Good morning, and welcome to the SpringWorks Therapeutics conference call to discuss the Phase III DEFY trial top-line results. At this time, I'd like to turn the call over to Kim Diamond, Vice President of Communications and Investor Relations. Thank you, Kevin, and welcome to the SpringWorks Therapeutics conference call to discuss the top-line data from our Phase III DEFY trial evaluating nirogacestat in adult patients with progressing desmoid tumors. Leading the call today will be SpringWorks' CEO, Saqib Islam. Saqib is joined by our Chief Development Officer, Dr. L. Mary Smith, and our Chief Operating Officer, Dr. Badreddin Edris. Following our prepared remarks, we will be taking questions. Slides to accompany this conference call are posted in the investors and media section of our website at www.springworkstx.com, and an audio webcast with the corresponding slides is also available on the website. Before Saqib begins, I'd like to remind you that today's presentation will contain forward-looking statements that involve risks and uncertainties, and that the company's actual results or outcomes of its development activities 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. With that, I'm pleased to turn the call over to Saqib Islam, Chief Executive Officer of SpringWorks. Saqib. Thank you, Kim, and good morning, everyone. It is my great pleasure to share the positive top-line data from our Phase III DEFY trial, which we announced earlier this morning. DEFY is a double-blind, placebo-controlled Phase III study evaluating Nirogacestat, our gamma secretase inhibitor, in adult patients with progressing desmoid tumors. We are very pleased that the trial met its primary endpoint of significantly improving progression-free survival as compared to placebo, as well as all key secondary endpoints, including objective response rate and patient-reported outcomes. We expect these data to serve as the basis of our first NDA filing later this year. This is a great day not only for SpringWorks, but also for the desmoid tumor community, since today's data represents an important step forward in our mission of bringing the first FDA-approved therapy to these patients. While today's call will focus on DEFY, I'll first provide a brief overview of SpringWorks to provide context for how today's results fit into our broader portfolio of opportunities, all of which are focused on achieving profound impact for patients suffering from devastating cancers. Our 18 research and development programs span early and late-stage clinical development and focus both on rare tumors and highly prevalent biomarker-defined cancers in areas of high unmet need. In addition to our standalone development efforts, we've also partnered with industry and academic leaders on several of our programs in order to advance our mission of bringing important new treatment options to cancer patients. As you can see on slide 5, our pipeline is organized across three distinct oncology segments: rare oncology, BCMA combinations in multiple myeloma, and biomarker-defined metastatic solid tumors. We see significant opportunity across each of our focus areas. Nirogacestat is our most advanced product candidate and has the potential to not only be the first FDA-approved treatment for desmoid tumors, but also the first FDA-approved gamma secretase inhibitor in any indication. Beyond our rare tumor efforts, we are comprehensively advancing this first-in-class gamma secretase inhibitor as a potential cornerstone of BCMA combination therapy in multiple myeloma, highlighted by our eight industry collaborations across four BCMA therapeutic modalities. In addition to the significant opportunities to serve patients with desmoid tumors and multiple myeloma, we expect continued expansion of nirogacestat development into an additional new oncology indication this year. mirdametinib, our MEK inhibitor, is our second most advanced program and is currently in a potentially registrational Phase 2b trial for patients with NF1-associated plexiform neurofibromas. We are also taking a precision oncology approach to highly prevalent solid tumors through six different monotherapy and combination therapy programs, with mirdametinib serving as the backbone for several of these efforts. We look forward to sharing more data and highlighting the breadth and depth of our portfolio in the coming weeks, starting first with ASCO and then immediately following the conference at our R&D day on June 10. Turning now to slide 6 for an overview of Nirogacestat and why we believe it has the potential to transform the treatment paradigm for patients with desmoid tumors. Nirogacestat is a potentially first-in-class oral gamma secretase inhibitor. It has received Fast Track, Breakthrough Therapy, and Orphan Drug designations from the FDA. In addition to securing these important regulatory designations, we have also focused on the manufacturing infrastructure required for the broad development programs that are underway, as well as our plans to make Nirogacestat commercially available following a regulatory approval. Furthermore, Nirogacestat has been granted several U.S. composition of matter and method of use patents that extend intellectual property protection into 2039. We are extremely gratified to share today that the DEFY trial met its primary and all key secondary endpoints, setting up the opportunity for SpringWorks to file an NDA in the second half of this year. I will now turn the call over to Dr. Mary Smith, our chief development officer, to walk us through the unmet need in desmoid tumors and the DEFY trial top line results. Mary. Thank you, Saqib. It is my great pleasure to discuss the DEFY top line results with you today. First, I'd like to emphasize that desmoid tumors are devastating for patients and their families. These are rare, aggressive, and locally invasive soft tissue tumors that can cause severe pain and morbidity, including disfigurement, vascular constriction, and loss of physical function. In rare cases, when near or involving