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spk12: Welcome to the Cyphera Pharmaceuticals First Quarter 2021 Financial Results Conference Call. Today's call is being recorded. At this time, I would like to hand the conference over to Jen Robinson, Vice President, Investor Relations.
spk07: You may begin. Thank you, Talanda. Welcome, and thank you for joining us today to discuss the Cyphera's First Quarter 2021 Financial Results. I'm Jen Robinson, Vice President, Investor Relations at DecipherUp. With me this afternoon to discuss the financial results and provide a general corporate update are Steve Herter, President and Chief Executive Officer, Dan Martin, Chief Commercial Officer, Matt Sherman, Chief Medical Officer, 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 Kinloch, and 2021 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 quarterly report on Form 10Q, 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. I will now turn the call over to Steve Herter, President and Chief Executive Officer of Decipher Us. Steve?
spk06: Thank you, Jen. It's been an exciting start to the year for Deciphera as we build upon all that we accomplished in 2020 and execute on our strategic priorities across the portfolio for 2021. We continue to make great progress against the three areas of focus for Kinloch this year, successfully launching Kinloch in the U.S., expanding the geographic reach of Kinloch by seeking regulatory approvals around the world, and moving Kinloch into earlier lines of therapy in GIST. Our successful launch of Kinloch in the U.S. demonstrates the significant unmet medical need in fourth-line GIST and the potential for Kinloch to offer a meaningful difference for patients in this setting. In a few minutes, Dan Martin, our Chief Commercial Officer, will outline our success in quickly establishing Kinloch as the standard of care in its approved indication. Our rapid penetration of this market and the very positive perceptions of Kinloch by GIST treaters create a solid foundation for our potential future expansion into the second-line setting. In the first quarter, we made important progress on our goal to expand the geographic reach of Kinloch. Our partner in Greater China, Xilab, received approval for Kinloch from both the China National Medical Products Administration and the Hong Kong Department of Health. An estimated 30,000 new patients are diagnosed with JIS in China each year, and we look forward to supporting XI as they launch Kinloch in China later this quarter. We expect to receive approval for Kinloch from the European Medicines Agency in the fourth quarter of this year. As we await action from the EMA, we are actively laying the groundwork for our commercial organization in Europe and building an experienced and focused team that will allow us to quickly deliver Kinloch to patients in key markets once approved. As the first drug specifically designed to treat GIST, we believe Kinloch has the potential to fundamentally alter the treatment of this disease. One of the key elements of our strategy to expand the use of Kinloch into earlier lines of treatment is our ongoing phase three study, Intrigue, in the second line setting. We expect to announce top line results for Intrigue in the fourth quarter of this year. And beyond the Intrigue study, we are pursuing additional opportunities to benefit patients with GIST by evaluating the use of Kinloch as a backbone of a treatment combination that seeks to address one of the potential mechanisms of resistance to KIT inhibition. reactivation of the MAP kinase pathway. Matt Sherman, our chief medical officer, will discuss in more detail later in the call our plan to initiate later this year a phase 1b2 study of Kinloch in combination with Benimetinib, an approved MEK inhibitor. Finally, we remain very excited about our expanding pipeline of kinase inhibitors beyond Kinloch. Throughout 2021, we expect to have significant clinical and regulatory updates that we believe have the potential to create significant value for shareholders as we continue to deliver on our mission of discovering, developing, and commercializing new medicines for patients with cancer. I'll now turn the call over to Dan Martin, our Chief Commercial Officer, to discuss the U.S. Kenlock commercial results from Q1. Dan?
