Revolution Medicines (RVMD) Q1 FY26 earnings call: guidance and Q&A

Asked about the nature of data to be shared for RASolute 309 (zoldonrasib + daraxonrasib) and the additive efficacy needed to justify the combination over monotherapy.

Management stated it's too early to detail the presentation but expects it to justify their plans. They noted that durability is the most important parameter for additive efficacy, considering historical benchmarks and the totality of evidence.

“durability is the most important parameter.”

asked by Cory Kasimov (Evercore ISI) · answered by Mark Goldsmith

Inquired about the demand for the EAP for daraxonrasib, the potential number of patients benefiting, and the estimated size of the second-line pancreatic cancer opportunity in the U.S.

Management confirmed high demand for the EAP since its announcement, with resources being deployed to meet the need, but could not project specific patient numbers. For 2L pancreatic cancer, they estimated 60,000 new cases annually in the U.S., with 50-60% diagnosed with metastatic disease, and about half of those receiving first-line treatment proceeding to second-line.

“The demand has been very clear from the moment that it was announced. And we don't expect that to slow down anytime soon.”

asked by Michael Schmidt (Guggenheim Securities) · answered by Mark Goldsmith

Asked for clarification on the reasons for upsizing the RASolve 301 study (daraxonrasib in NSCLC), previous and current power, and impact on readout timeline.

Management stated the upsizing from 420 to 590 patients was to further prioritize and increase statistical power for the overall survival component of the dual primary endpoint, given high conviction from 302 results and Phase I data. They do not expect the upsizing to change the timeline for substantial enrollment completion this year due to the high pace of enrollment.

“we've realized the importance of overall survival and given the results that we've seen in 302 and also the Phase I monotherapy data, we have a very high conviction that on our ability to obtain overall survival benefit.”

asked by Faisal Khurshid (Jefferies) · answered by Alan Bart Sandler

Questioned why RASolute 309 (zoldonrasib + daraxonrasib) compares to chemotherapy, suggesting daraxonrasib monotherapy might be a more appropriate comparator given its strong survival data.

Management explained that chemotherapy remains the standard of care until FDA approves a different treatment as such. They acknowledged the potential of daraxonrasib monotherapy and combinations (like with chemo in 303) but emphasized providing a 'fulsome set' of options based on science and clinical data, as patient needs vary.

“today, standard of care is chemotherapy. And until there's a data set that moves the FDA to approve a different treatment and a different treatment at the level that people consider the new standard of care then chemotherapy is the standard of care.”

asked by Marc Frahm (TD Cowen) · answered by Mark Goldsmith

Asked about the company's strategy and confidence in achieving a chemo-free option in frontline pancreatic cancer.

Management highlighted two main strategies: daraxonrasib monotherapy (already incorporated into Phase III first-line trial) and combining a mutant selective inhibitor with daraxonrasib (e.g., zoldonrasib + daraxonrasib for RAS G12D). They also mentioned exploring other combinations like immunologic agents or PRMT5 inhibitors.

“monotherapy daraxonrasib... the data -- single-arm data that we've shown so far are compelling enough that it just -- very much justified incorporating that into the Phase III first-line trial.”

asked by Jonathan Chang (Leerink Partners) · answered by Mark Goldsmith

Inquired about the sales force build-out and a more refined understanding of the 1L to 2L pancreatic cancer attrition rate, specifically what percentage are unfit for therapy versus unwilling to take more chemotherapy.

Anthony Mancini stated that U.S. field-based teams (med affairs, market access, sales) are in final stages of build-out, with MSL and market access teams already engaging. The U.S. sales force is being onboarded and will be ready for HCP engagements upon FDA approval. Mark Goldsmith explained that the reasons for 1L-2L attrition are varied and not always clear, including performance status, concurrent illness, patient preference to avoid chemo, or not surviving to 2L. He noted a more convenient, better-tolerated pill could impact patient decisions.

“we're in the final stages of onboarding our U.S. sales force. We're pleased with the team. They have deep expertise in solid tumors across GI malignancies and in oral oncology, and they'll be fully trained and ready to go with HCP engagements if we were to receive an FDA approval.”

asked by Kelsey Goodwin (Piper Sandler) · answered by Anthony Mancini

Asked if initial ORR for daraxonrasib is a good predictor for PFS and OS benefit in larger studies, and if third-line plus patients will be allowed into the EAP.

Management confirmed that the EAP includes previously treated patients beyond the pure second-line population of the 302 trial. Regarding ORR, they stated it broadly correlates with PFS but is not a tight stoichiometric relationship. They noted that RECIST ORR can be imprecise, with patients taking up to 6 months to meet definitions, and that multiparametric analysis is better for predicting PFS, which they consider a competitive advantage.

“ORR is broadly correlative with PFS. It's not such a tight stoichiometric relationship that you can actually say that the ORR is 5 percentage points higher than the PFS is going to be 5 percentage points higher.”

asked by Alec Stranahan (Bank of America) · answered by Stephen Kelsey