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spk05: Good morning, everyone, and welcome to the CIFRA Pharmaceuticals Second Quarter 2023 Financial Results 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?
spk01: Thank you, Operator. Welcome, and thank you for joining us today to discuss the CIFRA's Second Quarter 2023 Financial Results. I'm Jen Larson, Senior Vice President of Finance and Investor Relations. With me this morning to discuss the financial results and provide a general corporate update are Steve Herter, President and Chief Executive Officer, Dan Martin, Chief Commercial Officer, Matt Sherman, Chief Medical Officer, Margarita Duarte, Head of International, and Tucker Kelly, 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 for our preclinical and clinical programs, our commercialization of Kinloch and 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?
spk04: Thank you, Jen, and good morning, everyone. Thank you for joining us today as we provide an update from the second quarter, review our financial results, and look forward to the rest of the year. We've made tremendous progress so far in 2023 thanks to the exceptional work of our dedicated team at Decipherer. Our commercial business continues to drive strong results, highlighted by a record quarter for Kenlock, which generated over $38 million in Q2 revenue, an 18% increase over Q2 last year. We believe that we can significantly grow the Kenlock brand by expanding the label to include second line GIST patients with KIT exon 11 and 17 or 18 mutations. And we are pleased to announce today an important milestone toward that goal. The opening of the first sites for the phase three insight study. The compelling results of the exploratory analysis of circulating tumor DNA from the Intrigue phase three study of Kenlock and second line GIST patients were featured in an encore presentation at the 2023 ASCO Annual Meeting. These data continue to generate very positive feedback from physicians who are eager to enroll patients in the INSIGHT Study, which is designed to serve as the basis for a supplemental new drug application, or SNDA. We are also proud to announce today that we have initiated two new combination cohorts for DCC 3116, with Encurafenib and Cetuximab, and with Recretinib. On today's call, we will share a data update from the 3116 program, including data from both the phase one single agent escalation and the initial combination escalation cohorts. We're excited to generate additional data from this potential first in class program targeting the autophagy pathway. At the American Association of Cancer Research annual meeting in April, we presented eight posters on our early stage pipeline. including the first disclosure of our new pan-kit inhibitor, DCC3009, for which we expect to file an IND in the first half of 2024. The data we presented at AACR highlighted the sustained productivity of our kinase switch control research engine and its proven ability to generate product candidates with first and best-in-class potential. Now looking ahead, we are moving into an exciting second half of the year as we approach the top line readout for the pivotal phase three motion study of Vinsultinib in tenosynovial giant cell tumor and the IMD submission for DTC3084, our potential best-in-class pan-RAP inhibitor. Now I'd like to take a moment to recognize Dan Flynn, our founder and chief scientific officer, whose retirement was announced last week. On behalf of the entire Decipherit team, I want to thank him for his vision to found our company almost two decades ago, and his trailblazing innovations in switch control kinase inhibition, which have brought Decipherit to where it is today. It has been an honor working alongside Dan, and I wish him the very best in his retirement. We're excited to welcome Dr. Dash Danak as our new Chief Scientific Officer next month. Dash brings an exceptional background as a leader in drug discovery with over 30 years of experience. and joins DeCyphera from Insight Corporation, where he was most recently Executive Vice President and Chief Scientific Officer. On today's call, Dan Martin, our Chief Commercial Officer, will share insights on the U.S. commercial performance for the second quarter, and Margarita Duarte, our Head of International, will provide an update on Kenlock's ongoing fourth line just launched in Europe. Matt Sherman, our Chief Medical Officer, will provide an update on our R&D efforts, including data from the DCC 3116 Phase 1-2 study. Finally, Tucker Kelly, our Chief Financial Officer, will review the financial results from the second quarter. First, I'll turn the call over to Dan and Margarita to discuss our Q2 commercial performance.
spk02: Dan? Thanks, Steve. Q2 was a record quarter for Kinloch in the U.S. We achieved launch-to-date highs in terms of net product revenue, as well as many of our core brand metrics. U.S. net product revenue was $28.9 million in the second quarter, which represents a 17% increase versus Q1 in and a 22% year-over-year increase versus Q2 of 2022. During the quarter, we saw continued momentum in core drivers of demand, including new prescriber growth, new patient acquisition, and average duration therapy. Together, these factors drove strong volume growth in Q2, as demand bounced back from the seasonality-driven softness we saw in Q1. Additionally, gross net declined slightly in Q2 versus Q1, whereas PATH increased slightly quarter over quarter. Our commercial team continues to execute at a very high level, again delivering the highest reach frequency and share avoidance of any company in the GIST market and maintaining high awareness and positive product perceptions among both academic and community physicians. New prescriber growth has continued at a very consistent pace. In Q2, we surpassed 1,000 Kinlon prescribers launched to date Our market research and KOL interactions continue to highlight that Kinloch is firmly entrenched as a clear standard of care in fourth-line GIST. At ASCO in June, we had the opportunity to sit down with many of the leading sarcoma experts from across the country. GIST KOLs consistently highlighted their positive clinical experience with Kinloch and the tremendous impact Kinloch has had for their patients. In particular, KOLs highlighted Kinloch's impressive efficacy and tolerability, which they noted is a combination that can be challenging to deliver to patients receiving . We remain very pleased with our commercial momentum in the U.S. and look forward to continuing a strong institution in the second half of the year. We expect to see continued growth in demand balanced with modest increases in PATH. Consistent with prior years, we expect the PATH percentage in Q3 and Q4 to be near the high end of our estimated range of 20 to 30%. In addition, we expect to see modestly higher growths to net in Q4 related to the Medicare inflation rebates required by the Inflation Reduction Act. I will now turn the call over to Margarita Duarte, our head of international, to discuss the progress of the Kinloch launch in Europe. Margarita?