spk04: Thank you, Steve. Good afternoon. Today I'm pleased to report the results of our third full quarter of Kinloch sales and to provide additional color regarding our expectations as we look ahead. We continue to be very pleased with the Kinloch launch, including our rapid penetration of the fourth line opportunity and the overwhelmingly positive response we've received from GIST treaters. In Q1, we achieved $20 million in total net product revenue, including $19.3 million in the U.S. bringing total launch-to-date U.S. net product revenue to $57.3 million. As we have shared previously, prior to launch, our goals were to rapidly establish Kinloch as the standard of care in our initial fourth-line indication, while building clinical experience and positive product perceptions among the broad prescriber base in advance of a potential launch into the larger second-line opportunity. Thanks to the continuing efforts of our cross-functional teams to navigate the unprecedented challenges of the COVID-19 pandemic, we have continued to make excellent progress toward these goals. Our recent market research indicates that commercial execution was again a strong point in Q1. Despite the continuing need to operate largely through a virtual model, our sales and marketing teams maintained high levels of prescriber reach, frequency, and share of voice and grew our prescriber base to over 400 prescribers from more than 350 institutions since launch. Despite having limited opportunities for in-person meetings, our sales team has established an excellent reputation among GIST treating physicians. In a recent blinded survey, GIST prescribers cited the Decipher sales team as best in class among companies in the GIST market and ranked the team first across every performance metric evaluated. Our market research also shows that this continued strong execution has had a clear impact. Kinloch awareness and familiarity among prescribers treating fourth-line GIST remained extremely high, and GIST treaters again reported very positive perceptions of Kinloch's clinical attributes. In a recent survey, nearly 90% of all GIST treaters and 100% of physicians who have prescribed Kinloch agreed that Kinloch is the standard of care in fourth-line GIST. Among physicians who initiated a fourth-line GIST treatment within the prior 90 days, nearly all had prescribed Kinloch. In addition to the strong performance of our sales and marketing teams, our market access team continued to deliver broad patient access to Kinloch in Q1. Their coverage for Kinloch remained very positive with policies aligned to our FDA label. During the quarter, the percentage of patients that received free drug under our patient assistance program, or PAP, was at the low end of our estimated range of 20 to 30%. Prior to launch, data from the Invictus study gave us confidence that Kinloch had the potential to transform the treatment of advanced GIST. Now, early data from our fourth-line launch is providing insight into how Kinloch is benefiting patients in the real-world setting. Though it's still early days and the data are still maturing, the real-world persistency that we see for patients who have received Kinloch since launch is similar to what we saw in the Invictus study, consistent with our pre-launch expectations. Ultimately, based on data from our clinical trials, we would expect the average time on therapy to be somewhat longer than the median due to the impact of long responders. However, it will take time for this data to mature, and it's still too early to know how this trend will play out in the real-world setting. In terms of broader market dynamics, we may now be seeing more clearly the impact that the pandemic is having in oncology and specifically in GIST. Data from IQVIA show that the pandemic has had a persistent negative impact on oncology diagnosis visits since Q2 of last year, and IQVIA projects that this impact is likely to continue in the coming months. Further, a recent analysis of claims data for earlier line GIST patients showed a decline in new patient volume over the past year of approximately 10%. This trend is something that we will continue to assess as it could impact the volume of patients progressing to fourth line treatment this year. These data are consistent with our discussions with just thought leaders who indicate that patient volume and referral patterns have been inconsistent during the pandemic. Given Kinloch's rapid penetration of the fourth line opportunity, as well as the uncertain impact that the pandemic may continue to have in the near term, We expect the opportunity for growth to be limited until we are able to expand into the second line setting pending positive data from intrigue and subsequent approval. As we've discussed, we believe the opportunity for Kinloch is substantially larger in the second line compared to our initial fourth line indication. This is driven by a larger estimated incident patient population, as well as the fact that patients may experience increased clinical benefit and longer time on therapy when they receive Kinloch earlier in their course of disease. As we have shared previously, we believe the distribution of patients in the second line has weighted more heavily toward the community setting when compared to fourth line patients. With this in mind, we are extremely pleased to see that while academic prescribers made up the majority of our earliest adopters, we have also made tremendous progress in the community. In Q1, we estimate that more than half of Kinloch-treated patients and 70% of new prescribers came from the community setting. We believe our diverse prescriber base across both academic and community settings and the awareness and positive product perceptions we have established among GIST treaters more broadly positions us extremely well for a potential future second-line launch. Moving forward, our focus in the U.S. will continue to be on optimizing our fourth-line business while at the same time initiating our launch preparations for a potential approval in the second line. Kinloch has already had a profound impact on the treatment of advanced GIST, and we are extremely motivated by the potential opportunity to help patients even earlier in their course of disease when they may benefit most. I will now turn the call over to Matt Sherman to discuss the progress of our clinical programs.
