- Relapsed or
refractory AML patients with a TP53 mutation receiving Iomab-B led
allogeneic bone marrow transplant had a median Overall Survival of
5.49 months compared to 1.66 months in patients that did not
receive Iomab-B (hazard ratio=0.23, p=0.0002)
- Iomab-B's
mutation-agnostic mechanism overcomes TP53 mutations and produced
similar median Overall Survival outcomes of 6.37 months in TP53
negative patients and 5.72 months in TP53 positive patients
- Twenty-four
percent of patients enrolled on SIERRA had a TP53 mutation that is
typically associated with worse outcomes
- Oral
presentation scheduled for Sunday, December
10, 2023, with two additional poster presentations detailing
SIERRA trial results accepted for presentation
- Actinium
reports third quarter financial results and provides a business
update
NEW
YORK, Nov. 2, 2023 /PRNewswire/
-- Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM)
(Actinium or the Company), a leader in the development of targeted
radiotherapies, today announced that three abstracts detailing
results from the completed Phase 3 SIERRA trial of Iomab-B in
patients age 55 and above with active relapsed or refractory acute
myeloid leukemia (r/r AML) have been accepted for presentation at
the 65th Annual American Society of Hematology Annual
Meeting & Exposition (ASH) being held in San Diego on December
9-12, 2023. Outcomes of patients with a TP53 gene mutation
enrolled in the SIERRA trial have been accepted for an oral
presentation and results detailed in the abstract include the
following:
- Median Overall Survival (OS) of TP53 positive patients
receiving Iomab-B and a bone marrow transplant (BMT) was 5.49
months compared to 1.66 months in patients who did not receive
Iomab-B
- Iomab-B produced a statistically significant improvement in
median OS in TP53 positive patients with a hazard ratio of 0.23 and
p-value of 0.0002
- Median OS of 6.37 months in TP53 negative patients
receiving Iomab-B and 5.72 months for TP53 positive patients
demonstrating Iomab-B's mutation agnostic mechanism and ability to
overcome TP53 gene mutations
- 24% of patients (37/153) enrolled on the SIERRA trial had a
TP53 mutation, with 17 being randomized to the Iomab-B arm and
20 randomized to the control arm
Dr. Avinash Desai, Actinium's
Chief Medical Officer, commented, "We are very excited by these
results which show a statistically significant and greater than
three-times increase in median OS in TP53 positive patients
receiving Iomab-B. These results further support Iomab-B's
differentiated profile and ability to improve outcomes for the most
difficult to treat r/r AML patients. A TP53 gene mutation is
arguably the most unfavorable risk factor leading to the worst
patient outcomes as it is associated with inherent resistance to
available therapies, short duration of responses and the lowest
survival rates. Despite being a common mutation found in
approximately 10-15% of all AML cases and up to 25% of patients
over age 60, there are no approved therapies that target TP53. For
patients with high-risk AML, particularly those with r/r disease
and a TP53 mutation, BMT is associated with the best treatment
outcomes and is the only potentially curative therapeutic option.
Iomab-B's ability to facilitate a BMT in this patient population
continues to demonstrate a strong clinical benefit as supported by
these results and we look forward to presenting the full TP53
analysis at ASH in early December."
Detailed results will be presented in an oral presentation on
December 10, 2023, as follows:
Session Name: 721. Allogeneic Transplantation: Conditioning
Regimens, Engraftment and Acute Toxicities: Novel Conditioning
Regimens for Myeloid Malignancies
Session Date: Sunday, December 10,
2023
Session Time: 9:30 AM - 11:00 AM Pacific
Time
Presentation Time: 9:30 AM
Room: Marriott Marquis San Diego
Marina, Pacific Ballroom Salons 18-19
Publication Number: 469
Title: 131I-Apamistamab-Led Allogeneic Hematopoietic
Cell Transplant Significantly Improves Overall Survival in Patients
with TP53 Mutated R/R AML
Submission ID: 182177
Sandesh Seth, Actinium's Chairman
and CEO, added, "This oral presentation at ASH represents the
eighth oral presentation from the SIERRA results in 2023. Through
these presentations, we have built strong recognition for Iomab-B's
unique clinical profile and utility in this disease with high unmet
medical need amongst key medical and scientific communities
comprised of BMT physicians, hematologists, nuclear medicine
physicians, nurses and transplant coordinators. These additional
data in TP53 positive patients further supports the potential of
targeted radiotherapy in heterogenous, difficult-to-treat blood
cancers given its mutation-agnostic mechanism of action. Further,
we believe the broad expression of CD45 enables development of
Iomab-B across various blood cancers, as well as cell and gene
therapy with our next-generation conditioning agent, Iomab-ACT,
allowing Actinium to address a significant patient need."
