Actinium Pharmaceuticals, Inc.

Description of Our Business

We are a clinical-stage biopharmaceutical company pioneering the development of targeted radiotherapies to address significant unmet medical needs in oncology. We are focused on employing a biology-driven approach to develop differentiated, first-in-class radiopharmaceutical therapeutics for patients with solid tumors and hematologic malignancies. Our mission is to transform cancer treatment by delivering innovative radioconjugates that maximize therapeutic efficacy while minimizing toxicity to healthy tissue by combining our deep understanding of tumor biology and translational medicine with our expertise in radiochemistry.

Since our inception, we have focused on developing innovative and differentiated radiotherapies. Our pipeline of both early and later stage development programs is a testimony to our approach in three areas with: (1) two novel solid tumor product candidates, ATNM-400 and Actimab-A, with pan-tumor potential, (2) Actimab-A, which is also being developed as a therapeutic backbone for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in partnership with the National Cancer Institute (NCI), and (3) two targeted conditioning agents, Iomab-B for bone marrow transplant and Iomab-ACT for cell & gene therapies. Our solid tumor asset, ATNM-400, targets a novel, antigen which does not target PSMA, with demonstrated pre-clinical activity across metastatic castration-resistant prostate cancer (mCRPC), non-small cell lung cancer (NSCLC), and breast cancer. Actimab-A, targets myeloid derived suppressor cells (MDSC’s) and is being studied in multiple solid tumors in combination with immune checkpoint inhibitors where MDSC’s are known to act as an efficacy deterrent for these agents. Our hematology franchise includes: Actimab-A, a CD33-targeted therapy; as well as, Iomab-B and Iomab-ACT which are CD45-targeting conditioning agents. Both Actimab-A and Iomab-B are Phase 2/3 ready assets and are supported by extensive validation in over 15 clinical trials in which more than 500 patients were treated.

The radiopharmaceutical therapeutics market has experienced significant growth and validation in recent years. The FDA approvalsof Pluvicto® (177Lu-PSMA-617) for prostate cancer and Lutathera® (177Lu-DOTATATE) for gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have demonstrated the transformative potential of targeted radiotherapy. Pluvicto®is the first radiopharmaceutical to achieve blockbuster status and generated approximately $2 billion in sales in 2025 and is forecast by its sponsor Novartis to reach peak sales of $5 billion. Lutathera® isalso forecasted to attain blockbuster status by Novartis.

Many companies have entered the space, perhaps attracted by the success of the aforementioned products and also the acquisitions of several companies in recent years. However, most companies have focused on just a handful of targets. Consequently, we believe the radiopharmaceutical field remains in its early stages despite the number of companies now developing radiotherapies. This is apparent as a majority of the radiotherapy industry development pipeline is clustered around a handful of biological targets with most companies focused on prostate-specific membrane antigen (PSMA), somatostatin receptor type 2 (SSTR2) antagonists/agonists and variations on the theme (NSTR2, NSTR3, etc), and fibroblast activation protein (FAP). Each of these targets features multiple programs using different targeting moieties including but not limited to peptides, small molecules, antibodies as well as various isotope payloads including beta emitters like Lutetium-177 and alpha emitters such as Actinium-225 and Lead-212.

In contrast, we see a significant opportunity to broaden the patient populations benefiting from targeted radiopharmaceuticals by coupling our understanding of tumor biology and translational medicine with our expertise in radiochemistry to develop novel programs against differentiated targets with multi-indication potential. From 2013 to 2023, there was approximately $17 billion in high-value mergers and acquisitions focused on radiopharmaceutical assets, capabilities and infrastructure. Six major pharmaceutical companies have a established radiotherapy presence via acquisitions, resulting in approximately 300,000 square feet of radiopharmaceutical manufacturing infrastructure which is largely underutilized as there are just three approved radiopharmaceutical therapeutics. Since 2024, there has been $8 billion in strategic investments and licensing transactions specifically targeting assets that offer novelty and differentiation in the radiotherapy space. We believe this activity demonstrates both the validation of radiotherapies as a viable treatment modality and the larger companies urgent need for truly differentiated assets to fill their pipelines.

Our Competitive Strengths

We believe we are well-positioned to capitalize on the radiopharmaceutical opportunity based on the following competitive strengths:

Biology-Driven Approach to Radiopharmaceutical Development

Weemploya biology first approach to identify targets that are implicated in underlying tumor biology, disease progression and/or treatment resistance. In doing so, we believe our targeted radiotherapiesare differentiated from the rest of the radiopharmaceutical industry pipeline and have first-in-class potential. The recent acquisitions and licensing transactions in the radiopharmaceutical field have been driven by novel assets and platforms beyond targets such as PSMA, SSTR and FAP. To our knowledge, ATNM-400 and Actimab-A MDSC are the only radiopharmaceuticals in development pursuing their respective targets and indications. Similarly, Actimab-A, Iomab-B and Iomab-ACT, are the only CD33 and CD45 targeting radiotherapies in clinical development to our knowledge. We will continue to identify and evaluate novel radiopharmaceutical assets leveraging our biology-driven methodology.

Differentiated, First-in-Class Pan-Tumor Programs Addressing Large Solid Tumor Indications

Our pipeline features multiple first-in-class programs targeting novel antigens not currently addressed by existing radiopharmaceutical platforms. ATNM-400 represents a differentiated approach in prostate cancer by targeting a non-PSMA antigen, potentially addressing patients who do not respond to or progress after PSMA-targeted therapy such as Pluvicto®, as well as enabling earlier line combinations with androgen receptor pathway inhibitors (ARPIs). With demonstrated pre-clinical efficacy across prostate cancer, NSCLC, and breast cancer, ATNM-400 has pan-tumor potential addressing a combined patient population exceeding 800,000 in the United States. Our pre-clinical data demonstrate that ATNM-400 outperformed leading approved therapies by 3-5 fold in EGFR-mutant NSCLC models as a monotherapy in terms of tumor growth inhibition, produced cures in combination with Tagrisso®, and achieved complete tumor regression in combination with Herceptin® in HER2-resistant breast cancer models.

Actimab-A represents another differentiation opportunity through its mechanism of depleting CD33+ MDSCs, potentially unlocking synergy with PD-1 checkpoint inhibitors such as Keytruda® and Opdivo®in MDSC-rich solid tumors. This approach addresses a well-documented mechanism of PD-1 resistance, with clinical data demonstrating that high MDSC levels correlate with poor outcomes on PD-1 therapy. This positions Actimab-A to potentially expand the $40+ billion PD-1 inhibitor market.

De-Risked Late-Stage Hematology Franchise with Near-Term Partnership Potential

Our hematology programs are supported by extensive clinical validation and represent potential near-term value creation opportunities. Iomab-B has been evaluated in over 500 patients across multiple clinical trials and has received FDA alignment on a Phase 2/3 trial design in an expanded relapsed/refractory (R/R) AML patient population. The program benefits from composition of matter patents extending into 2037, an existing network of 24 clinical sites with continued interest from the Study of Iomab-B in Elderly Relapsed Refractory AML (SIERRA) trial, and potential market expansion across six disease indications representing approximately 150,000 addressable patients who can benefit from improved bone marrow transplant conditioning.