spk05: Matt? Thank you, Dan. As Steve mentioned, we remain focused on demonstrating Kinloch's profile as a best-in-class broad-spectrum kit inhibitor in our ongoing Phase III Intrigue Study comparing Kinloch 2-2-2-Submitinib in patients with second-line GIFs. Based on the progress of the Intrigue Study, we expect to announce top-line data in the fourth quarter of this year. We remain very optimistic about the potential for Kinloch to demonstrate superiority over Submitinib based on the strong results of the Phase I Study, where Kinloch showed a median progression-free survival of 10.7 months in second-line patients. We believe that to demonstrate a clinically meaningful benefit in Intrigue, we will need to show a two to three month increase in PFS relative to the expected PFS for the arm of approximately six months. Finally, we believe that the exceptional results of the phase three Invictus study showing a median PFS of 6.3 months in fourth line plus GIST patients receiving Kinloch strongly supports the likelihood of success in Intrigue. We are excited to announce today our plans to initiate a phase 1B2 study of Kinloch in combination with binimetinib, an improved MEK inhibitor, to address one of the potential resistance mechanisms in GIST. Despite the benefit that Kinloch and other approved kit inhibitors provide for many GIST patients, resistance remains a significant challenge, and we have long thought about how dual pathway inhibition might increase responses in GIST patients. The goal of the new study is to see whether we can deepen and prolong initial responses by combining broad kit inhibition from Kinloch with inhibition of the MAP kinase pathway using a MEK inhibitor. First-line imatinib has proven to be effective in stabilizing disease progression in most just patients, but less than 10% of patients experience complete regression. Just often becomes imatinib resistant after acquiring secondary mutations, most often in kit, or the MAP kinase pathway can be reactivated, increasing KIT expression. These patients experience progressive disease that no longer responds to treatment. Our Phase 1B2 clinical study is supported by exciting preclinical data that was recently published online in Molecular Cancer Therapeutics, as well as preclinical data presented at the EORTC NCI AACR meeting in 2018 showing that treatment with Kinloch in combination with MEK inhibitors effectively induced and enhanced apoptotic responses and prevented growth of resistant colonies in just cell lines. In addition, Kinloch demonstrated superior efficacy to imatinib in combination with MEK inhibitors. The Kinloch-MEK inhibitor combination was better than the imatinib-MEK inhibitor combination in inhibiting cell growth even after removal of drug. One major advantage of using Kinloch as a combination partner with a MEK inhibitor over imatinib is that Kinloch treatment did not result in the generation of resistance mutations in preclinical studies. We expect to initiate a Phase 1b2 open-label study in the coming months to evaluate the safety, efficacy, and pharmacokinetics of Kinloch in combination with binimetinib in patients with GIST who have progressed on at least a magnet or are intolerant to a magnet. The study will consist of a dose escalation phase and an expansion phase. The dose escalation phase will follow a three plus three study design and will enroll patients with advanced GIST who have not been previously treated with Kinloch. The expansion phase is a single cohort study to evaluate the efficacy and safety of the recommended phase two dose of the combination in a cohort of patients who have progressed on or are intolerant to single-agent imatinib. We are focused on exploring the full potential of what we believe is Kinloch's best-in-class kit profile to benefit patients with GIST and believe that this combination therapy could give GIST patients a new treatment option that provides enhanced clinical benefit compared to kit inhibition alone. In addition to our clinical activities, we're executing well on our robust publication presentation strategy. There have been a number of recent publications highlighting the use of Kinloch in the GIST treatment landscape. Building on the intrapatient dose escalation data we presented last year from the phase one study of Kinloch, I'm pleased to announce that we plan to present intrapatient dose escalation data from the phase three Invictus study in an e-poster at the American Society of Clinical Oncology, or ASCO, annual meeting in June. We are also making great progress in our other ongoing pipeline programs. Let me start with ribastinib since we will be providing updated data from this program in ASCO this year. Ribastinib is our potential first-in-class selective inhibitor of the Ti2 kinase. We presented highly encouraging anti-tumor activity for both the endometrial cancer and platinum-resistant ovarian cancer cohorts from the Phase 1b2 study in combination with paclitaxel last year. Focusing on the endometrial cancer cohort, we have completed our target enrollment of 33 patients in part two of the study, and we are excited to present updated data from this cohort at the upcoming ASCO annual meeting. We briefly reported an encouraging objective response rate in this heavily pretreated cohort, with a median of four prior lines of treatment. And further follow-up will now enable us to present progression-free survival for these patients. In regard to the treatment landscape for endometrial cancer, there are limited options after paclitaxel and carboplatin in the first-line setting and levatinib and pembrolizumab in the second-line setting. The expected activity for paclitaxel retreatment in later lines of endometrial cancer patients is a response rate of 10 to 20% and a PFS of three to four months. This was recently reinforced by the data presented at the Society of Gynecologic Oncology, or SGL, from Keynote 775, a Phase III study in patients with advanced endometrial cancer who progressed after only one prior regimen, which compared levatinib pembrolizumab to physician's choice of chemotherapy of either weekly paclitaxel or doxorubicin. The chemotherapy arms show the confirmed response rate of 15% and a PFS of 3.8 months, which is consistent with our expectations with a limited activity of single-agent paclitaxel retreatment and endometrial cancer. In addition, we remain on track to present updated results from the ongoing Phase I-II study of ribacinib in combination with papilitaxel in the platinum-resistant ovarian cancer cohort in the third quarter of the year. We are focused on driving this program forward as efficiently as possible, and we expect to finalize a potential pivotal development plan for ribacinib in combination with papilitaxel in the coming months. The other two programs in our pipeline, VimSultanit, are a potential best-in-class inhibitor of CSF1R in development for the treatment of tenosynovial giant cell tumor and DCC3116, a potential first-in-class oak kinase inhibitor in development for the treatment of mutant RAS-RAF cancers, remain on track. For VimSultanit this year, we expect to present updated data from the ongoing Phase 1-2 study in patients with TGCT in the third quarter and finalize the Pivotal Development Plan for this program in the second half. To DCC 3116, we are excited to initiate the first in human study this quarter. We look forward to the continued progress of these programs, each of which has the potential to make a meaningful difference in the lives of patients and fulfill current unmet medical needs. I will now turn the call over to Tucker Kelly our Chief Financial Officer, to review the financial results. Tucker?
