Good morning, ladies and gentlemen, and welcome to the SpringWorks Therapeutics conference call to discuss the phase II-B ReNeu trial topline results. At this time, I would like to turn the call over to Samantha Sandler, Senior Director of Investor Relations. Good morning, and thank you for joining us today for the ReNeu trial topline results call. Slides to accompany this conference call will be posted in the Investors and Media section of our website at www.springworkstx.com. A recording of this webcast will also be made available on our website following this call. Before we begin, I'd like to remind you that today's discussion will contain forward-looking statements that involve risks and uncertainties, and that the company's actual results may differ materially from what is discussed during today's call. For a description of risk factors associated with investing in SpringWorks Therapeutics, please refer to our recent filings with the Securities and Exchange Commission. Leading the call today will be SpringWorks' CEO, Saqib Islam. Saqib is joined by our Chief Medical Officer, Dr. Jim Cassidy, and our Chief Operating Officer, Dr. Badreddin Edris. Following our prepared remarks, we will be taking questions. With that, I will turn the call over to Saqib. Thank you, Sam, and thank you, everyone, for joining our call today. It is our great pleasure to share the positive topline data from our pivotal phase II-B ReNeu trial, evaluating our MEK inhibitor, mirdametinib, in both pediatric and adult patients with Neurofibromatosis Type 1 associated plexiform neurofibromas or NF1-PN. We are very pleased that our trial demonstrated the potential for class-leading efficacy for both pediatric and adult patients, highlighted by our strong, confirmed objective response rates by blinded independent central review, unprecedented depth of response, as well as a differentiated tolerability profile that allowed patients to stay on therapy for extended durations of time. In addition, as you will hear, mirdametinib provided significant improvements in key patient-reported outcomes, including pain and overall quality of life. These data are very meaningful for the NF1-PN community, as they illustrate mirdametinib's potential to become a differentiated treatment option with a best-in-class profile for pediatric patients and the first approved therapy for adult patients with NF1-PN. Jim will walk through the data in greater detail, but first, I'd like to take a moment to highlight the significant impact that plexiform neurofibromas have on patients' lives and the substantial need that remains for this group of patients and their families. Turning to slide six, NF1-PN is a devastating disease. These tumors can grow aggressively along peripheral nerves and can lead to extreme pain, disfigurement, and other morbidities, including loss of mobility, compression of vital organs, and neurological impairments. Plexiform neurofibromas negatively impact the quality of life for patients and their caregivers, exacting a profound emotional and social toll on all those touched by the disease. NF1-PN affects both children and adults, though there are no approved treatments for the adult population at this time. Furthermore, plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, which are aggressive cancers with limited treatment options and a dire prognosis. These tumors are also very difficult to remove surgically, since their infiltrative growth pattern along nerves makes complete surgical resection unlikely. These operations are not only difficult to perform but also provide limited long-term benefit and can lead to permanent nerve damage and disfigurement. Systemic therapies are rapidly becoming the foundation of NF1-PN treatment, and MEK inhibitors as a class represent the most validated treatment option. There is currently one approved therapy for pediatric patients with NF1-PN. However, significant limitations remain with this therapy, including a suboptimal response profile combined with challenging tolerability, which makes it difficult for patients to stay on treatment. Together with daily fasting requirements, which are especially onerous on children and their caregivers, and the lack of a pediatric formulation, we believe that the data you will see presented today paints a clear and compelling picture for mirdametinib to be the leading therapy for plexiform neurofibroma patients of all ages. In addition, we know from our extensive market research that physicians and patients alike are seeking a treatment with an efficacy and tolerability profile that is suitable for long-term dosing. This is especially important since NF1-PN is a lifelong disease that can require chronic treatment. We believe that mirdametinib has the opportunity to address the substantial unmet needs that remain for both children and adults with NF1-PN. I will now turn the call over to our CMO, Jim Cassidy, to discuss the ReNeu trial topline data, and then to our Chief Operating Officer, Badreddin Edris, to discuss the overall opportunity