Actimab-A has demonstrated what we believe to be compelling clinical data in combination with CLAG-M chemotherapy, achieving high rates of measurable residual disease (MRD) negativity and improved survival outcomes in high-risk R/R AML patients. In Phase 1b clinical trials, patients treated with Actimab-A plus CLAG-M achieved a 24-month median overall survival among the 70% who proceeded to bone marrow transplant, comparing favorably to the less than 2-4 month overall survival typically observed in TP53-positive or prior venetoclax-treated patient populations. We have received FDA alignment on Phase 2/3 trial design for Actimab-A in combination with CLAG-M for R/R AML patients and are actively seeking strategic partnerships to advance these programs.

The targeted conditioning franchise, including Iomab-B for bone marrow transplant and Iomab-ACT for cell and gene therapies, addresses the fundamental challenge of establishing donor cell engraftment while reducing toxicities associated with traditional chemotherapy based myeloablative conditioning regimens. Iomab-ACT has the potential to serve as a universal conditioning agent, improving patient access and outcomes for CAR-T and other cell therapies, with three active clinical trials currently underway.

End-to-End Supply Chain and Demonstrated Ability to Execute Complex Clinical Trials

Our clinical assets have been studied in over 500 patients to date and we have executed multiple Phase 1 – 3 clinical trials across our Actimab-A, Iomab-ACT and Iomab-ACT programs. In doing so, we have established and actively managed an end-to-end supply chain that encompasses sourcing of radioisotopes, manufacturing targeting agents, production of final drug product candidates and their delivery to the point of care. We believe our demonstrated ability to execute radiopharmaceutical trials at approximately 50 treatment centers including leading comprehensive cancer centers can be leveraged for our ongoing and planned clinical development efforts. We executed a phase 3 trial of Iomab-B which utilized extremely high doses of Iodine-131 (I-131) which required specialized handling. Additional operational parameters included the need for patient isolation in a transplant setting which added to the complexity of the trial yet the company successfully executed the trial without missing a single dose. We are exploring improved methods for efficiently generating quality clinical data by working with centers of excellence both in and outside the United States. We believe these capabilities have strategic value to enable the successful and timely clinical execution of our own planned trials for product candidates we may in-license, partner or acquire.

Vertically Integrated Capabilities and Infrastructure

We are in the process of establishing comprehensive end-to-end capabilities across the radiopharmaceutical value chain. We have invested in establishing an operational radiopharmaceutical manufacturing facility expected to be commissioned in 2H:2026, which will provide clinical supply capabilities by year-end. This facility, combined with our established distribution network to approximately 50 leading hospitals and multiple redundant isotope supply agreements, positions us to serve patient demand at scale. Our proprietary cyclotron-based Ac-225 production technology for which we are seeking a partnership, can help us secure reliable isotope supply at commercial scale via an internal back-up source. We believe our manufacturing process achieves radiochemical purity equivalent to the gold-standard thorium decay method without generating long-lived radioactive contaminants. We have demonstrated leading-edge pre-clinical radiochemistry and translational biology capabilities that enable rapid advancement from target selection through clinical development. This vertical integration provides us with significant strategic flexibility and insulates us from supply chain disruptions that have historically challenged radiopharmaceutical development.

Strong Intellectual Property Position

We have built an intellectual property portfolio comprising approximately 250 issued patents and pending patent applications, including critical composition of matter patents, method of use patents, and proprietary Ac-225 production technology. Our intellectual property estate provides extensive protection for our product candidates and platform technologies across major global markets, with issued and pending patent coverage over key programs. We believe our IP position creates substantial barriers to entry and positions our assets as attractive opportunities for strategic partnerships and out-licensing.

Our Strategy

Our goal is to establish Actinium as a leading, fully integrated targeted radiotherapy company delivering transformative medicines tocancer patients. Key elements of our strategy include:

Rapidly Advance ATNM-400 Through Clinical Development Across Multiple Indications

We are focused on rapidly advancing ATNM-400 into clinical development, leveraging the pre-clinical validation we have established across multiple solid tumor indications. In mCRPC, the pre-clinical dataset demonstrating mechanistic synergy with ARPI’s such as enzalutamide, superiority to both single-agent enzalutamide and 177Lu-PSMA-617, and strong combination activity supports the therapeutic potential in this indication. Based on this data, we believe ATNM-400, a non-PSMA targeting radioconjugate, demonstrates the potential to benefit patients who progress on or are ineligible for PSMA-targeted therapy and potentially enable earlier-line combination approaches with ARPIs.

ATNM-400 also demonstrates clinical development potential in EGFR-mutant NSCLC, where ourpre-clinical data demonstrated 3-5 fold superiority compared to approved EGFR inhibitors including osimertinib (Tagrisso®), datopotamab deruxtecan (Dato-DXd), and amivantamab, as well as 100% complete responses in combination with osimertinib. We have established mechanistic rationale for this combination through demonstrated upregulation of the ATNM-400 target following osimertinib treatment. Furthermore, in pre-clinical studies, both ATNM-400 monotherapy and ATNM-400 in combination with osimertinib is superior to an osimertinib combination with chemotherapy. This positions ATNM-400 for potential development across first-, second-, and third-line EGFR-mutant NSCLC treatment settings.

In breast cancer, we have demonstrated efficacy across HR-positive, triple-negative breast cancer (TNBC), and HER2-resistant models, with complete tumor eradication observed for ATNM-400 in combination with trastuzumab (Herceptin®) in trastuzumab-resistant models. The ATNM-400 target shows increased expression in trastuzumab-resistant tumors, providing mechanistic support for clinical development in this setting. We believe ATNM-400 represents a differentiated approach that can avoid the off-target toxicities such as interstitial lung disease observed with HER2 and TROP-2 antibody-drug conjugates such as Ehertu® and Datroway®, respectively.

Establish Actimab-A MDSC in Combination with Checkpoint Inhibitors

We currently intend to conduct a basket trial evaluating Actimab-A in combination with PD-1 inhibitors (Keytruda® or Opdivo®) across four MDSC-rich solid tumor types: head and neck squamous cell carcinoma (HNSCC), NSCLC, glioblastoma (GBM), and high microsatellite instability (MSI-high) colorectal cancer. This trial, expected to report initial data in 2H:2026, is supported by pre-clinical evidence demonstrating that Actimab-A selectively homes to and depletes tumor-resident CD33+ MDSCs, which are primed for depletion and correlate with poor outcomes on PD-1 therapy. Our pre-clinical data show that Actimab-A treatment is cytotoxic to patient-derived MDSCs ex vivo and enhances T-cell responses.

The trial design includes comprehensive biomarker assessments to evaluate MDSC depletion patterns in both tumor microenvironment and peripheral blood, as well as T-cell activity restoration. We will compare clinical outcomes including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) against real-world data comparators. Success in this trial could position Actimab-A as a foundational combination partner for checkpoint inhibitors across multiple solid tumor indications. In addition, we are evaluating the potential for further clinical evaluation of Actimab-A inpatients with GBM and NSCLC with other PD-1 inhibitors. GBM has a unique microenvironment in which ~40% of the glioma mass is comprised of tumor associated myeloid (TAM’s) cells which play an important role in immunosuppression and inhibition of anti-tumor responses. Selective eradication of these TAM’s which express CD33 within the GBM tumor microenvironment with Actimab-A has the potential to enhance anti-tumor T-cell immunity thereby increasing the effectiveness of immunotherapies for the treatment of GBM.

