Poorna Kannan

Poorna Kannan from Needham & Company, on for Ami Fadia, asked if there was a scenario for seeking accelerated approval for RESOLUTE-302 following the 2026 data update. She also requested an explanation for how combining a RasOn inhibitor with a PD-1/VEGF inhibitor could improve efficacy in RAS-driven tumors.

Answer

CEO Mark Goldsmith clarified that the trial is designed to generate a complete data package for a standard review, not an accelerated approval pathway, but noted the Breakthrough Therapy Designation could speed up the review process. Chief Medical Officer Wei Lin and CEO Mark Goldsmith explained the biological rationale, citing historical precedent with EGFR/VEGF combinations and preclinical data showing RAS inhibitors can reverse local immunosuppression, making tumors more sensitive to PD-1 blockade.

Poorna Kannan, on behalf of Ami Fadia at Needham & Company, asked what additional data is needed for zoldonrasib to support initiating pivotal combination trials and if updates would include other indications like CRC.

Answer

CEO Dr. Mark Goldsmith explained that the company is currently evaluating zoldonrasib in combination with daraxonrasib and other standard-of-care agents. He stated that generating this data is a high priority for the year, with additional clinical data on zoldonrasib expected mid-year. The goal is to use this information to define at least one pivotal trial for a mutant-selective inhibitor to start in 2026.

Poorna Kannan, on for Ami Fadia, asked for details on Cimbravo's sampling program, including utilization, conversion rates to prescriptions, and any initial barriers to the launch.

Answer

Chief Commercial Officer Ari Maizel confirmed the existence of a sampling program and a patient savings program, noting encouraging early signs of samples being accompanied by prescriptions. He added that they are already seeing covered claims, which helps mitigate access barriers.

Poorna Kannan from Needham & Company asked how baseline MADRS scores in KOASTAL-1 compared to the severity in the successful Phase II study and inquired about the gender mix being observed in the ongoing KOASTAL-2 and -3 trials.

Answer

Daljit Aurora, Chief Operating and Development Officer, stated that while different scales were used (MADRS vs. HAMD-17), both the Phase II and KOASTAL-1 studies targeted a similar moderate-to-severe MDD population. He also confirmed that the gender mix in KOASTAL-2 and -3 is now more representative of historical norms (approx. 2/3 female) compared to the anomalous male-heavy mix in KOASTAL-1.