Good morning everyone, and welcome to Deciphera Pharmaceuticals Third Quarter 2022 Financial Results Conference Call. Today's call is being recorded. At this time, I would like to turn the call over to Jennifer Larson, Senior Vice President of Finance and Investor Relations. Jen? Thank you, operator. Welcome, and thank you for joining us today to discuss Deciphera's third quarter 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 a general corporate update are Steve Hoerter, President and Chief Executive Officer, Dan Martin, Chief Commercial Officer, Matt Sherman, Chief Medical Officer, Margarida 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 pre-clinical and clinical programs, our commercialization of QINLOCK, and 2022 guidance. Forward-looking statements made on this call involve substantial risks and uncertainties that could cause the actual results to differ materially from those expressed or implied by the forward-looking statements, and we cannot assure you that our expectations will be achieved. Such risks and uncertainties include those set forth in our most recent quarterly report on Form 10-Q, as well as our SEC filings. We assume no obligation to update or revise any forward-looking statements. Following this call, a replay will be available on the company's website, www.deciphera.com. With that, I will now turn the call over to Steve Hoerter, President and Chief Executive Officer of Deciphera. Steve? Thank you, Jen, and good morning, everyone. Thank you for joining us today as we provide an update from the third quarter, review our financial results, and discuss upcoming corporate milestones. We achieved another record for QINLOCK revenue in the third quarter, reflecting our success delivering this breakthrough medicine to patients in the United States and around the world. Our efforts to expand the global reach of QINLOCK continued as we submitted a reimbursement application to authorities in Italy and initiated the market access process in Spain. We are proud of the difference QINLOCK has made in the lives of fourth-line GIST patients around the globe, and we remain committed to ensuring this important medicine reaches the patients who need it most. We made significant progress in the third quarter across our clinical stage portfolio and presented exciting new data updates from the vimseltinib and DCC 3116 programs at the European Society of Medical Oncology or ESMO Congress in Paris. At ESMO, we presented the initial phase I dose escalation data for DCC 3116, our first-in-class ULK inhibitor targeting the autophagy pathway in patients with advanced metastatic tumors with a mutant RAS or RAF gene. We demonstrated 3 key outcomes in the phase I data. DCC 3116 demonstrated dose-dependent pharmacokinetics, a favorable tolerability profile, and strong target inhibition across all dose levels tested. Since the presentation at ESMO, we completed enrollment in the phase I single agent dose escalation portion of the study and selected the starting dose for these cohorts. We announced today that we opened enrollment of these dose escalation combination cohorts with the first patient treated last week. At ESMO, we also presented updated data from the phase I/II study of vimseltinib, our orally administered inhibitor of CSF1 receptor for the treatment of patients with tenosynovial giant cell tumor or TGCT, not amenable to surgery. The updated data underscored the best-in-class potential of vimseltinib, demonstrating strong clinical activity, positive patient-reported outcomes, and a favorable tolerability profile. Finally, we announced today that we have nominated DCC 3084, a selective inhibitor of BRAF and CRAF kinases, as the next clinical candidate to enter our portfolio. Discovered using the same proprietary kinase inhibitor platform that has brought us QINLOCK, vimseltinib, and DCC 3116, we believe DCC 3084 has the potential to be best in class and demonstrates our ability to discover novel agents for the treatment of cancer. I'll now turn the call over to Dan Martin, our Chief Commercial Officer, to share more details on our strong U.S. commercial performance, and then to Margarida Duarte, our Head of International, to provide an update on QINLOCK's ongoing fourth-line launch in Europe, which has continued its positive momentum throughout the year. Dan? Thanks, Steve. In Q3, we continued to execute on our commercial goals for QINLOCK in the US, reinforcing its position as the clear standard of care in fourth-line GIST, while continuing to grow our prescriber footprint and physician experience with QINLOCK. During the quarter, we achieved $24.5 million in total net product revenue in the US, which represents a 23% increase from Q3 of last year. Our key performance metrics continued to reflect strong commercial execution. In Q3, our sales and marketing teams again drove strong unit demand volume across all business segments. Our launch to date prescriber base has continued to grow at a very consistent pace quarter- over- quarter, exceeding 750 physicians through Q3, with the majority of new prescribers again coming from the community setting. Our market access team has continued to deliver excellent payer access with 100% payable claims for on-label patients during the quarter. We again saw strong persistency and time on therapy. The percentage of patients receiving free drug under our patient assistance program, or PAP, was at the high end of our 20%-30% estimated range as anticipated. Consistent with