spk07: Thanks, Dan. We remain very excited with the strength of the international business and the launch momentum of Kinloch in Europe. For the second quarter, international revenue was $8.4 million, up from 7.8 million in the prior year, driven by continued volume growth from the successful entry in Europe and partially offset by a lower monthly price in Germany following the expiration of the free pricing period in 2022 and by timing of orders from distributor markets outside Europe. Kinla continues to be very well received by physicians and patients in Europe based on the high and met medical needs and its unprecedented benefit in fourth-line juice. In Germany, we continue to see strong demand as we work to unlock a significant opportunity in the more dispersed and fragmented community setting. On the heels of the strong pricing we achieved in Germany, the team continues to work diligently on achieving reimbursements for Kinloch with authorities in Spain, France, the United Kingdom, and elsewhere. Last quarter, we shared that we expected to launch Kinloch in Italy in the coming months, And today we are delighted to announce that we are very close to launch. We have successfully finalized the reimbursement negotiation process and are waiting for the publication of the IFA resolution in the official Gazette, which is the last step before launch. We look forward to getting Kinloch in the hands of patients in Italy shortly. Turning to the rest of the world, we are excited that negotiations with the Pan-Canadian Pharmaceutical Alliance were successfully completed. The agreement supports the public listing and reimbursement of Kinloch by provinces in Canada, and is a major step in enabling broad access to Canadian patients with forced-line GIST. Kinloch is already available in the first provinces, and our partner in Canada continues to work with the remaining ones to finalize public reimbursement. Additionally, we are pleased to have recently received approval for Kinloch in Singapore. All in all, these are very positive developments, and we expect our international revenue to continue to grow as reimbursement agreements and approvals are achieved around the world alongside the growth from our initial launch markets. I will now turn the call over to Matt to provide an update on our clinical programs. Matt?
spk16: Thanks, Margarita. We continue to compliment our commercial success with substantial progress across our growing pipeline of clinical and preclinical programs, enabling Decipher to solidify its position as a leading oncology company. There is excitement at all stages of our pipeline from the upcoming top line results of the phase three motion study to the start of the INSIGHT trial and to the opening of cohorts for DCC 3116. I'm confident about the prospects we have to apply our discovery, development, and commercial capabilities to benefit patients with cancer. First, I'd like to start with our DCC 3116 program. 3116 is designed to be a first-in-class backbone combination agent across a wide range of cancers. As Steve mentioned earlier, we are excited to announce today that we've opened the first site for two new 3116 combination cohorts, one with Encorafenib and Cetuximab, and the second with Ripritinib. We look forward to continued progress as we work to demonstrate clinical proof of concept for the inhibition of Oc-1,2 mediated autophagy to treat cancer. Moving now to discuss updated Phase 1-2 data from both the single-agent escalation and the combination escalation cohorts. At our initial clinical update at ESMO last year, we presented data on the first 18 patients in the single-agent dose escalation part of the study, and that selected a starting dose of 3116 of 50 milligrams BID for the initial combination cohorts. I'll first provide a brief update on the additional data we have generated from the single-agent dose escalation that includes 10 additional patients. In the full 28 patients, single-agent 3116 remained well-tolerated at doses from 50 milligrams BID to 300 milligrams BID with no maximum tolerated dose reached. The AE profile was shown to be consistent with prior data disclosed at ESMO 2022, and only one dose-limited toxicity was observed, a grade 3 ALT increase at 100 milligrams BID. The updated pharmacokinetic profile continued to demonstrate 3116 exposure associated with the anti-cancer efficacy in preclinical combination studies. The PK profiles show that 3116 exposure increased the doses between 50 and 200 milligrams PID with associated variability. And at the dose of 300 milligrams PID, 3116 exposure appeared to approach plateau. We continue to see pharmacodynamic effects that were associated with anti-cancer efficacy in preclinical studies. At the end of last year, we began evaluating 3116 with two MEK inhibitors, Tremetinib and Bidimetinib, and a KRAS G12C inhibitor, Sothiracid, in patients with advanced solid tumors. As of August 4th, 2023, we had enrolled 27 patients in the combination cohorts across a variety of solid tumors. Those limiting toxicities were observed at 50 milligrams BAD of 3116 in combination with the approved doses of Tremetinib and Bidimetinib. Based on these DLTs and the updated PK and PD data from the single-agent dose escalation