SpringWorks Therapeutics, Inc.

After the speaker's remarks, there will be a question and answer session. Please limit your questions to one. Thank you. I would now like to hand the conference over to Samantha Sandler, Senior Director of Investor Relations at SpringWorks Therapeutics. Samantha, you may now begin the conference.

Thank you, and good morning, everyone. Welcome to SpringWorks Therapeutics' second quarter 2024 earnings conference call. This morning, we issued a press release which outlines our financial and operational results for the second quarter. You can access the press release as well as the slides that we will be presenting today by going to the Investors and Media section of our website at www.springworkstx.com. Joining me today are Saqib Islam, Chief Executive Officer, Bhavish Asher, Chief Commercial Officer, Dr. Jim Cassidy, Chief Medical Officer, Frank Perrier, Chief Financial Officer, and Dr. Badraveen Idrees, Chief Operating Officer. Before we begin, I would like to remind you that some of the statements made during the call today are forward-looking statements that are subject to a number of risks and uncertainties. This may cause our actual results to differ materially, including those described in our reports filed with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements, and SpringWorks disclaims any obligation to update such statements. I will now turn the call over to Saqib.

Thank you, Sam, and thank you all for joining this morning. I'm pleased to share our second quarter results and how we are delivering on our objective to make a profound impact on the lives of patients with devastating diseases. Starting with OXIVIO for patients with desmoid tumors, we are encouraged by the strong momentum of our U.S. launch. In the second quarter of 2024, we reported $40.2 million in net product revenue. This robust and continued growth is driven by the transformative clinical benefits from OXIVIO, high demand from patients and physicians across treatment settings, and strong commercial execution. Since our FDA approval last November, OXIVIO has rapidly become the standard of care systemic therapy for patients with desmoid tumors. As Bhavesh will discuss in more detail, we are seeing steady growth in new patient starts, as well as strong persistence from those who previously initiated OXIVIO therapy. Importantly, patients are reporting rapid and meaningful symptomatic relief, which is contributing to their overall improved quality of life and their enthusiasm for OXIVIO for their treatment. We are pleased with our early launch experience and believe that we have only reached a small proportion of people with desmoid tumors who can benefit from OXIVIO. Our confidence in the overall patient population has continued to increase as we have gained further insights from the launch and from emerging desmoid tumor specific claims data. our conviction remains high in the opportunity we have in front of us to serve an increasing number of desmoid tumor patients. Turning to our investigational MEK inhibitor, mirtimetinib, in the second quarter, we completed our NDA submission to the FDA for the treatment of children and adults with neurofibromatosis type 1 associated plexiform neurofibromas, or NF1PN. Our NDA submission is based on positive data from our Pivotal Phase 2b Renew Trial, which support the potential for miridometinib to be a best-in-class therapy for both children and adults living with these devastating lifelong tumors. There is a substantial unmet need for the approximately 40,000 people living with NF1PN in the United States alone, 30,000 of whom are adults and 10,000 are pediatric patients. Challenges with administration and tolerability limit the use of currently available options for children, and there are no FDA-approved therapies for adults. We look forward to working with the FDA throughout our NDA review process and to advancing our commercial preparations in anticipation of our second medicine introduced to patients in 2025. We are also excited about the opportunities in our emerging portfolio. We have several important efforts in development to serve additional patient populations with high unmet needs, including patients with ovarian granulosa cell tumors, multiple myeloma, and MAPK mutant solid tumors. In addition, we recently began enrollment in our phase one study of our investigational TID inhibitor, SW682, in hippo mutant solid tumors. which represent up to 10% of cancers. Finally, we have durable IP protections for our lead molecules and a robust balance sheet that we expect to fund us through profitability. I'll now hand the call to Bhavesh to discuss our progress with Oxivio for patients with desmoid tumors. Bhavesh?

