All right, so welcome to this fireside chat with SpringWorks Therapeutics. It's my great pleasure to welcome Saqib Islam, CEO, and Badreddin Edris, Chief Operating Officer. Welcome. Thanks for joining us. Thank you for having us, Michael. Saqib, I'll just jump right in. I know you've just reported earnings yesterday. Yeah. But just first with a high-level question, and then we dig into details. So just on Ogsiveo, now that it's been just about a year on the market. Yeah. How has the drug performed commercially relative to your initial expectations? You know, thanks for the question, Michael. Thank you for having us here, as always. I think we are in a very, very fortunate position right now. I think what is clear is some of the things we talked about on our earnings call yesterday is that, first and foremost, this is a bigger market than I think we anticipated, right? So we've got data from ICD-10 codes indicating that there are over 10,000 people who have had unique claims for desmoid tumor diagnosis. We have talked in the past about 5,500-7,000 people currently being treated in the U.S. with a desmoid tumor. What is incredibly clear is that, you know, we have undercalled that substantially, and we've got data to support that view. Second, I think what we've seen in our survey data, sell-side survey data, and other investors' survey data is clearly we are the systemic standard of care. So while the denominator is also significantly bigger, it's clear that when you think of a desmoid tumor, that if you're going to get a systemic therapy, that now doctors are reaching first for Ogsiveo. So the impact of that, you know, as we think of launch curve trajectory is, you know, people have, you know, revised upward their views four or five times this year. And our view consistently is that this is going to be, you know, well north of a $1 billion commercial peak sales opportunity in the U.S. alone. Everything that we have seen, both in terms of the number of patients that are out there, the doctor's likelihood to prescribe, and then now data that we are going to be putting out at the CTOS conference this weekend showing the benefits of longer duration therapy on Ogsiveo, I think that, I think ultimately makes this a kind of a very robust opportunity. So if your question is one of expectations, I think we've had to revise upward our expectations, and I think we continue to do so from this point. Great. So maybe then just diving into this a little bit deeper, and I think you're right. So I think Ogsiveo has clearly exceeded our internal forecast. Sure. Earlier this year and sell-side estimates. But in the third quarter, you did see, as you reported yesterday, a slowdown here. I know you talked about kind of the introduction of new dosage strengths and the blister packs this summer. Just walk us through the dynamics here again in the third quarter and what happened indeed. Absolutely, and so I'd say that there wasn't a slowdown. We still increased by 25% quarter- on- quarter and still continued growth. It's less than I think the revised projections were, right, as consensus has gone up. But what we did experience, though, is we made the conscious decision in the third quarter to introduce new formulations of our medicine, so currently, you take pills, 50 milligrams pills, you know, three in the morning, three at night, 150 milligrams twice a day. We introduced blister packaging, so two pills, either 150 milligrams, you take one in the morning, one at night, clear delineation AM, PM that we think is going to help with adherence and compliance, but also a 100 milligrams formulation AM, PM, and we think that the opportunity for that is quite substantial. Now, the consequences of that were we had a slow July, as expected, but perhaps even, I think, more than we expected because you had people having to get on new prescriptions. So we had a couple of weeks where people were waiting to get their prescriptions renewed. That was followed by our largest month ever, which was August, which was then followed by our largest month ever, which was September. So we're about two-thirds of the way as of the end of the third quarter through the migration into the blister packs, and we expect this to be completed by the end of the year. Let's talk about why that matters, though. If you think of our phase 3 study, our DEFY study upon which Ogsiveo was approved, you had approximately 40% of patients down-dosed from 150 milligrams to 100 milligrams. Why is that relevant? In the real-world setting, when you are prescribed your dosage of Ogsiveo, you get 180 pills. If you are stretching that out, your refill times go beyond 30 days. You get to 45 days and beyond that. That is what we saw. We saw an opportunity here to introduce blister packaging that is more convenient for patients, certainly going to lead to better compliance and adherence, but also that is going to result in more consistent refills. The benefit, as you start to think about that, is think of 40% of the phase three trial, so potentially 40% of patients not extending their, you know, their time with the medicine by 50%, and that becomes quite substantial. And so important to highlight that we are priced at parity between the 100 milligram and 150 milligram dose, so we are indifferent as