Thanks for joining this session with SpringWorks Therapeutics. My name is Alec Stranahan. I'm Vice President and Senior Biotech Analyst covering SpringWorks here at BofA, and I'm pleased to be joined by Saqib Islam, Chief Executive Officer, and Badreddin Edris, Chief Operating Officer, of SpringWorks. Thanks for being here, guys. Thanks so much for having us again, and appreciate the opportunity. Yeah, great. I mean, it's crazy to think how last year on this stage, we were talking about the probability of an OGSIVEO approval and what the ReNeu top line from mirdametinib could look like as the next big pipeline catalyst. And we're obviously well beyond that, and I'd say the company is in a very different place than it was even just 12 months ago. So Saqib, maybe just to start, to set the stage, you know, for OGSIVEO, you know, what does the desmoid tumor market look like? This is where OGSIVEO has been approved end of last year. You know, what does this look like, and how do you see the approved label for OGSIVEO setting the launch up for success? Well, I think, you know, we've always described the opportunity, as you think of... You know, certainly from a patient perspective, the individual patient will benefit dramatically from OGSIVEO treatment. You know, you look at it from an efficacy standpoint, controlling the tumor, shrinking the tumor, seven of seven patient-reported outcome tools that showed that, you know, they were improving physical function, pain, kind of a whole host of things, I think. So at, you know, at the most important level, at the individual patient level, we think, you know, it's kind of revolutionary for them. Now, I believe you're asking a commercial question, which is kind of the aggregate size of the opportunity, and I think, where we sit at the moment is actually in a place of incredible confidence in the peak opportunity. And what I mean by that is as follows: you know, we have said, in the past that there are approximately 5,500-7,000 people in the United States currently getting treated for a desmoid tumor. We have the benefit of being in the market for the last few months. We have ICD-10 data now, so we can actually see when the patients come in in a much more specific way. We've got, you know, field force now, that is, you know, interacting with clinicians. And I would say that our views of that current group is, you know, likely conservative, as we think of that group that's currently receiving treatment. So let's use that as a base. You've got your 7,000 or so people, as a base currently receiving treatment for a desmoid tumor in the United States. In addition, you've got about 1,700 newly diagnosed patients every year, right? So the opportunity for us, as we build this, the commercial set, is stacking patients over time. Yeah, right? So 1,700 per year being added to the funnel. Now, we know from the data set has come, since we've launched, certainly survey work that we and a number of our investors have done, is that this is viewed as the standard of care now for people who are currently getting treated, and will be the first line treatment for people who will be treated for the first time, you know, as they're newly diagnosed. And so those two elements, plus the fact that, you know, there are about 30,000 people in the United States who've ever had a desmoid tumor, a lot of people who are not getting treated for various reasons, we think the opportunity, the depth of the opportunity is significant. The aggregate potential here, when you look at the fact that, you know, pricing has been set, right? We're out there with our public price of $29,000 a month. There is clarity there. There's a long duration here with respect to our IP into 2043, that the commercial opportunity, we think, is quite dramatic, and even with a very strong launch, you know, we're only scratching the surface. Right. You know, I think the label checked a lot of boxes for us at least. You know, how did that sort of meet or exceed your expectations for what you were hoping for? Well, this time last year, we were, you know, being asked by you and others, you know, what would be a great label? And I think that what we were the beneficiaries of is exactly what we were hoping for, a label that is clear on, you know, the time to treat. You'll treat through progression, you know, and you don't see people progress on this drug, so we think, you know, it has a meaningful time for people to get treated. No limitation, and certainly including the concept of pain. You know, and that benefit to patients that you've seen in the New England Journal and since then, in the clinical setting, is patients are seeing a early, deep, and consistent benefit, including in symptoms like pain, which is obviously critical to, you know, kind of patient satisfaction on OGSIVEO. And from the New England Journal, you see that as long as you are on the medication, you will get that benefit. And that's a tremendous outcome for these patients, who, up until now, have had nothing. And so the breadth of the label, the absence of restriction, and certainly that focusing