NEW YORK, Oct. 30, 2018 /PRNewswire/ -- Actinium
Pharmaceuticals, Inc. (NYSE American: ATNM) announced
today that the next stage of development for its CD33 ARC (Antibody
Radiation Conjugate) Ac-225-Lintuzumab program, after successful
completion of the Actimab-A phase 2 trial in Acute Myeloid Leukemia
(AML), will incorporate two key initiatives; a pivotal trial
pathway for its Actimab-MDS program for Myelodysplastic Syndromes
(MDS), and also in two combination trials with Venetoclax for AML.
Actinium's development strategy for its CD33 program is being
informed by: clinical data from 4 trials totaling over 100 patients
including the recent Actimab-A Phase 2 trial in AML; positive
interactions with the FDA regarding its Actimab-MDS trial; company
research findings regarding potential synergy with Venetoclax;
support from leading physicians; and attractiveness of the targeted
indications given the unmet medical need and potential of its
differentiated ARC modality in combination with chemotherapy.
Actinium highlighted the outcome of its successful discussions
with the FDA for the Actimab-MDS program, which resulted in
guidance for an accelerated pathway to a pivotal trial after a
short dose finding Phase 1 portion. Actinium's initial
proposal to the FDA was to conduct a larger Phase 2 trial prior to
a pivotal trial in patients with a TP53 mutation, however, the
company was encouraged by the FDA to expand the trial to include
all high-risk patients with poor or very poor and complex
cytogenetics. The program will use the ARC Ac-225-lintuzumab
for targeted conditioning in combination with a reduced intensity
dose of fludarabine and melphalan prior to a BMT or Bone Marrow
Transplant in patients with high-risk Myelodysplastic Syndrome
(MDS).
Dr. Mark Berger, Actinium's Chief
Medical Officer said, "In our studies to date, we've seen that
Ac-225 – Lintuzumab can achieve remissions with minimal
extramedullary toxicities even in patients progressing to AML from
MDS. Typically, high-risk MDS patients undergoing a BMT do poorly
with standard conditioning resulting in poor outcomes. The goal of
the Actimab-MDS program is to use our ARC AC-225 – Lintuzumab to
target cells of the myeloid lineage including progenitor cells in
combination with reduced intensity conditioning with the goal of
achieving improved conditioning and BMT outcomes, as successful BMT
is the only potentially curative treatment option for these
patients. We are building on the data we already have from
our CD33 program and we are excited to have a quicker pathway to a
pivotal trial that targets a larger patient population than
originally envisaged."
Actinium's two combination trials with Venetoclax, a BCL-2
inhibitor that was jointly developed by AbbVie and Genentech, will
leverage Actimab-A's unique and differentiated mechanism of action
to explore synergies between the two agents for patients with
relapsed or refractory AML. Venetoclax is an approved drug for
patients with chronic lymphocytic leukemia (CLL) and small
lymphocytic lymphoma (SLL) and a supplemental New Drug Application
(NDA) has been submitted to the FDA for patients newly diagnosed
with AML. The first proposed study will evaluate Actimab-A in
combination with Venetoclax and will be led by Dr. Gary Schiller, Director, Hematology/Stem Cell
Transplantation at UCLA Medical center. The second study will
evaluate Actimab-A in combination with Venetoclax and
hypomethylating agents and will be conducted in collaboration with
Dr. Hagop Kantarjian and Dr.
Tapan Kadia of the MD Anderson
Cancer Center. The company is pursuing these combination
trials with Actimab-A and Venetoclax on the basis of internal
preclinical studies which have demonstrated a synergistic effect
between these two agents that is supported by a mechanistic
rational. Specifically, patients with AML have high levels of
MCL-1, a protein that mediates resistance to Venetoclax, which is
known to be depleted by DNA damage caused by external radiation
treatment. Preclinical studies have demonstrated that MCL-1
is effectively depleted by DNA damage caused by external radiation
and Actinium believes that Actimab-A's targeted radiation mechanism
will therefore lead to a greater effect of Actimab-A plus
Venetoclax, as demonstrated in the Company's preclinical work.
