Laura Prendergast

Laura Prendergast asked about the possibility of an accelerated approval pathway for Diraxonrasib in first-line PDAC and how a potential second-line approval for Diraxonrasib might factor into the statistical design for overall survival in the first-line study.

Answer

Mark Goldsmith, Chairman and CEO, stated that accelerated approval is an FDA decision, and while initial data is encouraging, the company generally prioritizes full approval strategies. Wei Lin, Chief Medical Officer, explained that the frontline study is still designed as a fully powered randomized trial for overall survival. He noted that second-line data provides confidence for both monotherapy and combination arms, and a potential second-line approval would primarily impact operational footprint, leading to increased ex-U.S. site assignments to minimize crossover effects.

Laura Prendergast asked about the possibility of an accelerated approval pathway for first-line PDAC and how Diraxonrasib's potential approval in second-line PDAC might impact overall survival statistics for the first-line study.

Answer

Mark Goldsmith, Chairman and CEO, stated that accelerated approval is an FDA decision, but noted initial data was encouraging. He emphasized the company's focus on full approval strategies. Wei Lin, CMO, explained they are designing a fully powered randomized trial for overall survival in frontline PDAC, independently testing both monotherapy and combination arms. He added that second-line approval impacts operational footprint, leading to more ex-U.S. sites to minimize crossover.

Laura Prendergast of Raymond James asked for the data disclosure cadence for colorectal cancer (CRC), including potential chemo or EGFR inhibitor combinations, and guidance on a registrational path for CRC.

Answer

CEO Dr. Mark Goldsmith stated there is no new guidance on future CRC data disclosures. He highlighted the recent December 2024 data release on the elironrasib and daraxonrasib combination in advanced CRC patients. He confirmed the company continues to evaluate various combination strategies and will share updates when a clear path forward is identified.

Laura Prendergast asked for comments on a recent Nature paper from MSK suggesting RMC-6236 has an additional mechanism of action, and whether the company was aware of or investigating this.

Answer

Dr. Mark Goldsmith, Chairman and CEO, confirmed that the company was not only aware of the mechanism but had in fact discovered and disclosed it at a scientific conference a few years prior. He stated that this effect likely contributes to the therapeutic index of RMC-6236 by impacting RAS signaling more profoundly in cancer cells with up-regulated RAS(ON) signaling compared to normal cells.

Inquired about the components of the updated revenue guidance, the timeline for HARBOR study data, and whether the $2 billion by 2030 forecast includes elenestinib.

Answer

The $2 billion by 2030 forecast is driven entirely by AYVAKIT. The updated guidance is based on strong patient starts and duration, with the free goods mix now derisked. It is too premature to provide a timeline for HARBOR data as the study is just beginning enrollment.

Inquired about the possibility of seeing BLU-808 data in urticaria by year-end, the potential need for a proprietary symptom score for BLU-808 in MCAS, and the methods for identifying MCAS patients with the D816V mutation.

Answer

The company expects to report initial BLU-808 data by the end of the year. For MCAS, they will leverage their SM experience to refine symptom measurement. They are using existing tests like Digital Droplet PCR to identify patients with the KIT mutation and are working to commercialize a more sensitive test. MCAS is viewed as a significant upside opportunity beyond the current SM market.

Laura Prendergast from Raymond James & Associates, Inc. asked for more detail on the registrational path for the Foresight MRD test and how it aligns with the regulatory pathway for cema-cel.

Answer

Dr. Zachary Roberts, EVP of R&D and CMO, confirmed the plan is for a concurrent launch of cema-cel and its companion diagnostic. He stated that they do not foresee the diagnostic's regulatory path creating an issue for cema-cel's approval and referred specific questions on the test's registration to Foresight's management.

Laura Prendergast pointed out that cell therapy trial enrollment in autoimmune indications has been slow and asked how Allogene plans to navigate these potential headwinds as it launches the Phase I study for ALLO-329.

Answer

Dr. David Chang, President and CEO, acknowledged the topic, noting his sense is that enrollment is now accelerating as rheumatologists gain familiarity with CAR-T therapy. He expressed optimism, stating that Allogene's use of an allogeneic product removes significant logistical complexities for physicians, which should help facilitate smoother trial execution compared to autologous therapies.