Actinium Presents Data Showing ATNM-400 is More Efficacious than Pluvicto and is Highly Efficacious after Pluvicto Resistance in Prostate Cancer Tumor Models at the American Association for Cancer Research Annual Meeting
Actinium Pharmaceuticals (NYSE: ATNM) has presented promising preclinical results for ATNM-400, a novel targeted radiotherapy for prostate cancer, at the AACR Annual Meeting. The data shows ATNM-400 outperforms Pluvicto, achieving 99.8% tumor growth inhibition with a single 40 µCi/kg dose.
Unlike Pluvicto and most prostate cancer radiotherapies that target PSMA, ATNM-400 is a first-in-class treatment targeting a distinct non-PSMA receptor that remains highly expressed even after Pluvicto treatment. The therapy utilizes Actinium-225, a more potent alpha-particle emitter than Lutetitium-177, causing irreversible DNA breaks with potentially fewer off-target effects.
Key findings demonstrate ATNM-400's efficacy in Pluvicto-resistant tumors, rapid internalization, sustained tumor uptake, and efficient clearance from essential organs. The treatment was well-tolerated with no apparent toxicities at both tested dose levels.
Actinium Pharmaceuticals (NYSE: ATNM) ha presentato risultati preclinici promettenti per ATNM-400, una nuova radioterapia mirata per il cancro alla prostata, durante l'AACR Annual Meeting. I dati mostrano che ATNM-400 supera Pluvicto, raggiungendo un 99,8% di inibizione della crescita tumorale con una singola dose di 40 µCi/kg.
A differenza di Pluvicto e della maggior parte delle radioterapie per il cancro alla prostata che mirano al PSMA, ATNM-400 è un trattamento innovativo che prende di mira un recettore non-PSMA distinto, ancora altamente espresso anche dopo il trattamento con Pluvicto. La terapia utilizza Actinio-225, un emettitore di particelle alfa più potente del Lutetio-177, causando rotture irreversibili del DNA con potenzialmente meno effetti collaterali.
I risultati chiave dimostrano l'efficacia di ATNM-400 nei tumori resistenti a Pluvicto, una rapida internalizzazione, un assorbimento tumorale prolungato e una clearance efficiente dagli organi essenziali. Il trattamento è stato ben tollerato senza tossicità evidenti a entrambi i livelli di dose testati.
Actinium Pharmaceuticals (NYSE: ATNM) ha presentado resultados preclínicos prometedores para ATNM-400, una nueva radioterapia dirigida para el cáncer de próstata, en la Reunión Anual de AACR. Los datos muestran que ATNM-400 supera a Pluvicto, logrando una inhibición del crecimiento tumoral del 99,8% con una sola dosis de 40 µCi/kg.
A diferencia de Pluvicto y la mayoría de las radioterapias para cáncer de próstata que se dirigen al PSMA, ATNM-400 es un tratamiento innovador que apunta a un receptor no PSMA distinto, que se mantiene altamente expresado incluso después del tratamiento con Pluvicto. La terapia utiliza Actinio-225, un emisor de partículas alfa más potente que Lutecio-177, causando rupturas irreversibles del ADN con potencialmente menos efectos fuera del objetivo.
Los hallazgos clave demuestran la eficacia de ATNM-400 en tumores resistentes a Pluvicto, rápida internalización, captación tumoral sostenida y una eliminación eficiente de órganos esenciales. El tratamiento fue bien tolerado sin toxicidades aparentes en ambos niveles de dosis probados.
Actinium Pharmaceuticals (NYSE: ATNM)는 AACR 연례회의에서 전립선암을 위한 새로운 표적 방사선 치료제인 ATNM-400의 유망한 전임상 결과를 발표했습니다. 데이터에 따르면 ATNM-400은 단일 40 µCi/kg 투여로 99.8%의 종양 성장 억제 효과를 보여 Pluvicto보다 우수합니다.
Pluvicto 및 대부분의 PSMA 표적 전립선암 방사선 치료제와 달리, ATNM-400은 Pluvicto 치료 후에도 높은 발현을 유지하는 별개의 비-PSMA 수용체를 표적으로 하는 최초의 치료제입니다. 이 치료법은 Lutetium-177보다 강력한 알파 입자 방출체인 Actinium-225를 사용하여 DNA를 돌이킬 수 없게 손상시키며, 부작용은 적을 가능성이 있습니다.
주요 결과는 Pluvicto 내성 종양에서의 ATNM-400 효능, 빠른 세포 내 흡수, 지속적인 종양 흡수 및 주요 장기에서의 효율적인 배설을 입증합니다. 두 가지 투여 용량 모두에서 독성 없이 잘 견뎠습니다.