Execute Strategic Partnerships for Late-Stage Hematology Programs

We are actively seeking strategic partnerships to advance our Phase 2/3-ready hematology programs, Actimab-A and Iomab-B. These programs benefit from substantial clinical validation, clear regulatory pathways following FDA alignment, and concentrated commercial markets focused on approximately 100 quaternary care centers in the United States and Europe. The complementary nature of these programs—spanning AML/MDS therapeutics and targeted conditioning for bone marrow transplant and cell/gene therapies—creates strong commercial synergies and represents blockbuster market opportunities.

Our partnership strategy prioritizes collaborations that can provide the resources and infrastructure necessary to execute global pivotal trials while preserving meaningful economics for Actinium. We are leveraging our existing relationship with the National Cancer Institute (NCI), which has established a Cooperative Research and Development Agreement (CRADA) supporting Actimab-A development, to advance clinical programs in a cost-effective manner while retaining commercial rights.

Build Fully Integrated cGMP Manufacturing and End-to-End Supply Chain

We are completing construction of our internal cGMP radiopharmaceutical manufacturing facility, which is being designed to manufacture Ac-225 based radioconjugates and provide drug product manufacturing to support clinical trials. This facility, expected to be operational in 2H:2026, will complement our established network of hospital administration sites and isotope suppliers. Our hybrid internal-external manufacturing strategy is designed to provide supply reliability, cost efficiency, and geographic flexibility to serve global patient populations at commercial scale. In addition, we will opportunistically seek partnerships to manufacture Ac-225 utilizing our patented cyclotron production technology.

Continue Platform Innovation and Pipeline Expansion

We are committed to continued innovation in radiopharmaceutical discovery and development. Our proven track record of generating highly differentiated programs positions us to expand our pipeline through both internal discovery efforts and potential strategic acquisitions of complementary assets or technologies. We maintain rigorous criteria for program advancement, requiring demonstration of clear differentiation, compellingpre-clinical validation, and significant market opportunities before committing substantial resources to clinical development.

Our Pipeline

Solid Tumor Programs

ATNM-400: First-in-Class Pan-Tumor Radiotherapy

ATNM-400 is our lead solid tumor program, representing a first-in-class Ac-225 antibody radioconjugate targeting a novel, undisclosed, non-PSMA targeting antigen with expression across multiple solid tumor types. The ATNM-400 targetis implicated in disease biology during tumor progressionandis also overexpressed when tumors become resistant to many approved therapies in multiple solid tumors.

Our pre-clinical translational data demonstrated that ATNM-400 is superior to:

These data show that ATNM-400 works well as monotherapy but is even better in combination in resistant settings where the target is overexpressed as part of the resistance mechanism. Evidence of target expression has been observed ranging from 60%-80%+ in mCRPC, NSCLC, and breast cancer patient tumors, representing a significant addressable population of over a hundred thousand patients in the United States based on our existing datasets. This number may expand as we continue our work to demonstrate the potential of ATNM-400 in various additional disease and treatment settings.

Our pre-clinical development program has generated robust efficacy and mechanism-of-action data across multiple indication-specific animal models:

Prostate Cancer: ATNM-400 demonstrated specific tumor uptake and decreased tumor cell proliferation inpre-clinical models, with significantly greater efficacy than both 177Lu-PSMA-617 (the active agent in Pluvicto®)and next-generation 225Ac-PSMA-617 in PSMA-low 22Rv1 prostate cancer xenograft models that are resistant to ARPI therapy.

Importantly, ATNM-400 also demonstrated superior efficacy to enzalutamide and 177Lu-PSMA-617 in ARPI-resistant prostate cancer models, with strong and durable combination activity when combined with enzalutamide. This combination activity is mechanistically supported by our observation that enzalutamide resistance increases ATNM-400 target expression in both prostate cancer models and mCRPC patient samples.

These data support ATNM-400 development in post-Pluvicto® and post-ARPI patient populations. Between 45,000 to 55,000 patients will progress on ARPI in the mCRPC and metastatic hormone sensitive prostate cancer (mHSPC) settings annually. With a potential of Pluvicto® approval in mHSPC based on the Phase 3 PSMAddition study, the number of eligible patients nearly doubles from 44,000 patients in the mCRPC population to 86,500 patients in both mHSPC and mCRPC. Given that the response rates for Pluvicto® in the VISION and PSMAfore population are approximately 30% and 50%, respectively, a significant proportion of patients remain with few options following treatment. Additionally, Pluvicto® refractory patients will receive as few as 2 cycles if no response is observed. The mechanistic synergy with ARPIs also supports potential expansion to earlier treatment lines in combination with standard-of-care hormonal therapies, representing an addressable population exceeding 100,000 patients across all lines of treatment in the mCRPC and mHSPC settings.

EGFR-Mutant NSCLC: ATNM-400 demonstrated 3-5 fold greater tumor growth inhibition compared to approved EGFR-targeted therapies including osimertinib (first-line), datopotamab deruxtecan (second-line), and amivantamab (third-line) in NCI-H1975 human lung cancer models harboring L858R and T790M EGFR mutations.

In combination with osimertinib, ATNM-400 achieved 100% complete responses with durable efficacy extending throughout the study period.

We have established mechanistic support for ATNM-400 combinations with EGFR inhibitors, demonstrating that osimertinib treatment increases ATNM-400 target expression both in vitro and in vivo. This mechanistic synergy, combined with clinical data showing improved outcomes when osimertinib is combined with external beam radiotherapy, supports ATNM-400 development across multiple EGFR-mutant NSCLC treatment settings.

EGFR-mutant NSCLC represents approximately 30,000 U.S. patients annually, with current treatment dominated by AstraZeneca’s Tagrisso®(osimertinib) and Johnson & Johnson’s Rybrevant®(amivantamab) combinations. ATNM-400 offers a novel EGFR inhibitor plus radiotherapy combination approach with potential differentiation across first-, second-, and third-line settings. Additionally, given tumor cell apoptosis driven by the irreversible double-stranded DNA damage from actinium-225, ATNM-400 could potentially provide benefit for the approximately 200,000 NSCLC patients diagnosed annually regardless of oncogenic driver mutation.

Breast Cancer: ATNM-400 demonstrated robust anti-tumor activity and tumor regression as monotherapy and in combination with trastuzumab inpre-clinical breast cancer models, including trastuzumab-resistant BT474-Clone5 model, HR+ breast cancer MCF-7 model and triple-negative breast cancer (TNBC)and triple-negative MDA-MB-468 model. In the trastuzumab-resistant setting, we observed increased expression of both the survival pathway marker p-AKT and the ATNM-400 target, with ATNM-400 treatment inducing DNA double-strand breaks as measured by p-H2AX staining. ATNM-400 achieved 66% tumor growth inhibition as monotherapy and 103% tumor growth inhibition (representing tumor regression) in trastuzumab-resistant models.

The ATNM-400 target is overexpressed in breast cancer, including tumors resistant to endocrine therapies such as tamoxifen and HER2-targeted therapies, as well as in TNBC.

We believe that this broad expression pattern supports multi-lineage development in breast cancer. Current second-line therapies in HER2-positive disease, including trastuzumab deruxtecan and sacituzumab govitecan, are limited by off-target toxicities including interstitial lung disease. ATNM-400 represents a novel therapeutic approach designed to avoid these toxicity concerns while providing efficacy across HR-positive, HER2-resistant, and TNBC patient populations representing approximately 300,000 U.S. patients annually.