in on pain as being a key symptom within the label, that allows a physician to prescribe OGSIVEO without limitation, you know, I think we're seeing the benefits of that in the early, early innings of the launch, and I think patients are certainly seeing the benefits of that, you know, from where we sit at the moment. Great. And, you know, maybe talking about the first few quarters of the launch, you guys were able to assure pretty quickly that your drug was available, and payer access, post-approval came on board very fast- Yeah ... end of last year. You know, how, how do you see these factors, as maybe benefiting the first few quarters of launch? I think they'll benefit the first few quarters. I think they'll benefit us all the way through, because the same things that drive the payer willingness to quickly give patients access to medicine are the things that will drive patient adoption here, which is the strength of the data, right? You've got data that show that not only do you stop tumors from growing, you shrink them, and you reduce pain, you improve physical function, and I think those are the same factors that payers look at. Now, where we sit at the moment, we've said this kind of in various stages of where we are, kind of the best depiction of that motivation of payers is the fact that from where we stand right now in mid-May, we've got 98% of commercially covered lives in the United States who are getting access to OGSIVEO without restriction. Of that group, almost three quarters are already on policy, so the time from prescription to reimbursement is going to be quicker. Our goal is when a patient gets prescribed OGSIVEO, we make sure that they get it as soon as possible. Now, made easier by the fact that it, some things on policy, but I think the fact that the commercial environment, you know, which is kind of, you know, a very, clinical interpretation of the data, sees that benefit, so quickly, I think certainly helps, but it will help us going forward beyond even the first few quarters. We've had reimbursement also from Medicare, from Medicaid as well. So I think the, you know, the drivers of that fundamentally are the benefit to the patients, and, you know, I think as we- as long as we focus in on that, I think continued access will, you know, will be there. Right. A lot of boxes already checked. Yeah. You know, when you look at 4Q and then 1Q more recently, both beat expectations on revenue, any dynamics at play in those prints that could continue over the next few quarters? And I guess, you know, any factors that are maybe specific to year-end, such as stocking or January softness in terms of seasonality? Sure. So the answer to that is yes, right? I think what you see in... You know, we had December numbers, which obviously benefits somewhat from, you know, it's the first launch, a little bit of inventory is certainly part of that, as we discussed on our call. And then you move right into January, where, you know, you have people reloading on their co-pays, reauthorizations required from insurers, and so there's a natural kind of, as people call it, donut hole. Mm-hmm. Early into the year. Now, putting all of that stuff aside, there is a pretty quick ramp from what that is to $21 million at the end of the first quarter. But even saying that, I think all you have to understand from where we sit is that we're only scratching the surface, because quite frankly, as I said, our view is that 7,000 number is, we think, you know, somewhat conservative with respect to the patients currently getting treatment. There is no question about the 1,700 newly diagnosed a year, and so with the confidence in those numbers, you know you're only just scratching the surface of patients. So, you know, we have got publicly we've seen four months of sales. Privately, we've seen a little bit more. Obviously, as we, you know, as we're in mid-May, you know, our confidence remains very, very high. Great. I appreciate most people, as is typical for a new midcap launch, are still very focused on, you know, what happens quarter to quarter, which is important, but maybe doesn't tell you everything about the total value from the OGSIVEO program. And you mentioned the pancaking or the stacking effect. Could you maybe speak at a high level of the anticipated growth from here, or how that stacking effect could feed into not just the next 6 months, but the next, you know, 12 months - 18 months? Yeah, no, I, I think we'll see that actually more than within the next 6 months, the 12 months -18 months. We'll see that right up until, from my perspective, right up until loss of exclusivity, because typically, you know, you are adding patients. You are adding patients at a greater rate than you are losing patients because, because you're seeing patients. You know, if I think of our phase II, our median time on treatment was 4 years. Our phase III median time on treatment was just over 2 years when we stopped the study, and obviously, we had patients continue through an open label extension. And you have a label that says, "Treat to progression," where patients tend