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spk08: Good morning, everyone, and welcome to Decipher of Pharmaceuticals' fourth quarter and full year 2022 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you would need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, Please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Jen Larson, Senior Vice President of Finance and Investor Relations. Please go ahead.
spk07: Operator, welcome and thank you for joining us today to discuss Decipher's fourth quarter and full year 2022 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 general corporate updates 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. reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements made during this conference call include our expectations for our preclinical and clinical programs, our commercialization of KMLOC, and 2023 guidance. Forward-looking statements made on this call 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 annual report on Form 10-K, 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.decipher.com. With that, I will now turn the call over to Steve Herter, President and Chief Executive Officer of Decipher.
spk13: Thank you and good morning, everyone. Thank you for joining us today as we provide an update from the fourth quarter and full year 2022, review our financial results, and provide additional context on our strategic outlook and planned corporate milestones for 2023. 2022 was a year of exceptional execution for Deciphera. Global Kinloch product revenue grew 44% compared to 2021, driven by very strong performance in the U.S. as well as launches outside of the U.S. Kenlock is now approved for fourth-line gastrointestinal thermal tumor, or GIST, in 12 jurisdictions around the world. Last month, we outlined our key strategic priorities for the year, which will enable Decipher to continue its evolution toward being a fully integrated company with multiple approved medicines and capabilities ranging from international commercialization to early-stage discovery, all powered by our proprietary switch control kinase inhibitor platform. These priorities include expanding the market potential for Kenlock into earlier lines of GIST by initiating the INSIGHT Pivotal Phase III study of Kenlock versus sunitinib in second-line GIST patients with mutations in KIT exon 11 and 1718 in the second half of 2023. If successful, we believe the INSIGHT study has the potential to change practice in second-line KIT-driven GIST and to double the U.S. revenues for Kenlock. We were very pleased at the circulating tumor DNA or ctDNA data from our Phase III intrigue study of Kenlock in second-line GIST was selected for presentation at the ASCO Plenary Series session a few weeks ago. Matt Sherman, our Chief Medical Officer, will review the data later in the call and outline our plans for the new Phase III Insight Study. As we begin enrollment in the new Phase III Insight Study for Kenlock, we also expect to read out another pivotal trial, the Phase III Motion Study of imseltenib, our highly selective switch control kinase inhibitor of CSF1 receptor in patients with tenosynovial giant cell tumor, or TGCT, in the fourth quarter of this year. We have been very pleased with the pace of enrollment and are excited to announce today that we now expect to complete enrollment in the motion study in the first quarter and report top-line data in Q4 of this year. For DCC3116, our first-in-class inhibitor of the OLK12 kinases designed to inhibit autophagy, we expect to present updated data from the single-agent dose escalation portion of the Phase 1-2 study and initial combination data in the second half of 2023. Finally, we were very pleased to announce a clinical trial collaboration and supply agreement with Pfizer for a new combination dose escalation study of DCC3116 and incarafenib and cetuximab in colorectal cancer that we plan to initiate in the second half of this year. We look forward to presenting the preclinical data supporting this new combination cohort in the first half of this year, along with additional new preclinical data for DCC3116. We continue to complement these commercial and clinical stage advancements with investment in our research pipeline. Our discovery platform continues to drive new growth opportunities with potential first-in-class or best-in-class precision oncology agents, including DCC 3084, our newly nominated Pan-RAF clinical development candidate, for which we expect to present preclinical data in the first half of this year and to file an investigational new drug application in the second half of the year. DTC 3084 was discovered using the same proprietary switch control kinase inhibitor platform that has brought us Kinloch, Vimseltinib, and 3116, and we look forward to quickly advancing this program to the clinic. In addition, we plan to debut a new development candidate from our proprietary discovery engine in the coming months, as well as preclinical data from other research programs our team has been working on. Matt Sherman, our chief medical officer, will provide more detail about upcoming milestones for our pipeline programs on today's call. Ken Martin, our Chief Commercial Officer, will then share insights on the U.S. commercial performance for the quarter, and Margarita Duarte, our Head of International, will provide an update on Kinloch's ongoing fourth-line launch in Europe, which has sustained its strong momentum throughout 2022. We'll end with Tucker Kelly, our Chief Financial Officer, who will review highlights from the fourth quarter and full-year 2022 financial results and the recent highly successful follow-on equity offering that will allow us to continue to execute on our goals. First, I'll turn the call over to Matt Sherman to provide an update on our R&D efforts. Matt?
spk04: Thanks, Steve. We are thrilled with the progress we have made across our clinical and preclinical pipeline in 2022 and already in the first few weeks of this year. As Steve mentioned, it was our privilege to present additional ctDNA data from the Intrigue Phase III study at Kinloch at the ASCO Clementary Session last month, which we believe represents a potential practice-changing event in the treatment of second-line kit-driven GIST. The results strongly support our planned INSIGHT study and the potential to expand Kinloch's label, which, if approved, will allow physicians for the first time to optimize treatment for patients in the second-line setting based on their mutational profile to improve outcomes over the current standard of care. In the ctDNA analysis for patients with KIT, exon 11, and 1718 mutations, Kinloch showed a striking benefit compared to suzantinib across all efficacy measures. beginning with a 44% confirmed objective response rate, with all patients on Kinloch achieving either a partial response or a stable disease. In contrast, there were no objective responses in the student NIP arm. Similarly, Kinloch demonstrated a greatly improved PFS with a median of 14.2 months, compared to only 1.5 months for a student NIP. In fact, half of the patients receiving student NIP had progressed or died by their first restaging scan at six weeks. This resulted in the hazard ratio of 0.22, meaning that treatment with Kinloch resulted in a 78% reduction in the risk of disease progression or death. We also saw a strong trend for overall survival in favor of Kinloch in this subgroup of patients. The OS results are based on an updated data cut as of September 2022 and show that the Kinloch arm still had not reached the median, while patients randomized to Sinitinib had an overall survival of 17.5 months. This resulted in the hazard ratio of 0.34, or a 66% reduction in the risk of death. And the landmark analysis showed that the number of patients alive at 30 months on Kinloch was estimated to be nearly twice that of patients randomized to Sinitinib. Kinloch was generally well tolerated, and the subgroup safety and tolerability profile was consistent with the primary analysis of the INTRIG study. For patients with mutations in KIT, exon 11, and 1718, Fewer patients in the Kinloch arm experience grade 3-4 treatment emergent adverse events compared to sunitinib. Based on the intrigued CT data and regulatory input, we plan to initiate INSIGHT, a new pivotal phase 3 study of Kinloch versus sunitinib in this group of second-line GIST patients. If positive, we believe the results of the INSIGHT study will support an expanded label for Kinloch in select second-line GIST patients and transform how physicians treat these patients. Moving from one pivotal Phase III program to another, I now want to talk about vimsultinib, which we believe will become the second approved product from our proprietary switch control kinase inhibitor platform. We are strongly encouraged by the compelling clinical data we have generated to date, supporting the potential of vimsultinib to be the standard of care treatment for patients with TGCT not amenable to surgery. We began enrolling patients in the Phase III motion study in early 2022, and are very pleased to announce today that we now anticipate completing enrollment this quarter, enabling us to read out the top-line results in the fourth quarter of this year. We also expect to present updated data from the Phase 1-2 study of Vimseltinib in the second half of this year that will focus on longer-term safety and efficacy and provide additional support for the clinical and commercial opportunity for Vimseltinib. Turning now to DCC 3116, we were excited to announce our first clinical trial collaboration and supply agreement for the program a few weeks ago. Under the agreement, Pfizer will supply ingorafenib at no cost as part of a new dose escalation combination, evaluating 3116 with ingorafenib and cetuxentamab in patients with colorectal cancer. Additionally, we plan to present updated data from the single-agent dose escalation cohorts and initial data from the combination dose escalation cohorts of the Phase 1-2 study. and initiate one or more expansion cohorts in the second half of this year in combination with the MEK inhibitors, trimetinib or binimetinib, or the KRAS G12C inhibitor, sotiracib. We remain optimistic about the potential for DCC3116 to broadly impact the treatment of cancer as a first-in-class autophagy inhibitor based on the strong preclinical in vitro and in vivo data we have generated showing additive or synergistic activity in combination with multiple agents targeting the RTK, RAF, and MAP kinase pathways. Finally, the next program slated to enter the clinic is DCC3084, our pan-RAF inhibitor, for which we expect to submit an IND in the second half of this year. We plan on presenting in vitro and in vivo data in the coming months, demonstrating its preclinical profile as a potent and selective inhibitor of BRAF-CRAF kinases, with optimized pharmaceutical properties for potential development in both single-agent and combination opportunities, as well as data from additional undisclosed research programs, and look forward to the expected nomination of our newest development candidate. I'll now turn the call over to Dan Martin, our Chief Commercial Officer, to provide an update on the U.S. commercial efforts. Dan?