and the preclinical combination efficacy study with once-daily dosing of 3116, we reduced the dose of 3116 to 50 milligrams QD for both the trimetinib and benimetinib combination cohorts. In the ceteracid cohort, the first dose level of 3116 at 50 milligrams BID and ceteracid 240 milligrams QD was well-tolerated with no DLTs observed. We subsequently dose escalated 3116 to 200 milligrams QD, and enrollment is ongoing. We expect to have sufficient data in the first half of 2024 to make decisions about opening the MEK or KRAS C12C expansion cohorts after we have completed the dose escalation combinations. We remain excited about opening our two new PCC31 escalation combination cohorts, and we will continue to follow the clinical data to invest in the right expansion combinations to demonstrate clinical proof of concept. Moving on to Vimseltinib in the first quarter, we announced completion and enrollment in the Motion Pivotal Phase 3 study, which we believe will become the second approved product from our Switch Control kinase inhibitor platform. We remain on track to read out top learning results from Motion in the fourth quarter. We also expect to present updated efficacy and longer-term safety data from the Phase 1-2 study in the fourth quarter. We are strongly encouraged by compelling clinical data we have generated, supporting the potential to be the standard of care treatment for patients with TGCT non-amenable to surgery. We also opened the first site for INSIGHT, a new pivotal phase three study of Kinloch versus Submitinib in second-line GIST patients with KIT mutations in exons 11 and 17 or 18, and look forward to enrolling the first patients. If positive, we believe the results of the INSIGHT study will support an expanded label for Kinloch and significantly improved clinical outcomes for patients based on a more precise understanding of the GIST tumors that allows physicians to select the best therapy for their patients. Lastly, we remain on track to submit an IND for DCC3084, a potential best-in-class pan-RAF inhibitor in the fourth quarter, and another IND for our new pan-KIT inhibitor, DCC3009, in the first half of 2024. I will now turn the call over to Tucker Kelly, our Chief Financial Officer, to review the second quarter financial results. Tucker?
spk14: Thanks, Matt. Total revenue for the second quarter of 2023 was $38.3 million, which includes $37.3 million of net product revenue, Kinloch, and $1 million of collaboration revenue, an increase of 18% compared to total revenue of $32.5 million in the second quarter of 2022, including $31.5 million of net product revenue. The $1 million in collaboration revenue this quarter was comprised of product royalty revenue under our agreement . Cost of sales were $0.2 million in the second quarter of 2023, compared to cost of sales of $1.8 million for the second quarter of 2022. Cost of product revenue was $100,000 in the second quarter, compared to $1 million in the same period last year. In the second quarter, total operating expenses were $90.9 million, compared to operating expenses of $74.5 million in the same period in 2022. Research and development expenses for the second quarter were $58.3 million compared to $44.9 million for the same period last year. Selling, general, and administrative expenses for the second quarter of 2023 were $32.6 million compared to $29.6 million for the same period in 2022. We expect quarterly operating expenses in the second half of the year to be consistent with what we saw in the second quarter of 2023. As of June 30, 2023, cash, cash equivalents, and marketable securities worth $389.4 million, and our cash flow and rate guidance into 2026 remains unchanged. With that, I'll now turn the call back over to Steve.
spk04: Thanks, Tucker. The first half of 2023 was a strong start to what we expect to be a very significant year for Deciphera. We made significant strides across our commercial business, as well as our early and late-stage pipeline, and we are now well-positioned to achieve important milestones in the second half of the year. We are excited for the top-line readout of the Motion Pivotal Phase 3 study of themselves in the fourth quarter, as this program has the potential to address the significant unmet needs of TGCT patients and become our second approved medicine. Additionally, we look forward to enrolling the first patients in the INSIGHT Pivotal Phase 3 study of Kinloch, as we seek to change the treatment paradigm for second-line GIST patients with mutations in KIT Exon 11 and 17 or 18, all while we continue to advance our earlier stage clinical pipeline. With that, operator, I'd now like to open the call for Q&A.
spk05: Thank you. And as a reminder, to ask a question, simply press star 11 on your telephone and wait for your name to be announced. One moment for our first question. It comes from the line of Tyler Van Buren with TD Cal, and please proceed.
spk10: Hey, guys. Good morning. For the registrational motion trial reading out next quarter, Assuming success, which is likely, how quickly can you file BIM for TCGT? And as a follow-up or related question, what specifically should we look forward to from the Phase 1-2 update expected next quarter relative to what we saw last year?
