Actinium Pharmaceuticals, Inc.

Previous wording

Actinium Pharmaceuticals, Inc. (“Actinium”, the “Company”, or “we”) develops Antibody Radiation Conjugates (“ARCs”) and other targeted radiotherapies intended to meaningfully improve outcomes for patients with relapsed or refractory cancer who have failed existing therapies. We are deploying our technology platform, which we believe to be industry-leading, and intellectual property with over 230 issued and pending patents worldwide, to develop ARCs and next-generation radiotherapies against validated cancer targets.

Current wording

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 and preclinical 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 240 issued and pending patents worldwide, to develop targeted and next-generation radiotherapies.

Previous wording

Actimab-A is being developed as a targeted radiotherapeutic that uses the Actinium-225 (“Ac-225") isotope payload directed against CD33, a target expressed ubiquitously in patients with AML 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 AML, an extremely heterogenous and radiosensitive disease, as a single agent or in combinations with chemotherapy, targeted agents, cellular therapy and immunotherapy. Actimab-A has been studied in over 150 patients and is being developed in collaboration with the National Cancer Institute (“NCI”) under a Cooperative Research and Development Agreement (“CRADA”).

Current wording

Actimab-A is being developed as a targeted radiotherapeutic to leverage the Ac-225 isotope payload directed against CD33, a target expressed ubiquitously in patients with AML, MDS and 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 as a single agent and in combination with other modalities. This clinical experience is informing our current clinical development strategy for Actimab-A. 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 based on promising results with this combination in a Phase 1b trial. 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 Actimab-A trial initiated under the CRADA is being conducted in patients with frontline AML in combination with Venetoclax, an oral Bcl-2 inhibitor and ASTX-727, an oral hypomethylating agent (“HMA”) developed by Taiho Oncology, an Otsuka Holdings company. We anticipate that additional trials will be initiated under the NCI CRADA as multiple proposals have been submitted for review.

Previous wording

We have active R&D efforts leveraging our in-house preclinical and translational capabilities and are primarily focused on advancing several preclinical programs for solid tumor indications.

Current wording

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.

Previous wording

Iomab-ACT is our next-generation CD45 targeted conditioning agent being developed for cell and gene therapies for both malignant and non-malignant hematologic indications. We are developing Iomab-ACT with the goal of improving patient access and outcomes for potentially curative cell and gene therapies. Iomab-ACT is currently being studied in three clinical trials, including with a commercial CAR-T therapy, prior to allogeneic BMT for patients with sickle cell disease, which is intended to inform a trial design with gene therapy for sickle cell disease, and with a novel CD19 CAR-T therapy.

Current wording

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 are relevant to this program and uses the Iodine-131(“I-131") radioisotope payload. We are developing Iomab-ACT as conditioning for cell and gene therapies in 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. In May 2025, we announced that the first patient was enrolled in the Iomab-ACT commercial CAR-T trial at the University of Texas Southwest Medical Center (“UTSW”).

Previous wording

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.

Current wording

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.

Previous wording

In the third quarter of 2024, we met with the FDA to discuss the continued development of Actimab-A in combination with CLAG-M in patients with r/r AML. We have aligned with the FDA on an operationally seamless randomized Phase 2/3 clinical trial design. 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. 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. We are also working to evaluate and develop multiple clinical trials for Actimab-A across the treatment journey in AML and other myeloid indications, which could be conducted under the NCI CRADA, investigator sponsored trials (“ISTs”) or Actinium’s sponsorship.

Current wording

We have aligned with the FDA on a 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 the second half of 2025. Once the optimized Actimab-A dose is determined, we expect the trial will advance to the Phase 3 portion of the study, which may reduce time and resources required compared to separate Phase 2 and Phase 3 studies.

Previous wording

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. The NCI CRADA is anticipated to have a balance sheet sparing impact over the next several years. 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. To date, multiple Actimab-A study proposals have been submitted to the NCI, which are being mutually reviewed and considered. We expect the NCI to initiate further development of Actimab-A in combination with CLAG-M and other targeted agents to broaden the scope of its development in AML and other myeloid malignancies.

Current wording

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 support for and may 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 may 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.

Previous wording

On October 23, 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 myelodysplastic syndrome (“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.

