SteveHoerter: Yes. Hi Michael, good morning, it’s Steve. I’m happy to take the question. So, first, we’re excited about the potential to expand vimseltinib and its utility beyond TGCT and into a new potential indication in chronic GVHD. And certainly one of the factors that enables us to do that, in addition to the strong data we have now in TGCT, is the very long IP runway that we have for vimseltinib with a composition of matter patent that takes us to 2034 plus PTE, which we believe takes us to the end of the decade. And that doesn’t include secondary patents for vimseltinib. So ample opportunity for us to make additional investments in vim, to take it into additional indications where we’ll have the opportunity to benefit patients.
So in terms of the landscape of GVHD and how we see differentiation at this early stage, first I would just comment that certainly the target CSF1 receptor is now clinically validated in this disease, which is very important, so it’s a derisked mechanism in GVHD. We believe the data that we’ve generated in Tenosynovial Giant Cell Tumor demonstrates that we have a very potent and selective inhibitor against the target. And in a disease where the current backbone of treatment is all oral regimens, we believe that an oral agent like vimseltinib, an oral CSF1 receptor inhibitor could play an important role as an add-on therapy in addition to a monotherapy in later lines, but as an add-on therapy to current standard of care, whether that be a JAK inhibitor or whether that be a drug like Rezurock, as an example.
So we haven’t yet disclosed full details of our clinical development strategy in GVHD. I’m sure we’ll have incremental additional disclosures over time, particularly once we get the Phase 2 study stood up at the end of this year. But we’re excited about the potential now to expand the places where Vim can benefit patients.
Operator: Thank you. One moment for questions. Our next question comes from Christopher Raymond with Piper Sandler. You may proceed.
Christopher Raymond: Hi, thanks. Just another question, I guess on vimseltinib, and this is on the adjuvant opportunity. I know this has come up in the past, but what do you guys see as sort of the go, sort of no-go points to running a study in the adjuvant setting? As you guys even note in your market landscape slide, that’s a pretty sizable opportunity. Just any sort of plan there that you guys can articulate? And then maybe a second part of that question is, is there an opportunity or a chance that you can get a broad label that could be potentially inclusive of the adjuvant setting? Thanks.
SteveHoerter: Yes. Hi, Chris. It’s Steve. Thanks for the two questions. Really good questions. So you know, we’re of course, excited about the data from MOTION, which will give us this initial label in Tenosynovial Giant Cell Tumor. As you’ll remember, the patient population that we treated in the MOTION study is patients who are not amenable to surgery. So it’s too early for me to comment on what ultimately FDA will decide as the indication statement or the label for Vimseltinib in TGCT. But we too have heard also from investigators interest in exploring a role of an inhibitor like vimseltinib in other lines or earlier lines of treatment for Tenosynovial Giant Cell Tumor. So recall, this is a disease that, particularly in the localized form of the disease, is often curable through surgery alone.
So we’d probably be speaking about a patient population that would not be amenable to surgery, but potentially could be made amenable to surgery with adjuvant or neoadjuvant treatment. So again, too early for us to comment on any specific plans, but certainly with the evidence that we have now in the patient population that we’ve studied, it’s very clear we have strong activity in this disease with vimseltinib, and there may be opportunity for us to pursue whether label enabling studies or non-label enabling studies to further characterize the potential of vimseltinib to benefit patients here.
Christopher Raymond: Great. Thank you so much.
Operator: Thank you. One moment for questions. Our next question comes from Andrew Berens with Leerink Partners. You may proceed.
Unidentified Analyst: Hi, this is Ken on for Andy. Thanks for taking the question. So you guys, I think, have been saying that the average duration for QINLOCK in the fourth-line setting has started to come up, I believe about seven months now, increasing potentially up to eight and a half. So wondering, do you have any color on the penetration in the fourth-line where that could be right about now? Thanks.
SteveHoerter: Yes, thanks for the question. Dan, would you like to take that?
