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spk01: Good morning, everyone, and welcome to the Decipher Our Pharmaceuticals Motion Top Line Data and Third Quarter 2023 Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Jen Larson, Senior Vice President of Finance and Investor Relations. Jen?
spk08: Thank you, Operator. Welcome, and thank you all for joining us today. I'm Jen Larson, Senior Vice President of Finance and Investor Relations. With me this morning to discuss the VINCEL Team of Data and our third quarter financial results and to provide a general corporate update are Steve Herter, President and Chief Executive Officer, Matt Sherman, Chief Medical Officer, Dan Martin, Chief Commercial Officer, Margarita Duarte, Head of International, and Tucker Kelly, our Chief Financial Officer. Before we begin, I would like to remind you that any statements we make on this call that are not historical facts are forward-looking statements. made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples include our expectations of our pre-clinical and clinical programs, including themselves in it, our commercialization of Kinloch, and corporate guidance. Forward-looking statements involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, and we cannot assure you that our expectations will be achieved. Such risks and uncertainties include those set forth in our most recent quarterly report on Form 10-Q, as well as our other SEC filings. We assume no obligation to update or revise any forward-looking statements. Following this call, a replay will be available on the company's website, www.deciphera.com. With that, I will now turn the call over to Steve Herter, President and Chief Executive Officer of Deciphera. Steve?
spk02: Thank you, Jen, and good morning, everyone. Thank you for joining us today. We're thrilled to host this morning's call to review the exceptional top-line results from the Pivotal Motion Phase 3 study of Vimseltinib and TGCT that we announced earlier today, as well as compelling updated data from the Vimseltinib Phase 1-2 study. This morning, we also announced our third quarter financial results, showcasing record Kenlock sales. The motion study was a resounding success, achieving its primary and all key secondary endpoints, showing that Vimseltinib has the potential to offer substantial benefit to TGCT patients across a wide range of clinical measures and patient-reported outcomes with a favorable safety profile. Based on the totality of the data, we believe Vimseltinib offers an exceptional clinical profile for people who suffer from TGCT, a chronic debilitating condition with significant unmet medical needs. In addition, we announced updated data today from the Vimsaltinib Phase 1-2 study in TGCT, highlighting that treatment over much longer periods of time can deliver even greater benefits for patients. After another year of follow-up, we now see median treatment duration extending to approximately two years, with the longest patient on treatment for almost four years. We look forward to engaging with regulatory authorities as we prepare to submit an NDA in the U.S. in the second quarter of next year and an MAA in the EU shortly thereafter. Today represents a significant step in our journey to become a fully integrated, self-sustaining biotechnology company. Together, Ken Locke and himself and I have the potential to benefit thousands of patients around the world and generate more than $1 billion in peak global revenue. Bolstering our view of Kenlock's potential, we are also very excited to report another record quarter for Kenlock, with Q3 net product revenue increasing 29% year-over-year and 12% quarter-over-quarter. Dan Martin, our Chief Commercial Officer, will discuss the factors driving the strong U.S. commercial performance over the last two quarters, which we believe are the results of continued focused execution in our fourth-line business as well as increased unpromoted use of Kenlock and earlier lines of GIST based on physician decision. Margarita Duarte, our head of international, will then share more details about Kenlock's strong international performance and our dedication to expanding access to Kenlock to patients around the world. We also remain focused on advancing our deep pipeline of product candidates with first in class and best in class potential. and expect to file the IND for DCC3084, our pan-RAF inhibitor, later this quarter, and we are on track to file the IND for DCC3009, our pan-KIT inhibitor, in the first half of next year. Meanwhile, our potential first-in-class ALK inhibitor, DCC3116, is being studied in multiple combination cohorts as we seek to generate proof-of-concept data to validate a novel approach to treating a wide range of cancers. Before I hand it over to Matt Sherman to discuss the motion and Phase 1-2 study results, I'd like to take a moment to thank the patients who participated in these clinical studies, along with their caregivers and families. Their commitment and resilience have inspired us to deliver on the potential for a new standard of care treatment for TGCT. We're also grateful for the hard work of the investigators, study teams, and healthcare professionals who have participated in the Vimseltinib development program. With that, I'll now turn the call over to Matt.