spk04: Yeah, good morning, Tyler. Thanks for joining. Thanks for the questions. It's Steve. I'll take the first question about the readout and potential timing for filings. And I'll ask Matt to comment on expectation setting for the phase one, two update. So as we noted on the call, we reiterated our guidance to report out the top line for the phase three motion study in quarter four of this year. We're excited to get to that milestone. We think the data we presented so far clearly demonstrate the potential for Vimseltinib to be best in class for the treatment of patients with tenosynovial giant cell tumor. And so when we get to the report out of the top line in quarter four, We believe we'll be in a position then to provide an update on potential filing timeline. Of course, you know, once we get to the top line report ad, you know, we will engage with FDA as we usually do in the ordinary course and have that conversation with them as we prepare for that potential filing. And we're excited about the program, as you know, because there's very nice overlap with the prescriber base for the existing business we have with Kenlock and GIST. And we think that this product has a very high likelihood of being our next commercial product here in the U.S. and outside of the U.S., allowing us to transition to be a multi-product company. So, Matt, you want to comment on the Phase 1-2 expectations?
spk16: Yes. So, good morning, Tyler. So, in regard to the updated data for the Phase 1-2 study of imsultinib and TTCT that we plan to present later this year, as you know, a year ago, we presented the data at the ESMO 2023-2022 meeting, and at that time, we were able to report really a very strong objective response rate for both the dose escalation cohorts and cohorts A and B in patients with previously untreated or treated TGCT. So with longer follow-up, as we saw previously, patients may respond. So that would be part of the update, as well as longer safety information. And importantly also, again, looking at the patient-reported outcomes and quality measures that we had measured previously, both pain and for stiffness, because those are very important about how patients feel and function. So there will be updated data for those as well.
spk06: Thank you. One moment for our next question.
spk05: It comes from the line of Yun Yang with Jefferies. Please proceed.
spk08: Thank you. So I have a couple of questions. One is on Phase III Insight Trial, which just began. According to the clinicaltrials.gov, the primary completion is in February 2026. And this is a two-to-one randomization with a team log showing 14 months of PFS in Phase II intrigue. So does this timeline assume about 18 months, maybe 12 to 18 months enrollment period? And second question is for Tucker. In terms of a collaboration revenue for this year, my understanding is that it's going to be around $8 million. and based on the first half of this year run rate, what are the kind of collaboration partnership revenues they wish to be expecting in second half of this year, aside from Xyle Lab royalties? Thank you.
spk04: Hi, Yun. Good morning. Thanks for the two questions. I'll take your first question with regard to Insight, and then Tucker can take your second question. So we were excited, as you heard you announce, that we've opened now the first sites for the Insight study. And in the conversations we've been having with investigators and with thought leaders, there continues to be really palpable enthusiasm for the study and for this notion of being able to better understand the genetic profile of patients' tumors in order to guide therapy in GIST. And as you know, this is, in essence, the first time in GIST that we're able to advance the field in this way. we're looking forward to getting additional sites open as we begin now screening and then enrollment in the study. As we've noted before, as we get into a cadence of enrollment, we think we'll be in a much better position to provide updates on when we'd expect to get to full enrollment in the study and when we might expect the study to read out. So I would use the ct.gov listing. I would take that with a pinch of salt for the moment until we really get into enrollment, having more sites open, and we have a better sense of what that cadence of enrollment will be. And as I just said, we'll provide updates along the way so we can share our progress on the study. But we're looking forward to, as I said, opening more sites and remain enthusiastic about what we hear from investigators who are going to be participating in the study.
spk14: Okay, units. Tucker, for your second question, so as a reminder, collaboration revenue at the moment consists exclusively of revenue we recognize under our collaboration agreement with Xi Labs for Kinloch in greater China. So we recognize so far this year 1.2 million roughly. The two key components historically for collaboration revenue have been product royalties as well as commercial supply revenue. In the first half of this year, particularly in the second quarter, it was really almost exclusively royalty-based revenue, so only a small amount outside of that. The first quarter was a bit different. in that they had been taking a price adjustment based on the NRDL listing, which happened earlier this year. So I think we've got a nice quarter for royalty revenue. It was just under $1 million for Zai in Q2. And we haven't brought any guidance as to the balance of the year. I think what we'd say is that we continue to expect royalty revenue to increase over time as they progress. expand the market opportunity in China. And then the commercial supply revenue is more episodic, and we don't provide guidance. But from time to time, in particular quarters, you may see that as well. But the royalty revenue should be the consistent piece.
spk06: Ms. Yang, does that answer your question?
spk08: Yes. Thank you very much.
spk05: Thank you. One moment for our next question, please. It comes from the line of Michael Smith with Guggenheim. Please proceed.
spk12: Hey, guys. Good morning. Thanks for taking my questions. I had one on DCC 3116. You know, it's interesting, you mentioned these DLTs in the Trimetinib and Binimetinib combination cohorts at 50 milligrams twice a day. Could you talk about that some more and, you know, what were some of those DLTs? Do you think this could be mechanism related or perhaps off target? It's just interesting given the single agent Dose up to 300 was well-tolerated. It's curious if there's anything else going on in that particular combination.
spk04: Yeah, thanks, Michael. Matt, do you want to take that?
