Brad Canino

Brad Canino asked about the triggers for initiating KT-621 Phase 3 studies, including how far into Phase 2s they need to reach, what data needs to be collected, and whether it will involve one or multiple study starts simultaneously.

Answer

Nello Mainolfi, Founder, President, and CEO, explained that Phase 3 studies require the completion of Phase 2 and a subsequent FDA meeting. He assured that Kymera will expedite this process as much as possible. He anticipates starting multiple Phase 3 studies in parallel, similar to the paradigm of three Phase 3 studies for atopic dermatitis registration, once the dose is selected.

Brad Canino sought clarification on the regulatory benefit of an interim PFS analysis for HARMONi-3, given the presumed need for overall survival (OS) data for filing. He also asked if the company's regulatory strategy, including the eGFR mutant approach, suggests an evolving view towards frontline lung cancer approvals based on PFS benefits and OS trends.

Answer

Dave Gancarz, Chief Business and Strategy Officer, and Manmeet Soni, Chief Operating Officer and Chief Financial Officer, explained that interim data enables earlier discussions with regulatory agencies, accelerating timelines. They emphasized that studies are powered for both PFS and OS, and that the magnitude of PFS benefit combined with OS trends could support approvals, aiming to accelerate drug availability to patients.

Brad Canino sought clarification on the regulatory benefit of adding an interim PFS analysis for HARMONi-3, given that final PFS is expected before OS data. He also asked if this strategy, combined with the EGFR mutant regulatory approach, indicates an evolving view towards frontline lung approvals based on PFS benefits and OS trends.

Answer

Dave Gancarz, Chief Business and Strategy Officer, explained that the interim analysis generates primary endpoint data, enabling earlier discussions with regulatory agencies without significantly delaying final PFS or interim OS. Manmeet S. Soni, Chief Operating Officer and Chief Financial Officer, added that depending on the magnitude of interim PFS data, it could accelerate submission. Dave Gancarz noted that approvals depend on a combination of factors, including magnitude of benefit and OS trends, with studies powered for both PFS and OS.

Brad Canino questioned the strategic rationale behind submitting the HARMONi study BLA first, given potential OS review issues, instead of waiting for the HARMONi-3 data (PFS and OS) expected in the second half of 2026. He also asked for qualitative details on the undisclosed in-house colorectal phase III data, its extent, and when it might be presented.

Answer

Urte Gayko, Chief Regulatory Quality and Safety Officer, explained that each indication has its own submission, and the HARMONi package is ready, representing a timely opportunity. Bob Duggan, Chairman of the Board and Co-CEO, provided historical context on FDA's support for the HARMONi trial. Dave Gancarz, Chief Business and Strategy Officer, described the colorectal data, mentioning previous ESMO 2024 presentations, expansion to U.S. patients with FOLFOX, and confidence in the regimen, while noting Akeso is also running a phase III.

Brad Canino asked about the clinical development plan for the STAT6 degrader, questioning which TH2 disease would be best to demonstrate a Dupilumab-like effect and whether biomarker data alone would suffice for initial patient studies.

Answer

Founder, President, and CEO Nellie Monofi explained that after the Phase 1 study, a small, rapid biomarker study in atopic dermatitis (AD) patients could quickly validate the drug's impact, leveraging the well-defined biomarker signature of Dupilumab. This could accelerate the program's progression into larger pivotal studies.

Brad Canino from Stifel asked about the company's confidence in TIC2 as a target for IBD given external news, and also questioned how Chimera balances its discovery efforts with its advancing clinical pipeline.

Answer

CMO Jared Golub expressed confidence in TIC2 for IBD, noting their degrader's selectivity spares IL-10 signaling, a key advantage. CEO Nello Manalfi added that discovery efforts remain robust, focused on validated pathways and difficult-to-drug targets in immunology, with the ambition to build the industry's leading oral immunology pipeline.

Asked about the evolution of patient eligibility for AYVAKIT as physicians gain experience, the profile of patients starting therapy at experienced practices, and the long-term vision for the eligible patient population.

Answer

Physicians with experience are broadening their view of eligible patients beyond the most severe cases. This trend is supported by claims data. The company believes almost all SM patients are eligible under the broad label and that the true prevalence of the disease may be underestimated, suggesting the peak opportunity could be even larger than currently projected.