vital organs, desmoid tumors can also be life-threatening. While they do not metastasize, desmoid tumors are associated with high rates of recurrence following surgery, making surgical interventions increasingly less favored in clinical practice today. Desmoid tumors are most commonly diagnosed in patients between their third and fifth decades of life and are more prevalent in women. It is estimated that there are 1,000-1,650 new cases diagnosed per year in the United States. As Saqib mentioned, there are currently no FDA-approved therapies for the treatment of desmoid tumors, and systemic therapies being used off-label are often poorly tolerated with inconsistent efficacy. All of this points to a very serious disease with a significant unmet need for patients, many of whom have had significant morbidity and decreased quality of life as a result of their disease. Turning to slide 9, here is the DEFY trial design. DEFY is a double-blind, placebo-controlled, event-driven trial that randomized 142 adult patients across sites in North America and Europe. Patients were randomized 1:1 to receive 150 mg of Nirogacestat twice daily or placebo. Eligible patients had desmoid tumors that had grown by greater than or equal to 20% as measured by RECIST within 12 months prior to study screening. DEFY also includes an open label extension for patients who had progressed radiographically while in the double-blind portion of the trial, or for those who were still ongoing in the double-blind Phase of the study at the time of the primary analysis. The primary endpoint is progression-free survival as assessed by blinded independent central review, and this applied both to radiographic and clinical progressions. Key secondary and exploratory endpoints include safety and tolerability, objective response rate, duration of response, changes in tumor volume as assessed by MRI, and changes in patient-reported outcomes, including desmoid tumor symptoms, pain, physical functioning, and health-related quality of life. Now turning to the top line data on slide 10. As we announced this morning, the DEFY trial met its primary endpoint of improving progression-free survival, as assessed by blinded independent central review. This result was statistically significant with a hazard ratio of 0.29 and a P value of less than 0.001. In addition, the study also met all of its key secondary endpoints, including objective response rate and several patient-reported outcome measures. Nirogacestat was also generally well-tolerated in the DEFY trial with a manageable safety profile. The majority of women of childbearing potential had adverse events consistent with ovarian dysfunction. Other adverse events were generally consistent with safety data reported in earlier trials of Nirogacestat. Overall, we believe these data provide compelling evidence of the clinical benefit that Nirogacestat may offer patients with desmoid tumors and look forward to a comprehensive data presentation at an upcoming medical conference. With that, I will now turn it back over to Saqib. Saqib. Thank you, Mary. We are very pleased with these top-line results from our DEFY trial, and we look forward to working closely with the FDA as we prepare to file our NDA later this year. We take our commitment to the desmoid tumor community very seriously, and today's announcement puts us closer to achieving our goal of providing the first FDA-approved treatment for people living with this devastating disease. Turning to additional near-term milestones for SpringWorks, we look forward to ASCO in early June, where investigators from the National Cancer Institute will report long-term follow-up data from the Phase II study of nirogacestat in adults with progressing desmoid tumors, a similar patient population that was evaluated in DEFY. Also at ASCO, initial clinical data from our combination study with GSK evaluating nirogacestat in combination with low-dose Blenrep will be presented by our collaborator. The objective here is to determine if low-dose Blenrep in combination with Nirogacestat results in similar efficacy with an improved ocular toxicity profile as compared to single-agent Blenrep at its approved dose and schedule. We believe these data will have important read-through for the totality of our BCMA combination programs. We also see significant opportunity for our MEK inhibitor, Mirdametinib, both as a monotherapy in rare tumors like NF1-associated plexiform neurofibromas and low-grade gliomas, as well as combination therapy in biomarker-defined metastatic solid tumors. We look forward to discussing our broader pipeline at our R&D Day on June 10, which will include clinical data across our rare oncology BCMA combinations in multiple myeloma and biomarker-defined metastatic solid tumor programs, as well as our commercial preparations for serving patients with desmoid tumors. In closing, these positive top line results from our DEFY trial represent a significant milestone for SpringWorks and for the patients that we aim to serve. I would like to thank the patients, their families, and the DEFY trial investigators for their participation in this study. I would also like to thank our dedicated and tenacious team of SpringWorkers who worked with urgency to help achieve this very important milestone. With that, operator, please open the call for questions. Ladies and gentlemen, if you have a question or a comment at this time, please press the star then the one key on your touchtone telephone. If your question has been answered or you wish to move yourself from the queue, please press the pound key. Our first question comes from Anupam Rama with J.P. Morgan. Hi, guys. Congratulations on the data, and thanks so much for taking the questions. Two quick ones from me. Could you put the ovarian dysfunction into context here? Is this a class effect? Can you remind us how was it managed in the study? Is it reversible? How does this ovarian dysfunction compare to existing therapies that are used for desmoid tumors? That's question one. A second