what we saw in 2021, we expect the PAP percentage in Q4 of this year to again be at the high end of our estimated annual range of 20%-30%. Turning to vimseltinib, as the clinical team continues to rapidly enroll patients in the phase III MOTION study, our commercial team continues to prepare for the potential launch of our second marketed product. Given the limitations of existing therapies, there is a clear unmet medical need for TGCT patients who are not amenable to surgery. In market research, physicians and patients consistently cite the desire for an effective therapy without having to sacrifice safety and tolerability. Our recent market research with TGCT treaters further supports the potential for vimseltinib to establish a new standard of care. We conducted detailed interviews with TGCT treaters to gain their feedback on the vimseltinib data generated to date and on how it compares to existing treatment options. After reviewing product profiles for vimseltinib, pexidartinib, and imatinib, TGCT treaters consistently rated the vimseltinib profile as highly compelling across all key product attributes. When asked which of the three products they would be most likely to recommend to their TGCT patients, every physician interviewed selected vimseltinib, commonly citing what they perceived to be best-in-class efficacy and safety. This feedback from TGCT treaters further underscores why we believe vimseltinib has the potential to deliver a best-in-class profile and the opportunity to provide tremendous clinical benefit to TGCT patients globally. I will now turn the call over to Margarida Duarte, our head of international, to discuss the results from the third quarter of the commercial launch of QINLOCK in Germany and the progress we are making in other European countries and around the world. Margarida? Thanks, Dan. We are very proud of the strength and continued momentum of QINLOCK's European market entry, driven by our launch in Germany and the post-approval paid access program in France. We remain very pleased with the launch trajectory in Germany, with continued growth in the number of prescribers and number of patients under treatment with QINLOCK throughout the third quarter. As we build awareness in Germany, we are also working hard to conclude the reimbursement negotiations and pursue pricing that reflects the major additional benefits that QINLOCK brings to fourth-line use patients. Despite some expected softness in volume driven by the summer period in France, QINLOCK continues to be very well received with exceptional KOL advocacy and very strong product perception. The team continues to make good progress with price and reimbursement and successfully preparing the market for the launch next year. International QINLOCK net product revenue was $7.8 million in the third quarter, which includes net revenue from sales in Europe as well as product revenue from distributors in other countries. While we continued growth in Germany, overall international QINLOCK revenue was negatively impacted by lower product sales outside Europe and by the continued weakness of the euro in Q3. In parallel with the strong commercial performance, our team continues to tirelessly pursue market access on a country-by-country basis, and we are excited by our recent progress in two key territories with the recent reimbursement application submission in Italy and the initiation of the market access process in Spain. We also continue to advance our process with NICE for access in England and Wales and look forward to sharing updates on future calls. I will now turn the call over to Matt Sherman, our Chief Medical Officer, to discuss the exciting progress we have made across our clinical and research pipeline. Matt? Thanks, Margarida. We are encouraged by the excellent progress we have made throughout the last quarter advancing our pipeline of novel kinase inhibitors as we continue to bring innovative new medicines to cancer patients. As Steve mentioned, it was our privilege to present new data from the DCC-3116 and vimseltinib programs at the ESMO Congress in September. At ESMO, we reported positive preliminary data on the phase I single-agent dose escalation portion of the DCC-3116 study. The results show that DCC-3116 was well tolerated and achieved exposure in ULK1/2 inhibition on all dose levels that were associated with anticancer efficacy with MEK inhibitors in preclinical studies. As of the data cut off at ESMO, DCC-3116 was evaluated in 18 patients across four dose levels from 50 mg BID- 300 mg BID and was well tolerated, with most treatment emergent adverse events being grade 1 or 2. DCC-3116 exposure appeared to increase dose proportionally and demonstrated targeted inhibition with significant decreases in the phosphorylation of ATG14, a direct ULK1/2 substrate in peripheral blood mononuclear cells across all dose levels tested. As we noted at ESMO, we expanded the 100 mg BID-300 mg BID dose cohorts with additional patients to further characterize DCC-3116 and better inform the selection of the starting dose for the combination dose escalation cohorts. After enrolling 10 more patients to the study, I am pleased to announce that we have not reached the maximum tolerated dose in a single-agent dose escalation and have selected 50 milligrams BID as a starting dose level for the combination cohorts. The first three combination dose escalation cohorts will include two cohorts in combination with MEK inhibitors, trametinib and