spk09: Thanks, Matt. In 2022, we continue to execute on our commercial goals for Kinloch in the U.S. further reinforcing its status as the clear standard of care and fourth line gist, irrespective of mutational profile, while continuing to expand our prescriber footprint. U.S. net product revenue was 25.6 million in Q4, and for the full year 2022, Kinloch sales grew to 97.2 million, representing an increase of about 20% over 2021. Approximately half of this growth came from increased demand volume with the remainder coming from net price growth and a lower percentage of patients receiving free drug under our Patient Assistance Program, or PAP. The higher demand volume seen in 2022 was driven principally by an increasing average duration of therapy as the real-world persistency curve continues to mature and more fully reflects the impact of patients who receive prolonged clinical benefit from Kinloch. Specifically, we estimate that the average duration of therapy in 2022 grew to approximately seven months. We expect the average duration of therapy to continue to increase gradually over time and could ultimately reach as high as eight to eight and a half months. As expected, the percentage of patients receiving free drug under our PAP program increased in the fourth quarter versus the prior quarter. Consistent with what we saw in Q4 of 2021, the PAP percentage was slightly above the high end of our estimated annual range of 20 to 30%. This PAP seasonality is common and is driven by patient affordability challenges that tend to increase as the year progresses due to the Medicare Part D drug benefit design. The development and approval of Kinloch for fourth-line GIST addressed a major unmet medical need and fundamentally changed the treatment paradigm in advanced GIST. Based on the compelling data from the ctDNA analysis of Intrigue, we are eager to start the INSIGHT study, and we believe approved for this new indication, Kinloch has the potential to advance the GIST treatment paradigm yet again, this time in the second-line setting based on mutational profile. We believe that if we are successful in expanding the label with a second-line kit exon 11 plus 17 or 18 indication, that it would double the Kinloch peak revenue potential to $350 to $400 million in the U.S. alone. Turning to Vimseltinib, With the readout of the Phase III Motion Study fast approaching, the commercial team continues to prepare for a potential approval and launch. We remain highly encouraged by the market opportunity in TGCT, where we have estimated a total addressable market of $850 million in the U.S. With a potentially best-in-class product profile, we believe in Sveltenand is uniquely positioned to address the high unmet medical need within TGCT. And given the approximately 90% overlap among GIST and TGCT prescribers, we believe Vimseltinib will be an excellent addition to our commercial business, and that Kinloch and Vimseltinib together have the potential to generate in excess of $1 billion in global peak revenue. I will now turn the call over to Margarita Duarte, our head of international, to discuss the progress of our Kinloch launch in Europe. Margarita?
spk02: Thanks, Dan. We are very proud of the strengths and sustained momentum of Kinloch's European market entry. 2022 was a key year that saw very successful execution in two critical markets, our launch in Germany and the post-approval paid access program in France. It was also a year in which we made significant progress towards market access in other major European markets, with the submission of the reimbursement application to NICE for access in England and in Wales, and to IFA for access in Italy. and the initiation of the market access process in Spain. For the full year 2022, international net product sales were 28.3 million, up significantly from 5.9 million in 2021. These strong results reflect Kinloch's best-in-class clinical profile in fourth-line Gs and the significant unmet need, and I'm very proud of the team's superb execution of our launch strategy that enabled such exceptional performance. Our fourth quarter international net product revenue of 7.3 million was driven primarily by continued growth in demand in Germany and in France. However, net product revenue for the fourth quarter did include a one-time reserve for keynote product sales in Germany. It would change in German law effective as of November 2022, shortening the free pricing period retroactively to six months from 12 months. In Germany, our team is in the last stages of the price negotiations. And although we are not yet in a position to disclose the details, we remain confident that our final negotiated price will reflect the high value that Kinloch brings to patients and payers in Germany. We also continue to advance our access discussions with NICE, as well as with the authorities in Italy and Spain, and look forward to sharing updates on future calls. Turning to the rest of the world, We were pleased to see that the national reimbursement work list released by China's National Healthcare Security Administration was recently updated to include Kinloch, which will provide access to Kinloch for many more patients in China for our partner Xilab. In 2022, we recognize 8.5 million in collaboration revenue under our agreement with XI and look forward to their continued strong commercial execution in greater China. In addition, we are excited to announce that we recently received approvals for Kinloch in New Zealand, Israel, and Macau, increasing the number of jurisdictions around the world to 12, in which Kinloch is approved for fourth-line GIST. I will now turn the call over to Tucker Kelly, our Chief Financial Officer, to review the fourth quarter and full-year financial results and recent financing. Tucker?
spk10: Thanks, Margarita. Total revenue for the fourth quarter was $36.3 million, which included $32.9 million in net product revenue at Kinloch and $3.4 million in collaboration revenue. For the full year, total revenue grew 39% to $134 million, including net product sales of $125.5 million and collaboration revenue of $8.5 million. Cost of sales in the fourth quarter was $3.2 million, including $0.7 million in cost of net product revenue and 2.5 million in cost of collaboration revenue. For the full year, cost of sales was 8.8 million, including 2.7 million in cost of net product revenue, and 6.1 million in cost of collaboration revenue. In 2021, total cost of sales was 2.9 million, of which 1.6 million was cost of collaboration revenue, and 1.3 million was cost of net product revenue. In the third quarter of 2022, we completed the sale of zero-cost inventories that had been expensed as R&D, prior to FDA approval in 2020. In Q4, total operating expenses were $83.5 million compared to operating expenses of $112.6 million in the same period in 2021. For the full year 2022, total operating expenses were $316.8 million, a decrease of approximately 20% compared to operating expenses of $396.2 million in 2021. Research and development expenses in the fourth quarter of 2022 were $48.1 million compared to $74.9 million for the same period in 2021. In 2022, R&D expenses were $187.8 million compared to $257 million in 2021. Selling, general, and administrative expenses in the fourth quarter were $32.2 million compared to $37.2 million in Q4 of 21. For the full year, SG&A was $120.2 million compared to $136.3 million in 2021. We ended the year with cash, cash equivalents, and marketable securities of approximately $339 million. In January of this year, we raised an additional $134.7 million in net proceeds through a very successful public offering that further strengthened our financial position and extended our cash runway into 2026. The strong support we received from both existing and new investors in the offering will allow us to increase shareholder value as we strive to become a company with multiple approved products. With that, I'll now turn the call back over to Steve.
spk13: Thank you, Tucker. The outstanding progress we've made at Deciphera over the past year, along with our planned 2023 milestones, puts us firmly on the path to becoming a company with multiple approved products around the world. As we near enrollment completion and prepare to announce top line results from our phase three motion study, We look forward to also initiating our Phase III Insight Study later this year. We are proud to leverage our proprietary switch control, kinase inhibitor platform, and deep pipeline to make a difference for people living with cancer. With that, operator, I would like to now open the call for Q&A.
spk08: As a reminder, to ask a question, please press star 1-1 on your telephone, and please wait for your name to be announced. Please stand by while we compile the Q&A roster. Our first question comes from Daniel Wall with JP Morgan. Your line is now open.
spk15: Daniel Wall Good morning, everyone. Thank you for taking my question. Just a couple of questions. First, for insight, With the idea of combining Kinloch with SUTEN considered for the pivotal trial, second, you're able to refine the timeline for enrollment completion for motion from first half 23 to 1Q23. What can you attribute this acceleration to? And then for DCC 3116, while results from the dose escalation combination study are not expected until second half, What should investors expect with initial data? And specifically, should there be an expectation for anti-tumor activity? Thank you.
spk13: Hi, good morning, Daniel. Thanks for joining and thanks for the three questions. So let me take those in order. First, you broke up on the first part of your question with respect to insight. I believe it was related to a combination. Can you just repeat that for me, operator?
spk15: Yes.
spk13: Go ahead.
spk15: Sure. I guess the question was, was the idea of combining Kinloch with SUTEN considered as one arm of the pivotal study?
spk13: I see. Okay. Thanks for that question. So I'll take the question on insight and on motion, then ask Matt just to speak to 3116 and expectations here in the second half for the accommodation dose escalation data. So first, Daniel, with respect to insight, the data that we presented at the ASCO plenary series session just last month, and we, of course, disclosed at the beginning of the year. We view as being very, very clear, very compelling in terms of the activity of Kinloch in this group of patients relative to SUTENT. So, no, as a result, we did not consider adding a third arm to the study looking at a combination because we don't believe that a combination with SUTENT in particular would add any additional activity in the selected group of patients. With respect to motion, we were very pleased, as we announced today, that we'll be reaching full enrollment in the motion study in quarter one instead of the first half of this year, still reporting out in quarter four of this year. And the enrollment in the study, as we've been telegraphing over the course of the last six to nine months, we've been really pleased with the pace of enrollment, how enthusiastic investigators and patients are to enroll in the study. And it's really that enthusiasm and the pace of enrollment that allowed us to enroll the study faster than we previously anticipated and is going to allow us to get to full enrollment here in this first quarter. So we look forward to reporting out the study in quarter four of this year. Matt, do you want to speak to the 3116 question?
spk04: Yeah. Hi, Daniel. It's Matt. So, yeah, in regards to the 3116 program, as you know, ESMO last year, we were able to present the monotherapy dust escalation data, and we're very pleased with the results. showing that we had good dose proportional PK, that we had a very good safety profile, and also were able to inhibit the target of autophagy in patients treated with 3116. So as we announced earlier as well, taking that forward into combination escalation cohorts with two MEK inhibitors, binimetinib and trimetinib, as well as the KRAS T12C inhibitor, so the RASCIP. So as we've announced, we'll expect to have an update on the combination cohorts in the second half of this year, And our expectation there will be to continue to show the PK as well as the safety profile of the drug. And in terms of efficacy, you know, certainly, you know, it is designed as dose escalation in small cohorts of patients. But, of course, if there's a signal of efficacy, you know, we'd be very pleased to have that information for updating in the second half later this year. Okay.
spk15: Got it. One last question. With multiple KRAS inhibitors in development and on the market, As you continue development of 3016, is there an opportunity for you to select the best fit partner as you advance into late-stage development?
