successfully increase the manufacturing capacity for any approved product in a timely or economic
manner, or at all. Significant scale-up of manufacturing may require additional validation studies, which the FDA must review
and approve. If third party manufacturers are unable to successfully increase the manufacturing capacity for a product candidate,
or we are unable to establish our own manufacturing capabilities, the commercial launch of any approved products may be delayed
or there may be a shortage in supply, which in turn could have a material adverse effect on our business.
In
addition, the facilities used by our contract manufacturers to manufacture our product candidates must be approved by the FDA
pursuant to inspections that will be conducted after we submit a BLA to the FDA. We do not control the manufacturing process of,
and are completely dependent on, our contract manufacturing partners for compliance with cGMPs. If our contract manufacturers
cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA
or other regulatory authorities, they will not be able to secure and/or maintain regulatory approval for their manufacturing facilities.
If the FDA or a comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates
or if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would significantly
impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
We
may have conflicts with our partners that could delay or prevent the development or commercialization of our product candidates.
We
may have conflicts with our partners, such as conflicts concerning the interpretation of preclinical or clinical data, the achievement
of milestones, the interpretation of contractual obligations, payments for services, development obligations or the ownership
of intellectual property developed during our collaboration. If any conflicts arise with any of our partners, such partner may
act in a manner that is averse to our best interests. Any such disagreement could result in one or more of the following, each
of which could delay or prevent the development or commercialization of our product candidates, and in turn prevent us from generating
revenues: unwillingness on the part of a partner to pay us milestone payments or royalties we believe are due under a collaboration;
uncertainty regarding ownership of intellectual property rights arising from our collaborative activities, which could prevent
us from entering into additional collaborations; unwillingness by the partner to cooperate in the development or manufacture of
the product, including providing us with product data or materials; unwillingness on the part of a partner to keep us informed
regarding the progress of its development and commercialization activities or to permit public disclosure of the results of those
activities; initiating litigation or alternative dispute resolution options by either party to resolve the dispute; or attempts
by either party to terminate the agreement.
We
face significant competition from other biotechnology and pharmaceutical companies.
Our
product candidates face, and will continue to face, intense competition from large pharmaceutical companies, as well as academic
and research institutions. We compete in an industry that is characterized by (i) rapid technological change, (ii) evolving industry
standards, (iii) emerging competition and (iv) new product introductions. Our competitors have existing products and technologies
that will compete with our product candidates and technologies and may develop and commercialize additional products and technologies
that will compete with our product candidates and technologies. Because several competing companies and institutions have greater
financial resources than us, they may be able to (i) provide broader services and product lines, (ii) make greater investments
in research and development, or R&D, and (iii) carry on broader R&D initiatives. Our competitors also have greater development
capabilities than we do and have substantially greater experience in undertaking preclinical and clinical testing of product candidates,
obtaining regulatory approvals, and manufacturing and marketing pharmaceutical products. They also have greater name recognition
and better access to customers than us.
Our
product candidates may cause undesirable side effects or have other properties that could halt their clinical development, prevent
their regulatory approval, limit their commercial potential, or result in significant negative consequences
Undesirable
side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials
and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other comparable foreign
authorities. The drug-related side effects could affect patient recruitment or the ability of enrolled patients to complete the
trial or result in potential product liability claims. Any of these occurrences may harm our business, financial condition and
prospects significantly. Even if any of our product candidates receives marketing approval, as greater numbers of patients use
a product following its approval, an increase in the incidence of side effects or the incidence of other post-approval problems
that were not seen or anticipated during pre-approval clinical trials could result in a number of potentially significant negative
consequences, including:
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regulatory
authorities may withdraw their approval of the product;
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regulatory
authorities may require the addition of labeling statements, such as warnings or contraindications;
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we
may be required to change the way the product is administered, conduct additional clinical trials or change the labeling of
the product;
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we
may elect, or we may be required, to recall or withdraw product from the market;
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we
could be sued and held liable for harm caused to patients; and
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our
reputation may suffer.
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Any
of these events could substantially increase the costs and expenses of developing, commercializing and marketing any such product
candidates or could harm or prevent sales of any approved products.
Risks
Related to Our Intellectual Property
We
depend upon securing and protecting critical intellectual property.
We
are dependent on obtaining and maintaining patents, trade secrets, copyright and trademark protection of our technologies in the
United States and other jurisdictions, as well as successfully enforcing this intellectual property and defending this intellectual
property against third-party challenges. The degree of future protection of our proprietary rights is uncertain for product candidates
that are currently in the early stages of development because we cannot predict which of these product candidates will ultimately
reach the commercial market or whether the commercial versions of these product candidates will incorporate proprietary technologies.
Our
patent position is highly uncertain and involves complex legal and factual questions.
Accordingly,
we cannot predict the breadth of claims that may be allowed or enforced under our patents or in third-party patents. For example,
we or our licensors might not have been the first to make the inventions covered by each of our pending patent applications and
issued patents; we or our licensors might not have been the first to file patent applications for these inventions; others may
independently develop similar or alternative technologies or duplicate any of our technologies; it is possible that none of our
pending patent applications or the pending patent applications of our licensors will result in issued patents; our issued patents
and issued patents of our licensors may not provide a basis for commercially viable technologies, or may not provide us with any
competitive advantages, or may be challenged and invalidated by third parties; and, we may not develop additional proprietary
technologies that are patentable.
As
a result, our owned and licensed patents may not be valid, and we may not be able to obtain and enforce patents and to maintain
trade secret protection for the full commercial extent of our technology. The extent to which we are unable to do so could materially
harm our business.
We
or our licensors have applied for and will continue to apply for patents for certain products. Such applications may not result
in the issuance of any patents, and any patents now held or that may be issued may not provide us with adequate protection from
competition. Furthermore, it is possible that patents issued or licensed to us may be challenged successfully. In that event,
if we have a preferred competitive position because of such patents, such preferred position would be lost. If we are unable to
secure or to continue to maintain a preferred position, we could become subject to competition from the sale of generic products.
Failure to receive, inability to protect, or expiration of our patents for medical use, manufacture, conjugation and labeling
of Ac-225, the antibodies that we license from third parties, or subsequent related filings, would adversely affect our business
and operations.
Patents
issued or licensed to us may be infringed by the products or processes of others. The cost of enforcing our patent rights against
infringers, if such enforcement is required, could be significant, and we do not currently have the financial resources to fund
such litigation. Further, such litigation can go on for years and the time demands could interfere with our normal operations.
There has been substantial litigation and other proceedings regarding patent and other intellectual property rights in the pharmaceutical
industry. We may become a party to patent litigation and other proceedings. The cost to us of any patent litigation, even if resolved
in our favor, could be substantial. Some of our competitors may be able to sustain the costs of such litigation more effectively
than we can because of their substantially greater financial resources. Litigation may also absorb significant management time.
Unpatented
trade secrets, improvements, confidential know-how and continuing technological innovation are important to our scientific and
commercial success. Although we attempt to and will continue to attempt to protect our proprietary information through reliance
on trade secret laws and the use of confidentiality agreements with our partners, collaborators, employees and consultants and
other appropriate means, these measures may not effectively prevent disclosure of our proprietary information, and, in any event,
others may develop independently, or obtain access to, the same or similar information.
Certain
of our patent rights are licensed to us by third parties. If we fail to comply with the terms of these license agreements, our
rights to those patents may be terminated, and we will be unable to conduct our business.
If
we are found to be infringing on patents or trade secrets owned by others, we may be forced to cease or alter our product development
efforts, obtain a license to continue the development or sale of our products, and/or pay damages.
Our
manufacturing processes and potential products may violate proprietary rights of patents that have been or may be granted to competitors,
universities or others, or the trade secrets of those persons and entities. As the pharmaceutical industry expands and more patents
are issued, the risk increases that our processes and potential products may give rise to claims that they infringe the patents
or trade secrets of others. These other persons could bring legal actions against us claiming damages and seeking to enjoin clinical
testing, manufacturing and marketing of the affected product or process. If any of these actions are successful, in addition to
any potential liability for damages, we could be required to obtain a license in order to continue to conduct clinical tests,
manufacture or market the affected product or use the affected process. Required licenses may not be available on acceptable terms,
if at all, and the results of litigation are uncertain. If we become involved in litigation or other proceedings, it could consume
a substantial portion of our financial resources and the efforts of our personnel.
Our
ability to protect and enforce our patents does not guarantee that we will secure the right to commercialize our patents.
A
patent is a limited monopoly right conferred upon an inventor, and his successors in title, in return for the making and disclosing
of a new and non-obvious invention. This monopoly is of limited duration but, while in force, allows the patent holder to prevent
others from making and/or using its invention. While a patent gives the holder this right to exclude others, it is not a license
to commercialize the invention where other permissions may be required for commercialization to occur. For example, a drug cannot
be marketed without the appropriate authorization from the FDA, regardless of the existence of a patent covering the product.
Further, the invention, even if patented itself, cannot be commercialized if it infringes the valid patent rights of another party.
We
rely on confidentiality agreements to protect our trade secrets. If these agreements are breached by our employees or other parties,
our trade secrets may become known to our competitors.
We
rely on trade secrets that we seek to protect through confidentiality agreements with our employees and other parties. If these
agreements are breached, our competitors may obtain and use our trade secrets to gain a competitive advantage over us. We may
not have any remedies against our competitors and any remedies that may be available to us may not be adequate to protect our
business or compensate us for the damaging disclosure. In addition, we may have to expend resources to protect our interests from
possible infringement by others.
The
use of hazardous materials, including radioactive and biological materials, in our research and development efforts imposes certain
compliance costs on us and may subject us to liability for claims arising from the use or misuse of these materials.
Our
research, development and manufacturing activities involve the controlled use of hazardous materials, including chemicals, radioactive
and biological materials, such as radioactive isotopes. We are subject to federal, state, local and foreign environmental laws
and regulations governing, among other matters, the handling, storage, use and disposal of these materials and some waste products.
We cannot completely eliminate the risk of contamination or injury from these materials and we could be held liable for any damages
that result, which could exceed our financial resources. We currently maintain insurance coverage for injuries resulting from
the hazardous materials we use; however, future claims may exceed the amount of our coverage. Also, we do not have insurance coverage
for pollution cleanup and removal. Currently the costs of complying with such federal, state, local and foreign environmental
regulations are not significant, and consist primarily of waste disposal expenses. However, they could become expensive, and current
or future environmental laws or regulations may impair our research, development, production and commercialization efforts.
We
may undertake international operations, which will subject us to risks inherent with operations outside of the United States.
Although
we do not have any international operations at this time, we intend to seek market clearances in foreign markets that we believe
will generate significant opportunities. However, even with the cooperating of a commercialization partner, conducting drug development
in foreign countries involves inherent risks, including, but not limited to difficulties in staffing, funding and managing foreign
operations; unexpected changes in regulatory requirements; export restrictions; tariffs and other trade barriers; difficulties
in protecting, acquiring, enforcing and litigating intellectual property rights; fluctuations in currency exchange rates; and
potentially adverse tax consequences.
If
we were to experience any of the difficulties listed above, or any other difficulties, any international development activities
and our overall financial condition may suffer and cause us to reduce or discontinue our international development and registration
efforts.
We
are highly dependent on our key personnel, and if we are not successful in attracting and retaining highly qualified personnel,
we may not be able to successfully implement our business strategy.
Our
future operations and successes depend in large part upon the continued service of key members of our senior management team whom
we are highly dependent upon to manage our business. If any member of our current senior management terminates his employment
with us and we are unable to find a suitable replacement quickly, the departure could have a material adverse effect on our business.
Our
future success also depends on our ability to identify, attract, hire or engage, retain and motivate other well-qualified managerial,
technical, clinical and regulatory personnel. There can be no assurance that such professionals will be available in the market,
or that we will be able to retain existing professionals or meet or continue to meet their compensation requirements. Furthermore,
the cost base in relation to such compensation, which may include equity compensation, may increase significantly, which could
have a material adverse effect on us. Failure to establish and maintain an effective management team and workforce could adversely
affect our ability to operate, grow and manage our business.
Managing
our growth as we expand operations may strain our resources.
We
expect to need to grow rapidly in order to support additional, larger, and potentially international, pivotal clinical trials
of our product candidates, which will place a significant strain on our financial, managerial and operational resources. In order
to achieve and manage growth effectively, we must continue to improve and expand our operational and financial management capabilities.
Moreover, we will need to increase staffing and to train, motivate and manage our employees. All of these activities will increase
our expenses and may require us to raise additional capital sooner than expected. Failure to manage growth effectively could materially
harm our business, financial condition or results of operations.
We
may expand our business through the acquisition of rights to new product candidates that could disrupt our business, harm our
financial condition and may also dilute current stockholders’ ownership interests in our company.
Our
business strategy includes expanding our products and capabilities, and we may seek acquisitions of product candidates, antibodies
or technologies to do so. Acquisitions involve numerous risks, including substantial cash expenditures; potentially dilutive issuance
of equity securities; incurrence of debt and contingent liabilities, some of which may be difficult or impossible to identify
at the time of acquisition; difficulties in assimilating acquired technologies or the operations of the acquired companies; diverting
our management’s attention away from other business concerns; risks of entering markets in which we have limited or no direct
experience; and the potential loss of our key employees or key employees of the acquired companies.
We
can make no assurances that any acquisition will result in short-term or long-term benefits to us. We may incorrectly judge the
value or worth of an acquired product, company or business. In addition, our future success would depend in part on our ability
to manage the rapid growth associated with some of these acquisitions. We cannot assure that we will be able to make the combination
of our business with that of acquired products, businesses or companies work or be successful. Furthermore, the development or
expansion of our business or any acquired products, business or companies may require a substantial capital investment by us.
We may not have these necessary funds, or they might not be available to us on acceptable terms or at all. We may also seek to
raise funds by selling shares of our preferred or common stock, which could dilute each current stockholder’s ownership
interest in the Company.
Risks
Related to Ownership of Our Common Stock
The
sale of securities by us in any equity or debt financing could result in dilution to our existing stockholders and have a material
adverse effect on our earnings.
We
have financed our operations primarily through sales of stock and warrants. It is likely that during the next twelve months we
will seek to raise additional capital through the sales of stock and warrants in order to expand our level of operations to continue
our research and development efforts.
Any
sale of common stock by us in a future offering could result in dilution to our existing stockholders as a direct result of our
issuance of additional shares of our capital stock. In addition, our business strategy may include expansion through internal
growth or by establishing strategic relationships with targeted customers and vendors. In order to do so, or to finance the cost
of our other activities, we may issue additional equity securities that could dilute our stockholders’ stock ownership.
We may also assume additional debt and incur impairment losses related to goodwill and other tangible assets if we acquire another
company and this could negatively impact our earnings and results of operations.
We received a deficiency notice
from NYSE American. We may be required to effectuate a reverse stock split to be able to maintain compliance with applicable listing
requirements or standards of the NYSE American. If we are unable to cure this deficiency and meet the NYSE American continued
listing requirements, we could be delisted from NYSE American, which would negatively impact the trading of our common stock.
On April 29, 2020,
we received a deficiency letter from the NYSE American, indicating that we are not in compliance with certain NYSE American continued
listing standards. The deficiency letter states that our shares of common stock have been selling for a low price per share for
a substantial period of time. Pursuant to Section 1003(f)(v) of the Company Guide, the NYSE American staff determined that our
continued listing is predicated on us effecting a reverse stock split of our common stock or otherwise demonstrating sustained
price improvement within a reasonable period of time, which the staff determined to be until October 29, 2020. In addition, the
NYSE American has advised us that its policy is to immediately suspend trading in shares of, and commence delisting procedures
with respect to, a listed company if the market price of its shares falls below $0.06 per share at any time during the trading
day.
We may be required to effect a reverse
split to maintain compliance with NYSE American listing standards. On October 18, 2019, our board of directors unanimously approved,
subject to stockholder approval, an amendment to our certificate of incorporation to effect a reverse stock split of our outstanding
common stock by combining outstanding shares of common stock into a lesser number of outstanding shares of common stock by a ratio
of not more than 1-for-75 prior to December 18, 2020, with the exact ratio to be set within this range by our board of directors
at its sole discretion. On December 18, 2019, at our 2019 Annual Meeting of Stockholders, our stockholders approved such proposed
amendment to our certificate of incorporation. The primary intent of effecting the reverse stock split, if our board of directors
determines to do so, would be to ensure that we are able to maintain compliance with the listing standards of the NYSE American.
If we implement a reverse stock split, although
we expect that a reverse stock split will result in an increase in the market price of our common stock, such reverse stock split
may not result in a permanent increase in the market price of our common stock, which is dependent on many factors, including general
economic, market and industry conditions and other factors detailed from time to time in the reports we file with the Securities
and Exchange Commission. There can be no assurance that the market price per new share of our common stock after the reverse stock
split will remain unchanged or increase in proportion to the reduction in the number of old shares of our common stock outstanding
before the reverse stock split.
If our common stock is delisted by NYSE
American, our common stock may be eligible for quotation on an over-the-counter quotation system or on the pink sheets. Upon any
such delisting, our common stock would become subject to the regulations of the Securities and Exchange Commission relating to
the market for penny stocks. The regulations applicable to penny stocks may severely affect the market liquidity for our common
stock and could limit the ability of stockholders to sell securities in the secondary market. In such a case, an investor may find
it more difficult to dispose of or obtain accurate quotations as to the market value of our common stock, and there can be no assurance
that our common stock will be eligible for trading or quotation on any alternative exchanges or markets.
Delisting from NYSE American could adversely affect our ability
to raise additional financing through public or private sales of equity securities, would significantly affect the ability of investors
to trade our securities and would negatively affect the value and liquidity of our common stock. Delisting could also have other
negative results, including the potential loss of confidence by employees, the loss of institutional investor interest and fewer
business development opportunities.
Our common stock is subject to price volatility which
could lead to losses by stockholders and potential costly security litigation.
The trading volume of our common stock
has been and may continue to be extremely limited and sporadic. We expect the market price of our common stock to fluctuate substantially
due to a variety of factors, including market perception of our ability to achieve our planned growth, quarterly operating results
of other companies in the same industry, trading volume in our common stock, changes in general conditions in the economy and
the financial markets or other developments affecting our competitors or us. This volatility has had a significant effect on the
market price of securities issued by many companies for reasons unrelated to their operating performance and could have the same
effect on our common stock.
The trading price of our common stock may
be highly volatile and could fluctuate in response to factors such as:
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actual or anticipated variations in our operating
results;
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announcements of developments by us or our competitors;
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the timing of IND and/or BLA approval, the completion
and/or results of our clinical trials;
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regulatory actions regarding our products;
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announcements by us or our competitors of significant
acquisitions, strategic partnerships, joint ventures or capital commitments;
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adoption of new accounting standards affecting
our industry;
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additions or departures of key personnel;
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introduction of new products by us or our competitors;
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sales of our common stock or other securities
in the open market; and
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other events or factors, many of which are beyond
our control.
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The stock market is subject to significant
price and volume fluctuations. Moreover, the COVID-19 pandemic has resulted in significant financial market volatility and uncertainty
in recent months. In the past, following periods of volatility in the market price of a company’s securities, securities
class action litigation has often been initiated against such a company. Litigation initiated against us, whether or not successful,
could result in substantial costs and diversion of our management’s attention and our resources, which could harm our business
and financial condition.
We do not intend to pay dividends
on our common stock, so any returns will be determined by the value of our common stock.
We have never declared
or paid any cash dividends on our common stock. For the foreseeable future, it is expected that earnings, if any, generated from
our operations will be used to finance the growth of our business, and that no dividends will be paid to holders of our common
stock. As a result, the success of an investment in our common stock will depend upon any future appreciation in its value. There
is no guarantee that our common stock will appreciate in value.
Certain provisions of our Certificate
of Incorporation and Bylaws and Delaware law make it more difficult for a third party to acquire us and make a takeover more difficult
to complete, even if such a transaction were in our stockholders’ interest.
Provisions of our certificate of incorporation
and bylaws may delay or discourage transactions involving an actual or potential change in our control or change in our management,
including transactions in which stockholders might otherwise receive a premium for their shares, or transactions that our stockholders
might otherwise deem to be in their best interests. Therefore, these provisions could adversely affect the price of our stock.