Thank you, Saqib. I'm happy to share an update on the U.S. launch of Oxivio. Two full quarters into our launch, Oxivio is already the most prescribed systemic therapy for adults with desmotumors. As Saqib highlighted, in the second quarter of 2024, we generated $40.2 million in net product revenue, driven by strong demand for Oxivio by patients and physicians across treatment sites, real-world experience of Oxivio's meaningful benefits, and focused commercial execution in delivering the first and only FDA-approved medicine to the desmoid tumor community. We're seeing robust adoption, with broad use aligned with our FDA-approved label, including in newly diagnosed patients and in those seeking their next line of therapy after unsatisfactory outcomes with previous interventions. Physicians at centers of excellence were strong early adopters of OXIVIO. The majority of them have now treated multiple patients and continue to add new patients. We're also pleased with the continued uptake amongst physicians and other academic and community centers, where we are also seeing steady new patient starts. In addition, we've received consistent feedback from both patients and physicians on Oxivio's life-altering impact. Patients are experiencing rapid and significant symptom relief, notably pain reduction, helping them to get back to their daily lives. Enhancing the patient experience with Oxivio has been an area of focus this quarter. We're pleased with the successful introduction of the 150 milligram and 100 milligram strength Oxivio tablets in convenient blister packaging. The new product format has seen strong adoption to date, validating the importance of this innovation for patients. Patients prescribed OXIVIO continue to have broad access with reimbursement across payers. Commercial and government insurers are broadly reimbursing OXIVIO, and formal coverage policies are in place for over 90% of commercially covered lives. Across the payer landscape, there is clear recognition of the clinical value of our medicine as an NCCN Category 1 preferred treatment. And in June, the Desmoid Tumor Working Group Guidelines were published in JAMA Oncology, highlighting Oxivio's incorporation into the treatment algorithm as the first and only approved drug for Desmoid tumors. In just seven months on market, Oxivio has become the systemic standard of care for Desmoid tumors based on our analysis of prescription data, and we're excited to leverage this position of strength to reach many more patients with this disease. We've also continued to receive highly positive feedback from prescribers and patients on their experiences with OXIVIO. In a recent survey of 110 oncologists, 95% of OXIVIO prescribers expressed satisfaction with their experience. More than 85% of prescribers prefer it over off-label systemics, which are known to have inconsistent efficacy and tolerability challenges, further supporting OXIVIO's position as the systemic therapy of choice. In addition, most physicians said that they are likely to use Oxivio as a frontline treatment, indicating treatment with Oxivio at the earliest opportunity for their adult patients. Further, we're hearing consistent feedback from patients of profound symptom relief on Oxivio, including patients experiencing rapid and meaningful improvements in pain within days of initiating treatment. The strength of the real-world feedback which is consistent with our clinical trial experience, will continue to solidify OXIVIO as the standard of care systemic treatment for patients with desmoid tumors. Turning now to the opportunity we see ahead of us. There are up to 1,650 newly diagnosed patients annually. Our market research supports that the vast majority of physicians are likely to use OXIVIO as a frontline treatment. And we're already seeing uptake of OXIVIO as the first intervention. Our research has previously pointed to up to 7,000 actively managed patients in the U.S. each year. Our early launch results, as well as desmoid tumor-specific ICD-10 claims data, have continued to validate the size of this currently addressable patient pool. And we now view this estimate as conservative. The role of systemic therapy is continuing to increase among patients who require active treatment, with surgery being deprioritized in treatment guidelines. With OXIVIO as the first choice systemic, we're confident that there continues to be a substantial opportunity for growth in this patient population. In addition, there's a sizable diagnosed prevalent population