spk13: Yeah, thanks for the question, Daniel, with respect to KRAS G12C inhibitors. And you're right, there are a variety of agents now, two approved in the U.S. And as we've reported previously, the effect that we see with 3116 addressing autophagy as an escape when used in combination with a KRAS G12C inhibitor is not specific to an individual KRAS G12C inhibitor. It's certainly a class effect. It's a mechanistic effect that we see. So we've seen that and reported that preclinically both with sideracib but also with adagracib. So there would be an opportunity going forward for us to consider additional KRAS G12C combinations as we think about the ideal partner for a potential 3116 KRAS G12C inhibitor combination.
spk15: Great. Thank you very much.
spk08: Please stand by for our next question. Our next question comes from Michael Schmidt with Guggenheimer. Your line is now open.
spk05: Hey, good morning. Thanks for taking our question. This is Paul on for Michael. One from us on recruitment for the inside study. So your analysis sort of suggests that only a portion of GIST patients have detectable acute mutations through ctDNA, and there is some discussion at the ASCO plenary about GIST as a relatively low ctDNA-shedding cancer. So I just wanted to get your expectations on the speed of recruitment of patients for this target mutation population at INSIGHT once that study kicks off later this year and whether you anticipate any sort of challenges in that aspect. And then secondly, on 3116, maybe just provide some color on what drug you're decision to combine with and carafinib and cetuximab and where you see that potential for the combination in colorectal cancer. Thank you.
spk13: Yeah, hi, good morning. Paul, it's Steve. So I'll take the insight question that you posed and then ask Matt to speak to the 3116 and carafinib and cetuximab combination. So first, with respect to insight and enrollment in that study, You know, we've now demonstrated very clearly the capability to enroll these large randomized studies in GIST globally. So we have a clear capability in terms of getting these studies up and running and enrolling them rapidly. With respect to patients with the specific mutation that we'll be looking for, patients who don't shed ctDNA, this is a very similar fraction in GIST versus other solid tumors. So we don't see that as being a differentiating factor. And with a simple blood-based diagnostic with a rapid turnaround time of five to 10 days, we don't see that as being a barrier at all. In fact, we see it as being an advantage to enrolling in the study. And then lastly, I would just offer that what we continue to hear from investigators and from thought leaders is a considerable amount of enthusiasm, given the data that's now been reported at ASCO, for the potential of Kenlock in this selected group of patients. And I think that's going to serve as a real tailwind in terms of not only getting sites up and running, but also getting patients enrolled on study. Matt?
spk04: Yeah, hi, Paul. It's Matt. So, yeah, in regard to our plan to initiate a cohort of 3116 in combination with angorafenib and cetuxenab, you know, we're obviously very excited overall with the, you know, with the preclinical data we've generated to date. showing that we can inhibit multiple nodes along the RTK, RAS, and MAP kinase pathway in combination with 3116 and show an additive or even a synergistic combination effect on tumor killing. So, as we've initiated a number of these combination cohorts now, looking at the unmet medical need in treating advanced stage colorectal cancer, And, you know, while cetuximab and agorafenib have activities demonstrated in the BEACON study a number of years ago, that was somewhat limited activity, you know, with an objective response rate of approximately 20% and the PFS of about four months. So there's certainly a lot of headroom for improving and treating these patients. And, you know, recognizing this might be a huge opportunity for 3116 and colorectal cancer.
spk05: Got it. Very helpful. Thanks so much.
spk12: Please stand by for our next question.
spk08: Our next question comes from Tyler Van Buren with Cohen. Your line is now open.
spk20: Great. Thank you. Good morning, guys. Had a couple for you.
spk19: The first is, can you help us understand what the magnitude of the one-time reserve for Kinloch sales in Germany was and elaborate more on your expectations for the cadence of ex-US sales throughout the year? And the second is, for VIM and TGCT, you've presented an extensive claims analysis, but what other data points give you confidence in this market, given that patients are so diffused throughout the country and not necessarily concentrated in centers of excellence?
spk13: Yeah, good morning, Tyler. Thanks for the set of questions. I'll ask Tucker to comment first on the reserve in Germany. Margarita, perhaps you can then comment on what you see as the cadence in terms of the commercial business across Europe. And then, Dan, why don't you take the final question with respect to themselves and claims analysis and the confidence we have in the size of the opportunity. Tucker?
spk10: Sure, Tyler. So we haven't quantified the amount of the reserve in Germany that we took in the fourth quarter, but just to remind folks, what happened is that the German authorities in November changed the law. It used to be that you had a 12-month period of free pricing and that got shortened to six months effective retroactively based on the law change in November. So in the fourth quarter, we took a reserve based on the net sales we had booked at our free pricing price in the third quarter. And then in the fourth quarter, the sales in Germany were booked at an estimate, because we're still not at our final price in Germany, but an estimate of where we think we may end up with the German authorities on pricing. So we haven't quantified it, but it certainly was a A larger number in the quarter that we want to make sure people understood that as they looked at the quarter-for-quarter change in international product sales.
spk02: Okay, I will take the second one. Thanks, Tyler, for the question. So I would say that the cadence for the rest of the year in Europe will come from two key strategic drivers. The first one is to continue to successfully drive price and reimbursement. in the countries where we don't have yet access so that you can launch in new markets in the future. And the second one, I would say to continue to successfully execute on our launch strategy and continue to raise awareness to drive demand and to expand the prescriber base. And I would also offer to say that I am extremely pleased with the success that we are seeing so far and with the strong demand that we continue to see.
spk09: And Tyler, this is Dan Martin. I'll take your question on what gives us confidence in the TGCT market. I think what gives us confidence is several factors. First, you mentioned the claims analysis that we've presented on. That was just a component of our overall analysis of the opportunity. We actually conducted a couple different methodologies, all of which gave very similar answers. We conducted a more typical sort of literature-based epi buildup. And totally separately, we conducted the claims analysis. And both resulted in really similar findings in terms of the overall patient journey for TGCT, as well as the size of the addressable opportunity. As it relates to the claims data, the 1,300 to 1,400 patients that we have noted as being the incident RX treated patients in the U.S. in this data set, we've always viewed that as really a floor of the opportunity and one that gives us real confidence because this is an analysis that doesn't provide indicators of patients. It actually sees the patients. And so we can see these patients being treated in the data, which gives us great confidence. Lastly, I would just note that one of the things that we get asked is, our view of sort of products used in the space and market share, and we've presented the findings from the claims database there as well, showing that only about 15% of the patients received pexidartanib in this data set. And that enables us to sort of triangulate or crosswalk back to the opportunity that we've laid out. So across, you know, multiple different views of the market, we land in very similar places, which gives us great confidence that the opportunity is there. Lastly, I'll just note that diffuse markets with patients being spread between both academic and community settings is a bit of a specialty of ours. We've developed real capability in being successful in that space because that's very much the description of GIST. GIST is very similar in that way. And frankly, one more point is that we know that the overlap between GIST and TGCT is really high. So for all these reasons, we have great confidence that the market is there and that we're uniquely positioned to be successful.
spk21: Thank you very much.
spk08: Please stand by for our next question.
spk12: Our next question comes from Inyoung with Jefferies.
spk08: Your line is now open.
spk02: Thank you. I have actually a few questions. First, you mentioned that in 2022, the treatment duration for Kinlog was seven months and expected that to increase to 8 to 8.5 months. What's driving the increase in the treatment of a duration? And do you expect to achieve 8 to 8.5 months of this year? Second question is on the NCCN guidelines. I don't know, it's just something, I understand it's something that we cannot predict, but you have submitted your data for second-line intrigue data, but in light of the subgroup analysis in Exxon 11, 17, and 18 patient population, do you expect the NCCN decision could be on that subgroup? Thank you.
spk13: Yeah, hi, good morning, Yoon. Thanks for the great questions. So I'll take the second question first with respect to NCCN, and then I'll ask Dan to cover off on the treatment duration for Kinloch that we see in the real-world experience in the U.S. market. So first for NCCN, you're exactly right, Yoon. It's not something that we can predict in terms of whether the NCCN is going to update the guidelines, when that might occur, or what might be reflected in the guideline update. We were excited to present the data from the subgroup as part of the ASCO plenary series session just last month. Very compelling data in this group of patients with Ken Block. So we're excited about that. I think the field is very excited about it, as you will have seen from the presentation and the discussion at the ASCO session at the end of January. And so we await, as you do, any potential updates to the guidelines. Difficult for us to predict in what shape or form or timing that might be in. So we'll stay tuned for that and see if there are any updates. Dan?
spk09: Yeah, thanks, Yoon, for the question regarding adversarial therapy. It's a really important dynamic that was key in driving the really solid growth that we saw year over year. As I noted in my prepared remarks, we demonstrated about 20% growth year over year. with 97 million in the US in 2022. And that was driven by a number of factors, but importantly, by volume growth. And the volume growth was driven principally by this increasing average duration of therapy that we see. And the driver for that is really just a maturing of the real-world persistency curve, or said another way, maturing of the real-world sort of prevalent treated pool that now more fully reflects Patients who have had extended and prolonged benefit from Kinloch, which just pulls the average duration of therapy up now beyond the median PFS that we saw in the Invictus study. And that's really important because we expect that to continue to be a gradual growth driver over time. We had noted we expect that could potentially reach eight to eight and a half months. And there's a number of proof points for that, which I could certainly go into, but we feel confident that ultimately eight to eight and a half month average duration of therapy is very achievable. However, we have noted that that's a gradual phenomenon. That's a gradual trend that we will expect to see develop over time. So it's hard to predict exactly what timetable that will develop in, but that's why we underscored we see that as a peak average duration of therapy. And we don't expect that to be something that changes dramatically quarter to quarter, so likely something that we will share additional color on sort of as warranted over time.
