PORT-6 / Portage - LARVOL DELTA

ADPORT-601: TT-10 (PORT-6) and TT-4 (PORT-7) as Single Agents and in Combination in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=90 | Recruiting | Sponsor: Portage Biotech | Active, not recruiting ➔ Recruiting | Trial completion date: Aug 2025 ➔ Dec 2027 | Trial primary completion date: May 2025 ➔ Jun 2026

Enrollment open • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Colorectal Cancer • Endometrial Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Portage Biotech Resumes Enrollment in Final Cohort of Dose Escalation for Port-6 in ADPORT-601 Trial (GlobeNewswire) - "Portage Biotech Inc...announced the resumption of patient enrollment in the fourth and final cohort of the dose escalation stage for PORT-6, a highly selective A2A antagonist, within its ADPORT-601 Phase 1b clinical trial. Portage had previously paused this trial due to funding concerns; this resumption of the trial underscores the encouraging findings observed in earlier cohorts. After the completion of the PORT-6 arm of the ADPORT-601 study, Portage will evaluate the continuation of the study into its PORT-7 (potent and selective A2B antagonist) and combination arms, on a segment-by-segment basis."

Trial status • Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Portage Biotech Reports Fiscal Year-Ended March 31, 2024 Financial Results and Business Update (GlobeNewswire) - "'After reviewing Portage’s funding requirements, which necessitated discontinuing the clinical development of its iNKT program and pausing patient enrollment in the ADPORT-601 clinical trial of PORT-6 (adenosine 2A inhibitor) and PORT-7 (adenosine 2B inhibitor), we continue to explore strategic alternatives'...Operating expenses, which include research and development ('R&D') costs and general and administrative ('G&A') expenses, were $18.2 million in Fiscal 2024, compared to $16.6 million in Fiscal 2023, an increase of $1.6 million. This increase was primarily due to additional clinical development costs related to the PORT-6 clinical trial and the iNKT clinical trial for PORT-2, prior to discontinuing the Company’s iNKT trial and pausing further enrollment in the ADPORT-601 clinical trial of PORT-6 (adenosine 2A inhibitor) and PORT-7 (adenosine 2B inhibitor)."

Commercial • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ADPORT-601: First-in-human study of adenosine 2A (A2A) and adenosine 2B (A2B) receptor antagonists in patients with select advanced solid tumors. (ASCO 2024) - P1/2 | "TT-10 (PORT-6) and TT-4 (PORT-7) are potent and selective antagonists of A2AR and A2BR, respectively. PORT-6 is well tolerated to date. The TME within mCRPC bone metastases provides a unique target for A2AR and A2BR antagonism. Longitudinal blood and tissue samples, including bone biopsies, are being collected to enable biomarker analyses, allowing for elucidation of the relative contribution of A2AR and A2BR in suppressing anti-tumor immunity."

Clinical • IO biomarker • Metastases • P1 data • Castration-Resistant Prostate Cancer • Fatigue • Lung Cancer • Metastatic Castration-Resistant Prostate Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

ADPORT-601: TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=90 | Active, not recruiting | Sponsor: Portage Biotech | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Castration-Resistant Prostate Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Portage Biotech Announces Plans to Expand its Evaluation of Strategic Alternatives (GlobeNewswire) - "Portage Biotech Inc...reported that it is expanding its evaluation of strategic alternatives and implementing additional measures to extend its available cash runway. After a review of the Company’s future funding needs for clinical development of its adenosine antagonist platform as well as the current capital raising market for the Company, the Board of Directors has made the decision to pause further enrollment in the ADPORT-601 clinical trial of PORT-6 (adenosine 2A inhibitor) and PORT-7 (adenosine 2B inhibitor)."

Enrollment status • Genito-urinary Cancer • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Portage Biotech Reports Results for Fiscal Quarter Ended December 31, 2023, and Business Update (GlobeNewswire) - "Following the Trial Safety Committee recommendation, the Company commenced the third dose escalation cohort for PORT-6 Phase 1a portion of the ADPORT-601 trial....The Company looks forward to presenting interim and final data from Phase 1a portion of ADPORT-601 (PORT-6) at ASCO in June and SITC in November, respectively."