spk03: Thanks, Matt. I'd like to review the highlights from our first quarter financial results. Total revenue for the first quarter was $25.2 million, which includes $20 million in net product revenue of Kinloch, $19.3 of which was from sales in the U.S. The growth to net adjustment of the first quarter was in line with our annualized estimate of approximately 15%. Collaboration revenue of $5.2 million included a $5 million development milestone under our license agreement with Xilab, triggered by the regulatory approval of Kinloch in China in March. Once Xilab begins to commercialize Kinloch in Greater China, we will receive royalties based on annual net sales levels that range from the low to high teens. In addition, we are eligible for up to $135 million in commercial milestones based on achievement of certain annual sales of Kinloch in Greater China, as well as additional development. Cost of sales for the three months ended March 31st, 2021 was immaterial as the majority of the manufacturing costs related to Kinlot sales were incurred prior to FDA approval and thus were recorded as R&D expense. As we have said previously, we expect the cost of sales will remain immaterial through at least this year and would not expect cost of sales to be significant until the initial pre-launch inventory is depleted and additional inventory is manufactured and sold. Total operating expenses were 86.4 million in the first quarter of 2021, compared to total operating expenses of $75.3 million in the same period in 2020. Research and development expenses in the first quarter were $55.7 million compared to $51.4 million in the same period in 2020. And selling, general, and administrative expenses in the first quarter were $30.7 million compared to $23.9 million in the same period last year. We continue to expect that our operating expenses will increase modestly this year as we invest in the development of our clinical pipeline, execute on the commercial launch of Kinloch in the U.S., and prepare for a potential commercial launch in Europe. We ended the first quarter in a strong financial position and remain well capitalized with cash, cash equivalents, and marketable securities of approximately $502 million, which we now expect will be sufficient to fund our operations into the first half of 2023. And with that, I'll now turn the call back over to Steve.
spk06: Thanks, Tucker. I'm proud of the work our team has done in the first quarter of this year to sustain the momentum we built in 2020. As we continue to establish Kenlock as the standard of care for fourth-line GIST, we are excited to expand its reach to patients and prescribers around the world with both the recent approval in China and our pending approval in Europe later this year. As we realize the transformational potential Kenlock has for patients with fourth-line GIST, we look forward to announcing top-line results from Intrigue in Q4 and unlocking the potential for Kenlock in the second line. 2021 is also expected to bring significant updates across the balance of our pipeline, including the dosing of our first patient and the Phase I study of DCC3116, as well as new data and potential pivotal development plans for both themselves and Robastinib. With that, operator, I'd like to open the call for Q&A.
spk12: Thank you. Ladies and gentlemen, to ask the question, you will need to press star then 1 on your telephone. To withdraw your question, press the pound key. Again, that's star one to ask the question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Jessica Five with JP Morgan. Your line is open.
spk09: Hi, this is Daniel for Jessica. Thanks for taking our question. First question is, you have stated in your prepared remark that it will take time for data on duration of treatment to mature. With the product now in the market for almost a year, when do you expect to have better insight on the average time on therapy? And when you talk about persistency similar to Invictus, can you elaborate for us and provide some more detail?
spk06: Yeah, Daniel, thanks for the question. It's a good set of questions. Dan, would you like to take this?
spk04: Sure, absolutely. So with respect to persistency looking similar to what we saw in Invictus, when we mapped the persistency curve that's emerging for patients who have received Kinloch since launch. It looks quite similar to the Kaplan-Meier curve for PFS from Invictus. So we think that's a sort of a good guide for kind of what we're seeing in the persistency data thus far. And then the comment about it will take time to develop. That was more about the average as opposed to sort of percent of patients on therapy at different time points in these early days. So the average, of course, will be impacted by a potential long tail, long responders in the persistency curve. And given that we're only, as you say, about a year into launch, give or take, we're just not there yet. You know, if you think about the clinical data from phase one trial, for example, it took, you know, multiple years to sort of fully develop. those long responders. So that was why I said, you know, if we look at the data from clinical trials today, we would expect the average to be somewhat longer than the median, but it'll just take us some time for that data to mature.