and next steps for the mirdametinib program in NF1-PN. Jim? T hank you, Saqib, and good morning, everyone. I'm delighted to present the top line data from our pivotal phase II-B ReNeu trial. I'll begin with some quick background on the compound and the clinical study. Mirdametinib is an investigational oral, potent allosteric, small molecule MEK inhibitor that demonstrated antitumor activity and a favorable safety profile in an earlier phase IIa study in adults with NF1-PN. That phase IIa study utilized the same dose and schedule as ReNeu. Looking at slide eight, ReNeu is a pivotal phase II-B study, an open label trial that enrolled 114 NF1-PN patients, with 56 patients in the pediatric cohort and 58 in the adult cohort. The trial enrolled patients from 50 sites in the USA. Patients received 2 mg/m² of mirdametinib twice daily, up to 4 mg twice daily, on an intermittent dosing schedule of three weeks on, one week off. A pediatric formulation was available to study participants to aid with swallowing, and mirdametinib was dosed without regard to food. Patients were treated for up to 24 cycles of 28 days each, with the option to continue receiving mirdametinib in a long-term follow-up phase. The primary endpoint was objective response rate, as defined by a greater than or equal to 20% reduction in target tumor volume as compared to the baseline. All responses had to be confirmed before the end of the 24-cycle treatment phase and were assessed by blinded independent central review of MRIs per the REiNS criteria. As many of you know, blinded independent central review is considered the gold standard for response assessment in oncology, particularly in registrational trials, because it minimizes the potential for inter-reviewer variation and bias and provides greater objectivity than just investigator assessment. The REiNS criteria are an accepted clinical endpoint recommendation for NF1, that in prior discussion with the FDA, were accepted for the ReNeu trial. Secondary and exploratory endpoints included safety and tolerability, duration of response, time to response, and patient-reported outcomes such as pain, physical functioning, and quality of life. Slide nine summarizes the baseline demographics and disease characteristics for patients in ReNeu. Looking first at the pediatric cohort, the 56 patients included in the trial had a median age of 10 years. In the adult cohort, the 58 patients enrolled had a median age of 34.5 years. The study enrolled a difficult-to-treat population with significant morbidities. About half the patients in both cohort, cohorts had a target plexiform neurofibroma in the head and neck region, which have a higher likelihood of being disfiguring and impacting vital structures with continuing tumor growth. The most common morbidity at baseline in both the pediatric and the adult cohort was pain, which was reported in 70% of pediatric participants and in 90% of the adults. The ReNeu trial population also had a high rate of disfigurement, which was seen in approximately half of patients. Many patients also came into the study with motor dysfunction or airway dysfunction. In addition, this population had an unusually high rate of progressive tumors at entry, with 63% of patients in the pediatric cohort and 53% of patients in the adult cohort progressing at baseline. All of these features, taken together, underline that the study enrolled a difficult-to-treat population. Moving to the efficacy results and starting with the pediatric cohort. On slide 10, here you see a waterfall of the best percentage change in target volume from baseline. The data cutoff for this primary analysis was September twentieth. The confirmed objective response rate in the pediatric cohort, as assessed by blinded independent central review, was 52%. This does not include one patient who achieved a confirmed response after cycle 24 in the long-term follow-up portion of the study. While this response is not captured in the 52% overall response number, it does emphasize the importance of continuous long-term treatment in this disease. In addition to the overall response rate itself, we were also tremendously encouraged to see deep responses in the pediatric cohort, with a median best percent change of -42% in the target plexiform neurofibroma volume from baseline. Some of the responses were very deep, with a maximum tumor volume reduction reaching up to 90%. Not only was this depth of response much better than has been reported for any other agent in pediatric NF1 trials, but it's doubly encouraging given the hard-to-treat population enrolled in the ReNeu study. Overall, this combination of high objective response rate by blinded central review and deep tumor shrinkage highlight mirdametinib's potential best-in-class efficacy profile in pediatric patients with NF1-PN. Building on our robust overall response rate and deep responses, on slide 11, you can see that pediatric patients on mirdametinib had durable responses and were able to stay on treatment for an extended period of time. Here you can see that the median duration of treatment was 22 months as of the data cutoff, and the median time to first response was 7.9 months. Importantly, 45% of patients had their onset of confirmed response by the time of their first assessment at cycle five or approximately four months into treatment. Given the durability of these responses, the median duration of response was not reached. 