Actimab-A (lintuzumab-Ac225) / Actinium Pharmaceuticals - LARVOL DELTA

Lintuzumab-Ac225 with Combination with Intensive Chemotherapy Yields High Response Rate and MRD Negativity in R/R AML with Adverse Features (ASH 2022) - "Induction consisted of G-CSF, 300mcg/d, given D1-6, cladribine 5mg/m2, given D2-6, cytarabine 2g/m2, given D2-6, and mitoxantrone 10mg/m2, given D2-4. Actimab-A at 0.75uCi/kg, combined with CLAG-M is feasible and safe, and this combination demonstrates a high response rate and MRD negativity in a high-risk AML population. Pharmacokinetics at the RP2D indicate rapid drug clearance. Furthermore, responses appear durable, particularly among patients who are able to proceed to alloHCT."

Minimal residual disease • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Infectious Disease • Mucositis • Neutropenia • CD33 • CSF3 • MCL1 • TP53

Phase 1 study of lintuzumab-Ac225 combined with CLAG-M salvage therapy in relapsed/refractory acute myeloid leukemia. (PubMed, Leukemia) - "The composite complete remission (CRc) rates (CR/CRi) were 56.6% overall, 50% in patients with mutated TP53, and 38.5% in prior venetoclax-treated patients. Among all patients (n = 26), estimated 2-year OS was 23.1% (95% CI, 9.4-40.3) and estimated 1-year PFS was 30.8% (95% CI, 14.6-48.5). Lintuzumab-Ac225 plus CLAG-M was well tolerated with expected, manageable toxicities, while yielding deep and meaningful responses in high-risk R/R AML patients."

Journal • P1 data • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • TP53

Actimab-A treatment of low peripheral blast AML (PRNewswire) - "Actinium Pharmaceuticals announces Actimab-A Intellectual Property....US 12,410,249 issued, with a term to 12 October 2039, and Canadian application 3,022,802 entered pre-grant status, with a term to 25 May 2037. Additional patents in this family have already issued in the United States and Japan; applications remain pending in the United States and Europe."

Patent • Acute Myelogenous Leukemia

Actimab-A venetoclax (BCL-2 inhibitor) combination therapy for the treatment of AML (PRNewswire) - "Actinium Pharmaceuticals announces Actimab-A Intellectual Property....Canadian application 3,059,752 entered pre-grant status, with a term to 26 April 2038, covering the use of Actimab-A together with venetoclax in AML. Three patents have already issued in the United States and one in Mexico; applications remain pending in the United States, Europe, Japan and China."

Patent • Acute Myelogenous Leukemia

Actinium Pharmaceuticals Announces…Manufacturing Advances… (PRNewswire) - "Actinium has amended its Investigational New Drug (IND) application to add an additional manufacturer. The additional manufacturer will supply studies conducted under the Company's Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI), together with additional Company-sponsored studies, which carry clinical milestones expected from the second half of 2026 and throughout 2027. Establishing an additional manufacturing source is intended to expand capacity and supply flexibility as Actimab-A advances into a broader set of studies across hematologic malignancies and solid tumors."

Commercial • Hematological Malignancies • Solid Tumor

Actimab-A targeting of myeloid-derived suppressor cells (MDSCs) for the treatment of solid tumors (PRNewswire) - "Actinium Pharmaceuticals Announces Actimab-A Intellectual Property....Two United States patents issued - US 12,491,274 for the treatment of sarcoma, expiring 15 October 2043, and US 12,539,340 for the treatment of solid tumors generally, alone or with checkpoint therapy, expiring 31 October 2043. Together they extend the anti-CD33 franchise beyond hematologic malignancy into solid tumors by targeting the immunosuppressive myeloid cells of the tumor microenvironment rather than the tumor cells themselves. Applications remain pending in the United States, Canada and Europe."