spk09: Got it. And then I know that you have said the next leg of meaningful growth will come from self and second line. But should we think about this roughly 20 million quarterly run in the U.S. as a good run rate? to use going forward for the U.S. sportline opportunity, or is there a potential for that to change as the impact of COVID lessens going forward?
spk06: Daniel, Steve, it's a good question, and I think as Dan mentioned in his prepared remarks, we do see data both in claims as well as from third-party providers that suggest that there has been and is an ongoing impact from the pandemic, and I think it's just inherently uncertain as to how that unfolds for us with Kenlock during the course of this year. As Dan mentioned, our view is that we'll see limited growth as a result of the context here going forward as we get to the readout of Intrigue in the second line and a potential approval that would come subsequent to that.
spk09: Okay. And last one, the PR states that the cost of sales will not be significant until the initial prelaunch inventory is depleted and additional inventory is manufactured and sold. Do you have an estimate of when you'll exhaust that inventory?
spk03: So we don't, other than that we don't expect it to be material this year and that as we move forward we'll be able to provide updated guidance on what the COGS might look like in terms of when we'll be selling inventory that was not capitalized at the time of approval.
spk09: Great. Again, thank you very much for taking my question.
spk12: Thank you. Our next question comes from the line of Chris Raymond with Piper Sandler. Your line is open.
spk08: Hey, thanks for taking the questions. Just help me understand the math a little bit. I think I heard you guys say that there's more than 400 prescribers this quarter. And I think by my math, that's about a 15% prescriber growth quarter on quarter. And I remember last quarter you guys mentioned that the percentage of docs that had multiple patients on therapy was still pretty low. And I think I hear what you're saying with respect to COVID, but Maybe just, if you can, maybe first of all, just square that. If you've got a 15% prescriber growth, how does that square with flat quarter-to-quarter revenue? And maybe can you talk about any sort of dynamics with respect to, like, free drug or anything like that that might be also impacting the revenue number? Thanks.
spk06: Yeah, thanks for the set of questions, Chris. Dan, would you like to take those?
spk04: Yeah, absolutely. Thanks. Thanks for the question, Chris. Yes, so the key insight here, the key thing to keep in mind, is that not all prescribers contribute patients each quarter. This is a rare, you know, cancer in the fourth line setting. And so we can see new prescriber growth since launch, but that doesn't mean that every one of those prescribers, and therefore every one that's contributing to that 15% growth you mentioned, is contributing patients in any given quarter. We've said previously that, you know, especially once you get out in the community setting, you know, physicians may only see a fourth line GIST patient every 12 to 18 months. So it's just, it's really rare and that's really the driver. I think hopefully that helps square the math a little bit for you.
spk08: Well, yeah, it does. But I guess, you know, just the inference that the fourth line GIST market opportunity is $80 million. I guess that, you know, seems to also sort of raise some questions, I guess, that I'm getting from some investors. How is that sizably lower, I think, than the patient numbers that we've gotten? And I know you mentioned COVID, but if you have any sort of sense of if patients aren't getting treated, what is happening with these folks? Sorry for the kind of dumb question there, but yeah.
spk04: No, it's a good question. So I think a couple important things to keep in mind. We've shared previously that, you know, it's important to recognize that when you use a persistency curve, that really reflects the amount of patients on therapy at any given time point. And when you use an average you plug that average in, that tends to overestimate the number of active patients in the early days of launch. So I don't know if that is, you know, a delta in how you've built your model. But what I can say is that given all of the data that, you know, we've shared previously in this call and in prior calls, you know, we think we've done a great job rapidly penetrating the opportunity. The response from the physicians, both academic and community, has been overwhelmingly positive. And I think it sets up great for the larger opportunity in second line pending approval. Thank you.
spk12: Thank you. Our next question comes from the line of Ian Yang with Jefferies. Your line is open.
spk11: Thank you. So, Phase III Intrigue Study patient enrollment was completed at the end of November last year. So I want to ask you a couple of questions there. One, are you still comfortable with your PFS assumption? around six months. And second question is, I want to ask you if PFS events have been occurring in line with your expectations.
