Deciphera Pharmaceuticals Inc

F:D05

Earnings Call Analysis

Impressive QINLOCK Growth, Vimseltinib NDA Plans

In a recent earnings call, the company reported a record quarter with global net product revenue for QINLOCK reaching $41.8 million, up 29% year-over-year. The drug remains the standard care for fourth-line treatment and is starting to be used earlier in treatment due to its safety profile and efficacy. The company is also preparing for the launch of Vimseltinib, which could potentially redefine care for TGCT with a $500 million addressable U.S. market. Regulatory submissions for Vimseltinib are planned for the second and third quarters of 2024 in the U.S. and EU, respectively. Additionally, the data suggests that combined with QINLOCK, both drugs have the capability to surpass $1 billion in peak global revenue, and the company is unequivocally bullish on its future.

Vimseltinib Shows Promise in Treating TGCT with Strong Study Results

The latest results from the MOTION study indicate Vimseltinib could significantly improve treatment for Tenosynovial Giant Cell Tumor (TGCT) patients. A striking 67% response rate was achieved compared to a 0% placebo rate. Its effectiveness extended to all six key secondary endpoints, such as tumor volume, mobility, and quality of life. The findings not only show Vimseltinib's potential to improve patients' physical functioning, with about a 5-fold increase in active range of motion, but also point to a favorable long-term safety profile.

Safe and Sustained: Vimseltinib Exhibits Long-term Benefits

Updated results from the Phase 1/2 study of Vimseltinib indicate sustained efficacy with long-term use. The treatment has continued to demonstrate encouraging anti-tumor activity with response rates growing over time, and the longest duration of response nearing four years. With a well-tolerated safety profile and only 9% of patients discontinuing due to adverse events, Vimseltinib's durable clinical benefits may be exactly what TGCT patients need.

Regulatory Milestones in Sight for Vimseltinib

The compelling results have set the stage for regulatory submissions with plans to file a New Drug Application (NDA) to the FDA and a Marketing Authorization Application (MAA) to the EMA in 2024. This pace sets Vimseltinib on a clear path toward addressing the unmet medical needs in the TGCT patient population.

QINLOCK Continues Strong Performance with Record Revenue

For QINLOCK, a record quarter was observed with a 29% increase year-over-year, reaching $41.8 million in global net product revenue. This surge is influenced by robust patient acquisition and utilization in earlier lines of therapy, indicating QINLOCK's firm establishment as a trusted treatment option.

QINLOCK Gaining Momentum in European Markets

The brand continues to gain traction internationally, showing a 17% increase in product revenue and accolades such as full innovation status in Italy. These achievements underscore the strategic success in positioning QINLOCK as a standard of care for GIST in key European regions.

Positive Financial Trajectory and Cash Position

With $377 million in cash and equivalents at the quarter's end, the company maintains a robust financial position. The cash forecast suggests sustainability well into 2026, providing a solid foundation for ongoing development and commercial activities.

Potential Expansion of QINLOCK's U.S. Market Opportunity

The INSIGHT study could be a game changer, potentially doubling peak sales revenue to over $400 million within the U.S. for QINLOCK. While there is some uncertainty about the continuation of unpromoted earlier line use, strong growth in recent quarters provides a positive outlook for the drug's market reach.

Closing Remarks: A Year of Achievement for Deciphera

In 2023, Deciphera has delivered on its strategic priorities across discovery, clinical, and commercial programs, moving closer to achieving key milestones such as the upcoming IND submission to the FDA for DCC-3084. The record-breaking year is a testament to the company's strong momentum and potential for growth.

Earnings Call Transcript 2023-Q3

[Operator]

Good morning, everyone, and welcome to the Deciphera 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?

[Jennifer Larson, executive]

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 Vimseltinib data and our third quarter financial results and to provide a general corporate update are Steve Hoerter, President and Chief Executive Officer; Matt Sherman, Chief Medical Officer; Dan Martin, Chief Commercial Officer; Margarida 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 preclinical and clinical programs, including Vimseltinib, our commercialization of QINLOCK 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 Hoerter, President and Chief Executive Officer of Deciphera. Steve?