Current wording

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.

Previous wording

The opportunity exists for better conditioning in other areas of cellular therapy, and we are working on a next generation 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 sickle cell disease. 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. In October 2023, we announced the extension of a NIH Small Business Technology Transfer grant to support the clinical collaboration with MSKCC. Most recently, 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”). 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.

Current wording

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”). 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.

Previous wording

In May 2024, we announced FDA clearance of an IND for a new clinical trial that will study Iomab-ACT as targeted conditioning prior to patients receiving an FDA approved commercial CAR-T therapy. 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. We expect to commence patient enrollment of this study in the first quarter of 2025 and generate proof of concept clinical data by year end 2025.

Current wording

We have initiated an investigator-sponsored trial studying Iomab-ACT as targeted conditioning prior to patients receiving an FDA approved commercial CAR-T therapy at UTSW. To our knowledge, this is 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. In May 2025, we announced that the first patient was enrolled in this trial, which will enroll up to 30 patients. We expect to generate initial proof-of-concept clinical data by year end 2025. The primary objectives of this study are safety, tolerability and efficacy. Secondary 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.

Previous wording

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 sickle cell disease 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 with initial safety and efficacy results from the initial cohort of patients receiving Iomab-ACT prior to a BMT for their sickle cell disease beginning in 2025. If successful, 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.).

Current wording

Iomab-ACT is also being studied in an investigator-led clinical trial 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 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 24 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.).

Previous wording

The pipeline of CAR-T and gene therapies has rapidly expanded, with the addressable patient population expected to nearly double and reach approximately 93,000 patients in the U.S. by 2030 based on the current pipeline of therapies. The CAR-T market size in terms of revenue is estimated to grow at a CAGR of approximately 11% over the next five years. Currently, there are six CAR T-cell therapies approved by the FDA that are used to treat patients with lymphomas, leukemia and multiple myeloma, which collectively had total sales over $3.5 billion in 2023. The addressable market for Iomab-ACT is in line with the patient population for cellular therapy as all patients receive conditioning of some type prior to these treatments. We will 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.

Current wording

We plan to continue to develop Iomab-ACT based on early encouraging 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.

Previous wording

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 did not, however, meet the secondary endpoint in achieving a statistically significant improvement in overall survival in the intent to treat (“ITT”) population.

Current wording

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 durable Complete Remission (“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.

Previous wording

Our R&D programs inform the advancement of our clinical programs. We have utilized our technology platform to develop our clinical portfolio in hematology – Iomab-B and Actimab-A, in conditioning for transplant and as a therapeutic, respectively. Our differentiated R&D efforts are further exemplified by our next-generation Iomab-ACT conditioning program for rapidly growing cell and gene therapies. Our platform has been used to develop a pipeline of novel radiotherapeutic assets to drive company growth. We are working on several preclinical programs which include novel approaches to validated cancer targets, as well as novel targets that we believe to show immense potential for radiotherapeutic approaches. Preclinical pharmacology studies with our targeted radiotherapeutics, such as HER2, CD33 and CD38, have shown strong improvement in tumor growth inhibition in various preclinical tumor models. These results have prompted our R&D team to spearhead expansion of our efforts into multiple solid tumor programs in the preclinical stage with IND enabling studies underway. Leveraging our platform and expertise in developing ARCs, we are exploring how nanobodies, single chain variable fragment (“scFv”), and other related modalities can be combined with novel linkers and radioisotopes to enhance delivery to solid tumors.

Current wording

Our R&D capabilities have the potential to yield differentiated, high-value targeted radiotherapy programs that demonstrate our experience across multiple validated cancer targets and isotopes and cover broad areas of focus leveraging our clinical development experience across hematology, targeted conditioning, solid tumors, and next-generation radiotherapies. We have internal R&D capabilities with our research laboratory capable of executing in vitro and in vivo experiments and translational research. We are working on several preclinical programs which include novel approaches to validated cancer targets, as well as novel targets that we believe show immense potential for radiotherapeutic approaches. Preclinical pharmacology studies with our targeted radiotherapeutics, such as HER2, CD33 and CD38, have shown strong improvement in tumor growth inhibition in various preclinical tumor models.

