Jeet Mukherjee

Jeet Mukherjee asked for Kymera's thoughts on ITK as a target and recent data, comparing and contrasting it with STAT6, in the context of the evolving competitive landscape for next-generation oral agents in atopic dermatitis.

Answer

Nello Mainolfi, Founder, President, and CEO, emphasized that STAT6 targets the most validated pathway (IL-4/IL-13) with established safety and efficacy, and KT-621 has shown preclinical efficacy mimicking biologics and good safety in chronic toxicology studies. He stated that Kymera decided against pursuing ITK due to human genetics indicating challenges with clearing EBV and potential lymphoma development, which did not align with Kymera's risk/benefit profile. He reiterated that more mechanisms, especially complementary ones, are beneficial for patients and market expansion.

Jeet Mukherjee asked for Kymera's perspective on ITK as a target in the evolving atopic dermatitis (AD) competitive landscape, comparing and contrasting it with STAT6, and commenting on recent ITK data.

Answer

CEO Nello Mainolfi emphasized that STAT6 targets the highly validated IL-4/IL-13 pathway, with KT-621 demonstrating strong safety and efficacy, including completion of chronic toxicology studies without adverse events. He explained that Kymera previously decided against ITK as a target due to human genetic data indicating challenges with EBV clearance and lymphoma development, which did not meet the company's risk/benefit criteria for target selection, while acknowledging that more mechanisms are beneficial for patients.

Jeet Mukherjee from BTIG inquired about payer willingness to cover an oral therapy with Dupixent-like efficacy, questioning if superior efficacy would be required for market access.

Answer

CEO Nello Mainolfi argued that an oral option with comparable efficacy offers significant value through convenience, improved quality of life, and ease of use, which should resonate with payers. He pointed to the market success of a current oral AD drug with a black box warning as evidence of the high demand for oral therapies, and noted that new options are needed to expand the low market penetration in moderate-to-severe AD.

Jeet Mukherjee from SVB Securities asked about the potential for KT-621 in patients who have previously been treated with DUPIXENT and whether this is an area Kymera plans to evaluate more fully.

Answer

CEO Nello Mainolfi clarified that while there is an opportunity post-dupi, the primary goal is to provide a first-line option for the millions of patients not on biologics. He positioned KT-621 as a drug to expand patient access and become a primary Th2 therapy, rather than focusing on the smaller post-biologic setting.

Jeet Mukherjee inquired about the strategic decision to discontinue the TYK2 degrader program, asking if it was purely a capital allocation decision or if the molecule's profile or the competitive landscape influenced the choice, noting the apparent swap for the IRF5 program.

Answer

President and CEO Nello Mainolfi explained the decision was driven by resource prioritization. He emphasized the need to allocate capital and personnel to the STAT6 program (KT-621), which he described as potentially one of the largest in the industry. He contrasted the high competitive intensity in the TYK2 space with the IRF5 program, which Kymera views as a first-in-class opportunity with a highly differentiated profile and minimal competition.

Jeet Mukherjee asked about investigators' willingness to use Zifdomenib off-label in frontline or combination settings post-approval, and also inquired about the percentage of clinical trial site overlap with Kura's approved competitor.

Answer

Chief Medical Officer Dr. Mollie Leoni indicated that physicians will do what is best for the patient and that Kura's frontline trial offers a formal option for those patients. Regarding site overlap, she noted it was minimal for the monotherapy study and expects it to decrease significantly for Phase 3 trials, as sites typically cannot run multiple similar large studies.

Jeet Mukherjee asked if Arvinas and Pfizer have fundamentally different views on maximizing Vepdeq's value, given the ongoing discussions. He also inquired if Arvinas is already in active dialogue with other potential partners for the asset.

Answer

CEO John Houston asserted that Arvinas and Pfizer are aligned on the goal of maximizing Vepdeq's value, even if their views on its future development differ. He clarified that Arvinas cannot run an active partnering process while the collaboration with Pfizer is still in place. However, he expressed confidence that if the asset is returned, there would be strong interest from other companies to license and develop the near-approved drug.

Jeet Mukherjee asked for expectations regarding the ARV-102 data update in Parkinson's patients later in the year, including any potential biomarkers for functional improvement. He also questioned if abstract embargo rules might limit the details in the top-line press release for VERITAC-2.