spk02: Thank you. Can I ask you some follow-up questions?
spk14: Please do, Yun. Go ahead.
spk02: Yeah. So a question on the INSIGHT trial. So based on the subgroup analysis that you've done from the intrigue, it looks like you may need to screen about 400 to 500 patients. So question number one is how long do you think it would take to enroll about 54 patients? And secondly, In the currently in practice, is this a mutational analysis after Imatinib done routinely? Thank you.
spk13: Yeah, again, thanks for the two questions. Good questions. So I'll take both of those. So first, with respect to the INSIGHT study, you're right. Sites will need to screen patients for eligibility for enrollment in the study. We, you know, from our experience with Intrigue, which we ran as a large global study, multiple sites. You know, we have the capability, of course, and have demonstrated the capability to run these large studies to open multiple sites and to find patients for enrollment. At the site level, of course, we know that physicians will be using an easy liquid diagnostics or liquid biopsy where they simply draw blood and there's a five to ten day turnaround time to identify patients. And furthermore, sites will know generally the primary mutation status for their patients already from their time of diagnosis. So we would expect that physicians would really be interested in looking at their primary exon 11 patients, of course, and understanding what their secondary mutation profile is as they consider them for enrollment in the study. So we have a lot of confidence based on our demonstrated capabilities in this area of running these sorts of studies, and we're looking forward to getting insight up and running at the end of this year. Now with respect to practice within the U.S. or globally even, There isn't a need, hasn't been a need up until now for physicians to consider looking at the emergence of secondary mutations post-Omatinib treatment. But what we know from other analogs, whether it's looking at lung cancer or other solid tumors, is that these sorts of liquid biopsies, these blood-based diagnostics, see very good adoption. As I noted, these are easy to run. It's simply a tube of blood that's sent off to a lab with a five- to ten-day turnaround time. So we don't expect, especially given the nature of the data that we've now presented with Kenlock in this group of patients, we don't expect adoption of a diagnostic to be a barrier to use at all. In fact, we think there'll be a considerable amount of enthusiasm among physicians and patients to understand what their secondary mutation status is so they'll know whether Kenlock could be an option for them in the second-line setting.
spk02: Thank you.
spk12: Please stand by for our next question.
spk08: Our next question comes from Chris Raymond with Piper Sandler. Your line is now open.
spk18: Thanks, and good morning. This is Nicole Gabreski on for Chris. Thanks for taking the questions. Maybe just two from us. One, just in terms of using ctDNA as a potential companion diagnostic for patient identification, I guess, can you talk about how that would be integrated if the subset analysis data is included early in NCCN guidelines, maybe versus if you get regulatory approval in the second-line kit exon 11 and 1718 setting? Are there any differences just in the setup? I guess we're trying to understand if it's important to have a cleared or approved companion diagnostic in the setting. And then maybe second, just around vinsultinib, you know, going back to your ESMO presentation last year, I know that you guys were highlighting that responses deepen over time, but ORR at the 25-week time point for vinsultinib matched the pexidartinib label. And, you know, we understand that the safety profile will be the key differentiator, you know, allowing patients to stay on therapy longer. But I guess, how will that be effectively captured within the phase three motion study? And how does that translate into a potential label?
spk13: Good questions, Nicole. Thanks for those. So let me take first the ctDNA question, and then I'll ask Matt just to comment on the motion study and the data we presented last year at ESMO and touched on the data we're collecting as part of motion that would then inform a label and the profile of the drug in a commercial setting upon a potential approval. But first, for the ctDNA data in GIST today, and I think your question, Nicole, was in the present-day environment, even absent a regulatory approval for Kenlock in this patient population, what could physicians do in practice? We know that, of course, these sorts of blood-based panels are already available, so from companies like Foundation Medicine, Garden Health, and the like, and so physicians today, if they were so inclined, could draw a tube of blood and send it off to Foundation or to Garden for analysis, and these these panels today will pick up the secondary mutations seen in just patients and report back on that. So physicians, if they chose to do so, they could run that analysis and then make treatment decisions, which would be off-label today. So this isn't something that we can or would promote to. But physicians could then make treatment decisions, and they would have to work with the patient's insurance provider to obtain coverage for that off-label use. But I guess my point is just that these diagnostics are available today for physicians who are interested in understanding the secondary mutation status for their patients. Matt, do you want to comment then on Vimseltinib in motion?
spk04: Yeah, good morning, Nicole. So, yeah, as you note, you know, for the 25-week endpoint in the Vimseltinib TGCT study, we had a 38% response rate, which was similar to what was reported for the enlivened Pestinib study in their label. But also, as we also know, you know, these patients, you know, continue on therapy for longer than six months and can have a response beyond that. And we reported for the Phase I dose isolation cohorts who were on study the longest, a 69% overall response rate in the TGCT patients in the Phase I-II study. And in terms of a label, it's also noted that in Liven's label, or Pace-Dartner's label, based on the Liven study, also shows their overall response rate in the open-label portion of the study, and that's 61% in the current label for Pesidartinib. So we could expect that our label for consultative may contain some long-term follow-up and a higher overall response rate.
spk08: Great. Thanks.
spk12: Please stand by for our next question.
spk08: Our next question comes from Brad Canino with Stiefel. Your line is now open.
spk03: Good morning, and thank you. Steve, maybe a follow-up on your previous comments. I guess I want to know, based on the KOL and physician feedback to the subgroup analysis, do you expect the material enough proportion of practices to adopt a second-line ctDNA-guided treatment paradigm in the next few years to impact Kinloch cells? And then a second question, would the top line readout for themselves been inflated for 4Q? When you think about the degree of data that you would include in the package to the FDA if successful, can you add any comments about how long you expect it to take to reach an NDA filing? Thank you.
spk13: Yeah, thanks, Brad. Two good questions. So with respect to expectations around taking the data that we presented at ASCO and that being translated or changing practice today, it's an uncertainty. So, you know, of course, we can't promote to that use We don't have extensive market research that tells us whether physicians will adopt the use of the drug on an off-label basis. What we've seen so far in our experience is that use has been, for Kenlock, has been generally within our approved label. So we'll continue to monitor and understand how physicians, if they choose to change practice, how that practice changes over time. But we don't have any information at the moment with respect to what changes might occur. You know, clearly having a label in the second line setting in this patient population is what will ultimately allow us to drive share and drive utilization, and that is one of the reasons that we've decided to conduct the INSIGHT study and seek a label in the second line, is to be able to promote that use upon approval. Your second question, I think, Brad, was related to Vimseltinib and our announcement this morning that we expect to complete enrollment in the first quarter of this year and read out the study in Q4, and your question was, around the timing for a potential NDA. So it's really premature for us to share our thoughts around what the timing could be for an NDA post-topline readout. What I can say is that our team has demonstrated, certainly with Kenlock and our fourth-line label, our ability to quickly move from top-line data readout to get a filing in. This will be no different, and when we have a readout of the study, of the top line results. I'm sure we'll be in a position at that time to offer some additional color around what the timing could be for a potential filing in the U.S. and filings outside of the U.S.
spk08: As a reminder, to ask a question, please press star 11 on your telephone. Please stand by for our next question.
spk12: At this time, please stand by for our next question.
spk08: Our next question comes from Peter Lawson with Barclays. Your line is now open.
spk11: Great. Thank you. Thanks for taking my question. Just on NCCN guidelines, are you looking to gain guideline inclusion for exon 11, 17, 18?
spk13: Yeah, thanks for the question, Peter, with respect to NCCN. So we're going to continue to monitor what NCCN decides to do with respect to any guideline update, and that will guide our decision about any future submissions of data. That's the approach that we plan on taking with respect to NCCN going forward.
spk11: Gotcha. I mean, does the Exxon 11, 17, and 18 data plus, you know, various other mutations, does that make the NCCN guideline changes for second-line newcomers difficult then to make that judgment call?
spk13: Yeah, I think what we've learned, Peter, from the analysis is that there's a level of complexity and nuance, I think, to the data. I mean, certainly the 11, 17, 18 population, the result is very clear in terms of the benefit of Kenlock versus Sunitinib. And we have this group of patients in whom ctDNA is not detectable. Where we see on the forest plot, the hazard ratio for PFS is virtually in the center of that forest plot. I think it's unclear at the moment what NCCN might choose to do. We know that physicians generally are interested in having more options available to treat their patients. We don't think that this situation with GIST is any different. So we would expect that that will be of interest to physicians on the panel as they think about providing options to patients going forward.
spk11: Thank you. And then just on China, just kind of the size of the opportunity, how we should think about pricing and kind of how you think it could of revenues in the next couple of years, 2023 or 2024.
spk13: Sure. Margarita, would you like to address the China opportunity and ZEISS disclosures?
spk02: Absolutely. Thank you. Thanks for the question, Peter. So we view this listing, you know, very positively as it will increase affordability and access for Chinese patients moving forward. So we do expect this to be a key contributor of volume growth over time. How quickly that happens, we do not have a lot of details yet, but all in all, we view this extremely positively.
spk06: Thank you so much. Thank you, Peter.
spk08: I show no further questions at this time. I would now like to turn the conference back to Steve Herter for closing remarks.
spk13: Great. Thank you, Michelle. Thanks to all of you for joining us on today's call. Thank you for your continued support of the work that we're doing here at Decipher. We look forward to keeping you updated on our progress for the balance of this year and hope you have a great rest of your day.
spk08: This concludes today's conference call. Thank you for participating. You may now disconnect.
spk02: The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1 1. Thank you. Thank you. Thank you. Thank you.