spk12: Thanks, Steve. Vimseltinib is an oral switch control kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor that we've been developing to address the significant unmet medical needs in TGCT and to create an effective therapy with a favorable safety profile. If approved, we believe Vimseltinib has the potential to become the standard of care in TGCT based on the very positive results we announced today. TGCT can be a difficult chronic condition associated with severe pain, swelling, stiffness, and loss of mobility, all of which can severely limit patients' daily activities and quality of life, including their ability to continue to work or function independently. Patients with TGCT are typically diagnosed in their 30s, 40s, or 50s and are expected to have a normal lifespan. But without effective treatments, a TGCT diagnosis can have a profound impact on their ability to lead a normal, active, healthy life. While surgical resection is a standard treatment and curative for many, some patients are not amenable to surgery or their disease may recur after their initial or subsequent surgeries. Most patients receive a variety of pharmaceutical treatments, including steroid and pain medications to treat their significant morbidity. As Dan will discuss later, Some patients in the U.S. also receive a TKI, typically either off-label imatinib, which is a weak CSF1 receptor inhibitor, or pexidartanib, which is the only approved therapy in the U.S. Pexidartanib is an effective agent, but it has a challenging safety profile due to off-target cholestatic hepatotoxicity that resulted in the black box warning and a REMS program. It's important to note that these serious side effects have not been seen with other CSF1 receptor inhibitors and are believed to be specific to pexidartanib. Given its risk-benefit profile, the EMA did not approve pexidartanib. We see a large unmet medical need in the U.S. and around the world for a safe and well-tolerated drug that can help improve the lives of people with TGCT. The MOTION study is a two-part randomized double-blind placebo-controlled study to assess the efficacy and safety of Vimseltinib in patients with TGCT non-inventable surgery. One hundred twenty-three patients were randomized two to one to receive 30 milligrams twice weekly of either Vimseltinib or placebo. The primary endpoint of the study is objective response rate at week 25 as measured by RESIST and assessed by blinded independent radiologic review compared to placebo. In addition to ORR, MOTION evaluated a number of key secondary endpoints that are an essential part of the overall efficacy picture. These measures of how patients feel and function play an incredibly important role in how treatment decisions are made and for patients' interest in starting and staying on TKI therapy. Today, we will review the top-line results from Part 1 of the study. The second part of the study is an open-label period in which patients from both arms are able to receive treatment with VimSultanib. will present updated results on the longer-term efficacy and safety from motion as part two of the study matures. The baseline demographics of the patients in motion were as expected, with a median age of 44 years and the most common disease location being the knee. A majority of the patients had diffuse disease and had had at least one prior surgery, and approximately one-quarter of patients had been previously treated with systemic TKI therapy. We are excited to report that MOTION met its primary endpoint, demonstrating statistically significant and clinically meaningful improvement in response rate at week 25 based on IRR compared to placebo. The ORR was 40% for the VimSultanum arm compared to zero for the placebo, with a p-value of less than 0.0001. We expect that the resist response rate will increase over time as patients remain unstudied past week 25. consistent with cohort A of the phase two study, with a response rate increase from 38% at week 25 to 64% as of the most recent data cut we disclosed today. Demsiltinib also provided significant improvement in all six key secondary endpoints, including tumor volume score, active range of motion, physical function, stiffness, quality of life, and worse pain response. These results were clinically meaningful and highly statistically significant compared to placebo. Success in the first of the key sector endpoints, response by tumor volume score, is shown here, with VIMSULTIV demonstrating a 67% response rate compared to 0% response rate for a placebo. Measuring TGCT with resist can be challenging due to its irregular shape and asymmetric growth. And as a result, tumor volume score has become an important method of measuring response. DGCT can have a significant impact on patients' range of motion, and we were very pleased that Vimseltinib showed approximately a five-fold improvement in active range of motion at week 25 compared to placebo. Treatment with Vimseltinib showed an improvement of 18.4%, while placebo patients showed an improvement of 3.8%. We've always known that not only would strong efficacy be important, but a well-tolerated safety profile would also be essential in order for VIMS Ultimate to become the treatment of choice for TGCT patients. In a motion study, VIMS Ultimate delivered a favorable safety profile that was consistent with previously disclosed data and that we think will be a strong competitive advantage when patients and their physicians are making decisions about whether to use systemic therapy to treat their disease. The most common treatment emergent adverse events were mostly grade one or two. The only grade three or four event in more than 5% of patients were increased levels of CPK. It is important to remember that the increase in serum enzymes seen in treatment are consistent with the known effects of CSF1 receptor inhibitors. CSF1 receptor inhibition impacts the ability of macrophage-derived Kupfer cells in the liver to clear these enzymes resulting in increased serum levels. This observation is distinct from the colostatic hepatotoxicity reported with pexidartanib, which we have not seen in the MOTION and the Phase I-II studies. Only 6% of patients in the Vimseltin arm discontinued treatment due to a treatment emergent adverse event. In addition to the positive top-line results of the MOTION study, We are also excited to share updated results from the Phase 1-2 study, as it provides an important window into how well efficacy can continue to improve after Week 25, along with how well-tolerated themselves can continue to be, even with long-term exposure. These results are being presented at the CTAS Annual Meeting in Dublin later this week. As of the June 27 data cutoff, we had enrolled 97 patients across the Phase 1 and 2 Phase 2 cohorts. And after data cut, we completed enrollment in cohort B. VIM cells continued to demonstrate encouraging anti-tumor activity across all cohorts, regardless of prior CSF1 receptor therapy, with best ORR of 72% in phase 1, 64% in phase 2 cohort A, and 44% in phase 2 cohort B. In the fully enrolled cohorts, these response rates continued to increase over time, and the median duration of response still had not been reached as of the data cutoff date. with the longest duration of response now approaching four years. This update is an important complement to our top-line motion results, demonstrating vimseltinib's increasing efficacy over time and its potential to make a difference in the lives of TGCT patients. Building upon this encouraging efficacy profile is the increasing duration of therapy and durable clinical benefit observed across all Phase I and Phase II cohorts. Since the prior data cut, the median duration of treatment increased to 25.1 months in the Phase I and to 21 months in CoR A, with the longest patient on treatment for nearly four years. Importantly, 47% of Phase I patients and 48% of CoR A patients remained on study. We expect that the average treatment duration will continue to increase as the study matures. Finally, the long-term safety data we announced today continues to highlight the favorable risk-benefit profile of Vimseltinib. In a pooled analysis of the 95 patients from the Phase 1-2 study, Vimseltinib remained well-tolerated with longer-term exposure. Consistent with motion, only 9% of patients discontinued treatment due to a treatment emergent adverse event. We are truly proud of the VimSultan results we have shared today, and we believe they represent an opportunity to change the way TGCT is treated. Motion delivered exceptional results across the primary and all six key secondary endpoints, and the Phase I-II study data showed how impactful treatment can be over time. And the combined data from both studies shows that VimSultan offers a very favorable safety profile that we believe TGCT patients and their physicians have been waiting for. Our highest priority continues to be getting Vimseltinib to TGCT patients as quickly as possible, and we look forward to engaging with regulatory authorities as we work to submit an NDA to the FDA in the second quarter of 2024 and an MAA to the EMA in the third quarter of 2024. Now, to discuss the Vimseltinib market opportunity, I'll turn the call over to Dan Martin, our Chief Commercial Officer. Dan? Thanks, Matt.