of 30,000 people overall. We know that the majority of desmoid tumor patients receive active intervention over the course of their disease. And hence, a meaningful proportion of these patients who are currently on the sidelines could potentially be addressed with a new treatment option. We have seen robust adoption to date and continue to have strong conviction in the sizable opportunity ahead of us to continue serving adults with desmoid tumors at all stages of treatment. Our success thus far positions us well for continued momentum in the second half of the year and beyond. We're gratified to have earned the advocacy of desmoid tumor experts through their collaboration in the DEFY study, as well as engagement following the approval of OxyVial. Our commercial efforts aim to amplify their voices to educate and improve outcomes for patients. This comes in the form of providing opportunities for these leaders to educate the broader desmoid tumor community, including physicians, nurses, advocates, patients, and caregivers, on guideline-recommended treatment approaches. Importantly, this includes educating on the role of systemics, the limitations of surgical intervention, and the availability of OXIVIO as an FDA-approved and NCCN Category 1 preferred treatment option. Education and peer-to-peer information and experience sharing are critical avenues to increasing awareness of OXIVIO and will continue to support increased breadth and depth of prescribing. Continuing to address the needs of patients also remains paramount, and we're highly focused on supporting positive experiences with OXIVIO. In mid-May, we successfully introduced our 150-milligram and 100 milligram strength tablets in convenient blister packaging. This new product format was developed as an innovation for patients to increase convenience and adherence by reducing the daily pill intake and simplifying morning and evening dosing. We have seen a strong transition to this new format through the second quarter and expect this transition to continue over the next three months. Additionally, we're expanding our educational resources and delivering best-in-class patient services through SpringWorks Care Connections to further support the treatment journey with OXIVIO. We also continue to generate data to support the strong clinical profile of OXIVIO and are advancing our efforts to expand OXIVIO into additional geographies. In the second quarter, we presented additional data from our Phase III to V trial at ASCO that reinforced the robust efficacy and manageable safety profile of auxilio, including in hard-to-treat subgroups, such as patients with characteristics associated with poor prognosis, and those with APC mutations, which can be a more aggressive form of the disease. In an oral presentation at ASCO, DeFi was also showcased as an exemplar of one of the most comprehensive assessments of ovarian function in an oncology clinical trial to date, and a best practice for evaluating a drug's effect on ovarian function for future cancer trials in accordance with ASCO guidelines. This analysis included updated data on investigator-reported resolution of ovarian toxicity in DeFi, which further supported the transient nature of ovarian toxicity in both the majority of patients who stay on auxilio therapy and all those who stop treatment for any reason. Turning to upcoming milestones, we're working closely with the European regulators as they review our marketing authorization application, and we are excited by the potential to receive approval from the European Commission in 2025. We also look forward to sharing long-term follow-up data from DeFi at a medical conference before the end of the year. In our phase one and phase two studies, patients remained on OxyVial for a median of over four years, and at the time of the phase three DeFi trial data cutoff, median treatment duration was approaching two years. With these long-term follow-up data from DeFi, we plan to provide an update on the continued anti-tumor activity and overall clinical benefit provided by Alcibio with longer durations of treatment. The ability for patients to stay on therapy is critical given the persistent morbidities associated with this disease. And we believe these longer term results from Defy will further support the potential for extended treatment durations. I'll now turn over to Dr. Jim Cassidy, our Chief Medical Officer to discuss the progress we're making with our MEK inhibitor, Mirdometinib, for children and adults with NF1PN. Jim?

