Portage Biotech Reports Confirmatory Preclinical Results in Mesothelioma Supporting First-In-Human Trial of PORT-7
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.
Portage Biotech ha annunciato dati preclinici promettenti per il suo farmaco antitumorale PORT-7, un inibitore selettivo del recettore dell'adenosina A2B. I risultati, che saranno presentati al AACR Annual Meeting di Chicago, mostrano che PORT-7 ha superato il trattamento con anticorpi anti-PD1 in un modello murino di mesotelioma.
I risultati principali includono:
- PORT-7 ha dimostrato un'attività superiore come singolo agente rispetto all'anticorpo anti-PD1
- La combinazione di PORT-7 e anti-PD1 ha mostrato risultati migliori rispetto a ciascun trattamento singolarmente
- È stata osservata la formazione di strutture linfatiche terziarie nel trattamento combinato
- Un aumento delle cellule effettrici del sistema immunitario è stato rilevato nella terapia combinata
L'azienda si sta preparando per le prime sperimentazioni cliniche sull'uomo con PORT-7, mentre procede con l'escalation di dose di PORT-6, il loro inibitore del recettore dell'adenosina A2A. Portage prevede di combinare entrambi i farmaci nella sperimentazione ADPORT-601 in corso, segnando la prima combinazione mai effettuata di antagonisti selettivi A2A e A2B nei pazienti, con l'obiettivo di bloccare completamente l'immunosoppressione indotta dall'adenosina nell'ambiente tumorale.
Portage Biotech ha anunciado datos preclínicos prometedores para su fármaco contra el cáncer PORT-7, un inhibidor selectivo del receptor de adenosina A2B. Los resultados, que se presentarán en la AACR Annual Meeting en Chicago, mostraron que PORT-7 superó al tratamiento con anticuerpos anti-PD1 en un modelo murino de mesotelioma.
Los hallazgos clave incluyen:
- PORT-7 demostró una actividad superior como agente único en comparación con el anticuerpo anti-PD1
- La combinación de PORT-7 y anti-PD1 mostró mejores resultados que cualquiera de los tratamientos por separado
- Se observó la formación de estructuras linfoides terciarias en el tratamiento combinado
- Se notó un aumento de células efectoras inmunes en la terapia combinada
La compañía se está preparando para los primeros ensayos clínicos en humanos con PORT-7 mientras avanza en la escalada de dosis de PORT-6, su inhibidor del receptor de adenosina A2A. Portage planea combinar ambos fármacos en el ensayo ADPORT-601 en curso, marcando la primera combinación de antagonistas selectivos A2A y A2B en pacientes, con el objetivo de bloquear completamente la inmunosupresión inducida por adenosina en el entorno tumoral.
포티지 바이오텍은 선택적 아데노신 A2B 수용체 억제제인 암 치료제 PORT-7의 유망한 전임상 데이터를 발표했습니다. 시카고에서 열리는 AACR 연례회의에서 발표될 결과에 따르면, PORT-7은 중피종 마우스 모델에서 항-PD1 항체 치료보다 우수한 효과를 보였습니다.
주요 발견 사항은 다음과 같습니다:
- PORT-7은 단독제로서 항-PD1 항체보다 뛰어난 활성을 나타냈습니다
- PORT-7과 항-PD1 병용 치료는 단독 치료보다 더 나은 결과를 보였습니다
- 병용 치료에서 제3 림프구조체 형성이 관찰되었습니다
- 병용 요법에서 면역 효과 세포가 증가했습니다
회사는 PORT-7의 최초 인체 임상시험을 준비 중이며, 동시에 A2A 아데노신 수용체 억제제인 PORT-6의 용량 증량도 진행하고 있습니다. 포티지는 두 약물을 현재 진행 중인 ADPORT-601 임상시험에서 병용할 계획이며, 이는 환자에서 선택적 A2A 및 A2B 길항제를 결합하는 최초의 시도로, 종양 환경에서 아데노신 유도 면역 억제를 완전히 차단하는 것을 목표로 합니다.
Portage Biotech a annoncé des données précliniques prometteuses pour son médicament anticancéreux PORT-7, un inhibiteur sélectif du récepteur de l'adénosine A2B. Les résultats, qui seront présentés lors du AACR Annual Meeting à Chicago, ont montré que PORT-7 a surpassé le traitement par anticorps anti-PD1 dans un modèle murin de mésothéliome.
Les principales conclusions sont les suivantes :
- PORT-7 a démontré une activité supérieure en tant qu'agent unique comparé à l'anticorps anti-PD1
- La combinaison de PORT-7 et de l'anti-PD1 a donné de meilleurs résultats que chaque traitement pris isolément
- La formation de structures lymphoïdes tertiaires a été observée lors du traitement combiné
- Une augmentation des cellules effectrices immunitaires a été notée avec la thérapie combinée
L'entreprise se prépare à des essais cliniques de phase I avec PORT-7 tout en poursuivant l'escalade de dose de PORT-6, leur inhibiteur du récepteur de l'adénosine A2A. Portage prévoit de combiner les deux médicaments dans l'essai en cours ADPORT-601, marquant la première combinaison jamais réalisée d'antagonistes sélectifs A2A et A2B chez les patients, visant à bloquer complètement l'immunosuppression induite par l'adénosine dans l'environnement tumoral.
Portage Biotech hat vielversprechende präklinische Daten für sein Krebsmedikament PORT-7, einen selektiven Adenosin-A2B-Rezeptor-Inhibitor, bekannt gegeben. Die Ergebnisse, die auf dem AACR Annual Meeting in Chicago vorgestellt werden, zeigten, dass PORT-7 in einem Mesotheliom-Mausmodell die Behandlung mit Anti-PD1-Antikörpern übertraf.
Wichtige Erkenntnisse umfassen:
- PORT-7 zeigte als Einzelwirkstoff eine überlegene Aktivität im Vergleich zum Anti-PD1-Antikörper
- Kombinierte Behandlung mit PORT-7 und Anti-PD1 erzielte bessere Ergebnisse als jede Behandlung allein
- Bildung tertiärer lymphoider Strukturen wurde bei der Kombinationstherapie beobachtet
- Erhöhte Anzahl von Immun-Effektorzellen wurde bei der Kombinationstherapie festgestellt
Das Unternehmen bereitet erste klinische Studien am Menschen mit PORT-7 vor und führt gleichzeitig eine Dosissteigerung von PORT-6, ihrem A2A-Adenosinrezeptor-Inhibitor, durch. Portage plant, beide Medikamente in der laufenden ADPORT-601-Studie zu kombinieren, was die erste Kombination selektiver A2A- und A2B-Antagonisten bei Patienten darstellt, mit dem Ziel, die adenosininduzierte Immunsuppression im Tumormilieu vollständig zu blockieren.
- 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
- 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
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For More Information:
Portage Biotech
Alexander Pickett, Chief Executive Officer
ir@portagebiotech.com
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