Made me run from that other hotel to here, so good afternoon. I hope everyone's doing well. My name's Akash Tewari. I am a pharm and biotech analyst here at Jefferies, and we have the pleasure of hosting the SpringWorks management team. Saqib, thanks so much for joining us. I personally don't cover SpringWorks, so I'm personally also excited to learn more about this story. Saqib, why don't I hand it off to you for some introductory remarks, and then we'll get started with. Sure, sure. It'll give you a chance to catch your breath too. So, I mean, normally we get conversations, and there's breathless anticipation. So I'm glad that you're able to. It works out. You know, be consistent with that approach here. So at SpringWorks Therapeutics, we are a company with one product that is approved for a rare tumor, that is for desmoid tumors. We are about a year into the launch of that. I'm sure we'll talk more about that program. Certainly, we believe that the opportunity there is significant, and we are the first and only approved treatment for patients, for adults with desmoid tumors. And certainly, everything that we have seen and that we'll share with you today kind of gives us confidence in the aggregate size of the opportunity, our position within the market for that opportunity, and the durability of it. So, we are well underway that launch, you know, with the approval about 12 months ago. Our next program is for a disease called neurofibromatosis-associated plexiform neurofibromas, NF1-PN. We have a February 28th PDUFA date, where we have data that we believe is certainly best in class for children with NF1-PN, and will be first in class for adults with NF1-PN. We have said publicly, so I will say it here, but you may want to catch your breath here, Akash, as I say this. Sure. You're all set now. Good. That is, you know, each of these opportunities represent north of $1 billion potential in the U.S. alone. So with that, that is, we obviously have a number of programs that are in our portfolio that are earlier in the portfolio, certainly, as it relates to both data expectations as well as the regulatory path. But I think typically the focus is on our two most advanced programs. Sure. With Ogsivio approved for desmoid tumors and mirdametinib for NF1-PN. Understood. I mean, I look at your company, obviously, I cover you guys, $2.5 billion market cap, $500 million cash. You have potentially two blockbuster products and one's already on the market. Mm-hmm. When you think, I mean, the way you kind of think about that, that could be a $6-$7 billion company. I agree. And in oncology. I agree. When you look at the biggest landmarks, the things you must win on from a commercial execution perspective, from a data execution perspective, what is your team most focused on? And what do you think will be the real inflection point to allow that valuation between what you should have and what you are right now? Sure. More importantly. A number of embedded questions in that. I don't make a business of kind of playing the market and deciding when the market fully realizes value. When you're in the early stages of a launch, you could have asked that same question of a company with similar lineages as Blueprint Medicines. You know, early launch, you have the noise, and then when it's clear that you have a market, then you have something that's worth $6-7 billion. Sure. But let me do the math for you as you ask the question. So what excites us about the desmoid tumor opportunity? I'll talk about what we just literally mentioned at our earnings call last week. What is clear, and we'll do math among friends for a moment, right, that as we think of the number of patients to serve, so as you build your model, it's number of patients, what's your percentage of those patients you'll get, how long will you maintain those patients, and what is the price, right? It's not that complicated. Even a CEO can do it. But let's start with the number of patients. We shared for the first time our view that we have ICD-10 claims, so that is the claims code associated with desmoid tumors that has been in existence for less than a year. Mm-hmm. We've been approved for less than a year. So it's been in existence for less than a year where we have had over 10,000 unique claims for a desmoid tumor in less than a year. That is undercalling the opportunity, because it takes a couple of years for ICD-10s to actually be used more regularly. And we, so we've had less than a year. And then also we are certainly still seeing patients come on with claims that were filed with the old sarcoma claims form. So we had always said publicly that it's about five to six thousand people in the U.S. with a desmoid tumor that are being treated, plus you add about 1,600, 1,700 newly incident patients per year. That number has been a, you know, kind of a pretty meaningful undercall. We think it's certainly well north of 10,000. Now you've got a denominator that is large. Now, the likelihood of treating this group, remember, this is an enriched sample. If you went to go get diagnosed for a desmoid tumor, you are dealing with a symptom. That's why you went to go get the diagnosis. This is not something you will see in an annual scan or in your normal annual review. Chances are you're dealing with some symptomatology. You've