Among other things, the certificate of incorporation and bylaws:
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provide that the authorized number of directors may be changed by resolution of the board of directors;
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provide that all vacancies, including newly-created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office, even if less than a quorum;
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divide the board of directors into three classes;
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provide that stockholders seeking to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide notice in writing in a timely manner, and meet specific requirements as to the form and content of a stockholder’s notice;
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In addition, we are governed by Section
203 of the Delaware General Corporation Law. In general, Section 203 prohibits a public Delaware corporation from engaging in a
“business combination” with an “interested stockholder” for a period of three years after the date of the
transaction in which the person became an interested stockholder, unless the business combination is approved in a prescribed manner.
A “business combination” includes mergers, asset sales or other transactions resulting in a financial benefit to the
stockholder. An “interested stockholder” is a person who, together with affiliates and associates, owns, or within
three years, did own, 15% or more of the corporation’s outstanding voting stock. These provisions may have the effect of
delaying, deferring or preventing a change in our control.
Compliance with the reporting requirements of federal
securities laws can be expensive.
We are subject to the information and reporting
requirements of the Exchange Act and other federal securities laws, and the compliance obligations of the Sarbanes-Oxley Act. The
costs of preparing and filing annual and quarterly reports and other information with the Securities and Exchange Commission and
furnishing audited reports to stockholders are substantial. In addition, we will incur substantial expenses in connection with
the preparation of registration statements and related documents with respect any offerings of our common stock.
Our ability to utilize our net operating loss carryforwards
and certain other tax attributes may be limited.
Our ability to utilize our federal net operating
loss and tax credit carryforwards may be limited under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended, or
the Code. The limitations apply if we experience an “ownership change”, generally defined as a greater than 50
percentage point change in the ownership of our equity by certain stockholders over a rolling three-year period. Similar provisions
of state tax law may also apply. We have not assessed whether such an ownership change has previously occurred. If we have
experienced an ownership change at any time since our formation, we may already be subject to limitations on our ability to utilize
our existing net operating losses and other tax attributes to offset taxable income. In addition, future changes in our stock ownership,
which may be outside of our control, may trigger an ownership change and, consequently, the limitations under Sections 382 and
383 of the Code. As a result, if or when we earn net taxable income, our ability to use our pre-change net operating loss
carryforwards and other tax attributes to offset such taxable income may be subject to limitations, which could adversely affect
our future cash flows.
Failure to establish and maintain adequate finance infrastructure
and accounting systems and controls could impair our ability to comply with the financial reporting and internal controls requirements
for publicly traded companies.
As a public company, we operate in an increasingly
demanding regulatory environment, including with respect to more complex accounting rules. Company responsibilities required by
the Sarbanes-Oxley Act of 2002, as amended, or the Sarbanes-Oxley Act, include establishing and maintaining corporate oversight
and adequate internal control over financial reporting and disclosure controls and procedures. Effective internal controls are
necessary for us to produce reliable financial reports and are important to help prevent financial fraud.
Our compliance with Section 404 of the Sarbanes-Oxley
Act requires that we incur substantial accounting expense and expend significant management efforts. We complied with Section 404
at December 31, 2019 and 2018 and while our testing did not reveal any material weaknesses in our internal controls, any material
weaknesses in our internal controls in the future would require us to remediate in a timely manner so as to be able to comply with
the requirements of Section 404 each year. If we are not able to comply with the requirements of Section 404 in a timely manner
each year, we could be subject to sanctions or investigations by the SEC, NYSE American or other regulatory authorities which would
require additional financial and management resources and could adversely affect the market price of our common stock. Furthermore,
if we cannot provide reliable financial reports or prevent fraud, our business and results of operations could be harmed, and investors
could lose confidence in our reported financial information.
If securities or industry analysts do not publish research
or publish inaccurate or unfavorable research about our business, the price of our common stock and trading volume could decline.
The trading market for our common stock
will depend in part on the research and reports that securities or industry analysts publish about us or our business. Multiple
securities and industry analysts currently cover us. If one or more of the analysts downgrade our common stock or publish inaccurate
or unfavorable research about our business, the price of our common stock would likely decline. If one or more of these analysts
cease coverage of us or fail to publish reports on us regularly, demand for our common stock could decrease, which could cause
the price of our common stock and trading volume to decline.
Our amended and restated bylaws, as amended, designate
the U.S. federal district courts as the exclusive forum for the resolution of any complaint asserting a cause
of action arising under the Securities Act of 1933, as amended.
Our amended and restated bylaws, as amended, provide
that, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States of
America will be the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act of
1933, as amended. In addition, our amended and restated bylaws, as amended, state that any person purchasing or otherwise acquiring
any interest in our security shall be deemed to have notice of and to have consented to such provision. Such choice of forum provision
may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our
directors, officers or other employees, which may discourage such lawsuits, if successful, might benefit our stockholders. Stockholders
who do bring a claim in the federal district courts of the United States of America could face additional litigation costs in pursuing
any such claim.
Additional Risks Related to this Offering
Purchasers in this offering will likely experience immediate
and substantial dilution in the book value of their investment.
Because the effective public offering price
per share is substantially higher than the net tangible book value per share of our common stock, you will suffer substantial dilution
in the net tangible book value of the common stock you purchase in this offering. After giving effect to the April 2020 Offering
and the sale by us of 55,653,846 shares of our common stock and our pre-funded warrants to purchase 21,269,231 shares
of common stock at an effective public offering price of $0.325 per share of common stock, assuming exercise of all pre-funded
warrants sold in this offering at $0.0001 per share of common stock and after deducting placement agent fees and estimated
offering expenses payable by us, you will suffer immediate and substantial dilution of $0.2000 per share in the pro forma as adjusted
net tangible book value of the common stock you purchase in this offering. See “Dilution” on page S-39 for a more detailed
discussion of the dilution you will incur in connection with this offering.
To
the extent outstanding stock options or warrants are exercised, there may be further dilution to new investors. In addition, to
the extent we need to raise additional capital in the future, and we issue additional equity or convertible debt securities, our
then existing stockholders may experience further dilution. Pursuant to the Lincoln Park Agreement and the ATM Sales Agreement,
we may issue and sell from time to time shares of our common stock, in an aggregate amount not to exceed $108.1 million. As of
June 12, 2020, an aggregate of $96.8 million of common stock remains available for sale under the Lincoln Park Agreement and the
ATM Sales Agreement. In connection with this offering, we have suspended, and during the duration of this offering we are no longer
offering, any securities pursuant to the Lincoln Park Agreement and the ATM Sales Agreement. To the extent that we sell additional
shares of our common stock pursuant to the Lincoln Park Agreement or the ATM Sales Agreement subsequent to this offering, investors
purchasing securities in this offering could experience further dilution.
Our management team may invest or spend the proceeds of
this offering in ways with which you may not agree or in ways which may not yield a significant return.
Our management will have broad discretion
over the use of proceeds from this offering. We currently intend to use the net proceeds from the sale of securities offered by
this prospectus to complete our ongoing pivotal, Phase 3 SIERRA trial for our lead product candidate Iomab-B, prepare and submit
a BLA to the FDA and MAA to the EMA, as well as commercialization activities for Iomab-B in the United States. We will also use
the net proceeds to progress Phase 1 trials for our refocused CD33 program to the proof of concept stage, to support our AWE Technology
Platform, Iomab-ACT program and research and development and for general working capital needs. However, our management will have
broad discretion in the application of the net proceeds from this offering and could spend the proceeds in ways that do not improve
our results of operations or enhance the value of our common stock. The failure by management to apply these funds effectively
could result in financial losses that could have a material adverse effect on our business, cause the price of our common stock
to decline and delay the development of our drug candidates.
Holders of pre-funded warrants
purchased in this offering will have no rights as stockholders of common stock until such holders exercise their pre-funded warrants
and acquire our common stock.
Until holders of pre-funded
warrants acquire our common stock upon exercise of the pre-funded warrants, holders of pre-funded warrants will have no rights
with respect to our common stock underlying such pre-funded warrants. Upon exercise of the pre-funded warrants, the holders will
be entitled to exercise the rights of a stockholder of our common stock only as to matters for which the record date occurs after
the exercise date.
There is no established public trading market for the
pre-funded warrants being offered in this offering.
There is no established public trading
market for the pre-funded warrants being offered in this offering, and we do not expect a market to develop. In addition, we do
not intend to apply to list the pre-funded warrants on any national securities exchange or other nationally recognized trading
system, including the NYSE American. Without an active market, the liquidity of the pre-funded warrants will be limited.
Sales of a substantial number of shares of our common
stock, or the perception that such sales may occur, may adversely impact the price of our common stock.
Sales of a substantial number of shares
of our common stock in the public market could occur at any time. These sales, or the perception that such sales may occur, may
adversely impact the price of our common stock, even if there is no relationship between such sales and the performance of our
business.
As of June 11, 2020, we had 339,500,880 shares
of common stock outstanding, as well as outstanding options to purchase an aggregate of 10,936,421 shares of our common stock at
a weighted average exercise price of $1.20 per share, outstanding warrants to purchase an aggregate of 86,140,575 shares of our
common stock at a weighted average exercise price of $0.69 per share, and outstanding pre-funded warrants to purchase 46,500,001
shares of our common stock at an exercise price of $0.0001 per share. The exercise of such outstanding options and warrants may
result in further dilution of your investment.
Special
Note Regarding Forward-Looking Statements
This prospectus supplement and accompanying
prospectus and the information incorporated by reference in this prospectus supplement and accompanying prospectus contain “forward-looking
statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities
Exchange Act of 1934, as amended (the “Exchange Act”), which include information relating to future events, future
financial performance, strategies, expectations, competitive environment and regulation. Words such as “may,” “should,”
“could,” “would,” “predicts,” “potential,” “continue,” “expects,”
“anticipates,” “future,” “intends,” “plans,” “believes,” “estimates,”
and similar expressions, as well as statements in future tense, identify forward-looking statements. Forward-looking statements
should not be read as a guarantee of future performance or results and will probably not be accurate indications of when such
performance or results will be achieved. Forward-looking statements are based on information we have when those statements are
made or our management’s good faith belief as of that time with respect to future events, and are subject to risks and uncertainties
that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking
statements. Important factors that could cause such differences include, but are not limited to:
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our history of recurring losses and negative
cash flows from operating activities, significant future commitments and the uncertainty regarding the adequacy of our liquidity
to pursue our complete business objectives;
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our ability to complete clinical trials as anticipated
and obtain and maintain regulatory approvals for our products;
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our ability to adequately protect our intellectual
property;
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disputes over ownership of intellectual property;
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our dependence on a single manufacturing facility
and our ability to comply with stringent manufacturing quality standards and to increase production as necessary;
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the risk that the data collected from our current
and planned clinical trials may not be sufficient to demonstrate that our products are an attractive alternative to other
procedures and products;
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intense competition in our industry, with competitors
having substantially greater financial, technological, research and development, regulatory and clinical, manufacturing, marketing
and sales, distribution and personnel resources than we do;
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entry of new competitors and products and potential
technological obsolescence of our products;
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loss of a key customer or supplier;
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adverse economic conditions;
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adverse federal, state and local government
regulation, in the United States;
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price increases for supplies and components;
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inability to carry out research, development
and commercialization plans;
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loss or retirement of key executives and research
scientists;
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our ability to regain and maintain compliance with
the continued listing requirements of the NYSE American and the risk that our common stock will be delisted if we cannot
do so;
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the geographic, social and economic impact of
COVID-19 on the Company’s business and liquidity; and
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other factors discussed in this prospectus supplement.
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You should review carefully the section
entitled “Risk Factors” beginning on page S-11 of this prospectus supplement for a discussion of these and other risks
that relate to our business and investing in our securities. The forward-looking statements contained or incorporated by reference
in this prospectus supplement are expressly qualified in their entirety by this cautionary statement. Except as required by applicable
law, we do not undertake any obligation to publicly update any forward-looking statement contained in this prospectus supplement,
the accompanying prospectus or the documents incorporated by reference herein to reflect events or circumstances after the date
on which any such statement is made or to reflect the occurrence of unanticipated events.
Use
of Proceeds
We estimate the net proceeds from this offering
will be approximately $22.8 million, after deducting
placement agent fees and estimated offering expenses payable by us.
We currently intend to use the net proceeds
from the sale of securities offered by this prospectus to complete our ongoing pivotal, Phase 3 SIERRA trial for our lead product
candidate Iomab-B, prepare and submit a BLA to the FDA and MAA to the EMA, as well as commercialization activities for Iomab-B
in the United States. We will also use the net proceeds to progress Phase 1 trials for our refocused CD33 program to the proof
of concept stage, to support our AWE Technology Platform, Iomab-ACT program and research and development and for general working
capital needs.
Investors are cautioned, however, that
expenditures may vary substantially from these uses. Investors will be relying on the judgment of our management, who will have
broad discretion regarding the application of the proceeds of this offering. The amounts and timing of our actual expenditures
will depend upon numerous factors, including the amount of cash generated by our operations, the amount of competition and other
operational factors. We may find it necessary or advisable to use portions of the proceeds from this offering for other purposes.
From time to time, we evaluate these and
other factors and we anticipate continuing to make such evaluations to determine if the existing allocation of resources, including
the proceeds of this offering, is being optimized. Circumstances that may give rise to a change in the use of proceeds include:
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a change in development plan or strategy;
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the addition of new products or applications;
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delays or difficulties with our clinical trials;
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negative results from our clinical trials;
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difficulty obtaining FDA approval;
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failure to achieve sales as anticipated; and
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the availability of other sources of cash including
cash flow from operations and new bank debt financing arrangements, if any.
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Pending other uses, we intend to invest
the proceeds to us in investment-grade, interest-bearing securities such as money market funds, certificates of deposit or direct
or guaranteed obligations of the U.S. government, or hold as cash. We cannot predict whether the proceeds invested will yield
a favorable, or any, return.
Dilution
If you purchase shares of our common stock
(and/or pre-funded warrants) in this offering, you will experience dilution to the extent of the difference between the effective
public offering price per share of common stock in this offering and our as adjusted net tangible book value per share immediately
after this offering. Net tangible book value is total assets minus the sum of liabilities and intangible assets. Net tangible
book value per share is net tangible book value divided by the total number of shares of common stock outstanding. As of December
31, 2019, our net tangible book value was $4.6 million, or approximately $0.0280 per share. Dilution with respect to net tangible
book value per share represents the difference between the amount per share or pre-funded warrant paid by purchasers in this offering
and the net tangible book value per share of our common stock immediately after this offering.
Our pro forma net tangible book value as of
December 31, 2019, after giving effect to the issuance of 128,333,333 shares of common stock and pre-funded warrants to purchase
82,500,001 shares of common stock in the April 2020 Offering and assuming exercise of all pre-funded warrants sold in the April
2020 Offering at $0.0001 per share, after deducting underwriting discounts and commissions and estimated offering expenses payable
by us in connection with the April 2020 Offering, would have been approximately $33.7 million, or approximately $0.0898 per share.
After giving effect to the sale of 55,653,846 shares
of our common stock in this offering at a public offering price of $0.325 per share and pre-funded warrants to purchase 21,269,231 shares
of common stock in this offering at a public offering price of $0.3249 per pre-funded warrant, and assuming exercise of all
pre-funded warrants sold in this offering at $0.0001 per share of common stock, after deducting placement agent fees and estimated
offering expenses payable by us, our pro forma as-adjusted net tangible book value as of December 31, 2019, would have been approximately
$56.5 million , or $0.1250 per share. This represents an immediate increase in net tangible book value of $0.0352 per share
to existing stockholders and immediate dilution of $0.2000 per share to purchasers purchasing our securities in this offering at
the public offering price.
The following table illustrates the dilution
in net tangible book value per share to new investors:
Effective public offering price per share:
|
|
|
|
|
|
$
|
0.3250
|
|
Net tangible book value per share as of December 31, 2019
|
|
$
|
0.0280
|
|
|
|
|
|
Increase in pro forma net tangible book value per share attributable to
the April 2020 Offering
|
|
$
|
0.0618
|
|
|
|
|
|
Pro forma net tangible book value per share as of December 31, 2019, after giving effect to the
April 2020 Offering
|
|
$
|
0.0898
|
|
|
|
|
|
Increase in net tangible book value per share attributable
to this offering
|
|
$
|
0.0352
|
|
|
|
|
|
Pro forma as adjusted net tangible book value per share as of December
31, 2019, after giving effect to the April 2020 Offering and this offering
|
|
|
|
|
|
$
|
0.1250
|
|
Dilution per share to new investors
|
|
|
|
|
|
$
|
0.2000
|
|
The foregoing discussion and table do not
take into account further dilution to new investors that could occur upon the exercise of outstanding options or warrants having
a per share exercise price less than the public offering price in this offering. To the extent that we raise additional capital
through the sale of equity or convertible debt securities, the issuance of those securities could result in further dilution to
our stockholders.
The above discussion and table are based
on 164,701,167 shares outstanding as of December 31, 2019 and excludes:
|
●
|
11,385,301 shares of common stock issuable upon
the exercise of stock options outstanding as of December 31, 2019 under our equity incentive plans, with a weighted average
exercise price of $1.17 per share;
|
|
●
|
21,802,069 shares of common stock available
for future grants under our equity incentive plans as of December 31, 2019; and
|
|
●
|
86,140,575 shares of common stock issuable upon
the exercise of warrants outstanding as of December 31, 2019, with a weighted average exercise price of $0.69 per share.
|
In addition, the number of shares of
our common stock to be outstanding immediately after this offering as shown above does not include (i) up to approximately
$29.2 million of shares of our common stock that remained available for sale at March 31, 2020 under the Lincoln Park
Agreement, and (ii) up to approximately $67.6 million of shares of our common stock that remained available for sale at
March 31, 2020 under the ATM Sales Agreement. In connection with this offering, we have suspended, and during the duration of
this offering we are no longer offering, any securities pursuant to the Lincoln Park Agreement or the ATM Sales
Agreement.
Description
of Securities we are Offering
Common stock
The material terms and provisions of our common
stock are described under the caption “Description of Capital Stock” in the accompanying prospectus beginning on page
9 and the Description of Securities included as Exhibit 4.14 to our Annual Report on Form 10-K for the year ended December 31,
2019, filed with the Securities and Exchange Commission on May 8, 2020, and as subsequently amended on Form 10-K/A filed with the
Securities and Exchange Commission on June 16, 2020. As of June 11, 2020, we had 339,500,880 shares of our common stock outstanding.
Our common stock is listed on the NYSE American under the symbol “ATNM”.
Pre-Funded Warrants
The following is a summary of the material terms and provisions
of the pre-funded warrants that are being offered hereby. This summary is subject to and qualified in its entirety by
the form of pre-funded warrants, which has been provided to the investors in this offering and which will be filed with
the Securities and Exchange Commission as an exhibit to a Current Report on Form 8-K in connection with this offering
and incorporated by reference into the registration statement of which this prospectus supplement forms a part. Prospective investors
should carefully review the terms and provisions of the form of pre-funded warrant for a complete description of the terms and
conditions of the pre-funded warrants.
Duration and Exercise Price
The pre-funded warrants offered
hereby will have an exercise price of $0.0001 per share. The pre-funded warrants will be immediately exercisable and
may be exercised at any time after their original issuance until such pre-funded warrants are exercised in full. The
exercise price and number of shares of common stock issuable upon exercise are subject to appropriate adjustment in the event
of share dividends, share splits, reorganizations or similar events affecting our shares of common stock. Pre-funded warrants
will be issued in certificated form only.
Exercisability
The pre-funded warrants will
be exercisable, at the option of each holder, in whole or in part, by delivering to us a duly executed exercise notice accompanied
by payment in full for the number of shares of common stock purchased upon such exercise (except in the case of a cashless exercise
as discussed below). A holder (together with its affiliates) may not exercise any portion of such holder’s warrants to the
extent that the holder would own more than 4.99% (or, at the election of the purchaser, 9.99%) of our outstanding shares of common
stock immediately after exercise, except that upon at least 61 days’ prior notice from the holder to us, the holder may
increase the amount of ownership of outstanding shares of common stock after exercising the holder’s pre-funded warrants
up to 9.99% of the number of shares of common stock outstanding immediately after giving effect to the exercise, as such percentage
ownership is determined in accordance with the terms of the pre-funded warrants. Purchasers in this offering may also
elect prior to the issuance of pre-funded warrants to have the initial exercise limitation set at 9.99% of our outstanding
shares of common stock.
Cashless Exercise
At the time a holder exercises its pre-funded
warrants, in lieu of making the cash payment otherwise contemplated to be made to us upon such exercise in payment of the aggregate
exercise price, the holder may elect instead to receive upon such exercise (either in whole or in part) the net number of shares
of common stock determined according to a formula set forth in the pre-funded warrant.
