Tuesday, June 27, 2023
Portage Biotech Inc., a clinical-stage immuno-oncology company focused on advancing innovative multi-targeted therapies for use in single-agent and combination treatments, has announced the initiation of its Phase 1a trial, ADPORT-601 (NCT04969315). The trial marks an important milestone as the first patient has been dosed with PORT-6, Portage's adenosine 2A receptor (A2AR) antagonist candidate. This Phase 1a trial aims to evaluate the safety and efficacy of PORT-6 in patients with solid tumors, including prostate cancer, renal cancer, and non-small cell lung cancer.
Dr. Ian Walters, CEO and Chairman of Portage Biotech, expressed enthusiasm about the trial and the collaboration with academic partners. The company believes that targeting the adenosine pathway could lead to improved outcomes across multiple cancer types. PORT-6, as a next-generation A2AR antagonist, is expected to be more potent, durable, and selective compared to other agents, based on promising pre-clinical studies.
The ADPORT-601 trial is designed as an adaptive Phase 1a/1b study that will not only assess the safety and efficacy of PORT-6 but also evaluate Portage's adenosine 2B receptor (A2BR) antagonist, PORT-7. The trial will incorporate proprietary biomarkers to identify patients with high expression of A2A and A2B receptors. This personalized treatment approach aims to select patients who are more likely to respond and benefit from the treatment based on their tumor characteristics.
Experts involved in the trial have highlighted the significance of targeting the adenosine signaling pathway in overcoming tumor immune evasion. Dr. Sumit Subudhi of MD Anderson Cancer Center expressed confidence in Portage's A2AR and A2BR antagonists, considering them to be leading candidates for addressing this immunosuppressive pathway.
Dr. Lawrence Fong of the Hellen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, commented on the potential of the PORT-6 A2AR antagonist and PORT-7 A2BR antagonist trial to shed light on therapeutic implications by targeting each pathway alone or in combination. This trial presents an opportunity to improve patient selection strategies by identifying tumors with high adenosine expression and evaluating the efficacy of Portage's adenosine antagonists.
Portage Biotech's Phase 1a trial of PORT-6 in select solid tumors represents a significant step forward in their pursuit of novel immuno-oncology therapies and provides hope for patients in need of effective treatments.
Adenosine, a key factor in cancer immune evasion, is known to play a crucial role in generating immunosuppression within the tumor microenvironment (TME). Studies indicate that the TME exhibits significantly elevated levels (100-500 fold) of extracellular adenosine. Engagement with adenosine receptors A2A and A2B triggers immune response dampening, suppressing the function of effector cells and promoting the stability of immunosuppressive regulatory cells. Overexpression of A2A and A2B receptors is associated with unfavorable prognosis in various cancers, including prostate cancer, colorectal cancer, and lung adenocarcinoma, as it impairs the immune response against tumors. Consequently, targeting A2A and A2B receptors has become a high-priority approach for immunotherapeutic interventions. Portage Biotech is advancing four novel adenosine antagonists that cover the entire range of adenosine-targeting strategies. This comprehensive approach enables the exploration of how targeting the adenosine pathway can enhance treatment response across multiple cancer types and non-cancer indications.
The ADPORT-601 trial, an adaptive Phase 1a/1b study, aims to investigate Portage Biotech's small molecule adenosine antagonists, PORT-6 and PORT-7. The study will assess their effectiveness as monotherapies, in combination with each other, and potentially in combination with other Portage assets. In Phase 1a, the safety of PORT-6 and PORT-7 will be evaluated as monotherapies and in combination with immune checkpoint inhibitors. The primary objective is to identify the recommended Phase 2 dose. Phase 1b, on the other hand, will focus on exploring PORT-6 and PORT-7 as monotherapies in a select patient population, comparing them to standard-of-care treatments through randomized trials.