got pain, you've got a restriction of motion. Right. You've got an issue. So to go out there and get a diagnosis that leads to that ICD-10 claim, we estimate over 90% of these people over their lives are going to get treated. So that's your denominator is well over 10,000. Where are we right now with patient, physician enthusiasm? That has been unequivocally high. For any of you, and most of you are certainly new to the story, certainly as in this audience, right? The feedback from physicians has been uniformly strong. It is the first and only approved treatment for a desmoid tumor. Within less than a year, we are already the systemic standard of care with a 70% market share of any new prescription for a desmoid tumor. But here is where the data is actually really interesting. Once you use Ogsivio, over 95% of doctors will use it again. 90% of doctors now say they will use it in frontline. 60% of that same group say they expect to use it more next year, so let's start with the denominators well north of 10,000, plus you're adding 1,700 newly diagnosed patients per year. You get to what is the physician feedback and the patient feedback, and it's, you know, our label is very strong. We've certainly, you know, we don't see any progression of patients on drug. We've had kind of meaningful reduction in patient-reported outcome. Pain is actually in our label. So if people have a symptomatology issue related to pain, that is enough for a physician to prescribe, so there's the second element. The third element as you think of this is you get to duration of treatment. Right. Just this weekend, we put out data at the Connective Tissue Oncology Society, CTOS, that showed our open-label extension data from our phase three, which indicates the following: patients who had already been on drug for two years, right? That was the duration of the phase three study. They stayed on the open-label extension for an additional year. So what here is what we saw in that third year: continued improvement, continued reduction in tumor size, more PRs, more CRs, improvement in patient-reported outcomes, no change in the adverse event profile. So now there is a clear case. We've always said, because this was true, in our phase one, the median time on treatment was four years. In our phase two, the median time on treatment was four years. The question that we often get is, how long will people stay on medicine? And we have now data to make the case for at least three years of dosing and continued benefit out to three years, even from two to three, there's that benefit. So we've taken the denominator is well north of 10,000. We've got doctors that are very satisfied. You've got the case for multi-year dosing. And now, and our price is already set, right? It's $29,000 a month. We have got insurance coverage in the United States at 95% plus of covered lives in the U.S. that we are already on policy for. And I think that we are, you know, from this vantage point, we talk about the leverage of where we are. We also gave an indication at our earnings that as of September, we had 800 unique prescriptions written for patients. Right. And so because you don't have all patients renewing at the same time, I think, you know, our total patients under coverage is larger than that. But as we think of where we are, less than 10% penetrated in the opportunity that we have with the only approved treatment with meaningful benefit for patients, I think the wind is at our back for execution. So you asked what are we excited about? Those are the elements that are. Understood. I think our pivot points for us. I mean, if I were to think about just low-hanging fruit, okay, you did about $50 million already out of the gate. You're talking about. Last quarter. Last quarter. Yeah. So you're analyzing at 250, you know, 200, 200, 250. 200. You're going to have this waterfall effect 'cause patients are gonna stay on. Correct. The treatment duration. If, let's say, that SpringWorks only gets strong uptake in the newly diagnosed patients, right? Roughly 1,000-1,200 patients that are newly diagnosed. 1,600, 1,700 newly. Okay. So Okay. So 1,600. Yeah, newly diagnosed. Right. Yeah. What do you think your growth trajectory would be if you just focused on that population? Well, I think we should get. So here are the puts and takes of that statement. We've got. I've given you the data of physicians saying they wanna use this in frontline, right? So I think we should get a meaningful portion of those newly diagnosed patients. The typical treatment algorithm that physicians had used in the past without an approved treatment is you do some watchful waiting for a period of time, then you'll either take surgery, chemotherapy, TKIs, opioids, kind of the whole gamut of things you do when you've got nothing that works. We expect that a patient who is diagnosed with a desmoid tumor, it's not a function of whether they're gonna be treated with Ogsivio, it's just when. So even after a period of watchful waiting, we will wind up getting these patients. Now, the reason I think your question, while interesting as you think of just a newly diagnosed, is undercalling the opportunity is that if you think of what we showed in our phase 3 study, the average patient had been on a median of four prior lines of treatment. So they've failed