Pathios Therapeutics Begins Phase 1/2 Trial of GPR65 Inhibitor PTT-4256 for Advanced Solid Cancers

Pathios Therapeutics, a biotechnology firm focusing on pioneering treatments for cancer, has commenced the administration of its first patient in the initial stage of a Phase 1/2 clinical trial for PTT-4256. This investigational drug is described as a first-in-class GPR65 inhibitor, developed internally by Pathios. The drug is an oral, highly potent, and selective small molecule inhibitor targeting the pH-sensing GPR65 receptor.

The trial, known as RAISIC-1 (Relief of Acidic Immune Suppression in Cancer), is a multi-stage, multi-arm open-label study occurring in Australia, aimed at assessing the safety, tolerability, preliminary efficacy, and pharmacokinetics of PTT-4256 in patients with advanced solid tumors. The trial's design includes subsequent modules that will investigate the drug's potential in specific types of tumors, both as a standalone treatment and in combination with standard therapies.

Paul G. Higham, CEO of Pathios, highlighted this development as a critical progress marker for the company, signifying the potential of their novel approach and the concerted efforts of the Pathios team. The trial is designed to yield comprehensive data on PTT-4256, essential for further clinical development. In addition to safety and pharmacokinetic assessments, the trial aims to explore the activity of this novel mechanism in human subjects by monitoring disease response and analyzing biomarker correlations to understand the effects of the treatment.

Pathios Therapeutics' innovative strategy in immunooncology focuses on reversing the immunosuppressive polarization of immune cells within the acidic tumor microenvironment by inhibiting GPR65, an acid-sensing G protein-coupled receptor. This receptor is exclusively expressed on immune cells and is implicated in promoting an immunosuppressive phenotype that hinders the immune system's ability to attack cancer cells. Genetic analyses conducted by Pathios indicate that decreased GPR65 function correlates with significantly improved survival rates in various solid tumors, making it a promising target for cancer therapy.

Preclinical studies of PTT-4256 have shown that the drug exhibits excellent properties and significant anti-tumor activity as a monotherapy. The RAISIC-1 trial is being managed by Pathios Therapeutics Pty Ltd, in collaboration with Australian clinical trial sites, contract research organizations, and M:M Bio Pty Ltd, part of the global Molecule to Medicine (MTM) ecosystem. The trial has received approval from relevant Australian Ethics Committees and is conducted under the Australian Therapeutic Goods Administration's Clinical Trial Notification scheme. It is registered on ClinicalTrials.gov with the identifier NCT06634849.

Pathios Therapeutics, founded by seasoned professionals from the biotech and pharmaceutical industries, focuses on developing small molecule inhibitors of the GPR65 receptor to counteract its role in immunosuppressive polarization in cancer. To date, the company has secured $58 million in funding from top venture capital firms and strategic investment from Bristol Myers Squibb. The UK team operates from the Innovation Centre at Milton Park, near Oxford, UK, as part of the MTM drug discovery and development ecosystem alongside Grey Wolf Therapeutics and ThirtyFiveBio.