Patent • Sarcoma • Solid Tumor

Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment (clinicaltrials.gov) - P1 | N=18 | Suspended | Sponsor: National Cancer Institute (NCI) | N=30 ➔ 18

Enrollment change • Monotherapy • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • CD33

Testing the Combination of Anti-cancer Drugs Actimab-A and Cemiplimab (REGN2810) to Improve Outcomes for Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jun 2026 ➔ Dec 2026

IO biomarker • Trial initiation date • Tumor mutational burden • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor • CTLA4 • IDH1 • IDH2 • MGMT • PD-L1

Actinium Pharmaceuticals… announced that the Canadian Intellectual Property Office (CIPO) has issued Notices of Allowance for two patent applications spanning the Company's Actimab-A and Iomab-ACT programs (PRNewswire) - "The allowed application covers the use of Actimab-A in combination with the CLAG-M chemotherapy regimen for the treatment of AML....The Canadian patent issuing from Application No. 3,087,346 titled 'Combination Immunotherapy and Chemotherapy for the Treatment of a Hematological Malignancy' will have a patent term running into January 2039....The allowed application covers Actinium's targeted CD45 conditioning approach used to prepare patients for gene-edited cell-based therapies....The Canadian patent issuing from Application No. 3,078,963 titled 'Anti-CD45-Based Conditioning Methods and Uses Thereof in Conjunction with Gene-Edited Cell-Based Therapies' will have a patent term running into October 2038."

Patent • Acute Myelogenous Leukemia

Actimab-A, a CD33-targeted actinium-225 radioconjugate, drives mutation-agnostic anti-leukemic activity and synergizes with standard therapies in AML through transcriptional reprogramming (AACR 2026) - "Clinical studies have shown encouraging responses when combined with CLAG-M chemotherapy in relapsed/refractory AML, including in patients with TP53 mutations or venetoclax resistance...To explore mechanisms of synergy, AML cell lines harboring common mutations (FLT3, KMT2Ar: MV-4-11, MOLM-13 cells, NPM1c: OCI-AML3, and mutant TP53: Kasumi-1, HL-60 cells) were treated for 24 hours with standard-of-care (SOC) therapies: FLT3 inhibitors (gilteritinib, quizartinib), menin inhibitors (revumenib, ziftomenib) or azacitidine alone or in combination with lintuzumab-Ac225... Lintuzumab-Ac225 shows broad mutation-independent anti-leukemic activity in AML cell lines and primary AML patient samples. When combined with standard therapies, it drives complementary transcriptional programs that enhance depth and durability of response. Together, these findings support the clinical evaluation of lintuzumab-Ac225-based combinations as a strategy to overcome resistance and enhance..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • FLT3 • KMT2A • MYC • NPM1

Key Data and Highlights of the Actimab-A AACR Presentation (PRNewswire) - "Transcriptional Reprogramming as a Key Mechanism for Actimab-A Combination Activity...Combination treatment produced consistent pathway-level changes compared with monotherapy. Gene set enrichment analyses (GSEA) showed enhanced myeloid differentiation signatures with the addition of Actimab-A (lintuzumab-Ac225) to revumenib, gilteritinib, and azacitidine; Broad Activity of Actimab-A as Monotherapy and in Combination in Primary AML Patient Samples...Actimab-A (LinT-Ac225) showed robust cytotoxicity in primary AML patient samples, independent of FLT3, KMT2A, NPM1, IDH1, IDH2, or TP53 mutation status, positioning Actimab-A to treat the full AML population, including TP53-mutant patients who lack effective targeted options, and to serve as a universal combination partner rather than a mutation-restricted therapy."

Clinical data • Acute Myelogenous Leukemia

Actinium Pharmaceuticals Announces New Pan-Tumor Preclinical Data for ATNM-400 in Solid Tumors and Differentiated Mechanism for Actimab-A in AML to be Presented at 2026 AACR Annual Meeting (PRNewswire) - "New data underscoring the potential of ATNM-400 as a first-in-class Ac-225 radioconjugate with broad pan-tumor efficacy across multiple solid tumor models. Actimab-A demonstrates mutation-agnostic efficacy and a novel mechanism that enhances response to standard AML therapies. Multiple data catalysts for ATNM-400 and Actimab-A in 2026; and posters for each to be presented on April 21, 2026 at AACR 2026 in San Diego, CA."

