James Christensen: Hi, Neil. I’ll take the first part of that. So CNS as you know is continues to be important differentiator for us. But part of the overall picture of where the picture is really about overarching efficacy including our overall survival response rates as well as CNS penetration. We are expecting to have a publication in not too distant future, which will be out won’t be an update to the data that is initially been shown and continues to show promising results for KRAZATI. And I’ll pass may be to Alan for the second part of the question.
Alan Sandler: Yes. I believe the second part of the question was looking at the combination in frontline in CNS metastases. And I think the plan moving forward with K7 initially when you looking at studies with these Phase 2 studies, you want to have the best group of patients possible so that includes stable and previously treated brain mets. If they have them, we will, as we get more and more data and begin to broaden the patient population and take a look at that because we, of course, would have every confidence that with adagrasib working in the second line setting, we’d anticipate efficacy in that frontline setting as well.
Operator: The next question comes from Eric Joseph of JPMorgan. Please go ahead.
Noah Burhance: Hi, this is Noah on for Eric. Thanks for taking our question. Regarding 1719, is there a meaningful biomarkers for MTAP deletions and MTAP biology that can be used to further enrich for patients with sensitive tumors? And also, is there a distinction between targeting MTA 2a versus PRMT5 and MTAP deleted cancers?
James Christensen: For that category, I would say we do not yet have insight. We have preclinical data where we’ve done some molecular profiling and we continue to study the biology of MTAP-deleted tumors including things that are associated with the PRMT5 biomechanism like RNA splicing p53 status and otherwise. We will continue to study those in patients. The second class of biomarkers, we’ll take a look at, are those that give us insight towards the level of target inhibition that we can achieve in patient tumors. And here, we believe, we want to be at 95% inefficient level for as much of the dose interval as possible. There will be looking at symmetrical dimethyl arginine as a target-driven biomarker and we plan on doing that as the program advances.
Finally, you touched on PRMT5 versus MAT2A. And I think, as you know, there has been some MAT2A data out there reported previously by Agios. Now, is developing that molecule. I think they have commented publicly on their program as well. I think really the key difference here is that we believe that in MTAP-deleted tumors where PRMT5 dependency is present, you really have to suppress the target biomarker. Again, this is known as SDMA to the full degree to drive anti-tumor activity and I believe that this is a more precise way in this tumor sub population to do this. Just note that for MAT2A, when you effect cellular levels of methylation that you probably affecting 20 plus methyltransferase. It’s a less precise way with a different therapeutic index than PRMT5.
We are looking at the possibility that you could combine PRMT5 inhibitors with MAT2A inhibitors, but really no clear conclusion here. But again, for MTAP-deleted tumors, believe that the most precise way to target these tumors is through what we’re doing with 1719.
Operator: The next question comes from Jason Gerberry at Bank of America. Please go ahead.