spk07: Given the outstanding data from MOTION and the Phase 1-2 study, we believe that Vimseltinib has the potential to offer a best-in-class profile and to change the standard of care in TGCT. Our launch preparations are well underway, and we have been working to hone our go-to-market strategies based on our deep understanding of the TGCT patient journey and market opportunity. If approved in the U.S., Our focus at launch will be on the approximately 1,400 incidents and 9,000 prevalent patients who were diagnosed and treated with systemic therapy and, importantly, have recently engaged with an oncologist. These patients are actively seeking treatment options for their disease and, in many cases, are engaging with the same oncologist we have called on for over three years since we launched Kinloch. In fact, there's approximately 70 to 80 percent overlap between the oncologists who are seeing patients with TGCT and those who treat patients with GIST. We believe this high degree of overlap offers multiple advantages, including a highly capital-efficient commercial footprint and the ability to leverage established relationships with key prescribers at launch. We estimate a $500 million total addressable market opportunity in the U.S. based on the 1,400 incident patients alone. which may be conservative given the potential for longer duration of therapy. Beyond this core opportunity, we see significant additional opportunity. This includes patients who are diagnosed and treated with systemic therapy, but who have not yet engaged an oncologist, as well as the opportunity in the EU where we expect comparable epidemiology and where there are no approved therapies for TGCT. Our analysis of U.S. claims data has helped to paint a clear picture of how these approximately 1,400 incident and 9,000 prevalent patients are treated. These patients receive extensive polypharmacy to manage their significant disease morbidity. In our analysis, almost all of these patients received prescription pain and or steroid medications to palliate their disease burden, and approximately half of the treatment incident patients received a TKI. Patients receiving pexidartinib represented only 27% of the incident TKI-treated patients, and our longitudinal data show that, on average, the duration of therapy for patients receiving pexidartinib is approximately 10 months. Conversely, off-label imatinib, despite having limited efficacy, was used much more commonly than pexidartinib and had a significantly longer average duration of therapy of about 18 months. Based on our market research and the results of the motion study, we believe Vimseltinib can become the new standard of care in TGCT. In blinded market research based on our Phase 1-2 data presented last year, oncologists consistently cited the vinsultinib product profile as offering the best combination of efficacy and safety when compared to pexidartinib and imatinib. Respondents rated multiple aspects of the vinsultinib profile as highly compelling, including tumor response, impact on patient-reported outcomes, low incidence of grade 3, 4 AEs, and no evidence of cholestatic hepatotoxicity. Now that the motion results strongly validate these positive product attributes, we are extremely excited to help bring the benefits of vansultanib to patients in need pending approval. Turning to Kinloch, as Steve mentioned, this was yet another record quarter. Global net product revenue was $41.8 million, which is a 29% year-over-year increase and 12% quarter-over-quarter increase. This includes 32.7 million in the U.S., representing a 33% increase year-over-year and a 13% increase quarter-over-quarter. In Q3 in the U.S., we again saw strong new patient acquisition and new prescriber growth, as well as increasing average duration of therapy. Our commercial team has continued to execute at an extremely high level, and Kinloch remains the clear standard of care in the fourth-line setting. In addition, we believe recent demand growth has been positively impacted by an increase in unpromoted use in earlier lines of therapy as a result of physician decision. Recall that in January of this year, we presented compelling data from the ctDNA analysis of the intrigue study supporting the ongoing pivotal phase three insight study in second line GIST patients with KIT mutations in exons 11 and 17 or 18. Additionally, in March, the NCCN listed Kinloch as a second-line treatment option for patients who are intolerant of sunitinib. While we do not promote off-label uses, we believe that these two factors have contributed to the strong commercial results we have seen over the last two quarters. We look forward to following these trends and providing updates on future calls. We are encouraged by the continued growth of Kinloch revenue and are eager to build upon it with the exciting Vimseltinib commercial opportunity that we have outlined on the call today. Together, we believe Kinloch and Vimseltinib have the potential to exceed $1 billion in peak global revenue. And we believe we have the right team in place to capitalize on this opportunity. I will now turn the call over to Margarita Duarte, our head of international, to discuss our global commercial progress in greater detail. Margarita.
spk10: Thanks, Dan. We remain very pleased by the European launch momentum exemplified by our record Kinloch sales in the third quarter. International net product revenue was 9.1 million, a 17% increase over 7.8 million in the third quarter of 2022. Additionally, Kinloch generated 1.5 million in collaboration revenue, including royalties and supply revenue from Xilab, our partner in China. I am thrilled to share that Kinloch has received full innovation status in Italy, the highest possible recognition for a non-curative treatment. Full innovation allows Kinloch to be funded from a centralized fund, which is reserved for innovative treatments and significantly shortens access timelines in the multiple Italian regions. In concert with the major additional benefit rating Kinloch received in Germany and the unanimous ASMR3 rating by the French National Authority, this is yet another example of an important healthcare authority recognizing the exceptional value of Kinloch. I am proud of the work of our international team as we continue to expand the reach of Kinloch in existing markets and open new ones. At the end of last quarter, we successfully launched Kinlock in Italy, underscoring the ongoing commitment to our European launch strategy, which seeks to establish Kinlock as a standard of care for fourth-line Gs in Europe's largest markets. Turning to rest of the world, we were pleased to see that the updated Cisco guidelines in China were released, and Kinlock is now listed as a category 1a recommendation in second line for KIPP ADS-11 patients, emphasizing the strength of the clinical data in this setting and its global recognition. To walk us through what all of the exciting updates presenting on today's call mean for the future of our company, I will now turn it back over to Steve.
spk02: Thank you, Margarita. Decipher has never been in a stronger position. Kenlock continues to deliver impressive commercial performance as we expand access to Kinloch around the world and pursue a potentially broader use in second-line GIST based on the INSIGHT study. And now, with the unequivocal success of the Motion Pivotal Phase III study of MSultimate, we have the potential to become a multi-product company on a path to achieving meaningful scale and critical mass. We ended the third quarter in a strong financial position with approximately $377 million in cash and cash equivalents, and our cash runway guidance remains unchanged with cash into 2026. Today's VemCeltinib results are the latest exciting development in what has been a catalyst-rich year for the company. At the beginning of 2023, we laid out our strategic priorities for each of our pipeline programs and provided a roadmap of expected milestones, ranging from the continued commercial growth for Kinloch to new preclinical data and development candidate nominations from our proprietary drug discovery platforms. I'm proud to say we are now very close to accomplishing all of these goals as we expect to submit an IND to the FDA for DCC 3084 later this quarter, capping a year of strong momentum across our discovery, clinical, and commercial stage programs. We remain steadfast in our commitment to deliver important new medicines that can improve the lives of people with cancer and to create value for our shareholders. With that, operator, we'll now open the call for Q&A.