spk08: Good morning, everyone, and welcome to Decipher of Pharmaceuticals' fourth quarter and full year 2022 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you would need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, Please press star 11 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Jen Larson, Senior Vice President of Finance and Investor Relations. Please go ahead.
spk07: Operator, welcome and thank you for joining us today to discuss Decipher's fourth quarter and full year 2022 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 general corporate updates 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. reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Examples of forward-looking statements made during this conference call include our expectations for our preclinical and clinical programs, our commercialization of KimLoss, and 2023 guidance. Forward-looking statements made on this call 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 annual report on Form 10-K, 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.decipher.com. With that, I will now turn the call over to Steve Herter, President and Chief Executive Officer of Decipher.
spk13: Thank you and good morning, everyone. Thank you for joining us today as we provide an update from the fourth quarter and full year 2022, review our financial results, and provide additional context on our strategic outlook and planned corporate milestones for 2023. 2022 was a year of exceptional execution for Deciphera. Global Kinloch product revenue grew 44% compared to 2021, driven by very strong performance in the U.S. as well as launches outside of the U.S. Kenlock is now approved for fourth-line gastrointestinal thermal tumor, or GIST, in 12 jurisdictions around the world. Last month, we outlined our key strategic priorities for the year, which will enable Decipher to continue its evolution toward being a fully integrated company with multiple approved medicines and capabilities ranging from international commercialization to early-stage discovery, all powered by our proprietary switch control kinase inhibitor platform. These priorities include expanding the market potential for Kenlock into earlier lines of GIST by initiating the INSIGHT Pivotal Phase III study of Kenlock versus sunitinib in second-line GIST patients with mutations in KIT exon 11 and 1718 in the second half of 2023. If successful, we believe the INSIGHT study has the potential to change practice in second-line KIT-driven GIST and to double the U.S. revenues for Kenlock. We were very pleased at the circulating tumor DNA or ctDNA data from our Phase III intrigue study of Kenlock in second-line GIST was selected for presentation at the ASCO Plenary Series session a few weeks ago. Matt Sherman, our Chief Medical Officer, will review the data later in the call and outline our plans for the new Phase III Insight Study. As we begin enrollment in the new Phase III Insight Study for Kenlock, we also expect to read out another pivotal trial, the Phase III Motion Study of imseltenib, our highly selective switch control kinase inhibitor of CSF1 receptor in patients with tenosynovial giant cell tumor, or TGCT, in the fourth quarter of this year. We have been very pleased with the pace of enrollment and are excited to announce today that we now expect to complete enrollment in the motion study in the first quarter and report top-line data in Q4 of this year. For DCC3116, our first-in-class inhibitor of the OLC1-2 kinases designed to inhibit autophagy, we expect to present updated data from the single-agent dose escalation portion of the Phase 1-2 study and initial combination data in the second half of 2023. Finally, we were very pleased to announce a clinical trial collaboration and supply agreement with Pfizer for a new combination dose escalation study of DCC3116 and incarafenib and cetuximab in colorectal cancer that we plan to initiate in the second half of this year. We look forward to presenting the preclinical data supporting this new combination cohort in the first half of this year, along with additional new preclinical data for DCC3116. We continue to complement these commercial and clinical stage advancements with investment in our research pipeline. Our discovery platform continues to drive new growth opportunities with potential first-in-class or best-in-class precision oncology agents, including DCC 3084, our newly nominated Pan-RAF clinical development candidate, for which we expect to present preclinical data in the first half of this year and to file an investigational new drug application in the second half of the year. DTC 3084 was discovered using the same proprietary switch control kinase inhibitor platform that has brought us Kinloch, Vimseltinib, and 3116, and we look forward to quickly advancing this program to the clinic. In addition, we plan to debut a new development candidate from our proprietary discovery engine in the coming months, as well as preclinical data from other research programs our team has been working on. Matt Sherman, our chief medical officer, will provide more detail about upcoming milestones for our pipeline programs on today's call. Ken Martin, our Chief Commercial Officer, will then share insights on the U.S. commercial performance for the quarter, and Margarita Duarte, our Head of International, will provide an update on Kinloch's ongoing fourth-line launch in Europe, which has sustained its strong momentum throughout 2022. We'll end with Tucker Kelly, our Chief Financial Officer, who will review highlights from the fourth quarter and full-year 2022 financial results and the recent highly successful follow-on equity offering that will allow us to continue to execute on our goals. First, I'll turn the call over to Matt Sherman to provide an update on our R&D efforts. Matt?
spk04: Thanks, Steve. We are thrilled with the progress we have made across our clinical and preclinical pipeline in 2022 and already in the first few weeks of this year. As Steve mentioned, it was our privilege to present additional ctDNA data from the Intrigue Phase III study at Kinloch at the ASCO Clementary Session last month, which we believe represents a potential practice-changing event in the treatment of second-line kit-driven GIST. The results strongly support our planned INSIGHT study and the potential to expand Kinloch's label, which, if approved, will allow physicians for the first time to optimize treatment for patients in the second-line setting based on their mutational profile to improve outcomes over the current standard of care. In the ctDNA analysis for patients with KIT, exon 11, and 1718 mutations, Kinloch showed a striking benefit compared to CisNIP across all efficacy measures. beginning with a 44% confirmed objective response rate, with all patients on Kinloch achieving either a partial response or a stable disease. In contrast, there were no objective responses in the student NIP arm. Similarly, Kinloch demonstrated a greatly improved PFS with a median of 14.2 months compared to only 1.5 months for a student NIP. In fact, half of the patients receiving student NIP had progressed or died by their first restaging scan at six weeks. This resulted in the hazard ratio of 0.22, meaning that treatment with Kinloch resulted in a 78% reduction in the risk of disease progression or death. We also saw a strong trend for overall survival in favor of Kinloch in this subgroup of patients. The OS results are based on an updated data cut as of September 2022 and show that the Kinloch arm still had not reached the median, while patients randomized to Sinitinib had an overall survival of 17.5 months. This resulted in the hazard ratio of 0.34, or a 66% reduction in the risk of death. And the landmark analysis showed that the number of patients alive at 30 months on Kinloch was estimated to be nearly twice that of patients randomized to Sinitinib. Kinloch was generally well tolerated, and the subgroup safety and tolerability profile was consistent with the primary analysis of the INTRIG study. For patients with mutations in KIT, exon 11, and 1718, Fewer patients in the Kinloch arm experience grade 3-4 treatment emergent adverse events compared to sunitinib. Based on the intrigued CT data and regulatory input, we plan to initiate INSIGHT, a new pivotal phase 3 study of Kinloch versus sunitinib in this group of second-line GIST patients. If positive, we believe the results of the INSIGHT study will support an expanded label for Kinloch in select second-line GIST patients and transform how physicians treat these patients. Moving from one pivotal Phase III program to another, I now want to talk about vimsultinib, which we believe will become the second approved product from our proprietary switch control kinase inhibitor platform. We are strongly encouraged by the compelling clinical data we have generated to date, supporting the potential of vimsultinib to be the standard of care treatment for patients with TGCT non-amendable to surgery. We began enrolling patients in the Phase III motion study in early 2022, and are very pleased to announce today that we now anticipate completing enrollment this quarter, enabling us to read out the top-line results in the fourth quarter of this year. We also expect to present updated data from the Phase 1-2 study of Vimseltinib in the second half of this year that will focus on longer-term safety and efficacy and provide additional support for the clinical and commercial opportunity for Vimseltinib. Turning now to DCC 3116, we were excited to announce our first clinical trial collaboration and supply agreement for the program a few weeks ago. Under the agreement, Pfizer will supply angorafenib at no cost as part of a new dose escalation combination, evaluating 3116 with angorafenib and cetuxentamab in patients with colorectal cancer. Additionally, we plan to present updated data from the single-agent dose escalation cohorts and initial data from the combination dose escalation cohorts of the Phase 1-2 study, and initiate one or more expansion cohorts in the second half of this year in combination with the MEK inhibitors, trimetinib or binimetinib, or the KRAS G12C inhibitor, sotiracib. We remain optimistic about the potential for DCC3116 to broadly impact the treatment of cancer as a first-in-class autophagy inhibitor based on the strong preclinical in vitro and in vivo data we have generated showing additive or synergistic activity in combination with multiple agents targeting the RTK, RAF, and MAP kinase pathways. Finally, the next program slated to enter the clinic is DCC3084, our pan-RAF inhibitor, for which we expect to submit an IND in the second half of this year. We plan on presenting in vitro and in vivo data in the coming months, demonstrating its preclinical profile as a potent and selective inhibitor of BRAF-CRAF kinases. with optimized pharmaceutical properties for potential development in both single-agent and combination opportunities, as well as data from additional undisclosed research programs, and look forward to the expected nomination of our newest development candidate. I'll now turn the call over to Dan Martin, our Chief Commercial Officer, to provide an update on the U.S. commercial efforts. Dan?