binimetinib, as well as one cohort with sotorasib, an approved KRAS G12C inhibitor. All three cohorts are now open for enrollment, and last week we treated the first patient. The robust results from the single-agent portion of the study provide an excellent foundation for our clinical strategy of combining DCC-3116 with a broad range of partner drugs across many different mechanisms of action, which could potentially revolutionize the treatment paradigm for a large number of cancer patients. Now turning to vimseltinib, our CSF1 receptor kinase inhibitor that has the potential to be a best-in-class treatment for TGCT and a substantial improvement on the currently available therapy. The updated data presented at ESMO from phase I/II study continued to demonstrate vimseltinib's antitumor activity and support its encouraging safety profile. vimseltinib's strong efficacy was highlighted by high response rates across all parts of the study, with early and sustained responses for many patients and response rates that continue to increase over time. In the phase I study, which is the most mature part of the study, we saw an objective response rate of 69%. In Cohort A of the phase II portion of the study, the objective response rate was 53%. In addition, for the first time, we also presented response data from Cohort B of the phase II portion of the study, which includes patients with prior therapy that inhibits a CSF1 receptor. Even in this pre-treated population, vimseltinib showed an impressive initial objective response rate of 46%, including responses in some patients who had not achieved a previous response or who progressed on or after receiving prior CSF1 receptor-directed therapies. Treatment duration continued to increase in the most recent data cut. In the phase I study, which included the most mature data, the median treatment duration was 17.5 months, and 53% of patients in phase I remained on study. We look forward to providing an update on the vimseltinib's impressive treatment duration at the next data disclosure. In addition to the deepening and durable responses observed, we were very pleased by the updated safety profile with longer-term follow-up across all phase I dose cohorts and at the recommended phase II dose in Cohorts A and B. We believe vimseltinib has the potential to address the limitations of existing therapies with a best-in-class product profile and are encouraged by substantial clinical data we have generated to date, along with the progress of our phase III registration-enabling MOTION study. Enrollment continues to progress very well, and we look forward to providing an update in the coming months on our estimated times to reach full enrollment. Moving to our preclinical pipeline, we are excited to announce today the nomination of our pan-RAF clinical development candidate, DCC-3084. This molecule is a selective inhibitor of the BRAF, CRAF kinases and inhibits Class 1, 2, and 3 BRAF mutants, BRAF fusions, and NRAS mutant cell lines. Preclinical studies of DCC-3084 demonstrate both single-agent and combination activity and favorable pharmaceutical properties, a key potential differentiator from other pan-RAF programs in development. I will now turn the call over to Tucker Kelly, our chief financial officer, to provide the financial update. Tucker? Thanks, Matt. I'd like to review the highlights from our third quarter financial results. Total revenue for the third quarter was $36 million, which includes $32.3 million in net product revenue of QINLOCK and $3.7 million in collaboration revenue, the majority of which is QINLOCK commercial supply revenue under our agreements with Zai Lab for Greater China, as well as royalty revenue. Cost of sales for the three months ended September 30, 2022 was $3.3 million, which included approximately $700,000 in cost of net product revenue and cost of collaboration revenue of $2.7 million. In Q3, we completed the sale of zero cost inventories that had been expensed as R&D prior to FDA approval in 2020. As we transition to selling inventory that reflects the full cost of manufacturing, we do not expect the cost of product sales as a percentage of net sales of QINLOCK to increase significantly. Total operating expenses were $80.9 million in the third quarter, a decrease of 21% compared to operating expenses of $102.9 million in the same period in 2021. Research and development expenses in the third quarter were $47.5 million, compared to $66.4 million for the same period in 2021. Selling, general, and administrative expenses for the third quarter were $30 million, compared to $35.5 million for the same period in 2021. Cash, cash equivalents, and marketable securities as of September 30 was approximately $372 million, sufficient to fund our operations into 2025. With that, I'll now turn the call back over to Steve. Thank you, Tucker. Today's updates demonstrate the breadth of progress we've made across our pipeline this year, from expanding our geographic reach with QINLOCK to providing exciting new clinical updates for both the vimseltinib and DCC-3116 programs at the ESMO Congress in September, and most recently, treating the first patient in the combination dose escalation portion of the DCC-3116 phase I study and declaring a development candidate from our pan-RAF program. We look forward to a strong finish to the year and setting the stage for an exciting year ahead in 2023. With that, operator, I'd now like to open the call for Q&A. If you'd like to ask a