20 pediatric patients remained on treatment at the time of data cutoff. Notably, 85% of patients who completed the treatment phase elected to enter the long-term follow-up phase. The number of patients rolling into the long-term follow-up phase is indicative of the enduring clinical benefit that these patients experienced, as well as the tolerability profile, and highlights their desire to remain on mirdametinib. Moving to slide 12. The ReNeu trial met several PRO endpoints in the pediatric cohort. At cycle 13, which was the pre-specified cycle for patient-reported outcome analysis, mirdametinib demonstrated statistically significant improvements compared to the baseline in PRO measurements, including the NRS-11 pain scale, pain interference indices, and the Pediatric Quality of Life Inventory. These results are meaningful since physicians, patients, and their caregivers point to quality of life as an area of high unmet need, with pain relief and symptom management among the top treatment goals when managing this disease. The safety data from the pediatric cohort is shown on slide 13. The majority of adverse events were grade one or two, with the most common adverse events being rash, diarrhea, and vomiting. Rates of grade three or four treatment-emergent adverse events were low across the board. Rash is a class-wide effect seen with MEK inhibitors that significantly impacts quality of life in adolescents and may lead to subsequent treatment discontinuation. With that in mind, it is notable that rates of rash across all grades and grade three or higher in the trial were lower than has been reported with other MEK inhibitors used to treat pediatric NF1-PN. Similarly, GI toxicity, such as diarrhea and vomiting, are a significant concern for other NF1-PN MEK inhibitors. Mirdametinib demonstrated low rates of all grade and grade three or more GI toxicities relative to other products in this class used for NF1-PN. These factors contribute to the low overall rate of adverse events, leading to dose interruptions, dose reductions, and discontinuations, as seen on the slide. This safety profile is consistent with our prior clinical experience with mirdametinib and continues to demonstrate a potentially best-in-class tolerability profile for a MEK inhibitor in this patient population. When combined with the robust efficacy data we just reviewed, we believe that we are well on our way to bringing the leading systemic therapy to children with NF1-PN. Now I will present the efficacy and safety results from the adult cohort. ReNeu is the largest and first potentially registrational study conducted in adults with NF1-PN. ReNeu is also the first and only company-sponsored trial that shows clinically meaningful efficacy in this group of patients. Looking at the waterfall chart on slide 14, 41% of the 58 adult patients achieved a confirmed objective response rate, as assessed by blinded independent central review, within that 24-cycle treatment phase of the study. In the adult cohort, there were two additional patients who had responses confirmed after that 24-cycle treatment period. Again, further emphasizing the importance of long-term treatment. Adult patients also showed deep responses with a median best percentage change of -41% in their target plexiform neurofibroma volume from baseline, which is similar to our pediatric cohort findings. Historically, it's been difficult to achieve deep responses in adult NF1-PN patients, so these robust volumetric changes demonstrate the unique activity profile of mirdametinib in this disease. As with the pediatric cohort, mirdametinib also demonstrated durable responses in adults, as seen on slide 15. Median duration of treatment was 21.8 months as of the data cutoff, and the median time to first response in adults was 7.8 months. 46% of patients had their first response by cycle five, and the median duration of response was not reached. Similar to the pediatric population, 84% of adult patients who completed the treatment phase chose to continue receiving mirdametinib in the long-term follow-up portion of the study here as well. Taken together, these data are the first to demonstrate an opportunity for encouraging durability of response in adult NF1-PN patients. Moving on to slide 16. Mirdametinib also demonstrated statistically significant improvements in key PRO endpoints at cycle 13 compared to the baseline, including pain and other quality-of-life measures in adult patients. This is the largest study done to date in adult NF1 patients and is the first pivotal study to show improvements in clinical outcomes, which are supported by PRO improvements in the adult population. The