Fundamental Transactions
In the event of any fundamental transaction,
as described in the pre-funded warrants and generally including any merger with or into another entity, sale of all
or substantially all of our assets, tender offer or exchange offer, or reclassification of our shares of common stock, then upon
any subsequent exercise of a pre-funded warrant, the holder will have the right to receive as alternative consideration,
for each share of common stock that would have been issuable upon such exercise immediately prior to the occurrence of such fundamental
transaction, the number of shares of common stock of the successor or acquiring corporation or of our company, if it is the surviving
corporation, and any additional consideration receivable upon or as a result of such transaction by a holder of the number of
shares of common stock for which the pre-funded warrant is exercisable immediately prior to such event.
Transferability
In accordance with its terms and subject
to applicable laws, a pre-funded warrant may be transferred at the option of the holder upon surrender of the pre-funded warrant
to us together with the appropriate instruments of transfer and payment of funds sufficient to pay any transfer taxes (if applicable).
Fractional Shares
No fractional shares of common stock will
be issued upon the exercise of the pre-funded warrants. Rather, the number of shares of common stock to be issued will,
at our election, either be rounded up to the nearest whole number or we will pay a cash adjustment in respect of such final fraction
in an amount equal to such fraction multiplied by the exercise price.
Trading Market
There is no established trading market
for the pre-funded warrants, and we do not expect a market to develop. We do not intend to apply for a listing for the
pre-funded warrants on any securities exchange or other nationally recognized trading system. Without an active trading market,
the liquidity of the pre-funded warrants will be limited.
Rights as a Stockholder
Except as otherwise provided in the pre-funded warrants
or by virtue of the holders’ ownership of shares of common stock, the holders of pre-funded warrants do not have
the rights or privileges of holders of our shares of common stock, including any voting rights, until such pre-funded warrant
holders exercise their warrants.
PLAN
OF DISTRIBUTION
We engaged H.C.
Wainwright & Co., LLC (“Wainwright” or the “exclusive lead placement agent”) to act as our
exclusive lead placement agent to solicit offers to purchase the securities offered by this prospectus supplement. The
exclusive lead placement agent is not purchasing or selling any securities, nor are they required to arrange for the purchase
and sale of any specific number or dollar amount of securities, other than to use their “best efforts” to arrange
for the sale of securities by us. Therefore, we may not sell the entire amount of securities being offered. We may enter into
a securities purchase agreement directly with certain institutional investors who purchase our securities in this offering.
We will not enter into securities purchase agreements with all other investors and such investors shall rely solely on this
prospectus supplement in connection with the purchase of our securities in this offering.
Upon the closing of this
offering, we will pay the placement agents a cash transaction fee equal to 7.0% of the gross proceeds to us from the sale of the
securities in the offering.
The following table shows
the per share of common stock and per pre-funded warrant and total placement agent fees we will pay assuming the sale of all of
the securities offered pursuant to this prospectus.
|
|
Per Share
|
|
|
Per Pre-
Funded Warrant
|
|
|
Total
|
|
Placement Agent Fees
|
|
$
|
0.02275
|
|
|
$
|
0.02275
|
|
|
$
|
1,750,000.00
|
|
Total
|
|
$
|
1,266,125.00
|
|
|
$
|
483,875.00
|
|
|
$
|
1,750,000.00
|
|
We will also pay the
exclusive lead placement agent a non-accountable expense allowance of $25,000, reimburse the exclusive lead placement
agent $12,900 for the clearing expenses of the exclusive lead placement agent and reimburse the exclusive lead placement
agent’s legal fees and expenses in an amount up to $100,000 in connection with this offering.
We estimate the total offering
expenses of this offering that will be payable by us, excluding the placement agent fees and expenses, will be approximately $300,000.
After deducting the fees
due to the placement agents and our estimated offering expenses, we expect the net proceeds from this offering to be approximately
$22.8 million.
The placement agents
may be deemed underwriters within the meaning of Section 2(a)(11) of the Securities Act and any fees received by them and any
profit realized on the sale of the securities by them while acting as principal might be deemed to be underwriting discounts or
commissions under the Securities Act. The placement agents will be required to comply with the requirements of
the Securities Act and the Exchange Act of 1934, as amended (the “Exchange Act”), including,
without limitation, Regulation M under the Exchange Act. These rules and regulations may limit the timing of
purchases and sales of our securities by the placement agents. Under these rules and regulations, the placement agents may not
(i) engage in any stabilization activity in connection with our securities; and (ii) bid for or purchase any of our
securities or attempt to induce any person to purchase any of our securities, other than as permitted under the Exchange
Act, until they have completed their participation in the distribution.
Other Relationships
The
placement agents may, from time to time, engage in transactions with or perform services for us in the ordinary course of
their business and may continue to receive compensation from us for such services, but we have no present agreements with the
placement agents to do so. In particular, the exclusive lead placement agent served as representative of the several
underwriters in the April 2020 Offering, for which they received, together with the other underwriters, an aggregate of $2.2
million in discounts and commissions and approximately $138,000 in reimbursement of fees and expenses.
Determination of offering price
The public offering price
of the securities offered hereby was negotiated between us and the investors, in consultation with the placement agents, and other
advisors to us, based on the trading of our common stock prior to the offering, among other things. Other factors considered in
determining the public offering price of the securities offered hereby include our history and prospects, the stage of development
of our business, our business plans for the future and the extent to which they have been implemented, an assessment of our management,
general conditions of the securities markets at the time of the offering and such other factors as were deemed relevant.
Lock-up Agreements
We have agreed with the exclusive lead
placement agent and certain investors in the offering, subject to specified exceptions and until the date that is 30
days after the date of the closing of this offering not to issue, enter into any agreement to issue or announce the
issuance or proposed issuance of any shares of our common stock or any securities that are substantially similar to our
common stock, including but not limited to any options or warrants to purchase shares of our common stock or any securities
that are convertible into or exchangeable for, or that represent the right to receive, common stock or any such substantially
similar securities, without the prior written consent of the exclusive lead placement agent.
As of closing of this offering, our
directors and executive officers will have agreed with the exclusive lead placement agent, subject to specified exceptions,
not to (i) offer, pledge, announce the intention to sell, sell, contract to sell, sell any option or contract to purchase,
purchase any option or contract to sell, grant any option, right or warrant to purchase, make any short sale or otherwise
transfer or dispose of, directly or indirectly, any shares of our common stock or any securities convertible into,
exercisable or exchangeable for or that represent the right to receive our common stock (including without limitation, our
common stock which may be deemed to be beneficially owned in accordance with the rules and regulations of the Securities and
Exchange Commission and securities which may be issued upon exercise of a stock option or warrant), whether now owned or
hereafter acquired, or (ii) enter into any swap or other agreement that transfers, in whole or in part, any of the economic
consequences of ownership of our common stock, whether any such transaction is to be settled by delivery of our common stock
or such other securities, in cash or otherwise. These restrictions will apply through and including the date that is 30 days
after the date of the closing of this offering.
We have also agreed to
a restriction on the issuance of any variable priced securities for 6 months following the closing of this offering, except that
we may use our existing at-the-market offering facility and/or may enter into new at-the-market offering facilities through a registered
broker-dealer following the date that is 30 days after the closing date of the offering.
Listing
Our common stock is listed
on the NYSE American under the symbol “ATNM.”
Indemnification
We have agreed to indemnify the placement
agents against certain liabilities, including liabilities under the Securities Act, and to contribute to payments that the
placement agents may be required to make for these liabilities.
Selling Restrictions
Canada
Resale Restrictions
The distribution of securities in Canada
is being made only in the provinces of Ontario, Quebec, Alberta and British Columbia on a private placement basis exempt from
the requirement that we prepare and file a prospectus with the securities regulatory authorities in each province where
trades of these securities are made. Any resale of securities in Canada must be made under applicable securities laws which
may vary depending on the relevant jurisdiction, and which may require resales to be made under available statutory
exemptions or under a discretionary exemption granted by the applicable Canadian securities regulatory authority. Purchasers
are advised to seek legal advice prior to any resale of the securities.
Representations of Canadian Purchasers
By purchasing securities in Canada and accepting
delivery of a purchase confirmation, a purchaser is representing to us and the dealer from whom the purchase confirmation is received
that:
|
●
|
the purchaser is entitled under applicable provincial securities laws to purchase securities without the benefit of a prospectus qualified under those securities laws as it is an “accredited investor” as defined under National Instrument 45-106—Prospectus Exemptions,
|
|
●
|
the purchaser is a “permitted client” as defined in National Instrument 31-103—Registration Requirements, Exemptions and Ongoing Registrant Obligations,
|
|
●
|
where required by law, the purchaser is purchasing as principal and not as agent, and
|
|
●
|
the purchaser has reviewed the text above under Resale Restrictions.
|
Conflicts of Interest
Canadian purchasers are hereby notified that
the placement agent(s) are relying on the exemption set out in section 3A.3 or 3A.4, if applicable, of National Instrument 33-105
— Underwriting Conflicts from having to provide certain conflict of interest disclosure in this document.
Statutory Rights of Action
Securities legislation in certain provinces
or territories of Canada may provide a purchaser with remedies for rescission or damages if the offering memorandum (including
any amendment thereto) such as this document contains a misrepresentation, provided that the remedies for rescission or damages
are exercised by the purchaser within the time limit prescribed by the securities legislation of the purchaser’s province
or territory. The purchaser of these securities in Canada should refer to any applicable provisions of the securities legislation
of the purchaser’s province or territory for particulars of these rights or consult with a legal advisor.
Enforcement of Legal Rights
All of our directors and officers as well as
the experts named herein may be located outside of Canada and, as a result, it may not be possible for Canadian purchasers to effect
service of process within Canada upon us or those persons. All or a substantial portion of our assets and the assets of those persons
may be located outside of Canada and, as a result, it may not be possible to satisfy a judgment against us or those persons in
Canada or to enforce a judgment obtained in Canadian courts against us or those persons outside of Canada.
Taxation and Eligibility for Investment
Canadian purchasers of securities should
consult their own legal and tax advisors with respect to the tax consequences of an investment in the securities in their
particular circumstances and about the eligibility of the securities for investment by the purchaser under relevant Canadian
legislation.
European Economic Area
In relation to each Member State of the European
Economic Area that has implemented the Prospectus Directive, each referred to as a Relevant Member State, an offer to the public
of any of our securities may not be made in that Relevant Member State, except that an offer to the public in that Relevant Member
State of any securities may be made at any time under the following exemptions under the Prospectus Directive, if they have been
implemented in that Relevant Member State:
|
(a)
|
to any legal entity which is a “qualified investor” as defined in the Prospectus Directive;
|
|
(b)
|
to fewer than 150 natural or legal persons (other than qualified investors as defined in the Prospectus Directive), subject to obtaining the prior consent of the placement agent(s) for any such offer; or
|
|
(c)
|
in any other circumstances falling within Article 3(2) of the Prospectus Directive,
|
provided that no such offer of securities shall result
in a requirement for the publication by us or any placement agent of a prospectus pursuant to Article 3 of the Prospectus Directive.
For the purposes of this provision, the expression
an “offer to the public” in relation to any of our securities in any Relevant Member State means the communication
in any form and by any means of sufficient information on the terms of the offer and any securities to be offered so as to enable
an investor to decide to purchase any securities, as the same may be varied in that Relevant Member State by any measure implementing
the Prospectus Directive in that Relevant Member State and the expression “Prospectus Directive” means Directive 2003/71/EC
(and amendments thereto, including by Directive 2010/73/EU) and includes any relevant implementing measure in each Relevant Member
State.
United Kingdom
Each placement agent has represented and agreed
that:
|
(a)
|
it has not made or will not make an offer of our securities to the public in the United Kingdom within the meaning of section 102B of the Financial Services and Markets Act 2000 (as amended) (FSMA) except to legal entities which are authorized or regulated to operate in the financial markets or, if not so authorized or regulated, whose corporate purpose is solely to invest in securities or otherwise in circumstances which do not require the publication by us of a prospectus pursuant to the Prospectus Rules of the Financial Services Authority;
|
|
(b)
|
it has only communicated or caused to be communicated and will only communicate or cause to be communicated an invitation or inducement to engage in investment activity (within the meaning of section 21 of FSMA) to persons who have professional experience in matters relating to investments falling within Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005 or in circumstances in which section 21 of FSMA does not apply to us; and
|
|
(c)
|
it has complied and will comply with all applicable provisions of the FSMA with respect to anything done by it in relation to the securities in, from or otherwise involving the United Kingdom.
|
Hong Kong
No securities have been offered or sold, and
no securities may be offered or sold, in Hong Kong, by means of any document, other than to persons whose ordinary business is
to buy or sell shares or debentures, whether as principal or agent; or to “professional investors” as defined in the
Securities and Futures Ordinance (Cap. 571) of Hong Kong and any rules made under that Ordinance; or in other circumstances which
do not result in the document being a “prospectus” as defined in the Companies Ordinance (Cap. 32) of Hong Kong or
which do not constitute an offer to the public within the meaning of the Companies Ordinance (Cap. 32) of Hong Kong. No document,
invitation or advertisement relating to the securities has been issued or may be issued or may be in the possession of any person
for the purpose of issue (in each case whether in Hong Kong or elsewhere), which is directed at, or the contents of which are likely
to be accessed or read by, the public of Hong Kong (except if permitted under the securities laws of Hong Kong) other than with
respect to securities which are or are intended to be disposed of only to persons outside Hong Kong or only to “professional
investors” as defined in the Securities and Futures Ordinance (Cap. 571) of Hong Kong and any rules made under that Ordinance.
This prospectus has not been registered with
the Registrar of Companies in Hong Kong. Accordingly, this prospectus may not be issued, circulated or distributed in Hong Kong,
and the securities may not be offered for subscription to members of the public in Hong Kong. Each person acquiring the securities
will be required, and is deemed by the acquisition of the securities, to confirm that he is aware of the restriction on offers
of the securities described in this prospectus and the relevant offering documents and that he is not acquiring, and has not been
offered any securities in circumstances that contravene any such restrictions.
Singapore
This prospectus has not been, and will not be,
registered as a prospectus with the Monetary Authority of Singapore. Accordingly, this prospectus and any other document or material
in connection with the offer or sale, or invitation for subscription or purchase, of the securities may not be circulated or distributed,
nor may the securities be offered or sold, or be made the subject of an invitation for subscription or purchase, whether directly
or indirectly, to persons in Singapore other than (i) to an institutional investor (as defined in Section 4A of the Securities
and Futures Act, Chapter 289 of Singapore (the “SFA”)) pursuant to Section 274 of the SFA, (ii) to a relevant person
(as defined in Section 275(2) of the SFA) pursuant to Section 275(1), or any person pursuant to Section 275(1A), and in accordance
with the conditions specified in Section 275 of the SFA or (iii) otherwise pursuant to, and in accordance with the conditions of,
any other applicable provision of the SFA, in each case subject to compliance with conditions set forth in the SFA.
Where the securities are subscribed or purchased
under Section 275 of the SFA by a relevant person which is:
|
(a)
|
a corporation (which is not an accredited investor (as defined in Section 4A of the SFA)) the sole business of which is to hold investments and the entire share capital of which is owned by one or more individuals, each of whom is an accredited investor; or
|
|
(b)
|
a trust (where the trustee is not an accredited investor) whose sole purpose is to hold investments and each beneficiary of the trust is an individual who is an accredited investor,
|
securities (as defined in Section 239(1) of the SFA) of that corporation
or the beneficiaries’ rights and interest (howsoever described) in that trust shall not be transferred within six months
after that corporation or that trust has acquired the securities pursuant to an offer made under Section 275 of the SFA except:
|
(a)
|
to an institutional investor pursuant to Section 274 of the SFA or to a relevant person pursuant to Section 275(1) of the SFA, or to any person arising from an offer referred to in Section 275(1A) or Section 276(4)(i)(B) of the SFA;
|
|
(b)
|
where no consideration is or will be given for the transfer;
|
|
(c)
|
where the transfer is by operation of law;
|
|
(d)
|
as specified in Section 276(7) of the SFA; or
|
|
(e)
|
as specified in Regulation 32 of the Securities and Futures (Offers of Investments) (Shares and Debentures) Regulations 2005 of Singapore.
|
Switzerland
The securities may not be publicly offered in
Switzerland and will not be listed on the SIX Swiss Exchange, or the SIX, or on any other stock exchange or regulated trading facility
in Switzerland. This document has been prepared without regard to the disclosure standards for issuance prospectuses under art.
652a or art. 1156 of the Swiss Code of Obligations or the disclosure standards for listing prospectuses under art. 27 ff. of the
SIX Listing Rules or the listing rules of any other stock exchange or regulated trading facility in Switzerland. Neither this document
nor any other offering or marketing material relating to the securities or the offering may be publicly distributed or otherwise
made publicly available in Switzerland.
Neither this document nor any other offering
or marketing material relating to the offering, or the securities have been or will be filed with or approved by any Swiss regulatory
authority. In particular, this document will not be filed with, and the offer of securities will not be supervised by, the Swiss
Financial Market Supervisory Authority FINMA, and the offer of securities has not been and will not be authorized under the Swiss
Federal Act on Collective Investment Schemes, or CISA. Accordingly, no public distribution, offering or advertising, as defined
in CISA, its implementing ordinances and notices, and no distribution to any non-qualified investor, as defined in CISA, its implementing
ordinances and notices, shall be undertaken in or from Switzerland, and the investor protection afforded to acquirers of interests
in collective investment schemes under CISA does not extend to acquirers of securities.
United Arab Emirates
This offering has not been reviewed, approved
or licensed by the Central Bank of the United Arab Emirates (the “UAE”), the Emirates Securities and Commodities Authority
of the UAE (the “SCA”) and/or any other relevant licensing authority in the UAE including any licensing authority incorporated
under the laws and regulations of any of the free zones established and operating in the territory of the UAE (the “Free
Zones”), in particular the Dubai Financial Services Authority (the “DFSA”), a regulatory authority of the Dubai
International Financial Centre the (“DIFC”) or the Financial Services Regulatory Authority (the “FSRA”),
a regulatory authority of Abu Dhabi Global Market (“ADGM”).
This offering is not intended to, and does not,
constitute an offer, sale or delivery of shares or other securities under the laws of the UAE. The securities have not been and
will not be registered with or licensed by the SCA or with the UAE Central Bank, the Dubai Financial Market, the Abu Dhabi Securities
Exchange or with any other UAE regulatory authority or exchange.
The issue and/or sale of the securities has
not been approved or licensed by the SCA, the UAE Central Bank or any other relevant licensing authority in the UAE, and does not
constitute a public offer of securities in the UAE, DIFC, ADGM and/or any other Free Zone in accordance with the Commercial Companies
Law, Federal Law No 2 of 2015 (as amended), the Markets Rules of the DFSA, (the “DFSA Markets Rules”), the Markets
Rules of the FSRA (the “FSRA Markets Rules”) and/or Nasdaq Dubai Listing Rules or under any other law of the UAE. The
securities may not be offered to the public in the UAE and/or any of the Free Zones.
No marketing or promotion of the securities
has been or will be made from within the UAE and no sale of or subscription for the securities may or will be consummated within
the UAE. It should not be assumed that Primo Water Corporation, Primo Water Corporation’s advisors, their advisors or any
other person is a licensed broker, dealer or investment adviser under the laws of the UAE or that they advise as to the appropriateness
of investing in or purchasing or selling securities or other financial products.
This offering is not intended to constitute
a financial promotion, an offer, sale or delivery of shares or other securities under the DIFC Markets Law (DIFC Law No. 1 of 2012,
as amended) (the “Markets Law”), the DFSA Markets Rules, the Collective Investment Law 2010 (DIFC Law No. 2 of 2010)
(the “Collective Investment Law”), the ADGM Financial Services and Markets Regulations 2015 (the “FSMR”),
the FSRA Markets Rules, the Funds Rules of the FSRA (“FSRA Funds Rules”), or any other laws and regulations of the
DIFC, the DFSA, ADGM or the FSRA.
This offering and the issue or transfer of any
securities related to it have not been approved or licensed by the DFSA, and do not constitute an offer of securities in the DIFC
in accordance with the Markets Law or the DFSA Markets Rules or the Collective Investment Law or any other laws and regulations
of the DIFC or the DFSA. This offering and the issue or transfer of any securities related to it have not been approved or licensed
by the FSRA, and do not constitute an offer of securities in ADGM in accordance with the FSMR or the FSRA Markets Rules or the
FSRA Funds Rules or any other laws and regulations of ADGM or the FSRA.
