Item 1A. Risk Factors 28
Item 1B. Unresolved Staff Comments 63
Item 1C. Cybersecurity 63
Item 2. Properties 64
Item 3. Legal Proceedings 64
Item 4. Mine Safety Disclosures 64
Item 6. Reserved 66
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 69
Item 8. Financial Statements and Supplementary Data F-1
Item 9A. Controls and Procedures 70
Item 9B. Other Information 70
Item 9C Disclosure Regarding Foreign Jurisdictions That Prevent Inspections 70
Item 10. Directors, Executive Officers and Corporate Governance 71
Item 11. Executive Compensation 84
Item 12. Security Ownership of Certain Beneficial Owners and Management 88
Item 14. Principal Accountant Fees and Services 89
Item 15. Exhibits, Financial Statement Schedules 90
Signature Page 95
i
CAUTIONARY
NOTE REGARDING FORWARD-LOOKING STATEMENTS
This
Annual Report on Form 10-K (this “Report”) contains forward-looking statements that involve risks and uncertainties, principally
in the sections entitled “Description of Business,” “Risk Factors,” and “Management’s Discussion
and Analysis of Financial Condition and Results of Operations.” All statements other than statements of historical fact contained
in this Report, including statements regarding future events, our future financial performance, business strategy and plans and objectives
of management for future operations, are forward-looking statements. We have attempted to identify forward-looking statements by terminology
including “anticipates,” “believes,” “can,” “continue,” “could,” “estimates,”
“expects,” “intends,” “may,” “plans,” “potential,” “predicts,”
“should,” or “will” or the negative of these terms or other comparable terminology. Although we do not make forward-looking
statements unless we believe we have a reasonable basis for doing so, we cannot guarantee their accuracy. These statements are only predictions
and involve known and unknown risks, uncertainties and other factors, including the risks outlined under “Risk Factors” or
elsewhere in this Report, which may cause our or our industry’s actual results, levels of activity, performance or achievements
expressed or implied by these forward-looking statements. Moreover, we operate in a very competitive and rapidly changing environment.
New risks emerge from time to time and it is not possible for us to predict all risk factors, nor can we address the impact of all factors
on our business or the extent to which any factor, or combination of factors, may cause our actual results to differ materially from
those contained in any forward-looking statements. All forward-looking statements included in this document are based on information
available to us on the date hereof, and we assume no obligation to update any such forward-looking statements.
You
should not place undue reliance on any forward-looking statement, each of which applies only as of the date of this Report. Before you
invest in our securities, you should be aware that the occurrence of the events described in the section entitled “Risk Factors”
and elsewhere in this Report could negatively affect our business, operating results, financial condition and stock price. Except as
required by law, we undertake no obligation to update or revise publicly any of the forward-looking statements after the date of this
Report to conform our statements to actual results or changed expectations.
ii
PART
I
ITEM
1. BUSINESS.
Description
of Our Business
Actinium Pharmaceuticals,
Inc. (“Actinium”, the “Company”, or “we”) is a pioneer in the development of targeted radiotherapies
intended to meaningfully improve outcomes for patients with advanced cancers including relapsed or refractory (“r/r”) disease
who have failed existing therapies. We are advancing a pipeline of differentiated clinical stage product candidates focused on validated
cancer targets. Our current pipeline is focused on indications in myeloid malignancies, solid tumors and conditioning for cell and gene
therapies that we believe have high unmet needs that are not addressed by currently available treatment options. Our goal is to create
a specialty radiopharmaceutical company with capabilities across radioisotope production, final drug product manufacturing, preclinical
research and development (“R&D”) and clinical development. We are deploying our technologies and capabilities, which we
believe to be industry-leading, and intellectual property with approximately 230 issued and pending patents worldwide, to develop targeted
and next-generation radiotherapies.
Our Product Candidate Pipeline
We are advancing two clinical stage product candidates that are directed
against validated cancer targets. Actimab-A is our lead product candidate in development and is intended to address the significant unmet
medical needs of patients with myeloid malignancies including acute myeloid leukemia (“AML”) and myelodysplastic syndromes
(“MDS”). We are also evaluating Actimab-A’s potential to synergize with PD-1 immune checkpoint inhibitors (“ICIs”)
in solid tumor indications through the depletion of immune cells known as myeloid derived suppressor cells (“MDSCs”). Iomab-ACT
is a next-generation targeted conditioning agent we are developing with the intent to improve patient access to and outcomes with cellular
therapies such as CAR-T for various blood cancer indications and gene therapies for non-malignant hematologic disorders such as sickle
cell disease (“SCD”). We are also developing ATNM-400, a novel preclinical, non-prostate specific-membrane antigen (“PSMA”)
targeting, first-in-class radiotherapy utilizing the Actinium-225 (“Ac-225”) radioisotope payload intended for patients with
prostate cancer directed against a novel radiotherapy target.
Actimab-A is being developed
as a targeted radiotherapeutic to leverage the Actinium-225 (“Ac-225") isotope payload directed against CD33, a target expressed
ubiquitously in patients with AML, MDS and expressed in other myeloid malignancies. We are attempting to leverage the mutation-agnostic
ability of Ac-225 to establish Actimab-A as a backbone therapy in myeloid malignancies, which are extremely heterogenous and radiosensitive,
as a single agent or in combinations with chemotherapy, targeted agents, cellular therapy and immunotherapy. Actimab-A has been studied
in over 150 patients. We plan to initiate a Phase 2/3 trial with Actimab-A in combination with the chemotherapy regimen CLAG-M in patients
with r/r AML. In addition to our internal development efforts, we entered into a Cooperative Research and Development Agreement (“CRADA”)
with the National Cancer Institute (“NCI”) in February 2023 for the development of Actimab-A for AML and other myeloid malignancies.
The first clinical trial to be conducted under our CRADA with NCI will evaluate the triplet combination comprised of Actimab-A, Venetoclax
and ASTX-727, a novel oral HMA developed by Taiho Oncology, an Otsuka Holdings company, in frontline AML patients. Venetoclax in combination
with HMAs (Ven-HMA) is approved for patients with newly diagnosed AML. We believe this trial is supported by our Actimab-A + Venetoclax
combination trial that showed that combination was well-tolerated and showed supportive anti-leukemic activity. Additional clinical trial
concepts for Actimab-A have been submitted under the CRADA and are being reviewed. We anticipate that additional clinical trials with
Actimab-A will be initiated in 2025 including under the CRADA to leverage Actimab-A’s mutation agnostic mechanism.