a whole bunch of things by the time they get to us. The typical patient that we have added over the course of this year are people who have tried other treatments because. Mm-hmm. Things don't work. We have the opportunity to get to this full market. And, I think it will kind of slowly start chopping away. And, we've been adding patients steadily over the course of the year. There hasn't been kind of a big bolus effect or anything. And it's what we have seen continually. As I said on our earnings call, you know, our largest month of revenue was August. Then our largest month of revenue was September. And now our largest month of revenue is October. Understood. As we continue to stack patients going forward. When you think about patient experience, can you talk about the importance of having the blister pack available? Why, why would that have a meaningful impact on patients? Yeah. It's a great question. Our phase three, so the approved dose is 150 milligrams twice a day. That is the approved dose that is in the label. In our, and that was what we ran the phase three at. In the phase three, we saw by the protocol design, approximately 40% of patients dosed to 100 milligrams, right? They have an adverse event, they go down to 100 milligrams, and they stay on 100 milligrams. For certain patients, that's what works. What we saw in the real-world setting, how you see that play out is the refill rates. So people, instead of refilling at 30 days, so if you or I got prescribed, you know, a month's worth of Ogsivio for our desmoid tumors, you get, you know, you get a container with 180 pills. You take three in the morning, you take three at night, six a day for 30 days, that's your usage. What we saw is that some patients were not refilling at 30, 35 days. They were refilling at 45 or 50 days 'cause they're extending, you know, these 50 milligram pills over a longer period of time. There is your opportunity. Mm-hmm. If 40% of your patients are extending the use for their one-month supply to a month and a half, that's a pretty meaningful change. The blister packs do the following things. So we introduced the blister packs, and we got them approved about a year ago. We introduced them last quarter. They do the following. Instead of taking six pills a day, patients take two pills a day. There's an AM, there's a PM that helps with adherence. It's less to manage. If you are going, there are two different doses in the blister pack. There's 150 milligrams, and 100 milligrams. If you are a 100 milligram patient, you get the 100 milligram dose. You take it in the morning, you take it at night, and you refill at 30 days. We are priced at parity from the 100 to the 150. That is the logic behind the introduction of the blister pack is that it is certainly more convenient for patients. It results in better adherence, better compliance, and we are economically indifferent between those who dose down and those who maintain the 150 dose. Understood. Now, when we think about, you know, you mentioned in the, you know, in your clinical trials, you're seeing duration going out to three to four years. But, you know, like you mentioned, 40%, down-dosing in some of your studies. Mm-hmm. And then there is ovarian, too, you know, toxicity that it could be associated with this drug. You have your clinical data, but then you've also learned from it, right? Yeah. So talk to me about, A, the safety signals you saw in your phase three studies? Yeah. And then B, what your commercial team is doing to ensure that the compliance rate is even higher than what you saw in your phase 3 trials? Yeah. It's really important, and that's a function of what we do. So let's say, let me give you what I've said publicly, right? We said on our last earnings call, discontinuation rate is less than 10%. So consistent with our phase three, actually better than our phase three, the discontinuation rate, from being on the medicine. What we've found is typically when people do discontinue, it's early. Mm-hmm. You know, if it's related with AEs, you know, for example, GI issues. But if they're treated early and treated prophylactically, patients who then stay on are able to stay on for an extended period of time. So I think our experience in the commercial setting is not that different from our experience in the clinical setting, except it's probably a little bit better, you know, as, as it relates to discontinuations. Understood. Now, you know, obviously anything in oncology, there's gonna be competition that enters on, to the market. You have a substantial head start versus any potential competitor, you know, competitors. Mm-hmm. Where do you think there is room to differentiate at this point? And by the time competition does not enter onto the market, what long-term data are you really gonna be able to show, whether it's payer access, whether it's long-term durability? Yeah. Where do you feel like you're gonna build a real moat in the desmoid? I mean, this is a rare disease, right? So the next earliest potential competitor is an old compound that is being repurposed here that is three years behind us. Three years behind us in a rare disease where I think we've told you we're, you know, already well underway of capturing this with patient and physician enthusiasm, and we've got 10 plus years of history with