DanMartin: Sure. Absolutely. So, yes, you had mentioned about the average duration of therapy, in fact, we think that’s a really important dynamic to our continued growth. As we think about 2024, we look to the continued strength in our fourth-line opportunity. We look to a continuing increasing average duration of therapy. And as we’ve noted in earlier questions, contribution from unpromoted earlier line use. So as we think about the opportunity for 2024, we’re looking forward to another potential record year in the U.S. for QINLOCK as it relates to penetration in the fourth-line setting. As we’ve said in the past, we feel as though we’ve done a really good job penetrating that opportunity, and that it’s pretty highly penetrated opportunity as a result of not only a really strong drug at high unmet need and our ability to execute over the last number of years.
Operator: Thank you. One moment for questions. Our next question comes from Brad Canino with Stifel. You may proceed.
Brad Canino: Good morning and thank you. Another question for me on vimseltinib. I wonder how many doses you think you plan to use in the proof-of-concept study in chronic GVHD. And I’m asking in light of the inverse dose response noted for the antibody and the working hypothesis there around allowing for some degree of macrophage function recovery. Thank you.
SteveHoerter: Yes, thanks for the question Brad. Matt, would you like to take that on GVHD?
MattSherman: Sure. Good morning Brad. Yes, this is Matt. So what you’re referring to is the pivotal study was done with axatilimab in GVHD where they tested three dose levels in different schedules as well too. And what they did demonstrate an inverse dose-response where some of the lower doses had more efficacy and were much better tolerated than higher doses. That may be more unique to antibody because there will be antibody inhibition of the T cell receptor has led to a much more prolonged on target effect, and it’s been difficult in other indications to develop those antibodies clinically. So as Steve said earlier, you know we’re excited about moving forward with our proof-of-concept study in the second half of this year in GVHD. We haven’t yet given the details of the study, but as we get closer to the initiation of that study, we certainly will be speaking to the design of that study and what we expect to achieve.
Operator: Thank you. One moment for questions. Our next question comes from Reni Benjamin with Citizens JMP. You may proceed.
Reni Benjamin: Hi, good morning guys. Thanks for taking the questions and congratulations on the progress. Maybe just to start off, Steve, can you give us any sort of color on the INSIGHT study and how that’s progressing? Have you kind of hit all the trial sites? Are they all kind of open or are you still ramping that up? Any sort of color as to how that’s progressing because that seems to be key in terms of unlocking the second-line GIST opportunity. And then just as a follow-up with vimseltinib. You’re filling the NDA and MAA. Any chance that we could get some sort of a priority review or is the base case scenario standard review both in the U.S. as well as Europe? And how long does it take in Europe just to get the decision?
SteveHoerter: Yes, hi Ren, it’s Steve. Good morning. Thanks for the great question. So first for INSIGHT, as you’re aware, I should first note that we published the results from the analysis of INTRIGUE in Nature Medicine last month. So really exciting to see the data in such a top-tier journal. And the noise that, that analysis has generated both with the presentation at ASCO and now with the publication in Nature Medicine has been a real tailwind in terms of building enthusiasm for the ongoing INSIGHT study. So we continue to make really good progress in getting sites open, actively screening and enrolling patients in that study. And the enthusiasm from investigators is really palpable. I think they’re really excited not only about the data that’s been published and presented so far from the analysis of INTRIGUE, but just also the potential to be part of advancing how second line GIST is treated based on INSIGHTs into a patient’s tumor using circulating tumor DNA.
So drawing a simple tube of blood in order to understand a secondary mutation status, that is an aim or a goal, I think that the field and thought leaders in the field are really excited about. And their participation in the INSIGHT study, we believe, will help us to achieve that goal of demonstrating prospectively this outsized benefit of QINLOCK versus sunitinib in this selected patient population. So we continue to be moving forward very much on schedule and on track with the INSIGHT study. And we’ll have further updates, I’m sure, over the coming quarters on our progress with that specific study in second line GIST patients. Your second question was related to vimseltinib, and what our expectations are in terms of regulatory review and timing.