Actinium Pharmaceuticals (NYSE : ATNM) a présenté des résultats précliniques prometteurs pour ATNM-400, une nouvelle radiothérapie ciblée contre le cancer de la prostate, lors de la réunion annuelle de l'AACR. Les données montrent qu'ATNM-400 surpasse Pluvicto, atteignant une inhibition de la croissance tumorale de 99,8 % avec une seule dose de 40 µCi/kg.
Contrairement à Pluvicto et à la plupart des radiothérapies pour le cancer de la prostate ciblant le PSMA, ATNM-400 est un traitement de première classe ciblant un récepteur non-PSMA distinct, toujours fortement exprimé même après un traitement par Pluvicto. La thérapie utilise l'Actinium-225, un émetteur de particules alpha plus puissant que le Lutétium-177, provoquant des cassures irréversibles de l'ADN avec potentiellement moins d'effets hors cible.
Les résultats clés démontrent l'efficacité d'ATNM-400 sur les tumeurs résistantes à Pluvicto, une internalisation rapide, une absorption tumorale soutenue et une élimination efficace des organes essentiels. Le traitement a été bien toléré sans toxicités apparentes aux deux doses testées.
Actinium Pharmaceuticals (NYSE: ATNM) hat auf dem AACR-Jahrestreffen vielversprechende präklinische Ergebnisse für ATNM-400, eine neuartige zielgerichtete Radiotherapie gegen Prostatakrebs, vorgestellt. Die Daten zeigen, dass ATNM-400 Pluvicto übertrifft und mit einer einzigen Dosis von 40 µCi/kg eine 99,8 % Tumorwachstumshemmung erreicht.
Im Gegensatz zu Pluvicto und den meisten Prostatakrebs-Radiotherapien, die auf PSMA abzielen, ist ATNM-400 eine Erst-in-Klasse-Therapie, die einen anderen, nicht-PSMA-Rezeptor ins Visier nimmt, der auch nach Pluvicto-Behandlung stark exprimiert bleibt. Die Therapie nutzt Actinium-225, einen potenteren Alphateilchen-Emitter als Lutetium-177, der irreversible DNA-Brüche verursacht und möglicherweise weniger Nebenwirkungen hat.
Wesentliche Ergebnisse zeigen die Wirksamkeit von ATNM-400 bei Pluvicto-resistenten Tumoren, schnelle Internalisierung, anhaltende Tumoraufnahme und effiziente Ausscheidung aus wichtigen Organen. Die Behandlung wurde bei beiden getesteten Dosierungen gut vertragen, ohne erkennbare Toxizitäten.
- Achieved 99.8% tumor growth inhibition with a single dose
- Demonstrated efficacy in Pluvicto-resistant tumors
- Novel non-PSMA targeting mechanism remains effective after Pluvicto treatment
- Well-tolerated with no apparent toxicities
- Rapid clearance from essential organs with sustained tumor uptake
- Still in preclinical stage, requiring further clinical validation
- Results to animal models, human efficacy yet to be demonstrated
Insights
ATNM-400 shows promising preclinical efficacy against prostate cancer with novel non-PSMA targeting, potentially addressing Pluvicto resistance.
Actinium Pharmaceuticals' ATNM-400 represents a significant innovation in the radiotherapeutics landscape for prostate cancer. Unlike Pluvicto and most developmental radiotherapies that target PSMA, ATNM-400 targets a distinct non-PSMA receptor that crucially remains expressed after Pluvicto treatment—creating a potential solution for treatment-resistant patients.
The preclinical data is particularly compelling: 99.8% tumor growth inhibition with a single 40 µCi/kg dose and statistically significant (p < 0.0001) tumor volume reduction compared to Pluvicto in prostate cancer models. Most notably, ATNM-400 demonstrated robust antitumor activity in Pluvicto-failed tumors, addressing an emerging clinical need.
Mechanistically, ATNM-400 leverages Actinium-225's alpha-particle emission properties, which produce lethal double-stranded DNA breaks—a more potent cell-killing mechanism than Pluvicto's Lutetium-177 beta emission. The shorter path length of alpha radiation potentially offers improved safety profile through reduced off-target effects.
The biodistribution profile showing sustained tumor uptake with efficient clearance from essential organs by 48 hours is encouraging from a safety perspective. The absence of apparent toxicities in the tested models provides initial reassurance, though human studies will ultimately determine clinical safety.
For the metastatic castration-resistant prostate cancer population, these findings point to a potential therapeutic option where limited alternatives exist following Pluvicto failure.