P1 data • Trial status • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

Portage Biotech Reports Business and Strategic Update (GlobeNewswire) - "The ADPORT-201 adaptive Phase 1a/1b clinical trial of PORT-6 (adenosine 2A inhibitor) and PORT-7 (adenosine 2B inhibitor) has been progressing well with strong interest from our eight academic centers in the US. The phase 1a dose escalation portion of the trial is enrolling quickly and there have been no safety signals of concern at the doses evaluated to date. The company looks forward to presenting data from this portion of the trial at a conference later this year...After a review of Portage’s funding requirements, the Board of Directors has made the difficult decision to pause further drug development in the PORT-2 iNKT program...'This was a difficult decision considering the promising phase 1 safety and translational data from the non-small cell lung and melanoma trial.'....Portage does not intend to disclose developments with respect to this evaluation unless and until it determines that further disclosure is appropriate or necessary."

Discontinued • P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

Portage Biotech Presents Updates on its iNKT and Adenosine programs at the Society for Immunotherapy of Cancer’s (SITC) 38th Annual Meeting (GlobeNewswire) - "Portage Biotech...announced the presentations of updates from its ongoing IMPORT-201 Phase 1/2 trial of PORT-2 (IMM60)...and its ADPORT-601 adaptive Phase 1a/1b trial for PORT-6 (A2A inhibitor) and PORT-7 (A2B inhibitor) in multiple solid tumors at SITC....The patient data from IMPORT-201, a multi-arm Phase 1/2 trial evaluating PORT-2 in multiple settings, included front-line and refractory NSCLC, and refractory melanoma, as a monotherapy and in combination with Merck’s anti-PD-1 therapy, KEYTRUDA....Dr. Sumit K. Subudhi...presented the design of the ADPORT-601 trial. This trial will evaluate a potent and selective A2A inhibitor (PORT-6), and an A2B inhibitor (PORT-7), alone and in combination with other immunotherapies specifically in tumors that overexpress adenosine. This trial is being conducted in collaboration with Merck and is being designed to explore A2A + pembrolizumab, A2B + pembrolizumab, and the triplet of A2A + A2B (both at the optimal biologic dose) + pembrolizumab."

Clinical protocol • P1/2 data • Melanoma • Non Small Cell Lung Cancer

ADPORT-601 (TT-10–101): first-in-human study of adenosine 2A (A2A) and adenosine 2B (A2B) receptor antagonists in participants with selected advanced solid tumors (SITC 2023) - P1/2 | "TT-10 (PORT-6) and TT-4 (PORT-7) are novel, potent and selective antagonists of A2AR and A2BR, respectively. Secondary endpoints include Objective Response Rate, Duration of Response, and Progression-Free Survival. Longitudinal blood and tissue samples will be collected."

IO biomarker • IO Companion diagnostic • Metastases • P1 data • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Portage Biotech Announces Collaboration with Merck to Evaluate Two Next-Generation Adenosine Antagonists in Combination with KEYTRUDA (Pembrolizumab) in Solid Tumors (GlobeNewswire) - "Portage Biotech Inc...announced that it has entered into a clinical trial collaboration agreement with Merck (known as MSD outside the US and Canada) to evaluate Portage’s next-generation adenosine antagonists in combination with KEYTRUDA^® (pembrolizumab), Merck’s anti-PD-1 (programmed death receptor-1) therapy, for patients with solid tumors. The collaboration will explore Portage’s adenosine 2A receptor (A2AR) antagonist, PORT-6, its adenosine 2B receptor (A2BR) antagonist, PORT-7, individually and together in combination with KEYTRUDA in prostate, renal, head and neck, colorectal, endometrial, ovarian and non-small cell lung cancers. Under the terms of the agreement, Merck will provide KEYTRUDA for Portage Biotech’s ADPORT-601, an adaptive Phase 1a/1b trial which plans to integrate proprietary biomarkers for selecting patients with high adenosine expression in order to identify those more likely to respond and have potential to benefit most from treatment."