Additional SIERRA data will be presented in two poster
presentations as follows:
Session Name: 721. Allogeneic Transplantation: Conditioning
Regimens, Engraftment and Acute Toxicities: Poster I
Session Date: Saturday, December 9,
2023
Presentation Time: 5:30 PM - 7:30 PM Pacific
Time
Location: San Diego Convention
Center, Halls G-H
Publication Number: 2159
Title: 131I-Apamistamab Effectively Achieved Durable
Responses in Patients with R/R AML Irrespective of the Presence of
Multiple High-Risk Factors
Session Name: 721. Allogeneic Transplantation: Conditioning
Regimens, Engraftment and Acute Toxicities: Poster II
Session Date: Sunday, December 10,
2023
Presentation Time: 6:00 PM - 8:00 PM Pacific
Time
Location: San Diego Convention
Center, Halls G-H
Publication Number: 3529
Title: High-Dose Targeted Radiation with
131I-Apamistamab Prior to HCT Demonstrated a
Dose-Response for Durable Complete Remission in Patients with R/R
AML
Financial results and business update
On November 2, 2023, Actinium
reported financial results for the third quarter 2023 and provided
a business update. For additional information, refer to the
Company's Form 10-Q for the third quarter 2023 filed with the SEC
on November 2, 2023, which should be
read in addition to this press release.
Cash and cash equivalents: The Company reported cash and
cash equivalents of approximately $82.9
million as of September 30,
2023, and maintains its prior cash runway guidance through
year-end 2025 based on its current operating plan.
Research and Development Expense, net of reimbursements:
Research and development expenses of $11.6
million for the third quarter of 2023 increased $4.8 million from $6.8
million for the same period in 2022. Higher research and
development expenses were primarily due to increased CMC activity
related to BLA-enabling work for Iomab-B. Once complete, CMC
expenses are expected to decrease in 2024 as we expect to use final
drug product material produced to support the BLA filing and to
supply initial Iomab-B commercialization. Additionally,
compensation expense increased $1.1
million as a result of higher headcount necessary to support
BLA-enabling CMC activity.
General and Administrative Expense: General and
administrative expenses of $2.7
million for the third quarter 2023 decreased by $0.4 million from $3.1
million for the same period in 2022. Lower professional and
consulting fees of $0.5 million,
lower legal fees of $0.1 million and
lower non-cash equity compensation of $0.1
million were partially offset by increased compensation of
$0.3 million as a result of higher
headcount.
Other Income: Other income is comprised of net interest
income in both reporting periods. The amount for the third quarter
2023 of $1.1 million increased from
$0.3 million for the same period in
2022 due to a higher average interest rate.
Net Loss: Net loss of $13.3
million for the third quarter 2023 increased by $3.8 million from $9.5
million for the same period in 2022 primarily due to higher
research and development expenses, primarily due to increased CMC
BLA-enabling activity and CMC headcount that was partially offset
by lower general and administrative expenses and higher other
income.
Actinium also provided an update on its regulatory activity
pertaining to its planned Biologics License Application (BLA) for
Iomab-B as well as the planned marketing authorization application
(MAA) to the European Medicines Agency (EMA) that will be completed
by Immedica Pharma AB (Immedica), Actinium's European, Middle East and North Africa commercial partner for Iomab-B.
The Company has been meeting with the FDA regarding its BLA
strategies, and has received positive feedback regarding the
Chemistry, Manufacturing and Controls (CMC) package for Iomab-B. As
a continuation of its regulatory interactions with the FDA, the
Company will request a meeting prior to completion of the CMC
package to further discuss the clinical and non-clinical modules
that will determine the finalization and timing of its planned BLA
filing. As a result of the CMC meeting, as well as updated project
timelines necessitated by the now complete facility modifications
at one of its third-party manufacturers, the Company is progressing
with completion of CMC activities and believes it is on track to
complete the CMC modules and be in a position to submit a BLA
filing in the first half of 2024. The Early Access Program for
Iomab-B is also anticipated to start post completion of these
activities. Actinium is also simultaneously working with Immedica
to support its planned MAA filing for Iomab-B. Europe represents a large commercial market
opportunity with approximately twice as many transplants performed
in Europe compared to the U.S.
About Iomab-B and the Pivotal Phase 3 SIERRA Trial
Iomab-B is a first-in-class targeted radiotherapy intended to
improve patient access to potentially curative BMT by
simultaneously and rapidly depleting blood cancer, immune and bone
marrow stem cells that uniquely express CD45. Multiple studies have
demonstrated increased survival in patients receiving BMT, however,
an overwhelming majority of patients with blood cancers do not
receive BMT as current approaches do not produce a remission, which
is needed to advance to BMT, or are too toxic. Studied in over 400
patients, prior studies with Iomab-B have demonstrated nearly
universal access to BMT, increased survival and tolerability in
multiple clinical trials including the recently completed pivotal
Phase 3 SIERRA trial in patients with active (leukemic blasts
>5%), relapsed or refractory acute myeloid leukemia (r/r AML)
age 55 and above.