Preclinical • Acute Myelogenous Leukemia • Solid Tumor

Lintuzumab-Ac225 has potent mutation agnostic antileukemic activity in preclinical models of AML (AACR 2025) - "In clinical trials, lintuzumab-Ac225 had positive responses when combined with CLAG-M chemotherapy in relapsed/refractory AML patients, including those with high-risk features like venetoclax resistance and TP53 mutations...FLT3 inhibitors (gilteritinib, quizartinib), KMT2A inhibitors (revumenib, ziftomenib) and azacitidine were evaluated as single agents and in combination with Lintuzumab-Ac225... Lintuzumab-Ac225 shows broad anti-leukemic activity in AML cell lines, in a mutation (FLT3, KMT2A, NPM1, TP53) agnostic manner. It improves AML control in high-risk cases and enhances response durability when combined with standard of care treatments. These findings support its potential as a backbone therapy for relapsed/refractory AML, warranting further clinical evaluation."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CDKN1A • FLT3 • KMT2A • NPM1 • TP53

Testing the Combination of Anti-cancer Drugs Actimab-A and Cemiplimab (REGN2810) to Improve Outcomes for Patients With Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

IO biomarker • New P1 trial • Tumor mutational burden • Brain Cancer • Glioblastoma • Glioma • Gliosarcoma • Oncology • Sarcoma • Solid Tumor • CTLA4 • IDH1 • IDH2 • MGMT • PD-L1

Actinium Pharmaceuticals, Inc. to Present Two Abstracts at the 2026 AACR Annual Meeting (PRNewswire) - "AACR Presentations to Feature ATNM-400 and Actimab-A Programs Across Solid Tumors and Hematologic Oncology Applications....The AACR 2026 data will highlight Actinium's differentiated biology-driven approach to targeted radiotherapy development including: Targeting resistance-associated biology rather than tumor surface expression alone; Leveraging the high-linear energy transfer (LET) of Ac-225 to deliver potent, tumor-specific cytotoxicity; Building a radiotherapy franchise comprised of multiple pan-tumor assets."

Clinical • Preclinical • Acute Myelogenous Leukemia • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Triple Negative Breast Cancer

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=53 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Trial suspension • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Updated Results from Phase 1 Study of Targeted Radiotherapy with Lintuzumab-Ac225 in Combination with Venetoclax in Relapsed/Refractory AML (ASH 2023) - "The combination of lintuzumab-Ac225 and venetoclax had a manageable safety profile and no early mortality at day 30. The MTD was not reached and no significant toxicities have been reported during the follow-up period. Modified dosing schedule in Cohort 4 of the combination demonstrated improved anti-leukemic effects."

Combination therapy • IO biomarker • P1 data • Acute Myelogenous Leukemia • Cardiovascular • Heart Failure • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Thrombocytopenia • BCL2L1 • CD33

Outcome of Patients with TP53 Mutated Relapsed/Refractory AML with Lintuzumab-Ac225 in Combination with CLAG-M Following Venetoclax Plus Hypomethylating Agent Therapy (ASH 2024) - "Among these patients who were fit for intensive therapy, our data indicated that CLAG-M followed by Lintuzumab-Ac225 had a tolerable safety profile and yielded high responses with high MRD negativity translating to improved overall survival including in patients with TP53 mutated AML. Given these promising results in a historically challenging patient population, these results support a larger clinical study investigating CLAG-M followed by Lintuzumab-Ac225."

Clinical • Combination therapy • IO biomarker • Acute Myelogenous Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • CD33 • MCL1 • TP53

Lintuzumab-Ac225, a CD33-Directed Antibody Radiotherapy, Targets AML in a Mutation Agnostic Manner (ASH 2023) - "Actimab-A, an anti-CD33 antibody conjugated with Actinium-225 (Ac-225) alpha particle-emitting radionuclide (lintuzumab-Ac225), has demonstrated promising therapeutic responses in AML patients, including in combination trials with chemotherapy regimen CLAG-M and targeted therapy venetoclax...Single agent cytotoxicity of Gilteritinib or Revumenib was also observed, but the combination of lintuzumab-Ac225 with FLT3 or MLL inhibitors was additive and synergistic at all dose levels studied...Combination of CD33-targeted radiation with either FLT3 or menin inhibitors significantly improves AML control, suggesting how FLT3 and/or menin efficacy may be augmented by radiation-induced DNA damage. The combination of lintuzumab-Ac225 to existing mutation-targeted standard-of-care may enhance AML targeting and treatment durability versus single-agent approaches."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • FLT3 • KMT2A

