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.
|
|
Per Share |
|
|
Per Pre-Funded Warrant |
|
|
Total |
|
Public offering
price |
|
$ |
0.32500 |
|
|
$ |
0.32490 |
|
|
$ |
24,997,873.10 |
|
Placement agent fees(1)
|
|
$ |
0.02275
|
|
|
$ |
0.02275
|
|
|
$ |
1,750,000.00
|
|
Proceeds, before
expenses, to Actinium Pharmaceuticals, Inc. |
|
$ |
0.30225 |
|
|
$ |
0.30215 |
|
|
$ |
23,247,873.10 |
|
|
(1) |
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.” |
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 |
JonesTrading |
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. |
|
|
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. |
|
● |
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. |
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 |
|
Actinium
Pharmaceuticals, Inc. |
|
|
|
Common
Stock Offered by Us |
|
55,653,846 shares
of common stock. |
|
|
|
Pre-funded
warrants offered by us |
|
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. |
|
|
|
Common
Stock to be Outstanding Immediately After this Offering
(1) |
|
416,423,957 shares,
assuming all of the pre-funded warrants issued in this offering are
exercised. |
Use
of Proceeds |
|
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.
|
|
|
|
Risk
Factors |
|
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. |
|
|
|
NYSE
American symbol |
|
“ATNM.” |
(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:
|
● |
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; |
|
● |
22,250,949
shares of common stock available for future grants under our equity
incentive plans; |
|
● |
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 |
|
● |
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. |
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:
|
● |
theft
or misappropriation of funds; |
|
● |
loss,
corruption, or misappropriation of intellectual property, or other
proprietary, confidential or personally identifiable information
(including supplier, clinical data or employee data); |
|
● |
disruption
or impairment of our and our business operations and safety
procedures; |
|
● |
damage
to our reputation with our potential partners, patients and the
market; |
|
● |
exposure
to litigation; |
|
● |
increased
costs to prevent, respond to or mitigate cybersecurity
events. |
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; |
|
● |
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; |
|
● |
potential FDA audit of the nonclinical
study and clinical trial sites that generated the data in support
of the BLA; and |
|
● |
FDA review and approval, or denial,
of the BLA. |
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. |
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. |
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; |
|
● |
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. |
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. |
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:
|
● |
restrictions
on the marketing or manufacturing of our product candidates,
withdrawal of the product from the market, or voluntary or
mandatory product recalls; |
|
● |
fines,
warning letters or holds on clinical trials; |
|
● |
refusal
by the FDA to approve pending applications or supplements to
approved applications filed by us or suspension or revocation of
license approvals; |
|
● |
product
seizure or detention, or refusal to permit the import or export of
our product candidates; and |
|
● |
injunctions
or the imposition of civil or criminal penalties. |
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. |
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. |
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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|
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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; |
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:
|
● |
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; |
|
● |
our
ability to complete clinical trials as anticipated and obtain and
maintain regulatory approvals for our products; |
|
● |
our
ability to adequately protect our intellectual
property; |
|
● |
disputes
over ownership of intellectual property; |
|
● |
our
dependence on a single manufacturing facility and our ability to
comply with stringent manufacturing quality standards and to
increase production as necessary; |
|
● |
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; |
|
● |
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; |
|
● |
entry
of new competitors and products and potential technological
obsolescence of our products; |
|
● |
loss
of a key customer or supplier; |
|
● |
adverse
economic conditions; |
|
● |
adverse
federal, state and local government regulation, in the United
States; |
|
● |
price
increases for supplies and components; |
|
● |
inability
to carry out research, development and commercialization
plans; |
|
● |
loss
or retirement of key executives and research
scientists; |
|
|
|
|
● |
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;
|
|
|
|
|
● |
the
geographic, social and economic impact of COVID-19 on the Company’s
business and liquidity; and |
|
|
|
|
● |
other
factors discussed in this prospectus supplement. |
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:
|
● |
a
change in development plan or strategy; |
|
● |
the
addition of new products or applications; |
|
● |
delays
or difficulties with our clinical trials; |
|
● |
negative
results from our clinical trials; |
|
● |
difficulty
obtaining FDA approval; |
|
● |
failure
to achieve sales as anticipated; and |
|
● |
the
availability of other sources of cash including cash flow from
operations and new bank debt financing arrangements, if
any. |
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:
|
— |
Removing the
use of low dose cytarabine from the Phase 2 protocol; |
|
|
|
|
— |
Stipulating
Peripheral blast burden as an inclusion criteria with 200 ML being
the threshold; |
|
|
|
|
— |
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 |
|
|
|
|
— |
Mandating
the use of granulocyte colony-stimulating factor (GCSF)
support. |
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 |
|
Description |
|
US
Expiration |
|
US
Status |
|
Owner/
Licensor |
|
|
|
|
|
|
|
|
|
Platform
technology |
|
Antibody
conjugates with DOTA chelators; methods of treating cancer using
the same |
|
2021 |
|
Issued |
|
MSKCC |
|
|
|
|
|
|
|
|
|
Platform
technology |
|
Radioimmunoconjugate
generation |
|
2029 |
|
Issues |
|
Owned |
|
|
|
|
|
|
|
|
|
Drug
preparation methods |
|
Actinium
225 labeling method (binding to an antibody) |
|
2030 |
|
Pending |
|
Owned |
|
|
|
|
|
|
|
|
|
Drug
preparation methods |
|
Bismuth
213 labeling method (binding to an antibody) |
|
2019 |
|
Issued |
|
MSKCC |
|
|
|
|
|
|
|
|
|
Isotope
production methods |
|
Actinium
225 manufacturing in a cyclotron |
|
2026/2027 |
|
Issued |
|
Owned |
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:
|
● |
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; |
|
|
|
|
● |
our
ability to complete clinical trials as anticipated and obtain and
maintain regulatory approvals for our products; |
|
|
|
|
● |
our
ability to adequately protect our intellectual
property; |
|
|
|
|
● |
disputes
over ownership of intellectual property; |
|
|
|
|
● |
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; |
|
|
|
|
● |
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; |
|
|
|
|
● |
entry
of new competitors and products and potential technological
obsolescence of our products; |
|
|
|
|
● |
loss
of a key customer or supplier; |
|
● |
technical
problems with our research and products and potential product
liability claims; |
|
|
|
|
● |
adverse
economic conditions; |
|
|
|
|
● |
adverse
federal, state and local government regulation, in the United
States; |
|
|
|
|
● |
price
increases for supplies; |
|
|
|
|
● |
inability
to carry out research, development and commercialization plans;
and |
|
|
|
|
● |
loss
or retirement of key executives and research
scientists. |
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:
|
● |
a
change in development plan or strategy; |
|
|
|
|
● |
the
addition of new products or applications; |
|
|
|
|
● |
technical
delays; |
|
|
|
|
● |
delays
or difficulties with our clinical trials; |
|
|
|
|
● |
negative
results from our clinical trials; |
|
|
|
|
● |
difficulty
obtaining U.S. Food and Drug Administration approval;
and |
|
|
|
|
● |
the
availability of other sources of cash including additional
offerings, if any. |
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. |
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. |
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. |
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. |
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. |
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;
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if
specified events of bankruptcy, insolvency or reorganization
occur. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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. |
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
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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
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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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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;
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whether
the units will be issued in fully registered or global
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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;
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securities exchange or market on which the securities may be listed
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We may distribute the securities from time to time in one or more
transactions at:
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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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related to such prevailing market prices; or |
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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. |
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 |
JonesTrading |
June 16, 2020