Previous wording

We currently believe that our ARCs are less likely than small molecules to face pricing pressure and negotiation from the Inflation Reduction Act of 2022 (“IRA”), given that small molecules are at risk for pricing negotiations seven years after approval compared to eleven years for biologics with negotiated prices taking effect two years after selection. Further, a drug or biological product that has an orphan drug designation, which Iomab-B and Actimab-A both have, for only one rare disease or condition will be excluded from the IRA’s price negotiations requirements until such time the biological products has designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation. In addition, regulatory barriers for a generic ARC are much higher than for small molecule radioligands such as those under development or approved, namely, Pluvicto®, Lutathera®, and Xofigo®. While generic versions of certain radiopharmaceuticals utilizing peptides, which are considered small molecules, have been submitted to the FDA via the ANDA pathway, ARCs fall under biologics. For this reason, only the biosimilar approach pertains to ARCs filed under 351(k) BLA pathway. The regulatory pathway for biosimilar is much more comprehensive than the pathway for generics, and it has not been proven that biosimilars are interchangeable with the innovator’s ARCs. In addition, we are not aware of any regulations that would require us to provide Iomab-B or Actimab-A, including their respective monoclonal antibodies (“mAbs”), apamistamab and lintuzumab, to any third party or potential competitor.

Current wording

We currently believe that our targeted radiotherapies, which utilize biologic molecules, are less likely than small molecules to face pricing pressure and negotiation from the Inflation Reduction Act of 2022 (“IRA”), given that small molecules are at risk for pricing negotiations seven years after approval compared to eleven years for biologics with negotiated prices taking effect two years after selection. Further, a drug or biological product that has an orphan drug designation, which our Actimab-A and Iomab-B programs both have, for only one rare disease or condition will be excluded from the IRA’s price negotiations requirements until such time the biological products has designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation. In addition, regulatory barriers for generic large molecule biologic based targeted radiotherapies are much higher than for small molecule radioligands such as those under development or approved, namely, Pluvicto®, Lutathera®, and Xofigo®. Generic versions of certain radiopharmaceuticals utilizing peptides, which are considered small molecules, have been submitted to the FDA via the ANDA pathway. To our knowledge, only the biosimilar approach pertains to large molecule biologic-based radiotherapies filed under 351(k) BLA pathway. The regulatory pathway for a biosimilar is much more comprehensive than the pathway for generics, and it has not been proven that biosimilars are interchangeable with the innovator’s large molecule biologic targeted radiotherapy. In addition, we are not aware of any regulations that would require us to provide Actimab-A or Iomab-ACT, including their respective mAbs, lintuzumab and apamistamab, to any third party or potential competitor. Despite the above, we are aware that one or more of the policies or regulations that afford our pipeline candidates market protections may change in the future and that one or more of our product candidates may be disadvantaged by such change.

Previous wording

We seek to expand our capabilities and technologies across therapeutic modalities, linker technologies and in vivo cancer models, and build visibility through presentations at key conferences and publications in journals of high impact. Our R&D efforts are centered on the advancement of our key ARC programs with a robust “fast-to-clinic” approach.

Current wording

We seek to expand our capabilities and technologies across therapeutic modalities, linker technologies and in vivo cancer models, and build visibility through presentations at key conferences and publications in journals of high impact. Our R&D efforts are centered on the advancement of key programs with a robust “fast-to-clinic” approach. Underpinning our development programs is our expanded patent portfolio of approximately 240 issued patents and pending patent applications worldwide.

Previous wording

With our in-depth, long-term experience in clinical development of Ac-225 based radiopharmaceuticals, we have developed an end-to-end technology solution for producing Ac-225 that has demonstrated radiochemical and radionuclidic purity identical to current gold standard methods. This patented technology has been used to produce Ac-225 in a cyclotron that is essentially identical to that derived from a Th-229 generator and has the potential to be a lower-cost, commercially scalable higher-yielding approach. Using the cyclotron-produced Ac-225 technology allows for large commercial scale production with estimated cost of goods sold including capital expenditures and operational costs for a single cyclotron facility of between $650 and $1,000 per mCi, which is between 10 to 20 times less expensive than the price of currently available Ac-225 material.