spk16: Yes. Good morning, Michael. So, yeah, as you know, you know, we've reported some DLTs in the combination cohorts of 3116 with Trematinib and Midimetinib. And just to go back to the data that we presented initially at ESMO last year and then recently updated today, in the monotherapy cohorts, the doses of 50 milligrams BID up to 300 milligrams BID of 3116 as a single agent was well-tolerated. There was no dose-limiting, there was no maximum tolerated dose identified, and there's only one dose-limiting toxicity identified of asymptomatic reversible ALT elevation in a patient of 100 milligram BID dose level. And then in the combination cohorts with both trimetinib and binimetinib, at the starting dose level of 50 milligrams BID with the standard doses of those agents, we did observe a few DLTs. Interesting, those DLTs have been reported in the labels for both of those single agents, both of those drugs have single agents. So if you look at the warnings and precautions or the most common, as for events of trimetinib, rash and diarrhea are noted. And similarly for binimetinib, cardiac changes and ocular changes are also noted for binimetinib. So those may be related to the single agent of those standard of care drugs. But, of course, in the clinical trial setting, because the drugs are combined, the attribution is given to the combination. So we proceed with the desescalation cohorts for both trimetinib and binimetinib. In addition for sotiracib, we're also combining sotiracib with 3116. And we've now escalated to 200 milligrams QD in combination with sideracid. We have not seen any dose-living toxicities in that cohort.
spk12: So in the MEK inhibitor combination, so you're stepping down to 50 QD, but is there opportunity then to escalate after that cohort is completed?
spk16: Yes, so there's, you know, per the protocol, there's opportunities to, you know, modify the doses of both 3116 and or the standard of care combination drug. So once we start to, you know, complete enrollment in those cohorts and look at the, you know, all the information, we'll be able to make decisions about the next dose levels that we'll be able to move to in those combinations. Okay. Okay.
spk12: Then a question on Vimseltinib. Obviously, a lot of focus on the motion study, completing that, and discussing the data, but just curious if you, how do you think about potential other indications for Vimseltinib in the future? Are there other opportunities that you might be interested in pursuing for the C-type 1 iron killer?
spk04: Yeah, Michael, thanks for the question, Steve. I'm happy to take that. So, I think you're familiar with recent reports of CSF1R inhibition in chronic graft-versus-host disease as an example. So some recent data with an antibody confirming the potential role of CSF1 receptor inhibition in that disease. There have been other reports in the literature about a potential role for inhibitors in treating fibrotic diseases like IPF. So we haven't made any disclosures yet, as you know, about potential additional indications that we might pursue with Vimseltinib, but we are very actively evaluating additional opportunities for them, and at the right time, we'll have future disclosures with respect to our plans and the opportunity to broaden the role potentially for Vimseltinib to treat a variety of diseases. So that's where we stand, but we're pleased to see how the field continues to evolve, and certainly with a profile like we've demonstrated already with Vimseltinib being an oral agent And being very potent and selective, we think we have a great drug on our hands, which we want to make sure we explore fully. Great. Thank you.
spk05: Thank you.
spk06: One moment for our next question. It comes from the line of Chris Raymond with Piper Sandler.
spk13: Hey, thanks. I've got just two questions. Maybe first on Kinloch. Can you maybe talk about what you're seeing commercially in the second line setting at this point? You had a pretty strong second quarter print. I'm just kind of curious if you can give any color. as to the second line uptake that might be from the NCCN guidelines that may be driving that. And then a question on Vimseltinib. I don't think there's any suspense, at least as I talk to investors, in terms of meeting the primary endpoint of the motion study. But maybe can you just talk a little bit about what kind of expectations you'd like to set You've got the dynamic of deepening response rates over time. You've got the 69% at any time point. But this is a 25-week study, which one would argue is likely to skew on the lower end of some of the stuff you guys have shown. So maybe just set expectations, if you will, in terms of what that actual number should be when you see the readout. Thanks.
spk04: Thanks, Chris. Good morning. Thanks for joining us. So I'll ask Dan to take the first question. Matt can take the second. Maybe I'll just start before I turn it over to Dan and just say that, you know, as we said in the prepared remarks, we're really excited about the performance that we saw in quarter two and the strength of the business here in the U.S. and the growth that we saw and, of course, our continued launch in Europe and opportunities geographically to expand continues. But, Dan, you want to offer some more color commentary on what we're seeing in the U.S. business?