We have developed a theranostic strategy utilizing Zr-89 as a companion imaging agent to enable patient selection and tumor visualization. This approach allows for non-invasive assessment of target expression and drug biodistribution prior to therapeutic administration, potentially enhancing the therapeutic index by selecting patients most likely to respond.

Success in our clinical program could position ATNM-400 as a differentiated pan-tumor targeted radiotherapy across multiple large solid tumor indications, potentially addressing the several hundred thousand U.S. patients with mCRPC, EGFR-mutant NSCLC, and all sub-types of breast cancer, while also establishing a first-in-class radioconjugate with broad combination potential and attractive partnership and commercial potential in the rapidly growing radiopharmaceutical market.

Actimab-A for MDSC’s: Novel Immunomodulatory Approach in Solid Tumors

Actimab-A (lintuzumab-Ac-225) is a CD33-targeted Ac-225 radioconjugate that we are developing to enhance checkpoint inhibitor efficacy by depleting immunosuppressive CD33+ MDSCs in the tumor microenvironment.

MDSCs are a heterogeneous population of immature myeloid cells that accumulate in solid tumors and suppress anti-tumor T-cell responses, representing a well-validated mechanism of resistance to PD-1/PD-L1 checkpoint inhibitors. Clinical studies have demonstrated that patients with high circulating MDSC levels have significantly reduced progression-free and overall survival on PD-1 therapy compared to patients with low MDSC levels.

Low MDSC’s Associated with Statistically Significant Improvement in PFS and OS

Source: 1) Bronte et al. High Levels of Circulating Monocytic Myeloid-Derived Suppressive-Like Cells Are Associated With the Primary Resistance to Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: An Exploratory Analysis https://pmc.ncbi.nlm.nih.gov/articles/PMC9043492/. Frontiers in Immunology. 2022 Apr 13;13:866561

Ourpre-clinical studies have demonstrated that Actimab-A: (1) selectively homes to tumor-resident CD33+ MDSCs in vivo; (2) is cytotoxic to patient-derived MDSCs ex vivo; and (3) rescues T-cell proliferation and anti-tumor immune responses ex vivo following MDSC depletion. These data provide mechanistic support for combining Actimab-A with PD-1 inhibitors to overcome MDSC-mediated resistance.

We intend to conduct a Phase 1b basket trial evaluating Actimab-A in combination with pembrolizumab (Keytruda®)or nivolumab (Opdivo®)in patients with R/R locally advanced or metastatic HNSCC, NSCLC, GBM, and MSI-high colorectal cancer. These tumor types were selected based on high MDSC infiltration and limited response rates to PD-1 monotherapy. The trial design incorporates comprehensive correlative biomarker assessments to evaluate MDSC depletion in both tumor microenvironment and peripheral blood, as well as T-cell activity restoration.

Patients enrolled in the trial must have MDSC-rich tumor types, be checkpoint inhibitor-naïve, be at least 18 years of age, and demonstrate PD-1/PD-L1 expression. Primary endpoints include safety and tolerability of the combination, with secondary endpoints including ORR, PFS, and OS. Biomarker endpoints will evaluate the pattern of CD33+ MDSC depletion and T-cell activity in both tumor tissue and peripheral blood samples. Clinical outcomes will be compared against real-world data from similar patient populations treated with PD-1 monotherapy. We expect to report initial data from this trial in 2H:2026. In addition, we are also evaluating clinical opportunities with other immune checkpoint inhibitors in GBM and NSCLC.

We believe that success in this trial could position Actimab-A for development across multiple solid tumor indications in combination with checkpoint inhibitors, potentially expanding the utility of the $40+ billion PD-1/PD-L1 inhibitor market by addressing MDSC-mediated resistance.

Hematology Programs

Actimab-A: Backbone Therapy for AML and MDS

In hematologic malignancies, we are developing Actimab-A as a mutation-agnostic backbone therapy for AML and high-risk MDS. CD33 is expressed on leukemic blasts in the majority of AML patients and represents an established therapeutic target validated by the approval of gemtuzumab ozogamicin (Mylotarg®). However, antibody-drug conjugates like Mylotarg®have limitations including hepatotoxicity and limited efficacy in certain patient populations. Actimab-A, delivering the highly potent alpha-emitter Ac-225 to CD33+ cells, represents a differentiated approach designed to provide superior efficacy while maintaining a favorable safety profile.

Actimab-A incombination with CLAG-M for R/R AML: We have completed a Phase 1b clinical trial evaluating Actimab-A in combination with CLAG-M chemotherapy in R/R AML patients, results of which were published in a peer-reviewed journalLeukemia in February 2025. The trial enrolled high-risk patients including those with TP53 mutations, prior venetoclax treatment failure, and patientswho had prior allogeneic transplant. Results demonstrated high rates of MRD-negative complete remissions and improved survival outcomes compared to historical controls.

Among patients treated with Actimab-A plus CLAG-M, 70% of those deemed eligible for transplant proceeded to bone marrow transplant, and this population achieved a 24-month median overall survival. These results compare highly favorably to published data showing less than 2-4 month median overall survival in TP53-mutated or prior venetoclax-treated R/R AML patient populations. The combination was well-tolerated with a safety profile consistent with CLAG-M chemotherapy alone and no dose-limiting toxicities observed.

Based on these results, we have received FDA alignment on a Phase 2/3 trial design to evaluate Actimab-A plus CLAG-M in first or second salvage R/R AML patients.

We are currently actively seeking a strategic partner to execute this trial. The trial design allows for enrollment of a broad R/R AML population while enriching for patients most likely to benefit based on Phase 1b results.

Actimab-A Development Programs: Beyond R/R AML, we are developing Actimab-A in conjunction with the NCI across multiple AML and MDS treatment settings and exploring its potential in additional areas:

The programs are supported by our Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute, which enables cost-effective clinical development while retaining commercial rights to Actinium.

We believe that success in our hematology program could establish Actimab-A as a mutation-agnostic backbone therapy for R/R AML and high-risk MDS, addressing a combined patient population with limited treatment options, while generating important data to support regulatory approval and to enable a strategic partnership to commercialize Actimab-A across the estimated $2+ billion AML/MDS therapeutics market.

Iomab-ACT: Universal Conditioning for Cell and Gene Therapies

Iomab-ACT is our CD45-targeted conditioning platform being developed as a universal conditioning agent to improve access and outcomes for cell and gene therapies, including CAR-T, allogeneic hematopoietic stem cell transplant, and gene therapy. The cell and gene therapy field has been limited by the need for lymphodepleting chemotherapy conditioning, which is associated with significant toxicities and can limit the patient populations eligible for these potentially curative treatments.

Iomab-ACT is designed to provide targeted lymphodepletion and myeloablation when necessary while avoiding the off-target toxicities associated with chemotherapy conditioning. By delivering targeted radiation specifically to CD45+ hematopoietic cells, Iomab-ACT aims to create an optimal environment for therapeutic cell engraftment while minimizing treatment-related morbidity and mortality.