Thanks, Babesh. I'm glad to provide an update on our progress developing Mirdometinib as a potentially best-in-class therapy for patients with NF1PN, which is a highly morbid and lifelong disease that affects both children and adults. To start, there is a significant opportunity to improve outcome for these patients. There are approximately 100,000 people in the United States living with NF1. These individuals have a 30% to 50% lifetime risk of developing plexiform neurofibromas, which are tumors that grow along peripheral nerve sheaths and can cause severe disfigurement, pain, and functional impairment. We estimate that there are approximately 40,000 patients with NF1PN in the U.S. today, the majority of whom are adults who currently do not have an approved therapy, As there is no specific demographic link for this disease, we estimate that there are a proportionate number of people living with NF1PN outside of the United States as well. While systemic therapies are treatment of choice and MEK inhibitors have been clinically validated as a class in this indication, there are no formal treatment guidelines, and our market research shows that only a small portion of NF1PN patients have been treated with a targeted therapy. We have done considerable work to understand the disease state, current treatment paradigm, and physician and patient preferences. And taken as a whole, our research supports that patients are in need of new options. This is illustrated by a highly fragmented treatment landscape with significant use of off-label therapies, even in pediatric patients for whom there is an approved medicine. People living with NF1PN have substantial needs that are not met by current options. and bringing to market a new systemic therapy could allow many more patients to be treated. As we'll discuss, the positive results from our pivotal phase to be renewed trial support the potential to be a first-in-class therapy for adults with NF1PN and the best-in-class option for pediatric patients. The renewed results were presented at three medical conferences in the second quarter, including during an oral session at ASCO. These presentations are improving awareness and building enthusiasm for our positive results amongst the physician community. The efficacy data across both adult and pediatric cohorts in Renew showed significant reductions in the size of PN tumors with robust objective response rates confirmed by blinded independent central review. In addition, we saw very deep responses that have not been seen before in published studies of this disease. The majority of patients with a confirmed objective response experienced a tumor reduction of greater than 50% and reductions of up to 90% were seen in both cohorts. This is particularly significant when you consider the hard-to-treat patients that were enrolled in our study. Importantly, physician feedback suggests that these are unprecedented data and have the potential to be a meaningful differentiator. In both children and adults, medimetinib demonstrated a manageable safety profile with low rates of grade three adverse events and low discontinuation rates due to AEs. We believe medimetinib's tolerability profile supports the potential for extended treatment duration, which is important in a chronic disease like NF1PN where there are high rates of recurrence after stopping therapy. In RENEW across both cohorts, the median time on treatment was approaching two years. with some patients on murdine metanib therapy for nearly four years at the time of the primary analysis. Nearly all patients that completed the treatment phase continued on therapy in the long-term follow-up portion of the study. The potential for murdine metanib to enhance patient quality of life is also very meaningful. Pain is a common symptom in NF1PN, and current clinical practice recommendations indicate that this is a critical factor in treatment initiation decisions. In many cases, the primary goal of treatment is improvement of such pain-associated morbidities. Pain was the most commonly reported baseline morbidity in the RENEW trial, so it's significant that both adults and children, including those with the most ability to take in pain, reported early, sustained, and clinically significant reductions in pain severity and pain interference over the course of methamphetamine treatment. Lastly, we believe that Mivimitinib's convenient dosing regimen, which provides a built-in treatment in the holiday and a pediatric-friendly dispersible formulation, could further optimize the patient experience and potentially enhance compliance. In Renew, children and caregiver reports were highly positive in this regard, with maximum acceptability scores for ease of swallowing and willingness to continue to take the dispersible tablets. The totality of the new data reinforces our belief that myrmidonib can address strong desire amongst both physicians and patients for a new therapy that offers robust tumor and symptomatic control, a manageable safety profile, and convenient dosing regimen, all of which we expect will enable patients to remain on therapy for an extended period of time. Looking ahead, we are making meaningful progress advancing myrmidonib towards potential regulatory approval in 2025. Mildometinib was granted orphan drug designation by both the FDA and the European Commission, and the FDA also granted fast-track and rare pediatric disease designations for NF1PN. We completed our NDA submission to the FDA at the end of June, and we anticipate announcing our PDUFA date in the coming weeks. We're also on track to complete the submission of our European marketing authorization within this half. In addition, there are new results will continue to be showcased at upcoming medical congresses, and we expect the results to be published in a peer-reviewed journal later this year. And now, Frank Perrier, our Chief Financial Officer, will discuss our second quarter financial results. Frank?

