REVOLUTION MEDICINES INC earnings calls

CRC plans and lung G12C confidence

Q (Marc Frahm · TD Cowen): Analyst asked what proof-of-concept would look like in CRC after adagrasib's confirmatory trial and how confident management is that their G12C lung program can beat other first-line or second-gen trials.

A: Mark asked to defer CRC until they can show plans and data. Alan said elironrasib has a strong safety and efficacy profile and is competitive alone and in combinations. He also said their mutant-selective agents could target over 70% of RAS mutant NSCLC patients.

"We believe that elironrasib has a very good profile, both safety and efficacy." — Alan Bart Sandler

Where multi-selective fits in frontline

Q (Yue-Wen Zhu · LifeSci Capital): Analyst asked how they would position a RAS multi-selective drug in frontline given multiple mutant-selective agents, and whether the term referred to daraxonrasib or RM-055.

A: Management said all options remain on the table and they pursued both multi-selective and mutant-selective inhibitors to keep flexibility. They said it's premature to commit to a single regimen and they are advancing two mutant-selective inhibitors with a third coming, while not deprioritizing daraxonrasib or RM-055.

"We've intentionally pursued both the multi-selective as well as the mutant selective inhibitors to create the most optionality for us and then ultimately for patients." — Mark Goldsmith (CEO·CHAIR)

daraxonrasib EAP and Europe timing

Q (Michael Schmidt · Guggenheim): Analyst asked for early feedback from the daraxonrasib EAP versus trial results and what regulatory timelines in Europe might look like.

A: Management said the EAP is robust and serving many patients but they lack a mechanism for explicit quantitative feedback since it is a clinical access program. They get qualitative enthusiasm from institutions and anecdotal encouragement from patients. On Europe, they said EMA intends an expedited phase review but specific timing is a question for the EMA.

"We don't have a mechanism to get explicit or quantitative feedback from those who are prescribing it since that -- this is a clinical access program." — Mark Goldsmith (CEO·CHAIR)

PDAC crossover risk in frontline trial

Q (Cory Kasimov · Evercore): Analyst asked how they will handle control-arm dropouts who later get commercial daraxonrasib and whether that risks OS and PFS measurement; also asked about EAP-to-commercial conversion.

A: Mark said the first question is about first-line PDAC and crossover risk and passed the question to Wei Lin to comment. He said he would come back to answer the EAP conversion question after Wei's comments.

"The first question is about first-line PDAC in the Phase III trial, I think you're really raising the question of crossover, some form of crossover risk for patients moving on to daraxonrasib." — Mark Goldsmith (CEO·CHAIR)

How crossover and EAP affect PDAC trial

Q (Wei Lin · Evercore): Analyst asked whether control-arm dropouts could affect PFS or OS in the Phase III frontline PDAC trial and how EAP patients convert to commercial after approval.

A: Wei Lin said the Phase III has co-primary endpoints of PFS and overall survival and that dropouts would not affect PFS but could affect overall survival. He said they will be thoughtful about where they open sites and will work with investigators to ensure patients understand options. Mark added that once approved, patient support services will aim to minimize interruptions and transition patients to commercial supply within a few months.

EAP site experience and PD-L1 thresholds

Q (Lut Ming Cheng · JPMorgan): Analyst asked whether EAP patients come from experienced daraxonrasib sites, why over 90% of requests were accepted, and whether 307/308 trials set PD-L1 minimums or maximums.

A: Alan said they will not set strict PD-L1 quotas and will let a large Phase III study yield natural representation, with stratification to balance arms. Mark said EAP prescribers include both experienced and inexperienced sites and that approvals follow clear FDA-cleared protocol eligibility criteria. He said most rejections are simply due to ineligibility and qualified U.S. licensed physicians from approved institutions are approved.

"It comes down to the eligibility criteria that are established in the FDA-cleared protocol." — Mark Goldsmith (CEO·CHAIR)

PRMT5 combo potential and portfolio needs

Q (Faisal Khurshid · Jefferies): Analyst asked their view on PRMT5 combinations from partner Tango and whether RevMed needs its own PRMT5 inhibitor.

A: Management said PRMT5 is an intriguing biological and pharmacologic hypothesis and Tango's initial data show high response rates that need more patients, dose optimization and longer follow-up. They said they do not need to add a PRMT5 inhibitor to their own portfolio now and that daraxonrasib should serve as a backbone to which they may add various agents.

"Tango has now put forth some initial data that show high response rates." — Mark Goldsmith (CEO·CHAIR)

Possibility of first-line accelerated approval

Q (UBS): Analyst asked whether accelerated approval in the first-line setting is possible now that the NDA has been accepted.

A: Management said there was not much to add and that the NDA is primarily driven by the randomized 302 data set in second-line metastatic pancreatic cancer. They noted there are additional data the FDA can review and said how the agency will proceed is something they will learn over time.

"The NDA is primarily driven by the 302 data set, which is randomized data in patients being treated for second line -- in second line for metastatic pancreatic cancer." — Mark Goldsmith (CEO·CHAIR)

What data shared for breakthrough and pricing view

Q (Alec Stranahan · BofA): Analyst asked which data supported breakthrough therapy designation and whether there is any early thinking on pricing in combinations that use lower daraxonrasib doses.

A: Management said you generally must share nearly everything with the FDA and they cannot provide more specificity on what was shared. They also said it is too early to discuss pricing or combinations as none are near commercialization.

"You have to share pretty much everything with the FDA." — Mark Goldsmith (CEO·CHAIR)

CRC visibility and exploring other tumors

Q (Laura Prendergast · Stifel): Analyst asked what to expect from the fourth-quarter visibility into CRC strategy and whether they will pursue registrational moves outside the main three RAS indications.

A: Management said they will show data and lay out their development plan and that investors will judge the conviction themselves. They said daraxonrasib could be used across many tumor types, they have some public and some unpublished data, and they will continue to explore other contexts via collaborations though they have prioritized the big three for now.

"Visibility into our development strategy we'll show some data, and we'll tell you what we plan to do with it." — Mark Goldsmith (CEO·CHAIR)

Commercial planning and EAP patient cadence

Q (Leonid Timashev · RBC): Analyst asked whether the commercial sales force will be sized for second-line PDAC or also for frontline and NSCLC, and asked when the >2,000 EAP patients began to be added.

A: Mark said the EAP number he mentioned is greater than 2,000 and that the program was approved within a couple of days after filing and drug shipments began within three weeks, growing from a trickle to more as sites joined. He deferred the sales force sizing question to Anthony Mancini.

"As you might recall, I think that once we filed the EAP request, it was approved within a couple of days." — Mark Goldsmith (CEO·CHAIR)

Size and readiness of U.S. sales team

Q (Anthony Mancini · RBC): Analyst asked for detail on the commercial organization and sales force sizing for PDAC and future indications.

A: Anthony said they have prepared for some time and are ready for a successful PDAC launch. He said the commercialization infrastructure has broad parts that can apply to future indications and that their fully trained sales force is around 60 individuals with field access, patient services, MSL and thought-leader teams in place.

Need to run trial versus divarasib

Q (Gugan Raghuraman · Wolfe): Analyst asked whether, after Roche's win with sotorasib/adagrasib, they would need to run a head-to-head trial versus divarasib if it is approved.

A: Alan said they will discuss with the FDA but that the control arm is set by the standard of care and full approvals that exist when a study is started. He added that because a full approval by a competitor is not the case now, they do not feel a head-to-head against that agent would be necessary.

"The control arm is dictated by the current state of affairs at the time that the study is initiated, and that requires not necessarily a positive study, but that requires a full approval." — Alan Bart Sandler