Dr. Berger added, "Many therapeutic advances in oncology, and
also in AML, have been the result of combination therapies.
We are excited to be advancing our Actimab-A program in
combination with Venetoclax, which has the potential to lead the
next evolution of AML therapy, in collaboration with top thought
leaders from leading medical institutions. As indicated by
our collaborators during the CD33 Update webinar, while results
with Venetoclax in patients with AML are encouraging, there remains
a high unmet need for durable responses and curative outcomes.
We believe Actimab-A can be used in combination with
Venetoclax to improve patient outcomes, which is based on a strong
scientific rationale supporting the combination as well as
preclinical and clinical data. Our proposed trials with these
combinations demonstrate the strong investigator interest we have
seen for working with Ac-225 – Lintuzumab as an Antibody Radiation
Conjugate is a new therapeutic modality for patients with radiation
sensitive cancers such as AML, MDS and Multiple Myeloma that has
the potential to improve their outcomes."
Sandesh Seth, Actinium's Chairman
and Chief Executive Officer said, "Having a clear and relatively
quick pathway to a pivotal trial for Actimab-MDS materially
strengthens our targeted conditioning pipeline. It also
enhances our outlook for building a business focused on developing
and launching multiple products for targeted conditioning prior to
BMT or CAR-T that can improve both patient access and outcomes due
to their superior safety and efficacy balance compared to
non-targeted chemotherapy that is current standard of care.
With the solid progress of the Iomab-B Phase 3 trial for BMT, the
recent launch of the Iomab-ACT program for CAR-T and the solid
impetus for a near-term Actimab-MDS pivotal trial, our pipeline
prospects for targeted conditioning have never been better."
Mr. Seth added, "The Actimab-A trial which was recently closed
has been a big success as it has provided the foundation for the
near-pivotal Actimab-MDS program in an area where there is high
unmet need, no competing development programs by other companies
and a larger patient population than originally envisaged.
Additionally, our combination trials with Venetoclax and Actimab-A
are very exciting as we have the opportunity to validate our
preclinical research showing superiority of the combination in two
highly relevant clinical settings where the unmet medical need
continues to be high. Based on these recent developments, our
CD33 Program has evolved much beyond the narrow AML focused CD33
programs in the industry due to the versatility of our ARC
technology. The ARC approach has allowed us to expand into
other radiation sensitive diseases such as multiple myeloma and
MDS, and into targeted conditioning using high doses of the ARC as
well as therapeutic combinations at lower ARC doses which allow
incorporation of targeted radiation as another modality to treat
highly radiation sensitive cancers."
"In addition," said Mr. Seth, "from a strategic perspective, the
Actimab-MDS targeted conditioning trial strengthens our go-it-alone
outlook. However, the other CD33 program developments including
combination trials increase its attractiveness to potential
collaborators and are expected to provide our company with
attractive optionality going forward, as the period between now and
2019 are expected to yield several valuable clinical milestones and
data readouts. We look forward to providing updates as value
in this program continues to build."
About Actinium Pharmaceuticals, Inc.
Actinium Pharmaceuticals Inc. is focused on improving patient
access and outcomes to cellular therapies such as bone marrow
transplant (BMT) and CAR-T with its proprietary, chemotherapy free
or sparing, targeted conditioning technology. Actinium is the only
company with a multi-disease, multi-target, drug development
pipeline focused on targeted conditioning. Its targeted
conditioning technology is enabled by ARC's or Antibody
Radio-Conjugates that combine the targeting ability of monoclonal
antibodies with the cell killing ability of radioisotopes.
Actinium's pipeline of clinical-stage targeted conditioning ARCs
target the antigens CD45 and CD33 for patients with a broad range
of hematologic malignancies including acute myeloid leukemia (AML),
myelodysplastic syndrome (MDS) and multiple myeloma (MM), acute
lymphoblastic leukemia (ALL), Hodgkin's lymphoma and Non-Hodgkin's
lymphoma. Actinium's Iomab-ACT program is designed to be a
universal lymphodepletion technology intended to eliminate the need
for chemotherapy-based conditioning prior to CAR-T or other
adoptive cellular therapies.