adult safety data is shown here on slide 17, reflecting the pediatric cohort, the majority of adverse events were grade one or two. The most common adverse events were rash, diarrhea, and nausea. Overall, 16% of adults experienced a grade three or four treatment-related adverse event, the most common of which being rash, and we saw no grade four rash events. We also found that 31.1% of adult patients had a dose interruption, 17% had a dose reduction, and 22% discontinued treatment due to an adverse event. Low-grade dermatological events, which typically occurred early in the study, were the most common adverse event leading to treatment discontinuation. After implementing additional supportive care and site education measures through an early protocol amendment, the discontinuation rate due to these skin adverse events was considerably reduced throughout the remainder of the trial. In summary, these topline data underscore the potential for mirdametinib to be a best-in-class therapy for children with NF1-PN and a first-in-class therapy for adults with NF1-PN. I'll now turn over to Badreddin to discuss the NF1-PN program highlights and next steps. Badreddin? Thanks, Jim. As we've highlighted today, NF1-associated plexiform neurofibromas are devastating for patients and their families. Based on our market research, 70% of physicians note that there is still a high unmet need for both children and adults suffering from this disease. Starting with the patient population on slide 19, there are approximately 100,000 people in the United States living with NF1. These individuals have a 30%-50% lifetime risk of developing plexiform neurofibromas. We estimate that there is a total addressable market of approximately 40,000 NF1-PN patients in the U.S. today, with approximately a 75%-25% adult-to-pediatric split within this prevalent population. Among this group of 40,000 patients, our market research shows that only a small fraction have been treated with a targeted therapy to date, and that bringing them to market a new systemic option could allow many more patients to be treated. Our feedback from physicians and patients has consistently underscored the strong desire for a new therapy to offer better tumor and symptomatic control, an improved tolerability profile that enables patients to remain on therapy, and a more convenient product experience that supports compliance. The right-hand side of this slide summarizes the key attributes that we believe differentiate mirdametinib from existing treatment options for NF1-PN. First of all, mirdametinib has the potential to be the first therapy approved for pediatric and adult patients with NF1-PN. This would be a significant advance for the NF1-PN community, especially for adult patients who do not currently have an approved treatment. Second, the results of the ReNeu trial demonstrate that mirdametinib has the potential to have a best-in-class efficacy profile in both children and adults. Using stringent, blinded independent central review criteria, both the pediatric and adult cohorts experienced robust anti-tumor activity. Mirdametinib demonstrated high objective response rates, depths of response that have not been seen with other therapies, durable activity across both cohorts, and multi-year durations of treatment. Furthermore, patients in ReNeu experienced significant improvement in patient-reported outcomes, including pain and quality of life. This represents the first time that such robust, positive quality of life data has ever been reported for the NF1-PN adult population in particular, and points to a potentially class-leading profile for pediatric patients as well. As a testament to the clinical benefit that these patients are experiencing, a high number of patients chose to enroll in the long-term follow-up portion of the study and remain on mirdametinib treatment today. Third, and complementing this efficacy profile, were low rates of grade three or higher adverse events, low rates of dose interruptions, and low rates of dose reductions due to AEs across both the adult and pediatric cohorts. Importantly, as compared to the only approved option for pediatric NF1-PN patients today, mirdametinib had lower rates of all grade and grade three or higher rash, as well as GI toxicity, such as nausea, vomiting, and diarrhea. We believe this highlights mirdametinib's potential best-in-class tolerability profile in pediatric patients with lower rates of treatment discontinuations due to AEs, and sets the standard for adult patients as well. With a lack of food effect to help support compliance and a dispersible tablet formulation for patients who have difficulty with swallowing, we are confident that mirdametinib has a differentiated profile for NF1-PN. Turning to slide 20. As a reminder, mirdametinib has been granted orphan drug designation by the FDA and European Commission, as well as fast track designation for NF1-PN by the FDA. Also, in July of this year, we were pleased that mirdametinib was granted rare pediatric disease designation