spk09: Thanks, Matt. In 2022, we continue to execute on our commercial goals for Kinloch in the U.S. further reinforcing its status as the clear standard of care in fourth-line GIST, irrespective of mutational profile, while continuing to expand our prescriber footprint. U.S. net product revenue was $25.6 million in Q4, and for the full year 2022, Kinloch sales grew to $97.2 million, representing an increase of about 20% over 2021. Approximately half of this growth came from increased demand volume with the remainder coming from net price growth and a lower percentage of patients receiving free drug under our patient assistance program, or PAP. The higher demand volume seen in 2022 was driven principally by an increasing average duration of therapy as the real-world persistency curve continues to mature and more fully reflects the impact of patients who receive prolonged clinical benefit from Kinloch. Specifically, we estimate that the average duration of therapy in 2022 grew to approximately seven months. We expect the average duration of therapy to continue to increase gradually over time and could ultimately reach as high as eight to eight and a half months. As expected, the percentage of patients receiving free drug under our PAP program increased in the fourth quarter versus the prior quarter. Consistent with what we saw in Q4 of 2021, the PAP percentage was slightly above the high end of our estimated annual range of 20 to 30%. This PAP seasonality is common and is driven by patient affordability challenges that tend to increase as the year progresses due to the Medicare Part D drug benefit design. The development and approval of Kinloch for fourth-line GIST addressed a major unmet medical need and fundamentally changed the treatment paradigm in advanced GIST. Based on the compelling data from the CT DNA analysis of Intrigue, we are eager to start the Insight Study, and we believe approved for this new indication, Kinloch has the potential to advance the GIST treatment paradigm yet again, this time in the second line setting based on mutational profile. We believe that if we are successful in expanding the label with a second line kit exon 11 plus 17 or 18 indication, that it would double the Kinloch peak revenue potential to 350 to 400 million in the U.S. alone. Turning to Vimseltinib, With the readout of the Phase III Motion Study fast approaching, the commercial team continues to prepare for a potential approval and launch. We remain highly encouraged by the market opportunity in TGCT, where we have estimated a total addressable market of $850 million in the U.S. With a potentially best-in-class product profile, we believe in Sveltenand is uniquely positioned to address the high unmet medical need within TGCT. And given the approximately 90% overlap among GIST and TGCT prescribers, we believe Vimseltinib will be an excellent addition to our commercial business, and that Kinloch and Vimseltinib together have the potential to generate in excess of $1 billion in global peak revenue. I will now turn the call over to Margarita Duarte, our head of international, to discuss the progress of our Kinloch launch in Europe. Margarita?
spk02: Thanks, Dan. We are very proud of the strengths and sustained momentum of Kinloch's European market entry. 2022 was a key year that saw very successful execution in two critical markets, our launch in Germany and the post-approval paid access program in France. It was also a year in which we made significant progress towards market access in other major European markets, with the submission of the reimbursement application to NICE for access in England and in Wales, and to IFO for access in Italy. and the initiation of the market access process in Spain. For the full year 2022, international net product sales were 28.3 million, up significantly from 5.9 million in 2021. These strong results reflect Kinloch's best-in-class clinical profile in fourth-line Gs and the significant unmet needs, and I'm very proud of the team's superb execution of our launch strategy that enabled such exceptional performance. Our fourth quarter international net product revenue of 7.3 million was driven primarily by continued growth in demand in Germany and in France. However, net product revenue for the fourth quarter did include a one-time reserve for Kinloch product sales in Germany. It would change in German law effective as of November 2022, shortening the free pricing period retroactively to six months from 12 months. In Germany, our team is in the last stages of the price negotiations. And although we are not yet in a position to disclose the details, we remain confident that our final negotiated price will reflect the high value that Kinloch brings to patients and payers in Germany. We also continue to advance our access discussions with NICE, as well as with the authorities in Italy and Spain, and look forward to sharing updates on future calls. Turning to the rest of the world, We were pleased to see that the national reimbursement work list released by China's National Healthcare Security Administration was recently updated to include Kinloch, which will provide access to Kinloch for many more patients in China for our partner Xilab. In 2022, we recognize 8.5 million in collaboration revenue under our agreement with XI and look forward to their continued strong commercial execution in greater China. In addition, we are excited to announce that we recently received approvals for Kinloch in New Zealand, Israel, and Macau, increasing the number of jurisdictions around the world to 12, in which Kinloch is approved for fourth-line GIST. I will now turn the call over to Tucker Kelly, our Chief Financial Officer, to review the fourth quarter and full-year financial results and recent financing. Tucker?
spk10: Thanks, Margarita. Total revenue for the fourth quarter was $36.3 million, which included $32.9 million in net product revenue at Kinloch and $3.4 million in collaboration revenue. For the full year, total revenue grew 39% to $134 million, including net product sales of $125.5 million and collaboration revenue of $8.5 million. Cost of sales in the fourth quarter was $3.2 million, including $0.7 million in cost of net product revenue and 2.5 million in cost of collaboration revenue. For the full year, cost of sales was 8.8 million, including 2.7 million in cost of net product revenue and 6.1 million in cost of collaboration revenue. In 2021, total cost of sales was 2.9 million, of which 1.6 million was cost of collaboration revenue and 1.3 million was cost of net product revenue. In the third quarter of 2022, we completed the sale of zero-cost inventories that had been expensed as R&D prior to FDA approval in 2020. In Q4, total operating expenses were $83.5 million compared to operating expenses of $112.6 million in the same period in 2021. For the full year 2022, total operating expenses were $316.8 million, a decrease of approximately 20% compared to operating expenses of $396.2 million in 2021. Research and development expenses in the fourth quarter of 2022 were $48.1 million compared to $74.9 million for the same period in 2021. In 2022, R&D expenses were $187.8 million compared to $257 million in 2021. Selling, general, and administrative expenses in the fourth quarter were $32.2 million compared to $37.2 million in Q4 of 21. For the full year, SG&A was $120.2 million compared to $136.3 million in 2021. We ended the year with cash, cash equivalents, and marketable securities of approximately $339 million. In January of this year, we raised an additional $134.7 million in net proceeds through a very successful public offering that further strengthened our financial position and extended our cash runway into 2026. The strong support we received from both existing and new investors in the offering will allow us to increase shareholder value as we strive to become a company with multiple approved products. With that, I'll now turn the call back over to Steve.
spk13: Thank you, Tucker. The outstanding progress we've made at Deciphera over the past year, along with our planned 2023 milestones, puts us firmly on the path to becoming a company with multiple approved products around the world. As we near enrollment completion and prepare to announce top-line results from our Phase 3 Motion Study, We look forward to also initiating our Phase III Insight Study later this year. We are proud to leverage our proprietary switch control, kinase inhibitor platform, and deep pipeline to make a difference for people living with cancer. With that, operator, I would like to now open the call for Q&A.
spk08: As a reminder, to ask a question, please press star 1-1 on your telephone, and please wait for your name to be announced. Please stand by while we compile the Q&A roster. Our first question comes from Daniel Wall with JP Morgan. Your line is now open.
spk15: Daniel Wall Good morning, everyone. Thank you for taking my question. Just a couple of questions. First, for insight. With the idea of combining Kinloch with SUTEN considered for the pivotal trial, second, you are able to refine the timeline for enrollment completion for motion from first half 23 to 1Q23. What can you attribute this acceleration to? And then for DCC 3116, while results from the dose escalation combination study are not expected until second half, What should investors expect with initial data? And specifically, should there be an expectation for anti-tumor activity? Thank you.
spk13: Hi, good morning, Daniel. Thanks for joining and thanks for the three questions. So let me take those in order. First, you broke up on the first part of your question with respect to insight. I believe it was related to a combination. Can you just repeat that for me? Operator, go ahead.
spk15: Sure. I guess the question was, was the idea of combining Kinloch with SUTEN considered as one arm of the pivotal study?
spk13: I see. Okay. Thanks for that question. So I'll take the question on insight and on motion, then ask Matt just to speak to 3116 and expectations here in the second half for the accommodation dose escalation data. So first, Daniel, with respect to insight, the data that we presented at the ASCO plenary series session just last month, and we, of course, disclosed at the beginning of the year. We view as being very, very clear, very compelling in terms of the activity of Kinloch in this group of patients relative to SUTENT. So, no, as a result, we did not consider adding a third arm to the study looking at a combination because we don't believe that a combination with SUTENT in particular would add any additional activity in the selected group of patients. With respect to motion, we were very pleased, as we announced today, that we'll be reaching full enrollment in the motion study in quarter one instead of the first half of this year, still reporting out in quarter four of this year. And the enrollment in the study, as we've been telegraphing over the course of the last six to nine months, we've been really pleased with the pace of enrollment, how enthusiastic investigators and patients are to enroll in the study. And it's really that enthusiasm and the pace of enrollment that allowed us to enroll the study faster than we previously anticipated and is going to allow us to get to full enrollment here in this first quarter. So we look forward to reporting out the study in quarter four of this year. Matt, do you want to speak to the 3116 question?
spk04: Yeah, hi, Daniel. It's Matt. So, yeah, in regards to the 3116 program, as you know, ESMO last year were able to present the monotherapy dust escalation data, and we're very pleased with the results. showing that we had good dose proportional PK, that we had a very good safety profile, and also were able to inhibit the target of autophagy in patients treated with 3116. So as we announced earlier as well, taking that forward into combination escalation cohorts with two MEK inhibitors, binimetinib and trimetinib, as well as the KRAS T12C inhibitor, so the RASCIP. So as we've announced, we'll expect to have an update on the combination cohorts in the second half of this year, And our expectation there will be to continue to show the PK as well as the safety profile of the drug. And in terms of efficacy, you know, certainly, you know, it is designed as dose escalation in small cohorts of patients. But, of course, if there's a signal of efficacy, you know, we'd be very pleased to have that information for updating in the second half later this year. Okay.
spk15: Got it. One last question. With multiple KRAS inhibitors in development actually and on the market, As you continue development of 3016, is there an opportunity for you to select the best fit partner as you advance into late-stage development?