to the dosage strength that patients get, but they get that benefit. Certainly, we think the opportunity is substantial there, and that's why we made that move in the third quarter, knowing full well that might create a little bit of an air pocket. So while we had great growth and continued to add patients, we knew there was going to be a period of stasis there, and that's what we experienced. Right. And just to understand this, so is it because patients have to re-undergo insurance, you know, coverage, or what drives that gap to switch from one to the other? So initially, it was having to get a new prescription. So a patient would go ask for a prescription to be renewed. That prescription would be denied. They would have to go back to their physician for a new prescription in the blister pack formulation and then wait for approval of that. We're at a place now where we are on 90-plus% of policy for drugs for reimbursement from insurance companies. And so that time has now been truncated, and that obviously includes the blister pack formulations as well. But at the initial moment of the introduction, you had this two-step that was creating a lag. Gotcha. And so it sounds like you expect the remaining one-third of existing patients, I suppose, switch over the rest of the year. Anything you need to do to facilitate that, or is that just a? No, I think that is a kind of a supply inventory dynamic that we expect to go through over the course of, you know, this next quarter. Okay, understood. And then just outside the switch dynamic, and, you know, you mentioned there's potential for, you know, higher revenue per patient at the end of the day using the new dosing. But in terms of demand, what are you seeing in terms of some organic demand for therapy in terms of new patient starts? You know, I know you I think you mentioned you've seen over 400 different prescribers now. Yeah. Used the drug. And so how do you increase that further? Is that, yeah, what are areas where you can see, you know, actively? For sure. So a number of questions embedded in there. I think we've had a steady new patient adds, you know, over the course of the year, and we saw that in the third quarter. We're seeing it in the fourth quarter. And I think part of that is driven by what I said at the outset, is that the denominator, quite frankly, of patients is quite bigger, is quite large. I should say it's bigger than we thought. So with that group of patients now migrating over, we expect to see more prescribers. But our data thus far, and we shared this on our earnings call, is that, you know, if you have used Ogsiveo, 95+% of prescribers expect to use it again. So the more familiarity physicians have with the drug, the more they're likely to use. In fact, our data showed that of all prescribers, over 60% expect to use it more next year than they're currently doing. We talked about having about 800 unique prescriptions in the month of September at one point in time. We have more patients than that, but that is one point in time for 800 unique. That is your numerator, your denominator is in excess of 10,000, in addition to 1,700 newly diagnosed patients per year. Our opportunity, as we said, we're scratching the surface; it's to break into that group steadily over time. What we are dealing with, though, is a non-lethal disease and still relatively new in the market. The more we can get people getting access to the drug, more familiarity with the drug, the more usage we're going to get. What is clear is that this is the standard. This is the therapy of choice among systemic treatments, and that has only increased quarter- on- quarter, and so our opportunity set, as we think of breaking into the rest of the patient category, really falls into a couple of different buckets. One, making sure that we are the first-line treatment so if you're newly diagnosed, that you will go to Ogsiveo first. All survey data would indicate that that is going to be the case, and two, making sure that you are the next treatment, because inevitably people, you know, if you've started on surgery or a chemotherapy or a TKI, eventually you are going to wind up on Ogsiveo. That has been our experience. It's not whether you will be using Ogsiveo for your desmoid tumor, but when. And so as we steadily add these patients, and I think eventually you reach a tipping point where there are enough physicians who are familiar, enough patients who have had that experience, where I think you start to see that benefit over time. Add to that, the amplifying force here is the data that we're going to share at CTOS that shows that that is our open label extension data. So for patients in the DEFY study, you know, who had benefited from treatment, this is one year more on drug. And those patients, we've shown and will show in the formal setting, continue to benefit. So, deepening tumor responses, more PRs, more CRs, better patient-reported outcomes, all of that logic that a physician has to have to say, "Listen, my patient will benefit not just for three years, but if you're at two years, that third year they will continue to benefit." And so that is how you will stack patients over time. And as we work through the, you know, the opportunity that is more than 10,000 patients in the U.S. alone who are