Current wording

With our in-depth, long-term experience in clinical development of Ac-225 based radiopharmaceuticals, we have developed an end-to-end technology solution for producing Ac-225 that has demonstrated radiochemical and radionuclidic purity identical to current gold-standard methods. This patented technology has been used to produce Ac-225 in a cyclotron that is essentially identical to that derived from a Th-229 generator and has the potential to be a lower-cost, commercially scalable higher-yielding approach. Importantly, the Ac-225 material produced by our proprietary method contains no long-lived contaminants and less than 0.001% Actinium-227 (“Ac-227”). Using the cyclotron-produced Ac-225 technology may allow for large commercial scale production with estimated cost of goods sold including capital expenditures and operational costs for a single cyclotron facility to be several times less expensive than the price of currently available Ac-225 material.

Previous wording

Our extensive know-how related to this production technology is supported by five issued patents in the U.S. and 41 patents internationally and covers:

Current wording

Our extensive know-how related to this production technology is supported by 5 issued patents in the U.S. and 33 patents internationally and covers:

Previous wording

With our Ac-2225 based Actimab-A program and the rapidly increasing number of Ac-225 based programs in development, we believe that we are well positioned to leverage this technology to produce Ac-225 to address the growing clinical demand.

Current wording

With our Ac-2225 based Actimab-A and ATNM-400 programs and the rapidly increasing number of Ac-225 based programs in development, we believe that we are well positioned to leverage this technology to produce Ac-225 to address the growing clinical and potential commercial demand.

Previous wording

Actinium has established significant manufacturing and supply chain expertise due to the unique manufacturing and distribution requirements of radiotherapeutics. Due to the short half-life of radioisotopes, the finished drug product is shipped “hot” and must be administered within days. We have established core competencies in the process of manufacturing radiotherapeutics, coordinating with the hospital’s care team, and delivering “just-in-time” doses. We have delivered over 500 doses for 18 clinical trials at 45 large cancer hospitals and have never missed a dose.

Current wording

We believe this experience provides us with insights that are highly relevant to the unique manufacturing and distribution requirements of radiotherapeutics. Due to the short half-life of radioisotopes, our finished drug products are shipped “hot” and must be administered within days. Actinium has established core competencies in the process of manufacturing radiotherapeutics, coordinating with the hospital’s care team, and delivering “just-in-time” doses.

Previous wording

Isotope supply is critical for the manufacturing of radiotherapeutics, and we have engaged several sources for the procurement of alpha (e.g., Ac-225) and beta (e.g., I-131 and Lu-177) emitters. We also have multiple isotope supply agreements and qualified vendors in place to supply isotopes for commercial production.

Current wording

Isotope supply is critical for the manufacturing of radiotherapeutics, and we have engaged several sources for the procurement of alpha (e.g., Ac-225) and beta (e.g., I-131 and Lu-177) emitters. We also have multiple isotope supply agreements and qualified vendors in place to supply isotopes for our active and planned clinical trials. In March 2025, we announced that we entered into Ac-225 supply agreement with Eckert & Ziegler, a leading specialist in isotope-related components for nuclear medicine and radiation therapy, to support our comprehensive development including U.S. and international clinical trials.

Previous wording

We have established an actively managed end-to-end supply chain that encompasses isotope sourcing through drug administration at the point of care and as a result of our approach, we have reliably supplied drug to all patients enrolled in our clinical trials. We believe we have a thorough understanding and working knowledge of the intricacies required to manufacture and distribute radiotherapies. Through our clinical experience with, we have developed a wealth of proprietary knowledge to enable coordination between us and all key stakeholders including, but not limited to hematologists/oncologists, infusion center and in patient rooms, nuclear medicine and radiology, hot labs and radio-pharmacies, and radiation safety committees, among others. We utilize contract development and manufacturing organizations (“CDMOs”) to manufacture our finished drug products and have selected CDMOs based on their clinical and commercial supply capabilities including significant experience in the international supply of radiotherapies. We have scaled deliberately for manufacturing flexibility and will continue to evaluate additional CDMOs.