Lintuzumab-Ac225 Exerts Mutation Agnostic Antileukemic Activity in Preclinical Models of AML (ASH 2024) - "In clinical trials, lintuzumab-Ac225 has demonstrated promising therapeutic responses when added to CLAG-M chemotherapy in heavily pretreated relapsed/refractory AML patients, including high risk populations with venetoclax failures and TP53 mutations...Although the single agent cytotoxicity of FLT3 inhibitors (gilteritinib, quizartinib) and KMT2A inhibitors (revumenib, ziftomenib) was observed with varied sensitivity in both MV-4-11 and MOLM-13 FLT3/KMT2A mutation-carrying cells, the combinations with lintuzumab-Ac225 were additive at all studied dose levels (p<0.01)...CD33-targeted radiation-induced damage improves AML control in adverse-risk settings, and further potentiates response durability when added to standard-of-care, including molecularly targeted therapy. Collectively, these data support the backbone therapy potential of lintuzumab-Ac225 in a mutation agnostic manner, warranting further clinical evaluation in difficult to treat relapsed/refractory AML."

Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CD33 • CDKN1A • FLT3 • IDH1 • IDH2 • KMT2A • NPM1 • TP53

Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment (clinicaltrials.gov) - P1 | N=30 | Suspended | Sponsor: National Cancer Institute (NCI) | Recruiting ➔ Suspended

Monotherapy • Trial suspension • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Testing the Combination of Targeted Radiotherapy With Anti-Cancer Drugs, Venetoclax and ASTX-727, to Improve Outcomes for Adults With Newly Diagnosed Acute Myeloid Leukemia (clinicaltrials.gov) - P1 | N=53 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2025 ➔ Dec 2028 | Initiation date: Jul 2025 ➔ Apr 2026 | Trial primary completion date: Sep 2025 ➔ Dec 2028

Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

Testing an Anti-cancer Radio-Active Immunotherapy Called Lintuzumab Ac225 in Patients With High-Risk Myelodysplastic Syndrome That Has Not Responded to Other Treatment (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jul 2025 ➔ Apr 2026 | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Trial initiation date • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

Actinium Highlights Mutation Agnostic Antileukemic Activity of Actimab-A Against FLT3, NPM1, KMT2A and TP53 Mutations in AML Models Demonstrating Backbone Potential for Acute Myeloid Leukemia Treatment at the American Association for Cancer Research Annual Meeting (PRNewswire) - "The preclinical data demonstrate that the combination of Actimab-A with standard of care AML therapies including menin and FLT3 inhibitors and the hypomethylating agent (HMA) azacitidine resulted in significant antileukemic activity in AML cells lines with FLT3, NPM1, KMT2A and TP53 mutations. Additionally, in animal models, Actimab-A significantly enhanced tumor growth inhibition, prolonged the duration of response and survival when combined with the menin inhibitor revumenib (Syndax Pharmaceuticals, Inc.), and potentiated AML cell killing in combination with the FLT3 inhibitor gilteritinib (Astellas Pharma US, Inc.) and HMA azacitidine."

P53mut • Preclinical • Acute Myelogenous Leukemia

Actinium outlined its 2025 business objectives for its revitalized and expanding clinical pipeline as follows (PRNewswire) - "Establish In-house Radiopharmaceutical Manufacturing & Production: Advance build-out of manufacturing facility; Explore strategic partnerships leveraging proprietary Actinium-225 cyclotron manufacturing technology...Actimab-A as a mutation agnostic...Initiate additional clinical trials in myeloid malignancies....Actimab-A as a pan solid tumor therapy in combination with PD-1 inhibitors including KEYTRUDA and OPDIVO by depleting myeloid derived suppressor cells (MDSCs)...Explore additional solid tumor indications for future trials."

Commercial • New trial • Hematological Malignancies • Solid Tumor