[Steven Hoerter, executive]

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 in 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 QINLOCK 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 benefits 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 Vimseltinib 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 2 years, with the longest patient on treatment for almost 4 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, QINLOCK and Vimseltinib 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 QINLOCK's potential, we are also very excited to report another record quarter for QINLOCK, 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 2 quarters, which we believe are the result of continued focused execution in our fourth line business as well as increased unpromoted use of QINLOCK in earlier lines of GIST based on physician decision. Margarida Duarte, our Head of International, will then share more details about QINLOCK's strong international performance and our dedication to expanding access to QINLOCK 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 DCC-3084, our pan-RAF inhibitor later this quarter, and we are on track to file the IND for DCC-3009, our pan-KIT inhibitor in the first half of next year. Meanwhile, our potential first-in-class ULK inhibitor, DCC-3116, 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.

[Matthew Sherman, executive]

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 lives, 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. Those patients receive a variety of pharmaceutical treatments, including steroids and pain medications to treat their significant morbidity. As Dan will discuss later, some patients in the U.S. will also receive a TKI, typically either off-label imatinib, which is a weak CSF1 receptor inhibitor or pexidartinib, which is the only approved therapy in the U.S. Pexidartinib 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 pexidartinib. Given its risk-benefit profile, the EMA did not approve pexidartinib. 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 2-part randomized, double-blind, placebo-controlled study to assess the efficacy and safety of Vimseltinib in patients with TGCT nonamenable to surgery. 123 patients were randomized 2:1 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 RECIST and assessed by blinded independent radiologic review compared to placebo. In addition to ORR, MOTION evaluated a number of key secondary endpoints that are in the special 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 Vimseltinib. We'll present updated results on the longer-term efficacy and safety promotion as part 2 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 have had at least 1 prior surgery and approximately 1/4 patients have 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 Vimseltinib arm compared to 0 for the placebo with a p-value of less than 0.0001. We expect that the RECIST response rate will increase over time as patients remain on study past week 25, consistent with Cohort A, the Phase 2 study with a response rate increase from 38% at week 25% to 64% as of the most recent data cut we disclosed today.Vimseltinib also provides a significant improvement in all 6 key secondary endpoints, including tumor volume score, active range of motion, physical function, stiffness, quality of life and worst 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 Vimseltinib demonstrating a 67% response rate compared to 0% response rate for placebo. Measuring TGCT with RECIST 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. TGCT can have a significant impact in patients' range of motion, and we were very pleased that Vimseltinib showed approximately 5-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 have always known that not only was strong FCB important, but a well-tolerated safety profile would also be essential in order for Vimseltinib to become the treatment of choice with TGCT patients. In the MOTION study, Vimseltinib 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 the physicians are making decisions about whether to use systemic therapy to treat their disease.The most common treatment emergent adverse events were mostly grade 1 or 2. The only grade 3 or 4 event in more than 5% of patients were increased levels of CPK. It is important to remember that the increase in serum enzymes seems in potent treatment are consistent with the known effects of CSF1 receptor inhibitors. CSF1 receptor inhibition [indiscernible] of macrophage provide Kupffer cells in the liver to clear these enzymes resulting in increased serum levels. This observation is distinct from the cholestatic hepatotoxicity reported with pexidartinib, which we have not seen in the MOTION and the Phase 1/2 studies. Only 6% of patients in the Vimseltinib 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 FC can continue to improve after week 25, along with how well tolerated Vimseltinib continues to be even with long-term exposure. These results are being presented at the CTOS annual meeting in Dublin later this week. As of the June 27 data cutoff, we have enrolled 97 patients across the Phase 1 and 2 Phase 2 cohorts. And after data cut, we completed enrollment in Cohort B. Vimseltinib continued to demonstrate encouraging antitumor 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 continue 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 4 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 1 and Phase 2 cohorts. Since the prior data cut, the median duration of treatment increased to 25.1 months in the Phase 1 and to 21 months in Cohort A, with the longest patient on treatment for nearly 4 years. Importantly, 47% of Phase 1 patients and 48% of Cohort 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 the 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 treatment-emergent adverse events. We are truly proud of the Vimseltinib 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 6 key secondary endpoints and the Phase 1/2 study data showed how impactful treatment can be over time. And the combined data from both studies shows that Vimseltinib 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?

