Portage Biotech Reports Promising Preclinical Results in Mesothelioma Supporting First-In-Human Trial of PORT-7

Rhea-AI Summary

Portage Biotech (NASDAQ: PRTG) has presented promising preclinical data for PORT-7, their selective Adenosine A2B receptor inhibitor, at the 2025 European Lung Cancer Congress. The study showed significant results in a murine mesothelioma model, demonstrating:

• Single agent activity for PORT-7
• Over 90% tumor growth inhibition when combined with anti-PD1 antibody
• Significant infiltration of CD3 and CD45 positive immune effector cells in tumors

The company is preparing to initiate a first-in-human clinical trial with PORT-7. Additionally, Portage is advancing the dose escalation of PORT-6, their A2A adenosine receptor inhibitor, with plans to co-administer both drugs in the ongoing ADPORT-601 trial. This combination aims to achieve complete blockade of adenosine-induced immunosuppression in the tumor microenvironment.

Positive

• First demonstration of antitumor activity against mesothelioma using selective A2B receptor inhibitor
• Strong preclinical efficacy with >90% tumor growth inhibition in combination therapy
• Advancement to first-in-human trials for PORT-7
• Novel dual-drug approach targeting both A2A and A2B receptors

Negative

• Still in preclinical stage, requiring extensive clinical trials before potential commercialization
• Results to animal models, human efficacy yet to be demonstrated

Insights

Oncology Research Expert

The preclinical data for PORT-7 demonstrates promising efficacy in mesothelioma models that could translate to meaningful clinical outcomes. The 90%+ tumor growth inhibition when combined with anti-PD-1 therapy is particularly impressive, as is the significant infiltration of CD3 and CD45 immune cells into the tumor microenvironment. This suggests effective reversal of immune suppression, a critical factor in overcoming treatment resistance.

Adenosine pathway targeting represents a scientifically sound approach. In the immunosuppressive tumor microenvironment, adenosine accumulates and binds to different receptors (primarily A2A and A2B) on immune cells, effectively shutting down anti-tumor responses. By specifically blocking the A2B receptor with PORT-7, Portage is targeting a pathway particularly relevant in hypoxic tumor conditions like those seen in mesothelioma.

The planned dual-blockade strategy combining PORT-6 (A2A antagonist) with PORT-7 (A2B antagonist) makes mechanistic sense. While other companies have pursued adenosine pathway inhibition, most have focused on either single receptors or less selective compounds. This would be the first clinical attempt at comprehensive adenosine signaling blockade using two highly selective agents.

For mesothelioma patients, who have very treatment options despite recent immunotherapy advances, this approach could provide much-needed new options. However, as with all preclinical findings, these results must be confirmed in human trials, where complex tumor biology and heterogeneity present significant challenges.

Biotechnology Investment Analyst

These preclinical results represent a meaningful pipeline advancement for Portage Biotech. The data establishes proof-of-concept for PORT-7 and supports the progression to first-in-human trials, an important value-creating milestone for early-stage biotech companies.

The mesothelioma indication is strategically significant despite its relatively small market. As a rare, aggressive cancer with treatment options, mesothelioma development pathways can offer regulatory advantages including potential orphan drug designation, faster approval timelines, and pricing premiums if successful.

Portage's adenosine receptor antagonist platform is gaining validation through this data. The adenosine pathway has attracted significant interest from larger pharmaceutical companies as a complementary approach to existing immunotherapies, particularly in difficult-to-treat tumors with immunosuppressive microenvironments. The planned combination of PORT-6 and PORT-7 could create a differentiated position in this competitive landscape.

For a company with $7.1M market cap, pipeline progress is critical. Each clinical milestone increases potential partnership opportunities and reduces investment risk. However, investors should recognize the early stage of development - the bridge from preclinical to clinical success remains challenging, particularly in oncology where translation rates are typically below 10%.

The company's focus on selective adenosine receptor antagonists aligns with the industry trend toward precision immunomodulation rather than broad immunological approaches, potentially improving efficacy while reducing off-target effects.

Encouraging efficacy data in a murine mesothelioma model with a selective A2B adenosine receptor antagonist given as a single agent or in combination with anti-PD-1 antibody

DOVER, Del., March 27, 2025 (GLOBE NEWSWIRE) -- Portage Biotech Inc. (NASDAQ: PRTG), a clinical-stage immuno-oncology company with a portfolio of innovative therapeutics, presented new preclinical data for PORT-7 (TT-4), a selective Adenosine A2B receptor inhibitor, generated by Dr. Luciano Mutti, Gruppo Italiano Mesotelioma e Oncologia Ambientale, at the 2025 European Lung Cancer Congress (ELCC), held in Paris, France March 26-29. The new data demonstrate both single agent activity for PORT-7, and a dramatic >90% inhibition of tumor growth when PORT-7 was combined with an anti-PD1 antibody in a murine model of mesothelioma. Immunohistochemistry of the tumors revealed a significant infiltration of both CD3 and CD45 positive immune effector cells. Mesothelioma is an aggressive cancer with limited treatment options in need of novel approaches to overcome immune resistance. To our knowledge, this is the first report of antitumor activity against mesothelioma using a selective A2B receptor inhibitor. 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

What are the key preclinical results for Portage Biotech's PORT-7 (PRTG) in mesothelioma treatment?

PORT-7 showed single agent activity and achieved >90% tumor growth inhibition when combined with anti-PD1 antibody in murine mesothelioma models, with significant immune cell infiltration.

How does Portage Biotech (PRTG) plan to combine PORT-6 and PORT-7 in clinical trials?

Portage plans to co-administer PORT-6 and PORT-7 in the ADPORT-601 trial, marking the first combination of selective A2A and A2B antagonists in patients.

What is the significance of PORT-7's mesothelioma study results for PRTG?

It's the first reported antitumor activity against mesothelioma using a selective A2B receptor inhibitor, showing promise for treating this aggressive cancer with treatment options.

When will Portage Biotech (PRTG) begin human trials for PORT-7?

The company is currently preparing to commence first-in-human clinical trials with PORT-7, though specific timing was not disclosed.