Answer

Chief Medical Officer Noah Berkowitz outlined that initial healthy volunteer data will be shared in April, with an update on at least the single ascending dose data in Parkinson's patients hoped for later in the year. Chief Scientific Officer Angela Cacace added that nonclinical studies suggest potential to move neuroinflammation and lysosome function biomarkers. CEO John Houston confirmed that embargo rules would likely place some limits on the top-line data disclosure.

Jeet Mukherjee asked what target product profile the higher 44.5mg dose would need to show to be chosen over the 67.4mg dose for a pivotal study. He also asked if the H2 expansion update would be limited to TNBC or include other cancers like ovarian.

Answer

An executive, likely CEO Dr. Martin Huber, explained that the higher dose would need to demonstrate meaningfully better efficacy, such as getting patients into response faster, to justify its selection over the simpler 67mg regimen. He also clarified that due to the recent restructuring, the company is now focused on breast cancer. Therefore, the H2 update will be for TNBC only, and plans for expansion cohorts in other tumor types have been paused to extend the cash runway.

Jeet Mukherjee from BTIG asked about the primary infrastructure hurdles for regional centers adopting CAR-T therapy and whether the upcoming DLL-3 and Claudin 18.2 data would be in abstracts or saved for conference presentations.

Answer

Alan Bash, President of CARVYKTI, identified capacity, space, and staff as factors, but highlighted that the outpatient setting helps overcome these hurdles. He also mentioned monitoring apheresis and cryopreservation capacity. Chief Medical Officer Mythili Koneru clarified that the DLL-3 program will have an oral presentation at ASGCT, and key dose-escalation data for both programs will be in the ASCO abstracts released next week.

Jeet Mukherjee inquired about whether the upcoming ASCO poster for the ROR2 program would feature an updated data cut and if the mid-year EpCAM update would include data from the 300-microgram and 900-microgram dose cohorts. He also asked about the potential pivotal trial design for the AXL program (Mec-V) and any options for accelerated approval.

Answer

Executive Eric Sievers confirmed the ROR2 (Oz-V) ASCO presentation will have an updated data cut with additional safety and long-term outcome data. For the EpCAM program, he anticipates a mid-year update on 25-30 patients but noted it was too early for data from the 900-microgram dose. Sievers also outlined a potential pivotal trial for Mec-V against docetaxel in 2nd/3rd-line mKRAS non-small cell lung cancer. CEO Jay Short added that the ROR2 asset has a potential path to accelerated approval in head and neck cancer.

Jeet Mukherjee of Leerink Partners inquired about the status of partnering discussions for the ROR2 and CTLA-4 programs and asked for details on the AXL program, specifically the percentage of patients positive for both AXL and mutant KRAS.

Answer

Executive Jay Short stated that partnering discussions for the ROR2 program are both advanced and new, with recent positive HPV data expected to attract more interest. Regarding the AXL program, he noted a strong correlation of over 70% between AXL and mKRAS expression. Executive Eric Sievers added that one patient with prior sotorasib treatment had a response, but no patients had prior exposure to a pan-KRAS inhibitor.

Jeet Mukherjee of BTIG requested color on the month-over-month new patient starts for Niktimvo, the proportion of new patients within the 1,250+ infusions, and any details on refill rates.

Answer

Chief Commercial Officer Steven Closter explained that it is very early in the launch. The 1,250+ infusion figure is an estimate from partner Incyte that includes some pent-up demand and patients from an EAP. He noted that while it's largely new patients, it will take another quarter to see a true run rate. The drug is being well-received, initially in the fourth-line setting, and onboarding at treatment centers has been smooth.

Jeet Mukherjee inquired if Viking is considering dosing regimens less frequent than once-daily for the oral formulation, given its observed weight loss maintenance. He also asked about expectations for the pace of enrollment in the Phase III trials.

Answer

Brian Lian, President and CEO, confirmed that the company plans to explore less frequent oral dosing in a future maintenance study. Regarding Phase III enrollment, he noted that while the rapid Phase II enrollment was encouraging, the pace for the much larger pivotal studies remains to be seen once they are initiated.