Notice to Prospective Investors in Israel
The securities offered by this prospectus supplement
and the accompanying prospectus have not been approved or disapproved by the Israeli Securities Authority (the “ISA”),
nor have such securities been registered for sale in Israel. The ISA has not issued permits, approvals or licenses in connection
with the offering or publishing this prospectus supplement and the accompanying prospectus; nor has it authenticated the details
included herein, confirmed their reliability or completeness, or rendered an opinion as to the quality of the securities being
offered. The shares of common stock or the pre-funded warrants will not be offered or sold, directly or indirectly, to the public
in Israel, except that the placement agent(s) may offer and sell such shares to Israeli investors who qualify, in accordance with
the Israeli Securities Law as “qualified investors” (as defined in the First Appendix to the Israeli Securities Law)
and completed and signed a questionnaire regarding such qualification and delivered it to the placement agent(s). Any resale in Israel,
directly or indirectly, to the public of the securities offered by this prospectus supplement and the accompanying prospectus is
subject to restrictions on transferability and must be effected only in compliance with the Israeli securities laws and regulations.
Legal
Matters
The validity of the securities offered by
this prospectus will be passed upon for us by Haynes and Boone, LLP, New York, New York. Certain legal matters will be passed upon
for the placement agents by Lowenstein Sandler LLP, New York, New York.
Experts
The financial statements incorporated in
this prospectus supplement by reference to the Annual Report on Form 10-K for the fiscal year ended December 31, 2019 has been
so incorporated in reliance on the report of Marcum LLP, an independent registered public accounting firm, given on the authority
of said firm as experts in auditing and accounting.
Where
You Can Find More Information
We are subject to the informational requirements
of the Securities Exchange Act of 1934, as amended, and in accordance therewith file annual, quarterly and current reports, proxy
statements and other information with the Securities and Exchange Commission. The Securities and Exchange Commission maintains
a website that contains reports, proxy and information statements and other information regarding registrants that file electronically
with the Securities and Exchange Commission. The address of the Securities and Exchange Commission’s website is www.sec.gov.
We make available free of charge on or
through our website at www.actiniumpharma.com, our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current
Reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange
Act of 1934, as amended, as soon as reasonably practicable after we electronically file such material with or otherwise furnish
it to the Securities and Exchange Commission.
We have filed with the Securities and Exchange
Commission a registration statement under the Securities Act of 1933, as amended, relating to the offering of these securities.
The registration statement, including the attached exhibits, contains additional relevant information about us and the securities.
This prospectus supplement does not contain all of the information set forth in the registration statement. You can obtain a copy
of the registration statement, at prescribed rates, from the Securities and Exchange Commission at the address listed above, or
for free at www.sec.gov. The registration statement and the documents referred to below under “Incorporation of Certain
Information By Reference” are also available on our website, www.actiniumpharma.com.
We have not incorporated by reference into
this prospectus supplement the information on our website, and you should not consider it to be a part of this prospectus supplement.
Incorporation
of Certain Information by Reference
The Securities and Exchange Commission
allows us to “incorporate by reference” the information we have filed with it, which means that we can disclose important
information to you by referring you to those documents. The information we incorporate by reference is an important part of this
prospectus supplement, and later information that we file with the Securities and Exchange Commission will automatically update
and supersede this information. We incorporate by reference the documents listed below and any future documents (excluding information
furnished pursuant to Items 2.02 and 7.01 of Form 8-K) we file with the Securities and Exchange Commission pursuant to Sections
13(a), 13(c), 14 or 15(d) of the Securities Exchange Act of 1934, as amended, subsequent to the date of this prospectus supplement
and prior to the termination of the offering:
|
●
|
Our Annual Report on Form 10-K for the fiscal year ended December 31, 2019, filed with the Securities and Exchange Commission on May 8, 2020, and as subsequently amended on Form 10-K/A filed with
the Securities and Exchange Commission on June 16, 2020;
|
|
●
|
The description of the Company’s common
stock and warrants contained in the Form 8-A filed with the Securities and Exchange Commission on March
24, 2014, including any amendments thereto or reports filed for the purposes of updating this description.
|
All filings filed by us pursuant to the
Securities Exchange Act of 1934, as amended, after the date of the initial filing of this registration statement and prior to
the effectiveness of such registration statement (excluding information furnished pursuant to Items 2.02 and 7.01 of Form 8-K)
shall also be deemed to be incorporated by reference into the prospectus supplement.
You should rely only on the information
incorporated by reference or provided in this prospectus supplement. We have not authorized anyone else to provide you with different
information. You should not assume that the information in this prospectus supplement is accurate as of any date other than the
date of this prospectus supplement or the date of the documents incorporated by reference in this prospectus supplement.
We will provide without charge to each
person to whom a copy of this prospectus supplement is delivered, upon written or oral request, a copy of any or all of the information
that has been incorporated by reference in this prospectus supplement but not delivered with this prospectus supplement (other
than an exhibit to these filings, unless we have specifically incorporated that exhibit by reference in this prospectus supplement).
Any such request should be addressed to us at: 275 Madison Avenue, 7th Floor, New York, New York 10016, Attention: Steve O’Loughlin,
Principal Financial Officer, or made by phone at (646) 677-3870. You may also access the documents incorporated by reference in
this prospectus supplement through our website at www.actiniumpharma.com. Except for the specific incorporated documents
listed above, no information available on or through our website shall be deemed to be incorporated in this prospectus supplement
or the accompanying prospectus.
PROSPECTUS
ACTINIUM PHARMACEUTICALS, INC.
$200,000,000
Common
Stock
Preferred
Stock
Debt
Securities
Warrants
Rights
Purchase
Contracts
Units
We
may offer and sell from time to time, in one or more series or issuances and on terms that we will determine at the time of the
offering, any combination of the securities described in this prospectus, up to an aggregate amount of $200,000,000.
We
will provide specific terms of any offering in a supplement to this prospectus. Any prospectus supplement may also add, update,
or change information contained in this prospectus. You should carefully read this prospectus and the applicable prospectus supplement
as well as the documents incorporated or deemed to be incorporated by reference in this prospectus before you purchase any of
the securities offered hereby.
These
securities may be offered and sold in the same offering or in separate offerings; to or through underwriters, dealers, and agents;
or directly to purchasers. The names of any underwriters, dealers, or agents involved in the sale of our securities, their compensation
and any over-allotment options held by them will be described in the applicable prospectus supplement. See “Plan of Distribution.”
Our
common stock is presently traded on the NYSE MKT under the symbol “ATNM.” On March 10, 2017, the last reported sale
price of our common stock was $1.42 per share. We recommend that you obtain current market quotations for our common stock prior
to making an investment decision. We will provide information in any applicable prospectus supplement regarding any listing of
securities other than shares of our common stock on any securities exchange.
You
should carefully read this prospectus, any prospectus supplement relating to any specific offering of securities, and all information
incorporated by reference herein and therein.
Investing
in our securities involves a high degree of risk. These risks are discussed in this prospectus under “Risk Factors”
beginning on page 8 and in the documents incorporated by reference into this prospectus.
Neither
the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or
passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense.
The
date of this prospectus is October 12, 2017
TABLE
OF CONTENTS
ABOUT
THIS PROSPECTUS
This
prospectus is part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission using a “shelf”
registration process. Under this shelf process, we may, from time to time, sell any combination of the securities described in
this prospectus in one or more offerings up to a total amount of $200,000,000.
This
prospectus provides you with a general description of the securities we may offer. Each time we sell securities, we will provide
a prospectus supplement that will contain specific information about the terms of that offering. The prospectus supplement may
also add to, update or change information contained in the prospectus and, accordingly, to the extent inconsistent, information
in this prospectus is superseded by the information in the prospectus supplement.
The
prospectus supplement to be attached to the front of this prospectus may describe, as applicable: the terms of the securities
offered; the public offering price; the price paid for the securities; net proceeds; and the other specific terms related to the
offering of the securities.
You
should only rely on the information contained or incorporated by reference in this prospectus and any prospectus supplement or
issuer free writing prospectus relating to a particular offering. No person has been authorized to give any information or make
any representations in connection with this offering other than those contained or incorporated by reference in this prospectus,
any accompanying prospectus supplement and any related issuer free writing prospectus in connection with the offering described
herein and therein, and, if given or made, such information or representations must not be relied upon as having been authorized
by us. Neither this prospectus nor any prospectus supplement nor any related issuer free writing prospectus shall constitute an
offer to sell or a solicitation of an offer to buy offered securities in any jurisdiction in which it is unlawful for such person
to make such an offering or solicitation. This prospectus does not contain all of the information included in the registration
statement. For a more complete understanding of the offering of the securities, you should refer to the registration statement,
including its exhibits.
You
should read the entire prospectus and any prospectus supplement and any related issuer free writing prospectus, as well as the
documents incorporated by reference into this prospectus or any prospectus supplement or any related issuer free writing prospectus,
before making an investment decision. Neither the delivery of this prospectus or any prospectus supplement or any issuer free
writing prospectus nor any sale made hereunder shall under any circumstances imply that the information contained or incorporated
by reference herein or in any prospectus supplement or issuer free writing prospectus is correct as of any date subsequent to
the date hereof or of such prospectus supplement or issuer free writing prospectus, as applicable. You should assume that the
information appearing in this prospectus, any prospectus supplement or any document incorporated by reference is accurate only
as of the date of the applicable documents, regardless of the time of delivery of this prospectus or any sale of securities. Our
business, financial condition, results of operations and prospects may have changed since that date.
PROSPECTUS
SUMMARY
This
summary provides an overview of selected information contained elsewhere or incorporated by reference in this prospectus and does
not contain all of the information you should consider before investing in our securities. You should carefully read the prospectus,
the information incorporated by reference and the registration statement of which this prospectus is a part in their entirety
before investing in our securities, including the information discussed under “Risk Factors” in this prospectus and
the documents incorporated by reference and our financial statements and notes thereto that are incorporated by reference in this
prospectus. As used in this prospectus, unless the context otherwise indicates, the terms “we,” “our,”
“us,” or “the Company” refer to Actinium Pharmaceuticals, Inc., a Delaware corporation, and its subsidiaries
taken as a whole.
The
Company
Business
Overview
Our
most advanced products are Iomab™-B, an antibody-drug construct containing iodine 131 (I-131), used in myeloconditioning
for hematopoietic stem cells transplantation (HSCT) in various indications and Actimab™-A, an antibody-drug construct containing
actinium 225 (Ac-225), currently in human clinical trials for acute myeloid leukemia (AML). We are currently conducting a pivotal
Phase 3 trial of Iomab™-B for bone marrow conditioning for HSCT in patients with relapsed or refractory AML age of 55 and
older, which upon successful completion of our clinical trials we intend to submit for marketing approval. We are currently also
considering filing an application with the U.S. Food and Drug Administration (FDA) for breakthrough therapy designation for Actimab™-A
and/or Iomab™-B. We are developing our cancer drugs using our expertise in radioimmunotherapy. In addition, our Ac-225 based
drug development relies on the patented Alpha Particle Immunotherapy Technology (APIT) platform technology co-developed with Memorial
Sloan Kettering Cancer Center (MSKCC). The APIT technology couples monoclonal antibodies (mAb) with extremely potent but comparatively
safe alpha particle emitting radioactive isotopes, in particular actinium 225. The final drug construct is designed to specifically
target and kill cancer cells while minimizing side effects. We intend to develop a number of products for different types of cancer
and derive revenue from partnering relationships with large pharmaceutical companies and/or direct sales of its products in specialty
markets in the United States.
In
December 2015, we announced that the FDA cleared our IND filing for Iomab-B. In June 2016, we announced the pivotal Phase 3 clinical
trial for Iomab-B was initiated and assuming that the trial meets its end points, it will form the basis for a Biologics Licensing
Application (BLA). We established an agreement with the FDA that the path to a BLA submission would include a single, pivotal
Phase 3 clinical study if it is successful. The population in this two arm, randomized, controlled, multicenter trial will be
refractory and relapsed AML patients over the age of 55. The trial size was set at 150 patients with 75 patients per arm. The
primary endpoint in the pivotal Phase 3 trial is durable complete remission, defined as a complete remission lasting at least
6 months and the secondary endpoint will be overall survival at one year. We believe there are currently no effective treatments
approved by the FDA for AML in this patient population and there is no defined standard of care. Iomab-B has completed several
physicians sponsored clinical trials examining its potential as a conditioning regimen prior to HSCT in various blood cancers,
including the Phase 1/2 study in relapsed and/or refractory AML patients. The results of these studies in over 300 patients have
demonstrated the potential of Iomab-B to create a new treatment paradigm for bone marrow transplants by: expanding the pool to
ineligible patients who do not have any viable treatment options currently; enabling a shorter and safer preparatory interval
for HSCT; reducing post-transplant complications; and showing a clear survival benefit including curative potential.
In
September 2016, we initiated the Phase 2 clinical trial for Actimab-A. This Phase 2 clinical trial is a multicenter, open-label
study that will enroll 53 patients. Patients will receive 2.0 µCi/kg/fractionated dose of Actimab-A via two injections given
at day 1 and day 7. The Phase 2 trial is designed to evaluate complete response rates at up to day 42 after Actimab-A administration,
where complete response is defined as complete remission (CR) or complete remission with incomplete platelet recovery (CRp). A
formal interim analysis is expected to occur in mid-2017 with topline results expected in the second half of 2017. The Phase 2
clinical trial includes peripheral blast burden as an inclusion criteria and in patients with high peripheral blast (PB) burden,
the use of Hydroxyurea will be mandated with the goal of bringing PB burden below a key threshold number that we have identified
from two previously complete Phase 1 clinical trials totaling 38 patients. In addition, the use of granulocyte colony-stimulating
factors (GCSF) will be mandated. Low dose cytarabine has been eliminated from the protocol and the Phase 2 clinical trial will
evaluate Actimab-A as a monotherapy. The secondary endpoint of the Phase 2 clinical trial will be overall survival.
In
February 2017, we initiated a Phase 1 investigator initiated clinical trial to study Actimab-M in multiple myeloma (MM). Multiple
myeloma is a cancer of plasma cells that is currently incurable. The Phase 1 trial will enroll up to 12 patients with relapsed
or refractory multiple myeloma who have positive CD33 expression. This Phase 1 study is designed as a dose escalation study intended
to assess safety, establish maximum tolerable dose (MTD) and assess efficacy. Patients will be administered Actimab-M on day 1
at an initial dose of 0.5 µCi/kg and then assessed at day 42 for safety and efficacy. The dose can be increased to 1.0 µCi/kg
or reduced to 0.25 µCi/kg based on safety assessment that will evaluate dose limiting toxicities (DLTs). Patients may receive
up to 8 cycles of therapy but in no event will cumulative administration exceed 4.0 µCi/kg of Actimab-M.
Business
Strategy
We
intend to potentially develop our most advanced clinical stage product candidates through approval in the case of Iomab™-B,
and up to and including a Phase 2 proof of concept human clinical trial (a trial designed to provide data on the drug’s
efficacy) in the case of Actimab™-A. If these efforts are successful, we may elect to commercialize Iomab™-B on our
own or with a partner in the United States and/or outside of the United States to out-license the rights to develop and commercialize
the product to a strategic partner. In the case of Actimab™-A, we will most likely seek to enter into strategic partnerships
whereby the strategic partner(s) co-fund(s) further human clinical trials of the drug that are needed to obtain regulatory approvals
for commercial sale within and outside of the United States. In parallel, we intend to identify and begin initial human trials
with additional actinium-225 product candidates in other cancer indications. We intend to retain marketing rights for our products
in the United States whenever possible and out-license marketing rights to our partners for the rest of the world. We may also
seek to in license other applicable opportunities should such technology become available.
Market
Opportunity
We
compete in the marketplace for cancer treatments estimated to reach over $83 billion in 2016 sales, according to “The Global
Use of Medicines: Outlook Through 2016 Report by the IMS Institute for Healthcare Informatics, July 2012.” While surgery,
radiation and chemotherapy remain staple treatments for cancer, their use is limited by the fact that they often cause substantial
damage to normal cells. On the other hand, targeted monoclonal antibody therapies exert most or all of their effect directly on
cancer cells, but often lack sufficient killing power to eradicate all cancer cells with just the antibody. A new approach for
treating cancer is to combine the precision of antibody-based targeting agents with the killing power of radiation or chemotherapy
by attaching powerful killing agents to precise molecular carriers called monoclonal antibodies (mAb). We use mAbs labeled with
radioisotopes to deliver potent doses of radiation directly to cancer cells while sparing healthy tissues. The radioisotopes we
use are the alpha emitter Ac-225 and the beta emitter I-131. I-131 is among the best known and well characterized radioisotopes.
It is used very successfully in treatment of papillary and follicular thyroid cancer as well as other thyroid conditions. It is
also attached to a monoclonal antibody in treatment of Non-Hodgkin’s Lymphoma (“NHL”). It is also used experimentally
with different carriers in other cancers. Ac-225 has many unique properties and we believe we are a leader in developing this
alpha emitter for clinical applications using our proprietary APIT technology.
Our
most advanced products are Iomab™-B, I-131 labeled mAb for preparation of relapsed and refractory AML patients for HSCT;
and Actimab™-A, Ac-225 labeled mAb for treatment of newly diagnosed AML, a cancer of the blood, in patients ineligible for
currently approved therapies. Iomab™-B offers a potentially curative treatment for these patients, most of whom do not survive
beyond a year after being diagnosed with this condition. Iomab™-B has also demonstrated efficacy in HSCT preparation for
other blood cancer indications, including myelodysplastic syndrome (“MDS”), acute lymphoblastic leukemia (“ALL”),
Hodgkin’s Lymphoma, and Non-Hodgkin’s Lymphoma (“NHL”). These are all follow-on indications for which
Iomab™-B can be developed and it is our intention to explore these opportunities at a future date. We believe the aggregate
worldwide market potential for the treatment of AML, MDS, ALL, Hodgkin’s Lymphoma, multiple myeloma
and NHL is approximately $4.1 billion.
In
December 2015, we announced that the FDA cleared our IND filing for Iomab-B, and that we will proceed with a pivotal, Phase 3
clinical trial. We anticipate the Phase 3, controlled, randomized, pivotal trial will complete enrollment of patients by 2018
and assuming that the trial meets its endpoints, it will form the basis for a BLA. We, in our recently approved IND filing, established
an agreement with the FDA that the path to a BLA submission would include a single, pivotal Phase 3 clinical study if it is successful.
The population in this two arm, randomized, controlled, multicenter trial will be refractory and relapsed AML patients over the
age of 55. The trial size was set at 150 patients with 75 patients per arm. The primary endpoint in the pivotal Phase 3 trial
is durable complete remission, defined as a complete remission lasting at least six months and the secondary endpoint will be
overall survival at one year. There are currently no effective treatments approved by the FDA for AML in this patient population
and there is no defined standard of care. Iomab-B has completed several physicians sponsored clinical trials examining its potential
as a conditioning regimen prior to HSCT in various blood cancers, including the Phase 1/2 clinical trial in relapsed and/or refractory
AML patients. The results of these clinical trials in over 300 patients have demonstrated the potential of Iomab-B to create a
new treatment paradigm for bone marrow transplants by: expanding the pool to ineligible patients who do not have any viable treatment
options currently; enabling a shorter and safer preparatory interval for HSCT; reducing post-transplant complications; and showing
a clear survival benefit including curative potential.
Other
potential product opportunities in which significant preclinical work is being undertaken include metastatic colorectal cancer,
metastatic prostate cancer and antiangiogenesis which reduces the blood supply to solid tumors. We believe the worldwide market
potential for the treatment of metastatic colorectal cancer is approximately $4.8 billion, and we believe the worldwide market
potential for the treatment of metastatic prostate cancer is approximately $6.0 billion. We also believe the worldwide market
potential for the treatment of Glioblastoma Multiforme, a potential indication based on an antiangiogenesis approach, is approximately
$1.1 billion. We estimate the market potential for these indications based on company research, published rates of disease incidence
and company calculations based on costs of currently used therapies.
We
believe that our biggest market opportunity lies in the applicability of our APIT platform technology to a wide variety of cancers.
A broad range of solid and blood borne cancers can be potentially targeted by mAbs to enable treatment with the APIT technology.