spk01: Certainly, ladies and gentlemen, to ask a question, you will need to press star 1-1 on your telephone and wait for your name to be announced. If you wish to withdraw your question, please press star 1-1 again. Please stand by while we compile the Q&A roster. And our first question coming from the line of Tyler Van Buren with TD Cowan-Yelan is open.
spk05: Hey guys, thanks and congratulations on meeting or exceeding every mark themselves in the data updates. I have a couple for you. So the first one, the 40% overall response rate at week 25 is great and better than PEX's 38%. But can you discuss your confidence that the pivotal overall response rate could reach the long-term 72% response rate observed in Phase 1 and compare that to the long-term response rate that Turalio or PEX showed. And then the second question is regarding the Phase 1-2 update. The 21 to 25-month median duration of treatment is well above that observed with imatinib and PEX, as you outlined. But is there a difference between the Phase 1 and Phase 2 patient populations that explains the four-month delta? Thanks.
spk02: Hi, Tyler. It's Steve. Thanks for the great questions. We'll take those in turn. First, with respect to the primary endpoint for the motion study, we, as we said on the call, are absolutely delighted with the result and to see a 40% response rate versus zero for placebo with very compelling statistical significance. And as you will have noted already, the other important endpoint, in fact, the first key secondary endpoint in the hierarchical testing of the six secondary endpoints, was response rate by tumor volume score. And this, as you may recall, is a 3D measurement of tumor volume, as the name suggests, which we believe could be a better indicator of what a patient's response actually looks like and a better measurement of tumor shrinkage. And that was 67% versus 0% for placebo. So we're really excited with the results that we've reported today. Matt can comment on the longer view based on the Phase 1-2 study and what's been seen with PECS and how we see this potentially evolving with greater data maturity.
spk12: Hi, Tyler. It's Matt. So, yeah, we are thrilled with the results that we were able to share today, both in the primary endpoint and all the key secondary endpoints, and really the consistency of the data across all these secondary endpoints that really speak to how patients feel and function. So, in regard to our expectation that the objective response rate can increase over time, As we've referenced, from the Core A of the Phase 1-2 study, the initial Week 25 objective response rate was 38%. And as we've reported today, that's increased to 64% with the latest data cut. So our starting point with motion of 40%, we have the expectation that will increase as well. As you say, for Enliven as well, they had a Week 25 objective response rate of 38%. and their best overall response increased to only 61%. So we feel we've already exceeded that in cohort A, and we're at a better starting point in the motion study. So we'll continue to evaluate the data and be able to disclose that as well. And importantly, too, the tumor volume score, we now have a 67% tumor volume score response rate at week 25, and we'll continue to follow that over time. As comparison, enliven had a 56%, so somewhat lower, at week 25, And then their best overall response for TBS was 68%. So we're nearly where they were at the best response in the pooled analysis. So, again, we have a high degree of expectation that themselves have this potential to continue to improve response rates over time in these patients.
spk02: And then, Tyler, the second question related to duration and the Phase I-II, do you want to comment on that as well?
spk12: Yeah. And that's really a function of the Phase I dose escalating cohorts were enrolled earlier. So they're... The median treatment duration now is 25.1 months. That four-month delta you referenced is more of a function that they were enrolled under the study longer, so they've just been followed for a longer period of time. But CoR-A now is actually very much catching up, and we still have 47% of patients in CoR-A on study, so those patients can continue to contribute to a longer treatment duration when we have another data cut in the future.
spk02: And as you may remember, Tyler, that cohort A in the phase two, that's the same patient population that we've treated in the motion study. So we think that could be a really good indication of, as the data matures, ultimately, of what median duration of treatment could look like.
spk01: Thank you. One moment, please, for our next question. And our next question coming from the line of Yun Yang with Jefferies. Your line is open.
spk11: Thank you. Congrats on the phase three success. In TGCT, we hear from physicians that each usage could be quite useful in new edge one, edge one settings. I'm wondering if you are planning for those trials. Second question is on Kinloch. Strong third quarter sales sounds like it's helped by uptake in second line usage. So are you expecting off-label use in second line going forward and continue to increase from here? Thank you.
spk02: Yeah, hi, good morning, Yun. Thanks for joining today's call. I'll take the first question and then ask Dan Martin to cover off on your question related to Kinloch and potential trends for unpromoted off-label use in earlier lines of treatment by physician decision. So first, with respect to the Vimseltinib development program, You're right. There is certainly a theoretical role for an inhibitor like Vimseltinib in an even earlier setting in this disease, in an adjuvant or neoadjuvant setting, where patients might be treated first with a drug like Vimseltinib and then potentially be able to go on to surgery, whereas perhaps they would not have been able to be surgically resected before, or perhaps it might result in superior surgical outcomes. We don't have plans that we've announced to pursue additional work in an earlier line setting in TGCT, but certainly to the extent that changes, Yoon, we'll of course be updating investors on our clinical development plans on an ongoing basis. Dan?