1
In March of 2025, we initiated
our Actimab-A solid tumor program that will combine Actimab-A with PD-1 checkpoint inhibitors. We initiated this program to evaluate if
Actimab-A can deplete CD33 expressing MDSCs and hence improve patient outcomes in combination with PD-1 ICIs such as KEYTRUDA® and
OPDIVO®. The Actimab-A solid tumor program is comprised of several controlled, head-to-head clinical trials that will evaluate
the combination of Actimab-A with KEYTRUDA® versus KEYTRUDA® alone, and Actimab-A with OPDIVO® versus
OPDIVO® alone. The initial tumors that are being targeted are Head and Neck Squamous Cell Carcinoma (“HNSCC”)
and Non-Small Cell Lung Cancer (“NSCLC”) with a separate trial for each indication.
ATNM-400 is our newest targeted
radiotherapy program that we are advancing for prostate cancer. Given the biology of the antigen targeted by ATNM-400 and the precise
and potent cell-killing of Ac-225, we believe ATNM-400 has the potential to address unmet needs in prostate cancer. We have generated
preclinical data with ATNM-400 showing selective tumor accumulation with minimal uptake in normal tissues. Our experiments also showed
dose-dependent cytotoxicity. We continue to study ATNM-400 with additional data expected from Pluvicto-resistant prostate cancer models.
Pluvicto (Lu-177-PSMA-617) is a prostate-specific membrane antigen (PSMA) directed targeted radiotherapy that uses the beta-particle emitting
radioisotope Lutetitium-177 (“Lu-177”) that is approved for patients with metastatic prostate cancer. ATNM-400 is differentiated
from Pluvicto as it targets a different marker than PSMA that has been shown to be overexpressed in patients with prostate cancer and
uses the alpha-particle emitter Ac-225, which is more potent than Lu-177 but has a shorter path length, which could result in fewer off-target
effects such as xerostomia.
In addition to ATNM-400, we
have active R&D efforts leveraging our in-house preclinical development and translational research capabilities that are primarily
focused on supporting our ATNM-400 preclinical program, the Actimab-A and Iomab-ACT clinical programs and advancing several preclinical
programs for solid tumor indications.
Iomab-ACT is our next-generation
targeted conditioning agent directed against CD45, a target expressed widely across the hematopoietic system including normal nucleated
immune cells such as lymphocytes that is relevant to this program and uses the Iodine-131(“I-131") radioisotope payload. We
are developing Iomab-ACT for cell and gene therapies for both malignant and non-malignant hematologic indications. Iomab-ACT utilizes
non-myeloablative doses of I-131, to not fully deplete the patient’s bone marrow and immune system with the goal of improving patient
access and outcomes for potentially curative cell and gene therapies by replacing the need for the non-targeted, chemotherapy-based conditioning
regimens that are currently used. Iomab-ACT is currently being studied in three clinical trials. These trials include Iomab-ACT with a
commercial CAR-T therapy, Iomab-ACT prior to allogeneic BMT for patients with SCD, which could potentially inform a trial design with
gene therapy for SCD, and Iomab-ACT with a novel investigational CD19 CAR-T therapy.
We
previously advanced our targeted conditioning program Iomab-B through the Phase 3 Study of Iomab-B in Elderly Relapsed and Refractory
AML (“SIERRA”) trial, a 153 patient, randomized multi-center trial conducted in the United States. and Canada. Iomab-B is
comprised of the anti-CD45 monoclonal antibody apamistamab with myeloablative doses of I-131 intended to enable patient access to bone
marrow transplant (“BMT”), the only potentially curative treatment option for patients with r/r AML. At this time, we are
seeking a strategic partner for Iomab-B to conduct an additional clinical trial based on feedback from the U.S. Food & Drug Administration
(“FDA”) and are committed to establishing the best development path forward for Iomab-B in the U.S., while keeping internal
resources and strategic priorities in focus. As previously disclosed and noted above, Actinium also has a License Agreement with Immedica,
granting Immedica the exclusive product rights for commercialization of Iomab-B in certain countries in the European Economic Area, Middle
East and North Africa (“EUMENA”) region.
Actinium’s Approach to Targeted Radiotherapy
Development
Radiation is a validated cancer
therapy that has been used to treat patients for over 100 years. It is used to treat over half of all patients diagnosed with cancer today.
Radiation therapy utilizes rays of energy to kill cancer cells and is commonly used in combination with other cancer treatment modalities.
Radiation therapy is primarily administered from outside of the body and therefore passes through normal healthy tissue and organs that
result in side effects and toxicities, which can be acute and/or chronic.
2
With our targeted radiotherapy
approach, we seek to address the limitations of external radiotherapy and achieve cellular level precision by leveraging the cancer cell
targeting ability of biologic molecules with the cancer cell killing ability of radioisotopes. In doing so, we seek to improve efficacy
outcomes, reduce toxicities and expand the use of radiation to cancer indications like blood cancers that cannot be addressed with externally
delivered radiation. In addition, we are also testing the use of targeted radiotherapies in solid tumor cancers where there are unmet
medical needs. Biological molecules have demonstrated high affinity for cancer cell identification and binding to biological markers on
the surface of cells known as antigens or ligands, which are the target receptors for our targeted radiotherapies.
Actinium’s Targeted Radiotherapies
Alpha particles emitted by
as the element Ac-225 are the heaviest and have the highest charge, resulting in high amounts of linear energy transfer, which is capable
of producing double strand DNA breaks. However, alpha-particles travel short distances of just several microns and as a consequence do
not exert radiation outside of the body. Alpha particles can be stopped by an ordinary sheet of paper. Therefore, alpha particle-based
therapies do not require special shielding or that patients remain isolated following treatment. Beta particle-based therapies have a
longer pathlength but have lower amounts of linear energy transfer and at certain dose levels may require isolation or special handling.
Comparison of Radioisotope Pathlength
We focus on producing drug candidates that match a specific targeting
agent with the appropriate isotope for a desired indication. We employ an isotope-agnostic approach to targeted radiotherapy development.
Our development efforts are centered on validated targets that are known to have high expression on cancer cells compared to normal healthy
cells. We are advancing our clinical product candidates targeting CD33 and CD45 and have completed preclinical studies against other blood
cancer targets such as CD38, as well as various validated solid tumors targets.