Iomab-B, Actinium's lead targeted conditioning product
candidate, is currently enrolling patients in the pivotal Phase 3
SIERRA trial in patients age 55 or older, with active, relapsed or
refractory AML. Iodine-131-apamistamab (Iomab-B), combines the
anti-CD45 monoclonal antibody labeled with iodine-131 for
myeloablation prior to a bone marrow transplant. CD45 is expressed
on leukemia, lymphoma and normal immune cells. Iomab-B has been
studied in over 500 patients in 10 clinical trials in numerous
hematologic diseases. Actinium's Iomab-ACT program is an expansion
of its CD45 program that is intended to be a universal,
chemotherapy-free solution for targeted lymphodepletion prior to
CAR-T. Through targeted lymphodepletion, the Iomab-ACT program is
expected to improve CAR-T cell expansion, reduce CAR-T related
toxicities and expand patient access to CAR-T treatment and
potentially other adoptive cell therapies. Due to its lower payload
dose, lymphodepletion with the Iomab-ACT program can be
accomplished through a single outpatient infusion. Actinium intends
to advance its Iomab-ACT program with CAR-T focused collaborators
from academia and industry.
Actinium's pipeline also includes a potentially best-in-class
CD33 program with its ARC comprised of the anti-CD33 antibody
lintuzumab labeled with the alpha-particle emitter actinium-225.
Its CD33 program is currently being studied in multiple clinical
trials for targeting conditioning and as a therapeutic as a single
agent or in combination in multiple diseases and indications
including AML, MDS and MM. Actinium applies its CD33 program at
high doses to target CD33+ cells of the myeloid lineage in
combination with reduced intensity conditioning (RIC), which
together are intended to result in myeloablative outcomes with a
more benign and well tolerated profile than high intensity
chemotherapy myeloablation. Actinium is focused on applying its
CD33 program at low doses in combination with other therapeutic
modalities including chemotherapy, targeted agents and
immunotherapies.
Actinium is also developing its proprietary AWE or Antibody
Warhead Enabling technology platform which utilizes radioisotopes
including iodine-131 and the highly differentiated actinium-225
coupled with antibodies to target a variety of antigens that are
expressed in hematological and solid tumor cancers. The AWE
technology enables Actinium's internal pipeline and with the
radioisotope Actinium-225 is being utilized in a collaborative
research partnership with Astellas Pharma, Inc. Actinium's clinical
programs and AWE technology platform are covered by a portfolio of
75 patents covering composition of matter, formulations, methods of
use and also methods of manufacturing the radioisotope Actinium-225
in a cyclotron.
More information is available at www.actiniumpharma.com and our
Twitter feed @ActiniumPharma, www.twitter.com/actiniumpharma.
Forward-Looking Statements for Actinium Pharmaceuticals,
Inc.
This press release may contain projections or other
"forward-looking statements" within the meaning of the
"safe-harbor" provisions of the private securities litigation
reform act of 1995 regarding future events or the future financial
performance of the Company which the Company undertakes no
obligation to update. These statements are based on management's
current expectations and are subject to risks and uncertainties
that may cause actual results to differ materially from the
anticipated or estimated future results, including the risks and
uncertainties associated with preliminary study results varying
from final results, estimates of potential markets for drugs under
development, clinical trials, actions by the FDA and other
governmental agencies, regulatory clearances, responses to
regulatory matters, the market demand for and acceptance of
Actinium's products and services, performance of clinical research
organizations and other risks detailed from time to time in
Actinium's filings with the Securities and Exchange Commission (the
"SEC"), including without limitation its most recent annual report
on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms
8-K, each as amended and supplemented from time to time.
Contact:
Actinium Pharmaceuticals, Inc.
Steve O'Loughlin
Principal Financial Officer
soloughlin@actiniumpharma.com
Investor Relations
Rx Communications Group
Paula Schwartz
917-322-2216
pschwartz@rxir.com
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