spk07: Yeah, thanks, Steve, and thanks, Yoon, for the question. So we are really excited about the performance in the U.S. over the last a couple of quarters in particular. It's really notable to see the 17% quarter over quarter growth and 22% year over year that we saw in Q2, and then the now 13% quarter over quarter growth on top of what was a very strong Q2 and 33% year-over-year growth in Q3. As we noted on the call, we do believe this continues to be a result of strength, and being the clear standard and fourth line, the team's done an outstanding job continuing to execute in that setting. And as we noted, of course, we don't promote any off-label uses, but these two factors that we had noted, both the ctDNA analysis showing the dramatic treatment benefit for patients in the second-line setting with the specific mutational profile in exon 11 and 17 or 18, and then the NCCN listing for patients who may be intolerant of sunitinib, we do think these have provided a meaningful impact, and we can see that in a number of places. In terms of our expectation as we look ahead, it's hard to say whether or not the trend that we've seen will continue. We will continue to monitor it. I think overall we continue to be just really pleased with the feedback we get from physicians. and see this most recent dynamic is really a continuing reflection of how highly physicians value Kinloch as part of their treatment arsenal for patients with GIST.
spk11: Thank you.
spk01: Thank you. One moment, please, for our next question. And our next question coming from the lineup. Michael Schnitt with Guggenheim, Yolanda Selvin.
spk03: Hey guys, good morning. Thanks for taking my questions and congrats on that positive trial outcome as well for me. I know you've talked about some of the secondary endpoints as well. Which of those are most important outcomes perhaps to increase the differentiation relative to pexidartinib on efficacy? I think you talked about QOL in particular before. Has that outcome, you know, matched with your expectations?
spk02: Yeah, thanks, Michael. Great question on the secondary endpoints. Matt, do you want to take that?
spk12: Yes. Hi, Michael. It's Matt. So, yeah, we are thrilled, of course, with all the secondary endpoints. So, we, you know, really expect that together, you know, the they will all contribute to, you know, the value of Vimseltinib in TGCT patients. We highlighted the tumor volume score initially today because that is one that actually I think shows even a more important aspect of how the tumor itself is responding compared to the standard RESIST criteria they use for tumor measurement. Of course, RESIST was first developed for solid tumors, so more of a spherical volume shape compared to the very irregular shape that TGCT tumors have in the joint. So the TBS score was developed as a computer-assisted quantification measurement of change in volume. And that really is now, I think, more important, showing how the tumor is responding to themselves in treatment. But importantly, the other secondary endpoints, including range of motion and the other quality of life measures that we've highlighted previously, are really important aspects of how patients feel and function. And that has been really a key way of differentiating therapies that not only just cause the tumor to shrink, but also improve the quality of life of patients. The limitation for pexidartanib is that they had a lot of missing data in their collection of the quality of life and PRO, patient-reported outcome measures, in their phase three in life and trial. So they were only limited to having range of motion in the U.S. label for pexidartanib. So we look forward to submitting the NDA to the FDA and, you know, including all of the outcome measures And just to share for a moment, we had the opportunity over the weekend to share some of these results with our key thought leaders and investigators. And some of the comments that came back, just to use a few words, is extremely positive, transformative, outstanding results, and really feel that it's not just about the tumor, but it's about how patients feel and function and all of these secondary endpoints that will contribute to the success of themselves to them.
spk03: Great, thank you. And then real quick, you know, with the data now in hand, and I know you talked about some of the 1,400 incident patients, the 9,000 prevalent patients in the U.S., but is there an opportunity for additional evaluation, perhaps in earlier stage patients, pre-surgery, or any other potential label expansion opportunities you could now think about with this result in hand? Thanks so much.
spk02: Yeah, thanks, Michael. It's a good question. You know, I think it kind of piggybacks on Yoon's question earlier, which is the potential for, in the adjuvant or neoadjuvant setting, is there a role for a drug like this in a disease where, up until now, the standard of care treatment has really been surgery. So, I think that remains certainly a theoretical possibility. We don't have an announcement today with respect to running such a study, but it is, we're certainly evaluating more broadly the additional places that we could explore the role of themseltinib and the opportunity to benefit patients, whether it be with TGCT or with other diseases.
spk04: Great. Thanks. Appreciate it.
spk01: Thank you. And our next question coming from the line of Christopher Raymond with 5%, where your line is open.
spk14: Hey, thanks, guys, and congrats from me as well on the data. Just maybe on the labeling, I know you guys still have to talk to FDA and stuff, but with the data showing clearly a safety advantage over pexidartanib, it's still a CF1R like pex. How should we be thinking, I guess, about the chances for a black box or are you thinking the data should speak for itself and are hoping to, I know you're hoping to avoid a black box, but just how are you communicating the chances there? And then maybe talk about the commercial implications of black box versus no black box. And then I have a follow-up on Kinloch.
spk02: Yeah, thanks for the question, Chris. And so I imagine the black box you're referring to is related to cholestatic hepatotoxicity. We don't believe this is a class effect. It's not been reported with any other agent other than with pexidartinib, Daiichi. As you may remember, back at the ODAC in 2019 asserted that this was an off-target effect of their drug, and we certainly believe that to be the case based on the data we've evaluated from other CSF1 receptor inhibitors and, of course, now our own data in the Phase I-II study and in the MOTION study. Dan can comment further with respect to commercial impact, but I think there's probably an important distinction to be made between the black box warning and the REMS program. And as you'll remember, PECS is subject to a REMS program which requires physicians to be certified to prescribe the drug, pharmacies certified to dispense it, and patients, of course, have to be well-informed of the potential benefits and the potential risks of pexidartanib treatment. And we think the notation of the risk of potentially fatal hepatotoxicity has been a real headwind in terms of both physicians as well as patients being willing to go on treatment. So that's our view of the landscape. I would just add that, of course, we'll engage with the FDA. We have a robust database. Matt outlined the updated Phase I-II data. We now have the longest patient on treatment is out to four years. So we have a very long-term follow-up from the Phase I-II experience. which we think helps to communicate the broad benefit of the drug as measured by efficacy, but also the safety of the drug with longer-term use.
spk14: Great. And then maybe on Kinloch, maybe. So just taking into account your comments on second-line use and the NCCN language, It's my sense 2024 is going to be sort of the first full year from a payer plan perspective, and obviously first full year as plans reset is kind of a big thing. Just maybe talk about any payer dynamics that you'd expect. I know this is not a promotion issue, but obviously you've got a payer dynamic to think about. Should we be thinking about any plan policy changes that could be a tailwind in that second line setting?