spk02: Yeah, absolutely. Thanks, Steve. And good morning, Chris. Thanks for the question. So extremely pleased with our performance and results in Q2, really a record quarter for Kinloch in the U.S. Clearly, Kinloch is entrenched as the standard of care in the fourth line setting, which we continue to be really pleased with. And importantly, we saw strength across virtually all of our core brand metrics this quarter, including new prescriber growth, new patient acquisition, and average duration of therapy, among others. Regarding your question about could there be growth in the off-label setting, first I'll just note, as we always do, that you know, any second line use is an off-label use that we can't and don't promote. And really there's sort of two elements to this. One is the 11, 17, 18 data that we presented at both the virtual ASCO plenary as well as the ASCO annual meeting in June where we continue to hear great excitement by KOLs around that data. They call it, you know, potentially practice changing and therefore real excitement for the insight study that we've just announced, we've opened. And then the second component that you touched on is the guidelines piece, which is listing of Kinloch for patients who may be intolerant of sunitinib. And what we hear from KOLs there is, It really is an appreciation for having another option, albeit some variation prescriber to prescriber in terms of how common it is for them to have a patient that's in talent of student, but certainly always appreciate having another option. So in terms of what those, either of those or both of those dynamics may be having on the business, we think it's still just a bit early to be able to discern what impact, if any, that's having. It's really just a bit early to know. Certainly something that we'll continue to monitor. And there's no question that overall we're extremely pleased with the strength and direction of the business.
spk16: Yeah, hi, Chris. This is Matt. So in regard to VIMSELT and TGCT, you know, as you noted, you know, we're very pleased with the data that we first reported at ESMO last year with really strong objective response rates across all three groups of patients from the Phase I dose escalation to the two expansion cohorts. And as we noted earlier today, too, we plan to have an update of that data as well later this year. And importantly, you know, it's not only just the regulatory endpoints, for approval at week 25. But as we noted previously, and has been previously shown with other agents, with continued treatment, the response rates go up. And that will be really important for how these patients' journeys will progress. Because as we noted, this is not a malignant disease. So patients have normal life expectancy, even though they suffer from their disease. So the chronicity of treatment will be really important for these patients' quality of life. And in regard to quality of life, Importantly, as well, too, as we first reported this last year, patient-reported outcomes are really critical to the use of this drug. This was a missing part of the Paxadartan approval because they had a lot of missing data in their evaluations of patients. But we've incorporated the quality of life measures, including pain and stiffness, and we reported those last year as well, too. Patients had very meaningful changes in both worse pain as well as in stiffness. And in addition, one of our other endpoints is range of motion. And this is really important as well, too, because the FDA asks for these diseases, not just how patients survive, but importantly, how they feel and function. So the quality of life measures, and particularly range of motion, can be an important secondary endpoint that we will look forward to speaking to in the future.
spk04: Yeah, just to build on Matt's comment, this is Steve. Chris, good question on expectation setting. You know, when we reported the data last from the Phase I-II at ESMO last year, what we noted was that we saw a week 25 or a six-month response rate that was at 38%. But yet, as Matt noted, we saw additional responses beyond that time point. So, I think when it comes to how this drug ends up getting commercialized, assuming success, it will be based on the totality of the data, including longer-term follow-up, which is very consistent with how Daiichi today markets PECSIDAR, and it's based on the totality of the PECS data as opposed to solely that week 25 endpoint. But we're really pleased with how the product has performed in the phase 1-2 and look forward to reporting out the top line in Q4.
spk16: And also one more comment on that question as well, too, is the duration of therapy is also very important. As we were able to report last year, in the patients who were in the dose escalation cohorts who had been on study for the longest, we had nearly an 18-month duration of therapy for those patients. And with additional follow-up that we expect to report later this year, too, with longer follow-up for those patients, that duration of therapy number also will report on an updated duration of therapy number for the patients.
spk13: Thank you very much.
spk05: Thank you. One moment for our next question.
spk06: It comes from the line of Andrew Behrens with Learing Partners.
spk15: Hi. Thanks, and congrats on the progress, guys. A couple from me. Now that the QNLOC, the Phase II INSIGHT trial is opening, can you give us some idea of how long you think it could take to enroll that trial? How many patients do you think you'll have to screen to identify one with exons 11 and 17 or 18? And then... Question on 3009, the pan-kit agent. Another pan-kit agent had a setback before the company got to a medically efficacious dose because of hand, foot, and skin reactions. Thoughts on that toxicity and how it can be dialed out or avoided? And then just to follow up on Michael's question, it sounds like 3116 and reactions with mechanism braptovi may be PK-related or a metabolic issue that's increasing the levels. Any insights about that?