currently getting treated, that is the opportunity we see. The one thing I'll add, Saqib, is that we're also seeing really favorable shifts in attitude among the physician community, and so when you look at the survey results that we had a year ago versus today, more physicians are willing to intervene purely on the basis of symptomatic presentation, whether it's pain or other functional limitations, as opposed to actually looking for, for example, formal radiographic progression for intervention, and so that becomes really important, especially when you think about the fact that our label has no restrictions with respect to the nature of progression required in the indication statement and also has pain reduction in the label, which becomes very meaningful, so in addition to those factors, we also have a shifting in attitudes among the prescribing community in terms of the desire and the proactiveness to intervene. Gotcha. And so I know the drug was well known in the sarcoma community based on a DEFY study. And just thinking about the 400 or so prescribers now, I'm sure the use has reached far beyond the sort of major academic centers in the U.S. at this point. And so do you feel that your commercial infrastructure is right-sized to address growing opportunity, or do you feel like there's more that you can do from a promotional perspective? I think we're largely right-sized because we're organized in our territories, but I do think we are looking to potentially supplement because, quite frankly, there is a lot in the community in addition to the centers of excellence. We would like to not wait for the patient to migrate because the typical path of a patient, wherever they enter, they wind up eventually with a surgeon or an oncologist, and typically within a tertiary center or a center of excellence. If we can get to them sooner, if we can actually intercede while they're waiting, we think there's an opportunity to help these patients who, quite frankly, are dealing with something specific. So let's think about what it means when I see 10% of 10,000+ claims. Remember, this is an enriched sample. So if you're going to go and get diagnosed for a desmoid tumor, you're not doing it for no reason. It doesn't show up on a normal exam. Chances are you have some symptomatologies, typically pain or a loss of function, that's making you go and get this assessment, which means you are more than likely to go out and seek a treatment because you have already made that affirmative step because something's bothering you enough. That is the opportunity we get to see. And so, you know, our opportunity is really how do you get to people, you know, sooner in, you know, for some physicians, they'll say, "Well, let's do some waiting. Let's, you know, you've shown up to me with this indication. Let's wait three months. Let's, you know, let's see how you're doing, and then we'll get you on some medication." How do we reduce that time of watchful waiting? And then you still have, in the United States, particularly outside the centers of excellence, you still see some certain percentage of people have surgery. We get to see those patients all the time because they get to be those who have had surgery or more surgery and have had a recurrence. And how do we get into that dialogue to prevent these unnecessary surgeries? And that, to me, is just it's all greenfield still from where we sit. Right. Maybe then a question about next year, 2025. So we've heard from other small molecule manufacturers that there may be another tailwind from IRA legislation coming that has to do with capping out-of-pocket expenses at a lower cap rate that could be a tailwind for high-priced oral drugs. Is that something that you expect to play a role for Ogsiveo as well next year? I mean, we are largely not an IRA population, right? So that's the other thing here. Not only are we a small molecule, most people first get diagnosed in their 30s, and so this is not largely a Medicare population base and, you know, exempt from a lot of the IRA issues. Right. Okay, great. And then at this stage in the launch, are you, you know, are you planning to provide 2025 guidance, sales guidance for the product next year? Haven't decided yet. I think, you know, the key to providing guidance is if you've got something that is meaningful, you know, if you've got information that people can rely on. And so, you know, for the first time, we give patient numbers, right, because we wanted to make sure that people see kind of the progress here, as well as understanding the denominator of how much more we have to go. We're going to make that assessment of guidance, you know, as we get closer to the year end, and we'll make that judgment at that time. If there's something that is useful, we can provide. Right. And I'm sure folks appreciate the additional visibility on some of those metrics that you put out now. So, and then just thinking about other opportunities, I know desmoid is the main market, a long way to go to penetrate that. But on the ovarian granulosa cell tumors where you have a phase 2 ongoing, I know you pushed out the timing a bit on the phase 2 data, but how should we think about that opportunity? Is that another indication where the drug could add value? Yeah, so that's another