Mark Goldsmith: Yes, that’s a very good question, Marc. I think our concept here is less about that they’re being gated by a particular result in the first wave and more about making sure we have the resources and focus to move those first 3 inhibitors forward as efficiently and effectively as possible. So I think that’s the main thing that’s gating it, it’s more about resources and less about getting to a particular result. With that said, obviously, amongst these first 3 inhibitors, we expect to see activity, tolerability and safety that guide us to confidence that the platform itself delivers as expected and so on. And that will also likely increase the availability of resources as well. As you know, there’s a relationship there.
So that at least indirectly would open up the availability resources for the second wave. So that’s how we think about it. I don’t think there’s a particular result. There are a number of things we could see next year that would give us and I think investors confidence that the platform is valid and that there should be things reading through to other inhibitors in the platform.
Operator: And our next question comes from Michael Schmidt with Guggenheim Partners.
Michael Schmidt: I had 2 development-side questions. Perhaps first on 6291, the G12C inhibitors. So what are your thoughts on the possible registration pathway down the road in context of these moving competitive environment in the KRAS G12C space where you probably have multiple OFF inhibitors fully approved in the second line perhaps registration studies ongoing in first line? How do you think that could affect — what are your thoughts on the ultimate development strategy for 691 in that context?
Mark Goldsmith: Yes. Steve, do you want to…
Steve Kelsey: Sure. I can. Yes. And I think Mark has just laid out the first premise which is that the most likely development part for RMC-6291 was going to be in combination with something rather than as a single agent. We are not going to exclude development to a single agent is demonstrably superior to the approved KRAS(OFF) inhibitors. But the most likely thing is it will be developed in combination. And then really, in that context, it’s going to be a combination of efficacy and tolerability in combination with whatever the best companion is. We have the opportunity to combine with something possibly even with RMC-6236 and go chasing after patients that have progressed or failed KRAS G12C(OFF) inhibitor, we can go head-to-head with them in that second-line space or we can go head-to-head with them in any of the first-line spaces that are currently all available to us.
And I think it really largely depends on what we see in the initial phase of the Phase I trial which, of course, will include combination, dose-escalation, components as we get further up the single-agent dose escalation. So I think let’s keep that in mind. We’re very optimistic about the potential for RMC-6291 and we’re not shying away from pretty much all of the potential opportunities for .
Mark Goldsmith: If I could add to Steve’s comment there, I think he said a couple of important things I want to tie back together. Preclinically, we, of course, showed a pretty extensive data set comparing it head-to-head with one of the leading care CBF inhibitors that didn’t necessarily foreshadow that, that’s going to be the primary path forward in the clinic. That was simply to demonstrate that the mechanism behind the inhibitor translates into the best possible RAS-pathway expression and therefore, antitumor effects regressions and durability. We believe that. Steve is often fund of saying that in a combination treatment regimen for RAS inhibitor, you want to combine the very best RAS inhibitor you can with the very best companion or companions you can.
