Mohammed Dar: Yes, sure. I’m happy to comment. So, really, the way to think about this is that there is no standard in the adjuvant setting, and so the bar — there’s no established bar. What we know is that the meeting time to relapse in this high risk population, which is the target population is about three years. And so the bar is that we have to improve above that. So this is the way to conduct a trial in the adjuvant setting, which is a randomized trial that’s global, that focuses on the high risk population.
Bahija Jallal: Okay.
Operator: Thank you. Our next question comes from the line of Patrick Trucchio with H.C. Wainwright. Please proceed with your question.
Patrick Trucchio: Thanks. Good morning, and congrats on the progress. I have a follow-up on the PRAME Phase 3 program. I’m wondering if you can discuss in more detail the strategy around pursuing first line treatment, as well as a design that includes that combination with nivo. How should we think about contribution of PRAME this regimen and understanding the studies expected to randomize the first patient this quarter? When do you anticipate initial data like ctDNA data to emerge? And what read through should we anticipate from that data to potential for the program success on the primary endpoint of PFS?
Bahija Jallal: Hey Patrick, thank you for the question. I think David and Mohammed can take that.
David Berman: Yes. So, Patrick, I’ll try to answer a couple of your questions. I hope I get them all. But in terms of the Phase 3 PRAME, first line trial, I think that’s what your question was. There — of course, multiple data points that led to that. The monotherapy activity of F106C, which we’ll share, the ability to combine with anti-PD1s, and then knowledge for our platform and it’s true with immunotherapies in general that you always see higher activity as you move from late to first line. In fact, with ctDNA clearance and KIMMTRAK, we see a tripling of clearance as we go from second line to first line. In terms of the design and the contribution of components, the design is claim plus nivolumab versus nivolumab. So that already has built in the contribution of components, because we have PRAME on top of nivolumab.
Now, there will be a minority of patients in the control arm who do get Opdualag, but — and so we’ll be able to draw a point estimate. But most of the patients, in comparison to Opdualag, but most of the patients will have received nivo monotherapy, so we’ll have contribution of components there. And the primary endpoint is progression free survival, which is globally accepted for approval, for regulatory approval. The secondary endpoint is overall survival. We do have an exploratory endpoint of ctDNA, but that won’t be available until the trial is open.
Operator: Thank you. Our next question comes from the line of Gil Blum with Needham. Please proceed with your question.
Gil Blum: Good morning, and thanks for squeezing me in. Maybe a quick one on your new PIWIL asset and CRC, so generally CRC is an immune desert. Could that be a potential issue for agents of this type? I mean, we’ve seen a lot of activity for TEBE-AM and PRAME asset and more T cell infiltrated tumors. Thank you.
Bahija Jallal: Yes. Thank you, Gil, for this question. I’ll pass it on to Mohammed. But I just want to remind you that the uveal melanoma is a complete cold tumor as cold as it gets. So that’s, I think, where our platform, you want to talk a little bit, Mohammed about that?
Mohammed Dar: Yes. This is part of the reason why we’re so excited about the PIWIL program and our mechanism, which is very distinct from checkpoints, where we don’t need preexisting immunity or infiltration by the immune system into the tumor. What we’ve shown with TEBE, as Bahija was alluding to is that we just need functional T cells in the periphery, and our mechanism drives T cells into a non-inflamed or immune desert. So this is one of the reasons why we’re excited about this program and its potential application in CRC.
Bahija Jallal: And then I’m going to let the data tell us.
Operator: Thank you. Our next question comes from the line of Naureen Quibria with Capital One Securities. Please proceed with your question.
Naureen Quibria: Hi, good morning. Congrats on the quarter and thanks for taking my question. So I guess just to follow-up on the KIMMTRAK Phase 2/3 TEBE-AM study. Obviously, you’re going to be looking at the ctDNA and the trends with the OS. I’m just curious, what kind of reduction in ctDNA do you expect in this setting, sort of to help you inform the decision to drop one arm? How big of a delta are you looking at? And are you going to be comparing between the two arms, or is it just baseline from the specific arm?
Bahija Jallal: Great. Naureen, thank you very much. David, you want to take this one?
David Berman: Yes. So hope you were saying it’s we have three arms, just as a reminder, we have tebentafusp monotherapy, tebentafusp pembrolizumab, and then, of course, the control arm. And the primary — the dual endpoints are ctDNA and survival. In terms of ctDNA, we believe it directionally gives us information, but since it’s still exploratory in cutaneous melanoma, we will rely on survival as well. And although the survival will not be fully mature, we have done some simulations showing that we will have sufficient power to see trends in order to drop one of the arms. The size is about 40 patients per arm, and so we think we have enough power in order to make that decision taking integrating ctDNA and survival.
Operator: Thank you. Our next question comes from the line of Jeffrey Hung with Morgan Stanley. Please proceed with your question.
Michael Riad: Hi, this is Michael Riad on for Jeff Hung. Thank you for taking our question. Could you talk a little bit more about ctDNA’s predictive power on OS and advanced cutaneous versus uveal melanoma? How far in the treatment course do you need to go to have confidence in its predictive power? And does that power get stronger as you move into earlier lines? Thank you.
Bahija Jallal: Thank you, Michael. David, you want to take it?