3
Our Strategy
We believe that the cell-killing power of linear energy transfer delivered
via radiotherapeutics is unmatched by other technologies and that there are multiple indications where radiotherapeutics can succeed over
other approaches. However, radiotherapeutics must be delivered on a just-in-time basis, and commercial and supply chain barriers are higher
than with other types of medicines. Actinium’s strategy is to build a specialty radiotherapeutics company with the capabilities
to produce radioisotopes, manufacture radiotherapies, conduct preclinical research, clinical development and supply radiotherapies to
the point of care. We believe our strategy will enable us to build a successful company with the potential for high operating efficiencies.
Our strategic priorities are to:
Establish Actimab-A as a mutation agnostic,
backbone therapy for myeloid malignancies including patients with AML and high-risk MDS;
Establish Actimab-A as a pan solid tumor therapy
in combination with PD-1 inhibitors including KEYTRUDA® and OPDIVO® by depleting myeloid derived suppressor
cells;
Determine the potential of ATNM- as a viable
treatment for patients with prostate cancer;
Establish Iomab-ACT as a universal targeted
conditioning agent for cell and gene therapies to improve patient access and outcomes;
Leverage our R&D capabilities and clinical
development experience to further advance pipeline assets for cancer indications with high unmet needs; and
Establish in-house manufacturing infrastructure
to support our planned later-stage clinical development and secure partnerships to enable the deployment of our proprietary Ac-225 cyclotron
manufacturing technology.
Market Opportunity for Our Targeted Radiotherapies
We believe our clinical programs
have the potential to address a significant number of patients with high unmet medical needs and therefore represent large potential market
opportunities. To our knowledge, Actimab-A, Iomab-ACT and ATNM-400 are first in class targeted radiotherapies for myeloid malignancies,
targeted conditioning for cell & gene therapies and multiple solid tumors, respectively, with each discrete opportunity representing
a range of over 100,000 to several hundred thousand addressable patients.
Four Large & Distinct Potential Market
Opportunities
4
Actimab-A Myeloid Malignancies Program
We are focused on developing
our lead targeted radiotherapy Actimab-A for patients with AML and MDS, which are the most common myeloid malignancies in adults. AML
and certain MDS can progress rapidly, especially in patients with high-risk features such as certain genetic mutations. To our knowledge,
Actimab-A is the only CD33 targeted radiotherapy in development for patients with myeloid malignancies.
Myeloid malignancies are a
group of cancers that affect blood-forming cells also referred to as hematopoietic cells in the bone marrow. These cells are from the
myeloid lineage and include white blood cells, red blood cells and platelets. Myeloid malignancies include AML, MDS, chronic myeloid leukemia
(“CML”) and myeloproliferative neoplasms (“MPNs”).
We believe Actimab-A can be used in multiple treatment settings across
the myeloid patient journey. For patients with AML, we plan to develop Actimab-A for both fit and unfit patients in the frontline, relapsed
or refractory and maintenance settings either as a monotherapy or in combination with other treatments. For patients with MDS, we plan
to develop Actimab-A for patients who have high-risk disease and in the maintenance setting. In the United States and the
five largest countries in Western Europe (France, Germany, Italy, Spain and the United Kingdom, which we refer to as “EU5”),
we estimate the patient population across our target treatment settings in these diseases to be greater than 100,000 patients annually.
U.S. and EU5 AML & MDS Addressable Patient
Population
AML is increasingly defined
by the presence of genetic mutations or cytogenetic abnormalities as well as prior therapy given the increased number of approved agents.
AML is a mutation rich disease that is genetically heterogeneous with identifiable mutations in over 95% of all patients. The most common
mutations for which there are approved therapies include fms-like tyrosine kinase 3 (“FLT3”), isocitrate dehydrogenase 1 &
2 (“IDH1”) (“IDH2”), and nucleophosmin 1 (“NPM1”) & KMT2A rearrangements.
Various treatments are currently
approved or utilized for patients with AML and MDS including chemotherapies, targeted therapies, antibody drug conjugates (“ADCs”),
hypomethylating agents (“HMAs”) and BMT. Since 2017, twelve therapies have been approved for patients with AML. As part of
our development strategy, we have evaluated and expect to continue to evaluate Actimab-A in combination with these approved therapies
and other emerging treatment options or therapeutic modalities to leverage its mutation agnostic and potentially synergistic mechanism
of action. Given the ubiquitous expression of CD33, we believe Actimab-A has the potential to be a backbone therapy for myeloid malignancies.
5
Fewer approved treatment options
exist for patients with MDS, particularly high-risk patients. Treatments currently approved or utilized for high-risk patients include
chemotherapies, HMAs and IDH1 inhibitors. We intend to evaluate the potential utility of Actimab-A in MDS either as single agent or in
combination with other therapies.
Given the complexity and aggressiveness
of AML and High-risk MDS, these patients are often referred to and treated in comprehensive treatment centers for in-patient treatment
as opposed to community, outpatient-based care. As a result, we believe the majority of AML and High-risk MDS patients largely occurs
in a finite number of centers, which implies efficiencies from concentration of commercialization efforts.
Actimab-A Solid Tumor Program
We believe a large market
opportunity also exists for Actimab-A in solid tumor indications by depleting MDSCs to synergize with PD-1 checkpoint inhibitors and potentially
other immune checkpoint inhibitors. Several solid tumor indications have shown to have high expression of MDSCs including non-small cell
lung cancer (“NSCLC”), melanoma, renal cell carcinoma (“RCC”), colorectal cancer (“CRC), triple negative
breast cancer (“TNBC”), head & neck squamous cell carcinoma (“HNSCC”), pancreatic cancer, glioblastoma (“GBM”)
prostate cancer and ovarian cancer. Cumulatively, over 600,000 patients are diagnosed with these cancers annually. PD-1 checkpoint inhibitors
are approved in a significant number of these indications and in 2024 generated sales totaling more than $45 billion.
We are planning to conduct our initial controlled, randomized clinical
trials in HNSCC and NSCLC in combination with the PD-1 checkpoint inhibitors KEYTRUDA® and OPDIVO®. These
two indications represent a potential addressable patient opportunity of over 250,000 patients. We expect to continue to evaluate additional
indications for potential future clinical trials assuming our initial efforts are successful.
