Revolution Medicines, Inc. Q2 FY2024 earnings call

• In pancreatic cancer, RMC-6236 has shown compelling preliminary progression-free survival and overall survival data. Safety findings were promising with most adverse events being low grade. Antitumor durability data were compelling with median progression-free survival and overall survival showing favorable comparisons to standard-of-care. - The company is preparing RMC-6236 to move into its first pivotal monotherapy studies. Progress with other RAS(ON) inhibitor pipeline includes RMC-6291 and RMC-9805. - Appointed Frank Clyburn to the Board of Directors and made several strategic leadership hires across various departments to scale the organization.

In the second quarter of 2024, Revolution Medicine ended with $1.59 billion in cash and investments, down from $1.7 billion at the end of Q1. R&D expenses for Q2 2024 were $134.9 million compared to $98.0 million in Q2 2023, primarily due to increases in clinical trial expenses, preclinical portfolio expenses, personnel-related expenses, and stock-based compensation expense. G&A expenses for Q2 2024 were $21.7 million compared to $14.6 million in Q2 2023, mainly due to increases in personnel-related expenses, commercial preparation activities, and stock-based compensation expense. Net loss for Q2 2024 was $133.2 million compared to $98.3 million in Q2 2023. The company expects full-year 2024 GAAP net loss to be between $560 million and $600 million, including estimated noncash stock-based compensation expense of between $70 million and $80 million.

• Expect full-year 2024 GAAP net loss to be between $560 million and $600 million, including noncash stock-based compensation expense of $70 million to $80 million. - Plan to initiate the first global, registrational Phase III study (RASolute 302) this year for RMC-6236 as a second-line therapy for metastatic pancreatic cancer. - RMC-6291 in combination with RMC-6236 study is ongoing and expects to share initial data in the fourth quarter of 2024. - RMC-9805's first-in-human monotherapy study is enrolling well, with dose optimization ongoing and expected to share initial safety, tolerability, and antitumor activity in the fourth quarter.

Q: Hey thanks for taking my questions. Maybe just to start off, when you think about the PFS data you released in pancreatic cancer the other day, it looks a little bit better than the -- what was achieved kind of with the G12C inhibitors in that subpopulation of pancreatic patients. Do you think that similar gap should kind of be expected when we look at monotherapy data in other settings where we kind of have mature G12C inhibitor data, whether that's lung cancer or ultimately some other settings like colorectal cancer? Or is just the biology just way too different across tumors?

A: Thanks, Mark. Appreciate your question. I think at this point, given that data will be rolling out in coming months and over the next year, I think it's best just to let the data speak for themselves. There's obviously -- there are many differences in the subtle aspects of biology comparing one tumor type to another. Whether or not that nets out in any particular direction, I think can just be determined empirically.

Q: Hey thanks for taking my questions. I had one on the potential Phase III study in second line non-small cell lung cancer for 6236. I mean one would think that the easiest or the simplest design would just be a one-to-one randomization compared to docetaxel. But I'm just curious, there may be a scenario where KRAZATI has full FDA approval in G12C-positive patients at some point in the future based on the KRYSTAL-12 study. And I was just wondering to what degree that might factor into the potential trial design. Would you, for example, allow KRAZATI in the control arm for G12C-positive patients, assuming that the trial obviously would include those patients? Or is that something that is not feasible, in your opinion?

A: Thanks, Michael. Maybe I'll just say something brief about it. And then if either Steve or Wei wants to add something, they can do that. Maybe my general comment is G12C is clearly the most complicated part of the lung cancer trial for RMC-6236. There are subtleties associated with that, as you just alluded to. We've not described our plan yet for lung cancer. We put forth sort of a prototype last October, but we've not laid that out in our expectations to do that in conjunction with disclosure of the data that would support it. So I think we'd be getting out a little bit over our skis to commit today, but whether there are any principles Steve or Wei wants to add to that, feel free to.

Q: Hi, thanks for taking the questions. I'm hoping you could just help us level set expectations into the Phase I non-small cell lung cancer update in fourth quarter in terms of patient numbers. Just kind of drafting from the update that we saw in July in pancreatic, should we expect a similar ramp-up in the number of evaluable patients across doses 160 to 300 milligrams? And then, just as a follow-up in pancreatic cancer, Mark, I guess how should we be thinking about sort of additional updates, either kind of within the data set that you presented in July, perhaps at medical meetings or sort of follow-on updates as that trial matures? Thank you.

A: Yes. Thanks, Eric. Nice to talk with you. On the second question of PDAC, I think we've made a pretty clear commitment to provide an update to those data when we have a meaningful update, but we've not been able to share a specific time line or setting in which that will happen. So I don't think we have anything new to add to that today. With regard to the lung cancer data, it's hard really to go into that level of forecasting what we'll communicate. I think generally speaking, we're going to be in the ballpark with the kind of numbers that we've enrolled previously for pancreatic cancer, but the analysis will just have to speak for self at the time.