spk06: Yeah, hi, Eunice, Steve. So I'd be happy to take those questions. So I think with respect to the first question about what we'd expect to see from SUTEN, our view of that hasn't changed. As we've talked about on prior calls, We would expect, based on the pivotal study for SUTENT, which is in the SUTENT label, that a PFS of 5.6 months, we would expect to see a PFS in the present-day environment of something in the range of six months. And that's very consistent with the feedback that we've heard historically and also to this day from thought leaders. So we're very comfortable with what we'd expect to see from SUTENT. And as you know from our Phase I experience, in our second-line cohort from the Phase I, we've seen really compelling results. data in that cohort with a median PFS of 10.7 months, and of course, you know, Invictus. So we think the totality of the clinical data we've generated so far with Kenlock is very positive, and our confidence in the potential for intriguing a positive study remains unchanged. In terms of accumulation of events, we haven't commented in terms of what the pace of events we would expect to be. I would just note that when we We first designed the study and loaded the information in clinicaltrials.gov. You know, we had expected at that time that we would get to the primary endpoint of the study in June of this year. And, of course, a number of things have changed along the way in terms of number of subjects in the study and also, you know, the environment in which we're operating. But we don't view the refinement of our guidance to Q4 in terms of the top line readout as being really a substantive sort of change.
spk11: Thank you. And then a question on the binimetinib combo study. So as you mentioned, in second line, you are already seeing close deliverance of PFS. So by adding binimetinib, post-binimetinib, considering likely potentially increased side effects, what are you aiming to achieve? Thank you.
spk06: Yeah, thanks, Eunice. It's Steve. I'll take that. And then, Matt, please feel free to chime in as well. I mean, we're really excited about the data that we've generated that now, as Matt said in his prepared remarks, has been published showing the real synergy between Kinloch and MEK inhibitors generally. And so our goal, given the fact that Kinloch is now established as monotherapy as the standard of care on the fourth line, we hope and expect that will certainly be the case when Intrigue reads out in Q4 of this year and as we move to advance the drug as monotherapy into an earlier line of treatment based on intrigue. But our goal in this disease with Kinloch is really to maximize the potential clinical benefit for patients. And we think based on the preclinical data we've generated, if we follow that science, that there is a real potential for us to potentially deepen and prolong responses that we see with the combination relative to monotherapy Kinloch. And we certainly have some indication of the potential for that based on data that's already been generated. But, Matt, anything else you would add to that commentary in terms of the potential for the MEK combination?
spk05: Yeah, no, thanks, Ewan, for the questions here. And also, just to add, I mean, we feel very excited about the combination. You know, combination therapy in oncology tends to be a very, you know, good way of increasing responses and increasing the durability of those responses. And based on the preclinical data that we highlighted today and that's available, we feel that the biological mechanism supports the combination of a MEK inhibitor with Kinloch. In terms of the safety, you know, we certainly know that Kinloch has a very, you know, good safety profile, you know, based on what's in the label as well as what we've heard from investigators. And we'll be starting off by doing a dose escalation study in combination with Bidimetinib and feel that, you know, we'll be able to monitor and manage any adverse events that may occur.
spk11: The question is more specifically what additional PFS benefits would be meaningful if you show about close to 11 months of PFS with repratinib alone in second line.
spk06: Yeah, I think put simply, we think there may be an opportunity to continue to raise the bar. So we're certainly not satisfied with 10.7 months. And we'll see the data from Intrigue as monotherapy coming up here in Q4. But to the extent there's an opportunity, as Matt outlined, through a combination approach with Kenlock is really the backbone of that combination to drive better PFS and a longer response for patients. That's certainly something that we're interested in pursuing.
spk11: Thank you.
spk12: Thank you. Our next question comes from the line of Michael Schmidt with Guggenheim. Your line is open.
spk14: Hey, guys. Thanks for taking my questions. I had a few more on the intrigue study. Just on the refined guidance for data now in the fourth quarter, I guess, has there been a change in the event rate relative to your initial expectations or perhaps the censoring rate?
spk06: Yeah, Michael, let's see. Thanks for the question. You know, we haven't disclosed, as you know, the event rate or when we expect the events to you know, to fully accrue and the timing for that. But, you know, as I said earlier in response to an earlier question, the refinement to Q4 is certainly within the range of what we got it to previously, which was the second half. So we're just now in a position where we can narrow that down a little bit better, which is the reason that we made the incremental disclosure today.
spk14: Perfect. Thanks. And then a question we've been getting from investors around, um, you know, how suit and, um, it can perform differently depending on the type of, uh, kid mutations. Uh, I think specifically in Exxon 1340 mutations, uh, Stephen has, has been shown to, to perform relatively well. Um, I guess, could you remind us how reprit net performs in Exxon 1340 mutations specifically? relative to season and perhaps what percent of second-line GIST patients have exclusively exonberg in 40 mutations?
spk06: Yeah, thanks for the question, Michael. So I'll start off and then I'll turn it over to Matt. I mean, I think as you know, as we've talked about previously, when we designed this drug, Specifically for JIS, the goal was to design a broad-spectrum inhibitor, and we think we've now very convincingly demonstrated that Kinloch is, in fact, a broad-spectrum inhibitor based on the strength of the data from Invictus and also the data that we've generated in the Phase I. And we're looking forward, of course, to the report out of Intrigue here later this year. But, Matt, what additional color commentary would you offer in terms of mutational background in the second one?
