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
Actinium Pharmaceuticals (NYSE: ATNM) presented data at the AACR Annual Meeting showcasing Actimab-A's mutation agnostic antileukemic effects in AML treatment. The preclinical studies demonstrated significant efficacy when combining Actimab-A with standard AML therapies against multiple mutations (FLT3, NPM1, KMT2A, and TP53).
Actimab-A, the only CD33-targeted radiotherapy using Actinium-225 isotope for AML treatment, showed enhanced tumor growth inhibition and prolonged survival when combined with various therapies including menin inhibitor revumenib, FLT3 inhibitor gilteritinib, and hypomethylating agent azacitidine.
The company is advancing multiple clinical trials, including a Phase 2/3 trial combining Actimab-A with CLAG-M in relapsed/refractory AML and another study with Venetoclax and ASTX-727 in frontline AML under an NCI CRADA. The addressable market spans over 100,000 patients in the U.S. and EU5.
Actinium Pharmaceuticals (NYSE: ATNM) ha presentato dati al Congresso Annuale AACR che evidenziano gli effetti antileucemici di Actimab-A, indipendenti dalla mutazione, nel trattamento della LMA. Gli studi preclinici hanno dimostrato un'efficacia significativa combinando Actimab-A con le terapie standard per la LMA contro diverse mutazioni (FLT3, NPM1, KMT2A e TP53).
Actimab-A, l'unica radioterapia mirata al CD33 che utilizza l'isotopo Actinio-225 per il trattamento della LMA, ha mostrato un aumento dell'inibizione della crescita tumorale e una sopravvivenza prolungata se combinata con diverse terapie, tra cui l'inibitore di menina revumenib, l'inibitore FLT3 gilteritinib e l'agente ipometilante azacitidina.
L'azienda sta portando avanti diversi studi clinici, tra cui una sperimentazione di Fase 2/3 che combina Actimab-A con CLAG-M nella LMA recidivante/refrattaria e un altro studio con Venetoclax e ASTX-727 nella LMA di prima linea nell'ambito di un accordo NCI CRADA. Il mercato potenziale riguarda oltre 100.000 pazienti negli Stati Uniti e nei cinque principali paesi europei (EU5).
Actinium Pharmaceuticals (NYSE: ATNM) presentó datos en la Reunión Anual de AACR que muestran los efectos antileucémicos de Actimab-A, independientes de la mutación, en el tratamiento de la LMA. Los estudios preclínicos demostraron una eficacia significativa al combinar Actimab-A con las terapias estándar para LMA contra múltiples mutaciones (FLT3, NPM1, KMT2A y TP53).
Actimab-A, la única radioterapia dirigida a CD33 que utiliza el isótopo Actinio-225 para el tratamiento de la LMA, mostró una mayor inhibición del crecimiento tumoral y una supervivencia prolongada cuando se combinó con diversas terapias, incluyendo el inhibidor de menina revumenib, el inhibidor FLT3 gilteritinib y el agente hipometilante azacitidina.
La compañía está avanzando en múltiples ensayos clínicos, incluyendo un ensayo de Fase 2/3 que combina Actimab-A con CLAG-M en LMA en recaída/refractaria y otro estudio con Venetoclax y ASTX-727 en LMA de primera línea bajo un acuerdo NCI CRADA. El mercado potencial abarca más de 100,000 pacientes en EE. UU. y los cinco principales países de la UE (EU5).
Actinium Pharmaceuticals (NYSE: ATNM)는 AACR 연례회의에서 Actimab-A가 AML 치료에서 돌연변이에 관계없이 항백혈병 효과를 나타낸다는 데이터를 발표했습니다. 전임상 연구에서는 Actimab-A를 표준 AML 치료제와 병용했을 때 FLT3, NPM1, KMT2A, TP53 등 다양한 돌연변이에 대해 유의미한 효능을 보였습니다.