spk04: Hey, Andy. Good morning. Thanks for joining. Three great questions. So, I'll take the first question on insight and enrollment expectations, and I'll also comment on the 3009 question you had on the setback from the other PanKIT inhibitor. And, Matt, you may want to offer some additional commentary there, and then you can take the 3116 question. So, first on insight, Andy, you know, we were excited to announce today that we have the first sites open for the study. As Matt has said, we continue to hear very positive feedback and excitement about enrolling patients on Insight from investigators, also from thought leaders, and I think really based on their enthusiasm to finally move, you know, just treatment into the 21st century and be able to better understand what's driving an individual patient's progression and offer a customized treatment for patients. So we're really pleased with the reception to the data that we reported from Intrigue and the ctDNA analysis and also the excitement and reception to the INSIGHT study itself. As we get the study underway, which we now are, and start to see enrollment in the study, we're going to be in a much better position to offer some perspective and color on what we see as the trajectory for enrollment and when we may reach full enrollment in the study. It's really just too early for us to be able to offer meaningful color commentary with respect to that. But State Scene, rest assured, will provide additional update on future quarterly calls as we see the cadence of enrollment in the Insect Study. And then for 3009, as we've disclosed, we expect to file the IND for 3009 in the first half of next year. And you referenced, Andy, a recent setback from a competitor agent, you know, despite a lot of sort of promise and expectation that had been created. they unfortunately were unable to reach exposures that were well tolerated, seeing, as you noted, some significant toxicities, namely pulmonary plantar atherosclerosis in patients. So for us, you know, we've now demonstrated, I think, our success in designing inhibitors like Repretinib or Kinloch. We've applied those same skills to our design and selection of 3009 as our candidate to take forward. And we believe, based on the selectivity profile that we've previously reported at AACR earlier this year, this candidate has an even more selective profile than repretinib, which is regarded as being very well tolerated. So we're looking forward to getting the IND filed and then getting this drug into patients and understanding the profile in patients. Matt, do you want to comment then on the 3116 question? Yeah.
spk16: Thanks. So, you know, just to clarify what we were talking about earlier, you know, we did see those living toxicities with 3116 in combination with Trematinib and Benimetinib. And as I noted, those events have been seen with those other agents alone. So, in the clinical trial setting, of course, you know, the relatedness is related to both drugs because both drugs are combined. But I noted that the DLTs that we noted have been seen either with Trematinib or Benimetinib alone.
spk15: Right. Would that suggest that it's a PK issue or a metabolic issue increasing the exposure levels of those drugs?
spk16: Yeah, no, no, not at all. No. So there's no thought that it might have anything to do with the metabolism of the drugs or PK issues. What I was commenting on is that when you see these effects with a combination, it could be due to the single agent alone. If you use that single agent, these are reported safety events, adverse events, warnings and precautions in the label. We don't know. We continue to enroll patients in those cohorts, and it's really the totality of data that will inform us about the overall combinability of 3116 with MEK inhibitors. But as you know, we continue to enroll patients. We're very pleased with the progress that we've had in the trial. So the RACIP cohort continues to enroll as well, too. So we're looking forward to having an update sometime in the future.
spk15: Okay.
spk06: Thank you. Appreciate it.
spk05: Thank you. One moment for our next question. It comes from Brad Canino with Stifo.
spk11: Good morning, thanks for the questions. Two for me. First, any changes in the US inventory you would flag and I guess where are you versus normal levels? And then a question for Tucker on how to think about R&D. You're pretty close to where you were around 60 million a quarter before the optimization following the intrigue results. Help us understand the puts and takes as you get towards the end of the Seltenib study, the ramp of insight, and you're investing into the pipeline. Should we expect continued increase in spend, and are you likely to exceed the peak spend that we saw in 2021? Thank you.
spk04: Hey, Brad and Steve. Thanks for the questions. I'll take the first one on inventory, and then Tucker, if you'd like to take the second one. So, Brad, in the quarter, we didn't see inventory as a significant driver of results. So this was principally driven by strong demand growth. in the quarter versus first quarter and versus prior year. Tucker?
spk14: Sure. So, Brad, thanks for the question on the R&D expense. So, what we said today is that, you know, we had 91 million of OPEX in the second quarter, 58 million of that was for R&D, and we expect that the balance of the year will be similar in terms of overall total OPEX from what we saw in the second quarter. As you noted, kind of a high watermark for R&D was back in 21. We had 257 million of R&D expense there based on the results last year. We had 187 after the restructuring and the portfolio prioritization. So, you know, I don't think we'll get back to that 257 this year. And if you can, again, roll forward our 58 million roughly in the second quarter. And then the balance for 24 and beyond will really just depend on, you know, how quickly we can move in success in the pipeline. So we've got a lot of really great things going on in our clinical development area, and assuming success, you know, we would continue to prudently invest kind of in the assets in the right place. So I don't think we're getting back there, you know, this year, and the balance of that will really depend on success in the clinic.
spk11: Appreciate the commentary. Congrats on the quarter. Thanks.
spk05: Thank you. One moment for our next question. comes from the line of Rennie Benjamin with JMP Securities.
spk03: Hey, good afternoon, guys, or good morning, guys. Congratulations on the quarter. Quick question on Vimselton. Can you talk about, you know, the remaining steps? You know, maybe remind us when the last patient was enrolled, you know, when you think the database might be locked and how long it takes from, you know, a database lock to reporting top-line results. And can you also remind us, is the filing going to be both in the U.S. and the EU? Will that be filed simultaneously, or is there more data that's required in the EU?