not to progress. Now, all of that together shows that people tend to stay on OGSIVEO for an extended period of time because they're seeing a benefit over an extended period of time, and that's what we expect to see. So the stacking, you know, I like the pancaking term because I'm hungry, is you start with, you know, that 7,000 or so patients. Over time, we will get them, right? They are currently on other treatments. As they get off other treatments, the survey data, any survey work that people have done to indicate that this will be the standard of care, you will get those patients. On an annual basis, you will then add whatever percentage of 1,700 wind up getting on therapy, and we expect that to be an increasing number in an environment where NCCN guidelines have evolved, where OGSIVEO is to the top of the list among, among NCCN providers, and with greater awareness comes greater, greater propensity to use OGSIVEO. Now, remember, when you think of 1,700 newly diagnosed patients per year, that's an enriched sample because you're not getting diagnosed for a desmoid tumor unless you are checking for a desmoid tumor. You're only checking for the disease because you have symptomatology, so your likelihood to require treatment, by definition, is going to be higher. Add those patients on an annual basis on top of where we are. Mm. Now, think about how long you keep people on, then the patients you add over time. That's how this builds out well beyond a 6-month, 12-month, 24- 36-month period, because you have that annual addition over time. Right. Okay. No, that makes sense. And I wanna turn now to mirdametinib, which is sort of the encore in the pipeline, for NF1-PN. You're just saying that because we're at a Wynn property? Yes. Yeah. Very apropos. Yeah. When you think about the NF1-PN market as it relates to MEK inhibitor adoption, it's not the same as OGSIVEO. Like, you're not gonna be the first- Correct. But you, based on the RENEW data, you could very well be the best. I think selumetinib is maybe the comp that people point to as, you know, maybe building out the market, but has fallen short for a variety of reasons. So maybe just to start, how does mirdametinib improve upon prior inhibitors in the class, in this indication? Sure. So, I mean, listen, I think the approval of selumetinib, I think, was a watershed moment for patients with NF1-PN, right? They had nothing, right? They, they are-- This is a disease that is even less likelihood to benefit from surgery. You've got patients with an incredible amount of pain, physical function, and as the disease progresses, you have kind of reduction in expected lifespan as well. So that approval, we applaud, and we're delighted to see that. Now, what we shared in November, now again, that's an approval in the pediatric setting. And, you know, one can debate whether it's short or not short of expectation. I think it's helping a considerable amount of people, and I think that it's an indication of how much help is needed. There are 40,000 people in the United States with NF1-PN, so there are a lot of people that need a lot of help, and obviously, a commensurate number outside the United States as well, where they've got a you know, they've got sales coming from both areas. Now, we haven't run head-to-head studies with them, and so, you know, it's, it's difficult to make cross, cross-study comparisons. What we do know, though, is the following, and we shared this in November, and there's going to be more data that comes out in, you know, at ASCO this year in an oral presentation, is that in terms of the depth of response, in terms of safety, tolerability, in many efficacy measures, we believe we have what what could be the standard of the, you know, the standard of care in the pediatric setting and the first approval in the adult setting. Mm-hmm. So an important thing to remember is that, you know, depends on where you sit, we think they've had a, you know, kind of a nice launch here, but it's only in the pediatric setting. The pediatric setting represents, we believe, a quarter of the commercial opportunity, given that you've got dosing based on size as well, and also a greater number of people as they grow into... You know, they may originally get, you know, diagnosed as under eighteen, but then, you know, they age, and, you know, then the treatment becomes, you've got a whole group of adults who need treatment. And so the commercial opportunity is significant. The data that we've got, as I said, depth of response, the safety, tolerability, and a whole host of efficacy measures, we think makes us kind of a very credible, best-in-class therapy, and we hope to be able to prove that. Our plan is to file our NDA in the next couple of months, and then follow that with a filing in Europe, you know, in a couple of months that follow. But, you know, hopefully, as we're sitting here at this time next year, we will have launched our second drug in another devastating disease with meaningful commercial opportunity and a meaningful benefit for patients. Right. Right, and then one, you know, advantage that