Actimab-A는 AML 치료를 위해 Actinium-225 동위원소를 사용하는 유일한 CD33 표적 방사선 치료제로, menin 억제제 revumenib, FLT3 억제제 gilteritinib, 저메틸화제 azacitidine 등 여러 치료제와 병용 시 종양 성장 억제 효과가 향상되고 생존 기간이 연장되었습니다.
회사는 재발/불응성 AML에서 Actimab-A와 CLAG-M을 병용하는 2/3상 임상시험과 NCI CRADA 하에 1차 AML에서 Venetoclax 및 ASTX-727과의 연구 등 여러 임상시험을 진행 중입니다. 대상 시장은 미국과 EU5 국가에서 10만 명이 넘는 환자에 달합니다.
Actinium Pharmaceuticals (NYSE : ATNM) a présenté des données lors de la réunion annuelle de l’AACR mettant en avant les effets antileucémiques mutation-agnostiques d’Actimab-A dans le traitement de la LMA. Les études précliniques ont démontré une efficacité significative en combinant Actimab-A avec les thérapies standards de la LMA contre plusieurs mutations (FLT3, NPM1, KMT2A et TP53).
Actimab-A, la seule radiothérapie ciblant CD33 utilisant l’isotope Actinium-225 pour le traitement de la LMA, a montré une inhibition accrue de la croissance tumorale et une survie prolongée lorsqu’elle est associée à diverses thérapies, notamment l’inhibiteur de menine revumenib, l’inhibiteur FLT3 gilteritinib et l’agent hypométhylant azacitidine.
L’entreprise fait progresser plusieurs essais cliniques, dont un essai de phase 2/3 combinant Actimab-A avec CLAG-M dans la LMA en rechute/réfractaire, ainsi qu’une autre étude avec Venetoclax et ASTX-727 dans la LMA de première ligne sous un accord NCI CRADA. Le marché adressable concerne plus de 100 000 patients aux États-Unis et dans les cinq principaux pays de l’UE (EU5).
Actinium Pharmaceuticals (NYSE: ATNM) präsentierte auf dem AACR-Jahrestreffen Daten, die die mutationsunabhängigen antileukämischen Wirkungen von Actimab-A bei der Behandlung von AML zeigen. Die präklinischen Studien zeigten eine signifikante Wirksamkeit bei der Kombination von Actimab-A mit Standardtherapien gegen AML bei verschiedenen Mutationen (FLT3, NPM1, KMT2A und TP53).
Actimab-A, die einzige CD33-gerichtete Strahlentherapie mit dem Isotop Actinium-225 zur AML-Behandlung, zeigte eine verstärkte Tumorwachstumshemmung und verlängertes Überleben in Kombination mit verschiedenen Therapien, darunter der Menin-Inhibitor Revumenib, der FLT3-Inhibitor Gilteritinib und der hypomethylierende Wirkstoff Azacitidin.
Das Unternehmen führt mehrere klinische Studien durch, darunter eine Phase-2/3-Studie, die Actimab-A mit CLAG-M bei rezidivierender/refraktärer AML kombiniert, sowie eine weitere Studie mit Venetoclax und ASTX-727 bei Erstlinientherapie von AML im Rahmen eines NCI-CRADA. Der adressierbare Markt umfasst über 100.000 Patienten in den USA und den fünf größten EU-Ländern (EU5).
- Demonstrated significant antileukemic activity against multiple mutations in AML
- Enhanced tumor growth inhibition and prolonged survival in combination studies
- Large addressable market of over 100,000 patients in U.S. and EU5
- Multiple advanced-stage clinical trials in progress
- Results are primarily from preclinical studies, requiring further clinical validation
- Clinical outcomes pending from ongoing trials
Insights
Actimab-A shows preclinical efficacy against multiple AML mutations, positioning it as a potential combination backbone therapy.
