Portage Biotech collaborates with Merck to evaluate two next-generation adenosine antagonists in combo with Keytruda in solid tumours

Portage Biotech Inc., a clinical-stage immuno-oncology company, announced that it has entered into a clinical trial collaboration agreement with Merck (known as MSD outside the US and Canada) to evaluate Portage’s next-generation adenosine antagonists in combination with Keytruda (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, for patients with solid tumours.

The collaboration will explore Portage’s adenosine 2A receptor (A2AR) antagonist, PORT-6, its adenosine 2B receptor (A2BR) antagonist, PORT-7, individually and together in combination with Keytruda in prostate, renal, head and neck, colorectal, endometrial, ovarian and non-small cell lung cancers.

Under the terms of the agreement, Merck will provide Keytruda for Portage Biotech’s ADPORT-601, an adaptive phase 1a/1b trial which plans to integrate proprietary biomarkers for selecting patients with high adenosine expression in order to identify those more likely to respond and have potential to benefit most from treatment.

“We are excited to initiate another collaboration with longstanding immunotherapy leader, Merck, to further explore the potential benefits of combining checkpoint blockade with PORT-6 and PORT-7,” said Dr. Ian Walters, chief executive officer of Portage Biotech. “Our suite of potentially best-in-class adenosine antagonists are designed to act on multiple immune cell types for potentially more robust immunological effect and have been demonstrated preclinically to be more selective, more potent and more durable than other adenosine antagonists in development. We look forward to expanding this collaboration, evaluating our adenosine antagonists and continuing our mission to offer transformational therapies for patients in need.”

Keytruda is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. LLC., Rahway, N.J., USA.

A critical mechanism of cancer immune evasion is the generation of high levels of immunosuppressive adenosine within the tumour microenvironment (TME). Research suggests that the TME has significantly elevated concentrations of extracellular adenosine. Engagement with adenosine receptors A2A and A2B triggers a dampening effect on the immune response, suppressing effector cell function and stabilizing immunosuppressive regulatory cells. Over-expression of the A2A and A2B receptors leads to poor prognosis in multiple cancers, including prostate cancer, colorectal cancer and lung adenocarcinoma, driven by a reduced ability to generate an immune response against the tumor. These findings have made A2A and A2B high-priority targets for immunotherapeutic intervention. Portage is advancing four first-in-class adenosine antagonists which together represent the full suite of adenosine-targeting approaches and will enable a comprehensive exploration of how targeting the adenosine pathway could improve response in multiple cancer and non-cancer indications.

The ADPORT-601 adaptive Phase 1a/1b study will explore Portage Biotech’s small molecule adenosine antagonists, PORT-6 and PORT-7, as monotherapies, as well as in combination with one another and potentially with other Portage assets. Phase 1a will evaluate the safety of PORT-6 and PORT-7 both as monotherapy and in combination with immune checkpoint inhibitors, with the goal of identifying a recommended phase 2 dose. phase 1b is designed to explore PORT-6 and PORT-7 monotherapies in an enriched population and in randomized trials vs. standard of care.

Portage is a clinical-stage immuno-oncology company advancing multi-targeted therapies to extend survival and significantly improve the lives of patients with cancer.

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