[Daniel Martin, executive]

Thanks, Matt.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 incident 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 oncologists we have called on for over 3 years since we launched QINLOCK. In fact, there's approximately 70% to 80% 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 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 administration 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 Vimseltinib product profile is offering the best combination of efficacy and safety when compared to pexidartinib, and imatinib. Responses rated multiple aspects of the Vimseltinib 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 Vimseltinib to patients in need pending approval.Turning to QINLOCK. 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 QINLOCK 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 3 INSIGHT study in second-line GIST patients with KIT mutations in exons 11 and 17 or 18. Additionally, in March, the NCCN listed QINLOCK 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 2 factors have contributed to the strong commercial results we have seen over the last 2 quarters. We look forward to following these trends and providing updates on future calls.We are encouraged by the continued growth of QINLOCK revenue and are eager to build upon it with the exciting Vimseltinib commercial opportunities that we have outlined on the call today. Together, we believe QINLOCK 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 Margarida Duarte, our Head of International, to discuss our global commercial progress in greater detail. Margarida?

[Margarida Duarte, executive]

Thanks, Dan.We remain very pleased by the European launch momentum identified by our active QINLOCK 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, QINLOCK generated $1.5 million in collaboration revenue, including royalties and supply revenue from Zai Lab, our partner in China. I am thrilled to share that QINLOCK has received full innovation status in Italy, the highest possible recognition for a noncurative treatment. Full innovation allows QINLOCK to be funded from a centralized fund, which is reserved for innovative treatment and significantly shortened access time lines in the multiple Italian regions. In concert with the major additional benefit rating QINLOCK received in Germany and the unanimous ASMR 3 rating by the French national authority, this is yet another example of an important healthcare authority recognizing the exceptional value of QINLOCK.I am proud of the work of our international team as we continue to expand the reach of QINLOCK in existing markets and open new ones. At the end of last quarter, we successfully launched QINLOCK in Italy, underscoring the ongoing commitment to our European launch strategy, which seeks to establish QINLOCK as a standard of care for fourth-line GIST in Europe's largest markets. Turning to rest of the world, we were pleased to see that the updated fiscal guidelines in China were released, and QINLOCK is now listed as a Category 1A recommendation in second line for KIT exon 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.

[Steven Hoerter, executive]

Thank you, Margarida.Deciphera has never been in a stronger position. QINLOCK continues to deliver impressive commercial performance as we expand access to QINLOCK 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 3 study of Vimseltinib, we have the potential to become a multiproduct 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 Vimseltinib 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 road map of expected milestones, ranging from the continued commercial growth for QINLOCK to new preclinical data and development candidate nominations from our proprietary drug discovery platform. 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.

[Operator]

[Operator Instructions] Our first question coming from the line of Tyler Van Buren with TD Cowen.

[Tyler Van Buren, analyst]

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 was 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- and 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 population that explains the 4-month delta?

[Steven Hoerter, executive]

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, as we said on the call, we're absolutely delighted with the results. and to see a 40% response rate versus 0 for placebo with very compelling statistical significance. And as you will have noted already, the other important end point, in fact, the first key secondary endpoint in the hierarchical testing of the 6 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. So now 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 pex and how we see this potentially evolving with greater data maturity.

[Matthew Sherman, executive]

Tyler, it's Matt. So yes, 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. But as we've referenced from the Cohort 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 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. At comparison, ENLIVEN had a 66%, 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 high grade expectation that Vimseltinib's potential continues to improve response rates over time in these patients.

[Steven Hoerter, executive]

And then, Tyler, second question related to duration in the Phase 1/2, do you want to comment on that as well, Matt?

[Matthew Sherman, executive]

Yes. And that's really a function of Phase 1 dose escalate cohorts were enrolled earlier. So there the median treatment duration of 25.1 months. That 4-month delta that you referenced is more of a function that they were enrolled on to the study longer, so they just didn't follow for a longer period of time. The Cohort A now is actually very much catching up, and we still have 47% of patients in Cohort A on study. So those patients can continue to contribute to a longer treatment duration when we have another data cut in the future.