you didn't mention is the with food or without food. Yeah, there's a food effect. You know, gradually, we expect, you know, an opportunity with a formulation advantage as well. And so, you know, I think that ultimately it is, there are a whole host of benefits. Yeah. You know, we hope to be able to, to bring those to patients over time. Makes sense. You know, thinking, let's assume it does get approved, and we're sitting here next year talking about the launch. You know, where, where do you think the early demand could come from? Is it from MEK-naive NF1-PN patients, or could we also see some patients currently on a MEK inhibitor switching to mirdametinib, given, you know, the convenience and the clinical- I think the short answer is both. Badreddin, I'll let you add. Yeah. Well, first and foremost, when we take the adult segment, which is about three-quarters of the market opportunity, we expect to be first to market there, and so those are patients that are gonna be largely MEK naive unless they got an agent off-label or through a clinical trial previously. So that's what we expect in that majority segment of the market. Within the peds, I think we have the opportunity to see both. Certainly, with the proviso that there are no head-to-head data, we think that our profile compares very favorably. That's been consistent with the market research that we've done since disclosing our top-line results. And so, we think that we have a real opportunity in untreated patients to be preferred after we're able to get the drug approved. Then we do know that anecdotally, some patients have been on prior MEKs that have received mirdametinib in various settings, and those patients have done well. So certainly for patients that have either progressed on a previous MEK inhibitor or were intolerant to it or otherwise unable to comply, we certainly think there's opportunity to serve some of those patients as well. Got it. Got it. And I guess for the rolling NDA submission, I think you guys have said it'll be completed in the first half, so, you know, maybe next month, by the end of next month. Could you maybe walk us through what's left in terms of the submission, and where a June submission would sort of put you guys in terms of possible approval timing? Yeah, so, everything's on track from a submission perspective. We started the rolling submission back in March. Just the typical modules that we need to to complete between now and getting that, on file within, you know, within the, the, the end of the first half. We also had a very successful, and I would say, efficient and brief pre-NDA meeting with FDA, so just further underscores, clarity around, approval requirements and so forth. With respect to timing of approval, so we would expect to have, a PDUFA date within 2 months of, of the filing being completed, and so that'll set the frame for whether it's a 6-month review or a 9-month review, in terms of an action date, which would put us sometime in the early to mid part of next year. Okay. And it's the expectation that it'll be an accelerated review at this point, just given your prior conversations? Yeah, we don't know at this point. We're gonna have to wait until the NDA is in and get a review designation and PDUFA date from FDA. So we're not guiding one way or the other. Okay. Thought I'd ask anyway. You know, as you look to the commercial launch in 2025, obviously, you've got your sales force for OGSIVEO. What kind of prep would you need to do? What kind of additional build-out would you need? And what are you already doing today that'll help drive the launch from day one? You know, I'd say that from a commercial readiness standpoint, you know, we have a template, right, that we can follow, certainly with OGSIVEO, and there are some similarities here with respect to the desmoid market versus the NF1 market. It is different in that you're, you know, we're second to market in one, first in the other, but it's a very large market in the second. Mm-hmm. So, you know, as far as the on-the-ground sales force, that will be unique. Like, it'll, we've got 35 people for desmoid. We'll probably have a similar number for NF1-PN in the United States. We are able to take advantage of some common infrastructure, which is quite important, whether marketing, payer, you know, reimbursement, access, you know, all of that, which we're going to be able to use as far as readiness goes. But, you know, we're, you know, we're in the process of, you know, as you think of the timing of an approval, you know, we're hiring that team right now as we think of, getting ourselves prepared. But, you know, having done it once recently, I think we've got a pretty good playbook. Okay. And, yeah, I think in your 1Q filing, you, you said that we could expect maybe a second half filing in the EU, for, for mirdametinib. How have your interactions with the European regulators been to date, and how do you plan to approach commercialization ex-US? Yeah. So, the reason we were able to guide very specifically the second half filing is because we had been having interactions with European