We currently have three active clinical trials evaluating Iomab-ACT:

The cell and gene therapy market represents a rapidly growing opportunity, with over 30,000 patients annually receiving CAR-T or allogeneic transplant in the United States and Europe. Success in these trials could position Iomab-ACT as a universal conditioning platform applicable across multiple cell and gene therapy modalities, potentially expanding patient access to these curative therapies while improving safety and tolerability.

Iomab-B: Targeted Conditioning for Bone Marrow Transplant in R/R AML

Iomab-B (apamistamab-I-131) is a CD45-targeted radioimmunotherapy designed to enable bone marrow transplant in R/R AML patients who are ineligible for conventional myeloablative conditioning due to age, comorbidities, or prior treatment-related toxicities. CD45 is expressed on all hematopoietic cells, enabling Iomab-B to deliver targeted radiation to bone marrow while sparing non-hematopoietic organs from radiation exposure.

Conventional stem cell transplant conditioning regimens utilize high-dose chemotherapy with or without total body irradiation to ablate the patient’s hematopoietic system and create space for donor cell engraftment. These regimens are associated with significant toxicities including mucositis, hepatotoxicity, pulmonary toxicity, and treatment-related mortality. Many elderly patients and those with comorbidities are deemed ineligible for these intensive conditioning regimens, limiting access to potentially curative transplant therapy.

Iomab-B has been evaluated in over 500 patients across multiple clinical trials, including the Phase 3 SIERRA trial in R/R AML patients. The SIERRA trial demonstrated that Iomab-B enabled successful donor cell engraftment in elderly R/R AML patients who would otherwise be ineligible for conventional conditioning. The study metthe primary endpoint ofdurable complete remission(dCR). While the study did not meet the secondary endpoint of OS due to the cross over of two-thirds of the patients from the control arm to Iomab-B arm, it provided important insights into optimal patient selection and trial design for future development.

We have received FDA alignment on a Phase 2/3 trial design in an expanded R/R AML patient population that includes all patients age 18 and older with R/R AML. This expanded population reflects learnings from SIERRA regarding optimal patient selection. The trial design allows us to leverage both the Phase 2 results and the SIERRA database to support regulatory submissions.

Iomab-B benefits from composition of matter patents extending to 2038, a well-established network of 24 clinical sites from the SIERRA trial that maintains strong interest in the program, and potential for market expansion beyond R/R AML. Pre-clinical and clinical data support potential development in five additional disease indications including acute lymphoblastic leukemia, myelodysplastic syndromes, chronic myeloid leukemia, multiple myeloma, and lymphoma, representing a total addressable market of approximately 150,000 patients who could benefit from improved bone marrow transplant conditioning.

We are actively seeking a strategic partner to advance Iomab-B through pivotal development and commercialization.

We believe Actimab-A, Iomab-B and Iomab-ACT collectively have the potential to be successful commercial products based on the high unmet needs of their addressable patient segments. In total, we believe this opportunity exceeds 400,000 patients in the U.S. and EU.

Our Platform and Capabilities

Radiochemistry and Translational Science Capabilities

We have assembled a team with expertise in radiopharmaceutical discovery and development, spanning target selection, radioconjugate design, pre-clinical evaluation, and clinical development. Our capabilities include:

These capabilities enable us to efficiently advance programs from target selection through clinical development while maintaining high quality standards and generating comprehensive translational data packages to guide clinical development andsupport regulatory submissions and partnership discussions.

Ac-225 Production and Radiopharmaceutical Manufacturing

We have developed proprietary cyclotron-based technology for commercial-scale production of Ac-225, one of the most critical bottlenecks in radiopharmaceutical development. Our production method generates high-purity Ac-225 with radiochemical purity equivalent to the gold-standard thorium-229 decay method, while avoiding the generation of long-lived radioactive contaminants such as Ac-227. This production technology is protected by patents and if operationalized may represent a significant competitive and cost advantage.

We are currently completing construction of a radiopharmaceutical manufacturing facility designed to manufacture Ac-225-based final drug products for clinical supply. The facility, expected to be operational in 2H:2026, incorporates purpose-built infrastructure for alpha-emitter handling and a flexible manufacturing suite capable of supporting multiple trials.

We have also established an end-to-end supply chain spanning isotope production through patient administration. We maintain supply agreements with multiple redundant isotope suppliers, relationships with multiple contract manufacturing organizations, and a distribution network to approximately 50 leading cancer centers amassed via the execution of several Phase 1 – 3 clinical trials. This supply chain infrastructure provides geographic coverage across major metropolitan areas, minimizes risk of supply disruption, and positions us to reliably serve patient demand at clinical scale.

Competition

The radiopharmaceutical therapeutics field has experienced significant growth in recent years, with numerous companies and academic institutions developing targeted radiotherapy programs. We face competition from several categories of organizations:

Large Pharmaceutical Companies: Several major pharmaceutical companies have entered the radiopharmaceutical space through acquisitions or internal development, including Novartis (through acquisition of Advanced Accelerator Applicationsand Endocyte ), Eli Lilly (through acquisition of Point Biopharma), Bristol Myers Squibb (through acquisition of RayzeBio), AstraZeneca (through acquisition of Fusion Pharmaceuticals), Bayer (through acquisition of Algeta Pharmaceuticals, Noria Therapeutics, and PSMA Therapeutics), and Johnson & Johnson. These companies possess significantly greater financial resources, established commercial infrastructure, and broader development pipelines than we do. However, many of these companies are focused on PSMA-targeted therapies for prostate cancer or SSTR2-targeted therapies for neuroendocrine tumors and have stated a need for novel differentiated assets to expand their radiopharmaceutical portfolios.

Clinical-Stage Radiopharmaceutical Companies: We compete with several clinical-stage companies developing novel radiopharmaceutical approaches. A representative list of these competitors include Telix Pharmaceuticals, Perspective Therapeutics, Clarity Pharmaceuticals, Cellectar Biosciences, Bicycle Therapeutics, Molecular Partners, Ratio Therapeutics, Convergent Therapeutics, Aktis Oncology, Radiopharm Theranostics, and Plus Therapeutics. This is not a comprehensive list andnone ofthese or any other radiotherapeutics company currently competeare directly with Actinium’s product candidates in terms of biological targets.

Antibody-Drug Conjugate Companies: Particularly solid tumors, we may compete with companies developing antibody-drug conjugates (ADCs) that deliver cytotoxic chemotherapy payloads to tumor cells. However, we believe radiopharmaceuticals offer potential advantages compared to ADCs including the “crossfire” or “bystander” effect wherein alpha particles can kill neighboring tumor cells that do not express the target antigen, potentially overcoming tumor heterogeneity. Additionally, radiopharmaceuticals enable non-invasive imaging to assess target expression and drug biodistribution, potentially improving patient selection.

Therapeutic Area Competitor Companies: Several large pharmaceutical companies are legacy areas in the therapeutic areas that our pipeline agents are being developed. In prostate cancer, several marketed drugs are available from Johnson & Johnson, Astellas/Pfizer, Bayer, Novartis, and AstraZeneca/Merck. AstraZeneca, Johnson & Johnson, Roche, and Daiichi Sankyo have approved agents in EGFR mutant NSCLC. As for breast cancer, Roche, Pfizer, Lilly, Novartis, and AstraZeneca/Daiichi Sankyo have therapeutics available. AbbVie, Bristol Myers Squibb, Astellas, and Servier are primary companies with AML marketed agents. In addition, these companies have active pipelines exploring a multitude of mechanisms of action to maintain or grow their positions in these indications.