[Steven Hoerter, executive]

And as you may remember, Tyler, that Cohort A in the Phase 2, that's the same patient population that we've treated in the MOTION study. So we think that could be a really good indication, as the data matures, ultimately of what median duration of treatment could look like.

[Operator]

And our next question coming from Eun Yang with Jefferies.

[Eun Yang, analyst]

Congrats on the Phase 3 success. So in TGCT, we hear from physicians that its usage could be quite useful in neoadjuvant-adjuvant settings. So I'm wondering if you are planning for those trials? And second question is on QINLOCK. So 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?

[Steven Hoerter, executive]

I'll take the first question and then ask Dan Martin to cover off on your question related to QINLOCK 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 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, Eun, we will, of course, be updating investors on our clinical development plans on an ongoing basis. Dan?

[Daniel Martin, executive]

So we are really excited about the performance in the U.S. over the last 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 in fourth-line. The team has 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 2 factors that we had noted, both the ctDNA analysis showing the dramatic treatment benefit for patients in the second-line setting with a 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 QINLOCK as part of their treatment arsenal for patients with GIST.

[Operator]

And our next question coming from the line of Michael Schmidt with Guggenheim.

[Michael Schmidt, analyst]

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. And I think you talked about QOL,in particular before, has that outcome matched with your expectation?

[Steven Hoerter, executive]

Yes. Thanks, Michael. Quick question on the secondary endpoints. Matt, do you want to take that?

[Matthew Sherman, executive]

Yes. Michael, it's Matt. So yes, we are thrilled, of course, with all the secondary end points. So we really expect that together, they will contribute to 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 RECIST criteria they used for tumor measurement. Of course, RECIST was first developed for solid tumors, so more of a spherical volume shape compared to the very irregular shape that TGCT tumors having to join. 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 Vimseltinib treatment. But importantly, the other secondary endpoints, including range of motion and the other quality of life measures that we've highlighted previously, a very important aspect of how patients feel and function. And that has been really a key way of differentiating therapies that not only just because the tumor to shrink, but also improve the quality of life of patients. The limitation for pexidartinib 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 3 ENLIVEN trial. So they are only limited to having range of motion in the U.S. label for pexidartinib. So we look forward to submitting the NDA to the FDA and 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 the secondary endpoints that will contribute to the success of Vimseltinib.

[Michael Schmidt, analyst]

Great. And then real quick 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 presurgery or any other potential label expansion opportunities you could now think about with this result in hand?

[Steven Hoerter, executive]

I think I kind of figured back on Eun's question earlier, which is the potential 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 we're certainly evaluating more broadly the additional places that we could explore the role of Vimseltinib and the opportunity to benefit patients, whether it be with TGCT or with other diseases.

[Operator]

And our next question coming from the line of Christopher Raymond with Piper Sandler.

[Christopher Raymond, analyst]

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 pexidartinib, is still a CF1R-like toxin, how should we be thinking, I guess, about the chances for a black box where are you're thinking the data should speak for itself and 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 QINLOCK.

[Steven Hoerter, executive]

And so I imagine the Black Box you're referring to is related to cholestatic hepatotoxicity. We don't see 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 1/2 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, pex 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 pexidartinib 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 1/2 data, where we now have the longest patient on treatment is out to 4 years. So we have a very long-term follow-up from the Phase 1/2 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.

[Christopher Raymond, analyst]

Great. And then maybe on QINLOCK, maybe. So just taking into account your comments on second-line use in 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 with 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 planned policy changes that could be a tailwind in that second-line setting?

[Daniel Martin, executive]

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 and just broadly and the really strong product profile. We would 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, certainly provides a tool for them to engage with payers if there were any barriers to earlier line use. But we don't expect there to be any meaningful change in the payer access dynamic for QINLOCK.