orphan oncology indication where we have on the order of 1,000-2,000 new diagnoses per year. This is a fatal disease, so median OS from recurrence post-surgery, depending on the data you look at, tends to be on the order of 5-10 years. And so there's a, you know, a small but meaningful population of patients here. There's nothing approved for these patients, and so they tend to cycle through Avastin, various types of platinum-based chemotherapy, anti-hormonal therapies, really searching for something to help prolong their ability to, you know, keep their disease at bay. When you look at the biology of ovarian granulosa cell tumors, these are almost uniformly driven by mutations in FOXL2, which is a transcription factor, and that really predisposes these tumors to signal heavily through the Notch pathway. And that's where the rationale for gamma-secretase inhibition came in. So in our phase 2 trial, which is fully enrolled, looking to put out the data in the first part of next year, that's a heavily pretreated patient population. They've seen basically everything that's available on guidelines and off-label by the time they made it to our trial. So really a patient population in dire need. And, you know, we think there's an opportunity there with Ogsiveo already being on the market to provide evidence that this could be beneficial to those patients as well. So we'll see it in the first half of. Correct. Yeah. Okay. And then I know for Ogsiveo, you have the European decision coming up next year too. And so how do you think about accessing the European market? We think it's a real market, and, you know, for a couple of reasons. One, you know, our phase 3 study, half of the sites of the phase 3 study were in Europe. So we've got, you know, pretty good penetration and visibility into the prescribers, the key opinion leaders, and we've got, you know, a group of patients who are waiting for the drug. There is no demographic predisposition for this disease. So the proportionate number that's in the U.S. should exist in the European territories where we're looking to get approval. So we think that the market is substantial. We think we've got a head start in it because we know the key prescribers and the key institutions that are, you know, collecting patients, which tends to be a little bit better organized as far as into centers of excellence in Europe. You know, we'll be launching hopefully next year, starting in Germany and working outside of Germany after that. The one thing I'll add just as a testament to the excitement for this drug in Europe is we actually have over 250 patients on compassionate use in Europe right now, and that's actually far in excess of what we had in the U.S. at the time that we launched. So it just gives you a sense of the fact that physicians are excited about this drug. They're aware of it. They're getting access to it for their patients, even in the pre-commercial setting. And obviously, starting next year, we can begin making that switch to the commercial drug. And it sounds like obviously you feel comfortable launching it on your own. Absolutely. Absolutely. I mean, our sales force in the U.S. is under 40 sales reps. We've started hiring our commercial leadership team and our commercial sales force for Europe as well. So obviously starting Germany and then other territories that follow. But we feel very good about our ability to access patients. Right. Sounds good. Okay. So I wanted to spend some time to talk about mirdametinib, which is your MEK inhibitor for NF1-PN, which is currently in front of the FDA with a PDUFA date coming up here in late February. And so, yeah, my question is really, as we think, we've seen the data, right? It looks great. And so as we think about labeling and prescribing information, things like that, are there any particular things that you're looking for as we head into the PDUFA date? Yeah, I think the most important thing here is the fact that we are going for both an adult and pediatric label at the same time, and importantly, adults comprise somewhere between 70%-75% of this market, and presently, there are no therapies approved for adults. So we think that's a real opportunity and a real potential for differentiation and certainly a head start on the market. As we think about what we really like about mirdametinib, it comes down to a number of factors. One is the clinical activity itself, so we've had really high objective response rates by blinded central review, very deep responses. We're actually presenting an abstract, an oral presentation at SNO looking at deep responders and how that's translating into really meaningful benefit for patients. And so the efficacy is very much there and something that has gotten physicians' enthusiasm, particularly that depth of response. Next really is the safety. And so as we think about the safety profile that we've put out, we're incredibly pleased with the relatively low rates of Grade 3 AEs, the low rates of discontinuations, the low rates of dose holidays. And that to us speaks to a product profile that can not only drive efficacy, but that can sustain it with longer-term dosing because patients are able to tolerate it so well. And then the third is really around the product's convenience as it relates to its formulation