Licensing / partnership • Colorectal Cancer • Endometrial Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

Portage Biotech Reports Results for Fiscal Quarter Ended June 30, 2023 and Business Update (GlobeNewswire) - "In recent weeks we have continued to build on the favorable interim data and early evidence of single agent activity from the Phase 1/2 trial of our lead program, PORT-2...'As a result, we are significantly expanding our clinical footprint to 17 planned sites with the goal of speeding up patient accrual by adding 15 additional sites, in the US, UK, and Spain. We expect final data from the Phase 1 portion of the trial in the first calendar quarter of 2024'....R&D costs increased by approximately $1.7 million to approximately $3.6 million, or approximately 89%, for the Fiscal 2024 Quarter from approximately $1.9 million in the Fiscal 2023 Quarter. The increase was primarily attributable to an overall increase in clinical trial costs of $0.8 million, part of $1.4 million of start-up and manufacturing costs associated with the adenosine assets (PORT-6 and PORT-7)...and the clinical trial costs and other R&D costs associated with the iNKT clinical trial for PORT-2 totaling $1.7 million."

Commercial • P1/2 data • Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

Portage Biotech Announces First Patient Dosed in Phase 1a Trial of PORT-6 in Select Solid Tumors (GlobeNewswire) - "Portage Biotech Inc...announced today that it has dosed the first patient in its Phase 1a trial, ADPORT-601...The trial is evaluating Portage’s adenosine 2A receptor (A2AR) antagonist candidate, PORT-6, in patients with solid tumors including prostate cancer, renal and non-small cell lung cancer."

Trial status • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=90 | Recruiting | Sponsor: Portage Biotech | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=90 | Not yet recruiting | Sponsor: Portage Biotech | Trial completion date: Sep 2023 ➔ Aug 2025 | Trial primary completion date: Jun 2023 ➔ May 2025

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor

[VIRTUAL] Phase I/II First-in-Human Study of TT-10 (A2AB inhibitor) as a Single Agent in Subjects with Advanced Selected Solid Tumors (AACR-NCI-EORTC 2021) - No abstract available

Clinical • P1/2 data • Oncology • Solid Tumor

Portage Biotech Announces Results for Fiscal Quarter Ended December 31, 2022 (GlobeNewswire) - "Company on track to initiate Phase 1 portion of ADPORT-601 trial by end of 2Q23; We anticipate establishing the recommended Phase 2 dose shortly and commencing the Phase 2 portion of the IMPORT-201 trial in the second quarter of 2023."

Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor

Portage Biotech Provides Research and Development Update (GlobeNewswire) - "Clinical Development Goals & Anticipated Readouts: Q4 2022 - Data from IMPORT-201 study to be presented at a major scientific conference in November; Activation of the ADPORT-601 adaptive Phase 1a/1b study of PORT-6 in multiple tumor types. 2023 - Initiation of IMPORT-201 Phase 2 trial (Q1); Submission to a major oncology conference with update on IMPORT-201 data (Q2; Addition of PORT-7 in the ADPORT-601 Phase 1a/1b study in multiple tumor types (1H); ADPORT-601 data and IMPORT-201 data presented at a major medical conference (Q4). 2024 - IMPORT Phase 2 ORR data submitted to a medical conference (1H); ADPORT-601 Phase 1b trial initiation (2H); IMPORT Phase 2 PFS data submitted to a medical conference (2H)."

New P1 trial • P2 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology

Portage Biotech Bolsters Pipeline with Acquisition of Four Candidates Targeting the Adenosine Pathway (GlobeNewswire) - "Portage Biotech...announced that it has signed an agreement to acquire Tarus Therapeutics, a private company developing adenosine receptor antagonists....The new assets acquired from Tarus Therapeutics include: (i) TT-10 (now PORT-6): an adenosine receptor type 2A (A2A) inhibitor to treat solid tumors. PORT-6 has received IND clearance and Portage expects to move into a Phase 1/2 clinical trial by the end of 2022 in an enriched patient population; (ii) TT-4 (now PORT-7): an adenosine receptor type 2B (A2B) inhibitor to treat solid tumors, which has received IND clearance and which Portage plans to initiate clinical development in 2023; (iiI) TT-53 (now PORT-8): a dual inhibitor of adenosine receptors 2A and 2B (A2A/A2B) to address solid tumors. Portage plans to submit an IND in the near future; (iv) TT-3 (now PORT-9): a gut selective A2B inhibitor to address gastrointestinal cancers, which is currently in preclinical studies."