spk13: Yeah, thanks for the question, Daniel, with respect to KRAS G12C inhibitors. And you're right, there are a variety of agents now, two approved in the U.S. And as we've reported previously, the effect that we see with 3116 addressing autophagy as an escape when used in combination with a KRAS G12C inhibitor is not specific to an individual KRAS G12C inhibitor. It's certainly a class effect. It's a mechanistic effect that we see. So we've seen that and reported that preclinically both with sideracib but also with adagracib. So there would be an opportunity going forward for us to consider additional KRAS G12C combinations as we think about the ideal partner for a potential 3116 KRAS G12C inhibitor combination.
spk15: Great. Thank you very much.
spk08: Please stand by for our next question. Our next question comes from Michael Schmidt with Guggenheimer. Your line is now open.
spk05: Hey, good morning. Thanks for taking our question. This is Paul on for Michael. One from us on recruitment for the inside study. So your analysis sort of suggests that only a portion of GIST patients have detectable acute mutations through ctDNA, and there is some discussion at the ASCO plenary about GIST as a relatively low ctDNA-shedding cancer. So I just wanted to get your expectations on the speed of recruitment of patients for this target mutation population at INSIGHT once that study kicks off later this year and whether you anticipate any sort of challenges in that aspect. And then secondly, on 3116, maybe just provide some color on what drug you're decision to combine with and carafinib and cetuximab and where you see that potential for the combination in colorectal cancer. Thank you.
spk13: Yeah, hi, good morning. Paul, it's Steve. So I'll take the insight question that you posed and then ask Matt to speak to the 3116 and carafinib and cetuximab combination. So first, with respect to insight and enrollment in that study, You know, we've now demonstrated very clearly the capability to enroll these large randomized studies in GIST globally. So we have a clear capability in terms of getting these studies up and running and enrolling them rapidly. With respect to patients with the specific mutation that we'll be looking for, patients who don't shed ctDNA, this is a very similar fraction in GIST versus other solid tumors. So we don't see that as being a differentiating factor. And with a simple blood-based diagnostic with a rapid turnaround time of 5 to 10 days, we don't see that as being a barrier at all. In fact, we see it as being an advantage to enrolling in the study. And then lastly, I would just offer that what we continue to hear from investigators and from thought leaders is a considerable amount of enthusiasm, given the data that's now been reported at ASCO, for the potential of Kenlock and this selected group of patients. And I think that's going to serve as a real tailwind in terms of not only getting sites up and running, but also getting patients enrolled on study. Matt?
spk04: Yeah, hi, Paul. It's Matt. So, yeah, in regards to our plan to initiate a cohort of 3116 in combination with angorafenib and cetuxenab, you know, we're obviously very excited overall with the, you know, with the preclinical data we've generated to date showing that we can inhibit multiple nodes along the RTK, RAS, and MAP kinase pathway in combination with 3116. and show an additive or even a synergistic combination effect on tumor killing. So, you know, as we've initiated a number of these combination cohorts now, you know, looking at the unmet medical need in treating advanced stage colorectal cancer, and, you know, while cetuximab and agorafenib have activities demonstrated in the BEACON study a number of years ago, that was somewhat limited activity, you know, with an objective response rate of approximately 20% and the PFS of about four months. So there's certainly a lot of headroom for improving and treating patients, and recognizing this might be a huge opportunity for 3116 and colorectal cancer.
spk05: Got it. Very helpful. Thanks so much.
spk12: Please stand by for our next question.
spk08: Our next question comes from Tyler Van Buren with Cohen. Your line is now open.
spk20: Great. Thank you. Good morning, guys. Had a couple for you.
spk19: The first is, can you help us understand what the magnitude of the one-time reserve for Kinloch sales in Germany was and elaborate more on your expectations for the cadence of XUS sales throughout the year? And the second is, for VIM and TGCT, you've presented an extensive claims analysis, but What other data points give you confidence in this market, given that patients are so diffused throughout the country and not necessarily concentrated in centers of excellence?
spk13: Good morning, Tyler. Thanks for the set of questions. I'll ask Tucker to comment first on the reserve in Germany. Margarita, perhaps you can then comment on what you see as the cadence in terms of the commercial business across Europe. And then, Dan, why don't you take the final question with respect to themseltinib claims analysis and the confidence we have in the size of the opportunity. Tucker?
spk10: Sure, Tyler. So we haven't quantified the amount of the reserve in Germany that we took in the fourth quarter, but just to remind folks, what happened is that the German authorities in November changed the law. It used to be that you had a 12-month period of free pricing, and that got shortened to six months. effective retroactively based on the law change in November. So in the fourth quarter, we took a reserve based on the net sales we had booked at our free pricing price in the third quarter. And then in the fourth quarter, the sales in Germany were booked at an estimate because we're still not at our final price in Germany. but an estimate of where we think we may end up with the German authorities on pricing. So we haven't quantified it, but it certainly was a larger number in the quarter that we wanted to make sure people understood that as they looked at the quarter-for-quarter change in international product sales.
spk02: Okay, I will take the second one. Thanks, Tyler, for the question. So I would say that the cadence for the rest of the year in Europe will come from two key strategic drivers. The first one is to continue to successfully drive price and reimbursement in the countries where we don't have yet access so that you can launch in new markets in the future. And the second one, I would say to continue to successfully execute on our launch strategy and continue to raise awareness, to drive demand, and to expand the prescriber base. And I would also offer to say that I am extremely pleased with the success that we are seeing so far and with the strong demand that we continue to see.
spk09: And, Tyler, this is Dan Martin. I'll take your question on what gives us confidence in the TGCT market. I think what gives us confidence is several factors. First, you mentioned the claims analysis that we've presented on. That was just a component of our overall analysis of the opportunity. We actually conducted a couple different methodologies, all of which gave very similar answers. We conducted a more typical sort of literature-based epi buildup, and totally separately we conducted the claims analysis. And both resulted in really similar findings in terms of the overall patient journey for TGCT, as well as the size of the addressable opportunity. We, as it relates to the claims data, the 1,300 to 1,400 patients that we have noted as being the incident RX treated patients in the US in this data set, we've always viewed that as really a floor of the opportunity and one that gives us real confidence because this is an analysis that doesn't provide indicators of patients. It actually sees the patients. And so we can see these patients being treated in the data, which gives us great confidence. Lastly, I would just note that one of the things that we get asked is our view of sort of products used in the space and market share. And we've presented the findings from the claims database there as well, showing that only about 15% of the patients received pexidartanib in this data set. And that enables us to sort of triangulate or crosswalk back to the opportunity that we've laid out. So across multiple different views of the market, we land in very similar places, which gives us great confidence that the opportunity is there. Lastly, I'll just note that diffuse markets with patients being spread between both academic and community settings is a bit of a specialty of ours. We've developed real capability in being successful in that space because that's very much the description of GIST. GIST is very similar in that way. And frankly, one more point is that we know that the overlap between GIST and TGCT is really high. So for all these reasons, we have great confidence that the market is there and that we're uniquely positioned to be successful.
spk21: Thank you very much.
spk08: Please stand by for our next question.
spk12: Our next question comes from Inyoung with Jefferies.
spk08: Your line is now open.
spk02: Thank you. I have actually a few questions. First, you mentioned that in 2022, the treatment duration for Kinlog was seven months and expected that to increase to 8 to 8.5 months. What's driving the increase in the treatment of a duration? And do you expect to achieve 8 to 8.5 months of this year? Second question is on the NCCN guidelines. I don't know, it's just something, I understand it's something that we cannot predict, but you have submitted your data for second-line intrigue data, but in light of the subgroup analysis in Exxon 11, 17, and 18 patient population, do you expect the NCCN decision could be on that subgroup? Thank you.
spk13: Yeah, hi, good morning, Yoon. Thanks for the great questions. So I'll take the second question first with respect to NCCN, and then I'll ask Dan to cover off on the treatment duration for Kinloch that we see in the real-world experience in the U.S. market. So first for NCCN, you're exactly right, Yoon. It's not something that we can predict in terms of whether the NCCN is going to update the guidelines, when that might occur, or what might be reflected in the guideline update. We were excited to present the data from the subgroup as part of the ASCO plenary series session just last month. Very compelling data in this group of patients with Ken Block. So we're excited about that. I think the field is very excited about it, as you will have seen from the presentation and the discussion at the ASCO session at the end of January. And so we await, as you do, any potential updates to the guidelines. Difficult for us to predict in what shape or form or timing that might be in. So we'll stay tuned for that and see if there are any updates. Dan?
spk09: Yeah, thanks, Yoon, for the question regarding adversarial therapy. It's a really important dynamic that was key in driving the really solid growth that we saw year over year. As I noted in my prepared remarks, we demonstrated about 20% growth year over year. with 97 million in the US in 2022. And that was driven by a number of factors, but importantly by volume growth. And the volume growth was driven principally by this increasing average duration of therapy that we see. And the driver for that is really just a maturing of the real world persistency curve, or said another way, maturing of the real world sort of prevalent treated pool that now more fully reflects Patients who have had extended and prolonged benefit from Kinloch, which just pulls the average duration of therapy up now beyond the median PFS that we saw in the Invictus study. And that's really important because we expect that to continue to be a gradual growth driver over time. We had noted we expect that could potentially reach eight to eight and a half months. And there's a number of proof points for that, which I could certainly go into, but we feel confident that ultimately eight to eight and a half month average duration of therapy is very achievable. However, we have noted that that's a gradual phenomenon. That's a gradual trend that we will expect to see develop over time. So it's hard to predict exactly what timetable that will develop in, but that's why we underscored we see that as a peak average duration of therapy. And we don't expect that to be something that changes dramatically quarter to quarter, so likely something that we will share additional color on sort of as warranted over time.
