Portage Biotech Reports Confirmatory Preclinical Results in Mesothelioma Supporting First-In-Human Trial of PORT-7
Rhea-AI Summary
Portage Biotech has announced promising preclinical data for its cancer treatment drug PORT-7, a selective adenosine A2B receptor inhibitor. The results, to be presented at the AACR Annual Meeting in Chicago, showed that PORT-7 outperformed anti-PD1 antibody treatment in a mesothelioma mouse model.
Key findings include:
- PORT-7 demonstrated superior single-agent activity compared to anti-PD1 antibody
- Combined PORT-7 and anti-PD1 treatment showed better results than either treatment alone
- Formation of tertiary lymphoid structures observed in combination treatment
- Increased immune effector cells noted in combination therapy
The company is preparing for first-in-human clinical trials with PORT-7 while advancing dose escalation of PORT-6, their A2A adenosine receptor inhibitor. Portage plans to combine both drugs in the ongoing ADPORT-601 trial, marking the first-ever combination of selective A2A and A2B antagonists in patients, aiming to fully block adenosine-induced immunosuppression in the tumor environment.
Positive
- PORT-7 showed superior single-agent efficacy compared to anti-PD1 antibody in preclinical mesothelioma trials
- Combination of PORT-7 and anti-PD1 demonstrated enhanced efficacy over individual treatments
- Positive immunological response observed through formation of tertiary lymphoid structures
- Company advancing with two complementary drugs (PORT-6 and PORT-7) targeting different adenosine receptors
- First-in-human clinical trial preparations underway for PORT-7
Negative
- Still in preclinical stage for PORT-7, indicating long pathway to potential commercialization
- No human clinical data available yet for the PORT-7 program
- Operating in highly competitive immuno-oncology space with established players
- Multiple clinical trials required, suggesting significant future capital requirements
Insights
Portage's PORT-7 advances to human trials following strong preclinical results in combination with checkpoint inhibitors.
The preclinical data package for PORT-7 demonstrates significant promise in mesothelioma treatment. In murine models, PORT-7 as a single agent outperformed anti-PD1 therapy, while the combination delivered superior efficacy to either treatment alone. The formation of tertiary lymphoid structures and increased immune effector cells indicates a robust immune response mechanism that could translate to clinical benefit.
This preclinical validation represents an important developmental milestone justifying progression to first-in-human studies. The data package appears particularly compelling with evidence of both monotherapy activity and combination potential with established immunotherapy approaches.
Portage's strategy to eventually combine PORT-6 (A2A antagonist) and PORT-7 (A2B antagonist) in their ADPORT-601 trial marks the first attempt to simultaneously block both adenosine receptors in patients. This mechanism-based approach aims to comprehensively neutralize adenosine-mediated immunosuppression in the tumor microenvironment.
The adenosine pathway represents a validated immuno-oncology target, as elevated adenosine levels in tumors contribute to immune evasion. By targeting both receptor subtypes, Portage's approach could potentially offer more complete pathway inhibition than single-receptor targeting strategies currently in development. The progression of PORT-7 to clinical testing advances Portage's adenosine receptor antagonist portfolio and validates their platform approach.
Novel dual adenosine receptor blockade shows promise in mesothelioma, addressing critical treatment gaps through enhanced immune activation.
The preclinical efficacy demonstrated by PORT-7 addresses a significant therapeutic gap in mesothelioma, an aggressive malignancy with treatment options and poor prognosis. The superior performance compared to anti-PD1 antibody therapy is particularly relevant, as checkpoint inhibitors have shown modest efficacy in mesothelioma patients.
The synergistic effect observed when combining PORT-7 with anti-PD1 suggests potential to overcome multiple immune resistance mechanisms simultaneously. This is critical in mesothelioma, which typically presents with an immunosuppressive tumor microenvironment resistant to single-agent approaches.
The immunohistochemistry findings revealing tertiary lymphoid structure formation represent a compelling immunological advantage. These organized lymphoid aggregates within tumors function as local immune training centers and correlate with improved clinical outcomes across multiple tumor types. Their presence, along with increased immune effector cells, suggests PORT-7 facilitates productive anti-tumor immunity rather than just blocking a suppressive signal.