question, please press star one one. Our first question comes from Daniel Wu with JP Morgan. Your line is open. Good morning, guys. Thanks for taking my question. A couple of questions. First, understanding that you could not actively market for second-line setting based on addition of QINLOCK to NCCN guideline, if that were to happen, how should we think about the opportunity that can open up? And do you believe that that will depend on the category of recommendation? Second, on DCC-3116, would you walk us through your thoughts on how you chose the 50 milligram BID dose as the go-forward dose? Can you also remind us of the profile, the AE profile at that dose? For vimseltinib, granted that overall response is the primary endpoint in MOTION, how should we think about the median duration of treatment, and what it means for the overall opportunity? Thank you. Hi, Daniel. Good morning. Thanks for your questions. Let me try and take those in turn, and I'll ask Dan and Matt Sherman also to comment on a couple of and add any additional color. Your first question was with respect to the potential for a listing in the NCCN guidelines for ripretinib for use in the second-line setting, which would be an off-label use. Just a couple of comments with respect to that. First, we have not seen any updates to the NCCN guidelines as of this morning. As we've shared previously, the data from the INTRIGUE study, which was our randomized phase III study in the second line versus Sutent, was submitted to the NCCN earlier this year, but we have not yet seen any modification to the treatment guidelines, and we don't believe that the panel yet has reviewed the application, at least not as it's been reflected in any update to the guidelines. As you know, there's some lag between the time of the meeting and the time when guidelines can be updated. In order for a physician to use the drug in the second line setting, assume that this off-label use is listed in the guidelines. Of course, the physician needs to be made aware of the data that use needs to be reimbursed by the payer, and then the physician would be in a position to be able to administer the product. Now, it's important to note that given that this is an off-label use of the drug or would be an off-label use of the drug, it's not a use that we can promote to and would promote to. So that's outside of label, and our promotion is limited to what is product's label. So I think it's too soon to tell first what updates to the guidelines might occur or when that might occur, and then what the subsequent impact in terms of actual use and practice in the market might be. Next on your question with respect to DCC-3116, I'll turn that over to Matt to address the selection of the 50 milligram BID dose as the initial dose for the combination dose escalation. Yeah. No. Thanks, Steve, and good morning, Daniel. Yeah, so as we noted today, we're very pleased with completing the enrollment in the monotherapy dose escalation part of the 3116 study. Of course, the three-dose cohort that we tested from 50 milligrams up to 300 milligrams did not reach a maximum tolerated dose. We also did not see any dose-limiting toxicities there. We felt that all dose levels were well tolerated in patients, in particular the 50 milligram dose level. Most of the adverse events were grades 1 or 2. There were no grade 3 adverse events. We also were able to demonstrate that at the lowest dose level, we were able to have good target engagement with inhibition of the phosphorylation of ATG14. It is one of the immediate downstream markers of ULK kinase inhibition. Taking all the data together, selected a 50 milligram BID dose level to initiate the combination dose escalation cohorts. As you know, Daniel, we announced this morning that the first patient in the combination dose escalation has been treated. We're really pleased with the rapid progress that we're making in moving into the combination dose escalation part of the study. Then the next question, I believe, Daniel, related to vimseltinib and response rate as being the primary endpoint in that study. I think your other embedded question was just around duration of treatment that we've seen so far as reported at ESMO, and how we think about that relative to the potential opportunity in the market. What I'd ask is perhaps, Dan, would you like to comment on that component of Daniel's question? Yes, absolutely, Daniel. Good morning. Thank you for the question. We think that duration is going to be a very important aspect of ultimately the benefit the patients receive from drugs in this space, as well as ultimately the commercial opportunity. We're really encouraged with what we've seen so far. We think it's really all very consistent. By that I mean, when we look in the claims data of patients who are treated with TGCT today, we see a meaningful difference in the duration of therapy between the drug that is used predominantly, albeit off label, which is imatinib. We see an average duration of therapy of around 18 months. When we look in the same dataset at pexidartinib, we see a much lower duration of therapy, somewhere around 8 months. We think that may be tied to the well-known safety concerns associated with the pexidartinib profile. When we, you know, look to the imatinib duration of therapy as somewhat of a benchmark, so to speak, that 18 months, and then we think about the duration that we're seeing maturing in our clinical studies, the most mature being the earliest