spk07: Yeah, thanks, Chris. Good question. So we don't anticipate any meaningful payer changes. We've seen outstanding payer access really since the beginning of launch, which is a clear reflection of how significant the unmet need is in GIS broadly and the really strong product profile. We would continue that, expect that to continue. The fact that the NCCN listing is quite broad, candidly, and quite open to physician discretion as it relates to patients who may be intolerant of sunitinib. It certainly provides a tool for them to engage with payers if there were any barriers to earlier line use. But no, we don't expect there to be any meaningful change in the payer access dynamic for Kinloch.
spk14: Great. Thanks very much.
spk01: Thank you. And our next question coming from the line of Andrew Behrens with Learing Partners. The line is open.
spk09: Hi. Thanks. Just a couple from me. Based on the Phase 1-2 trial, it sounds like most patients are getting good results for at least two years or more. Just wondering what treatment patients that drop off of VIM get. Are they getting surgery or are they moving to another agent? And then... A number of datasets have shown the CSF1R class has activity in GVHD. Just wondering if this is a consideration now that you have the results from TGCT. And then lastly, obviously it's early for official guidance, but since you've framed the overall addressable market, just wondering if you could give us some color on how quickly you think then could ramp. Is this going to be a rapid adoption and switching from existing drugs or more likely of a rare disease type launch.
spk02: Hi, good morning, Andy. It's Steve. So let me take first your second question about GVHD. We certainly have been following the space closely with the competitor program that's now generated data in chronic GVHD, which looks quite compelling and clearly showing mechanistic proof of concept using a CSF1 receptor inhibitor for the treatment of that disease. That, of course, is an antibody. We have the obvious benefit of being an oral agent against the backdrop of other oral agents that are being used to treat GVHD. So that is a space that we're very actively evaluating. So no announcement today, but it's something that's being actively evaluated, and especially now in the context of really strikingly positive motion study results, and we have a clear path, we believe, to get VIM to market for patients with TGCT. Now it's incumbent upon us to evaluate other places where VIM may be able to benefit patients. Matt can comment on the first question about subsequent treatment and then flip it over to Dan to talk about launch expectations for FemCeltinib. Matt?
spk12: Yeah, hi. Hi, Andy. So, you know, there hasn't been one, you know, single reason why patients have come off treatment, but certainly some have gone on to surgery. And I think that also speaks to the value that in these patients who were non-amenable or surgically unresectable prior to starting FemCeltinib, at least there was a decision in some patients that they could be potentially resectable. following treatment also these as we've mentioned earlier these are younger patients who are working with families and they may have you know other reasons you know during the trial come off therapy interestingly we had two patients who initially enrolled into the trial who had a stop one was a patient whose family moved to Europe so for work reasons he had a discontinued treatment from the phase one escalating part of the study he came back on the study and has remained on the study since then, and actually has had a very good response when he re-enrolled onto the trial. He was able to re-enroll in the patient of a previous CSO1 receptor inhibitor, and that previous treatment was insulted. And then also in cohort A, we had a second patient who enrolled in the trial, and that patient as well had to discontinue, but then later wanted to come back on the trial, went back on in cohort B as a previously treated patient, and continues on treatment as well, too. So that actually speaks to the possibility for retreatment within something that's very good use in the commercial setting.
spk07: Yeah, I'll take the last question on the VIM sort of launch dynamics that we anticipate. I think that, you know, it's still a bit early for us to be giving extensive color on our launch expectations. We'll certainly have more to say as we get closer to launch. But what we can definitely say is that this is a profile now that's validated by motion that physicians have continually told us looks like the best of both worlds. It looks like the efficacy that they want, that pexidartinib has demonstrated as a potent CSF1R inhibitor, but with, importantly, a safety and tolerability profile that's much more like a comfort level they would have with imatinib, for example. And so we think that given the strength of that profile, really we think a best-in-class profile, we think there is considerable opportunity at launch as it relates to these core patients that we talked about, those that are you know, diagnosed, they're receiving systemic therapies, they're actively pursuing treatment options for their disease in the oncology practices that in many cases we call on today. So we think that there's real considerable sort of core opportunity peri-launch there. And additionally, as you noted, It is important to keep in mind that this is overall a rare disease and sort of diffusely distributed, not unlike GIST. And so that means that there will be an opportunity to educate physicians more broadly, especially those that have not had as much active experience in TGCT because of the limitations of the PECS ART and PROFILE and the REMS program. And so we think that is growth opportunity over time as well. So we're viewing the opportunity in multiple layers there and are really looking forward to a potential launch.
spk09: Great. Thank you.
spk01: Thank you. One moment for our next question. And our next question coming from the lineup, Bradley Canino with Stiefel, your line is open.
spk06: Hey, good morning. This is for Brad Camino. Congratulations on the positive data in the quarter. Two questions. The first is on the . You know, our largest question is around the EU regulatory pathway. As you know, the EMA cited that both Teralio's benefit risk profile was negative, which then led to that rejection in that region. Do you think the EMA was negative on the benefit of a TSF1R inhibitor? Or was it the trial conduct and data collection for pexidartinib? And also, you know, what gives you confidence you've collected a better benefit and risk assessment for vinsultinib?