by the FDA, which may qualify us to receive a priority voucher upon FDA approval. With these topline results in hand, we plan to submit a new drug application to the FDA in the first half of 2024. We also look forward to presenting additional details from the ReNeu trial at a future medical conference and to publishing these results in a peer-reviewed journal. With that, I'll turn it back over to Saqib. Thank you, everyone. Today's results position us to deliver on our ambition of having two medicines approved for the treatment of two devastating diseases over the next 18 months. As many of you know, our PDUFA date for nirogacestat NDA in adults with desmoid tumors is set for November 27th. We are very pleased that the ReNeu top line data support a compelling clinical profile across measures of safety, tolerability, and efficacy, and believe there is a meaningful opportunity for mirdametinib to be the therapy of choice for children and the first approved therapy for adults with NF1-PN. As always, we would like to thank the patients, their families, and the ReNeu trial investigators for their participation in this study. We would also like to thank the patient organizations, such as the Children's Tumor Foundation and the NF Network, who continue to be steadfast partners and advocates for the NF community. We will now open the line for questions on the ReNeu top line data. Operator? Certainly. We will now open the call for your questions. Ladies and gentlemen, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. Please limit your question to one each. Our first question will come from Anupam Rama at J.P. Morgan. Your line is open. Hey, guys. Thanks so much for taking the question, and congrats on the update. I know that we're gonna learn a little bit more at medical conferences and in publication, but if you had to boil it down to the one or two points here that underscore differentiation relative to selumetinib, what would it be? And in particular, those points that would resonate with physicians to drive utilization, particularly in peds as well as adults. Thanks so much. Thanks, Anupam, for the question, and I'm gonna give you more than one or two, because I think, quite frankly, there are more than one or two points of differentiation here. So I'll preface this by saying it's always challenging to do cross-trial comparisons. However, we are comfortable pointing you to some key elements in our data that align with what, as you said, physicians and patients care most about. And speaking to precedented data, of course, is a point of context for the strength of these results. So first and foremost is efficacy. Our blinded independent central review objective response rates in peds is 52%. The only other equivalent peds objective response rate that has been reported is for Koselugo, which had a blinded independent central review of 44%. So you know, certainly those numbers favor us when it comes to peds. When it comes to adults, our data are the first to report blinded independent central review objective response rate, but absent a comparator, clearing the 40% mark, we believe is a very meaningful threshold for these patients. The second element I'd highlight is depth of response, which is a parameter that we point to as a very important differentiator. We think our data really shine here. Our median depth of volumetric response was over 40% in both pediatric and adult cohorts. We saw a significant number of responses that were deeper than 80% as well. Simply put, the field has not seen a depth of response like this in NF1-PN. Probably the most natural point of comparison, again, is Koselugo, where their median depth of response in pediatric patients was well under 30%, and they did not see the ultra-deep responses that we saw. I'd remind you that those numbers were reported with local review, not the much more stringent blinded independent central review as we did. The third thing I'd highlight are patient-reported outcomes, and those are generally even harder to compare across trials. But with this topline data set, you know, we haven't had the chance to fully analyze that. However, the nearly uniform statistical significance achieved across both pediatric and adult patients certainly points to pain and quality of life improvements that correspond to the robust antitumor activity that we demonstrated. You know, of course, as we analyze these data, as you know, as you said, we'll be providing more detail at a medical meeting upcoming. So those are the key points regarding efficacy. On safety, we think our data are really compelling. Again, with the caveat about cross-trial comparisons needing to be interpreted with some caution, we've long said that we expect mirdametinib to have best-in-class tolerability, and the ReNeu data really underscore why. Since the Koselugo SPRINT trial tends to be the one, again, that is most often cited, we were very pleased that our rates of dose interruptions, reductions, and discontinuations due to AEs were much lower in our pediatric cohort than theirs. In