Current wording

We have established an actively managed end-to-end supply chain that encompasses isotope sourcing through drug administration at the point of care to execute our clinical trials. Our end-to-end supply chain did not miss a patient dose in our international, 24-site SIERRA Phase 3 clinical trial, including 40 additional patients that crossed over from the control arm to receive Iomab-B. We believe we have a thorough understanding and working knowledge of the intricacies required to manufacture and distribute radiotherapies. Through our clinical experience with Iomab-B and Actimab-A, we have developed a wealth of proprietary knowledge to enable coordination between Actinium and all key stakeholders including, but not limited to hematologists/oncologists, infusion center and in patient rooms, nuclear medicine and radiology, hot labs and radio-pharmacies, and radiation safety committees, among others.** **

Previous wording

As of November 14, 2024, our patent portfolio is comprised of over 230 issued patents and pending patent applications worldwide, which we believe constitutes a valuable business asset. Our IP includes 47 patent families, including key patents that relate primarily to our radiotherapeutic candidates. Our patent portfolio includes 20 issued patents and 48 pending patent applications in the U.S., and over 165 that are issued or pending internationally. The effective lives of the issued patents in our portfolio, or patents that may issue from the pending applications in our portfolio, ranges from expirations between 2025 and 2045.

Current wording

As of May 2025, our patent portfolio is comprised of approximately 240 issued patents and pending patent applications worldwide, which we believe constitutes a valuable business asset. Our IP includes 48 patent families, including key patents that relate primarily to our radiotherapeutic candidates. Our patent portfolio includes 20 issued patents and 51 pending patent applications in the U.S., and 170 that are issued or pending internationally. The effective lives of the issued patents in our portfolio, or patents that may issue from the pending applications in our portfolio, ranges from expirations between 2026 and 2046.

Previous wording

For our Iomab-B product candidate, we have four issued patents in the U.S. and issued patents in Canada, Europe and Japan that relate to its composition. The basic patent terms of these patents expire in 2036 and 2037. Related patent applications are also currently pending in the U.S. and internationally. In addition, we own both U.S. and international pending patent applications that relate to the use of Iomab-B or Iomab-ACT with currently issued U.S. patent protection into 2040 for the use of Iomab-ACT in connection with genetically modified hematopoietic stem cell therapy for the treatment of non-malignant conditions.

Current wording

For our Iomab-B product candidate, we have four issued patents in the U.S. and issued patents in Canada, Europe and Japan that relate to the composition. The basic patent terms of these patents expire in 2036 and 2037. Related patent applications are also currently pending in the U.S. and internationally. In addition, we own both U.S. and international pending patent applications that relate to the use of Iomab-B or Iomab-ACT in the treatment of cancers and non-malignant conditions.

Previous wording

Our patents also cover key areas of our business such as manufacturing key components of our product candidate, Actimab-A, including producing Ac-225 in a cyclotron. We have expertise in utilizing the alpha emitting isotope Ac-225 including clinical experience in treating approximately 150 patients with our alpha-emitter-based therapies, “gold standard” linker technology and five issued patents in the U.S. and 41 patents internationally related to the manufacturing of Ac-225 in a cyclotron, which we believe has the potential to produce higher quantities of Ac-225 than currently utilized methods. In addition, we also own U.S. and international patents and pending patent applications that relate to the manufacturing of Actimab-A and its use in the treatment of cancers.

Current wording

Our patents also cover key areas of our business such as manufacturing key components of our product candidate, Actimab-A, including Ac-225 in a cyclotron. We have expertise in utilizing the alpha emitting isotope Ac-225 including clinical experience in treating approximately 150 patients with our alpha-emitter-based therapies, “gold standard” linker technology and 5 issued patents in the U.S. and 33 patents internationally related to the manufacturing of Ac-225 in a cyclotron, which we believe has the potential to produce higher quantities of Ac-225 than currently utilized methods. In addition, we also own U.S. and international patents and pending patent applications that relate to the manufacturing of Actimab-A and its use in the treatment of cancers.

Previous wording

General and administrative expenses of $2.8 million for the three months ended September 30, 2024 increased by $0.1 million from $2.7 million for the three months ended September 30, 2023, primarily due to higher non-cash stock compensation expense of $0.5 million, partially offset by lower compensation expense of $0.3 million due to lower headcount.