ATNM-400 Prostate Cancer Program
Prostate cancer is the
most common cancer in men, with approximately 1 in 8 men diagnosed with prostate cancer during their lifetime. According to the American
Cancer Society, an estimated 313,780 new cases of prostate cancer will be diagnosed in the United States in 2025. The global incidence
of prostate cancer is approximately 1.5 million new cases annually. Approximately 20% of prostate cancer cases are more aggressive forms
that progress to metastatic disease, which is associated with significantly worse survival outcomes. Radiotherapy is commonly used to
treat prostate cancer, and in 2022, the PSMA-targeting radiotherapy Pluvicto was approved by the FDA and the European Medicines Agency
(“EMA”) for the treatment of patients with metastatic castration-resistant prostate cancer. Pluvicto is marketed and sold
by Novartis and generated sales of $1.39 billion in 2024. ATNM-400 is differentiated from Pluvicto as it targets a different marker than
PSMA that has been shown to be overexpressed in patients with prostate cancer and uses the alpha-particle emitter Ac-225, which is more
potent than Lu-177 but has a shorter path length, which could result in fewer off-target effects such as xerostomia.
Iomab-ACT Cell & Gene Therapy Conditioning
Program
We are developing Iomab-ACT as a targeted conditioning agent to prepare
patients for cellular therapies such as CAR-T or BMT and gene therapies. Our current clinical trials are focused on patients with blood
cancers and non-malignant blood disorders such as SCD. The first CAR-T therapies was approved in 2017 and currently, there are 6 approved
CAR-T therapies for patients with lymphomas, leukemia and multiple myeloma, which generated sales of over $4.0 billion in 2024. We estimate
that there are approximately 125,000 patients diagnosed with blood cancers that can be potentially treated with CAR-T therapies, which
are currently approved for r/r patients. SCD is a rare, debilitating and life-threatening blood disorder with significant unmet needs
that affects approximately 100,000 people in the U.S. Patients with SCD have a mutation that causes red blood cells to develop a crescent
or “sickle” shape, which restrict the flow in blood vessels and limit oxygen delivery to the body’s tissues, leading
to severe pain and organ damage called vaso-occlusive events (“VOEs”) or vaso-occlusive crises (“VOCs”). The
recurrence of these events or crises can lead to life-threatening disabilities and/or early death. An allogeneic BMT is a potentially
curative treatment option for patients with sickle cell disease, particularly in pediatric and adolescent patients who have had complications
such as strokes, acute chest crises or recurring pain crises due to their disease. In addition, there are two approved gene therapies
for patients with sickle cell disease, Casgevy (Vertex Pharmaceuticals, Inc. and CRISPR Therapeutics) and Lyfgenia (Bluebird Bio, Inc.).
6
Our Clinical Product Candidates
Actimab-A: Mutation Agnostic Mechanism of Action
with Backbone Therapy Potential in Myeloid Malignancies including AML and high-risk MDS
Actimab-A (Ac-225-lintuzumab satetraxetan) is our lead radiotherapeutic
product candidate in development for patients with myeloid malignancies. To our knowledge, Actimab-A is the only CD33 targeting radiotherapy
in clinical development. We are focused on developing Actimab-A as both a monotherapy and in combination with other treatment regimens
to leverage both the potential mechanistic synergies of radiation and its mutation agnostic cell killing ability. In addition to our internal
development efforts, we entered into a CRADA with the NCI in February 2023 for the development of Actimab-A for AML and other myeloid
malignancies.
We intend to establish Actimab-A as a backbone therapy leveraging the
broad expression of CD33 in myeloid malignancies such as AML and MDS, which, like most blood cancers, are highly sensitive to radiation.
AML is a highly heterogenous, mutation rich cancer with over 70 identified driver genetic mutations. However, there are only approved
therapies for four mutations including FLT3, IDH1 & IDH2, and NPM1. CD33 is expressed regardless of other mutations being present
The Ac-225 isotope payload that we utilize with Actimab-A emits potent alpha-particles with high linear energy that kill cells via double
strand DNA breaks for which there is no known resistance or repair mechanism.
Actimab-A’s Mechanistic
Synergy and Potential Combinations
Our development strategy is
to exploit these properties of Actimab-A to address the unmet needs of patients with myeloid malignancies across the treatment journey
including the frontline, relapsed/refractory and maintenance settings. To accomplish this, we are leveraging our clinical development
experience, clinical data and preclinical work supporting Actimab-A’s mutation agnostic capabilities.
Actimab-A Clinical Development Experience
To our knowledge, Actimab-A
is one of the most studied alpha-particle based targeted radiotherapies in clinical development having been studied in over 150 patients
across multiple clinical trials. Actimab-A has been studied at multiple dose levels, different administration schedules and as a single
agent or in combination with chemotherapy and targeted agents in patients with AML in the front line and relapsed or refractory settings
with promising results to date.
7
Actimab-A Monotherapy Phase 2 Trial
Following multiple Phase 1
clinical trials, Actimab-A was studied in a 40-patient multi-center Phase 2 trial as a single agent in patients newly diagnosed with AML
age 60 and above who were ineligible for intensive chemotherapy. At the dose level of 2.0 μCi/kg, Actimab-A produced high overall response
rates (“ORR”) of 69% including Complete Remission (“CR”), Complete Remission with incomplete platelet recovery
(“CRp”) and Complete Remission with incomplete blood count recovery (“CRi”). Prolonged myelosuppression was the
most common adverse event and was expected as it is a known class effect of CD33 targeting therapies and given the advanced age of the
patients enrolled. The Actimab-A dose was adjusted to 1.5μCi/kg, which produced an ORR of 22%. Potent anti-leukemic effect was observed
at both dose levels. Of the patients treated with 1.5 μCi/kg of Actimab-A, the median age was 75 and over 50% of the patients had an
antecedent hematologic disorder including MDS, chronic myelomonocytic leukemia and myelofibrosis, which can compromise a patient’s
bone marrow function and ability to recover blood counts and proper function. This trial was conducted prior to the approval of many of
the targeted therapies that are routinely used in the treatment of patients with AML today. As a result of the prolonged myelosuppression
seen with doses of Ac-225 directed against CD33 expressing cells and the evolving AML treatment landscape, we adapted our development
strategy for Actimab-A to address the emerging unmet needs of patients in the era of precision medicines for AML.
Anti-Leukemic Activity
of Actimab-A Monotherapy
After completing the Phase
2 monotherapy trial, there was strong interest from trial investigators and other key opinion leaders to study Actimab-A in combination
with other treatment modalities to leverage its novel mutation agnostic radiotherapy mechanism. We evaluated several clinical trial concepts
and elected to pursue combination trials with Actimab-A with the salvage chemotherapy CLAG-M in patients with r/r AML and with the Bcl-2
inhibitor Venetoclax based on the potential for these combinations to address large segments of the AML patient population with high unmet
needs.
