Pathos AI Acquires Brain-Penetrant PRMT5 Inhibitor for Precision Cancer Therapy
Pathos AI has announced the acquisition of a worldwide license for PRT811, a SAM-competitive PRMT5 inhibitor, from Prelude Therapeutics. Renamed P-500, this potent, selective, and orally bioavailable brain-penetrant drug is designed to target difficult-to-treat cancers, particularly high-grade glioma and uveal melanoma.
Clinical Trial Results and Patient Outcomes
Originally developed by Prelude Therapeutics, PRT811 showed promising results in a Phase 1 clinical trial completed in March 2023. The trial included patients with solid tumors, such as high-grade glioma and uveal melanoma, both of which represent indications with high unmet medical needs.
Among the 16 patients with high-grade glioma harboring isocitrate dehydrogenase mutations (IDH+), two achieved confirmed complete responses (CR), with one response ongoing for over 31 months and the other lasting 7.5 months. Additionally, one patient exhibited an unconfirmed partial response (PR).
The trial also included 23 patients with uveal melanoma, 10 of whom had splicing factor 3B subunit 1 (SF3B1) mutations. In this subgroup, one patient achieved a confirmed PR with a duration of 10 months, and another displayed an unconfirmed PR.
Safety Profile and Adverse Events
The Phase 1 study involved 86 participants and identified the most common adverse events (AEs) of any grade as nausea (60.5%), vomiting (46.5%), fatigue (36.0%), constipation (29.1%), and thrombocytopenia (24.4%). Most of these AEs were grade 1-2. Severe adverse events (grade ≥3) occurring in over 5% of patients included thrombocytopenia (9.3%), anemia (9.3%), and fatigue (5.8%).
Strategic Developments and Future Prospects
Ryan Fukushima, CEO of Pathos AI, highlighted the potential of P-500 to improve treatment options for patients with high-grade glioma:
“These results from Prelude’s Phase 1 study are promising news for high-grade glioma patients and clinicians, who still have limited treatment options with chemotherapy and radiation that hasn’t changed in decades. With our AI Platform, we aim to increase the already encouraging response rate of P-500 through a novel biomarker-driven strategy, ultimately bringing this medicine to patients as efficiently as possible.”
P-500, a selective brain-penetrant small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5), holds potential not only for high-grade glioma and uveal melanoma but also for other cancer types. PRMT5 inhibition could sensitize cancer cells to other treatments, expanding P-500’s applicability in combination therapies.
Pathos AI’s Approach to Precision Medicine
Pathos AI, a clinical-stage biotechnology company, utilizes AI technologies to transform drug development and accelerate the delivery of precision medicines. With $40 million in funding, the company is developing its PathOS platform, which integrates advanced AI-driven analyses with biological modeling to optimize drug development and patient outcomes.
The PathOS platform processes vast multimodal oncology datasets, generating actionable insights at scale. Its self-learning therapeutics engine automates the identification and prioritization of drug targets, refining predictive capabilities with each new data point. By harmonizing data from discovery through clinical development, PathOS™ enhances the accuracy of patient response predictions and drives the development of precision therapies. Additionally, by validating AI-generated hypotheses through in-house biological modeling, Pathos ensures that its clinical trials are designed for speed and efficacy, aiming for successful drug approvals.
