Pathos Secures Global License for Phase 2 Brain-penetrant PRMT5 Inhibitor

Pathos AI, Inc., a Chicago-based biotechnology company, is making significant strides in precision medicine for cancer treatment through the utilization of machine learning. Recently, Pathos announced the worldwide license acquisition of PRT811, a highly potent and selective brain-penetrant PRMT5 inhibitor from Prelude Therapeutics, now renamed P-500. This molecule, which has shown promising results in clinical trials, is expected to revolutionize the treatment landscape for patients with high-grade glioma and uveal melanoma among other cancers.

PRT811, now P-500, underwent a Phase 1 clinical trial completed in March 2023 by Prelude Therapeutics. The trial included patients with solid tumors, focusing on those with high-grade glioma and uveal melanoma, and explored its potential for other cancers with high unmet medical needs. In the trial, 16 patients with high-grade glioma with isocitrate dehydrogenase mutations (IDH+) were treated, resulting in two confirmed complete responses (CR). One of these responses lasted for 31.0 months, while the other had a duration of 7.5 months. Additionally, there was an unconfirmed partial response (PR) observed in one patient.

The trial also involved 23 patients with uveal melanoma, including 10 patients with splicing factor 3B subunit 1 (SF3B1) mutations and 13 without. Among these, one patient with an SF3B1 mutation achieved a confirmed PR with a duration of 10 months, and another had an unconfirmed PR.

Regarding safety, the most common adverse events observed in the 86-patient safety population were nausea (60.5%), vomiting (46.5%), fatigue (36.0%), constipation (29.1%), and thrombocytopenia (24.4%), primarily of grade 1-2 severity. Grade ≥3 adverse events occurring in more than 5% of patients included thrombocytopenia (9.3%), anemia (9.3%), and fatigue (5.8%).

Pathos CEO, Ryan Fukushima, expressed optimism about the results, highlighting the potential of P-500 to improve treatment outcomes for high-grade glioma patients. The company plans to leverage its advanced AI platform to enhance the drug's response rate through a novel biomarker-driven approach, aiming to bring the treatment to patients swiftly and effectively.

Sean Brusky, Chief Business Officer of Prelude Therapeutics, lauded the collaboration, noting that PRT811 is one of several precision medicines developed by Prelude's discovery engine. He emphasized confidence in Pathos AI’s capability to advance the molecule's development, benefiting cancer patients with significant unmet needs.

P-500 works by selectively inhibiting protein arginine methyltransferase 5 (PRMT5), an enzyme critical for various cellular processes that promote cancer growth. By targeting PRMT5, which uses S-adenosylmethionine (SAM) to methylate proteins, P-500 holds promise not only for glioma and melanoma but potentially for other cancers as well. Preclinical studies suggest that inhibiting PRMT5 can sensitize cancer cells to other treatments, offering expanded therapeutic applications, including combination therapies.

Pathos AI is dedicated to re-engineering drug development by harnessing AI to deliver precision medicines through partnerships with biopharmaceutical companies. To date, the company has raised $40 million to expedite the development of precision medicines and expand its innovative platform that integrates computational methods with real-world data and patient-derived biological models.