[Operator]

And our next question coming from the line of Andrew Berens with Leerink Partners

[Andrew Berens, analyst]

Just a couple for me. Based on the Phase 1/2 trial, it sounds like most patients are getting good results for at least 2 years or more. Just wondering what treatment patients that drop off of them get? Are they getting surgery or are they moving to another agent? And then a number of data sets 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 frame 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 a rare disease-type launch?

[Steven Hoerter, executive]

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 and 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 them 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 I'll flip it over to Dan to talk about the launch expectations for Vimseltinib. Matt?

[Matthew Sherman, executive]

Andy. So there hasn't been one 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 nonamenable or surgically unresectable prior to Vimseltinib, at least there was a decision in some patients that they could be potentially resectable following treatment. Also as we've mentioned earlier, these are younger patients who are working with families and they may have other reasons during the trial period to come off therapy. Interestingly, we had 2 patients who initially enrolled into the trial who had stopped. One was a patient who's living within Europe. So for work reasons, he had a discontinued treatment from the Phase 1 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, and the patient was a previous CSF1 receptor inhibitor, and that previous treatment was Vimseltinib. And then also in Cohort A, we have 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 with Vimseltinib, very excellent use in the commercial setting.

[Daniel Martin, executive]

Yes. I'll take the last question on the Vim sort of launch dynamics that we anticipate. I think that 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 diagnosed, they're receiving systemic therapies or 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 pexidartinib profile and the REMS program. And so we think that is a growth opportunity over time as well. So we're viewing the opportunity in multiple layers there and really looking forward to a potential launch.

[Operator]

And our next question coming from the line of Bradley Canino with Stifel.

[Unknown Analyst]

And this is [ Bjorn ] on for Brad Canino. Congratulations on the positive data in the quarter. Two questions. The first is on Vimseltinib. Largest question is around the EU regulatory pathway. As you know, EMA prior to the [indiscernible] TURALIO's benefit risk profile was negative within less than that projection in that region. Do you think the EMA was negative on the benefit of a CSF1R inhibitor or was this a trial conduct in data collection for pexidartinib? And also, what gives you confidence you've collected a better benefit and risk assessment for Vimseltinib?

[Steven Hoerter, executive]

I'll take the question. So you're exactly right. I think I know 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 that 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 HCA 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 6 key secondary endpoints really bolstering the information we have and the positive view of the drug is measured by patient reported outcomes, whether that's range of motion or whether it's measures of pain, physical function and other quality of life measures. So we think the data package is quite compelling. Of course, we'll engage as we were 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 the EMA will view the data package in the same way.

[Unknown Analyst]

Very helpful. And then just one more on QINLOCK. 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 QINLOCK?

[Steven Hoerter, executive]

So on the last part of your question, what do we need to see to, I missed the last bit there.

[Unknown Analyst]

To consider broadening your disclosure for target peak sales for QINLOCK.

[Steven Hoerter, executive]

Dan, would you like to take the question?

[Daniel Martin, executive]

Yes, sure, absolutely. So a couple of thoughts there, [ Bjorn ]. So as we 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 from 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.

[Operator]

Our next question coming from the line Reni Benjamin with JMP Securities.

[Reni Benjamin, analyst]

Congratulations on these great results. Maybe just a couple for me. As we think about the sales force, I know in your prepared comments, you mentioned that the 70% to 80% or so of overlap with the existing marketing effort and just. But as you think about rightsizing the sales force and kind of taking advantage of the full opportunity, what does that look like upon launch or shortly after launch? And do we think this will be a priority review? Or since pexidartinib is already approved 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 Vimseltinib, are these going to be post imatinib, post-pex sort of patients? Will they be naive patients? Who do you think will be the ideal patients that physicians would place on Vimseltinib?

[Steven Hoerter, executive]

This is Steve. Thanks for the 3 good questions. First, let me take the priority review question and then I'll ask Dan and Margarida, I'm sure can also comment on implications for sales force as we think about adding the potential to add vimseltinib 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 vimseltinib. 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. Margarida, 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 and related to uptake in the U.S.

[Margarida Duarte, executive]

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 QINLOCK, so consistent with our cost optimized European infrastructure, the plan is to deploy a lean and a determined customer-facing team that will be focused in raising awareness and generating demand for Vimseltinib. 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.

