A2aR

March 12, 2025 -- Portage Biotech Inc. (“Portage” or the “Company”) (NASDAQ: PRTG), a clinical-stage immuno-oncology company with a portfolio of innovative therapeutics, today 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. Advancing to this final dose escalation reaffirms Portage’s confidence in the safety and therapeutic potential of PORT-6, bringing the Company closer to identifying an optimal dose range for further clinical development. “Our review of the preliminary data reinforces our confidence in PORT-6 and supports the decision to complete dose escalation,” said Alexander Pickett, Chief Executive Officer of Portage Biotech. “We remain encouraged by the trial’s progress and potential and look forward to sharing further clinical updates later this year.” Combining PORT-6 and PORT-7 for a More Comprehensive Immunotherapy Approach In parallel, Portage is making final preparations for PORT-7, a potent and selective A2B antagonist, before dose escalation can commence in the same trial. The planned co-administration of PORT-6 and PORT-7 in ADPORT-601 will mark the first time two highly selective A2A and A2B antagonists are combined in patients, aiming to achieve 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. 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. The content above comes from the network. if any infringement, please contact us to modify.

The scientific discovery behind Adoram has been published in the Journal of Medicinal Chemistry (ACS Publications). In the original article “Discovery of the First Efficacious Adenosine 2A Receptor Negative Allosteric Modulators for High Adenosine Cancer Immunotherapies”, the team behind Adoram describes the effort produced to to go from a library of thousands of compounds to a few lead compounds. The multidisciplinary team worked hand-in-hand to synthesize original compounds, assess their activity in functional and translational assays, and design new ones based on a rational structure-activity-relationship (SAR) model. This article has been selected as a featured article, highlighting the significant interest and impact that this article is predicted to have on the medicinal chemistry community, especially groups working on the adenosine 2A receptor (A2AR). Access to the full text: https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01691

iStock, Sundry Photography The news comes on the heels of promising Phase I/Ib data, which point to the potential of casdatifan as a more effective alternative to Merck’s Welireg in renal cell carcinoma. Gilead will not move forward with Arcus Biosciences’ casdatifan, an investigational HIF-2a blocker that is being tested for kidney cancer. As per the California biotech’s Tuesday press announcement, Gilead’s window to exercise its exclusive option to obtain rights to casdatifan has “expired.” Arcus will retain full control over the asset and its development path forward. Arcus also announced that it will run a $150 million common stock offering—which Gilead will participate in—to help bankroll future studies of casdatifan. Arcus CEO Terry Rosen in a statement said that the biotech is “thrilled” to keep ownership of casdatifan, which he says “represents a transformational change for Arcus” and allows it to “address a significant unmet need for patients with an estimated $5 billion market opportunity.” Investors, however, are not as enthused: Arcus’ shares dipped 16% to $10.96 on Tuesday, a new 52-week low for the company, per SeekingAlpha . Analysts at Mizuho Securities, on the other hand, appeared optimistic about Arcus, writing in a Tuesday note that the stock offering “could allow [Arcus] to advance the casdatifan program independently” and provide freedom to assess the candidate as a monotherapy or as part of combination regimens. Tuesday’s news comes just days after Arcus presented promising Phase I/Ib data for casdatifan at the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. Results, disclosed over the weekend, showed that a 100-mg dose, given once a day, resulted in a 33% confirmed overall response rate (ORR) and a 52% stable disease rate in patients with metastatic clear cell renal cell carcinoma (RCC). Patients treated with this casdatifan dosage did not reach median progression-free survival (PFS) at the time of the readout, though a different dose level—50 mg twice-daily—had a median PFS of 9.7 months. Arcus is taking the 100-mg dose forward. According to Mizuho, these data suggest that casdatifan is “superior” to Merck’s Welireg (belzutifan), which is also a HIF-2a inhibitor that is FDA-approved for advanced RCC. In particular, the analysts zeroed in on casdatifan’s 9.7-month PFS in the 50-mg, once-daily dose arm, which they say compares favorably to Welireg’s 5.6-month PFS, as indicated in its label . Additionally, casdatifan’s 33% ORR is higher than Welireg’s 22%, as per Mizuho. Cross-study comparisons are inconclusive, however, in the absence of direct head-to-head trials. Arcus plans to ramp up investment to “position casdatifan as the HIF-2a inhibitor of choice,” Rosen said in a statement. The biotech will unveil more data for the therapy throughout 2025 and is preparing to launch another study, dubbed PEAK-1, which will test casdatifan with Cabometyx , Exelixis’s VEGF2 inhibitor, in metastatic clear cell RCC patients who had previously undergone immune-oncology treatments.