dataset in the phase I escalation cohort, we see a 17.5-month median treatment duration thus far. We see this all sort of maturing in a way that looks really favorable, good for patients, and ultimately, we think, good for the market opportunity. Got it. Thank you very much, and congratulations on the progress. Thanks, Daniel. Our next question comes from Christopher Raymond with Piper Sandler. Your line is open. Good morning. This is Nicole Gabreski on for Chris. Thanks for taking our questions. I guess maybe just two from us. Just on phase I-B combo dose escalation cohorts for 3116, can you just talk a little bit about maybe what signal you need to see in each cohort to deem it successful as you move forward in development? Then just around your newly nominated pan-RAF inhibitor, I guess this is becoming a crowded space, so I'm just wondering, maybe if you could provide a little more color around the properties that you kind of alluded to differentiating 3084 from other pan-RAF inhibitors in development. Thanks, Nicole. Thanks for the two questions. I'll ask Matt to take your first question with respect to phase I-B part of the 3116 study, and selection of dose and what we're expecting to see, what we would hope to see in the combination dose escalation part of the study. Then I'd be happy to take the pan-RAF question that you tabled as well. Yeah. Hi, Nicole. Yeah, thanks for the question. You know, as we talked about, we're initiating the combination dose escalation cohorts with 3116 in combination with the three partner drugs that we initially selected, the 2 MEK inhibitors, trametinib and binimetinib, and the KRAS G12C inhibitor, sotorasib. As we also announced today, we enrolled the first patients in both combination dose escalation cohorts. I'm very excited about, you know, enrolling the complete cohorts and escalating to a safe dose in combination. Once we have the data from the combination cohorts, we'll move into tumor-specific expansion cohorts, and those will be defined both by mutation status and specific tumor indications. At that time, we'll be able to talk more about the signals that we'll be looking for to show proof of activity in those tumor-specific mutation-driven tumors. Then Nicole, with respect to your question on the pan-RAF inhibitor, we're certainly really excited to have nominated our development candidate from our pan-RAF program, and the number as we noted for that is DCC-3084. This is reflective, we believe, of how productive our research engine is, so we're excited to bring this next product forward. You're right. The landscape among pan-RAF inhibitors, there are a number of pan-RAF inhibitors that are in development. We're excited about the preclinical data that we've generated so far. We intend to publish that at a medical meeting early next year as we flesh out further and share further what the profile is of 3084 and how we view it as potentially being best in class. I think as Matt mentioned, during his prepared remarks, we think another element of differentiation could well be the favorable pharmaceutical properties that we see with DCC-3084. Again, we'll have more that we can talk about as we share the preclinical data at a medical meeting next year. Great. Thanks for taking the question. Our next question comes from Eun Yang with Jefferies. Your line is open. Thank you. Question on vimseltinib and QINLOCK. Vimseltinib, I think, historically, previously, you've said that enrollment update by end of this year, so we are expecting more definite kind of update as it's, you know, in terms of enrollment completion rather than continuing enrollment. Can you give us a little bit more color there? Second question is on QINLOCK on NCCN guidelines update for second-line GIST. Historically, when you look at the oncology products, when the product label the NCCN guideline update is including off-label use, have you seen in general uptake in sales? If so, what kind of what percentage of sales uptake should we expect? Thank you. Good morning, Eun. Thanks for the two great questions. Let me take the vimseltinib-related question, then I'll ask Dan Martin to comment on your NCCN guideline-related question. First for vimseltinib, we remain really pleased with the pace of enrollment in the MOTION Study. As you'll recall, this is a 120-patient study that we're enrolling in patients with tenosynovial giant cell tumor. It's a placebo-controlled study. We've previously shared that we were able to enroll about 40 patients over six months in the phase I/II study. Some of that data, of course, we presented at the ESMO conference back in September. That pace of enrollment was once we had gotten to site activations for the study. As we reflect on where we are so far year to date with the MOTION Study, we continue to be very pleased. As we've said, and as you alluded to, we'll provide a more fulsome update in the coming couple of months as we're able to better project when we might get to last patient in the study. We've been gratified to see the number of patients that are in the community who are seeking a systemic treatment option, and we think that's reflective of the significant unmet medical need today in the U.S., where there's only one approved product, pexidartinib, and then of course, outside of the U.S. and in Europe in particular, there are no approved products for systemic treatment for this disease. We're pleased to see these patients finding their ways to our sites that we've activated for