We believe our competitive position is differentiated by: (1) our focus on novel, first-in-class targets with pan-tumor potential rather than following validated targets already being pursued by multiple competitors; (2) our vertically integrated capabilities that we intend to span isotope production through drug product manufacturing; (3) our late-stage hematology programs with clear regulatory pathways; and (4) our comprehensive intellectual property position protecting our products and platform technologies.

However, we face significant competitive risks. Our competitors may develop therapies that are more effective, safer, more convenient, or more cost-effective than our product candidates. Competitors may also obtain regulatory approval before we do, establish superior market positions, or render our technologies obsolete. In the evolving landscape of targeted radiotherapies, mergers and acquisitions and collaborations can quickly reshape the competitive landscape. Large radiopharmaceutical companies are increasingly partnering with and acquiring small biotechnology companies in the field to access novel pipeline agents and manufacturing capabilities for radiopharmaceutical production and development. These deals and partnerships, through increased access to capital, regulatory expertise, and global infrastructure, can expedite clinical development timelines and hasten drug commercialization. The radiopharmaceutical field is characterized by rapid technological change and intense competition, and we cannot guarantee that we will be able to maintain our competitive position.

Government Regulation

United States Regulation

In the United States, pharmaceutical products are subject to extensive regulation by the FDA. The Federal Food, Drug, and Cosmetic Act (FDCA), and other federal and state statutes and regulations, govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical products. Failure to comply with applicable U.S. requirements may subject a company to a variety of administrative or judicial sanctions, such as FDA refusal to approve pending new drug applications (NDAs) or biologics license applications (BLAs), warning or untitled letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties, and criminal prosecution.

Pharmaceutical product development for a new product or certain changes to an approved product in the United States typically involves completion of preclinical laboratory tests, animal studies and formulation studies, all performed in accordance with the FDA’s Good Laboratory Practice (GLP) regulations, submission to the FDA of an IND which must become effective before clinical trials may begin, adequate and well-controlled clinical trials to establish the safety and effectiveness of the drug or biologic for each indication for which FDA approval is sought, and submission to the FDA of an NDA or BLA. FDA review is conducted the via NDA pathway for product candidates regulated as drugs and via the BLA pathway for product candidates regulated as biologics. Both pathways require an IND for investigation. Our lead product candidates are regulated as biologics.

Preclinical tests include laboratory evaluation of product chemistry, formulation and toxicity, as well as animal trials to assess the characteristics and potential safety and efficacy of the product. The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs. The results of preclinical testing are submitted to the FDA as part of an IND along with other information including information about product chemistry, manufacturing and controls and a proposed clinical trial protocol. Long-term preclinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue after the IND is submitted.

A 30-day waiting period after the submission of each IND is required prior to the commencement of clinical testing in humans. If the FDA has neither commented on nor questioned the IND within this 30-day period, the clinical trial proposed in the IND may begin. If the FDA raises concerns or questions about the conduct of the trial, such as whether human research subjects will be exposed to an unreasonable health risk, the IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can proceed.

Clinical trials involve the administration of the investigational drug to human subjects under the supervision of qualified investigators in accordance with Good Clinical Practice (GCP) requirements, which include the requirement that all research subjects provide their informed consent in writing before their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.

The FDA may order the temporary, or permanent, discontinuation of a clinical trial at any time, or impose other sanctions, if it believes that the clinical trial either is not being conducted in accordance with FDA requirements or presents an unacceptable risk to the clinical trial patients. The study protocol and informed consent information for patients in clinical trials must also be submitted to an institutional review board (IRB) for approval at each site at which the clinical trial will be conducted. An IRB may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or may impose other conditions.

Clinical trials to support NDAs and BLAs for marketing approval are typically conducted in three sequential phases, but the phases may overlap. In Phase 1, the drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness and to determine optimal dosage. Phase 2 usually involves trials in a limited patient population to identify possible adverse effects and safety risks, to determine the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage. Phase 3 trials are undertaken to further evaluate dosage, to provide substantial evidence of clinical efficacy and to further test for safety in an expanded patient population at geographically dispersed clinical trial sites.

After completion of the required clinical testing, an NDA or BLA is prepared and submitted to the FDA. FDA approval of the NDA is required before marketing of the product may begin in the United States. The NDA/BLA must include the results of all preclinical, clinical and other testing and a compilation of data relating to the product’s pharmacology, chemistry, manufacture and controls. The cost of preparing and submitting an NDA/BLA is substantial.

The FDA has 60 days from its receipt of an NDA/BLA to determine whether the application will be accepted for filing based on the agency’s threshold determination that it is sufficiently complete to permit substantive review. Once the submission is accepted for filing, the FDA begins an in-depth review. The FDA has agreed to certain performance goals in the review of NDAs and BLAs. Most such applications for standard review drug products are reviewed within 10 months of submission; most applications for priority review drugs are reviewed within six months of submission. Priority review can be applied to drugs that the FDA determines offer major advances in treatment, or provide a treatment where no adequate therapy exists. The review process for both standard and priority review may be extended by FDA for three additional months to consider certain late-submitted information, or information intended to clarify information already provided in the submission.

The FDA may also refer applications for novel drug products, or drug products that present difficult questions of safety or efficacy, to an advisory committee—typically a panel that includes clinicians and other experts—for review, evaluation and a recommendation as to whether the application should be approved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations. Before approving an NDA or BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.

Radiopharmaceuticals face additional regulatory considerations beyond conventional pharmaceuticals. Due to their radioactive nature, radiopharmaceuticals are also regulated by the Nuclear Regulatory Commission (NRC) or Agreement States under the Atomic Energy Act. We must obtain appropriate licenses for possession, use, and distribution of radioactive materials. These licenses impose requirements for radiation safety programs, personnel training and monitoring, facility design and monitoring, waste disposal, and security. We must also comply with regulations governing the transportation of radioactive materials, including such regulation by the US Department of Transportation.

The FDA has issued guidance documents specific to radiopharmaceuticals that address topics including dosimetry assessments, clinical trial design, and manufacturing controls. Radiopharmaceutical development programs typically require microdosing studies using imaging isotopes to assess biodistribution and dosimetry prior to therapeutic dose administration. Manufacturing of radiopharmaceuticals must account for short half-lives necessitating distributed manufacturing networks, specialized quality control testing, and just-in-time production and distribution systems.

International Regulation

In addition to regulations in the United States, we are subject to regulations in the foreign countries in which we conduct clinical trials or seek to market our products. Whether or not we obtain FDA approval for a product, we must obtain approval by the comparable regulatory authorities of foreign countries or economic areas, such as the European Union, before we may commence clinical trials or market products in those countries or areas. The approval process and requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from place to place, and the time may be longer or shorter than that required for FDA approval.

The European Union has centralized procedures for approving pharmaceuticals that allow companies to submit a single marketing authorization application (MAA) to the European Medicines Agency (EMA). Upon EMA approval, this centralized procedure results in a single marketing authorization that is valid across the European Economic Area. The EMA has specific guidelines for radiopharmaceuticals addressing dosimetry, manufacturing, and clinical development considerations similar to FDA guidance.

In many foreign countries, radiopharmaceuticals face additional complexities related to reimbursement structures, nuclear medicine facility requirements, and isotope supply chains that differ significantly from the U.S. market.