Current wording

General and administrative expenses of $8.9 million for the three months ended March 31, 2025 increased by $5.9 million from $3.0 million for the three months ended March 31, 2024, primarily due to higher non-cash stock-based compensation expense of $5.8 million.

Previous wording

Other income is comprised of net interest income in both reporting periods. The amount for the nine months ended September 30, 2024 of $3.0 million increased $0.9 million from $2.1 million for the nine months ended September 30, 2023 due to higher average interest rates.

Current wording

Other income is comprised of net interest income in both reporting periods. The amount for the three months ended March 31, 2025 of $0.7 million decreased from $0.9 million for the three months ended March 31, 2024 primarily due to a lower average cash balance during the respective time periods.

Previous wording

Historically, we have financed our operations primarily through sales of shares of our stock. The following table sets forth selected cash flow information for the periods indicated:

Current wording

The following table sets forth selected cash flow information for the periods indicated:

Previous wording

Net cash used in investing activities was $11 thousand and $153 thousand for the nine months ended September 30, 2024 and 2023, respectively, due to the purchase of equipment.

Current wording

There was no cash used in investing activities for the three months ended March 31, 2025. Cash used in investing activities was $11 thousand for the three months ended March 31, 2024 due to the purchase of equipment.

Previous wording

Net cash provided by financing activities was $29.3 million and $13.7 million for the nine months ended September 30, 2024 and 2023, respectively, primarily from the sale of common stock.

Current wording

Cash used in financing activities for the three months ended March 31, 2025 was not material. Net cash provided by financing activities of $14.8 million for the three months ended March 31, 2024 was primarily from the sale of shares of common stock.

Previous wording

In August 2020, we entered into the Capital on Demand™ Sales Agreement with JonesTrading Institutional Services LLC, or JonesTrading, pursuant to which we are able to sell, from time to time, through or to JonesTrading, up to an aggregate of $200 million of our common stock. On June 28, 2022, we entered into an Amendment and Restated Capital on Demand™ Sales Agreement, or the Amended Sales Agreement, with JonesTrading and B. Riley Securities, Inc. The Amended Sales Agreement modifies the original Capital on Demand™ Sales Agreement to include B. Riley as an additional sales agent thereunder. Shares of common stock are offered pursuant to a shelf registration statement on Form S-3 (File No. 333-273911), which was declared effective February 5, 2024, including a base prospectus covering the offering, issuance and sale of up to $500 million of common stock, preferred stock, warrants, units and/or subscription rights; and a sales agreement prospectus covering the offering, issuance and sale of up to a maximum aggregate offering price of $200 million of common stock that may be issued and sold under the Amended Sales Agreement. For the nine months ended September 30, 2024, we sold 3.5 million shares of common stock, resulting in gross proceeds of $29.9 million and net proceeds of $29.3 million. For the nine months ended September 30, 2023, we sold 3.0 million shares of common stock, resulting in gross proceeds of $18.9 million and net proceeds of $18.3 million.

Current wording

In August 2020, we entered into the Capital on Demand™ Sales Agreement with JonesTrading Institutional Services LLC, or JonesTrading, pursuant to which we are able to sell, from time to time, through or to JonesTrading, up to an aggregate of $200 million of our common stock. On June 28, 2022, we entered into an Amendment and Restated Capital on Demand™ Sales Agreement, or the Amended Sales Agreement, with JonesTrading and B. Riley Securities, Inc. The Amended Sales Agreement modifies the original Capital on Demand™ Sales Agreement to include B. Riley as an additional sales agent thereunder. Shares of common stock are offered pursuant to a shelf registration statement on Form S-3 (File No. 333-273911), which was declared effective February 5, 2024, including a base prospectus covering the offering, issuance and sale of up to $500 million of common stock, preferred stock, warrants, units and/or subscription rights; and a sales agreement prospectus covering the offering, issuance and sale of up to a maximum aggregate offering price of $200 million of common stock that may be issued and sold under the Amended Sales Agreement. During the three months ended March 31, 2025, there were no sales of shares of common stock. For the three months ended March 31, 2024, we sold 1.8 million shares of common stock, resulting in gross proceeds of $15.0 million and net proceeds of $14.7 million. On March 31, 2025, upon filing of our Annual Report on Form 10-K for the year ended December 31, 2024, we became subject to General Instruction I.B.6 of Form S-3, pursuant to which in no event will we sell our common stock in a registered primary offering using Form S-3 with a value exceeding more than one-third of our public float in any 12 calendar month period so long as our public float remains below $75 million.