spk02: Hey, Bijan. Thanks for joining this morning. I'll take the question. So you're exactly right, I think, in how you characterize Daiichi's approach to EMA with pex. And our understanding is that the rejection by EMA was principally based on the poor risk-benefit profile driven by the cholestatic hepatotoxicity. And I think probably what also contributed to that discussion in a negative way was the level of data missingness for the secondary endpoints, which in Europe we think are more important to both regulators, certainly to HTA bodies in Europe, to understand more broadly the impact of a drug on a patient population as measured by patient reported outcomes. So in our case, we, of course, have neither the cholestatic hepatotoxicity issue that has been reported with pexidartinib, and we have exceptional data from all six key secondary endpoints, really bolstering the information we have and the positive view of the drug as measured by patient-reported outcomes, whether that's range of motion or whether it's measures of pain, physical function, other quality-of-life measures. So we think the data package is quite compelling. Of course, we'll engage, as we will with the FDA, with EMA as we review that package and evaluate the potential for the drug in Europe. I'll just add that, as Matt had alluded to over the weekend, we had the opportunity to speak with a number of the investigators and steering committee members for the Vimseltinib Development Program, and that included a number of top sarcoma thought leaders from Europe, And that group of investigators and thought leaders remarked on how excited they were about the profile of the drug, how compelling the efficacy and safety data, but also importantly, how compelling the patient reported outcome data was in driving the point home that Vimseltinib treatment has the potential to improve patient outcomes other than just measuring tumor shrinkage. So we found that to be really helpful to hear. And we believe that EMA will view the data package in the same way.
spk06: Thank you. That's very helpful. And then just one more on Kinloch. This is the first quarter we're seeing some contribution from Second Line. What do you need to see to consider broadening your disclosure of target peak sales for Kinloch?
spk02: So, John, the last part of your question, what do we need to see to – I missed the last bit there.
spk06: to consider broadening your disclosure for target peak sales for Kinloch.
spk02: Okay, thanks for the question. Dan, would you like to take the question?
spk07: Yeah, sure, absolutely. So, a couple thoughts there, Bijan. Thank you. So, as we've communicated Up to this point, we think that the Insight Study has the potential to be really the sort of game changer for us in terms of the ultimate peak opportunity for the franchise in the U.S. We've communicated that we think it could double the peak sales revenue to upwards of $400 million in the U.S. alone. I think as it relates to the recent dynamic that we've seen over the last couple of quarters and the impact on unpromoted earlier line use, that's a dynamic that, as I mentioned on my response to an earlier question, that we'll just have to see how that goes. It's hard to predict whether that trend will remain or not. And so we'll just have to monitor that and provide additional color as we go as to what we think the future could look like.
spk06: Got it. Thank you.
spk01: Thank you. And our next question coming from the lineup, Rennie Benjamin with JMP Securities. Your line is open.
spk15: Hey, good morning, guys. Thanks so much for taking the questions and congratulations on these great results. Maybe just a couple for me. You know, as we think about the sales force, I know in your prepared comments, you mentioned that there's 70 to 80 percent or so overlap, you know, with the existing marketing effort. But as you think about right sizing the sales force and and kind of taking advantage of the full opportunity, what does that look like, you know, upon launch or shortly after launch? And do we think this will be a priority review or, you know, since Paxadartinib has already, you know, proved that this might actually be a full review from the FDA perspective? And I guess just following up, I think it was probably Andy's questions. As you think about the initial patients that will utilize themseltinib, are these going to be you know, post-imatinib, post-pax sort of patients? Will they be naive patients? Who do you think will be the ideal patients that physicians would place themselves in the model? Thank you.
spk02: Hey, Ren. Good morning. This is Steve. Thanks for the three good questions. First, let me take the prior to review question, and then I'll ask. Dan and Margarita, I'm sure, can also comment on implications for Salesforce as we think about adding the potential to add themselves to the bag. And then Dan can comment on U.S. launch dynamic and how we think about the initial opportunity and which sorts of patients might be initial targets, if you will, for being treated with themselves in it. So on the priority review question, Ren, it's too early for us to know. Of course, we'll engage with the FDA in our pre-meeting, and we'll have a better understanding, perhaps at that time, as to whether or not the drug will be considered for priority review. As you may remember, PEX was reviewed under priority review, so that's encouraging as a data point, but we look forward to engaging with FDA, and we'll certainly be exploring that as an option. Margarita, do you want to comment first on the European view on how you see Vimseltinib adding into the portfolio in terms of sales force deployment? And then Dan can take the same question and then follow that with an answer related to uptake in the U.S.
spk10: Sure, happy to. So consistent with the U.S., we also believe there is high overlap with the physicians that we are currently targeting for Kinwalk. So consistent with our cost-optimized European infrastructure, The plan is to deploy a lean and determined customer-facing team that will be focused in rating awareness and generating demand for consult needs. So we will continue to plan according to this thinking and also taking advantage of the high overlap that we believe also exists in Europe.
spk07: Yeah, hey, Ren. Thanks for the questions. So, in the latest CobraDEC, we put together a few summary slides that outline our most recent analysis, largely based on bringing the U.S. claims data in-house and really being able to go that much deeper into that data and our understanding of the patient journey and and the market opportunity. And I think, you know, I direct you to that because I think it's really informative in a number of ways that actually speak to both parts of your question. These 1,400 incident and 9,000 prevalent patients that we identified as really the primary or core U.S. opportunity, we think the way that we approach that is really important in a number of ways. So these are patients who are diagnosed, they're treated with systemic therapies, and really importantly, they've engaged with an oncologist recently. So that means that they are actively pursuing treatment options. for their disease, and they're often engaging with the oncologists that we know very well. And so a couple of important implications there. From a Salesforce expansion perspective, it enables us to take a really capital efficient approach. So we would anticipate an incremental addition, certainly not a dramatic addition in any way. And in that way, we'll be able to take advantage of that really strong synergy. I think the other thing that that core U.S. opportunity really outlines is what these patients are receiving today. We were able to see the significant polypharmacy that these patients receive in order to manage the burden of their disease. And just to take the 1,400 incident patients that we identified, just to take that for this purpose. We see about half of those patients getting a TKI today, and certainly newly treated TKI patients would be a clear target for us, and we believe with a best-in-class agent, we would be able to capture the lion's share of those patients. But beyond that, the other patients are receiving pain and steroid medications, so they're willing to be on drugs systemically to manage the burden of their disease. They're engaging with these oncologists, and we think that with a better option, we'll be able to penetrate this patient population as well. What we hear is that, you know, it's really concerns largely about the AE profile of pexidartinib that has tended those patients to continue to palliate their disease without actually going on a drug that treats the underlying cause. So we think that, excuse me, we think themselves will offer a real game changer there for those patients as well. So both types we think will be key opportunities for us at launch. Excellent.