spk05: Yeah, I think we could also just point to the very strong results of the Invictus study in fourth-line patients, and really those are the patients who are probably characterized by the most heterogeneity of their mutational burden, and that's what we showed in the presentation last year. And yet, despite that broad heterogeneity of mutations in the fourth-line just patient population, we had the outstanding results of the benefit of PFS as well as, you know, the clinical meaningful increase in overall survival. So again, just reinforcing the broad activity of repritinib against multiple KIPP mutations.
spk14: Okay, thanks. And then just on the binimetinib combination strategy, is that something that is, you know, to be pursued strictly in the post-imatinib setting, or is that a combination that could perhaps take on imatinib and first-line just down the road?
spk06: Yeah, Michael, it's a good question, and I think, you know, Matt can touch on this as well, but, you know, as he noted in his prepared remarks, it's we've seen in a preclinical setting, you know, the potential for the combination of MEK with Kinloch to be superior to that of imatinib plus the MEK inhibitors. So, you know, because Kinloch, of course, does a much better job than imatinib would at preventing additional mutations in KIT from emerging. So we do think that that combination has potential. Our initial step, of course, with this study is to generate the data once we get to doses of the two drugs that can be combined, but then generating data in the second line, and we'll of course have a very contemporaneous comparison with the Intrigue data that reports out later this year as monotherapy, really to understand what the incremental benefit may be of adding MEK inhibitor to Kinloch in that setting. Great, thank you.
spk12: Thank you. Our next question comes from the line of Ren Benjamin. with JMP Security. Your line is open.
spk02: Hey, good afternoon, guys. Thanks for taking the questions and congrats on the quarter. Maybe just focusing on the China approval, can you provide any sort of color as to how we should be thinking about the launch or how Scilabs is preparing for the launch, how big their sales force could be? And I guess I'm just trying to get an idea as to how we should be thinking about the trajectory. Is it more kind of like how things are going here in the U.S. is what you would expect there, or should we be thinking more along how things are going in the rest of the world or some mix of the two? And maybe just an accounting one for Tucker. Tucker, do we expect the royalty revenues to come in in the second quarter of this year, or is there a one-quarter delay? Okay.
spk06: Yeah, right. So I'll take the first part of that and then turn it over to Tucker. So, you know, we know what Zai Lab has disclosed with respect to GIST in China, which is that there are 30,000 new patients each year in China with GIST. So it's, of course, a sizable population and sizable opportunity. I think when it comes to a drug like Kinloch, which Zai, as they've guided to, plans to launch here later in quarter two, I think the launch trajectory and ultimate opportunity really depends upon the ability of Zai to access the full opportunity and for the patients with GIST in China, broadly speaking, to have access to an innovative medicine. I know that's something that Zai is really focused on. They haven't provided any additional color or refinement in terms of what to expect in terms of ramp of Kinloch with the China launch.
spk03: And, Ren, just to take the second part of your question, we would expect when they make a sale on their end and have patients being prescribed Kinloch that we would then recognize the royalty revenue. I think Zai hasn't yet guided exactly when they expect to be in market with the drug, so we just have to wait and see the specifics of their launch timing. But otherwise, we would expect it to be when they're making sales on their end.
spk02: Got it. And then maybe just as a quick follow-up, I saw the two ribacinib updates, one in the second quarter at ASCO, another one in the third. Am I missing the carboplatin study? Are we expecting an update from that at some point?
spk06: Yeah, thanks for the question, Ren. Matt, do you want to take that in terms of data flow coming from the ribacinib program?
spk05: Yeah, so as you highlight, we're continuing with the combination of abacitabine in combination with paclitaxel, which highlights this year for both the endometrial cancer cohort and the platinum-resistant ovarian cancer cohort. We also have a combination study in combination with carboplatin, and that's currently being studied in patients with platinum-sensitive ovarian cancer. We haven't provided an update yet. Mr. Wynn will be updating those data.
spk02: Okay, I just wanted to make sure it was continuing to move forward. Thanks very much, guys.
spk12: Thank you. As a reminder, ladies and gentlemen, that's star one to ask the question. Our next question comes from the line of Peter Lawson with Barclays. Your line is open.
spk13: Great. Thanks for the update. Just on the cash runway, Tucker, that was extended out. Was there a reason why?
spk06: Yeah, Tucker, it looks you may be on mute, Tucker.
spk03: Oh, apologies. Yep. Sorry, Peter. It's Tucker. Absolutely. Every quarter we look at our operating expenses and historicals and update our forecast going forward. So, no, there really wasn't a significant change by any means in our assumptions underlying it. We just have a little bit more history to look at and better ability to try and forecast the cash runway. And in this case, we're able to push it out into the first half of 2023. Great.