Actimab-A + Venetoclax Phase 1/2 Combination
Trial
Venetoclax is an oral therapy
that works by attaching to and blocking the actions of the B-cell lymphoma-2 (“Bcl-2”) protein. Bcl-2 is overexpressed in
several blood cancers and prevents cancer cells from undergoing normal programmed cell death or apoptosis, which can help the cancer cells
overexpressing Bcl-2 live longer or increase resistance to chemotherapy. In November 2018, Venetoclax received accelerated approval from
the FDA in combination with the HMA azacitidine and decitabine or low-dose cytarabine for the treatment of newly diagnosed AML in patients
age 75 years or older or patients ineligible for intensive induction chemotherapy. Venetoclax was granted regular approval by the FDA
in October 2020.
The Phase 1 portion of the
Actimab-A + Venetoclax trial enrolled 18 patients and was conducted at five clinical trial sites. Four dose levels of Actimab-A were evaluated
with the primary objective of evaluating the safety of the combination. Actimab-A + Venetoclax was well tolerated with an expected and
manageable adverse event profile with no early deaths observed. Efficacy was also evaluated with reduction in bone marrow blasts up to
93% reported.
8
Actimab-A + CLAG-M Phase 1b/2 Combination
Trial
The Medical College of Wisconsin
(“MCW”) was an active clinical trial site in the Phase 2 Actimab-A Monotherapy trial. MCW had previously conducted a study
evaluating salvage chemotherapies in patients with r/r AML including the regimens MEC, CLAG and CLAG-M. The results demonstrated that
CLAG-M produced superior outcomes based on rates of response and overall survival resulting in CLAG-M being the preferred salvage regimen
for patients with r/r AML. Based on MCWs experience with Actimab-A and CLAG-M, the team at MCW hypothesized that combining Actimab-A with
CLAG-M could improve patient outcomes compared to CLAG-M alone and lead to a clinical benefit by eliminating residual or resistant AML
blasts to produce higher rates of remissions and deep remissions including measurable residual disease (“MRD”) negativity.
MCW enrolled 26 adult patients
with high-risk r/r AML in the Phase 1b/2 trial of Actimab-A + CLAG-M with 23 patients evaluable for efficacy. Patients in the efficacy
cohort had a median age of 62 and 91.3% of patients being intermediate risk (13%) or adverse risk (78.3%) according to the 2017 ELN cytogenetic
risk classification. Additionally, 52.2% of patients had a TP53 mutation abnormality, 56.5% of patients had prior Venetoclax treatment
and 56.5% of patients had a prior allogeneic BMT with patients having a median of 2 lines of prior treatment (range: 1-5). This trial
evaluated four dose levels of Actimab-A in combination with CLAG-M ranging from 0.25 μCi/kg to 1.0 μCi/kg.
Patient Characteristics
The results from this trial
were published in the peer-reviewed journal Leukemia in February 2025. In this publication, it was reported that Actimab-A + CLAG-M
had a tolerable safety profile with manageable toxicities and demonstrated promising efficacy supporting additional trials to further
evaluate the efficacy of the combination including survival outcomes. Based on the results of the study, it was determined that 0.75 μCi/kg
is the recommended Phase 2 dose (“RP2D”). In addition to a safety analysis, the results of 5 patients treated in a pharmacokinetic
expansion cohort at the RP2D were reported. Treatment-emergent adverse events (“TEAE”) were primarily hematologic and all
grade 3/4 TEAEs were hematologic. No patients discontinued treatment due to TEAEs and no early deaths were attributed to the Actimab-A
+ CLAG-M. The pharmacokinetic analysis evaluated radioactivity in whole blood and results showed that Actimab-A cleared rapidly with no
detectable radioactivity after a median of 24.5 hours. Importantly, no significant kidney or liver toxicity has been reported to date
and no incidences of veno-occlusive disease (“VOD”) reported.
The efficacy analysis of this
trial evaluated rates of CR, composite Complete Remission (“CRc”) which includes CR and Complete Remission with Incomplete
Count Recovery (“CRi”) and ORR which include CR, CRi and Morphologic Leukemia-Free State (“MLFS”), as well as
MRD negativity and survival outcomes. As listed in the table below, CR, CRc and ORR rates were reported for all patients as well as patients
treated at the RP2D, by number of lines or prior therapy and high-risk patients including those with a TP53 mutation and prior Venetoclax
treatment.
Rates of CR, CRc and
ORR with Actimab-A + CLAG-M
9
In patients achieving a CRc,
MRD negativity was assessed including in patients in various high-risk subgroups. Across all patients, the MRD negativity rate was 75%
and was 100% in patients with prior Venetoclax treatment. In the ELN adverse risk patients and those with a TP53 mutation, MRD negativity
was 86% and 83%, respectively. We believe these high rates of MRD negativity support the rationale for conducting this study, which was
to determine if Actimab-A could deplete residual or resistant AML blasts to produce deep remissions.
MRD Negativity Rates
in Evaluable Patients Achieving CRc
Long-term survival outcomes
in the evaluable patients receiving Actimab-A + CLAG-M were also reported from this study from a 2-year follow-up. In the patients eligible
for a BMT, 60% of patients successfully received a BMT and had a median Overall Survival (“OS”) of 24 months. In patients
with one or two lines of prior salvage therapy, the median OS was 18.4 months. The median OS in patients with a TP53 mutation or prior
Venetoclax treatment was 9.6 months and 7.3 months, respectively. These survival outcomes compare favorably to outcomes reported in the
literature. In patients with prior Venetoclax treatment who then received intensive chemotherapy such as CLAG-M, OS has been reported
to be 2.4 - 4.6 months.
Overall Survival Outcomes
with Actimab-A + CLAG-M
Based on the positive findings
from this trial, we plan to evaluate Actimab-A + CLAG-M will be evaluated in a pivotal Phase 2/3 trial in patients with r/r AML.
10
Actimab-A + CLAG-M Pivotal Phase 2/3 Trial
We have aligned with the FDA
on an operationally seamless, randomized pivotal Phase 2/3 trial to compare Actimab-A + CLAG-M to CLAG-M alone in patients with r/r AML.