spk02: Thank you. Can I ask you some follow-up questions?
spk14: Please do, Yun. Go ahead.
spk02: Yeah. So a question on the INSIGHT trial. So based on the subgroup analysis that you've done from the intrigue, it looks like you may need to screen about 400 to 500 patients. So question number one is how long do you think it would take to enroll about 54 patients? And secondly, In the currently in practice, is this a mutational analysis after Imatinib done routinely? Thank you.
spk13: Yeah, again, thanks for the two questions. Good questions. So I'll take both of those. So first, with respect to the INSIGHT study, you're right. Sites will need to screen patients for eligibility for enrollment in the study. We, you know, from our experience with Intrigue, which we ran as a large global study, multiple sites. You know, we have the capability, of course, and have demonstrated the capability to run these large studies to open multiple sites and to find patients for enrollment. At the site level, of course, we know that physicians will be using an easy liquid diagnostics or liquid biopsy where they simply draw blood and there's a five to ten day turnaround time to identify patients. And furthermore, sites will know generally the primary mutation status for their patients already from their time of diagnosis. So we would expect that physicians would really be interested in looking at their primary exon 11 patients, of course, and understanding what their secondary mutation profile is as they consider them for enrollment in the study. So we have a lot of confidence based on our demonstrated capabilities in this area of running these sorts of studies, and we're looking forward to getting insight up and running at the end of this year. Now with respect to practice within the U.S. or globally even, There isn't a need, hasn't been a need up until now for physicians to consider looking at the emergence of secondary mutations post-Omatinib treatment. But what we know from other analogs, whether it's looking at lung cancer or other solid tumors, is that these sorts of liquid biopsies, these blood-based diagnostics, see very good adoption. As I noted, these are easy to run. It's simply a tube of blood that's sent off to a lab with a five- to ten-day turnaround time. So we don't expect, especially given the nature of the data that we've now presented with Kenlock in this group of patients, we don't expect adoption of a diagnostic to be a barrier to use at all. In fact, we think there'll be a considerable amount of enthusiasm among physicians and patients to understand what their secondary mutation status is so they'll know whether Kenlock could be an option for them in the second-line setting.
spk02: Thank you.
spk12: Please stand by for our next question.
spk08: Our next question comes from Chris Raymond with Piper Sandler. Your line is now open.
spk18: Thanks, and good morning. This is Nicole Gabreski on for Chris. Thanks for taking the questions. Maybe just two from us. One, just in terms of using ctDNA as a potential companion diagnostic for patient identification, I guess, can you talk about how that would be integrated if the subset analysis data is included early in NCCN guidelines, maybe versus if you get regulatory approval in the second-line kit exon 11 and 1718 setting? Are there any differences just in the setup? I guess we're trying to understand if it's important to have a cleared or approved companion diagnostic in the setting. And then maybe second, just around vinsultinib, you know, going back to your ESMO presentation last year, I know that you guys were highlighting that responses deepen over time, but ORR at the 25-week time point for vinsultinib matched the pexidartinib label. And, you know, we understand that the safety profile will be the key differentiator, you know, allowing patients to stay on therapy longer. But I guess, how will that be effectively captured within the phase three motion study? And how does that translate into a potential label?
spk13: Good questions, Nicole. Thanks for those. So let me take first the ctDNA question, and then I'll ask Matt just to comment on the motion study and the data we presented last year at ESMO and touched on the data we're collecting as part of motion that would then inform a label and the profile of the drug in a commercial setting upon a potential approval. But first, for the ctDNA data in GIST today, and I think your question, Nicole, was in the present-day environment, even absent a regulatory approval for Kinloch in this patient population, what could physicians do in practice? We know that, of course, these sorts of blood-based panels are already available, so from companies like Foundation Medicine, Garden Health, and the like, and so physicians today, if they were so inclined, could draw a tube of blood and send it off to Foundation or to Garden for analysis, and these these panels today will pick up the secondary mutations seen in just patients and report back on that. So physicians, if they chose to do so, they could run that analysis and then make treatment decisions, which would be off-label today, so this isn't something that we can or would promote to, but physicians could then make treatment decisions and they would have to work with the patient's insurance provider to obtain coverage for that off-label use. But I guess my point is just that these diagnostics are available today for physicians who are interested in understanding the secondary mutation status for their patients. Matt, do you want to comment then on Vimseltinib in motion?
spk04: Yeah, good morning, Nicole. So, yeah, as you note, you know, for the 25-week endpoint in the Vimseltinib TGCT study, we had a 38% response rate, which was similar to what was reported for the enlivened Pestinib study in their label. But also, as we also know, you know, these patients, you know, continue on therapy for longer than six months and can have a response beyond that. And we reported for the Phase I dose escalation cohorts who were on study the longest, a 69% overall response rate in the TGCT patients in the Phase I-II study. And in terms of a label, it's also noted that in Liven's label, or Pace-Dartner's label, based on the Liven study, also shows their overall response rate in the open-label portion of the study, and that's 61% in the current label for Pesidartinib. So we could expect that our label for consultative may contain some long-term follow-up and a higher overall response rate.
spk08: Great. Thanks.
spk12: Please stand by for our next question.
spk08: Our next question comes from Brad Canino with Stiefel. Your line is now open.
spk03: Good morning, and thank you. Steve, maybe a follow-up on your previous comments. I guess I want to know, based on the KOL and physician feedback to the subgroup analysis, do you expect the material enough proportion of practices to adopt a second-line ctDNA-guided treatment paradigm in the next few years to impact Kinloch cells? And then a second question, would the top line readout for themselves been inflated for 4Q? When you think about the degree of data that you would include in the package to the FDA if successful, can you add any comments about how long you expect it to take to reach an NDA filing? Thank you.
spk13: Yeah, thanks, Brad. Two good questions. So with respect to expectations around taking the data that we presented at ASCO and that being translated or changing practice today, it's an uncertainty. So, you know, of course, we can't promote for that use. We don't have extensive market research that tells us whether physicians will adopt the use of the drug on an off-label basis. What we've seen so far in our experience is that use has been, for Kenlock, has been generally within our approved label. So we'll continue to monitor and understand how physicians, if they choose to change practice, how that practice changes over time. But we don't have any information at the moment with respect to what changes might occur. You know, clearly having a label in the second line setting in this patient population is what will ultimately allow us to drive share and drive utilization, and that is one of the reasons that we've decided to conduct the INSIGHT study and seek a label in the second line, is to be able to promote that use upon approval. Your second question, I think, Brad, was related to Vimseltinib and our announcement this morning that we expect to complete enrollment in the first quarter of this year and read out the study in Q4, and your question was, around the timing for a potential NDA. So it's really premature for us to share our thoughts around what the timing could be for an NDA post-topline readout. What I can say is that our team has demonstrated, certainly with Kenlock and our fourth-line label, our ability to quickly move from top-line data readout to get a filing in. This will be no different, and when we have a readout of the study of the top-line results, I'm sure we'll be in a position at that time to offer some additional color around what the timing could be for a potential filing in the U.S. and filings outside of the U.S.
spk08: As a reminder, to ask a question, please press star 11 on your telephone. Please stand by for our next question.
spk12: At this time, please stand by for our next question.
spk08: Our next question comes from Peter Lawson with Barclays. Your line is now open.
spk11: Great. Thank you. Thanks for taking my question. Just on NCCN guidelines, are you looking to gain guideline inclusion for exon 11, 17, 18?
spk13: Yeah, thanks for the question, Peter, with respect to NCCN. So we're going to continue to monitor what NCCN decides to do with respect to any guideline update, and that will guide our decision about any future submissions of data. That's the approach that we plan on taking with respect to NCCN going forward.
spk11: Gotcha. I mean, does the Exxon 11, 17, and 18 data plus, you know, various other mutations, does that make the NCCN guideline changes for second-line newcomers difficult then to make that judgment call?
spk13: Yeah, I think what we've learned, Peter, from the analysis is that there's a level of complexity and nuance, I think, to the data. I mean, certainly the 11, 17, 18 population, the result is very clear in terms of Kenlock, the benefit of Kenlock versus Sunitinib. And we have this group of patients in whom ctDNA is not detectable, where we see on the forest plot the hazard ratio for PFS is virtually in the center of that forest plot. So I think it's unclear at the moment what NCCN might choose to do. We know that physicians generally are interested in having more options available to treat their patients. We don't think that this situation with GIST is any different. So we would expect that that will be of interest to physicians on the panel as they think about providing options to patients going forward.
spk11: Thank you. And then just on China, just kind of the size of the opportunity, how we should think about pricing and kind of how you think it could help revenues over the next couple of years, whether it's 2023 or 2024.
spk13: Sure. Margarita, would you like to address the China opportunity and ZEISS disclosures?
spk02: Absolutely. Thank you. Thanks for the question, Peter. So we view this listing, you know, very positively as it will increase affordability and access for Chinese patients moving forward. So we do expect this to be a key contributor of volume growth over time. How quickly that happens, we do not have a lot of details, you know, yet. But all in all, we view this extremely positively.
spk06: Thank you so much. Thank you, Peter.
spk08: I show no further questions at this time. I would now like to turn the conference back to Steve Herter for closing remarks.
spk13: Great. Thank you, Michelle. Thanks to all of you for joining us on today's call. Thank you for your continued support of the work that we're doing here at Decipher. We look forward to keeping you updated on our progress for the balance of this year and hope you have a great rest of your day.
spk08: This concludes today's conference call. Thank you for participating. You may now disconnect.
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