the study, and enrollment continues at a rapid pace, which we're really pleased with. I'll go ahead and jump into Dan. Eun, thanks for the question on the guidelines. So a couple thoughts. First, as we've laid out previously, after the two ASCO presentations last year on the INTRIGUE data, one at the virtual plenary and then at the ASCO meeting itself, we have gotten a lot of feedback from KOLs. Regarding the fact that they interpret this data as showing clear activity for the product in the second line, you know, comparable efficacy and really better overall safety profile than Sutent. They've told us that, you know, they find this data really interesting and supportive of the overall QINLOCK clinical profile and something that, you know, ideally might be considered for use in the second line setting. The challenge with this, of course, is that although we submit the data to the NCCN, as all companies do, number one, we have no way to know whether or not it may make its way into the guidelines, and we'll just have to see how the committee chooses to include it or not. Then importantly, you know, we've underscored this really consistently, and I'll just do it again here. You know, this is something that would be off label and therefore we can't and won't promote it. Steve has mentioned that, you know, there are a number of important steps to sort of what impact this could have in the marketplace. You know, physicians have to be aware of the data, aware of the update to the guidelines, and there's a desire to use and payer dynamics. We won't be promoting or driving any of that. We'll just have to see, number one, if there is a guideline update, and then number two, you know, how it plays out in the marketplace if there is. Your question about other products in the space in the oncology space and what kind of impact off-label listings had. It's really hard to make a direct comparison because so many different treatment areas are so different, has a lot to do with how the guidelines are updated. It has to do with what other alternatives may exist in those therapeutic areas. It's really tough to say that, you know, this XYZ is how it typically plays out and what we would expect here. You know, we're keeping an eye on it, and like you, we're eager to see what, if any, updates may be forthcoming. Thank you. Our next question comes from Michael Schmidt with Guggenheim Partners. Your line is open. Hey, good morning. This is Paul on for Michael. Thanks for taking our question. I guess first, following up on your ESMO data update for vimseltinib, just wanted to get some more color on the CPK increases that you observed in the study and perhaps how they compare with, you know, what's been observed with other CSF1R inhibitors or MABs. Do you see sort of any risk perhaps to more significant muscle tissue damage depending on patient baseline characteristics? Just would be great to get your thoughts here. Secondly, on 3116, you know, you've sort of shown some pre-clinical data showing combinations with osimertinib. I just wondering if you have any current plans to investigate EGFR mutant patients and sort of where that segment plays into your strategy. Sure. Thanks, Paul. Thanks for the two questions. I'll be happy to take the DCC-3116 question first, and then I'll ask Matt to take your question related to vimseltinib and CPK elevations. The way we think about our ULK inhibitor DCC-3116, which as you know is first in class, first into the clinic, which we believe is really exciting and gives us a key advantage as we explore a variety of different combination partners. As we've presented at medical meetings, gosh, over the course of the last two years, we see very broad activity of inhibiting autophagy pre-clinically, when combined with either MAP kinase pathway inhibitors or receptor tyrosine kinase inhibitors like osimertinib. There's a whole host, a whole range of possibilities for combination. The task ahead for us is as we're doing now with phase I-B study, is to begin to prosecute each of those. As we go through the preclinical data and we prioritize what we're going to pursue, then bringing that forward into the clinic and exploring those combination partners clinically to see what we see. There'll be more to come from us in terms of additional future combination partners with the program. While I can't comment specifically on osimertinib, I think that's a great example, osimertinib is of a receptor tyrosine kinase inhibitor where we see preclinical very strong effect when used in combination with 3116. That just suggests to us the potential very broad applicability of this approach to targeting the autophagy escape mechanism in cancer generally. Matt, do you wanna take the vimseltinib CPK question? Thanks, Steve, and, you know, thanks, Paul, for the question. As we noted before, you know, the elevations of CPK that we've seen in patients treated with vimseltinib is due to, inhibition of clearance of the, protein or enzyme from the blood. As we know, the resident macrophages within the liver are called Kupffer cells, and they are responsible for clearing normally circulating proteins and enzymes from the blood. In the context of inhibiting those, resident macrophages with the CSF1 receptor inhibitor such as vimseltinib, then there's slower clearance of those enzymes or proteins from the blood leading to, asymptomatic, just laboratory elevations of those protein levels such as CPK. This is denoted as a class effect across all