The APIT technology could potentially be applied to mAbs that are already approved by the FDA to create more efficacious and/or
safer drugs (“biobetters”).
In
March 2016, the FDA granted orphan drug designation for Ioamb-B and in October 2016 the European Medicines Agency (EMA) granted
orphan designation in the European Union (EU) for Iomab-B. In November 2014, the FDA granted orphan-drug designation for Actimab™-A
and in December 2016, we submitted an application to the EMA for orphan designation in the EU for Actimab-A. The FDA, through
its Office of Orphan Products Development, grants orphan status to drugs and biologic products that are intended for the safe
and effective treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United
States. Orphan drug designation provides a drug developer with certain benefits and incentives, including a period of marketing
exclusivity if regulatory approval is ultimately received for the designated indication; potential tax credits on United States
clinical trials; eligibility for orphan drug grants; and waiver of certain administrative fees. The EMA, through its Committee
for Orphan Medicinal Products (COMP), examines applications for orphan designation. To qualify for orphan designation, the prevalence
of the condition must be less than 5 in 10,000, it must be life threatening or chronically debilitating and there must be no satisfactory
method of treating the condition. Sponsors who obtain orphan designation receive numerous incentives including protocol assistance,
a reduction or waving of fees and 10 years of market exclusivity should the therapy be approved. The process of filing and receiving
the orphan medicines designation can take between eight to fourteen months in most cases.
Clinical
Trials
Iomab™-B
Iomab™-B
is our lead product candidate currently in a pivotal Phase 3 multicenter clinical trial. It consists of the monoclonal antibody
BC8 and beta emitting radioisotope iodine 131 (I-131). The indication for that trial is bone marrow conditioning for HSCT in patients
with relapsed and refractory AML over the age of 55.
Previous
Iomab™-B clinical trials leading to the planned Phase 3 trial currently in preparation included:
Indications
|
|
N
|
|
Key
Findings
|
|
|
|
|
|
AML,
MDS, ALL (adult)
|
|
34
|
|
–7/34
patients with median disease free state (DFS) of 17 years.
|
|
|
|
|
–18/34
patients in remission at day 80
|
|
|
|
|
|
AML
>1st remission (adult)
|
|
23
|
|
–15/23
in remission at day 28
|
|
|
|
|
|
AML
1st remission (age 16-50)
|
|
43
|
|
–23/43
DFS from 5-16 years
|
|
|
|
|
–30/43
in remission at day 28
|
|
|
|
|
–33/43
in remission at day 80
|
|
|
|
|
|
High-risk
MDS, advanced AML
|
|
68
in dose escalation study
|
|
–CR
(complete remission) in all patients
|
(age
50+)
|
|
31
treated at MTD
|
|
–1
yr survival ~40% for all patients
|
|
|
|
|
–1
yr survival ~45% for pts treated at MTD maximum tolerated dose)
|
|
|
|
|
|
High-risk
MDS, AML
(age 18–50)
|
|
14
in dose escalation
|
|
All
patients achieved full donor chimerism by day 28 post-transplant
|
|
|
|
|
|
High-risk
MDS, AML
–haploidentical donors (adult)
|
|
8
in dose escalation
|
|
–6/8
treated patients achieved CR by day 28
–8/8
patients 100% donor chimerism by day 28
|
Ongoing
Iomab™-B clinical trials include:
Indications
|
|
|
Phase
|
|
Relapsed and refractory Hodgkin Lymphoma and NHL (adult)
|
|
|
Phase
1
|
|
Advanced AML, ALL and MDS (adult)
|
|
|
Phase
2
|
|
AML 1st remission (age 16-50)
|
|
|
Phase
2
|
|
High-risk MDS, advanced AML (age 16-50)
|
|
|
Phase
2
|
|
There
are additional ongoing clinical trials with BC8 antibody labeled with yttrium 90 (Y-90).
Phase
3 Iomab™-B clinical trial in preparation:
We
have obtained FDA’s comment and guidance on the Iomab™-B Phase 3 clinical trial design, and the FDA has identified
the following design features as generally acceptable, dependent on the results of the trial:
|
—
|
Single
pivotal study, pending trial results;
|
|
|
|
|
—
|
Patient
population: refractory AML patients age of 55 and older, where refractory is defined as either primary failure to achieve
a complete remission after 2 cycles of induction therapy; relapsed after 6 months in complete remission; second or higher
relapse; or relapsed disease not responding to intensive salvage therapy;
|
|
|
|
|
—
|
Trial
arms: study arm and control arm with physician’s choice of conventional care with curative intent; and
|
|
|
|
|
—
|
Trial
size: 150 patients total (75 patients per arm).
|
Actimab™-A
Actimab™-A
is currently in the Phase 2 portion of a multicenter Phase 1/2 clinical trial in AML. It consists of the monoclonal antibody Lintuzumab
and alpha emitting radioisotope actinium 225 (Ac-225). The indication in the ongoing trial is newly diagnosed AML patients over
the age of 60.
Previous
clinical trials leading to this trial included:
|
—
|
Phase
1 clinical trial with Bismab-A, the first generation product consisting of the same monoclonal antibody Lintuzumab and Bi-213
alpha emitter, a daughter of Ac-225;
|
|
|
|
|
—
|
Phase
1/2 clinical trial with Bismab-A, the first generation product consisting of the same monoclonal antibody Lintuzumab and Bi-213
alpha emitter, a daughter of Ac-225; and
|
|
|
|
|
—
|
Dose
escalating pilot Phase 1 clinical trial with Actimab™-A, the current product consisting of the Lintuzumab monoclonal
antibody and Ac-225 alpha emitter.
|
Completed
Actimab™-A related clinical trials outcomes:
|
—
|
The
Phase 2 arm of the Bismab-A drug study has shown signs of the drug’s efficacy and safety, including reduction in peripheral
blast counts and complete responses in some patients. Bi-213 is a daughter, i.e., product of the degradation of Ac-225, with
cancer cell killing properties similar to Ac-225 but is less potent. The Phase 1 Actimab™-A trial at MSKCC with a single-dose
administration of Actimab™-A showed elimination of leukemia cells from blood in 67% of all evaluable patients who received
a full dose and in 83% of those treated at dose levels above 0.5 microcuries per kilogram (µCi/kg), and eradication
of leukemia cells in both blood and bone marrow in 20% of all evaluable patients and 25% of those treated at dose levels above
0.5 µCi/kg. Maximum tolerated single dose in this trial was established at 3 µCi/kg.
|
High
potency means that a relatively low amount of drug is needed to produce a given effect. In preclinical and Phase 1 clinical studies,
Actimab-A (225Ac-lintuzumab) has demonstrated at least 500-1000 times higher potency than the first-generation predecessor
(213Bi-lintuzumab) upon which it is based. This difference is due to intrinsic physicochemical properties of Actimab-A
that were first established in vitro, in which Actimab-A killed multiple cell lines at doses at least 1000 times lower
(based on LD50 values) than Bismab-A analogs. Key factors in Actimab-A’s higher potency are the yield of 4 alpha-emitting
isotopes per 225Ac (compared to 1 alpha decay for bismuth 213) and much longer half-life (10 day for 225Ac
vs 46 minutes for 213Bi).
In
preclinical animal models, doses in the nanocurie range prolonged survival. In humans, Actimab-A was previously studied in a Phase
I monotherapy trial of relapsed or refractory AML patients at MSKCC. Dose levels in that study re-confirmed the substantially
higher potency of Actimab-A, as compared to equivalent dosing of the first-generation Bismab-A (213Bi-lintuzumab) construct,
which had nevertheless established safety and efficacy in a Phase 1/2 trial in high-risk AML with cytoreduction.
Sources:
Jurcic JG. Targeted Alpha-Particle Immunotherapy with Bismuth-213 and Actinium-225 for Acute Myeloid Leukemia. J. Postgrad Med
Edu Res 2013, 47(1):14-17; ; JG Jurcic et al, Phase 1 Trial of the Targeted Alpha- Particle Nano-Generator Actinium-225 (225Ac)-Lintuzumab
in Acute Myeloid Leukemia (AML) J Clin Oncol 29:2011 (suppl, abstr 6516); McDevitt MR et al, “Tumor Therapy with Targeted
Atomic Nanogenerators” Science 2001, 294:1537—1540; Rosenblat TL et al, “Sequential cytarabine and alpha-particle
immunotherapy with bismuth- 213-lintuzumab (HuM195) for acute myeloid leukemia” Clin Cancer Res. 2010, 16(21):5303-5311;
Jurcic JG et al. “Phase I Trial of the Targeted Alpha-Particle Nano-Generator Actinium-225 (225Ac)-Lintuzumab in Acute Myeloid
Leukemia (AML)” Blood (ASH Meeting Abstracts) 2012.
Ongoing
Actimab™-A trial:
We
have completed the Phase 1 portion of our first company sponsored Phase 1/2 multi-center trial with fractionated (two) doses of
Actimab™-A, for the treatment of patients newly diagnosed with AML over the age of 60. Actimab-A consists of an AML specific
monoclonal antibody (HuM195, also known as Lintuzumab™) and the actinium 225 radioactive isotope attached to it. Results
from the Phase 1 portion of the trial showed that 28% (5 of 18) of patients had objective responses (2CR, 1CRp and 2 CRi (complete
remission with incomplete blood count recovery)) with median response duration of 9.1 months. Mean bone marrow blast reduction
amongst evaluable patients (14 of 18) was 67% with 57% of patients having bone marrow blast reduction of 50% or greater and 79%
(11 of 14) of patients having bone marrow blast reductions after Cycle 1 of therapy. Maximum tolerated dose (MTD) was not reached
in this trial. We have elected to progress to the Phase 2 portion of the trial at 2.0 μCi/kg/fraction, the highest dose level
from the Phase 1 portion of the clinical trial.
The
Phase 2 portion of the trial will enroll 53 patients and will study Actimab-A as a monotherapy. We received agreement from the
FDA for multiple revisions to the protocol for the Phase 2 portion of the clinical trial that include:
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Removing the use of low dose cytarabine from the Phase 2 protocol;
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Stipulating Peripheral blast burden as an inclusion criteria with 200 ML being the threshold;
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Mandating the use of hydroxyurea in patients with peripheral blast count above 200 ML to lower their peripheral blasts below 200ML/
prior to Actimab-A administration; and
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Mandating the use of granulocyte colony-stimulating factor (GCSF) support.
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Bismab-A
trials and the Phase 1 Actimab™-A trial were focused on relapsed, refractory and other difficult to treat acute myeloid
leukemia patients. The current multicenter Phase 1/2 trial is focused on newly diagnosed AML patients who have historically had
better outcomes.
Intellectual
Property
We
have developed or in-licensed numerous patents and patent applications and possess substantial know-how and trade secrets relating
to the development and commercialization of our products. In the past year, we have strengthened our intellectual property position
with the allowance of three additional patents and further allowances are anticipated in 2017. As of February 22, 2017, our patent
portfolio includes: 61 issued and pending patent applications, of which 10 are issued in the United States, 1 is pending in the
United States, and 50 are issued internationally and pending internationally. Additionally, several non-provisional patent applications
are expected to be filed in 2017 based on provisional patent applications filed in 2016. This is part of an ongoing strategy to
continue to strengthen our intellectual property position. About half of our patents are in-licensed from third parties and half
are held by us. These patents cover key areas of our business, including use of the actinium-225 and other alpha emitting isotopes
attached to cancer specific carriers like monoclonal antibodies, methods for manufacturing key components of our product candidates
including actinium-225 alpha emitting radioisotope and carrier antibodies, and methods for manufacturing finished product candidates
for use in cancer treatment. The table below classifies these patents by related family:
Area
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Description
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US
Expiration
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US
Status
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Owner/
Licensor
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Platform
technology
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Antibody
conjugates with DOTA chelators; methods of treating cancer using the same
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2021
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Issued
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MSKCC
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Platform
technology
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Radioimmunoconjugate
generation
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2029
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Issues
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Owned
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Drug
preparation methods
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Actinium
225 labeling method (binding to an antibody)
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2030
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Pending
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Owned
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Drug
preparation methods
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Bismuth
213 labeling method (binding to an antibody)
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2019
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Issued
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MSKCC
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Isotope
production methods
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Actinium
225 manufacturing in a cyclotron
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2026/2027
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Issued
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Owned
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A
patent whose claims address methods of treating hematopoietic malignancies with Iomab™-B is pending; still, we have developed
a proprietary strategy based on trade secret protection and the potential for orphan drug and data exclusivities. The BC8 antibody,
cell line and related know-how has been exclusively licensed by us from the Fred Hutchinson Cancer Research Center (FHCRC) in
exchange for milestones, royalties and research support.
Patents
related to the antibody component of Actimab-A have been exclusively licensed by us from AbbVie Biotherapeutics Corp. for use
with alpha-emitting radioisotopes in exchange for future development and commercialization milestones, a royalty on net sales
for a period of 12.5 years from first commercial sale, a negotiation right to be our clinical and/or commercial antibody supplier,
a negotiation right to co-promote Actimab™-A in the United States on terms to be negotiated, and the grant-back of IP rights
covering improvements to the antibody for use other than with an alpha-emitting isotope. Patents covering actinium-225 conjugated
to antibodies have been exclusively licensed by us from MSKCC in exchange for license fees, research support payments, development
milestones, 2% royalties on net sales for the term of the licensed patents or, if later, 10 years from first commercial sale,
and 15% of any sublicense income we may receive. We source actinium-225 under an agreement with the Oak Ridge National Laboratory
(ORNL) that expires at the end of 2017. We believe, but cannot guarantee, that we will be able to renew this contract for additional
annual periods.
Corporate
and Other Information
We
were organized in the State of Nevada on October 6, 1997 and reorganized in the State of Delaware on March 20, 2013. Our principal
executive offices are located at 275 Madison, 7th Floor, New York, New York 10016. Our telephone number is (646) 677-3870.
Our website address is www.actiniumpharmaceuticals.com. Information accessed through our website is not incorporated into this
prospectus and is not a part of this prospectus.
The
Securities We May Offer
The
descriptions of the securities contained in this prospectus, together with the applicable prospectus supplements, summarize the
material terms and provisions of the various types of securities that we may offer. We will describe in the applicable prospectus
supplement relating to any securities the particular terms of the securities offered by that prospectus supplement. If we so indicate
in the applicable prospectus supplement, the terms of the securities may differ from the terms we have summarized below. We will
also include information in the prospectus supplement, where applicable, about material U.S. federal income tax considerations
relating to the securities, and the securities exchange, if any, on which the securities will be listed.
We
may sell from time to time, in one or more primary offerings, our common stock, preferred stock, debt securities, warrants, rights,
purchase contracts or units, or any combination of the foregoing.
In
this prospectus, we refer to the common stock, preferred stock, debt securities, warrants, rights, purchase contracts or units,
or any combination of the foregoing securities to be sold by us in a primary offering collectively as “securities.”
The total dollar amount of all securities that we may issue under this prospectus will not exceed $200,000,000.
This
prospectus may not be used to consummate a sale of securities unless it is accompanied by a prospectus supplement.
RISK
FACTORS
An
investment in our securities involves a high degree of risk. The prospectus supplement applicable to each offering of our securities
will contain a discussion of the risks applicable to an investment in our securities. Before deciding whether to invest in our
securities, you should carefully consider the specific factors discussed under the heading “Risk Factors” in the applicable
prospectus supplement, together with all of the other information contained or incorporated by reference in the prospectus supplement
or appearing or incorporated by reference in this prospectus. You should also consider the risks, uncertainties and assumptions
discussed under Item 1A, “Risk Factors,” in our Annual Report on Form 10-K for the fiscal year ended December 31,
2016, all of which are incorporated herein by reference, as updated or superseded by the risks and uncertainties described under
similar headings in the other documents that are filed after the date hereof and incorporated by reference into this prospectus
and any prospectus supplement related to a particular offering. The risks and uncertainties we have described are not the only
ones we face. Additional risks and uncertainties not presently known to us or that we currently deem immaterial may also affect
our operations. Past financial performance may not be a reliable indicator of future performance, and historical trends should
not be used to anticipate results or trends in future periods. If any of these risks actually occurs, our business, business prospects,
financial condition or results of operations could be seriously harmed. This could cause the trading price of our common stock
to decline, resulting in a loss of all or part of your investment. Please also read carefully the section below entitled “Special
Note Regarding Forward-Looking Statements.”
SPECIAL
NOTE REGARDING FORWARD-LOOKING STATEMENTS
This
prospectus, each prospectus supplement and the information incorporated by reference in this prospectus and each prospectus supplement
contain “forward-looking statements,” which include information relating to future events, future financial performance,
strategies, expectations, competitive environment and regulation. Words such as “may,” “should,” “could,”
“would,” “predicts,” “potential,” “continue,” “expects,” “anticipates,”
“future,” “intends,” “plans,” “believes,” “estimates,” and similar
expressions, as well as statements in future tense, identify forward-looking statements. Forward-looking statements should not
be read as a guarantee of future performance or results and will probably not be accurate indications of when such performance
or results will be achieved. Forward-looking statements are based on information we have when those statements are made or our
management’s good faith belief as of that time with respect to future events, and are subject to risks and uncertainties
that could cause actual performance or results to differ materially from those expressed in or suggested by the forward-looking
statements. Important factors that could cause such differences include, but are not limited to:
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our
history of recurring losses and negative cash flows from operating activities, significant future commitments and the uncertainty
regarding the adequacy of our liquidity to pursue our complete business objectives;
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our
ability to complete clinical trials as anticipated and obtain and maintain regulatory approvals for our products;
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our
ability to adequately protect our intellectual property;
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disputes
over ownership of intellectual property;
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the
risk that the data collected from our current and planned clinical trials may not be sufficient to demonstrate that our products
is an attractive alternative to other products;
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intense
competition in our industry, with competitors having substantially greater financial, technological, research and development,
regulatory and clinical, manufacturing, marketing and sales, distribution and personnel resources than we do;
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entry
of new competitors and products and potential technological obsolescence of our products;
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loss
of a key customer or supplier;
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technical
problems with our research and products and potential product liability claims;
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adverse
economic conditions;
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adverse
federal, state and local government regulation, in the United States;
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price
increases for supplies;
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inability
to carry out research, development and commercialization plans; and
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loss
or retirement of key executives and research scientists.
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You
should review carefully the section entitled “Risk Factors” beginning on page 8 of this prospectus for a
discussion of these and other risks that relate to our business and investing in our securities. The forward-looking
statements contained or incorporated by reference in this prospectus or any prospectus supplement are expressly qualified in
their entirety by this cautionary statement. We do not undertake any obligation to publicly update any forward-looking
statement to reflect events or circumstances after the date on which any such statement is made or to reflect the occurrence
of unanticipated events.
USE
OF PROCEEDS
Unless
otherwise indicated in the prospectus supplement, we currently intend to use the net proceeds from the sale of securities offered
by this prospectus for general corporate purposes, including capital expenditures, the advancement of our drug candidates in clinical
trials, such as Iomab™-B and Actimab-A, preclinical trials, and to meet working capital needs.
Investors
are cautioned, however, that expenditures may vary substantially from these uses. Investors will be relying on the judgment of
our management, who will have broad discretion regarding the application of the proceeds of this offering. The amounts and timing
of our actual expenditures will depend upon numerous factors, including the amount of cash generated by our operations, the amount
of competition and other operational factors. We may find it necessary or advisable to use portions of the proceeds from this
offering for other purposes.
From
time to time, we evaluate these and other factors and we anticipate continuing to make such evaluations to determine if the existing
allocation of resources, including the proceeds of this offering, is being optimized. Circumstances that may give rise to a change
in the use of proceeds include:
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change in development plan or strategy;
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the
addition of new products or applications;
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technical
delays;
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delays
or difficulties with our clinical trials;
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negative
results from our clinical trials;
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difficulty
obtaining U.S. Food and Drug Administration approval; and
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the
availability of other sources of cash including additional offerings, if any.
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DESCRIPTION
OF CAPITAL STOCK
The
following description of common stock and preferred stock summarizes the material terms and provisions of the common stock and
preferred stock that we may offer under this prospectus, but is not complete. For the complete terms of our common stock and preferred
stock, please refer to our certificate of incorporation, as amended and our bylaws, as may be amended from time to time. While
the terms we have summarized below will apply generally to any future common stock or preferred stock that we may offer, we will
describe the specific terms of any series of preferred stock in more detail in the applicable prospectus supplement. If we so
indicate in a prospectus supplement, the terms of any preferred stock we offer under that prospectus supplement may differ from
the terms we describe below.