regulators, and they've been very favorable. And so, we're obviously very excited to be able to get that on file very quickly after the NDA goes in for the, for the U.S. approval. With respect to commercialization in Europe, it's, it's premature to talk about exactly how we'll tackle that, but certainly, as we get closer to a potential approval, we'll be able to give that kind of specificity externally. What is clear is that there is a meaningful ex-U.S. opportunity, right, in NF1-PN. I mean, that is, not just in the number of patients, but also in a reimbursable, kind of a reimbursement architecture that makes sense, too. So, more to come, certainly, but we think, you know, that there is, a real depth here to this market, both in the U.S. and outside the U.S. When you think about sort of the economics of, you know, building out your own launch team in Europe versus, you know, what kind of top-line bump that could provide, does it make sense to do it yourselves, or would a partnership be more in the cards and you can, you know, refocus on other pipeline? We're talking about NF1 right now? Yeah. Listen, I think that there is. From our perspective, it is. If we believe you can serve a patient equivalently one way or the other, then it's, that is it, and we believe we can, and if we had a partner who we thought could, then it is purely an economic decision. Yeah. Right? I think we've got a high degree of confidence in our ability to execute outside the U.S., and I think that, you know, the rest, we will kind of look at it as, as it comes. I think there will be, if OGSIVEO is any example, there will be no shortage of helpful hands if we want to take advantage of it. Okay. Okay, very good. And you, you mentioned you'll have some, some presence at ASCO this year. Could you maybe help frame the updates we should expect in a couple of weeks? And, you know, how will this feed, especially the OGSIVEO data, feed into, you know, our understanding of the ovarian dysfunction piece? Yeah. So we'll have four presentations at ASCO. First and foremost, we'll have an oral presentation describing the ReNeu top-line results. This will be largely similar to the company-sponsored presentation back in November. Given the timeline lag between when the top-line results were ready in November and ASCO, we sought to be more disclosive than not. And so I'll say it's largely incremental and more about getting that data out to a broader physician community in the form of the ASCO oral presentation. So obviously, there will be some incremental data and incremental color on PROs and other things, but by and large, I think from an investor perspective, we've disclosed that data in all material senses. On the OGSIVEO side, we have three presentations that will be at ASCO. The first one you highlighted is, the ovarian toxicity resolution long-term follow-up. And so, we actually published the same data in Cancer a couple of weeks ago. And the punchline here is, with longer follow-up, we actually see higher rates of resolution on, patients who remain on OGSIVEO therapy. So, patients who stay on the drug see their ovarian toxicity symptoms resolve, in three-quarters of cases. And obviously, the 100% of cases that resolve off therapy remains at that number. So largely incremental, but quite frankly, physicians are already very comfortable with the resolution data that we, presented at ESMO and published in NEJM last year, but good to see even more resolution, with more time on therapy. The other two presentations are really geared towards, subtype analyses within the DeFi trial. So we have one dataset that's looking at patients with APC mutations. That's obviously a high-risk group within the desmoid tumor community, and essentially what we show there is that the data is very favorable for nirogacestat in terms of response rate, PFS, everything else, even in high-risk patients. And then the second presentation, the fourth overall, looks at a variety of other high-risk subgroups within the DeFi trial and looking at how nirogacestat stacks up against placebo in all of those subgroups. And again, it's a very consistent benefit that we see overall, entirely consistent with the total treated population. So that's really the contours of what we expect to present at ASCO. Okay. Yeah, definitely looking forward to the data. You also have a study in ovarian granulosa for nirogacestat. It's in phase II. This could be, you know, another upside lever from that asset, specifically, data update in the second half. What kind of scope should we be expecting, and any framing you can provide around that up? Sure. So, this trial is fully enrolled. We have over 50 patients who are enrolled in the trial, and these are patients that have failed all available therapies. Step back for a second. Ovarian granulosa cell tumors, there's nothing approved for these patients. There's a number of agents, chemotherapeutic agents, hormonal agents, anti-angiogenic agents that are listed in guidelines, but nothing that has a formal FDA approval. And all those agents don't work particularly well, so they have very, very