Previous wording

In November 2023, FASB issued ASU 2023-07,Segment Reporting (Topic 280), Improvements to Reportable Segment Disclosures, which provides improvements to reportable segment disclosure requirements, primarily through enhanced disclosures around segment expenses. ASU 2023-07 requires us to disclose significant segment expenses that are regularly provided to the chief operating decision maker, or CODM, and included within each reported measure of segment profit or loss. ASU 2023-07 also requires that we disclose an amount for other segment items by reportable segment, a description of their composition and provide all annual disclosures about a reportable segment’s profit or loss and assets pursuant to Topic 280 during interim periods. We must also disclose the CODM’s title and position, as well as certain information around the measures used by the CODM and an explanation of how the CODM uses the reported measures in assessing segment performance and deciding how to allocate resources. For public entities with a single reportable segment, the entity must provide all the disclosures required pursuant to ASU 2023-07 and all existing segment disclosures under Topic 280. The amendments of ASU 2023-07 are effective for us for annual periods beginning January 1, 2024, and effective for interim periods beginning January 1, 2025. We will adopt this standard effective January 1, 2024, and report on it in our Annual Report on Form 10-K for the year ended December 31, 2024. We will update all required disclosures pursuant to ASU 2023-07 at that time.

Current wording

In November 2023, FASB issued ASU 2023-07,Segment Reporting (Topic 280), Improvements to Reportable Segment Disclosures, which provides improvements to reportable segment disclosure requirements, primarily through enhanced disclosures around segment expenses. ASU 2023-07 requires us to disclose significant segment expenses that are regularly provided to the chief operating decision maker, or CODM, and included within each reported measure of segment profit or loss. ASU 2023-07 also requires that we disclose an amount for other segment items by reportable segment, a description of their composition and provide all annual disclosures about a reportable segment’s profit or loss and assets pursuant to Topic 280 during interim periods. We must also disclose the CODM’s title and position, as well as certain information around the measures used by the CODM and an explanation of how the CODM uses the reported measures in assessing segment performance and deciding how to allocate resources. For public entities with a single reportable segment, the entity must provide all the disclosures required pursuant to ASU 2023-07 and all existing segment disclosures under Topic 280. We adopted this standard effective January 1, 2024, and reported in its Annual Report on Form 10-K for the year ended December 31, 2024.

Previous wording

In December 2023, FASB issued ASU 2023-09,Income Taxes (Topic 740): Improvements to Income Tax Disclosures, to enhance the transparency and decision usefulness of income tax disclosures. The amendments in ASU 2023-09 provide improvements primarily related to the rate reconciliation and income taxes paid information included in income tax disclosures. We would be required to disclose additional information regarding reconciling items equal to or greater than five percent of the amount computed by multiplying pretax income (loss) by the applicable statutory tax rate. Similarly, we would be required to disclose income taxes paid (net of refunds received) equal to or greater than five percent of total income taxes paid (net of refunds received). The amendments in ASU 2023-09 are effective January 1, 2025, including interim periods. Early adoption is permitted for annual financial statements that have not yet been issued or made available for issuance. We will evaluate the impact of ASU 2023-09 on our financial statements.

Current wording

** **In December 2023, FASB issued ASU 2023-09,Income Taxes (Topic 740): Improvements to Income Tax Disclosures, to enhance the transparency and decision usefulness of income tax disclosures. The amendments in ASU 2023-09 provide improvements primarily related to the rate reconciliation and income taxes paid information included in income tax disclosures. We would be required to disclose additional information regarding reconciling items equal to or greater than five percent of the amount computed by multiplying pretax income (loss) by the applicable statutory tax rate. Similarly, we would be required to disclose income taxes paid (net of refunds received) equal to or greater than five percent of total income taxes paid (net of refunds received). The amendments in ASU 2023-09 are effective January 1, 2025. Early adoption is permitted for annual financial statements that have not yet been issued or made available for issuance. We are currently evaluating the impacts of ASU 2023-09 on our financial statements.