The preclinical data presented at AACR demonstrates that Actimab-A exhibits mutation-agnostic antileukemic activity against several challenging AML mutations (FLT3, NPM1, KMT2A and TP53). This is particularly significant as these mutations represent difficult-to-treat subsets of AML with historically poor outcomes.
The mechanistic rationale is compelling - Actimab-A delivers Actinium-225, a potent alpha-emitting radioisotope that produces lethal double-strand DNA breaks in CD33-expressing leukemic cells. This mechanism of action differs fundamentally from conventional therapies and may explain its activity across multiple mutation profiles.
The synergy observed when combining Actimab-A with standard therapies (menin inhibitors, FLT3 inhibitors, and hypomethylating agents) suggests potential for enhanced efficacy without overlapping resistance mechanisms. The data showed Actimab-A significantly enhanced tumor growth inhibition and prolonged survival in animal models when combined with these agents.
The company reports that Actimab-A has previously demonstrated clinical activity in high-risk populations including those with TP53 mutations, prior Venetoclax treatment, and prior bone marrow transplant - patient groups with significant unmet needs.
The advancement to Phase 2/3 trials in relapsed/refractory AML with CLAG-M and in newly diagnosed patients with Venetoclax and ASTX-727 represents important next steps in clinical development, though these studies' outcomes will ultimately determine Actimab-A's therapeutic value.
Actinium's preclinical data strengthens scientific rationale for Actimab-A across multiple AML subtypes, supporting ongoing clinical trials.
Actinium's preclinical data package for Actimab-A provides additional scientific validation for their ongoing clinical development strategy. The CD33-targeted radiotherapy's activity across multiple mutation types suggests potential versatility in a disease characterized by genetic heterogeneity.
The combination approach being pursued aligns with evolving treatment paradigms in AML, where targeted combinations have generally shown greater promise than monotherapies. Demonstrating synergy with FLT3 inhibitors, menin inhibitors, and hypomethylating agents positions Actimab-A as a potential backbone therapy that could complement existing treatment modalities.
The company estimates an addressable market of over 100,000 patients across AML and myelodysplastic syndromes in the U.S. and EU5, representing a substantial commercial opportunity if clinical development succeeds.
The multiple parallel clinical trials underway show commitment to the program, with the Phase 2/3 trial in relapsed/refractory AML in combination with CLAG-M representing the most advanced development stage. The collaboration with the National Cancer Institute for the frontline trial with Venetoclax and ASTX-727 provides additional validation.
For Actinium Pharmaceuticals, with its current market cap of approximately $38 million, positive clinical outcomes from these trials could significantly impact company valuation. The company expects to generate clinical outcomes starting in the second half of this year, which will provide more definitive evidence of Actimab-A's potential in addressing the unmet needs in AML treatment.
- Actimab-A significantly potentiated and prolonged efficacy in combination with standard of care targeted therapies including hypomethylating agent azacitidine, FLT3 and menin inhibitors in in-vivo AML models
- Actimab-A is the only CD33 targeted radiotherapy with Actinium-225 isotope payload in development for AML and other myeloid malignancies
- Actimab-A is currently being advanced in several combination studies including a Phase 2/3 trial in combination with CLAG-M in relapsed/refractory AML and in combination with Venetoclax and ASTX-727, an oral hypomethylating agent from Taiho Oncology in frontline AML under a CRADA with the NCI
Sandesh Seth, Actinium's Chairman and CEO, said, "In multiple clinical trials, Actimab-A has demonstrated potent single agent activity, synergy with other therapeutic modalities and efficacy in patients with high-risk features such as a TP53 mutation. To our knowledge, Actimab-A is the only AML therapy to achieve all of these outcomes, which we attribute to its mutation agnostic, backbone therapy profile. The data presented at AACR further support Actimab-A's mutation agnostic mechanism of action across several of the most commonly expressed mutations and synergy with the targeted therapies approved for patients with these mutations. With multiple clinical trials underway and being planned across the AML treatment settings, we are focused on generating strong clinical outcomes starting in the second half of this year and committed to realizing Actimab-A's potential for patients who have significant unmet needs."