ATNM-400's differentiated approach targets unaddressed market segment complementing Pluvicto's $1.39B market.
Actinium's ATNM-400 demonstrates strategic market positioning through its novel non-PSMA targeting approach. Rather than competing directly in the increasingly crowded PSMA-targeting radiotherapeutic space, Actinium has identified an unaddressed segment: patients who progress after Pluvicto treatment.
This positioning is commercially significant as Pluvicto generated
The preclinical efficacy data showing ATNM-400 outperforming Pluvicto in tumor growth inhibition (
From a competitive standpoint, ATNM-400's unique mechanism offers differentiation in a field dominated by PSMA-targeting agents. The continued expression of ATNM-400's target receptor following Pluvicto therapy creates a potentially durable market opportunity as patients progress through treatment lines.
The planned release of additional data later this year provides near-term catalysts for investor assessment. While commercialization remains distant pending clinical development, these preclinical results represent meaningful progress in validating ATNM-400's potential in the expanding radiotherapeutics market for prostate cancer.
- Results highlight ATNM-400's potential as a transformative therapeutic option for prostate cancer patients with unmet clinical needs as expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working
- ATNM-400 showed greater tumor growth inhibition compared to Pluvicto in prostate cancer models with
- ATNM-400 was well tolerated with no apparent toxicities at two different dose levels, with efficient clearance from essential organs
ATNM-400 is a highly innovative, first-in-class prostate cancer candidate in comparison to Pluvicto and the majority of radiotherapies in development for prostate cancer which target PSMA and are either non-differentiated or barely differentiated, as it targets a distinct non-PSMA receptor. The receptor specifically targeted by ATNM-400 is highly expressed in metastatic castration-resistant prostate cancer (mCRPC) and continues to be expressed at a high level even after Pluvicto treatment which does not appear to impact target expression levels. ATNM-400 leverages the alpha-particle emitter Ac-225, which is more potent than Lu-177, can cause lethal double-stranded irreversible DNA breaks, and has a shorter path length that could result in fewer off-target effects.
Key Data and Highlights From the ATNM-400 AACR Presentation
In vivo studies demonstrated that ATNM-400 is more efficacious than Pluvicto and produced a statistically significant (p < 0.0001) reduction in tumor volume in 22Rv1 prostate cancer models demonstrating its transformative therapeutic potential.
In mice bearing Pluvicto-failed tumors, ATNM-400 was administered on day 14 following Pluvicto treatment, demonstrating robust antitumor activity and tumor growth inhibition in Pluvicto- resistant tumor models.
- Expression of the target receptor for ATNM-400 persists following Pluvicto therapy and ATNM-400 demonstrates sustained tumor control after Pluvicto stops working
- ATNM-400 demonstrated greater efficacy than Pluvicto in prostate cancer models with
99.8% tumor growth inhibition achieved with a single 40 µCi/kg dose of ATNM-400 supporting its potential to be offered as an alternative option - ATNM-400 internalizes rapidly, exhibiting potent cytotoxicity and prostate cancer cell killing via double strand DNA breaks that are produced by the Ac-225 alpha-particle emitting radionuclide payload of ATNM-400
- Biodistribution analyses showed sustained uptake in the tumor up to the 216-hour time point, with rapid clearance from the blood by the 48-hour time point and clearance from essential organs including the kidneys, intestines and liver
- ATNM-400 was well tolerated with body weight recovery and no apparent toxicity at both doses evaluated in vivo
Sandesh Seth, Actinium's Chairman and CEO, said, "We are thrilled to unveil these exciting results demonstrating the transformative therapeutic potential of ATNM-400. There is a significant unmet need for a therapy that can address patients who are treated with Pluvicto and progress, which we only expect to increase following the recent approval of Pluvicto in the earlier line, pre-taxane setting. Consistent with our focus on leading-edge innovation, ATNM-400 is highly novel given it is a non-PSMA target receptor, which is highly expressed in mCRPC, and as we have presented at AACR, continues to be expressed following Pluvicto therapy. ATNM-400 capitalizes on the potency and precision of the Ac-225 isotope payload that can overcome resistance via lethal double strand DNA breaks. Our enthusiasm for ATNM-400 was validated by the significant interest this data received at AACR and we look forward to validating the potential of this exciting radiotherapy candidate as we advance its development with additional data expected later this year".
The ATNM-400 AACR presentation is available for viewing on the Presentations & Webinars page of Actinium's website HERE.
Title: ATNM-400 is a novel Actinium-225 antibody radioconjugate with strong efficacy in preclinical models of prostate cancer
Abstract Number: 578
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/
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FAQ
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