Thank you, Jim. I'll now summarize a few highlights from our second quarter 2024 financial results. Starting with revenues, we recorded $40.2 million of OXIVIO net product revenue in the second quarter. This brings our 2024 year-to-date OXIVIO net product revenue to $61.2 million. Our total operating expenses increased compared to the second quarter and the first half of 2023, driven by the commercial activities to support the US launch of OXIVIO and the anticipated U.S. launch of mirimetinib in both adults and children with NF1PN. We have a strong balance sheet supporting our clear path to profitability with $522 million in cash, cash equivalents, and marketable securities as of the end of the second quarter. Lastly, we have a durable operating plan designed to fund multiple global product launches and to enable the continued investment and expansion opportunities across our pipeline. With that, I'll hand the call back over to Sakim.

Thank you, Frank. As we've discussed this morning, we are very pleased with the continued strong momentum of our U.S. launch of Onsivio for adults with desmoid tumors and are working with urgency to bring mirtamentinib to children and adults with NF1PN. In parallel with these commercial efforts, we are enthusiastic about our emerging portfolio. Neurogastastat is being studied in a phase two trial in ovarian granulosa cell tumors, which is fully enrolled. These tumors account for approximately 5% of all ovarian cancers. And like desmoid tumors, this is a meaningful patient population for which there are no FDA approved therapies. In multiple myeloma, we've established clinical proof of concept for neurogastastat in combination settings with several BCMA directed agents. and are continuing to collaborate with a number of industry and academic partners to further this strategy. We're also pursuing expansion opportunities for miridometinib in several monotherapy and combination therapy settings. Promising data from a Phase I-II study of miridometinib in pediatric low-grade glioma were recently presented at the International Symposium on Pediatric Neuro-Oncology Meeting, and several combination studies are currently ongoing. including a trial with MAPcure's brimboraphanib in advanced solid tumors with MAP kinase mutations and with Bayesian's lifiraphanib in NRAS mutant solid tumors. Brimboraphanib is also being explored as a monotherapy in adults with RAS mutant solid tumors. And we're looking to confirm the efficacy signal we reported last year in the dose escalation study in several ongoing dose expansion cohorts. Additionally, SW682, our oral TID inhibitor, is now in the clinic. This program is designed to treat tumors with HIPPO pathway mutations, which can occur in up to 10% of cancers, including mesothelioma and head and neck cancer. We believe that there is a meaningful opportunity with SW682 for SpringWorks to develop a novel medicine for these cancers. Lastly, We are also advancing several internally discovered preclinical stage programs, and we look forward to sharing more about these efforts as they progress. To close, we are very pleased with our accomplishments in the first half of this year and have multiple milestones and data readouts ahead that we look forward to sharing. These include long-term follow-up data from our DeFi trial, which we believe will support the benefits of extended treatment durations with OXIVIO in desmoid tumors. It also includes initial data from our phase two trial of nirogastastat in ovarian granulosa cell tumors, and we expect the full renewed trial results to be published in a peer-reviewed journal. Our focus for the remainder of the year will be to continue building on OXIVIO's momentum in the U.S. while working to bring this medicine to patients in Europe and other geographies. to advance our regulatory and commercial preparations for mirtometinib in anticipation of serving patients with NF1PN in the U.S. and Europe, and to progress our diversified emerging portfolio in an efficient manner. We are confident that our strong foundation will support our continued success as we deliver on our mission to change the lives of people suffering from devastating diseases. As always, I would like to thank the patients and investigators who participated in our clinical trials, our patient advocacy partners and collaborators, and our team of spring workers. We're now happy to take questions. Operator?

Thank you. We will now open the call for questions. To ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. As a reminder, please limit yourself to one question each. Please stand by while we compile the Q&A roster. Our first question will come from Anupam Rama at JPMorgan.

Hey, guys. Congrats on all the progress. Just a quick one for me. What are you seeing from both new prescribers and repeat prescribers for OXIVIO and in the early innings, the wait and watch population that's coming in to seek treatment for OXIVIO? Thanks so much.

Thanks, Anupam. Babesh, I'll let you take that.

Yeah. So thanks, Anupam. On the repeat versus new, obviously we saw a good amount of new prescribers in the initial months of the launch. As you'd expect, we've started to see refills coming in at a regular pace from these initial starts, but supported by continued new patient starts from new patients being acquired in the second quarter as well. As you'd expect, the total proportion of business coming from existing patients versus new patient starts is increasing over time, and so that's a positive development. From a wait and watch perspective, we do know obviously that the proportion of the DT patient population is under active surveillance at any point in time. However, we do know that over 90% of these patients receive some active intervention during the course of their disease. Now, with the availability of the first and only FDA approved treatment, the opportunity ahead of us and supported by treatment guidelines which favor systemic therapy, supported by the positive experiences that patients and physicians are seeing with OXIVIO in the early innings of the launch, the opportunity ahead of us is to try and drive faster treatment for these patients under active surveillance. And so we do expect the proportion of active surveillance patients to be dropping over time.

Thank you. One moment for our next question. Our next question comes from the line of Yaron Werber from TD Cowan.

Great. Thanks for taking my question. Congrats also on a nice quarter. Maybe I have kind of a couple of interrelated questions. One, can you just give us a sense on inventories for the quarter for Xivio? And then secondly, just to follow on Anupam's question, One would imagine that the academic centers are probably the early adopters, and they're moving kind of quickly as patients are coming in to use Exivio. What are you seeing in the community? Maybe just give us a little bit of sense of kind of the breadth of usage. Thank you.