We
have authorized 250,000,000 shares of capital stock, par value $0.001 per share, of which 200,000,000 are shares of common stock
and 50,000,000 are shares of preferred stock. On March 10, 2017, there were 55,807,742 shares of common stock issued and outstanding
and no shares of preferred stock issued and outstanding. There are no preferred issued and outstanding. The authorized and unissued
shares of common stock and the authorized and undesignated shares of preferred stock are available for issuance without further
action by our stockholders, unless such action is required by applicable law or the rules of any stock exchange on which our securities
may be listed. Unless approval of our stockholders is so required, our board of directors does not intend to seek stockholder
approval for the issuance and sale of our common stock or preferred stock.
We
also have warrants that are outstanding, which are described below.
Common
Stock
The
holders of our common stock are entitled to one vote per share. Our certificate of incorporation does not provide for cumulative
voting. Our directors are divided into three classes. At each annual meeting of stockholders, directors elected to succeed those
directors whose terms expire are elected for a term of office to expire at the third succeeding annual meeting of stockholders
after their election. The holders of our common stock are entitled to receive ratably such dividends, if any, as may be declared
by our board of directors out of legally available funds; however, the current policy of our board of directors is to retain earnings,
if any, for operations and growth. Upon liquidation, dissolution or winding-up, the holders of our common stock are entitled to
share ratably in all assets that are legally available for distribution. The holders of our common stock have no preemptive, subscription,
redemption or conversion rights. The rights, preferences and privileges of holders of our common stock are subject to, and may
be adversely affected by, the rights of the holders of any series of preferred stock, which may be designated solely by action
of our board of directors and issued in the future.
Our
common stock is listed on the NYSE MKT under the symbol “ATNM.”
Preferred
Stock
The
board of directors is authorized, subject to any limitations prescribed by law, without further vote or action by the stockholders,
to issue from time to time shares of preferred stock in one or more series. Each such series of preferred stock shall have such
number of shares, designations, preferences, voting powers, qualifications, and special or relative rights or privileges as shall
be determined by the board of directors, which may include, among others, dividend rights, voting rights, liquidation preferences,
conversion rights and preemptive rights. Issuance of preferred stock by our board of directors may result in such shares having
dividend and/or liquidation preferences senior to the rights of the holders of our common stock and could dilute the voting rights
of the holders of our common stock.
Prior
to the issuance of shares of each series of preferred stock, the board of directors is required by the Delaware General Corporation
Law and our certificate of incorporation to adopt resolutions and file a certificate of designation with the Secretary of State
of the State of Delaware. The certificate of designation fixes for each class or series the designations, powers, preferences,
rights, qualifications, limitations and restrictions, including, but not limited to, some or all of the following:
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the
number of shares constituting that series and the distinctive designation of that series, which number may be increased or
decreased (but not below the number of shares then outstanding) from time to time by action of the board of directors;
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the
dividend rate and the manner and frequency of payment of dividends on the shares of that series, whether dividends will be
cumulative, and, if so, from which date;
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whether
that series will have voting rights, in addition to any voting rights provided by law, and, if so, the terms of such voting
rights;
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whether
that series will have conversion privileges, and, if so, the terms and conditions of such conversion, including provision
for adjustment of the conversion rate in such events as the board of directors may determine;
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whether
or not the shares of that series will be redeemable, and, if so, the terms and conditions of such redemption;
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whether
that series will have a sinking fund for the redemption or purchase of shares of that series, and, if so, the terms and amount
of such sinking fund;
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whether
or not the shares of the series will have priority over or be on a parity with or be junior to the shares of any other series
or class in any respect;
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the
rights of the shares of that series in the event of voluntary or involuntary liquidation, dissolution or winding up of the
corporation, and the relative rights or priority, if any, of payment of shares of that series; and
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any
other relative rights, preferences and limitations of that series.
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Once
designated by our board of directors, each series of preferred stock may have specific financial and other terms that will be
described in a prospectus supplement. The description of the preferred stock that is set forth in any prospectus supplement is
not complete without reference to the documents that govern the preferred stock. These include our certificate of incorporation
and any certificates of designation that our board of directors may adopt.
All
shares of preferred stock offered hereby will, when issued, be fully paid and non-assessable, including shares of preferred stock
issued upon the exercise of preferred stock warrants or subscription rights, if any.
Although
our board of directors has no intention at the present time of doing so, it could authorize the issuance of a series of preferred
stock that could, depending on the terms of such series, impede the completion of a merger, tender offer or other takeover attempt.
Warrants
Common
Stock Warrants
On
December 27, 2013 and January 10, 2014, we issued common stock warrants to certain investors in a private placement of
common stock and warrants (the “Common Stock Warrants”). The Common Stock Warrants have a five year
term from each closing that occurred on December 27, 2013 and January 10, 2014, and are exercisable for an aggregate of up to
276,529 shares of the Company’s common stock at an initial per share exercise price of $9.00, subject to adjustments as
set forth below. As of March 10, 2017 we have 276,529 shares of Common Stock Warrants outstanding. The Company may also
call this warrant for redemption upon written notice to all warrant holders at any time the closing price of the common stock
exceeds $15.00 (as may be adjusted pursuant to warrant agreement) for 20 consecutive trading days, as reported by Bloomberg,
provided at such time there is an effective registration statement covering the resale of the shares underlying the
warrants. In the 60 business days following the date the redemption notice is deemed given in accordance with the
agreement, investors may choose to exercise this warrant or a portion of the warrant by paying the then applicable exercise
price per share for every share exercised. Any shares not exercised on the last day of the exercise period will be
redeemed by the Company at $0.001 per share.
The
exercise prices of the Common Stock Warrants are subject to adjustment upon certain events. If the Company at any time while the
warrants remain outstanding and unexpired shall declare a dividend or make a distribution on the outstanding Common Stock payable
in shares of its capital stock, or split, subdivide or combine the securities as to which purchase rights under this Warrant exist
into a different number of securities of the same class, the exercise price for such securities shall be proportionately decreased
in the case of a dividend, split or subdivision or proportionately increased in the case of a combination.
Series
B Warrants
The
Series B Warrants have a five year term from December 19, 2012 and are exercisable for an aggregate of up to 1,559,505 shares
of the Company’s common stock at an initial per share exercise price of $2.48, subject to adjustment as set forth
below. As of March 10, 2017, there were 1,317,195 warrants outstanding. These warrants have a cashless exercise
provision. The Company also has a right of first refusal on the holder’s sale of the warrant
shares. The Company may also call this warrant for redemption upon written notice to all warrant holders at any
time the closing price of the common stock exceeds $1.50 (as may be adjusted pursuant to warrant agreement) for 20
consecutive trading days, as reported by Bloomberg, provided at such time there is an effective registration statement
covering the resale of the shares underlying the warrants. In the 60 business days following the date the
redemption notice is deemed given in accordance with the agreement, investors may choose to exercise this warrant or a
portion of the warrant by paying the then applicable exercise price per share for every share exercised. Any
shares not exercised on the last day of the exercise period will be redeemed by the Company at $0.001 per share.
The
exercise price of the Series B Warrants is subject to adjustment upon certain events. If the Company at any time while the warrants
remain outstanding and unexpired shall declare a dividend or make a distribution on the outstanding Common Stock payable in shares
of its capital stock, or split, subdivide or combine the securities as to which purchase rights under this Warrant exist into
a different number of securities of the same class, the exercise price for such securities shall be proportionately decreased
in the case of a dividend, split or subdivision or proportionately increased in the case of a combination.
In
addition, for so long as there are any warrants outstanding, if and whenever at any time and from time to time after the warrant
issue date, as applicable, the Company shall issue any shares of common stock for no consideration or a consideration per share
less than the exercise price, as applicable, then, forthwith upon such issue or sale, the warrants shall be subject to a proportional
adjustment determined by multiplying such warrant exercise price by the following fraction:
Where:
N(0)
= the number of shares of common stock outstanding (calculated on a Fully Diluted Basis) immediately prior to the issuance of
such additional shares of common stock or common stock Equivalents;
N(1)
= the number of shares of common stock which the aggregate consideration, if any (including the aggregate Net Consideration Per
Share with respect to the issuance of common stock equivalents), received or receivable by the Company for the total number of
such additional shares of common stock so issued or deemed to be issued would purchase at the warrant exercise price, as applicable,
in effect immediately prior to such issuance; and
N(2)
= the number of such additional shares of common stock so issued or deemed to be issued.
Stock
Offering Warrants
The
Stock Offering Warrants have a term ending on January 31, 2019 and are exercisable for an aggregate of up to 2,682,155
shares of the Company’s common stock at an initial per share exercise price of $0.78, subject to adjustment as set
forth below (anti-dilution). As of March 3, 2017, there were 1,245,137 warrants outstanding. These warrants have a
cashless exercise provision. The Company also has a right of first refusal on the holder’s sale of the
warrant shares.
These
warrants have a cashless exercise provision. The Company also has a right of first refusal on the holder’s sale
of the warrant shares. The exercise prices of the Stock Offering Warrants are subject to adjustment upon certain
events. If the Company at any time while the warrants remain outstanding and unexpired shall declare a dividend or make a distribution
on the outstanding Common Stock payable in shares of its capital stock, or split, subdivide or combine the securities as to which
purchase rights under this Warrant exist into a different number of securities of the same class, the exercise price for such
securities shall be proportionately decreased in the case of a dividend, split or subdivision or proportionately increased in
the case of a combination.
Consulting
Firm Warrants
The
Consulting Firm Warrants have a term ending on December 17, 2019 and are exercisable for an aggregate of up to 3,755,560
shares of the Company’s common stock. As of March 10, 2017, there were 1,502,223 warrants outstanding. These
warrants may not be exercised by the Holder upon less than 90 days prior written notice of such exercise and provided further
that that the Holder may elect, in its sole discretion, to waive the Prior Notice Requirement, in whole or in part, upon 65
days prior written notice of such waiver. These warrants have a cashless exercise provision and were
issued at an initial per share exercise price of $0.001, subject to adjustment as if the Company at any time while the
warrants remain outstanding and unexpired shall declare a dividend or make a distribution on the outstanding Common Stock
payable in shares of its capital stock, or split, subdivide or combine the securities as to which purchase rights under this
Warrant exist into a different number of securities of the same class, the exercise price for such securities shall be
proportionately decreased in the case of a dividend, split or subdivision or proportionately increased in the case of a
combination. The warrants are also subject to piggy-back registration rights. The holder has also
agreed that following the consummation of the pubco transaction (which occurred on December 28, 2012), the holder will not
sell or otherwise transfer any shares of common stock of the Company owned by holder, as a result of the exercise of the
warrant until the date that is the earlier of (i) twelve (12) months from the closing date of the pubco
transaction; or (ii) six (6) months following the effective date of the Registration Statement of which this prospectus is a
part.
2015
Offering Warrants
The 2015 Offering Warrants have a term
ending February 11, 2019 and are exercisable for an aggregate of up to 3,333,333 shares of the Company's common stock at
$6.50 per share. As of March 14, 2017, there were 3,333,333 warrants outstanding. The exercise price and the number of
warrant shares shall be adjusted from time to time if the Company at any time on or after the issuance date subdivides (by
any stock split, stock dividend, recapitalization or otherwise) one or more classes of its outstanding shares of common stock
into a greater number of shares, the exercise price in effect immediately prior to such subdivision will be proportionately
reduced and the number of warrant shares will be proportionately increased. If the Company at any time on or after
the issuance date combines (by combination, reverse stock split or otherwise) one or more classes of its outstanding shares
of Common Stock into a smaller number of shares, the exercise price in effect immediately prior to such combination will be
proportionately increased and the number of warrant shares will be proportionately decreased.
If at any time prior to
the expiration date the Company grants, issues or sells any Options, Convertible Securities or rights to purchase stock, warrants,
securities or other property pro rata to the record holders of any class of shares of Common Stock (the “Purchase Rights”),
then the Holder will be entitled to acquire, upon the terms applicable to such Purchase Rights, the aggregate Purchase Rights
which the Holder could have acquired if the Holder had held the number of shares of Common Stock acquirable upon complete exercise
of this Warrant (without regard to any limitations on the exercise of this Warrant) immediately before the date on which a record
is taken for the grant, issuance or sale of such Purchase Rights, or, if no such record is taken, the date as of which the record
holders of shares of common stock are to be determined for the grant, issue or sale of such Purchase Rights (provided, however,
that to the extent that the Holder’s right to participate in any such Purchase Right would result in the holder exceeding
the Maximum Percentage, then the holder shall not be entitled to participate in such Purchase Right to such extent (or beneficial
ownership of such shares of Common Stock as a result of such Purchase Right to such extent) and such Purchase Right to such extent
shall be held in abeyance for the Holder until such time, if ever, as its right thereto would not result in the Holder exceeding
the Maximum Percentage (as defined in the warrant), at which time the Holder shall be granted such right to the same extent as
if there had been no such limitation).
Placement
Agent Warrants
The
Company issued three types of warrants to the Placement Agent, Placement Agent Stock Offering Warrants, Placement Agent Common
Stock Warrants, and Placement Agent December 2013 Offering Warrants.
Placement
Agent Stock Offering Warrants
The
Placement Agent Stock Offering Warrants have a term ending on January 31, 2019 and are exercisable for an aggregate of up to
1,251,022 shares of the Company’s common stock at an initial per share exercise price of $0.78, subject to adjustment
as set forth below (anti dilution). As of March 10, 2017, there were 359,440 warrants outstanding. These warrants
have a cashless exercise provision. The exercise prices of the warrants are subject to adjustment upon certain
events. If the Company at any time while the warrants remain outstanding and unexpired shall declare a dividend or make a
distribution on the outstanding Common Stock payable in shares of its capital stock, or split, subdivide or combine the
securities as to which purchase rights under this Warrant exist into a different number of securities of the same class, the
exercise price for such securities shall be proportionately decreased in the case of a dividend, split or subdivision or
proportionately increased in the case of a combination.
Placement
Agent Common Stock Warrants
The
Placement Agent Common Stock Warrants have a five year term from January 28, 2013 and are exercisable for an aggregate of up
to 467,845 shares of the Company’s common stock at an initial per share exercise price of $2.48, subject to adjustment
as set forth below. As of March 3, 2017, there were 298,065 warrants outstanding. These warrants have a
cashless exercise provision. The Company may also call this warrant for redemption upon written notice to all
warrant holders at any time the closing price of the common stock exceeds $1.50 (as may be adjusted pursuant to warrant
agreement) for 20 consecutive trading days, as reported by Bloomberg, provided at such time there is an effective
registration statement covering the resale of the shares underlying the warrants. In the 60 business days
following the date the redemption notice is deemed given in accordance with the agreement, investors may choose to exercise
this warrant or a portion of the warrant by paying the then applicable exercise price per share for every share
exercised. Any shares not exercised on the last day of the exercise period will be redeemed by the Company at
$0.001 per share.
The
exercise prices of the warrants are subject to adjustment upon certain events. If the Company at any time while the warrants remain
outstanding and unexpired shall declare a dividend or make a distribution on the outstanding Common Stock payable in shares of
its capital stock, or split, subdivide or combine the securities as to which purchase rights under this Warrant exist into a different
number of securities of the same class, the exercise price for such securities shall be proportionately decreased in the case
of a dividend, split or subdivision or proportionately increased in the case of a combination.
In
addition, for so long as there are any warrants outstanding, if and whenever at any time and from time to time after the warrant
issue date, as applicable, the Company shall issue any shares of common stock for no consideration or a consideration per share
less than the exercise price, as applicable, then, forthwith upon such issue or sale, the warrants shall be subject to a proportional
adjustment determined by multiplying such warrant exercise price by the following fraction:
Where:
N(0)
= the number of shares of common stock outstanding (calculated on a Fully Diluted Basis) immediately prior to the issuance of
such additional shares of common stock or common stock Equivalents;
N(1)
= the number of shares of common stock which the aggregate consideration, if any (including the aggregate Net Consideration Per
Share with respect to the issuance of common stock equivalents), received or receivable by the Company for the total number of
such additional shares of common stock so issued or deemed to be issued would purchase at the warrant exercise price, as applicable,
in effect immediately prior to such issuance; and
N(2)
= the number of such additional shares of common stock so issued or deemed to be issued.
Placement
Agent December 2013 Offering Warrants
The
Placement Agent December 2013 Offering Warrants have a five year term from January 10, 2014 and are exercisable for an
aggregate of up to 138,265 shares of the Company’s common stock at an initial per share exercise price of $9.00,
subject to adjustment as set forth below. As of March 10, 2017, there were 124,997 warrants outstanding. These
warrants have a cashless exercise provision. The Company may also call this warrant for redemption upon written
notice to all warrant holders at any time the closing price of the common stock exceeds $15.00 (as may be adjusted pursuant
to warrant agreement) for 20 consecutive trading days, as reported by Bloomberg, provided at such time there is an effective
registration statement covering the resale of the shares underlying the warrants. In the 60 business days
following the date the redemption notice is deemed given in accordance with the agreement, investors may choose to exercise
this warrant or a portion of the warrant by paying the then applicable exercise price per share for every share
exercised. Any shares not exercised on the last day of the exercise period will be redeemed by the Company at
$0.001 per share.
The
exercise prices of the warrants are subject to adjustment upon certain events. If the Company at any time while the warrants remain
outstanding and unexpired shall declare a dividend or make a distribution on the outstanding Common Stock payable in shares of
its capital stock, or split, subdivide or combine the securities as to which purchase rights under this Warrant exist into a different
number of securities of the same class, the exercise price for such securities shall be proportionately decreased in the case
of a dividend, split or subdivision or proportionately increased in the case of a combination.
Consultant Warrants.
As of December 31, 2016, the Company has outstanding
warrants exercisable for 507,833 shares of common stock issued to various consultants in consideration for services. The exercise
prices range from $0.98 to $11.66 per share. These warrants do not have a cashless exercise provision.
Registration
Rights
On
December 21, 2015, Actinium entered into an Investor Rights Agreement (the “Investor Rights Agreement”) with Memorial
Sloan Cancer Center (“MSKCC”). Under the terms of the Investor Rights Agreement, MSKCC has agreed to forebear from
transferring or otherwise disposing of its approximately 5.7 million Actinium shares (other than pursuant to a piggyback registration
as described below) until the start of the Actimab-A Phase 2 clinical study (but, in no event until later than March 31, 2016).
Thereafter MSKCC shall be permitted to sell its shares subject to a weekly volume limitation of 150,000 shares (which limit may
be increased to up to 250,000 shares per week to the extent any prior weekly allotments were not fully used) and applicable law
so long as MSKCC maintains at least 25% of its current shareholding in Actinium through December 31, 2016. Actinium has granted
MSKCC piggyback registration rights that would be triggered in the event Actinium were to engage in a public registered offering
of its shares for its own account where other shareholders are participating as selling shareholders or where such public registered
offering is for the account of other selling shareholders. In addition, following December 31, 2016, Actinium has granted MSKCC
unlimited Form S-3 registration rights with respect to its shares.
Delaware
Anti-Takeover Law, Provisions of our Certificate of Incorporation and Bylaws
Delaware
Anti-Takeover Law
We
are subject to Section 203 of the Delaware General Corporation Law. Section 203 generally prohibits a public Delaware corporation
from engaging in a “business combination” with an “interested stockholder” for a period of three years
after the date of the transaction in which the person became an interested stockholder, unless:
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prior
to the date of the transaction, the board of directors of the corporation approved either the business combination or the
transaction which resulted in the stockholder becoming an interested stockholder;
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the
interested stockholder owned at least 85% of the voting stock of the corporation outstanding at the time the transaction commenced,
excluding for purposes of determining the number of shares outstanding (i) shares owned by persons who are directors and also
officers and (ii) shares owned by employee stock plans in which employee participants do not have the right to determine confidentially
whether shares held subject to the plan will be tendered in a tender or exchange offer; or
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on
or subsequent to the date of the transaction, the business combination is approved by the board and authorized at an annual
or special meeting of stockholders, and not by written consent, by the affirmative vote of at least 66 2/3% of the outstanding
voting stock which is not owned by the interested stockholder.
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Section
203 defines a business combination to include:
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any
merger or consolidation involving the corporation and the interested stockholder;
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any
sale, transfer, pledge or other disposition involving the interested stockholder of 10% or more of the assets of the corporation;
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subject
to exceptions, any transaction that results in the issuance or transfer by the corporation of any stock of the corporation
to the interested stockholder; or
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the
receipt by the interested stockholder of the benefit of any loans, advances, guarantees, pledges or other financial benefits
provided by or through the corporation.