spk13: Gotcha. Thank you. And then just on the, I guess, the real world setting for Kinloch, just the duration of treatment you're seeing, if there's anything you can talk through.
spk06: Yeah, thanks, Peter.
spk04: Dan, do you want to comment on that? Sure. So, Peter, I just want to make sure I answer your question. In my prepared remarks I just laid out that we are starting to see that persistency care emerge, and it's looking similar to the KM curve for PFS from Invictus. Was there something specific that I could provide more color on?
spk13: Yeah, I guess that probably addresses it. I was just kind of trying to work out if it was longer, shorter than what you've seen in the trial, but it sounds like it's similar. Yes. Gotcha.
spk04: And then, you know, and just to note, sorry, Peter, um, And just to note, right, we always get asked about average versus median. It's just too early to know about whether the average will be longer than the median. We would expect it to be somewhat longer based on data that we've seen in clinical trials, but that's something that we'll continue to let the data mature to help inform. Gotcha.
spk13: Thank you. And then just, I guess, another question around the MEK inhibitor. It sounds like it enhances durability, but I mean, is there any chance that it enhances overall response rate, or that sounds like that's ruled out?
spk12: Thank you. Our next question comes from the line of Robin Conarchus with Truro Securities. Your line is open.
spk10: Hey, guys. This is for Robin.
spk06: Yes, please go ahead.
spk10: Thank you so much for taking my question. So barring the impact of COVID for Kinloch, do you see any additional levers to enhance uptake in Fourth Line? What sort of feedback have you been getting from doctors, especially around safety? And this is in relation also to the Second Line program that's ongoing. Can you remind us about safety concerns around SUTINT, and if you're hearing anything about down-dosing regimen that's used in the real-world setting?
spk06: Yeah, I can, but Steve, so I'll take that question, and Peter, if you're still listening, we'll come back to your question. I think we were having a mute issue, but I want to come back to the question that you asked as well. So with respect to SUTINT and how it's used in the real-world setting, yes, I mean, the very consistent feedback that we hear from investigators and from physicians who use this drug is that it is common for the drug to be dose reduced as a result of tolerability challenges. So that is something that we understand as a fairly common occurrence.
spk10: And are you hearing any sort of feedback around Kinloch safety in the real world that you think is different from what you saw in the clinical setting?
spk06: We hear, with respect to Kinloch, very consistent feedback that's consistent with our label and the clinical experience, and that the drug is well-tolerated. And I think physicians view it that way, especially relative to other options that are available to them and to their patients with GIST. So I think the drug is viewed as being a well-tolerated, effective option for patients.
spk10: Great. And one more question, if I may. For the data readout from the phase three trial and fourth quarter, what can you tell us about what to expect? Do we see top line data, whether it met the endpoint or not, or more detail than that, or should we expect more detailed presentations at a medical conference later with just the top line?
spk06: I think it's fair to expect that we'll have a relatively fulsome, you know, top line readout, similar to what we did for the Invictus study when we reported out those data. So, we'll seek to provide relevant information on the primary endpoint of the study, you know, as well as the tolerability profile of the drug based on the experience in the intrigue study.
spk10: Okay, great. Thank you so much.
spk06: Great, thanks. And then I just wanted to come back, Peter, to your question that you asked with respect to the MEK inhibitor combination and whether we might expect to see more tumor cell killing or more of a cytosidal response with that combination versus simply a prolongation of response. And Matt, I wanted to ask if you would like to address that based on the preclinical data that we've generated and what's been published now online just today.
spk05: Sure. Yeah, no, I think it's very important to recognize that there was a pilot study that was done. It was an investigative-sponsored study at Memorial Sloan-Kettering that was presented at ASCO last year. It was a combination of imatinib and lipidimatinib. So based on the same preclinical rationale that we've discussed today, the investigator there was able to show it was a cohort of about 40 patients, an objective response rate of 68%. And that compares very favorably to the historical activity of about 50% for single-agent imatinib. The progression-free survival from that combination was 29.9 months, again, greater than the reported PFS for single-agent imatinib of 18.9 months. And the overall survival had not been reached in the combination study that was presented. So, again, it gives us some, you know, real-world evidence and some, you know, early data to support the combination of imatinib with ripritinib in this planned study.
spk12: Thank you. I'm sure no further questions in the queue. I would now like to turn the call back over to Steve for closing remarks.
spk06: Great. I'd just like to thank all of you for joining us for today's call, and thank you for your continued support of Decipher. We look forward to keeping you updated on our progress throughout the rest of 2021. I hope you all have a great evening. Thank you.
spk12: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.
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