Bobby, I'll turn to you again for that.

Yeah, thank you.

So from an inventory standpoint, the overall impact of inventory in the second quarter was minimal. The stocking levels were generally aligned with the demand that we're seeing. And similar to prior quarters, inventory was not a key driver of performance this quarter. From a community dynamic perspective, first of all, I'll say that from, as we said in our prepared comments, there is a deeper pool of patients overall than we originally estimated. And we started to break into this aggregate pool of patients that are of greater than 7,000 actively managed patients. As you highlighted, we're pleased with the update in the Centers of Excellence. We saw breadth of prescribing in the early months of launch. We saw depth of prescribing in the second quarter. Specifically addressing your question around community, we've started to see good adoption in the community centers where we continue to drive breadth, but we still have an opportunity, right? With the broad pool of patients, we have an opportunity both to continue to drive breadth of prescribing but also those who experience, who do prescribe OXIVIO to drive depth of prescribing. Now, I'll highlight a couple of things in that regard. First of all, our ability to be in the right place at the right time for these community clinics has been significantly enhanced by the availability of the desmoid tumor-specific ICD-10 codes. And so we're able to direct our sales team to be in those clinics when a patient is available for treatment. And then secondly, the educational efforts that we're driving, both around the availability of OxyVial as the first and only treatment option for Desmond Tumor patients, but also treatment guidelines, which do favor systemic therapy, gives us confidence in the ability for us to drive depth in that community segment as well.

Thank you. One moment for our next question. Our next question comes from the line of Corin Johnson from Goldman Sachs.

Hey, good morning, guys. I guess you've talked a little bit about having some more visibility on this patient population given the ICD-10 codes and potentially as you kind of move to these blister packs in the forward. I guess as you look at that, where have you identified the pockets where you see kind of the greatest opportunity for near and intermediate-term growth? And what are you doing tactically to reach that patient population and keep them on therapy? And then I did want to ask also on myrtimetinib, maybe with the launch next year, where you see kind of like the low-hanging fruit with respect to initial adoption, and how should we think about the trajectory of the early launch compared to what you've accomplished here with Exivio?

Thanks, Corinne, for the series of questions, but we're going to try to answer all of them. I think as we think of myrtimetinib, we view that opportunity as actually quite meaningful. And as I think of low-hanging fruit, you know, I think we're very comfortable saying that this is an opportunity that is actually at least as large as what we see in Des Moines tumors. And that's driven by a number of factors. One, by the size of the patient population, right? We talked about 40,000 patients in the U.S. and a proportionate number outside the U.S. And a third of those are, excuse me, a quarter of those are pediatric and three quarters of those are adults. So the opportunity for us to have a best-in-class treatment for pediatric and a first-in-class treatment for adults we think gives us a meaningful target. Second, the physicians in this space actually themselves, even in the pediatric setting, believe that their patients are not being served as broadly as they could be. And so we think there's an opportunity there. And third, you know, you can use Coastal Lugo revenues, which now run rate just in the pediatric setting of about $500 million, annually as a proxy for the opportunity just in that one quarter of the market. And, you know, as you know, we're filing for both adults and peeds. So we think the opportunity, you know, beyond, I think, The low-hanging fruit implies that it's all easy. None of it is, but you've got a medicine that people are waiting for, an opportunity that is sizable, and data that we believe supports a potentially best-in-class profile for meridymetin at full distance each. Kavish, I'll turn to you to talk about Oxypio.

Yeah, no, I'd just reiterate a couple of the points. You know, first and foremost, we're fortunate to have with Oxivio to be in a position of delivering a drug with transformative benefit to Desmond Tumor patients, right? That is the foundation for the high awareness we have, the high satisfaction that we shared in the prepared comments, as well as the strong preference that we see amongst prescribers and patients supported by broad access by the payer community. So with just seven months on the market, we've become the systemic standard of care and the most prescribed systemic therapy for adult patients. with desmoid tumors, and so the opportunity for us is to continue to drive depth within the centers of excellence, as well as drive depth and breadth in the community segment, as I mentioned before. With the large pool of 7,000, more than 7,000 actively managed patients, we do see that we have a significant opportunity ahead of us to see continued growth for Auxillia.