Based on our interactions with the FDA, this trial will first complete a Phase 2 portion where the Actimab-A dose will be optimized in
combination with CLAG-M. We expect the Phase 2 portion of this trial to be initiated in 2025. Once the optimized Actimab-A dose is determined,
we expect the trial will seamlessly advance to the Phase 3 portion of the study, which is expected to reduce time and resources required
compared to separate Phase 2 and Phase 3 studies.
Actimab-A + CLAG-M Pivotal Phase 2/3 Trial
Design
The primary endpoint of the
Phase 3 trial will be Overall Survival. Event-Free Survival (“EFS”) and other efficacy measures as well as safety also being
evaluated. We are actively seeking potential strategic partners or collaborators to advance this trial.
Actimab-A NCI CRADA Trials
In 2023, we entered into a
CRADA with NCI to develop Actimab-A for the treatment of patients with AML and other hematologic malignancies. The NCI will serve as the
regulatory sponsor for any clinical trials mutually approved by both parties to study Actimab-A, and the CRADA will provide extensive
support for and accelerate the development of Actimab-A alone or in combination with chemotherapy, immunotherapy, targeted agents and
other novel combinations. The CRADA studies will be overseen by the NCI in collaboration with Actinium’s clinical development team,
where we have the right to review and approve all protocols and have full rights to all data. The NCI CRADA provides for us to supply
Actimab-A and for NCI to cover all clinical trial execution and development expenses, which we believe will be a cost-efficient approach
as opposed to a Company sponsored trial and will therefore spare our balance sheet. The NCI Cancer Therapy Evaluation Program (“CTEP”),
which sponsors approximately two thirds of all combination cancer studies, will accept Letters of Intent (“LOIs”) or concepts
for Phase 1, 2 or 3 studies of Actimab-A in AML and other hematological malignancies.
In October 2024, the NCI announced
that its myeloMATCH program was officially open to patient enrollment across the U.S. and Canda. MyeloMATCH is a portfolio of clinical
trials to test precision medicine treatments for adults with AML or MDS being designed and led by four leading cancer research organizations
including the Alliance for Clinical Trials in Oncology, Canadian Cancer Trials Group, ECOG-ACRIN Cancer Research Group, and SWOG Cancer
Research Network in collaboration with the NCI National Clinical Trials Network (“NCTN”). Collectively, the myeloMATCH program
expects to open trials at hundreds of cancer care sites across the U.S. and Canada with the goal of enrolling 5,000 or more patients over
the next several years. Under our CRADA with the NCI, Actimab-A is part of the myeloMATCH program and may be included in future clinical
trials.
11
Actimab-A, Venetoclax & ASTX-727 –
Frontline AML Triplet Phase 1b Combination Trial
In March 2025, we announced
the initiation of the first clinical trial to be conducted under our CRADA by NCI. The trial will evaluate the triplet combination comprised
of Actimab-A, Venetoclax and ASTX-727, a novel oral HMA developed by Taiho Oncology, an Otsuka Holdings company, in frontline AML patients.
Venetoclax in combination with HMAs (Ven-HMA) is approved for patients with newly diagnosed AML. We believe this trial is supported by
our Actimab-A + Venetoclax combination trial that showed that combination was well-tolerated and showed supportive anti-leukemic activity.
The frontline AML triplet trial is expected to enroll up to 48 patients who are newly diagnosed with AML that are age 75 and above and
not eligible for intensive chemotherapy. The trial will evaluate various dose levels of Actimab-A along with dosing regimens. We expect
initial clinical data to be generated from this trial in second half of 2025.
Triplet Combination Trial Design with Venetoclax,
HMA & Actimab-A Backbone
Additional clinical trial concepts for Actimab-A
have been submitted under the CRADA and are being reviewed. We anticipate that additional clinical trials with Actimab-A will be initiated
in 2025 including under the CRADA to leverage Actimab-A’s mutation agnostic mechanism.
Broad Development Strategy for Actimab-A
12
Data Supporting Actimab-A’s Mutation Agnostic Profile
To leverage Actimab-A’s
mutation agnostic capabilities and support its broad development, we have conducted preclinical experiments studying Actimab-A in combination
with targeted agents including Bcl-2 inhibitors, FLT-3 inhibitors, IDH inhibitors and menin inhibitors for NPM1 and KMT2A AML, chemotherapies
such as CLAG-M and in cell lines expressing TP53 mutations. The table below outlines the expression rates of these targets in patients
with AML.
Actimab-A Combination Data with Menin Inhibitors
In June 2024, we presented
the first-ever preclinical data demonstrating the combination of Actimab-A with leading menin inhibitors resulted in anti-tumor control
and potent leukemia cell killing in AML models at the 2024 European Hematology Association (“EHA”) Congress. We studied Actimab-A
in combination with the leading menin inhibitors, revumenib (Syndax Pharmaceuticals, Inc.) and ziftomenib (Kura Oncology, Inc.), which
are being developed for patients with KMT2A rearrangements and NPM1 mutations, which are present in approximately 10% and 30% of AML patients,
respectively. Actimab-A as a single agent showed potent in vitro AML cell killing activity in both MV-4-11 and MOLM-13 KMT2A mutant cell
lines, compared to the non-radio conjugated CD33 antibody lintuzumab (p<0.0001) and the combination of Actimab-A with leading menin
inhibitors triggered an acute increase in AML necrosis and cell death in vivo relative to single agent therapy within 72 hours of dosing.
Actimab-A enhanced AML cell death when combined with both revumenib and ziftomenib at all dose levels in difficult to treat KMT2A mutant
AML. Anti-tumor effect was significantly potentiated and prolonged when combining Actimab-A with a leading menin inhibitor compared to
monotherapies in xenograft leukemia models in vivo (p<0.0024 Actimab-A + menin).
Enhanced Tumor Control
with Actimab-A + Menin Inhibitor Revumenib
13
Actimab-A Combination Data with FLT3 Inhibitors
We have also evaluated Actimab-A
in combination with FLT3 inhibitors such as gilteritinib (Astellas Pharma, Inc.) and midostaurin (Novartis Pharmaceuticals, Inc.). FLT3
is one of the most commonly mutated genes in AML and is associated with aggressive disease with poor outcomes. Actimab-A was shown to
have single-agent activity against FLT3 mutant AML cell lines, supporting its mutation-agnostic mechanism, and enhanced the anti-leukemic
activity of the FLT3 inhibition in vitro. We will continue to evaluate the potential of Actimab-A in combination with FLT3 inhibitors.