spk04: Hi, Rand. Good morning. It's Steve. I'm happy to take those two questions. So, first, with respect to the timing for the readout of the Motion Phase 3 study, as you know, we've guided to Q4. We completed enrollment in the study in Q1, which was ahead of schedule, so we were really pleased with the pace of enrollment. And so we, as you know, the primary endpoint is response at 25 weeks or six months. And so once we get to that, all patients get to that time point for evaluation for efficacy, we're then able to do the work that we need to do to block clean the database. and then to be able to analyze data and get ready for the report out. So this is why we've been consistent here in the last couple of quarters in guiding to a Q4 readout for the stem cell tumor study. And your question with respect to where we may file, absolutely, of course, in the U.S. It's our intent to file in the U.S. And in Europe, you may recall, there are no approved agents to treat tenosynovial giant cell tumor in Europe. And so our goal would be to file in Europe as close as we can to a U.S. filing. So as we get to the readout of the top line of the study in Q4, we'll be in a position to provide some better guidance on filing timeline and how close we think we could make a U.S. filing and a European filing. But we know there's significant unmet medical need in Europe given no approved agents, also, of course, unmet need here in the U.S., and our goal is to get the drug to patients, again, assuming success as quickly as we can.
spk03: Got it. And then just, you know, maybe as a follow-up for 3116, are we on track then to report kind of recommended phase two doses by the end of the year? And would that be a good, you know, point no-go decisions, especially on maybe the Tremie and Demi, you know, combinations? Or do you really feel that you need to...
spk04: Yeah, Ren and Steve, we lost you there for the last bit of your question. I think your question was about timing for getting to recommended doses for the combinations in the existing cohorts. So, as Matt noted, you know, we continue to enroll patients across the Trematinib, the Benny, and the Sotiracid cohorts. Matt provided, I think, a really full update in terms of what we've seen so far, both from the updated Phase I monotherapy dose escalation data, but also the initial combination dose escalation data. We also noted in the prepared remarks that we now expect that in the first half of next year, we'll have sufficient data to make decisions around potential expansion cohorts in which we might pursue. And of course, we'll continue to be guided by the data and the science in terms of which expansions we might pursue. Meanwhile, we were also really pleased to announce today that we've now opened the first sites for the new combination dose escalation cohorts. One of those is with our very own Repretinib, as you know, And the second is the result of a clinical supply and collaboration agreement with Pfizer for enegraphenib and cetuximab combination. So we were pleased to get those sites open for enrollment for those two new cohorts. So we continue to make good progress, and we think we'll be in a position, as I said, in the first half of next year now to make decisions about the potential expansion. Great. Thanks for taking the questions.
spk05: Thank you. One moment for our next questions. It comes from the line of Peter Lawson with Barclays. Please proceed.
spk09: Hi, good morning. This is Cheyenne for Peter. Thanks for taking our question. I just wanted to get a bit of a better sense on the organic growth for U.S. versus ex-U.S. Maybe could you speak a little bit more to the volume growth in these two components, if there's any one-timers we should be thinking about, such as stocking orders or any pricing benefits? And just to follow up on the second line component, I appreciate that it's still early, but is there any metrics we could point to that suggest uptake here or any metrics you'd look to provide in the near term that might give a little more color on the second line uptake? Thanks so much.
spk04: Hi, Shay. Good morning. It's Steve. Thanks for the great set of questions. So I'll ask Dan to talk about, to answer your questions about the U.S. business and the growth that we saw in Q2 versus Q1 and versus last year. And then Margarita can comment on what we're seeing in the international business.
spk02: Yeah, thanks, Steve. So, Shay, thanks for the questions. In the U.S., the really strong quarter that we had was driven principally by demand volume. So, you asked to kind of understand how it breaks down volume versus price. You know, the 22% year-over-year growth that we delivered in the quarter for net revenue was driven largely by growth in demand, and that comes from Several sources, average duration of therapy being a really key one that we talked about previously, we continue to feel as though that will continue to gradually increase. We've said previously that it was about seven months on average in 2022, and we expect that to gradually grow to eight to eight and a half months, and we continue to believe that's very achievable. So demand was the primary driver in the U.S. during the quarter.
spk07: So for international markets, let me start by saying that it's very exciting to continue to see the strength of our launch in the first markets in international and to see all the progress that we are making with regards to market access to unlock new countries, which will allow future launches on Italy and Canada are great recent examples. So we are going from strength to strength, and we expect our international revenue to continue to grow in the future, keeping in mind that Q3 tends to be historically a softer quarter, driven by summer holidays, as we saw last year. But overall, Kinloch is very well positioned for growth, especially as new markets come online, which will be soon the case of Italy.
spk06: Peter, does that answer your question?
spk05: I'm sorry, Shay, does that answer your question?
spk09: Great. Thank you so much.
spk05: Thank you. Ladies and gentlemen, I will conclude the Q&A session now and turn it back to Steve Horter for closing remarks.
spk04: Great. Thanks, Carmen, and thanks to everyone for joining us on today's call, and thank you for your continued support. We look forward to keeping you updated on our continued progress here at Decipher. Hope you have a great rest of your day.
spk05: Thank you all for participating in today's program. You may now disconnect.
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