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In general, Section 203 defines an interested
stockholder as any entity or person beneficially owning 15% or more of the outstanding voting stock of the corporation and any
entity or person affiliated with, or controlling, or controlled by, the entity or person. The term “owner” is broadly
defined to include any person that, individually, with or through that person’s affiliates or associates, among other things,
beneficially owns the stock, or has the right to acquire the stock, whether or not the right is immediately exercisable, under
any agreement or understanding or upon the exercise of warrants or options or otherwise or has the right to vote the stock under
any agreement or understanding, or has an agreement or understanding with the beneficial owner of the stock for the purpose of
acquiring, holding, voting or disposing of the stock.
The
restrictions in Section 203 do not apply to corporations that have elected, in the manner provided in Section 203, not to be subject
to Section 203 of the Delaware General Corporation Law or, with certain exceptions, which do not have a class of voting stock
that is listed on a national securities exchange or authorized for quotation on the Nasdaq Stock Market or held of record by more
than 2,000 stockholders. Our certificate of incorporation and bylaws do not opt out of Section 203.
Section
203 could delay or prohibit mergers or other takeover or change in control attempts with respect to us and, accordingly, may discourage
attempts to acquire us even though such a transaction may offer our stockholders the opportunity to sell their stock at a price
above the prevailing market price.
Certificate
of Incorporation and Bylaws
Provisions
of our certificate of incorporation and bylaws may delay or discourage transactions involving an actual or potential change in
our control or change in our management, including transactions in which stockholders might otherwise receive a premium for their
shares, or transactions that our stockholders might otherwise deem to be in their best interests. Therefore, these provisions
could adversely affect the price of our common stock. Among other things, our certificate of incorporation and bylaws:
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permit
our board of directors to issue up to 50,000,000 shares of preferred stock, without further action by the stockholders, with
any rights, preferences and privileges as they may designate, including the right to approve an acquisition or other change
in control;
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provide
that all vacancies, including newly created directorships, may, except as otherwise required by law, be filled by the affirmative
vote of a majority of directors then in office;
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divide
our board of directors into three classes, with each class serving staggered three-year terms, with such three year term commencing
on the election of a director on and after the 2014 annual meeting;
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do
not provide for cumulative voting rights (therefore allowing the holders of a majority of the shares of common stock entitled
to vote in any election of directors to elect all of the directors standing for election, if they should so choose);
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provide
that special meetings of our stockholders may be called only by our Chairman of the Board, board of directors, chief executive
officer ,or the holders of not less than one-tenth of all the shares entitled to vote at the meeting; and
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set
forth an advance notice procedure with regard to business to be brought before a meeting of stockholders.
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DESCRIPTION
OF DEBT SECURITIES
We
may issue debt securities from time to time, in one or more series, as either senior or subordinated debt or as senior or subordinated
convertible debt. While the terms we have summarized below will apply generally to any debt securities that we may offer
under this prospectus, we will describe the particular terms of any debt securities that we may offer in more detail in the applicable
prospectus supplement. The terms of any debt securities offered under a prospectus supplement may differ from the terms
described below. Unless the context requires otherwise, whenever we refer to the indenture, we are also referring to any
supplemental indentures that specify the terms of a particular series of debt securities.
We
will issue the debt securities under the indenture that we will enter into with the trustee named in the indenture. The
indenture will be qualified under the Trust Indenture Act of 1939, as amended ("Trust Indenture Act").
We have filed the form of indenture as an exhibit to the registration statement of which this prospectus is a part, and supplemental
indentures and forms of debt securities containing the terms of the debt securities being offered will be filed as exhibits to
the registration statement of which this prospectus is a part or will be incorporated by reference from reports that we file with
the SEC.
The
following summary of material provisions of the debt securities and the indenture is subject to, and qualified in its entirety
by reference to, all of the provisions of the indenture applicable to a particular series of debt securities. We urge you
to read the applicable prospectus supplements and any related free writing prospectuses related to the debt securities that we
may offer under this prospectus, as well as the complete indenture that contains the terms of the debt securities.
General
Terms of the Indenture
The
indenture does not limit the amount of debt securities that we may issue. It provides that we may issue debt securities
up to the principal amount that we may authorize and may be in any currency or currency unit designated by us. Except for
the limitations on consolidation, merger and sale of all or substantially all of our assets contained in the indenture, the terms
of the indenture do not contain any covenants or other provisions designed to afford holders of any debt securities protection
with respect to our operations, financial condition or transactions involving us.
We
may issue the debt securities issued under the indenture as "discount securities," which means they may be sold at a
discount below their stated principal amount. These debt securities, as well as other debt securities that are not issued
at a discount, may, for U.S. federal income tax purposes, be treated as if they were issued with "original issue discount,"
or "OID," because of interest payment and other characteristics. Special U.S. federal income tax considerations
applicable to debt securities issued with original issue discount will be described in more detail in any applicable prospectus
supplement.
We
will describe in the applicable prospectus supplement the terms of the series of debt securities being offered, including:
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the
title of the series of debt securities;
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any
limit upon the aggregate principal amount that may be issued;
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the
maturity date or dates;
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the
form of the debt securities of the series;
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the
applicability of any guarantees;
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whether
or not the debt securities will be secured or unsecured, and the terms of any secured debt;
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whether
the debt securities rank as senior debt, senior subordinated debt, subordinated debt or any combination thereof, and the terms
of any subordination;
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if
the price (expressed as a percentage of the aggregate principal amount thereof) at which such debt securities will be issued
is a price other than the principal amount thereof, the portion of the principal amount thereof payable upon declaration of
acceleration of the maturity thereof, or if applicable, the portion of the principal amount of such debt securities that is
convertible into another security or the method by which any such portion shall be determined;
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the
interest rate or rates, which may be fixed or variable, or the method for determining the rate and the date interest will
begin to accrue, the dates interest will be payable and the regular record dates for interest payment dates or the method
for determining such dates;
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our
right, if any, to defer payment of interest and the maximum length of any such deferral period;
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if
applicable, the date or dates after which, or the period or periods during which, and the price or prices at which, we may,
at our option, redeem the series of debt securities pursuant to any optional or provisional redemption provisions and the
terms of those redemption provisions;
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the
date or dates, if any, on which, and the price or prices at which we are obligated, pursuant to any mandatory sinking fund
or analogous fund provisions or otherwise, to redeem, or at the holder's option to purchase, the series of debt securities
and the currency or currency unit in which the debt securities are payable;
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the
denominations in which we will issue the series of debt securities, if other than denominations of $1,000, and any integral
multiple thereof;
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any
and all terms, if applicable, relating to any auction or remarketing of the debt securities of that series and any security
for our obligations with respect to such debt securities and any other terms which may be advisable in connection with the
marketing of debt securities of that series;
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whether
the debt securities of the series shall be issued in whole or in part in the form of a global security or securities; the
terms and conditions, if any, upon which such global security or securities may be exchanged in whole or in part for other
individual securities; and the depositary for such global security or securities;
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if
applicable, the provisions relating to conversion or exchange of any debt securities of the series and the terms and conditions
upon which such debt securities will be so convertible or exchangeable, including the conversion or exchange price, as applicable,
or how it will be calculated and may be adjusted, any mandatory or optional (at our option or the holders' option) conversion
or exchange features, the applicable conversion or exchange period and the manner of settlement for any conversion or exchange;
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if
other than the full principal amount thereof, the portion of the principal amount of debt securities of the series which shall
be payable upon declaration of acceleration of the maturity thereof;
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additions
to or changes in the covenants applicable to the particular debt securities being issued, including, among others, the consolidation,
merger or sale covenant;
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additions
to or changes in the events of default with respect to the securities and any change in the right of the trustee or the holders
to declare the principal, premium, if any, and interest, if any, with respect to such securities to be due and payable;
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additions
to or changes in or deletions of the provisions relating to covenant defeasance and legal defeasance;
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additions
to or changes in the provisions relating to satisfaction and discharge of the indenture;
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additions
to or changes in the provisions relating to the modification of the indenture both with and without the consent of holders
of debt securities issued under the indenture;
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the
currency of payment of debt securities if other than U.S. dollars and the manner of determining the equivalent amount in U.S.
dollars;
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whether
interest will be payable in cash or additional debt securities at our or the holders' option and the terms and conditions
upon which the election may be made;
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the
terms and conditions, if any, upon which we will pay amounts in addition to the stated interest, premium, if any, and principal
amounts of the debt securities of the series to any holder that is not a "United States person" for federal tax
purposes;
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any
restrictions on transfer, sale or assignment of the debt securities of the series; and
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any
other specific terms, preferences, rights or limitations of, or restrictions on, the debt securities, any other additions
or changes in the provisions of the indenture, and any terms that may be required by us or advisable under applicable laws
or regulations.
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Conversion
or Exchange Rights
We
will set forth in the prospectus supplement the terms on which a series of debt securities may be convertible into or exchangeable
for our common stock or our other securities. We will include provisions as to settlement upon conversion or exchange and
whether conversion or exchange is mandatory, at the option of the holder or at our option. We may include provisions pursuant
to which the number of shares of our common stock or our other securities that the holders of the series of debt securities receive
would be subject to adjustment.
Consolidation,
Merger or Sale
Unless
we provide otherwise in the prospectus supplement applicable to a particular series of debt securities, the indenture will not
contain any covenant that restricts our ability to merge or consolidate, or sell, convey, transfer or otherwise dispose of our
assets as an entirety or substantially as an entirety. However, any successor to or acquirer of such assets (other than
a subsidiary of ours) must assume all of our obligations under the indenture or the debt securities, as appropriate.
Events
of Default Under the Indenture
Unless
we provide otherwise in the prospectus supplement applicable to a particular series of debt securities, the following are events
of default under the indenture with respect to any series of debt securities that we may issue:
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if
we fail to pay any installment of interest on any debt securities of that series, as and when the same shall become due and
payable, and such default continues for a period of 90 days; provided, however, that a valid extension of an interest payment
period by us in accordance with the terms of any indenture supplemental thereto shall not constitute a default in the payment
of interest for this purpose;
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if
we fail to pay the principal of (or premium, if any) on any debt securities of that series as and when the same shall become
due and payable whether at maturity, upon redemption, by declaration or otherwise, or in any payment required by any sinking
or analogous fund established with respect to that series; provided, however, that a valid extension of the maturity of such
debt securities in accordance with the terms of any indenture supplemental thereto shall not constitute a default in the payment
of principal or premium, if any;
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if
we fail to observe or perform any other covenant or agreement with respect to that series contained in the indenture or otherwise
established with respect to that series pursuant to the indenture, other than a covenant or agreement specifically included
solely for the benefit of one or more debt securities other than that series, and our failure continues for 90 days after
we receive written notice of such failure, requiring the same to be remedied and stating that such is a notice of default
thereunder, from the trustee or holders of at least 25% in aggregate principal amount of the outstanding debt securities of
the applicable series; and
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if
specified events of bankruptcy, insolvency or reorganization occur.
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If
an event of default with respect to debt securities of any series occurs and is continuing, other than an event of default described
in the last bullet point above, the trustee or the holders of at least 25% in aggregate principal amount of the outstanding debt
securities of that series, by notice to us in writing, and to the trustee if notice is given by such holders, may declare the
unpaid principal of (premium, if any) and accrued and unpaid interest, if any, due and payable immediately. If an event
of default specified in the last bullet point above occurs with respect to us, the principal amount of and accrued interest, if
any, of that series shall be automatically due and payable without any declaration or other action on the part of the trustee
or any holder.
The
holders of a majority in principal amount of the outstanding debt securities of an affected series may waive any default or event
of default with respect to the series and its consequences, except defaults or events of default regarding payment of principal,
premium, if any, or interest, unless we have cured the default or event of default in accordance with the indenture. Any
waiver shall cure the default or event of default.
Subject
to the terms of the indenture, if an event of default under an indenture shall occur and be continuing, the trustee will be under
no obligation to exercise any of its rights or powers under such indenture at the request or direction of any of the holders of
the applicable series of debt securities, unless such holders have offered the trustee reasonable indemnity. The holders
of a majority in principal amount of the outstanding debt securities of any series will have the right to direct the time, method
and place of conducting any proceeding for any remedy available to the trustee, or exercising any trust or power conferred on
the trustee, with respect to the debt securities of that series, provided that:
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the
direction so given by the holder is not in conflict with any law or the applicable indenture; and
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subject
to its duties under the Trust Indenture Act, the trustee need not take any action that might involve it in personal liability
or might be unduly prejudicial to the holders not involved in the proceeding.
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A holder of the debt securities of any series
will have the right to institute a proceeding under the indenture or to appoint a receiver or trustee, or to seek other remedies
only if:
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the
holder has given written notice to the trustee of a continuing event of default with respect to that series;
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the
holders of at least 25% in aggregate principal amount of the outstanding debt securities of that series have made written
request;
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such
holders have offered to the trustee indemnity satisfactory to it against the costs, expenses and liabilities to be incurred
by the trustee in compliance with the request; and
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the
trustee does not institute the proceeding, and does not receive from the holders of a majority in aggregate principal amount
of the outstanding debt securities of that series other inconsistent directions within 90 days after the notice, request and
offer.
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These
limitations do not apply to a suit instituted by a holder of debt securities if we default in the payment of the principal, premium,
if any, or interest on, the debt securities.
We
will periodically file statements with the trustee regarding our compliance with specified covenants in the indenture.
Modification
of Indenture; Waiver
We
and the trustee may change an indenture without the consent of any holders with respect to specific matters:
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to
cure any ambiguity, defect or inconsistency in the indenture or in the debt securities of any series;
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to
comply with the provisions described above under "Description of Debt Securities—Consolidation, Merger or Sale;"
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to
provide for uncertificated debt securities in addition to or in place of certificated debt securities;
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to
add to our covenants, restrictions, conditions or provisions such new covenants, restrictions, conditions or provisions for
the benefit of the holders of all or any series of debt securities, to make the occurrence, or the occurrence and the continuance,
of a default in any such additional covenants, restrictions, conditions or provisions an event of default or to surrender
any right or power conferred upon us in the indenture;
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to
add to, delete from or revise the conditions, limitations, and restrictions on the authorized amount, terms, or purposes of
issue, authentication and delivery of debt securities, as set forth in the indenture;
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to
make any change that does not adversely affect the interests of any holder of debt securities of any series in any material
respect;
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to
provide for the issuance of and establish the form and terms and conditions of the debt securities of any series as provided
above under "Description of Debt Securities—General" to establish the form of any certifications required
to be furnished pursuant to the terms of the indenture or any series of debt securities, or to add to the rights of the holders
of any series of debt securities;
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to
evidence and provide for the acceptance of appointment under any indenture by a successor trustee; or
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to
comply with any requirements of the SEC in connection with the qualification of any indenture under the Trust Indenture Act.
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In
addition, under the indenture, the rights of holders of a series of debt securities may be changed by us and the trustee with
the written consent of the holders of at least a majority in aggregate principal amount of the outstanding debt securities of
each series that is affected. However, unless we provide otherwise in the prospectus supplement applicable to a particular
series of debt securities, we and the trustee may make the following changes only with the consent of each holder of any outstanding
debt securities affected:
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extending
the fixed maturity of any debt securities of any series;
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reducing
the principal amount, reducing the rate of or extending the time of payment of interest, or reducing any premium payable upon
the redemption of any series of any debt securities; or
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reducing
the percentage of debt securities, the holders of which are required to consent to any amendment, supplement, modification
or waiver.
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Discharge
Each
indenture provides that we can elect to be discharged from our obligations with respect to one or more series of debt securities,
except for specified obligations, including obligations to:
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provide
for payment;
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register
the transfer or exchange of debt securities of the series;
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replace
stolen, lost or mutilated debt securities of the series;
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pay
principal of and premium and interest on any debt securities of the series;
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maintain
paying agencies;
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hold
monies for payment in trust;
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recover
excess money held by the trustee;
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compensate
and indemnify the trustee; and
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appoint
any successor trustee.
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In
order to exercise our rights to be discharged, we must deposit with the trustee money or government obligations sufficient to
pay all the principal of, any premium, if any, and interest on, the debt securities of the series on the dates payments are due.
Form,
Exchange and Transfer
We
will issue the debt securities of each series only in fully registered form without coupons and, unless we provide otherwise in
the applicable prospectus supplement, in denominations of $1,000 and any integral multiple thereof. The indenture provides
that we may issue debt securities of a series in temporary or permanent global form and as book-entry securities that will be
deposited with, or on behalf of, The Depository Trust Company, or DTC, or another depositary named by us and identified in a prospectus
supplement with respect to that series. To the extent the debt securities of a series are issued in global form and as book-entry,
a description of terms relating will be set forth in the applicable prospectus supplement.
At
the option of the holder, subject to the terms of the indenture and the limitations applicable to global securities described
in the applicable prospectus supplement, the holder of the debt securities of any series can exchange the debt securities for
other debt securities of the same series, in any authorized denomination and of like tenor and aggregate principal amount.
Subject
to the terms of the indenture and the limitations applicable to global securities set forth in the applicable prospectus supplement,
holders of the debt securities may present the debt securities for exchange or for registration of transfer, duly endorsed or
with the form of transfer endorsed thereon duly executed if so required by us or the security registrar, at the office of the
security registrar or at the office of any transfer agent designated by us for this purpose. Unless otherwise provided in
the debt securities that the holder presents for transfer or exchange, we will impose no service charge for any registration of
transfer or exchange, but we may require payment of any taxes or other governmental charges.
We
will name in the applicable prospectus supplement the security registrar, and any transfer agent in addition to the security registrar,
that we initially designate for any debt securities. We may at any time designate additional transfer agents or rescind
the designation of any transfer agent or approve a change in the office through which any transfer agent acts, except that we
will be required to maintain a transfer agent in each place of payment for the debt securities of each series.
If
we elect to redeem the debt securities of any series, we will not be required to:
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issue,
register the transfer of, or exchange any debt securities of that series during a period beginning at the opening of business
15 days before the day of mailing of a notice of redemption of any debt securities that may be selected for redemption and
ending at the close of business on the day of the mailing; or
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register
the transfer of or exchange any debt securities so selected for redemption, in whole or in part, except the unredeemed portion
of any debt securities we are redeeming in part.
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Information
Concerning the Trustee
The
trustee, other than during the occurrence and continuance of an event of default under an indenture, undertakes to perform only
those duties as are specifically set forth in the applicable indenture. Upon an event of default under an indenture, the
trustee must use the same degree of care as a prudent person would exercise or use in the conduct of his or her own affairs.
Subject to this provision, the trustee is under no obligation to exercise any of the powers given it by the indenture at the request
of any holder of debt securities unless it is offered reasonable security and indemnity against the costs, expenses and liabilities
that it might incur.
Payment
and Paying Agents
Unless
we otherwise indicate in the applicable prospectus supplement, we will make payment of the interest on any debt securities on
any interest payment date to the person in whose name the debt securities, or one or more predecessor securities, are registered
at the close of business on the regular record date for the interest.
We
will pay principal of and any premium and interest on the debt securities of a particular series at the office of the paying agents
designated by us, except that unless we otherwise indicate in the applicable prospectus supplement, we will make interest payments
by check that we will mail to the holder or by wire transfer to certain holders. Unless we otherwise indicate in the applicable
prospectus supplement, we will designate the corporate trust office of the trustee as our sole paying agent for payments with
respect to debt securities of each series. We will name in the applicable prospectus supplement any other paying agents
that we initially designate for the debt securities of a particular series. We will maintain a paying agent in each place
of payment for the debt securities of a particular series.
All
money we pay to a paying agent or the trustee for the payment of the principal of or any premium or interest on any debt securities
that remains unclaimed at the end of two years after such principal, premium or interest has become due and payable (or such shorter
period set forth in applicable escheat, abandoned or unclaimed property law) will be repaid to us, and the holder of the debt
security thereafter may look only to us for payment thereof.
Governing
Law
The
indenture and the debt securities will be governed by and construed in accordance with the laws of the State of New York, except
to the extent that the Trust Indenture Act is applicable.
DESCRIPTION
OF WARRANTS
As
of March 10, 2017, there were 8,964,752 shares of common stock that may be issued upon exercise of outstanding
warrants.
We
may issue warrants for the purchase of debt securities, common stock or preferred stock in one or more series. We may issue warrants
independently or together with debt securities, common stock or preferred stock, and the warrants may be attached to or separate
from these securities.