the different small molecules and even the biologics, directed against the CSF1 receptor. You know, felt very comfortable with the safety profile that we've seen to date in the phase I/II program. Certainly as we talked about this morning, you know, very pleased with the progress we're making at the moment in the phase III MOTION study. Great. Thank you. Our next question comes from Tyler Van Buren with Cowen. Your line is open. Good morning. It's Brittany Woods on for Tyler. Thank you for taking our questions, and congrats on all the execution this quarter. On the phase III MOTION trial, can you provide any additional color on how site activation is proceeding and also potentially on the balance of U.S. and ex-U.S. sites? Also on the potential of a NCCN recommendation for second-line QINLOCK use, would that affect your commercial strategy at all moving into 2023? Thank you. Yeah, thanks for the questions, Brittany. Good morning. I'll be happy to take the first question with respect to the MOTION study, and then I'll turn it over to Dan just to comment on the NCCN second line study. First, with respect to the MOTION study, as we noted earlier today, in our prepared remarks and also in the release, we're really pleased with the pace of enrollment for MOTION and how that's progressing. As I said a little while ago, I think it's reflective of the strength of the data that we've presented so far from the phase I, II, and I think it's reflective of the unmet need in a variety of different geographies, in terms of, you know, absence of good systemic therapies being available to treat these patients. While we haven't commented specifically on the exact number of sites that are open, certainly on ClinicalTrials.gov, it's listed and there are 32 sites that are now open for the MOTION study. We're pleased with the number of patients that we've seen enrolling from those sites. We have a number of sites in the U.S., a number of sites in Europe as well, and we have seen patients from both of those geographies enrolled on study. We're pleased with the progress we're making, and we're looking forward to providing a more fulsome update, as I was saying, in response to Eun's question, once we have some line of sight to last patient in the study and when that might occur. Dan, do you want to comment on the NCCN question? Sure, absolutely. Just to confirm, I wanna make sure I heard the question correctly. The question was, would a listing change our commercial strategy in 2023? Yes. Thank you for the question. The short answer is no. The point that we try to underscore each time is that it's really important to note that this would be an off-label use even if listed in the NCCN guidelines. From a commercial point of view, we have to always make sure we are really careful about our promotion and we stay on label. We can't and won't promote any off-label listing in the guidelines. Our commercial strategy in 2023 would continue to be focused on optimizing the opportunity within the fourth line setting and continuing to execute, driving really high awareness, really high share of voice in the space, maintaining really high attribute rating for the product among GIST treaters, continuing to make sure that QINLOCK is viewed as a standard of care in the fourth line as it is today, and making sure that we work to find every possible on-label patient that we can. That'll continue to be our focus as it relates to QINLOCK in the US. Our next question comes from Peter Lawson with Barclays. Your line is open. Steve, thanks for taking my questions. I joined late, but I apologize if this came up. Just around the EU revenue growth. Quarter-over-quarter, it's flat. I wonder if you can kind of talk through any of the underlying dynamics and kind of how it looks for 4Q. Thank you. Yeah, good morning, Peter. It's Steve. I'll start off and then ask Margarida also to comment on the trend in the quarter versus what we've seen earlier this year. First, just as a reminder, we received our European approval at the very end of last year. As you'll recall, the first market that we were able to launch in commercially was Germany. That's where our launch has been underway principally so far this year. We've also been able to provide QINLOCK to patients, to sell QINLOCK for patients in France under a post-approval paid access program. That has also contributed to our European revenue. Looking forward, as we noted in the prepared remarks today, we've now submitted for reimbursement in Italy. We've undertaken the same process in Spain. We also previously noted that we had submitted to NICE for England and Wales. We're continuing to make progress across other territories in Europe where we have to go through a pricing and reimbursement process. It's likely that those processes will conclude in the coming year. This, as you know, can take quite some time, particularly in southern European markets, to get to market access, to get to a pricing and reimbursement approval. As we look over the medium term, we're certainly really excited about the opportunity to get QINLOCK to these patients in the five largest markets across Europe, which represent about the same size of the population of the United States. Epidemiology we expect to be the same number of GIST patients in that territory. Once we're able to get to market access, we would then be able to unlock that opportunity for the company and also for patients to get access to QINLOCK. Margarida, do you wanna comment on