IND • M&A • New P1/2 trial • New trial • Gastrointestinal Cancer • Oncology • Solid Tumor

TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov) - P1/2 | N=90 | Not yet recruiting | Sponsor: Tarus Therapeutics, Inc. | Initiation date: Sep 2021 ➔ Aug 2022

Trial initiation date • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • CD4

Adenosine receptor antagonists A2AR (TT-10) and A2BR (TT-4) demonstrate anti-tumor activity in 4T1-induced syngeneic breast cancer mouse model (AACR 2022) - "TT-10 & TT-4 alone was superior (p<0.05) to the VC as well as single agent anti-PD-1 in slowing tumor growth, which was further supported by the increase in T-cell activity observed in the end of study TIL analysis. Lastly, striking reductions in MDSC populations were also observed in both TT-10 & TT-4 treated mice, when compared to single agent anti-PD-1 and the VC."

IO biomarker • Preclinical • Breast Cancer • Oncology • Solid Tumor • CD8 • ENTPD1 • ITGAM • PTPRC

Combination of Adenosine antagonists A2AR (TT-10) and A2BR (TT-4) with checkpoint inhibitors demonstrate anti-tumor activity in CT-26 Murine Colon Tumor Allograft Model (SITC 2021) - "Methods Balb/c mice were implanted with CT-26 cells and randomly assigned to 8 groups per study; (1) vehicle control, (2) adenosine antagonist - 1 mg/kg A2AR (TT-10) 1 mg/kg or 3 mg/kg A2BR (TT-4), (3) 10 mg/kg Anti-mPD-1, (4) 5 mg/kg Anti-mCTLA-4, (5) 100 mg/kg Irinotecan, (6) adenosine antagonist + Anti-mPD-1, (7) adenosine antagonist + Anti-mCTLA-4, (8) adenosine antagonist+ Irinotecan. However, the combination of TT-10 + Anti-mPD-1 and TT-4 + Anti-mCTLA-4 showed the greatest tumor response and growth suppression. Furthermore, a striking reduction of CD25+FoxP3+ within the tumor was observed at day 3 in mice treated with A2AR alone, A2AR + anti-mPD-1 and A2AR + anti-m-CTLA-4 when compared to the vehicle control."

Checkpoint inhibition • IO biomarker • Preclinical • Colon Cancer • Gastrointestinal Cancer • Oncology • ADORA2A • CD44 • CD69 • CD8 • FOXP3 • IL2RA • LAG3

TT-10 as a Single Agent in Subjects With Advanced Selected Solid Tumors (clinicaltrials.gov) - P1/2; N=90; Not yet recruiting; Sponsor: Tarus Therapeutics, Inc.

Clinical • New P1/2 trial • Gastrointestinal Cancer • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • CD4

Tarus Therapeutics Receives Clearance From the FDA To Initiate Clinical Trial of TT-10 (A2AR Antagonist) in Cancer Patients (BioSpace) - "Tarus Therapeutics Inc...announced that it has received clearance from the US Food and Drug Administration (FDA) for its Investigational New Drug (IND) application to proceed with a clinical study of TT-10, an oral small molecule drug targeting the Adenosine A2A receptor (A2AR). Tarus plans to initiate a Phase 1a/1b study in the third quarter of 2021 to evaluate TT-10 in patients with advanced solid tumors both as a monotherapy and in combination with other anti-cancer agents."

IND • New P1 trial • Oncology • Solid Tumor

Tarus Therapeutics Seeks to Initiate Clinical Trial of TT-10 (A2AR antagonist) in Cancer Patients (Issuer Direct) - “Tarus Therapeutics Inc…announced that it submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) on March 5, 2021 to support the initiation of a clinical study of TT-10, an oral small molecule drug candidate targeting the Adenosine A2A receptor (A2AR)….If the IND application is allowed by the FDA, the Company plans to initiate a Phase 1a/1b study in the second quarter of 2021 to evaluate TT-10 in patients with advanced solid tumors both as a monotherapy and in combination with other anti-cancer agents.”

IND • New P1 trial • Oncology • Solid Tumor