spk15: Thanks, guys, and good luck.
spk01: Thank you. And as a reminder, ladies and gentlemen, to ask a question, please press star 1-1. One moment for our next question. And our next question coming from the line of Peter Lawson with Barclays. Your line is open.
spk04: Great. Thanks so much. Thanks for taking the questions. Congrats on the data on the quarter. Anywhere quantifying the level of off-label use you've seen in the quarter, is that driving all the U.S. growth? and any kind of puts and takes we should be thinking about for Q. And then on to that TBS score of 57%. How does that compare to prior data?
spk02: Yeah. Hi, Peter. Good morning. Thanks for joining. I'll ask Dan to take your question about unpromoted off-label use in the U.S. and trying to quantify what that is. And then Matt can take the question on TBS for motion. and then also what we saw in the Phase 1-2 study in terms of TVS.
spk07: Yeah. Hey, Peter. It's Dan. Thank you for the question. So, yes, really, really strong growth over the last two quarters. We've been really excited to see that. I've noted that, you know, a big part of our success over the last couple of quarters has been continued execution in the fourth line setting that is, you know, really core and critical to our results. We have continued to see, as we've noted before, a gradually increasing average duration of therapy that we think is an important part of growth in the future moving forward. But yes, we definitely have seen a change in the trend as it relates to what we believe is this earlier line use, both in terms of impact on new patient acquisition and then, of course, flowing through to the demand volume over the last couple of quarters. It's hard of course to parse out exactly which bottles are which but given a considerable amount of anecdotal evidence that we have as to what may be driving this recent trend as well as the fact that we of course have a long history of relatively stable fourth line business and now this significant sort of break in trend, all of that taken together, you know, we feel confident that a significant portion of the increase over the last couple of quarters has come from this unpromoted earlier line use.
spk12: Peter, as we noted, you know, the tumor volume score is a computer-assisted quantification of the tumor volume. And when we used this in the cohort A population from Phase 1-2 study, we had a 51% TBS response at week 25. It did increase as we've updated the data today. It's now 62% with the longer-term follow-up. So this is similar with the motion study. We actually had a higher TBS response at week 25 in the treatment arm and motion at 67%. And as we mentioned earlier, this will continue to be followed over time and expect that it will go up as well.
spk04: Thank you. And then maybe as we think about the U.S. use in TGCT, what's your current estimate for pexediartinib use in the U.S.? And do you expect physicians to switch patients off of VIN or off of pex on the VIN?
spk07: Yeah, hi, Peter. Thanks, Dan, again. Appreciate the question. So our analysis of the claims data has shown that, you know, if you take the 1,400 treatment incident patients that we call out in the slides, about 52% of those patients, this is data from 2022, initiated on a TKI. And of those 52%, 27% initiated on pexidartinib. So certainly the minority there, most of the patients, most of the other patients receiving TKI received imatinib. And the, I'm trying to remember, what was the other part of your question?
spk04: Oh, yes.
spk07: Thank you, Steve.
spk04: Switching from either imatinib to pexidartinib.
spk07: Yes, very good. Thank you. So, we think that there certainly is the potential for some switching. Now that we have the motion data, we'll be doing additional market research to understand these types of questions. But we do think there's potential for switching given a best-in-class agent. And the fact that, you know, patients do tell us that even when they receive benefit from pexidartinib given that it, you know, has demonstrated good efficacy, it's always weighing on their minds, the side effect profile. So the hepatotoxicity and other issues that come with pexidartinib, including the frankly, hair whitening. We hear from patients that, you know, all of these dynamics are challenges to this patient population. And so there's always sort of way on the minds of these patients. So we think that given that and given a potential best-in-class agent, we will have the opportunity for some switches. Great. Thanks so much.
spk01: Thank you. And we have a follow-up question from
spk11: Thank you very much for putting me in again. So a couple of quick questions. For the second line GIST, what percent of our patients are considered intolerant to sunitinib? And the second question is to Tucker, for R&D, the motion trial has ended, but you are running second line GST trials and others. So how do you expect R&D run rate to go going forward? Would that be from third quarter number to be the run rate for 2024? Thank you.
spk02: Yeah, thanks for the follow-ups. Dan will take the question on sunitinib intolerance and put it to Tucker.
spk07: Yeah. Hi, Yoon. Thank you. So, of course, this relates to the NCCN listing in March for patients, second-line patients who may be intolerant of sunitinib. What we hear from physicians varies to some degree. Some physicians cite a higher percentage than others. But overall, what we tend to hear is somewhere in the 10 to 15 percent range. of patients may have some intolerance as it relates to sunitinib. So we think that, you know, that is a meaningful consideration for these physicians and something that, as we noted, has contributed to the recent increase in demand volume. And Tucker?
spk13: Yeah, Ian, thanks for the question on the R&D expenses. So we don't provide, you know, OPEX guidance, but we would expect that the R&D going forward would be in a similar range to a little bit higher, kind of modest increases depending on the quarter. We've obviously got launch expenses with VIM, CMC material, as well as the ongoing clinical studies. And then obviously for Kinloch, we're just getting up and running on the insights. trial as well. So more to come on that, but wouldn't expect significant increases, but could be some modest ones over time.
spk11: Thank you.
spk01: Thank you. And I see no further questions in the queue at this time. I will now turn the call back over to Ms. Stephen Hurler for any closing remarks.
spk02: Great, thank you very much. Thanks to everyone for joining us on today's call. Thank you for your continued support. We look forward to keeping you updated on our progress here at Decipher. Hope you have a great rest of your day and a great week ahead.
spk01: Ladies and gentlemen, that is our conference for today. Thank you for your participation. You may now disconnect.
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