Synergistic Anti-Leukemic
Effect with FLT3 Inhibitors
We expect to present additional data supporting
Actimab-A’s mutation agnostic capabilities and backbone potential at future scientific and medical conferences. In addition, we
will continue to explore potential clinical trials under our CRADA with NCI, investigator-initiated trials or under our sponsorship.
Actimab-A Solid Tumor Program: Potential Pan Solid Tumor Therapy
in Combination with PD-1 Checkpoint Inhibitors Including KEYTRUDA® and OPDIVO® by Depleting Myeloid Derived
Suppressor Cells
Given the significant number
of patients treated with PD-1 ICIs, there is extensive data in the medical literature on outcomes in these patients. PD-1 ICIs have significantly
improved patient outcomes across several solid tumor indications, however, not all patients have robust or durable responses. Multiple
therapeutic modalities have been studied in combination with PD-1 ICIs in attempt to improve patient outcomes, but few combinations have
produced a sufficient enough clinical benefit to have been approved. To our knowledge, our Actimab-A solid tumor program is the only CD33
targeted radiotherapy being evaluated in combination with PD-1 ICIs. The rationale for studying Actimab-A in combination with either KEYTRUDA® or
OPDIVO® is based on the premise that depleting MDSCs with Actimab-A will improve the efficacy of these drugs.
MDSCs are immune-suppressive cells that help tumors
evade immune detection and promote disease progression. They are overexpressed in the tumor microenvironment in several different solid
tumors and associated with poor outcomes. They work by multiple mechanisms but most relevant to PD-1 inhibitors which work by keeping
T-cells active is that MDSCs prevent T-cells from recognizing and attacking cancer cells.
MDSCs Immunosuppressive Effects
14
Studies have shown that MDSCs are overexpressed
in patients with cancers. For instance, a study by Bronte et al., in patients with NSCLC receiving ICIs evaluated the role of immune cells
on patient outcomes. In this study, MDSCs were the only immune cell subtype to show a statistically significant association with tumor
response. The median level of MDSCs was determined to be 1.9% with patients above that level being classified as “High-MDSC”
and patients below that level being classified as “Low-MDSC”. In this study, only Low-MDSC patients had a clinical response
with no responses observed in High-MDSC patients and over 80% of High-MDSC patients having progressive disease. In addition, Low-MDSC
patients had a statistically significantly improvement in progression-free survival (“PFS”) of 8.39 months compared to 1.94
months in High-MDSC patients and OS of 15.15 months compared to 3.03 months in High-MDSC patients.
There is considerable preclinical scientific evidence
in the literature that depleting MDSCs could be a viable strategy in improving the outcomes of PD-1 directed immunotherapy, however, there
have been no viable clinical approaches that have been tried successfully to our knowledge. MDSCs are known to express the CD33
antigen which is the target of Actimab-A. Actinium has also generated published and unpublished preclinical data showing that Actimab-A
can selectively deplete MDSCs in solid tumors.
Actimab-A Depletes MDSCs
in In Vivo Preclinical Models
We believe there is strong
scientific rationale supporting the potential for Actimab-A to deplete CD33 expressing MDSCs and hence improve patient outcomes with PD-1
ICIs such as KEYTRUDA® and OPDIVO®. Our Actimab-A solid tumor program is expected to be comprised of
several controlled, head-to-head clinical trials that will evaluate the combination of Actimab-A with KEYTRUDA® versus
KEYTRUDA® alone, and Actimab-A with OPDIVO® versus OPDIVO® alone. The initial
tumors that are being targeted are HSNCC and NSCLC with a separate trial for each indication.
15
The patient population for
these trials will be adults with PD-L1 expression and locally advanced metastatic HNSCC or NSCLC randomized to either Actimab-A alone
or Actimab-A with a specific checkpoint inhibitor. The objective of each trial would be to evaluate the safety and tolerability as well
as following endpoints including ORR, PFS and OS. Further, the following biomarker data would be collected including the pattern of depletion
of CD33+ MDSCs and T-cell activity in peripheral blood. We expect to present initial proof of concept clinical data from the first of
these trials in the second half of 2025 as well as provide an update on the outlook for the rest of the trials for the Actimab-A solid
tumor program.
ATNM-400 Program: Potential Novel, First-in-Class Ac-225 Prostate
Cancer Radiotherapy
In March 2025, we announced
ATNM-400, a novel, first-in-class Ac-225-based radiotherapy intended for patients with prostate cancer. We have generated preclinical
data with ATNM-400, which has been accepted for presentation at the American Association for Cancer Research (“AACR”) Annual
Meeting being held April 25 – 30, 2025. The abstract accepted for presentation highlighted the following:
We continue to study ATNM-400
and expect additional data from Pluvicto-resistant prostate cancer models to be presented at AACR.
Iomab-ACT Program: Potential Universal Targeted Conditioning Agent
for Cell & Gene Therapies to Improve Patient Access and Outcomes
The opportunity exists for
better conditioning regimens in the area of cellular therapies beyond the non-targeted chemotherapy-based regimens that are used currently.
We are working on a next generation targeted conditioning program, Iomab-ACT, for the rapidly growing cell and gene therapy market, as
well as BMT conditioning for non-malignant hematologic indications such as SCD.
We are studying Iomab-ACT
in collaboration with Memorial Sloan Kettering Cancer Center (“MSKCC”), for conditioning prior to CAR-T therapy for patients
with relapsed or refractory B-cell acute lymphoblastic leukemia (“B-ALL”) or diffuse large B-cell lymphoma (“DLBCL”).
This study funded by a NIH grant is the first study of its kind to use an ARC, with CAR-T therapy. At the 2024 Tandem Meetings | Transplantation
& Cellular Therapy Meetings of ASTCT and CIBMTR, we presented results from the ongoing Phase 1 trial. No patients (0/4) developed
Immune Effector Cell-Associated Neurotoxicity Syndrome (“ICANS”) of any grade, a major safety measure of the study, as ICANS
is observed in 25% or more of patients with r/r B-ALL and DLBCL treated with various CAR T-cell products and negligible incidence of cytokine
release syndrome (“CRS”) as outlined in the table below.
Minimal CRS and ICANS
in Iomab-ACT Pilot Trial
16
Additionally, Iomab-ACT demonstrated
transient depletion of peripheral blood lymphocytes and monocytes. Persistence of CAR T-cells up to 8 weeks and minimal non-hematologic
toxicities have been observed to date. These results prompted us to explore additional clinical trials with Iomab-ACT.
