Mark Goldsmith: Look, it’s barely bioavailable across multiple species and at percent that are considered very much appropriate for oral drugs. So we have to demonstrate that in humans. But based on the preclinical species, it’s an orally available drug. We’ll have no difficulty getting above the IC50 or even IC90 and it also has a relatively long half-life. And then it’s also retained in tissues because of the covalence fees. So you put all of those pieces together, it behaves very much like RMC-6291 in terms of dose PK/PD efficacy and selectivity relationships. Those are all fine. So I don’t think that the investigators are going to have concerns about that. This concerns not all the other drugs that are not orally bioavailable and not covalent.
But I’m not sure there should be any particular issue about Pharmacy 9805. Of course, we have to validate that in humans. What I just described to you is the preclinical but given how extensively they’ve been characterized, I guess, we’d be surprised if those properties don’t carry over into people.
Operator: And our next question comes from Marc Frahm with Cowen.
Marc Frahm: Maybe just to start with 6236, that trial has been open for a few months now and actively enrolling for a few months. And it has a pretty broad criteria in terms of mutations and tissue types that are eligible. Are you seeing a bias there of enthusiasm across different — for specific mutations or specific tumor types that we — that should be thinking about the population tending to be enriched in?
Mark Goldsmith: Thanks, Marc. Nice to hear from you. There is a tremendous amount of interest in it and there are far more patients who are interested in participating in the study that we’ve been able to release lots for. So I don’t think that there’s any bias other than that epidemiologically. There are some fetations that are more common than others. G12C and G12D here are significantly more common than other mutations and they have no available targeted therapy. And so they are tending to show up but they’re not the only ones showing up. They just are tending to show up. And they’re showing — tending to show up in gastrointestinal tumors because that’s where they’re most prevalent but they’re not only showing up in gastrointestinal tumors either.
So, I don’t think there’s anything from an investigator perspective that’s biasing these. Now keep in mind, we’ve restricted enrollment based on genotype initially to the KRAS G12 mutations to a small number of those, essentially excluding G12C initially because those patients have available to them a G12C inhibitor, including now RMC-6291 in the clinical trial. And eventually, we’ll come back to those G12C patients after we get to a dose that we think is going to be most appropriate for those who have, for example, failed the G12C inhibitor. But other than that, I don’t really think we’ve seen any particular figure on the scale.
Marc Frahm: Okay, that’s helpful. And then can you refer to these initial ones in the clinic as well as the G12D is the first wave and you have some of these other mutation-specific inhibitors that being held back as leave too? So just what’s your thoughts on what do you need to see from the first wave of agents in order to pull the trigger on Wave 2 and start moving those into the clinic?