We
will evidence each series of warrants by warrant certificates that we may issue under a separate agreement. We may enter into
a warrant agreement with a warrant agent. Each warrant agent may be a bank that we select which has its principal office in the
United States. We may also choose to act as our own warrant agent. We will indicate the name and address of any such warrant agent
in the applicable prospectus supplement relating to a particular series of warrants.
We
will describe in the applicable prospectus supplement the terms of the series of warrants, including:
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the
offering price and aggregate number of warrants offered;
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if
applicable, the designation and terms of the securities with which the warrants are issued and the number of warrants issued
with each such security or each principal amount of such security;
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if
applicable, the date on and after which the warrants and the related securities will be separately transferable;
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in
the case of warrants to debt securities, purchase common stock or preferred stock, the number or amount of shares of common
stock or preferred stock, as the case may be, purchasable upon the exercise of one warrant and the price at which and currency
in which these shares may be purchased upon such exercise;
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the
manner of exercise of the warrants, including any cashless exercise rights;
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the
warrant agreement under which the warrants will be issued;
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the
effect of any merger, consolidation, sale or other disposition of our business on the warrant agreement and the warrants;
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anti-dilution
provisions of the warrants, if any;
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the
terms of any rights to redeem or call the warrants;
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any
provisions for changes to or adjustments in the exercise price or number of securities issuable upon exercise of the warrants;
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the
dates on which the right to exercise the warrants will commence and expire or, if the warrants are not continuously exercisable
during that period, the specific date or dates on which the warrants will be exercisable;
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the
manner in which the warrant agreement and warrants may be modified;
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the
identities of the warrant agent and any calculation or other agent for the warrants;
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federal
income tax consequences of holding or exercising the warrants;
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the
terms of the securities issuable upon exercise of the warrants;
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any
securities exchange or quotation system on which the warrants or any securities deliverable upon exercise of the warrants
may be listed or quoted; and
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any
other specific terms, preferences, rights or limitations of or restrictions on the warrants.
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Before
exercising their warrants, holders of warrants will not have any of the rights of holders of the securities purchasable upon such
exercise, including, in the case of warrants to purchase common stock or preferred stock, the right to receive dividends, if any,
or, payments upon our liquidation, dissolution or winding up or to exercise voting rights, if any.
Exercise
of Warrants
Each
warrant will entitle the holder to purchase the securities that we specify in the applicable prospectus supplement at the exercise
price that we describe in the applicable prospectus supplement. Unless we otherwise specify in the applicable prospectus supplement,
holders of the warrants may exercise the warrants at any time up to 5:00 P.M. eastern time, the close of business, on the expiration
date that we set forth in the applicable prospectus supplement. After the close of business on the expiration date, unexercised
warrants will become void.
Holders
of the warrants may exercise the warrants by delivering the warrant certificate representing the warrants to be exercised together
with specified information, and paying the required exercise price by the methods provided in the applicable prospectus supplement.
We will set forth on the reverse side of the warrant certificate, and in the applicable prospectus supplement, the information
that the holder of the warrant will be required to deliver to the warrant agent.
Upon
receipt of the required payment and the warrant certificate properly completed and duly executed at the corporate trust office
of the warrant agent or any other office indicated in the applicable prospectus supplement, we will issue and deliver the securities
purchasable upon such exercise. If fewer than all of the warrants represented by the warrant certificate are exercised, then we
will issue a new warrant certificate for the remaining amount of warrants.
Enforceability
of Rights By Holders of Warrants
Any
warrant agent will act solely as our agent under the applicable warrant agreement and will not assume any obligation or relationship
of agency or trust with any holder of any warrant. A single bank or trust company may act as warrant agent for more than one issue
of warrants. A warrant agent will have no duty or responsibility in case of any default by us under the applicable warrant agreement
or warrant, including any duty or responsibility to initiate any proceedings at law or otherwise, or to make any demand upon us.
Any holder of a warrant may, without the consent of the related warrant agent or the holder of any other warrant, enforce by appropriate
legal action the holder’s right to exercise, and receive the securities purchasable upon exercise of, its warrants in accordance
with their terms.
Warrant
Agreement Will Not Be Qualified Under Trust Indenture Act
No
warrant agreement will be qualified as an indenture, and no warrant agent will be required to qualify as a trustee, under the
Trust Indenture Act. Therefore, holders of warrants issued under a warrant agreement will not have the protection of the Trust
Indenture Act with respect to their warrants.
Governing
Law
Each
warrant agreement and any warrants issued under the warrant agreements will be governed by New York law.
DESCRIPTION
OF RIGHTS
We
may issue rights to our stockholders to purchase shares of our common stock or preferred stock. We may offer rights separately
or together with one or more additional rights, debt securities, preferred stock, common stock or warrants, or any combination
of those securities in the form of units, as described in the applicable prospectus supplement. Each series of rights will be
issued under a separate rights agreement to be entered into between us and a bank or trust company, as rights agent. The rights
agent will act solely as our agent in connection with the certificates relating to the rights of the series of certificates and
will not assume any obligation or relationship of agency or trust for or with any holders of rights certificates or beneficial
owners of rights. The following description sets forth certain general terms and provisions of the rights to which any prospectus
supplement may relate. The particular terms of the rights to which any prospectus supplement may relate and the extent, if any,
to which the general provisions may apply to the rights so offered will be described in the applicable prospectus supplement.
To the extent that any particular terms of the rights, rights agreement or rights certificates described in a prospectus supplement
differ from any of the terms described below, then the terms described below will be deemed to have been superseded by that prospectus
supplement. We encourage you to read the applicable rights agreement and rights certificate for additional information before
you decide whether to purchase any of our rights.
We
will provide in a prospectus supplement the following terms of the rights being issued:
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the
date on which stockholders entitled to the rights distribution will be determined;
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the
aggregate number of shares of common stock or preferred stock purchasable upon exercise of the rights;
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the
exercise price;
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the
aggregate number of rights issued;
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the
date, if any, on and after which the rights will be separately transferable;
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the
date on which the ability to exercise the rights will commence, and the date on which such ability will expire;
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the
conditions to the completion of the offering, if any;
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the
withdrawal, termination and cancellation rights, if any;
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any
applicable material U.S. federal income tax considerations; and
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any
other terms of the rights, including terms, procedures and limitations relating to the distribution, exchange and exercise
of the rights.
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Each
right will entitle the holder of rights to purchase, for cash, the number of shares of common stock or preferred stock at the
exercise price provided in the applicable prospectus supplement. Rights may be exercised at any time up to the close of business
on the expiration date for the rights provided in the applicable prospectus supplement.
Holders
may exercise rights as described in the applicable prospectus supplement. Upon receipt of payment and the rights certificate properly
completed and duly executed at the corporate trust office of the rights agent or any other office indicated in the prospectus
supplement, we will, as soon as practicable, forward the shares of common stock or preferred stock, as applicable, purchasable
upon exercise of the rights. If less than all of the rights issued in any rights offering are exercised, we may offer any unsubscribed
securities directly to persons other than stockholders, to or through agents, underwriters or dealers or through a combination
of such methods, including pursuant to standby arrangements, as described in the applicable prospectus supplement.
DESCRIPTION
OF PURCHASE CONTRACTS
We
may issue purchase contracts, including contracts obligating holders to purchase from us, and for us to sell to holders, a specific
or variable number of our debt securities, shares of common stock, preferred stock, warrants or rights, or securities of an entity
unaffiliated with us, or any combination of the above, at a future date or dates. Alternatively, the purchase contracts may obligate
us to purchase from holders, and obligate holders to sell to us, a specific or variable number of our debt securities, shares
of common stock, preferred stock, warrants, rights or other property, or any combination of the above. The price of the securities
or other property subject to the purchase contracts may be fixed at the time the purchase contracts are issued or may be determined
by reference to a specific formula described in the purchase contracts. We may issue purchase contracts separately or as a part
of units each consisting of a purchase contract and one or more of our other securities described in this prospectus or securities
of third parties, including U.S. Treasury securities, securing the holder’s obligations under the purchase contract.
The purchase contracts may require us to make periodic payments to holders or vice versa and the payments may be unsecured or
pre-funded on some basis. The purchase contracts may require holders to secure the holder’s obligations in a manner specified
in the applicable prospectus supplement.
The
applicable prospectus supplement will describe the terms of any purchase contracts in respect of which this prospectus is being
delivered, including, to the extent applicable, the following:
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whether
the purchase contracts obligate the holder or us to purchase or sell, or both purchase and sell, the securities subject to
purchase under the purchase contract, and the nature and amount of each of those securities, or the method of determining
those amounts;
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whether
the purchase contracts are to be prepaid;
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whether
the purchase contracts are to be settled by delivery, or by reference or linkage to the value, performance or level of the
securities subject to purchase under the purchase contract;
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any
acceleration, cancellation, termination or other provisions relating to the settlement of the purchase contracts;
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any
applicable federal income tax considerations; and
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whether
the purchase contracts will be issued in fully registered or global form.
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The
preceding description sets forth certain general terms and provisions of the purchase contracts to which any prospectus supplement
may relate. The particular terms of the purchase contracts to which any prospectus supplement may relate and the extent, if any,
to which the general provisions may apply to the purchase contracts so offered will be described in the applicable prospectus
supplement. To the extent that any particular terms of the purchase contracts described in a prospectus supplement differ from
any of the terms described above, then the terms described above will be deemed to have been superseded by that prospectus supplement.
We encourage you to read the applicable purchase contract for additional information before you decide whether to purchase any
of our purchase contracts.
DESCRIPTION
OF UNITS
We
may issue units comprised of one or more of the other securities described in this prospectus or any prospectus supplement in
any combination. Each unit will be issued so that the holder of the unit is also the holder, with the rights and obligations of
a holder, of each security included in the unit. The unit agreement under which a unit is issued may provide that the securities
included in the unit may not be held or transferred separately, at any time or at any times before a specified date or upon the
occurrence of a specified event or occurrence.
The
applicable prospectus supplement will describe:
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the
designation and the terms of the units and of the securities comprising the units, including whether and under what circumstances
those securities may be held or transferred separately;
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any
unit agreement under which the units will be issued;
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any
provisions for the issuance, payment, settlement, transfer or exchange of the units or of the securities comprising the units;
and
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whether
the units will be issued in fully registered or global form.
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PLAN
OF DISTRIBUTION
We
may sell the securities being offered pursuant to this prospectus to or through underwriters, through dealers, through agents,
or directly to one or more purchasers or through a combination of these methods. The applicable prospectus supplement will describe
the terms of the offering of the securities, including:
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the
name or names of any underwriters, if any, and if required, any dealers or agents;
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the
purchase price of the securities and the proceeds we will receive from the sale;
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any
underwriting discounts and other items constituting underwriters’ compensation;
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any
discounts or concessions allowed or re-allowed or paid to dealers; and
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any
securities exchange or market on which the securities may be listed or traded.
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We may distribute the securities from time to
time in one or more transactions at:
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a
fixed price or prices, which may be changed;
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market
prices prevailing at the time of sale, directly by us or through a designated agent;
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prices
related to such prevailing market prices; or
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negotiated
prices.
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Only
underwriters named in the prospectus supplement are underwriters of the securities offered by the prospectus supplement.
If
underwriters are used in an offering, we will execute an underwriting agreement with such underwriters and will specify the name
of each underwriter and the terms of the transaction (including any underwriting discounts and other terms constituting compensation
of the underwriters and any dealers) in a prospectus supplement. The securities may be offered to the public either through underwriting
syndicates represented by managing underwriters or directly by one or more investment banking firms or others, as designated.
If an underwriting syndicate is used, the managing underwriter(s) will be specified on the cover of the prospectus supplement.
If underwriters are used in the sale, the offered securities will be acquired by the underwriters for their own accounts and may
be resold from time to time in one or more transactions, including negotiated transactions, at a fixed public offering price or
at varying prices determined at the time of sale. Any public offering price and any discounts or concessions allowed or reallowed
or paid to dealers may be changed from time to time. Unless otherwise set forth in the prospectus supplement, the obligations
of the underwriters to purchase the offered securities will be subject to conditions precedent, and the underwriters will be obligated
to purchase all of the offered securities, if any are purchased.
We
may grant to the underwriters options to purchase additional securities to cover over-allotments, if any, at the public offering
price, with additional underwriting commissions or discounts, as may be set forth in a related prospectus supplement. The terms
of any over-allotment option will be set forth in the prospectus supplement for those securities.
If
we use a dealer in the sale of the securities being offered pursuant to this prospectus or any prospectus supplement, we will
sell the securities to the dealer, as principal. The dealer may then resell the securities to the public at varying prices to
be determined by the dealer at the time of resale. The names of the dealers and the terms of the transaction will be specified
in a prospectus supplement.
We
may sell the securities directly or through agents we designate from time to time. We will name any agent involved in the offering
and sale of securities and we will describe any commissions we will pay the agent in the prospectus supplement. Unless the prospectus
supplement states otherwise, any agent will act on a best-efforts basis for the period of its appointment.
We
may authorize agents or underwriters to solicit offers by institutional investors to purchase securities from us at the public
offering price set forth in the prospectus supplement pursuant to delayed delivery contracts providing for payment and delivery
on a specified date in the future. We will describe the conditions to these contracts and the commissions we must pay for solicitation
of these contracts in the prospectus supplement.
In
connection with the sale of the securities, underwriters, dealers or agents may receive compensation from us or from purchasers
of the securities for whom they act as agents, in the form of discounts, concessions or commissions. Underwriters may sell the
securities to or through dealers, and those dealers may receive compensation in the form of discounts, concessions or commissions
from the underwriters or commissions from the purchasers for whom they may act as agents. Underwriters, dealers and agents that
participate in the distribution of the securities, and any institutional investors or others that purchase securities directly
for the purpose of resale or distribution, may be deemed to be underwriters, and any discounts or commissions received by them
from us and any profit on the resale of the common stock by them may be deemed to be underwriting discounts and commissions under
the Securities Act of 1933, as amended.
We
may provide agents, underwriters and other purchasers with indemnification against particular civil liabilities, including liabilities
under the Securities Act of 1933, as amended, or contribution with respect to payments that the agents, underwriters or other
purchasers may make with respect to such liabilities. Agents and underwriters may engage in transactions with, or perform services
for, us in the ordinary course of business.
To
facilitate the public offering of a series of securities, persons participating in the offering may engage in transactions that
stabilize, maintain, or otherwise affect the market price of the securities. This may include over-allotments or short sales of
the securities, which involves the sale by persons participating in the offering of more securities than have been sold to them
by us. In addition, those persons may stabilize or maintain the price of the securities by bidding for or purchasing securities
in the open market or by imposing penalty bids, whereby selling concessions allowed to underwriters or dealers participating in
any such offering may be reclaimed if securities sold by them are repurchased in connection with stabilization transactions. The
effect of these transactions may be to stabilize or maintain the market price of the securities at a level above that which might
otherwise prevail in the open market. Such transactions, if commenced, may be discontinued at any time. We make no representation
or prediction as to the direction or magnitude of any effect that the transactions described above, if implemented, may have on
the price of our securities.
Unless
otherwise specified in the applicable prospectus supplement, any common stock sold pursuant to a prospectus supplement will be
eligible for listing on a national securities exchange, such as the NYSE MKT or NASDAQ, subject to official notice of issuance.
Any underwriters to whom securities are sold by us for public offering and sale may make a market in the securities, but such
underwriters will not be obligated to do so and may discontinue any market making at any time without notice.
In
order to comply with the securities laws of some states, if applicable, the securities offered pursuant to this prospectus will
be sold in those states only through registered or licensed brokers or dealers. In addition, in some states securities may not
be sold unless they have been registered or qualified for sale in the applicable state or an exemption from the registration or
qualification requirement is available and complied with.
LEGAL
MATTERS
The
validity of the securities offered by this prospectus will be passed upon by The Matt Law Firm, PLLC Utica, New York.
EXPERTS
The
financial statements incorporated in this prospectus by reference to the Annual Report on Form 10-K for the fiscal year ended
December 31, 2016 have been so incorporated in reliance on the report of GBH CPAs, PC, an independent registered public accounting
firm, given on the authority of said firm as experts in auditing and accounting.
WHERE
YOU CAN FIND MORE INFORMATION
We
are subject to the informational requirements of the Securities Exchange Act of 1934, as amended, and in accordance therewith
file annual, quarterly and current reports, proxy statements and other information with the Securities and Exchange Commission.
Such reports, proxy statements and other information can be read and copied at the Securities and Exchange Commission’s
public reference facilities at 100 F Street, N.E., Washington, D.C. 20549, at prescribed rates. Please call the Securities
and Exchange Commission at 1-800-732-0330 for further information on the operation of the public reference facilities. In addition,
the Securities and Exchange Commission maintains a website that contains reports, proxy and information statements and other information
regarding registrants that file electronically with the Securities and Exchange Commission. The address of the Securities and
Exchange Commission’s website is www.sec.gov.
We
make available free of charge on or through our website at www.actiniumpharmaceuticals.com, our Annual Reports on Form 10-K,
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and amendments to those reports filed or furnished pursuant
to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, as soon as reasonably practicable after we
electronically file such material with or otherwise furnish it to the Securities and Exchange Commission.
We
have filed with the Securities and Exchange Commission a registration statement under the Securities Act of 1933, as amended,
relating to the offering of these securities. The registration statement, including the attached exhibits, contains additional
relevant information about us and the securities. This prospectus does not contain all of the information set forth in the registration
statement. You can obtain a copy of the registration statement, at prescribed rates, from the Securities and Exchange Commission
at the address listed above, or for free at www.sec.gov. The registration statement and the documents referred to below under
“Incorporation of Certain Information By Reference” are also available on our website, www.actiniumpharmaceuticals.com.
We
have not incorporated by reference into this prospectus the information on our website, and you should not consider it to be a
part of this prospectus.
INCORPORATION
OF CERTAIN INFORMATION BY REFERENCE
The
Securities and Exchange Commission allows us to “incorporate by reference” the information we have filed with it,
which means that we can disclose important information to you by referring you to those documents. The information we incorporate
by reference is an important part of this prospectus, and later information that we file with the Securities and Exchange Commission
will automatically update and supersede this information. We incorporate by reference the documents listed below and any future
documents (excluding information furnished pursuant to Items 2.02 and 7.01 of Form 8-K) we file with the Securities and Exchange
Commission pursuant to Sections l3(a), l3(c), 14 or l5(d) of the Securities Exchange Act of 1934, as amended, subsequent to the
date of this prospectus and prior to the termination of the offering:
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Our
Annual Report on Form 10-K for the fiscal year ended December 31, 2016, filed with the Securities and Exchange Commission
on March 16, 2017;
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The
description of our common stock, which is contained in our Form 8-K/A, filed with the Securities and Exchange Commission on
January 28, 2013.
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All
filings filed by us pursuant to the Securities Exchange Act of 1934, as amended, after the date of the initial filing of this
registration statement and prior to the effectiveness of such registration statement (excluding information furnished pursuant
to Items 2.02 and 7.01 of Form 8-K) shall also be deemed to be incorporated by reference into the prospectus.
You
should rely only on the information incorporated by reference or provided in this prospectus. We have not authorized anyone else
to provide you with different information. You should not assume that the information in this prospectus is accurate as of any
date other than the date of this prospectus or the date of the documents incorporated by reference in this prospectus.
We
will provide without charge to each person to whom a copy of this prospectus is delivered, upon written or oral request, a copy
of any or all of the information that has been incorporated by reference in this prospectus but not delivered with this prospectus
(other than an exhibit to these filings, unless we have specifically incorporated that exhibit by reference in this prospectus).
Any such request should be addressed to us at: 275 Madison Avenue, 7th Floor, New York, New York 10016, Attention: Steve O’Loughlin,
Vice President of Finance and Business Development, or made by phone at (646) 677-3875. You may also access the documents incorporated
by reference in this prospectus through our website at www.actiniumpharmceuticals.com. Except for the specific incorporated documents
listed above, no information available on or through our website shall be deemed to be incorporated in this prospectus or the
registration statement of which it forms a part.
55,653,846 Shares
of Common Stock
Pre-Funded Warrants to Purchase up to 21,269,231
Shares
of Common Stock
Prospectus Supplement
Exclusive Lead Placement Agent
H.C. Wainwright & Co.
Co-Placement Agents
Maxim Group LLC
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JonesTrading
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June
16, 2020
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