modest efficacy. And so, in our phase II trial, which is a single-arm study, we've enrolled a patient population that has largely seen all of those available off-label therapies. So it's a very advanced and heavily pretreated patient population, that's really out of options. And so for us, I think looking at the totality of the data is what's gonna govern next steps and certainly govern enthusiasm for the agent. But we want to see what kind of clinical benefit that we can give to patients that have exhausted all available therapies. In terms of framing, I mean, because this population has not been studied in a clinical trial setting, it's hard to give a framing, whether it relates to PFS6 or ORR or anything else. And so the feedback that we've had from our investigators and from physicians not involved in the trial is, you know, these patients are desperate. We're desperate to have something for them. We want to look at the totality of the data package and come to an assessment as to whether that could be a useful tool in the armamentarium, whether it's guideline listings or otherwise. And so we're obviously eager to see that data as it comes together in the second half and be in a position to release it. Great. And, you know, unfortunately, like, this is a very aggressive, advanced population of patients, so PFS is actually a metric that you can measure pretty quickly. Is there a, you know, sort of a bar or an appropriate benchmark we should be looking to, to gauge what a, what a meaningful PFS benefit would be for these patients? Yeah, I mean, PFS has typically been on the order of single digit months for these patients. When you look at precedent studies, whether it's with Avastin or various chemotherapeutic agents, but again, now we're looking at patients that, by and large, have actually failed all those available agents. So, that's really the framing for the unmet need and the rate of progression underlying the patients that were enrolled on this trial. Okay. Okay, makes sense. And you also have BGB-3245, and, you know, a few other assets earlier in development, but maybe just for the sake of time, we can mention this one. Could you maybe talk a little bit about what this is and, you know, what we could expect from the phase Ib dose escalation later this year? Sure. So, BGB-3245, now called brimarafinib, is a next gen BRAF dimer inhibitor. We're advancing it through a joint venture with BeiGene called MapKure. And the molecule has actually completed dose escalation. We disclosed those data at AACR last year and is currently in dose expansion, looking at patients either with Class II or BRAF fusions, or patients that have Class I BRAF mutations for which there are approved therapies, but that have failed those therapies. And so what we're looking for in the dose expansion data, later this year, really is what does the response rate look like in those subtypes? Do we continue to see the types of responses and depth of response, that we saw in dose escalation, right? And so that was very promising to see that even before arriving at a dose that we were moving forward in a dedicated expansion cohort. So that's really what we're looking for in the monotherapy expansion, really, whether we can sustain that activity in those defined patient populations and understand whether there's a registration path as a monotherapy, keying off of those data. We also have a number of combination studies ongoing with brimarafinib, so we have one with mirdametinib, our MEK inhibitor, which we spoke about at length in the context of NF1. So that's in dose escalation. And then recently we started dosing brimarafinib with with panitumumab from Amgen under a clinical collaboration in CRC, in pancreatic cancer patients with with MAP kinase mutation. We disclosed in the first quarter that we just started dose escalation there as well. More to come on that asset. Okay. Maybe in the last minute, you know, we talked about the OGSIVEO launch, we talked about mirdametinib getting approved in the next 12 months. We've talked about your pipeline priorities. How does your cash position... I think you ended Q1 with $573 million in cash and equivalents. How does this get you through those card flips? And you know, I guess, how are you looking at the runway vis-à-vis capital allocation? So, you know, obviously a lot of moving parts there because we have two launches, you know, embedded in a lot of these calculations. But we expect this cash to get us through profitability. So, if these launches have the, have the curve that we expect, even on a conservative way, and with the expense profile we currently have, where, excuse me, mirdametinib is our main launch, and there, there isn't really, from our perspective, other things that are gonna require major investments, this will get us through profitability. Okay. Very good. Very good. Well, with that, I think we'll have to end it there. But thanks so much for joining the conference, guys, and the great discussion, and really appreciate you participating. Thanks for having us out. All right. Thank you. Thanks, Alec. Bye now.