terms of the adverse events themselves, we saw lower rates overall and much lower severity. So for example, we reported grade three or higher adverse events of 39% and 36% in our pediatric and adult cohorts, respectively. In SPRINT, the Koselugo study, this value was 62%. We also had meaningfully lower rates and grades of rash and GI toxicities than were reported for Koselugo in SPRINT, and those adverse events, in particular, are often treatment limiting and likely contributing to what has been reported as modest real-world treatment durations of under 50% at one year for Koselugo. Now, in addition, we saw lower overall rates and no grade three events, again, painting a contrast with our pediatric data versus Koselugo. Now, again, these are topline data that we've had for a limited period of time, and we're still analyzing them, but when you overlay these features in efficacy, safety, tolerability, depth of response-... with what we knew even before having our top line results in hand, mirdametinib's lack of a food effect, its limited DDI liabilities, its enhanced product formulation, the broader age range treated at the trial. You can see why we're, you know, so enthusiastic about the data and why I'm so happy to extend the answer to your question on the phone. So thank you. Thank you. Next question, please. Thank you. Our next question coming from the line of Yaron Werber from TD Cowen. Yaron, your line is open. Great! Thanks for taking my questions. Congrats on the data. Quick question. When we're looking at the U.S. market size right now, Koselugo does about $40 million a quarter. I think it was $48 million. It's sort of been ranging $41 million-$48 million the last three quarters or so. Any sense how much do you think that's gonna grow? Maybe talk about the price. The price there, obviously, right now is fairly low, so we imagine your price is gonna be higher, but also how much, i s there any way to back into a little bit how much Koselugo is being used off label in adults? Thank you. Thank you, Yaron, and Badreddin, I'll turn to you to answer that question. Perhaps we'll start with a correction on the Koselugo last quarter, please. Sure. So, currently, Koselugo is, their last quarter was north of $80 million. So just to start with that data point, but let me take a step back and answer the question more broadly. So overall, we see NF1-PN as an opportunity to serve a really meaningful number of patients. And so as a reminder, we have 100,000 people in the U.S. living with NF1, and based on our internal work, we estimate that about 40,000 prevalent NF1-PN patients are in the U.S. today. And so that gives you a 75%-25% adult to pediatric split among this prevalent group, again, based on our research. So this is a lifelong disease. Many patients require active treatment at some point during their treatment journey. We talked this morning about why surgical resection does not work in this patient population, and so as a consequence, most actively treated patients receive a systemic therapy instead. And so what this does is it places a premium, I should say, on effective systemic options that have tolerability profiles that are suitable for long-term use, especially because patients are known to progress when they stop treatment. So the data we presented today really supports our view that mirdametinib could be a really important option for these patients across their treatment journey, and in fact, has a differentiated benefit risk profile that leads us to believe that we're gonna be able to position this as a best-in-class therapy. Now, in terms of more detail, on the market itself, vis-a-vis Koselugo. So we don't know exactly how many patients are on Koselugo today. However, we do know that it is a highly fragmented landscape, and Koselugo captures roughly only half of the patients that are receiving active systemic treatment today. So off-label therapies are still retaining a really meaningful share here. And so with that knowledge, we know that Koselugo has only been used in a small portion of the total addressable U.S. patient pool. And therefore, the vast majority of the prevalent patients still have not been treated with a MEK inhibitor. It's also really important to note that ReNeu is actually able to rapidly enroll U.S. patients despite Koselugo being on market during the period of enrollment. So for us, that really demonstrates the continued desire for alternatives and underscores some of the challenges with Koselugo's profile that Saqib just spoke about. So, you know, the fact that it is on market, we do not believe is gonna be a meaningful barrier to entry for mirdametinib, especially with the strength of the data that we shared this morning. And in fact, when we think about the opportunity for mirdametinib's approval here in the time ahead of us, we really see it as ungating for patients. So mirdametinib's profile demonstrated, in our view, greater efficacy, improved tolerability, improved administration, and all this really meets the needs that exist within the