Dr. Steve Kelsey: Okay. Let’s distill three questions. So firstly, we are not, firstly, we’re not in a position to report out on our regulatory interactions with regards to 6236 either in pancreatic cancer or non-small cell lung cancer. And I think we deliberately guided to second half of the year with regards to that because we really need to be able to report something that is definitive rather than speculative. Secondly, does the emerging data or will the emerging data on the combination of RMC-6236 with pembro enable a first line strategy? Absolutely. That’s what the study is designed to enable and we’ve deliberately focused. We’ve said several times that accelerating what is clearly an active drug into earlier lines of therapy where we expect the clinical benefit to be even more impactful is a very high priority for the Company.
The third question, like, I think was implicit in your question is whether or not if we were accelerating into first line lung cancer, whether we would do a second line lung cancer study. Right now, we have no reason to deviate from the plan that we have communicated. And if at any point in the future we do deviate from that plan, no doubt we’ll communicate that and the reasons for doing so. But right now, we are committed to a second line single agent non-small cell lung cancer study for RMC-6236. And at the same time in parallel, we’re trying to enable not just first line metastatic, first line advanced disease, but even treatment in non-small cell lung cancer in even earlier lines of therapy as well.
Eric Joseph: I appreciate it. Yes, go ahead, Mark.
Dr. Mark Goldsmith: Yes, I was just going to add one little line of color to that. I mean, bear in mind that for another G12C inhibitor coming in play, they do face quite a bit of competition for G12C patients in second line, so that it’s quite crowded there. Pharmacy 6236, more than half of the patients that we’d be targeting don’t have a G12C inhibitor option available to them. So, I think the dynamics aren’t exactly the same for a G12C inhibitor coming into play versus 6236. But with that said, as Steve pointed out, we have a current plan. If the plan changes, we’ll dispose of the plans change, but that is our current belief.
Eric Joseph: Should we expect any of the combination data with 6236, whether it’s with pembro or other regimens to be paired with either of the data updates with the monotherapy in pancreatic and then lung cancer, NSCLC?
Dr. Mark Goldsmith: I don’t know the answer to that, to be honest. I mean, as we pointed out, there’s, there are scientific meetings that we’d like to present at if we have an opportunity. There are corporate presentations that we can present sort of at our leisure when the opportunity when we have the data and we are ready to say something and how those all line up and how we sort of divvy up and allocate the data to different things, I don’t know the answer to that yet. I would just say, I think our goal here is to be really crystal clear about what we’re trying to enable, in the second half of the year, and that is number one priority, those second line studies that we’ve just talked about and those don’t really require any other information than the monotherapy data.
And then everything else is there to help guide our future studies, which are primarily first line studies or studies in other indications, etcetera. So, I think of them conceptually as being really different baskets, but that doesn’t mean we might not bundle them together in some context. I don’t really know.
Operator: Our next question comes from Jonathan Chang with Leerink Partners. Please go ahead.
Jonathan Chang: Two questions. First, for the initial RMC-6236 combination data with your mutant-selective inhibitors, can you discuss what you’re hoping to see that would give you confidence for further development of these combinations? And second question, how are you thinking about potential business development opportunities given the breadth of the Company’s efforts? Thank you.
Dr. Mark Goldsmith: Hi, Jonathan. Thanks for joining us. Thanks for your question. 6236 plus 6291, well, the first question of course is also a safety question, just like always, not that we have any particular concern, but we do need to establish that. And then the second one is an activity question. And in a perfect world, we’d identify situations where response rates or some other indicator of antitumor activity is low for monotherapy and where we’d look to see something from the combination that differentiates that. Obviously, much harder to do if you’re talking about, let’s say, G12C second line lung cancer, you’d have to run a pretty large Phase 2 trial, if you were trying to establish superiority of an ORR, for example.
And so, I don’t think that’s likely that we will be doing something like that. So that’s the conceptual framework. If we can find opportunities to sort of qualitatively differentiate them as opposed to looking for a difference of X percent in response rate, I think that would be more meaningful to us. With regard to business development, I think our posture in this is really very much the same as it’s been for quite a while now, which is that we have an integrated portfolio and rich portfolio of RAS(ON) inhibitors three of which are already in the clinic. That in and of itself is highly differentiated in the field today, and there may be interactions among these three, and we have a whole stack of compounds behind those that can be brought into the clinic targeting different mutant-selective profiles.
Therefore, it is hard to tease apart different parts of the portfolio for partnering purposes. It’s not impossible, but it’s just harder to do it. That’s one comment. The second is that we’re pretty committed, deeply committed to U.S. operations extending into the commercialization of these compounds. And at this point, don’t really see a need to have a partner help us do that in the U.S. If anything, that complicates things, and potentially if the partnership is around any slice of the portfolio, it might create strategic misalignment between the partners’ interests and ours. So, I think in the U.S., our intention is to commercialize on our own. The exact inverse of that is true outside the U.S., where we have no intention in the foreseeable future of commercializing ourselves, and therefore would expect a partner or multiple partners to be a part of that.
And again, the question dividing the portfolio and potentially creating strategic misalignment versus unifying the portfolio and having everybody on roughly the same page is going to be a factor in sorting all of this out. So, I think when you take all of that put together, I think it’s reasonable to expect that we would have one, potentially more than one, but one partner for marketing outside the U.S. and potentially development that involves, a footprint outside the U.S. as well. But inside the U.S., I think we can manage the commercialization on our own once we’ve built that capability, acknowledging that we don’t have that capability today, but we are very much already investing in it and expect to be able to feel the competitive sales force at the right time.
Operator: Our next question comes from Ellie Merle with UBS. Please go ahead.