the drug. The safety history here is very, very clear. The benefit's very, very clear. I don't think there's much room to play. I can't think of multiple scenarios where a rare disease comes three, four years later that could be on the same mechanism 'cause the one that's coming, that someone's got is, has the same mechanism that, you know, nothing indicating any differentiation that has less safety history that, you know, in an already satisfied market, there's really not much room to play. Understood. By the way, people who cover Bhavesh or Range should listen to this, on assignment. Okay. I I kid. Now the last thing I'll just say, I feel like there's always the combination in multiple myeloma with BCMA. Mm-hmm. This idea of upregulating soluble BCMA. Absolutely. I know there's some of the data that, you know, Kite and Juno were certainly generating even five years, five to ten years ago. Yeah. You're right. I feel like your team is suddenly talking about this a bit more now. Am I reading that correctly? I'm seeing this from an outside-in perspective. But A, has there been a shift in your confidence that, you know, the combo approach will make sense? And then number two, how do you see kind of the BCMA space playing out and the importance of these BCMA bispecifics maybe being bigger than what people are modeling, right? I think right now people view the CAR-Ts taking over. Is this really where you can get CAR-T efficacy in combination with a bispecific? Okay. So let me ask the questions that are relevant to us, which is I think that certainly in multiple myeloma, there are gonna be multiple modalities that are going to be relevant. You've got, you know, early data with bispecifics. You've got early data with CAR-Ts. Here is the biology that we see makes sense, right? That actually, if you can prevent the cleavage of these BCMA receptors off the cell surface, you will improve, either, you know, certainly the efficiency of whatever, you know, whatever multiple myeloma treatment you've got, whether it's a, you know, whether it's a bispecific or any other form of attack. What we have certainly shown is that inhibiting gamma secretase, which cleaves these BCMA receptors off the tumor cell surface, is going to allow for a more available target and less off-target effects than if you do it without gamma secretase inhibition. We have proven that again and again with data. We've got a number of partners who are bispecific players, whether it's Pfizer or Regeneron, etc., who are doing the work now. I think that it's going to be different, right? I'm not gonna make a blanket statement of what the CAR-Ts get, what they don't. Cell therapy has its own sets of challenges that. Sure. You know, I think the bispecifics and multiple bispecific players, you will have to distinguish somehow, with your bispecific versus another. And I think that's why some very thoughtful people like at Regeneron and Pfizer are doing work with us with our gamma secretase inhibitor in combination settings. Understood. And have you, has your team generated any data internally? 'Cause I think you see this often in these liquid tumors. You're gonna get a very strong response rate, but then when it comes to PFS and overall survival, there's a degradation that you end up seeing. What gives you confidence that, you know, the BCMA gamma secretase combo is actually gonna translate to a clinical benefit? I think that has to be proven. I think that the duration of that has to be. You can't prove durability without time. Sure. I think we'll have to prove that over time. Now, just in terms of pipeline expansion, and, you know, you're going into ovarian, granulosa cell tumors. Granulosa cells. Yeah. Talk to me about your confidence in showing, you know, a really meaningful effect in that population. When are we gonna get the next data? And what's the bar that you're setting externally to investors? Yeah. The bar is incredibly low. This is a group of patients who have been pretty beat down. It's post-platinum treatment, that this is really salvage therapy for a whole bunch of people. There's plenty of rationale for a gamma secretase inhibitor that inhibits NOTCH that is implicated for this subtype of ovarian cancer. We're gonna have data in the first half of next year, and we'll see on the basis of that data whether we want to or need to run a phase three or whether we may be able to just get on guidelines and start taking care of patients that way. The bar for improvement is actually relatively low given how difficult this, you know, this tumor is to treat. So tell me the data set that would say, you know what, let's just get this on the guidelines versus we wanna run a phase three again? Yeah. I wouldn't say that right now. I think we'll wait for the data to come out. Okay. Understood. On your MEK inhibitor, you have a PDUFA coming out in 2025. Just talk to me about commercial leverage between, you know, the desmoid tumor population and then NF1-PN. Sure. How much are you gonna be able to use, you know, commercial leverage, in order to launch both products? Is this going to be. Excuse me. Go ahead. So the leverage is less important than the size of the opportunity here. Mm-hmm. Let me explain why. I think we typically get this question late in the round, and it is, you know, even though I think this