NF1-PN community. And so really has the opportunity to remove barriers to treatment and erode share from both on and off-label options. So all in all, we're really confident that mirdametinib will serve as an option for patients across ages and across disease severity. As you highlighted, Koselugo's very encouraging revenue run rates set a nice backdrop for us to come in and have an agent that can really improve the treatment paradigm. Thank you. And our next question coming from the line of Corinne Jenkins from Goldman Sachs. Your line is open. Hey, good morning. I wanted to follow on that last line of conversation. You, you remarked that about 60% of patients that are being treated aren't switching to Koselugo from off-label therapies. So I guess, how do you plan to address or drive switching to mirdametinib from that population once on market? Badreddin, I'll turn to you for that answer. Yeah. So, thanks for the question, Corinne. Really, the opportunity is to highlight the differentiation in our data, to educate physicians and patient communities around the existence of a new therapeutic option for a broader age range, and to put in place the types of patient support programs that a comprehensive commercial effort typically has as an element to its structure. And that is intended to increase awareness of the therapy, increase awareness of the benefit of treatment with targeted therapy, and ease the path towards reimbursement and uptake for a novel therapy. So a very typical set of tactics associated with how we plan to drive that. But really, it comes back to the strength of the data that we believe will enable us to be able to grow that market and grow share within that market. Thank you. And our next question coming from the line of David Nierengarten from Wedbush. Your line is open. Hey, thanks for taking the question. I had a question on the nature of the cutaneous effects of the, you know, just the difference between the treatments with the pediatric and adult patients. So, you know, what caused the, you know, the adults to discontinue at a little bit higher rate than the children? Was it just monitoring? Was it, you know, something else? Thanks. Great. Thank you, David. I'll turn to Jim Cassidy to talk about that distinction between the adults and peds population and the data that we saw. Thank you for the question, David. In terms of safety, there are some discrepancies in the discontinuation rate between the adults and the pediatric cohorts. However, on the whole, the tolerability was actually very similar between children and adults. We saw the same types of AEs, generally consistent rates and severity grades. I should point out that in isolation, we think the adult tolerability is quite good, and the profile shared for the pediatric cohort is really exceptional in terms of the very low rates of high-grade AEs and discontinuations. What we did learn anecdotally in the context of the study is that with less parental discretion on decision-making, adults were more likely to discontinue therapy for less severe side effects. We saw this in the beginning of the trial, where we initially did have not have preventive measures in place to manage rash, and a number of adult patients stopped treatment for rather low-grade events. While the protocol was amended with additional rash supportive measures and guidance, and fewer patients discontinued due to similar events afterwards. So we may be seeing a slightly lower overall response rate in adults because of this initial group of patients discontinued. I will remind you that this is the largest and most rigorous study done to date in adult NF1 patients, and the only study to share data from a potentially registrational study. So we believe this is a turning point for adults and children with NF1-PN, and we're excited to be the first to show this clinically meaningful efficacy in this population. Thank you. One moment for next question. Our next question coming from the line of Peter Lawson from Barclays. Your line is now open. Great. Thanks so much. Thanks for taking the question, and thanks for the breakout of patient baseline and safety. On the dose interruptions, just wonder if you could add any details around that. Kind of how long were the interruptions, and did patients go onto a different dose? And then, kind of your expectations of how this gets used in the, in the sense of a real-world setting, if patients and physicians will get better at kind of understanding dose interruptions and discontinuations. For sure. So I will turn it over to Jim to answer that question. Thank you for your question, Peter. You know, I'd highlight that, you know, where we are right now with respect to those interruptions is class-leading, right? In a very meaningful way, in the pediatric setting and in an unprecedented way in the adult setting. But, we'll certainly expand upon that for you. Jim? Yeah. And so, of course, we've not had the data for very long. So in terms of durations of, you know, dose interruptions, I don't have that data to hand