[Daniel Martin, executive]

So in the latest corporate deck, 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 the market opportunity. And I think I direct you to that because I think it's really informative in a number of ways that actually speak to in both parts to 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 also engaging with the oncologists that we know very well. And so a couple of important implications there. From a sales force 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 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 the 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 will be able to penetrate this patient population as well. What we hear is that 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 Vimseltinib 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.

[Operator]

[Operator Instructions] And our next question coming from the line of Peter Lawson with Barclays.

[Peter Lawson, analyst]

Congrats on the data on the call. Just any way of quantifying the level of off-label use you've seen in the quarter? Is that driving all the U.S. ones? And any kind of puts and takes we should be thinking about 4Q? And then on Vimseltinib, that TVS score of 67%. How does that compare to prior data?

[Steven Hoerter, executive]

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 TVS for MOTION and then also what we saw in the Phase 1/2 study in terms of TVS.

[Daniel Martin, executive]

Yes. Peter, it's Dan. So yes, really, really strong growth over the last 2 quarters. We've been really excited to see that. I've noted that a big part of our success over the last couple of quarters has been continued execution in the fourth line setting that is 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 there's significant sort of break in trend. All of that taken together, we feel confident that a significant portion of the increase over the last couple of quarters has come from this unpromoted earlier line use.

[Matthew Sherman, executive]

Peter, as we noted, the tumor volume score is a computer-assisted quantification of the tumor volume. And when we used this in the Cohort A population from the Phase 1/2 study, we had a 51% TVS response at week 25 that did increase as we've updated the data today is now 62% with a longer-term follow-up. So this is similar, with the MOTION study, we actually had a higher TVS response at week 25 in the Vimseltinib treated arm in Motion at 67%. And as we mentioned earlier, this will be continue to be followed over time and expect that will go up as well.

[Peter Lawson, analyst]

Got you. And then maybe as we think about the U.S. use in TGCT, kind of what's your current estimate of pexidartinib use in the U.S.? And do you expect physicians to switch patients off of Vim, off of pex on beginning?

[Daniel Martin, executive]

Yes. Thanks, it's Dan again. I appreciate the question. So our analysis of the claims data has shown that 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, the most of the other patients receiving TKI received imatinib. I'm trying to remember what was the other part of your question?

[Peter Lawson, analyst]

Yes. Switching from either imatinib...

[Daniel Martin, executive]

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 patients do tell us that even when they receive benefits from pexidartinib given that it 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, frankly, hair whitening. We hear from patients that all of these dynamics are challenges to this patient population. And so those always sort of weigh on the minds of these patients. So we think given that and given the potential best-in-class agent, we will have the opportunity for some switches.

[Operator]

And we have a follow-up question from Eun Yang with Jefferies.

[Eun Yang, analyst]

Two quick questions. For second-line GIST, what percent of patients are considered intolerant to sunitinib? And the second question is to Tucker for R&D, with the MOTION trial ended, but you are running second-line GIST trials and others. So how do you expect R&D run rate to go going forward? Will that be from third quarter number to be the run rate for 2024?

[Steven Hoerter, executive]

Dan will take the question on sunitinib intolerance [indiscernible] Tucker.

[Daniel Martin, executive]

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% range of patients may have some intolerance as it relates to sunitinib. So we think that, 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?

[Thomas Kelly, executive]

Yes, thanks for the question on the R&D expenses. So we don't provide OpEx guidance, but we would expect that the R&D going forward would be in a similar range to a little bit higher than a modest increase 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 QINLOCK, we're just getting up and running on the INSIGHT trial as well. So more to come on that, but we would expect significant increases, but could be some modest ones over time.

[Operator]

Thank you. And I see no further questions in the queue at this time. I will now turn the call back over to Mr. Steven Hoerter for any closing remarks.

[Steven Hoerter, executive]

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 Deciphera. Hope you have a great rest of your day and a great week ahead.

[Operator]

Ladies and gentlemen, that does for our conference for today. Thank you for your participation. You may now disconnect.