Portage's comprehensive strategy to block both A2A and A2B adenosine receptors addresses a fundamental challenge in cancer immunotherapy. Adenosine accumulation in the tumor microenvironment suppresses multiple immune cell types through different receptor-mediated mechanisms. By neutralizing signaling through both receptor subtypes, this approach could potentially overcome a key immune evasion strategy employed by aggressive tumors like mesothelioma, where new therapeutic options are urgently needed.
DOVER, Del., April 28, 2025 (GLOBE NEWSWIRE) -- Portage Biotech Inc. (NASDAQ: PRTG), a clinical-stage immuno-oncology company today reports confirmatory preclinical efficacy data for PORT-7 (TT-4), a selective adenosine A2B receptor inhibitor. Dr. Luciano Mutti of the Department of Applied Clinical Sciences and Biotechnology at the University of L'Aquila, Italy, an internationally recognized expert in mesothelioma, will be presenting the data at the American Association for Cancer Research® (AACR) Annual Meeting at the McCormick Place Convention Center in Chicago, Illinois on April 28, 2025. The new data in a murine mesothelioma model demonstrated single agent activity for PORT-7 that was superior to treatment with single agent anti-PD1 antibody. Moreover, the combination of PORT-7 and anti-PD1 was superior to treatment with either anti-PD1 or PORT-7 alone. Immunohistochemistry of the tumors revealed the formation of tertiary lymphoid structures in the mice receiving the combination. This indication of a favorable immune response was accompanied by increases in immune effector cells in mice treated with the combination. Mesothelioma is an aggressive cancer with limited treatment options in need of novel approaches to overcome immune resistance. Portage is making preparations to commence a first-in-human clinical trial with PORT-7.
Combining PORT-6 and PORT-7 for a More Comprehensive Immunotherapy Approach
In parallel, Portage is advancing the dose escalation of PORT-6, a potent and selective inhibitor of the A2A adenosine receptor. Portage’s plan is to ultimately co-administer PORT-6 with PORT-7 in the ongoing ADPORT-601 trial. This will mark the first time two highly selective A2A and A2B antagonists are combined in patients, with the aim of achieving a complete blockade of adenosine-induced immunosuppression in the tumor microenvironment. This innovative approach is designed to fully neutralize adenosine-mediated immune suppression, enhance anti-tumor responses, and broaden the impact of immunotherapy in solid tumors.
About Portage Biotech
Portage Biotech is a clinical-stage immuno-oncology company advancing a pipeline of novel biologics to transform the immune system’s ability to fight cancer. For more information, visit www.portagebiotech.com.
Forward-Looking Statements
All statements in this news release, other than statements of historical facts, including without limitation, statements regarding the Company’s business strategy, plans and objectives of management for future operations and those statements preceded by, followed by or that otherwise include the words “believe,” “expects,” “anticipates,” “intends,” “estimates,” “will,” “may,” “plans,” “potential,” “continues,” or similar expressions or variations on such expressions are forward-looking statements. As a result, forward-looking statements are subject to certain risks and uncertainties, including, but not limited to: the risk that the Company may not secure financing, the uncertainty of the Company’s ability to continue as a going concern, scientific results may not be as expected, and other factors set forth in “Item 3 - Key Information-Risk Factors” in the Company’s Annual Report on Form 20-F for the year ended March 31, 2024 and “Business Environment – Risk Factors” in the Company’s Management’s Discussion and Analysis for the Three and Six Months ended September 30, 2024, filed as Exhibit 99.2 to the Company’s Form 6-K. Although the Company believes that the expectations reflected in these forward-looking statements are reasonable, undue reliance should not be placed on them as actual results may differ materially from these forward-looking statements. The forward-looking statements contained in this news release are made as of the date hereof, and the Company undertakes no obligation to update publicly or revise any forward-looking statements or information, except as required by law.
For More Information:
Portage Biotech
Alexander Pickett, Chief Executive Officer
ir@portagebiotech.com
FAQ
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