right now. But in general, in speaking with physicians, it's pretty clear that the key feature that they want in any new agent is better tolerability to enable long-term dosing, and the physicians are really not willing to make sacrifices in tolerability for the activity gains, given the lifelong nature of this disease. Koselugo is a difficult drug to take, and physicians are first and foremost concerned with improving patient adherence to therapy with a treatment option that minimizes some of the more troubling side effects. So although there are differences in the study design, the data in ReNeu not only demonstrated more robust and deeper responses in children with a much lower rate of AE-driven discontinuations, dose reductions, and interruptions compared to SPRINT. So Koselugo's label reported dose interruptions due to AEs in 80% of patients, reductions in 24%, and discontinuations in 12% of patients. In comparison, our pediatric data, we showed that, dose interruption was only in 30% of patients, dose reductions in 13%, and discontinuations in 9%. So far lower than Koselugo. Furthermore, rates of all grade and grade 3+ treatment-related rash was 59% and 4%, as well as 38% and 2% for diarrhea, and only 14% and 0% for vomiting. So again, these are much lower than was reported in SPRINT. So improving that tolerability is important for patients and their desire to stay on therapy and could potentially reduce the burden of care for physicians and their teams, since less side effects require less intervention by the medical team. Combining that with the ease of administration, we believe that the profile we have will enable us to take market share from Koselugo and off-label therapies. Mirdametinib's dispersible tablet formulation will be easier to administer in patients with difficulty swallowing a pill and allow for more accurate dosing, even compared to Koselugo's granule formulation, which must be sprinkled onto a suitable vehicle. And when it comes down to it, we still have some pretty compelling anti-tumor activity with mirdametinib on top of these potential improvements to [ADIMS]. So we believe that a drug with all the benefits on safety and convenience we've highlighted, and the ability to drive deep and sustained responses in patients, is very likely to move the needle for patients and physicians. So we do expect that will allow us to have a first-in-class profile for adults and a best-in-class profile to serve the pediatric population of NF1 patients as well. Thank you. And our last question will come from Alec Stranahan from Bank of America. Your line is now open. Hey, guys. Thanks for taking our questions and congrats from me as well on the data. Just one on the regulatory setup heading into NDA submission first half of next year. I believe you've received some guidance on NDA submission expectations, maybe at the end of last year from the FDA. Obviously, the primary endpoint or this precedence for that. I guess, how much weight do you see the regulator putting on duration of response? And would a median DOR need to be reached, or could something like a percentile greater than 12 months be sufficient for approval? And in terms of the bar, should we be thinking about adults and peds pretty much the same in terms of how the FDA would view an approval? Thanks. Badreddin, I'll turn to you to answer that question. Thank you for your question, Alex. Thanks, Alex. So, certainly we believe that the ReNeu trial, as designed and with the data that we have in hand, are gonna be sufficient to fulfill regulatory requirements. And this is based on the feedback that we've had from FDA. So, in the first instance, FDA met with us at the end of last year in a Type B meeting, and they provided guidance on submission expectations to support our filing. And so our data are absolutely in line with those expectations. In terms of our primary endpoint here, which is ORR, we clearly met statistical significance and comfortably exceeded futility thresholds that were determined for both the pediatric and adult cohorts separately. So, you know, our BICR-confirmed objective response rate against these thresholds that were agreed to with FDA come in at well under 0.001. And so you'll also note here that the regulatory precedent is Koselugo, which was approved, fully approved in the U.S. with a single- arm trial. And so, you know, our trial design is consistent with that. So, overall, we feel very good about where we are from a regulatory perspective. We are on track to file our NDA in the first half of 2024. With respect to some of your more detailed questions around you know, median duration of response not being reached and landmark thresholds therein, we can - we'll have to defer those for subsequent conversations. But at a high level, we can say is the data that we have in hand should support registration based on all of our interactions with FDA and, and the overall strength of the data. Thank you. Ladies and gentlemen, this concludes today's call. Thank you all for joining. You may now disconnect.