Thank you. One moment for our next question. Our next question comes from the line of Peter Lawson from Barclays.

Great. Thanks for taking the questions. Thanks for the updates, Ron, and congrats on the progress. The first question is really just about the patient trends, how they've been looking month after month, and to go into July, and then whether you're seeing any patients discontinuing. Thank you.

Yeah, thanks for the question, Peter. I think, you know, we aren't seeing any, you know, exceptional discontinuations. It's what we would have expected from the DEFY study, and I think that gives us confidence going into, you know, not just the third quarter, but the fourth quarter as well. So, I think that the trend holds well. As Bhavesh highlighted, we think the patient pool is actually deeper than what we had originally estimated. And I think that portends well for the aggregate opportunity here. Fundamentally, Where we are perhaps most excited is the feedback that we're getting, though. You've got patients seeing deep, immediate, and persistent benefits to their pain. That is causing them to want to get on therapy and want to stay on therapy.

So we believe that the opportunity here continues to be sizable.

Thank you. One moment for our next question. Our next question comes from the line of Michael Schmidt from Guggenheim.

Hey guys, good morning and congrats on a strong second quarter result. Just to follow up on OXIVIO, as we think about the third quarter here coming up, some other products sometimes experience seasonality over the summer months. Is that something you may expect as well with OXIVIO? And then a follow-up on Mirtimetinib as we think about the launch next year. Obviously, you have already a product on the market. Do you expect initial switching from Kosalugo over to Mirtimetinib, or would you expect predominantly penetration into the currently untreated patients with NF1 as we think about that next year? Thanks so much.

Thank you, Michael. So I'll take the question. I'll pass to Dr. Idris to take the question. Yeah, I don't think that we're immune from seasonality. I think as we see in many other products, you know, I would expect to see some seasonality in the summer months. But obviously, you know, as we've said, you know, from the outset, we think the pool is deep and we think the opportunity is significant.

Patrick? Yeah, so with respect to our opportunity within NF1PN for I'll remind you that our NDA filing is for both pediatric and adult patients, the latter of whom represent three-quarters of the market and do not have an approved therapy. So we think there's quite a bit of white space there with respect to being able to serve patients who are previously untreated. Within the pediatric population, I think there will certainly be some patients who have been treatment experienced over the years that are seeking their next line of therapy, but our market research shows that that market is minimally penetrated as well with respect to systemic therapy. So we think there's a significant number of pediatric patients who are also looking for their first systemic therapy option when Mirabat becomes available.

Thank you. One moment for our next question. Our last question will come from the line of Alex Stranahan from Bank of America.

Hey, guys. Thanks for taking my question, and congrats from us on the strong print. Any framing you can provide around the focus of the longer-term follow-up data from DeFi later this year? And maybe one quick one, if I can sneak it in. Is your expectation that you will receive accelerated review for imidamantinib? Just to clarify. Thank you.

Thank you, Alec. I'll turn to Beverly for the answer. Sure. So with respect to the longer-term follow-up data, Alec, I'll remind you that at the time of our primary analysis, the median time on treatment for patients that were randomized to the niragastastat arm was just under two years, and the majority of those patients were remaining on therapy. And so what we hope to be able to share an update on later this year is certainly a more mature median time on treatment figure for nirogasostat-treated patients, as well as the trends that we see in terms of responses, how they evolve over time, and the benefits that we are seeing with a longer-dated data cut on the patient-reported outcomes as well. So, that's what, you know, we're gearing up to be able to share. And I'll remind you that in Phase I and Phase II, our median time on treatment was over four years in each of those studies. the opportunity to really present longer-term data.

Thank you.

With respect to any expectations on review timing and then review designations for the mere-dominant filing, we have not given any guidance on that topic. We'll be in a position to receive the PDUFA date from FDA about 60 days from filing, so that'll be sometime late in August.

Thank you. This concludes today's call. Thank you for joining. You may now disconnect.