some of the specifics in terms of what we saw in the quarter? Sure. Thanks, Steve. Let me start by saying that it is very gratifying to see how well QINLOCK is being received in Europe, mainly in Germany, which is the only country we have launched so far, and where we continue our growth trajectory. Specifically on Q3 performance, so net revenue in Europe was higher in Q3 despite the summer period and also despite the FX headwinds which aggravated in Q3. However, let me say that the revenue in the distributor markets outside of Europe was lower when compared to Q2, so impacting the overall number for Q3. Thank you. Just digging into that. For Germany, do you think you've topped out on Germany and/or has there been kind of weakness in France? Just curious on what the underlying dynamics there for the kind of flat quarter-over-quarter. Sure. Thank you for the question. We continue our in launch mode in Germany, if we can say like that, and growing both in terms of patients under treatment with QINLOCK and in the number of prescribers. I should also add that the dynamics in terms of data access in GIST in Europe are not great, but I can tell you that the strong results so far speak to the exceptional clinical benefit of QINLOCK in the fourth line setting, the high unmet medical need and the hard work of the team in successfully executing our launch strategy. It is also important to note that we continue advancing with our price negotiations in Germany, and naturally the final price that we will be able to achieve will impact our net revenue in the future. Gotcha. Thank you so much. You're welcome. Our last question comes from Bradley Canino with Stifel. Your line is open. Good morning. One question on QINLOCK and one on vimseltinib. Looks like two price increases this year for QINLOCK. Can you comment on how much has been captured into net price? And then just the mix of price and volume growth that's attributed to the quarter-over-quarter U.S. growth for 2022. And then I'd like to ask any comments you can provide on European regulatory interactions for vimseltinib. You know, I do think you've shown that your drug is differentiated on the safety profile. We've heard really strong U.S. KOL feedback, but the EMA's CHMP did reject TURALIO both for safety and efficacy, you know, quoting that the tumor shrinkage didn't establish the activity for clinical benefit. So just any comments there about the opportunity in the E.U. would be great. Thank you. Great. Good morning, Brad. Thanks for the question. I'll ask Dan to take the QINLOCK related question first. Yeah. Cover this briefly. Thanks for the question. We have taken two price increases this year, one February 1st of 4.85% and one July 1st of 3.15%. The overall impact there is approximately 8% on a gross perspective. We haven't ever spoken exactly to what our gross to net numbers are each quarter, but we've always said that we have experienced it and continue to experience it being in the 16% range on average. You can use that as a metric there to get to the net. From a year-over-year, the 23% that we quoted, about half of that can be attributed to volume growth, and about half of that can be attributed to favorable changes in the net price, and the PAP percentage year-over-year. Great. Thanks, Dan. Brad, to your question specifically with respect to vimseltinib and how we think about the profile of the drug and how we think about the European opportunity, let me just comment on that. I mean, our definition, the way we're viewing the profile of the drug and how we think regulators will view it is really in three categories. Certainly about efficacy, the ability of vimseltinib to shrink tumors in patients. We believe we very clearly demonstrated that we have a potent and selective inhibitor that's highly efficacious based on the data that we showed at ESMO. The second is around tolerability. As you noted, that's incredibly important in this patient population, and we believe that we've demonstrated again also at ESMO, that vimseltinib is well tolerated. The third category is a different measure of efficacy, and that's patient reported outcomes. As you will recall, at ESMO, we reported for the first time some of the PRO data from the study from the phase I-II experience, where we see a meaningful impact on measures related to patient reported outcomes. We think that's going to be very relevant to European regulators. We think that will be relevant certainly to patients and also to prescribers for the product. Our focus is on making sure that we have a profile based on the MOTION study, which we're now conducting, that will allow us to provide the evidence that's going to be required to be successful in the U.S. market, also in Europe and in other territories around the world. While we don't comment specifically on regulatory interactions, I can say that we're pleased with the feedback that we've received on the regulatory front for the vimseltinib program, and that all was taken into consideration as we designed the MOTION study and launched that study. There are no further questions. I'd like to turn the call back over to Steve Hoerter for closing remarks. Great. Thank you, Michelle. I just wanna thank all of you for joining us on today's call, and thanks for your continued support of the work that we're doing here at Deciphera. We look forward to continued progress this year, and I hope you have a great rest of your day. This concludes the program. You may now disconnect.