Intellectual Property

We strive to protect and enhance the proprietary technologies that we believe are important to our business, including seeking, maintaining and defending patent rights, whether developed internally or licensed from third parties. Our policy is to seek to protect our proprietary position by, among other methods, filing U.S. and foreign patent applications related to our proprietary technology, inventions and improvements that are important for the development and implementation of our business. We also rely on trade secrets, know-how, continuing technological innovation and in-licensing opportunities to develop, strengthen and maintain our proprietary position.

Our intellectual property portfolio comprises approximately 250 patents and patent applications across multiple jurisdictions. Our patent estate includes:

Our patents provide market exclusivity in major territories including the United States, Europe, Canada, Japan, and key emerging markets. We actively monitor and enforce our intellectual property rights and investigate potential infringement of our proprietary technologies.

In addition to patents, we maintain proprietary know-how and trade secrets relating to our radiopharmaceutical development platform, manufacturing processes, and clinical development strategies. We seek to protect this information through confidentiality agreements with employees, consultants, advisors, and collaborative partners.

We also rely on regulatory exclusivity to protect our products from competition. In the United States, biologics such as our antibody radioconjugates may be eligible for 12 years of market exclusivity under the Biologics Price Competition and Innovation Act. Additionally, therapies receiving orphan drug designation may be eligible for seven years of market exclusivity in the United States, and similar exclusivity periods apply in other territories.

Manufacturing and Supply Chain

Our manufacturing strategy combines internal capabilities with external partnerships to create a flexible, redundant, and cost-effective supply chain capable of supporting both clinical development and commercial supply. This hybrid approach provides us with strategic flexibility, supply reliability, and the ability to scale production to meet patient demand.

Internal Manufacturing Capabilities

We are completing construction of a state-of-the-art cGMP radiopharmaceutical manufacturing facility located in New York, expected to be operational in 2H:2026. This facility has been purpose-built for alpha-emitter handling and radiopharmaceutical production with the following capabilities:

The facility has been designed for clinical stage supply of radiolabeled therapeutic drug product production**.**

External Manufacturing Partnerships

We have established partnerships with multiple contract manufacturing organizations providing geographic redundancy and production flexibility:

Supply Chain Management

Our supply chain team has established systems and processes to coordinate the complex logistics of radiopharmaceutical production and distribution:

Our manufacturing and supply chain capabilities position us to serve patient populations at clinical and commercial scale while maintaining the flexibility to respond to changing demand and expand into new geographic markets.

Human Capital

As of March 25, 2026, we had 25 full-time employees, 12 of whom have Ph.D. or M.D. degrees and 21 of whom are engaged in research and development and clinical development activities. We believe that we have been successful to date in attracting skilled and experienced personnel despite the competitive hiring marketing in the industry. Our employees are not covered by a collective bargaining agreement, and we believe that our relationship with our employees is excellent. We continue to engage external consultants on an as-needed basis to temporarily supplement existing staff.

Corporate Information

We were incorporated under the laws of the State of Delaware in 2013. Our principal executive offices are located at 100 Park Avenue, New York, NY 10017, and our telephone number is (646) 677-3870. Our website address is www.actiniumpharma.com. The information contained on our website or that can be accessed through our website is not incorporated by reference into this Report and should not be considered a part of this Report.

We make available free of charge through our website our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and any such amendments to those reports as soon as reasonably practicable after we electronically file such material with or furnish such material to the Securities and Exchange Commission (“SEC”). The SEC maintains a website at http://www.sec.gov that contains reports, proxy and information statements and other information regarding companies that file electronically with the SEC.

Government Regulation

Regulatory Compliance

Our research and development activities are all subject to stringent regulation, primarily by the FDA in the U.S. under the Federal Food, Drug, and Cosmetic Act (the “FDCA”) and its implementing regulations, and the Public Health Service Act (“PHSA”) and its implementing regulations, and by comparable authorities under similar laws and regulations in other countries. This includes research and development, testing, and oversight of suppliers and contract manufacturers involved in the production of our product candidates we are developing, as well as the design, manufacturing, safety, efficacy, handling, labeling, storage, record-keeping, advertising, promotion and marketing. If, for any reason, we do not comply with applicable requirements, such noncompliance can result in adverse consequences, including delays in approval of, or even the refusal to approve product licenses or other applications, the suspension or termination of clinical investigations, the revocation of approvals previously granted, as well as fines, criminal prosecution, recall or seizure of products, injunctions against shipping products and suspension of production and/or refusals of government contracts.

FDA Review Process and Product Approval

Our product candidates are regulated as biologics and must be approved by the FDA before they may be marketed in the U.S. This process generally involves the following:

Clinical trials generally are conducted in three sequential phases, although they may overlap or be combined.

The results of the preclinical and clinical testing, along with information regarding the manufacturing of the product and proposed product labeling, are evaluated and, if determined appropriate, submitted to the FDA through a BLA. Once the BLA submission has been accepted for filing, the FDA’s standard goal is to review applications within ten months of the filing date or, if the application relates to a drug that treats a serious condition and would provide a significant improvement in safety or effectiveness qualifying for Priority Review, six months from the filing date. The review process is often significantly extended by FDA requests for additional information or clarification.

The FDA offers certain programs, such as Breakthrough Designation (“BTD”) and Fast Track designation, designed to expedite the development and review of applications for products intended for the treatment of a serious or life-threatening disease or condition. For BTD, preliminary clinical evidence of the product indicates that it may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The FDA may initiate review of sections of a BLA before the application is complete, and the product may be eligible for accelerated approval. However, receipt of BTD or Fast Track designation does not ensure that a product will be developed or approved on an expedited basis, or at all.

The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, pure and potent, which includes determining whether it is effective for its intended use, and whether the product is being manufactured in accordance with cGMP, to assure and preserve the product’s identity, strength, quality, potency and purity. The FDA may refer an application to an advisory committee for review, evaluation and recommendation as to whether the application should be approved, and applications for new molecular entities and original BLAs are generally discussed at advisory committee meetings unless the FDA determines that this type of consultation is not needed under the circumstances.

After the FDA evaluates the BLA and conducts inspections of manufacturing facilities, it may issue an approval letter or a complete response letter (“CRL”). An approval letter authorizes commercial marketing of the biologic with specific prescribing information for specific indications. A CRL indicates that the review cycle of the application is complete, but the FDA cannot grant approval. A CRL may require additional inspections, and/or other significant, expensive and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. The FDA could approve the BLA with a Risk Evaluation and Mitigation Strategy (“REMS”) to mitigate risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling, development of adequate controls and specifications, or a commitment to conduct one or more post-market studies or clinical trials. Such post-market testing may include Phase 4 clinical trials and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.

Post-Approval Requirements

Any products manufactured or distributed by us or on our behalf pursuant to FDA approvals are subject to continuing regulation by the FDA and certain state agencies, including requirements for record-keeping, reporting of adverse experiences with the biologic, submitting biological product deviation reports to notify the FDA of unanticipated changes in distributed products, establishment registration, compliance with cGMP standards, and certain state licensing requirements.

