Actinium Pharmaceuticals Unveils ATNM-400: A Breakthrough Non-PSMA Targeted Radiotherapy for Prostate Cancer
核心洞察
Actinium Pharmaceuticals has developed ATNM-400 (搜索), a novel non-PSMA (搜索) targeting radiotherapy for prostate cancer (搜索) using Actinium-225 (搜索), achieving 99.8% tumor growth inhibition in preclinical models.
The new therapy demonstrates selective tumor accumulation for up to 144 hours with minimal uptake in healthy tissues, potentially reducing off-target effects compared to existing treatments.
ATNM-400 (搜索) aims to address unmet needs for patients who don't respond to or progress after Pluvicto therapy, with initial data to be presented at the upcoming AACR Annual Meeting in April 2025.
Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) announced today a potentially groundbreaking advancement in prostate cancer (搜索) treatment with its novel radiotherapy candidate ATNM-400 (搜索). The therapy, which utilizes the Actinium-225 (搜索) (Ac-225) radioisotope, has demonstrated remarkable efficacy in preclinical studies with 99.8% tumor growth inhibition achieved using a single dose.
Unlike current market leader Pluvicto, ATNM-400 (搜索) targets a non-PSMA (搜索) (prostate-specific membrane antigen) marker that is overexpressed in prostate cancer (搜索) patients. This differentiated approach could provide new options for patients who don't respond to existing therapies.
Initial preclinical data will be presented at the American Association for Cancer Research (AACR) Annual Meeting in Chicago from April 25-30, 2025.
Promising Preclinical Results
The preclinical studies revealed several encouraging findings:
- ATNM-400 selectively binds to prostate cancer cells, undergoes rapid internalization, and induces dose-dependent cytotoxicity
- In xenograft mouse models, the therapy accumulated in tumors for up to 144 hours while showing minimal uptake in normal tissues
- Small animal SPECT/CT imaging confirmed selective tumor accumulation and clearance from healthy tissues
- A single dose achieved 68.5% tumor growth inhibition at 20 μCi/kg and 99.8% at 40 μCi/kg, with all doses being well tolerated
The company is also expected to present data from Pluvicto-resistant prostate cancer (搜索) models at the AACR meeting, potentially demonstrating efficacy in patients who have progressed after standard treatments.
Addressing Limitations of Current Therapies
Pluvicto (Lu-177-PSMA (搜索)-617), marketed by Novartis, generated $1.39 billion in sales in 2024 as a leading targeted radiotherapy for metastatic prostate cancer (搜索). However, not all patients respond to PSMA-targeted approaches.
ATNM-400 (搜索) offers two key differentiators: it targets a different marker than PSMA (搜索), and it uses alpha-particle emitter Ac-225 instead of the beta-particle emitting Lutetitium-177 (搜索) (Lu-177) used in Pluvicto.
"The current era of radiotherapy is built on the clinical and commercial success of Pluvicto in prostate cancer (搜索). The field is now looking to address patients that do not respond or progress after Pluvicto therapy," said Sandesh Seth, Actinium's Chairman and CEO. "We believe ATNM-400 (搜索) can address this high unmet need and we are incredibly excited by our data to date."
Potential Advantages of Alpha-Particle Technology
The use of Ac-225 represents a significant technological advancement. Alpha particles deliver more potent radiation with a shorter path length compared to beta particles, potentially resulting in fewer off-target effects.
"As anticipated, we have seen robust tumor control and ATNM-400 (搜索) has shown to be well tolerated in preclinical studies, which we believe is due to the precise and potent cell-killing of Ac-225," Seth explained.
The company also believes ATNM-400 (搜索)'s non-PSMA (搜索) targeting approach could address some toxicities reported with Pluvicto and other PSMA-targeting radiotherapies, such as xerostomia (dry mouth).
Broader Pipeline Development
ATNM-400 (搜索) joins Actinium's growing portfolio of radiotherapeutics. The company is also advancing Actimab-A (搜索), a CD33-targeting therapeutic for acute myeloid leukemia (搜索) (AML), which has shown promising results in combination with chemotherapy.
Additionally, Actinium is developing Iomab-ACT as a next-generation conditioning agent to improve patient access and outcomes for cell and gene therapies.
The company holds 230 patents and patent applications, including several related to the manufacture of Ac-225 in a cyclotron, positioning it as a leader in the radiopharmaceutical space.
Looking Forward
The upcoming presentation at AACR represents a significant milestone for ATNM-400 (搜索)'s development. The abstract, titled "ATNM-400 is a novel Actinium-225 (搜索) antibody radioconjugate with strong efficacy in preclinical models of prostate cancer (搜索)," will be presented on April 27, 2025.
With prostate cancer (搜索) remaining one of the most common and deadly cancers in men worldwide, new therapeutic approaches like ATNM-400 (搜索) could significantly impact treatment paradigms, particularly for patients with limited options after progression on current therapies.
As the field of targeted radiotherapeutics continues to evolve, ATNM-400 (搜索)'s novel mechanism and impressive preclinical data position it as a potential breakthrough in addressing the unmet needs of prostate cancer (搜索) patients.