Actimab-A is Actinium's lead radiotherapy that delivers Actinium-225, a potent alpha-emitter radioisotope payload that can produce lethal double strand DNA breaks to kill targeted cells that express CD33. CD33 is expressed ubiquitously in AML and in other myeloid malignancies such as myeloid dysplastic syndromes (MDS), which Actinium estimates to be an addressable market of over 100,000 patients in the
The Actimab-A AACR presentation is available for viewing on the Presentations& Webinars page of Actinium's website HERE.
Title: Actimab-A (Lintuzumab-Ac-225) has potent mutation agnostic antileukemic activity in preclinical models of AML
Abstract Number: 594
About Actinium Pharmaceuticals, Inc.
Actinium is a pioneer in the development of targeted radiotherapies intended to meaningfully improve patient outcomes. Actinium is advancing its lead product candidate Actimab-A, a CD33 targeting therapeutic, as potential backbone therapy in acute myeloid leukemia (AML) and other myeloid malignancies leveraging the mutation agnostic alpha-emitter radioisotope payload Actinium-225 (Ac-225). Actimab-A has demonstrated potential activity in relapsed and refractory acute myeloid leukemia (r/r AML) patients in combination with the chemotherapy CLAG-M including high rates of Complete Remissions (CR) and measurable residual disease (MRD) negativity leading to improved survival outcomes and is being advanced to a pivotal Phase 2/3 trial. In addition, Actinium is engaged with the National Cancer Institute (NCI) under the Cooperative Research and Development Agreement (CRADA) for development of Actimab-A in AML and other myeloid malignancies. The first clinical trial under the CRADA will evaluate the triplet combination comprised of Actimab-A, Venetoclax (Abbvie/Roche) an oral Bcl-2 inhibitor and ASTX-727 (Taiho Oncology, an Otsuka holdings company) a novel oral hypomethylating agent (HMA) in frontline acute myeloid leukemia (AML) patients. Additionally, Actinium is developing Actimab-A as a potential pan tumor therapy in combination with PD-1 checkpoint inhibitors including KEYTRUDA® and OPDIVO® by depleting myeloid derived suppressor cells (MDSCs), which represents a potential multi-billion-dollar addressable market. ATNM-400 is Actinium's novel non-PSMA targeting Ac-225 radiotherapy for prostate cancer, which is supported by preclinical data demonstrating higher efficacy than Pluvicto (PSMA-617-Lutetium-177) and potent efficacy in Pluvicto resistant prostate cancer models. Iomab-ACT, Actinium's next generation conditioning candidate, is being developed with the goal of improving patient access and outcomes for potentially curative cell and gene therapies. Iomab-B is an induction and conditioning agent prior to bone marrow transplant in patients with r/r AML, which Actinium is seeking a potential strategic partner for the
For more information, please visit: https://www.actiniumpharma.com/
Forward-Looking Statements
This press release may contain projections or other "forward-looking statements" within the meaning of the "safe-harbor" provisions of the private securities litigation reform act of 1995 regarding future events or the future financial performance of the Company which the Company undertakes no obligation to update. These statements are based on management's current expectations and are subject to risks and uncertainties that may cause actual results to differ materially from the anticipated or estimated future results, including the risks and uncertainties associated with preliminary study results varying from final results, estimates of potential markets for drugs under development, clinical trials, actions by the FDA and other governmental agencies, regulatory clearances, responses to regulatory matters, the market demand for and acceptance of Actinium's products and services, performance of clinical research organizations and other risks detailed from time to time in Actinium's filings with the Securities and Exchange Commission (the "SEC"), including without limitation its most recent annual report on form 10-K, subsequent quarterly reports on Forms 10-Q and Forms 8-K, each as amended and supplemented from time to time.
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