and its limited DDI liability. So on the formulation front, we're actually launching, or we intend to launch with both a pill that can be swallowed as well as a tablet that can be dispersed in water. And the reason that's meaningful is for a lot of these patients that are either younger or even older but have head and neck tumors, swallowing is really, really challenging. And so to have a tablet for the first time on the market that can be dissolved in water, can be drank from a cup or given orally with a syringe, that becomes a real compliance benefit for patients and their caregivers as you think about long-term dosing. And so, you know, we've tested this product formulation in our clinical trial. We've done separate testing on it. The likability scores are incredibly high, so patients and caregivers really like this. So that makes it a lot easier from a compliance perspective. And then we have in mirdametinib a drug with very few intrinsic drug-drug interaction liabilities. And so obviously these patients can have complex medical pictures. And so oftentimes they have to be managed with multiple drugs for other symptoms. And so the ability to be able to have a drug that can, you know, behave well with other drugs on board is another really meaningful factor here. So we're incredibly excited. We are, you know, on track to be first to market in the adults and certainly provide a really compelling profile for kids as well where the unmet need remains really, really high. I think it's important, at least, you know, from my perspective, you know, we're coming to the end of the discussion, but we have a, you know, within three months we've got a PDUFA date for a disease where, you know, you've got one drug approved for one quarter of the market opportunity doing $500 million of revenue with a tough product profile. To us, like that is an indication of the magnitude of the opportunity in front of us here. First in adults, we think we have got a best-in-class drug for children, and you've got 40,000 patients in the United States with NF1-PN. So even with, you know, three years of activity, you know, a competitor drug has not done, you know, as much as they can. And I think that's a reflection of some of the inherent liabilities of what is available to the patient population that we think we're solving. Right. And I know you probably won't go into any details, but as us analysts and investors think about the launch potential for mirdametinib in this indication, obviously there is a drug on the market which is a little different than the Ogsiveo launch. But yeah, how should we think about it in terms of some of the dynamics with a player in the market? Are we, you know, is it more competing for newly diagnosed patients? Is there opportunity to switch patients? Is there a prevalence pool that you can address? We talk about the prevalence pool of 40,000 patients right now. You have a competitor drug where they themselves indicate that they lose 50% of their patients within a year. So even among those who are being treated, there are those who are no longer being treated because of issues of tolerability typically and issues of continuity on medication. And you do need to stay on drug in order to get the benefits of tumor suppression here. So I don't believe we're just playing for, you know, certainly for adults will be the only, you know, the only approved medicine if the timelines hold for a period of time. But even for children, I don't believe we're just playing for newly diagnosed. I think there is a better profile for all the reasons that Badreddin just highlighted of mirdametinib for this patient population. And so if you think of kind of this on a macro level, there are many more patients. We talk about, you know, 10+ thousand for desmoid tumors, which we think is very large and supporting a, you know, over a billion-dollar opportunity in the U.S. There's 40,000 patients here. Drug pricing has been set. We think we've got a better drug, and we think we'll have the only drug in, you know, in three quarters of the commercial opportunity for a period of time. That all adds up to a meaningful, you know, peak. I'm not going to get into the discussion of what the ramp looks like, but I think to the peak, I think you can look at it as very analogous to what we're doing in desmoid tumors. Right. And as we think about just modeling in terms of pricing, I know you probably won't say here today what pricing will look like, but just given the differentiated profile, sometimes companies price at a premium over available therapies. Is that something that you're considering? Sometimes they do. Yeah. Great. And then just, you know, two seconds left. Any near-term updates we should expect on the early pipeline as we close out the session here? Yeah, I think we've got data coming next year as we talked about ovarian granulosa cell tumor with the brimarafenib program as well. We have our TEAD inhibitor that started dosing patients this year in a phase 1-A. That'll continue to progress. Then we have a number of preclinical efforts underway that we hope to be able to disclose in a relevant timeframe. Great, well, awesome. Thank you so much. Thank you. Thank you for the time. Badreddin, it was great to talk to you. Great to see you. Thank you.