In May 2024, we announced
FDA acceptance of an IND for a new Phase 1b/2 clinical trial that will study Iomab-ACT as targeted conditioning prior to patients receiving
an FDA approved commercial CAR-T therapy. This is an investigator sponsored trial conducted at the University of Texas Southwestern (“UTSW”).
To our knowledge, this will be the first trial to study a targeted radiotherapy conditioning agent with a commercial CAR-T therapy. Given
the robust clinical data that exists with commercial CAR-T therapies, we believe this trial may demonstrate the potential for Iomab-ACT
to improve outcomes over current chemotherapy conditioning regimens, which we are seeking to replace and provide patients better access
to CAR-T. This trial will enroll up to 30 patients and we expect to commence patient enrollment of this study in the first half of 2025
and generate proof of concept clinical data by year end 2025. The primary objectives are safety, tolerability and efficacy. Second
objectives will evaluate incidences of CRS and ICANS as well as the persistence and expansion of CAR-T cells, which has been associated
with improved efficacy and patient outcomes. If successful, we believe this Phase 1b/2 trial could support a pivotal trial, which could
be initiated as early as 2026.
In July 2024, we announced
a program for Iomab-ACT focused on providing patients with sickle cell disease broader access to cellular therapies including bone marrow
transplant and gene therapies. We also announced in July 2024 the FDA clearance of an IND for an investigator led clinical trial to study
Iomab-ACT as targeted conditioning prior to a BMT for patients with SCD in collaboration with Columbia University. Sickle cell disease
is a rare, debilitating and life-threatening blood disorder with significant unmet need that affects approximately 100,000 people in the
U.S. Patients with sickle cell disease have a mutation that causes red blood cells to develop a crescent or “sickle” shape,
which restrict the flow in blood vessels and limit oxygen delivery to the body’s tissues, leading to severe pain and organ damage
called vaso-occlusive events (“VOEs”) or vaso-occlusive crises (“VOCs”). The recurrence of these events or crises
can lead to life-threatening disabilities and/or early death. A BMT is a potentially curative treatment option for patients with sickle
cell disease, particularly in pediatric patients who have had complications such as strokes, acute chest crises or recurring pain crises
due to their disease. We expect patient enrollment for the Phase 1 trial to commence in the first half of 2025 and enroll up to 15 patients
with initial safety and efficacy results from the initial cohort of patients receiving Iomab-ACT prior to a BMT for their SCD in the second
half of 2025.If safety is demonstrated, the trial is expected to inform a clinical trial to evaluate Iomab-ACT as a targeted conditioning
agent prior to gene therapy for which there are two approved agents for patients with sickle cell disease, Casgevy (Vertex Pharmaceuticals,
Inc.) and Lyfgenia (Bluebird Bio, Inc.).
Iomab-ACT Clinical Trials
and Objectives
We plan to continue
to develop Iomab-ACT based on early promising results, ultimately with the value proposition of improving overall access and outcomes
for patients who need cellular or gene therapies. We believe an opportunity exists for Iomab-ACT to potentially generate significant revenue,
if it can provide one or more clinical benefits related to lower CRS, less neurotoxicity, longer duration of response or a higher overall
success rate of cellular therapy due to benefits of targeted conditioning.
17
Iomab-B
In
February 2023, Actinium announced that the SIERRA trial met the primary endpoint with statistical significance, as 22% of patients (13/76)
on the Iomab-B arm achieved dCR compared to 0% of patients (0/77) on the control arm resulting in a p-value of <0.0001. The SIERRA
trial met the secondary endpoint of Event-Free Survival (“EFS”) with a 78% reduction in the probability of an event (Hazard
Ratio=0.22, p<0.0001 for both per protocol and ITT basis). EFS at 180 days for the Iomab-B arm was 28% compared to 0.2% for the control
arm. In the SIERRA trial, an event was defined as one of the following: a patient not achieving CR/CRp or crossing over, patient not
receiving BMT, a patient relapsing or death. The SIERRA trial did not, however, meet the secondary endpoint in achieving a statistically
significant improvement in OS in the intent to treat (“ITT”) population.
On
August 5, 2024, Actinium announced that it concluded both its clinical and Chemistry, Manufacturing and Controls (“CMC”) interactions
with the FDA regarding the BLA pathway for Iomab-B based on the SIERRA trial results. As previously disclosed, we had received positive
feedback from the FDA regarding our CMC package for Iomab-B and were also assigned a BLA number. However, in the third quarter of 2024,
the FDA provided definitive feedback that the SIERRA trial alone is not adequate to support a BLA filing for Iomab-B, despite (a) the
SIERRA trial meeting the primary endpoint of dCR with statistical significance (p-value<0.0001) and other positive secondary endpoints
including Event Free Survival (“EFS”) and safety, and (b) our presentation of several additional analyses from the SIERRA
study, including long-term follow-up demonstrating a trend towards improved overall survival and evidence of survival benefit in patients
with high-risk TP53 mutations, to support Iomab-B’s impact on overall survival. The FDA indicated that demonstrating an overall
survival benefit in a randomized head-to-head trial is necessary and has advised us to conduct a study to evaluate allogeneic BMT using
Iomab-B plus a reduced intensity conditioning regimen of fludarabine and total body irradiation (“Flu/TBI”) versus allogeneic
BMT using reduced intensity conditioning comprised of cyclophosphamide plus Flu/TBI. This proposed additional study differs from the SIERRA
trial, which allowed physician’s choice of salvage chemotherapies and heterogenous conditioning regimens in the control arm. Additionally,
the proposed new study will not allow patients to cross over from the control arm, which was allowed in the SIERRA trial and confounded
the overall survival analysis in the ITT patient population, as nearly 60% of patients crossed over from the control arm.
Actinium
continued interactions with the FDA in the third quarter of 2024 to further discuss the specifics of the additional head-to-head clinical
trial required by the FDA, including the patient population, which the FDA had suggested could include all adult AML patients. In the
fourth quarter of 2024, Actinium conducted a further meeting with the FDA. Based on this meeting, Actinium believes it has aligned with
the FDA on the patient population for a head-to-head Phase 3 clinical trial to further evaluate allogeneic BMT using Iomab-B plus a reduced
intensity conditioning regimen of Flu/TBI versus allogeneic BMT using reduced intensity conditioning comprised of cyclophosphamide plus