is as big an opportunity or bigger. Let me tell you why. NF1PN affects 40,000 people in the United States, right? Much bigger market. You don't have to guess on the proxy of the market because one quarter of that market are children, three quarters of that market are adults. There is already an approved treatment for children that AstraZeneca has a drug called Koselugo, that is already doing $500 million run rate in revenue just in the children. That is in one quarter of the opportunity. We have data that we have filed on that, that we believe has us a best-in-class drug for children and will be the first-in-class for adults. So that's three quarters of the opportunity right there. So we are sitting here with a February 28th PDUFA. We think we've got the best-in-class children, first-in-class adults in a market that has already been proven in terms of both the number of patients and you've got somebody out there already doing $500 million of revenue in one quarter of the revenue pie for NF1-PN. That I think is an enormous opportunity for us. We've got data that shows a distinction relative to Koselugo in efficacy, depth of response, safety, tolerability, product form, that we think positions us very well. We expect to launch in the U.S., you know, soon after approval. Our plan for 2025, as we're, you know, coming up to time, is we've got three launches. We've got the European launch for Ogsivio for desmoid tumor patients outside the U.S. We already have 250 patients on compassionate access outside the U.S. This is a disease without a demographic orientation, so we expect a proportionate number of patients outside the U.S. Half of our phase three was done in Europe, so we know that the demand and interest is there from physicians. We're going to be doing a U.S. launch for mirdametinib for NF1PN. I've highlighted that's 40,000 people in the U.S. in both adults and peds with data that is differentiated. And we're gonna be doing an ex-U.S. launch of mirdametinib, as we've got our CHMP opinion in the second half of the year. So relatively big 2025 for us, as it relates to both regulatory and commercial launch, in addition to what we're doing in the U.S. with desmoid tumors for Ogsivio. When you think about your commercial strategy with the MEK inhibitor, I mean, given you have, you know, you have better efficacy and meaningfully lower grade three AEs. Mm-hmm. Why not go for a switch population, right? Even in the pediatric setting, how aggressive are you gonna be in terms of taking share? I think, like I said, we've got a best-in-class drug. What we know for sure, because this is what they have said, is they lose 50% of their patients within a year. They have, you know, that is a tolerability challenge that they have that we do not have. We believe there are certainly many patients who are treatment experienced who are now looking to get back on something that they can stay on. Mm-hmm. As well as, we believe that they've only, you know, made small inroads into the overall patient population. Again, I'm just describing the children, so that's one quarter of the overall opportunity in addition to the three quarters where we expect to be the first approved. Now, with the same molecule, AZ, we expect them, you know, to get approved in adults. We think it's a good thing that they're doing so, but it's the same molecule. So the same liabilities that they have with children are the same liabilities that they'll have ultimately with adults. And we believe that there we've got a head start in addition to what we believe will be best-in-class treatment. Understood. But I mean, look, at the same time, this, we're talking about Novartis. We're talking about a large-cap pharma. We're talking about AZ. Oh, sorry. AZ. And you have, but either way, you're gonna have a geographic footprint. You have a much bigger salesforce you're competing against. Correct. How do you think about, so when you think about the balance of partnering ex-U.S.? Yeah. In order to kind of reach the same scale. Sure. Why not go with that approach versus, let's say, going on a loan? What's, you know, the. For mirdametinib in particular, you're asking? Yes, there is a. I think it's a fair question. There's a substantial ex-US opportunity that certainly AstraZeneca has demonstrated. And we have a lot of respect for their sales organization. They're working with the Alexion team that we have a lot of respect for, for sure. And we, but ultimately, this is not just about marketing. It is about medicine. And if you have a better drug for patients, you will find those patients. And it does not require. There's, it's a center of excellence. There is a, an orientation where it is a, rare disease and concentration of patients. And we believe that, you know, you win on data. And so, your question was, would we ever partner ex-US? Because it's a meaningfully large opportunity, I would say that we have a lot of friendly people willing to partner with us right now, and we have a decision to make. Sounds like it's important for you from a strategic perspective to retain those rights right now. Is that a fair take? No. I think we've, you know, we'll do whatever's right for patients. Whatever gets the medicine to more patients is where we're gonna head. Understood. Thanks so much for the time. Thank you very much.