Joseph Catanzaro: Okay, got it. Appreciate you taking my questions. Thanks.
Operator: Our next question is from the line of Soumit Roy with Jones Research. Please go ahead.
Soumit Roy: Hi, everyone. Thank you for taking the question. One question on MANTRA-2 trial, the Basket study. How extensive are the background genomic mutation status analysis are you doing? Are you just primarily focusing on the known obvious mutations in pancreas or breast and lung, or is fairly extensive?
Avanish Vellanki : Hi, Soumit, thanks for the question. I’ll turn that one over to Bob.
Robert Doebele: Thanks for the question. It’s actually a very extensive analysis. So you’ll recall that we’re using Tempus as our diagnostic vendor. So all patients are getting the Tempus XT test, which is currently comprised of more than 600 genes. So really comprehensive and covers almost all cancer related gene.
Soumit Roy: Got it. And are you doing any parallel preclinical analysis with those kind of co-mutations in the system to see if there is a p53 activation without adding any combination agent?
Robert Doebele: We’ve published several models already, some which have co-alterations, and we believe that there is a reason to think that there should be activity even in patients with co-alterations.
Operator: Our next question is from the line of Jeff Jones with Oppenheimer. Please go ahead.
Jeff Jones: Two questions. In the Basket trial, what type of signal are you looking for that would be considered supportive of approval down call it path A. And then, a follow up question to Bob’s discussion on the mechanism of action. Something I only caught part of. You had mentioned, that higher levels of MDM2 amplification didn’t necessarily correlate with higher sensitivity. Could you give a little more detail on that?
Avanish Vellanki: Thanks, Jeff. Yes, I’ll hand that both those questions over to Bob.
Robert Doebele: Yes, Jeff. Thanks for the question. So, in terms of the threshold, again, it’s a bit of a guessing game, but based on several agnostic approvals by the FDA for targeted therapies, we believe that the response rate probably needs to be in the range of around 30%, obviously, with reasonable durability. So that’s the benchmark for an agnostic path for MANTRA-2. In terms of the MDM2, copy number, we’ve received a lot of questions about whether higher copy number may lead to better sensitivity. And I think, you’ll recall several pieces of evidence that suggests that no, there is no correlation as long as you have some level of MDM2 amplification, that may be still an unknown target, what that level is. But higher levels won’t necessarily predict for that.
So we looked in the U101 study and looked at clinical outcomes versus copy number and patients with higher copy numbers in liposarcoma did not fare better than patients with lower copy numbers of MDM2. We’ve also seen no correlation yet also in the MANTRA-2 study. And then you’ll recall that we’ve also said that in preclinical data, there’s no correlation between copy number and sensitivity to milademetan. So, as long as we’re above a certain threshold for amplification, greater amplification doesn’t seem to predict for better outcome.
Operator: Thank you. Our next question is from the line of Yigal Nochomovitz with Citigroup. Please go ahead.
Yigal Nochomovitz: I had three quick questions. On MANTRA-2, I think you mentioned that the part C scenario would involve potential combos. I’m curious what you could say more there in terms of which combos, whether you’d use atezo or something else? And then on RAD-52, I’m just curious if you’d expand a little bit on the lessons learned from that program. I think you mentioned something about the assay sensitivity, not necessarily correlating with potency, if I understood that correctly, and how that might help you with target selection in the future? And then third on MANTRA, I know you have to hit the 105 and you can’t comment. But can you say the frequency with which you’re actually checking the events these days? Is it weekly every few weeks? And is it possible that you might exceed the 105 at the point where you actually do the analysis? Thank you.