Additionally, any significant change in the approved product or in how it is manufactured, including changes in formulation or the site of manufacture, generally require prior FDA approval. The packaging and labeling of all products developed by us are also subject to FDA approval and ongoing regulation. Noncompliance with any regulatory requirements can result in, among other things, issuance of warning letters, civil and criminal penalties, seizures, and injunctive action. Accordingly, manufacturers must continue to maintain compliance with cGMP and other aspects of regulatory compliance. The commercial distribution of prescription drugs is subject to the Drug Supply Chain Security Act (“DSCSA”), which regulates the distribution of the products at the federal level and sets certain standards for federal or state registration and compliance of entities in the supply chain.

The DSCSA preempts certain previously enacted state laws and the pedigree requirements of the Prescription Drug Marketing Act (“PDMA”). Trading partners within the drug supply chain must ensure certain product tracing requirements are met, and are required to exchange transaction information, transaction history, and transaction statements. Product identifier information (an aspect of the product tracing scheme) is also required. The DSCSA requirements, development of standards, and the system for product tracing were phased in over a period of years through 2023. In addition to new legislation, FDA regulations, guidance documents, and policies are often revised or reinterpreted by the agency in ways that may significantly affect our business and our product candidates.

Orphan Drug Act

We have received Orphan Drug designation for Iomab-B and Actimab-A for patients with AML. Under the Orphan Drug Act, FDA may grant Orphan Drug designation to drugs intended to treat a rare disease or condition, which is generally defined as a disease or condition that affects fewer than 200,000 individuals in the U.S. Orphan Drug designation must be requested before submitting a BLA. In the U.S., Orphan Drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages, and user-fee waivers. Orphan Drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. The first BLA applicant to receive FDA approval for a particular active ingredient to treat a particular disease with FDA Orphan Drug designation is entitled to a seven-year exclusive marketing period in the U.S. for that product, for that indication. During the seven-year exclusivity period, FDA may not approve any other applications to market the same drug for the same orphan indication, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or where the manufacturer of the approved product cannot assure sufficient quantities. As a result, there can be no assurance that our competitors will not receive approval of drugs or biologics that have a different active ingredient for treatment of the diseases for which our products and product candidates are targeted.

Pediatric Information

Under the Pediatric Research Equity Act (“PREA”), certain BLAs must contain data to assess the safety and efficacy of the drug or biologic for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The Food and Drug Administration Safety and Innovation Act (“FDASIA”), amended the FDCA to require that a sponsor who is planning to submit a marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study Plan (“PSP”) within 60 days of an end of Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 study. The initial PSP must include an outline of the pediatric study or studies that the sponsor plans to conduct or a justification for not including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver. The FDA may grant deferrals for submission of pediatric data or full or partial waivers. A sponsor can submit amendments to an initial PSP if changes to the pediatric plan need to be considered based on preclinical data collected, early phase clinical trials as well as other clinical development programs.

Foreign Regulation

In addition to regulations in the U.S., we are subject to foreign regulations governing clinical trials and commercial sales and distribution of our product candidates, and products being marketed outside of the U.S. We must obtain approval by the comparable regulatory authorities of foreign countries before we can commence clinical trials or marketing of our products in those countries. The approval process varies from country to country, and the time may be longer or shorter than required by the FDA for BLA licensure. The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. As in the U.S., we are subject to post-approval regulatory requirements.

Other Regulatory Considerations

We are also subject to regulation under the Occupational Safety and Health Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, The Clean Air Act, and other current and potential future federal, state, or local regulations. Our research and development activities involve the controlled use of hazardous materials, chemicals, biological materials and various radioactive compounds. We believe that our procedures comply with the standards prescribed by state and federal regulations; however, the risk of injury or accidental contamination cannot be completely eliminated. We may also be subject to healthcare regulation and enforcement by the federal government and the states and foreign governments where we may market our products and product candidates, if approved. These laws and regulations include, without limitation, state and federal anti-kickback, fraud and abuse, false claims, data privacy and security, aggregate spend reporting, and product price advertising.

The federal Anti-Kickback Statute (“AKS), which prohibits, among other things, persons and entities including pharmaceutical manufacturers from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, overtly or covertly, in case or in kind, to induce or reward, or in return for, or either the referral of an individual for, or the purchase, lease or order or recommendation of an item or service reimbursable, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs. The failure to meet all of the requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se illegal under the AKS. Instead, the legality of the arrangement will be evaluated on a case-by-case basis based on a cumulative review of all of its facts and circumstances.

In addition, Patient Protection and Affordable Care Act of 2010, as amended (“ACA”) codified as law that a claim including items or services resulting from a violation of the AKS constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act (“FCA”). The FCA prohibits individuals or entities from, among other things, knowingly presenting or causing the presentation of a claims for payment to, or approval by, the federal government that are false, fictitious or fraudulent, or knowingly making, using or causing to be made or used, a false record or statement material to a false or fraudulent claim to avoid, decrease or conceal an obligation to pay money to the federal government. Our activities relating to the reporting of wholesaler or estimated retail prices for products we may commercialize in the future, the reporting of prices used to calculate Medicaid rebate information and other information affecting federal, state and third-party reimbursement for products we may commercialize in the future, and the sale and marketing of products we may commercialize in the future, will be subject to scrutiny under the FCA. State statutes and regulations equivalent or substantially similar to the federal laws may extend to items and services reimbursed by commercial insurers and/or by patients directly. State law equivalents to the AKS and FCA may not have adopted exceptions and safe harbors available at the federal level and therefore, may implicate a broader range of activities.

The Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) imposes criminal and civil liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud or obtain, by any means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors, and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services. The federal physician payment transparency requirements, sometimes referred to as the “Sunshine Act,” created under the ACA, and its implementing regulations, which requires applicable manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the State Children’s Health Insurance Program (with certain exceptions) to annually report to the Department of Health and Human Services (“HHS”), information related to certain payments or other transfers of value made or distributed to physicians and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. Under recent legislation, the Sunshine Act will extend to payments and transfers of value to physician assistants, nurse practitioners, and other mid-level healthcare providers. The Centers for Medicare and Medicaid Services (“CMS”) has the potential to impose penalties for violations of the Sunshine Act, depending on the circumstances, and payments reported under the Sunshine Act also have the potential to draw scrutiny on payments to and relationships with physicians and teaching hospitals, which may have implications under the AKS and other healthcare laws.

We may also be subject to data privacy and security regulation by both the federal government and the state governments in which we conduct our business. HIPAA, as amended by the Health Information Technology and Clinical Health Act of 2009 (“HITECH”) and their respective implementing regulations, imposes, among other things, obligations, including mandatory contractual terms with respect to safeguarding the privacy, security and transmission of individually identifiable health information held by certain healthcare providers, health plans and healthcare clearinghouses, known as covered entities, and business associates. The HHS Office of Civil Rights (“OCR”) has increased its focus on compliance and continues to train state attorneys general for enforcement purposes. Even where HIPAA does not apply, according to the U.S. Federal Trade Commission (“FTC”), failing to take appropriate steps to keep consumers’ personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act (“FTCA”), 15 U.S. Code §45(a). Medical data is considered sensitive data that merits stronger safeguards. There are numerous other laws and legislative and regulatory initiatives at the federal and state levels addressing privacy and security concerns, and some state privacy laws apply in broader circumstances than HIPAA.

We are subject to the U.S. Foreign Corrupt Practices Act (“FCPA”), which prohibits corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working in an official capacity. Our present and future business has been and will continue to be subject to various other laws and regulations.