Portage Biotech Inc. (NASDAQ: PRTG) presented promising new preclinical data for its selective Adenosine A2B receptor inhibitor, PORT-7 (TT-4), demonstrating remarkable efficacy in mesothelioma models. The results, unveiled at the 2025 European Lung Cancer Congress (ELCC) in Paris, showed both significant single-agent activity and a dramatic tumor reduction when combined with immunotherapy.
The study, conducted by Dr. Luciano Mutti of Gruppo Italiano Mesotelioma e Oncologia Ambientale, revealed that PORT-7 combined with an anti-PD1 antibody achieved over 90% inhibition of tumor growth in a murine model of mesothelioma. Immunohistochemistry analysis of the tumors showed significant infiltration of both CD3 and CD45 positive immune effector cells, indicating robust immune system activation against the cancer.
"To our knowledge, this is the first report of antitumor activity against mesothelioma using a selective A2B receptor inhibitor," stated Portage Biotech in their announcement. The company is now preparing to initiate a first-in-human clinical trial with PORT-7.
Novel Dual-Receptor Targeting Strategy
Mesothelioma, an aggressive cancer typically associated with asbestos exposure, has historically had limited treatment options and poor outcomes. The disease represents a significant unmet medical need, with conventional therapies offering modest benefits.
In parallel to the PORT-7 development, Portage is advancing dose escalation studies of PORT-6, a potent and selective inhibitor of the A2A adenosine receptor. The company's innovative strategy involves eventually co-administering PORT-6 with PORT-7 in their ongoing ADPORT-601 trial.
This combination would mark the first time two highly selective adenosine receptor antagonists targeting different receptor subtypes (A2A and A2B) are combined in patients. The approach aims to achieve a complete blockade of adenosine-induced immunosuppression in the tumor microenvironment.
Alexander Pickett, Chief Executive Officer of Portage Biotech, explained the scientific rationale: "Adenosine signaling is a key immunosuppressive mechanism in the tumor microenvironment. By targeting both the A2A and A2B receptors simultaneously, we hope to fully neutralize adenosine-mediated immune suppression, potentially enhancing anti-tumor responses and broadening the impact of immunotherapy in solid tumors."
Mechanism of Action and Clinical Implications
The adenosine pathway has emerged as a critical immune checkpoint in cancer. In the tumor microenvironment, high levels of adenosine bind to receptors on immune cells, suppressing their anti-tumor activity. By blocking these receptors, PORT-7 and PORT-6 aim to restore immune function against cancer cells.
The preclinical results are particularly significant for mesothelioma patients. This rare but aggressive cancer affects the thin layer of tissue that covers the lungs and other organs, with approximately 3,000 new cases diagnosed annually in the United States. Five-year survival rates remain below 10% with current standard treatments.
If the promising preclinical results translate to humans, the PORT-7 therapy could represent a significant advancement for these patients. The dramatic tumor reduction observed when combined with anti-PD1 therapy suggests potential for enhancing the efficacy of existing immunotherapies.
Clinical Development Timeline
Portage Biotech has indicated that preparations are underway to commence the first-in-human trial with PORT-7. While specific timelines were not disclosed, the company appears to be moving swiftly following these encouraging preclinical results.
The ongoing ADPORT-601 trial, which is currently evaluating PORT-6, will eventually incorporate PORT-7 as well. This innovative dual-receptor targeting approach could potentially establish a new paradigm in adenosine pathway inhibition for cancer treatment.
Industry analysts note that if successful, this approach could have applications beyond mesothelioma to other solid tumors where adenosine-mediated immunosuppression plays a role in treatment resistance.
About Portage Biotech
Portage Biotech is a clinical-stage immuno-oncology company focused on developing novel biologics to transform the immune system's ability to fight cancer. The company's pipeline includes several innovative therapeutics targeting various immune pathways.
As a NASDAQ-listed company (PRTG), Portage continues to advance its portfolio of immunotherapy candidates through rigorous scientific investigation. The company's approach focuses on overcoming mechanisms of immune resistance in the tumor microenvironment to enable more effective anti-cancer responses.