Iomab-B met the primary endpoint of durable Complete Remission
(dCR) of 6 months after initial remission post-BMT in the pivotal
Phase 3 SIERRA trial with high statistical significance
(p<0.0001). Iomab-B produced a 75% post-BMT CR rate (44/59
patients), which is 12-times greater than the post-BMT rate of 6.3%
(4/64 patients) in the control arm. Patients receiving Iomab-B had
a 78% lower probability of an event, defined as not achieving a
CR/CRp, crossover, not receiving a BMT, relapse or death, with a
Hazard Ratio of 0.22 (p<0.0001). Iomab-B doubled 1-year overall
survival with 26.1% compared to 13.1% in the control arm for
patients who did not crossover as well as median overall survival
with 6.4 months vs 3.2 months. Overall survival statistics are
confounded by the crossover arm. Crossover patients had a 35.8%
1-year overall survival rate. Due to its targeted nature, Iomab-B
was well tolerated with four times lower rates of sepsis compared
to the control arm (6.1% vs. 28.6%) and lower rates of BMT
associated adverse events including febrile neutropenia, mucositis
and graft versus host disease (GVHD). Actinium intends to submit a
Biologics License Application (BLA) seeking approval for Iomab-B in
2024 to address patients age 55+ with r/r AML who cannot access BMT
with currently available therapies. Iomab-B has been granted Orphan
Drug Designation from the U.S. Food and Drug Administration (FDA)
and has patent protection into 2037.
The pivotal Phase 3 SIERRA (Study of Iomab-B in Elderly relapsed
or refractory AML) is a 153-patient, randomized, multi-center
clinical trial, studying Iomab-B compared to the control arm of
physician's choice of salvage therapy. Control arm options included
chemotherapies like cytarabine and daunorubicin and targeted agents
such as a Bcl-2 inhibitor (Venetoclax), FLT3 inhibitors and IDH 1/2
inhibitors. The SIERRA control arm reflects real-world treatment of
r/r AML patients with over 20 agents used alone or in combination
as no standard of care exists for this patient population. The
SIERRA trial enrolled patients at 24 leading transplant centers in
the United States and Canada that perform over 30% of AML BMTs.
Developed at the Fred Hutchinson Cancer Research Center, a
pioneer in the field of BMT, Iomab-B is supported by data in six
disease indications including leukemias, lymphomas and multiple
myeloma, which afflict over 100,000 patients annually. Actinium
intends to pursue additional indications for Iomab-B beyond AML.
Actinium also intends to pursue international regulatory approvals
independently and through partnerships. In April 2022, Actinium licensed the European,
Middle East and North African
commercial rights for Iomab-B to Immedica Pharma AB, a
fully-fledged independent pharmaceutical company headquartered in
Sweden. In exchange, Actinium
received an upfront payment of $35 million
USD with the potential for an additional $417 million USD in regulatory and sales
milestones and mid-twenty percent royalties. Europe represents a commercial opportunity
approximately double the size of the
United States by number of patients with AML receiving BMT.
Iomab-B has been granted Orphan Drug Designation by the European
Medicines Agency (EMA) and has received positive Scientific Advice
from the Committee for Medicinal Products for Human Use (CHMP) of
the EMA indicating that the Phase 3 SIERRA trial design, primary
endpoint and planned statistical analysis are acceptable as the
basis for a Marketing Authorization Application.
About Actinium Pharmaceuticals, Inc.
Actinium develops targeted radiotherapies to meaningfully
improve survival for people who have failed existing oncology
therapies. Advanced pipeline candidates Iomab-B (pre-BLA), an
induction and conditioning agent prior to bone marrow transplant,
and Actimab-A (National Cancer Institute CRADA pivotal development
path), a therapeutic, have demonstrated potential to extend
survival outcomes for people with relapsed and refractory acute
myeloid leukemia. Actinium plans to advance Iomab-B for other blood
cancers and next generation conditioning candidate Iomab-ACT to
improve cell and gene therapy outcomes. Actinium's technology
platform is the basis for collaborations with Astellas Pharma for
solid tumors, AVEO Oncology/LG Chem Life Sciences for HER3 solid
tumors, and several internal programs in solid tumors. Actinium
holds more than 220 patents and patent applications.
For more information, please
visit: https://www.actiniumpharma.com/
Forward-Looking Statements
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.
Investors:
investorrelations@actiniumpharma.com
Sources: Granowicz EM, Jonas BA.
Targeting TP53-Mutated Acute Myeloid Leukemia: Research
and Clinical Developments. Onco Targets Ther. 2022 Apr
21;15:423-436. doi: 10.2147/OTT.S265637. PMID: 35479302; PMCID:
PMC9037178.
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SOURCE Actinium Pharmaceuticals, Inc.