Revolution Medicines (RVMD) Q4 FY25 earnings call: guidance and Q&A

Clarify plans for daraxonrasib combination in first-line NSCLC, specifically if a registrational trial is still guided for this year.

Management confirmed high commitment to developing daraxonrasib in first-line lung cancer, exploring multiple options including dose optimization with expected combination partners and efficacy testing. They will share more information on their strategy later this year, noting the ongoing Ivonescimab combination studies as a factor.

“The reality is that there are a number of options available to us. We continue to both dose optimize daraxonrasib in combination with the combination partners that you might expect us to use for that indication and also do efficacy testing to get the requisite proof-of-concept required to invest in a large base through trial.”

asked by Albert Agustinus · answered by Stephen Kelsey

What efficacy measures to expect at the top-line readout for the second-line PDAC trial and color on the event rate.

Management stated the RASolute 302 readout is OS event-driven and powered for OS, but also overpowered for PFS, so an interim read on PFS information will be available. They could not provide specific expectations beyond direct comparison to standard of care.

“It is an OS event-driven readout. And the study is powered for OS, but it's, of course, also overpowered than for PFS. So we'll have an interim read on that information.”

asked by Lut Ming Cheng · answered by Mark Goldsmith

To what degree could daraxonrasib use post-progression in the control arm of first-line PDAC studies impact outcomes if 2L daraxonrasib is approved, and the importance of OS in these studies.

Management acknowledged a potential risk of crossover but noted that timing of 1L trial initiation relative to 2L approval and global enrollment (where 2L approval may not yet exist) could buffer this concern. They emphasized the broad coverage of PDAC patients from second-line to adjuvant, aiming for optionality including chemotherapy-free opportunities.

“There is some potential risk for that. Of course, the label would not necessarily indicate ability to cross over unless somebody was declared that they were now formally a second-line patient, we wouldn't be able to speak to what somebody might do off-label, but there is some risk associated with that.”

asked by Michael Schmidt · answered by Mark Goldsmith

Why combine with Bristol's PRMT5 inhibitor in addition to Tango's, and how go/no-go decisions will be made for Ivonescimab combo studies.

Management explained the Bristol collaboration for PRMT5 inhibitors is an inclusive approach, making their compounds available to others, and not a specific vote on any inhibitor. For Ivonescimab, decisions will be data-driven, recognizing its potential advantage over first-generation PD-1s, especially in GI tumors where it offers a significant opportunity.

“This isn't really a signal or a vote on our part about any particular inhibitor. It doesn't speak at all to the work that's ongoing with Tango or Amgen. It's rather more of an inclusive approach and to allow our compounds to be considered in other context as well.”

asked by Charles Zhu · answered by Mark Goldsmith

Confirmation on RASolute 302 interim analysis event thresholds and the long-term vision for the PDAC treatment paradigm.

Management stated they cannot comment on interim analysis thresholds. For the PDAC treatment paradigm, they envision a future with multiple options covering second-line, first-line (monotherapy and combination with chemotherapy), and adjuvant settings, potentially offering chemotherapy-free opportunities and impacting resectable cancer.

“We really are covering the gamut of patients of pancreatic cancer from second-line therapy all the way to resectable and potentially curable pancreatic cancer.”

asked by Marc Frahm · answered by Alan Bart Sandler

Are there restrictions on treatment beyond progression (TBP) in Phase III PDAC studies, and how might it impact overall survival.

Management clarified that TBP was not permitted in the RASolute 302 study because it was too far underway to modify. However, for newer, earlier-line studies coming online, investigators are encouraged to evaluate TBP where it makes sense to generate more information.

“It's not in the 302 study because that study was already too far underway to make that modification that would be difficult to do in the middle of the study. And so progression beyond -- treatment beyond progression was not permitted, is not permitted in the 302 study.”

asked by Laura Prendergast · answered by Mark Goldsmith

Vision and strategy for CRC, prioritizing partnerships vs. independent pursuit, and in-licensing opportunities.

Management stated that CRC is a complex and heterogeneous disease, making single-agent development difficult and requiring combinations. Their philosophy is to be a stand-alone global organization, not prioritizing partnerships over independent development. While in-licensing is possible, it's not the base case; the focus is on identifying and prosecuting effective RAS(ON) inhibitor combinations to registration.

“Our plan is to figure out which combinations involving a RAS(ON) inhibitor can make the biggest impact on colorectal cancer and prosecute those to registration.”

asked by Jay Olson · answered by Stephen Kelsey

Does RM-055 address secondary mutations or only RAS mutations, patient selection, and whether it replaces or is a next-line option to daraxonrasib.

Management clarified that point mutations have not emerged as the major form of resistance for daraxonrasib; rather, it's reactivation of the RAS pathway through other means (e.g., amplification, increased signaling). RM-055 is designed to address this, not primarily new oncogenic mutations. More details will be presented at an upcoming scientific meeting.

“What has emerged is reactivation of the RAS pathway through other means, typically amplification of the original mutant allele through increased signaling, for example, through RTKs to increase flux through the pathway and so on.”

asked by Leonid Timashev · answered by Mark Goldsmith