question, can you also confirm that duration of response and tumor volume change were also stat sig on the primary endpoint and secondary endpoints? Thanks so much. Thank you, Anupam, and I'll take the first question or the series of questions first here. I would say that Nirogacestat, as we said, was generally well-tolerated with a manageable safety profile. The ovarian dysfunction is a compilation of preferred terms that encompasses several symptoms associated with ovarian and reproductive function. I'd highlight that as you suggest, that there is a class effect here, as it relates to ovarian dysfunction. I would also highlight that alternative therapies, whether chemotherapies and tyrosine kinase inhibitors, also have an impact on ovarian function. Overall, we believe that the data to date are consistent with a favorable risk-benefit profile for Nirogacestat in desmoid tumor patients, including women of childbearing potential. As we mentioned this morning, we believe that Nirogacestat was generally well-tolerated with a manageable safety profile, and we look forward to sharing data at a medical congress in the second half of 2022, where we can get into some of the more specific questions around reversibility and more information here that we still think leads towards a very favorable risk-reward for women of childbearing age on Nirogacestat. As it relates to some of your other questions that were part of your one question, I would say that what we have highlighted for the moment is that all key secondary endpoints we met with meaningful statistical significance and more data to come at a medical congress in the second half of this year. Thanks for taking our question, guys, and congratulation again. Thank you, Anupam. Our next question comes from Yaron Werber with Cowen. Great. Thanks for taking my question, and congrats also. I have a couple of questions. Maybe the first one on the PFS endpoint. Can you give us any sense on how many of the events were clinical progression versus radiographic progression? Secondly, when one looks at the prior results with Nirogacestat in desmoid tumors, and one looks specifically at the ovarian insufficiency, I believe what I've seen is hot flashes and irregular menses, which were all grade one in nature. Can you talk about whether what you're seeing in the study is sort of consistent with that or, and again, whether one would expect women to potentially drop out because of that in the study? I mean, obviously you have such a huge PFS benefit here that it couldn't have been that a ton of people dropped out. Just wanna get your thoughts. Yeah, I mean, in the realm of what we can speak about at the moment, Yaron, I would say the vast majority as we've indicated were radiographic progressions. You know, with this amount of statistical significance, I think that we are very well positioned here, whether radiographic or clinical. The vast majority of the events were radiographic progressions. As it relates to you know, the challenges of ovarian dysfunction, as we said, it is a class effect. It is generally consistent with what we've seen elsewhere. We will share more data as we get to a medical congress in the second half of the year. As you know, as we tried to highlight, we think that it is not only is it consistent generally with what we've done and what we've seen in the past, it is also an indication. Elements that would exist in alternative therapies, and we think the risk-reward benefit profile, you know, argues heavily towards the use of Nirogacestat. You know, you made the comment about expected dropouts notwithstanding this effect, given the nature of the study and given the P value here, and I think that speaks for itself. Thank you. Our next question comes from David Nierengarten with Wedbush Securities. Hey, thanks for taking the question, and it's nice to see some positive data. Maybe a follow-up on discontinuation. I mean, is it fair to presume from, you know, some commentary around the open label extension that, you know, again, a majority of patients remained on therapy or switched over if they were on placebo to the Nirogacestat treatment and are, you know, essentially remaining on therapy. Is there, you know? I'm just checking in on any, you know, if you could provide any kind of detail on that, it would be helpful, or at least, you know, the number of patients who went on for the open label extension. Thanks. Sure. I'm happy to take that, David. This is Badreddin. We haven't disclosed any of that type of information on the number of patients on the open label extension at present or any of those dynamics, but we would anticipate doing so over time at an appropriate medical conference. Of course, there's one quick follow-up with that. Of course, there's a ClinicalTrials.gov study in ovarian granulosa tumors. I mean, is it fair to assume that that's the second indication we're talking about as a monotherapy? That is indeed a new monotherapy opportunity for us, the Phase II trial that we just launched in ovarian granulosa cell tumors. As indicated previously, we intend to share a lot more about why we're excited about that monotherapy opportunity for Nirogacestat at our upcoming R&D day on June tenth. Yeah. Got it. Thank you. Our next question comes from Peter Lawson with Barclays. Hey, thanks, Nicole. Thanks for taking the questions. Just, I guess a simple question. How many patients, how many events, was this reflective of? Was it 51 events or less? I've got a couple of follow-ups. What I would say is the trial ends at 51 events. We will be sharing the full data set on the back of this when you know when we share the full data set at the appropriate medical congress, Peter. I think the summary here is reflective of you know kind of the powering, the success of this study is pretty clear. The ASCO long-term follow-up data, will that give us any hints about the reversibility potential of this, the ovarian insufficiency? Yeah, we're certainly excited for the Phase II long-term follow-up data to be presented by the ASCO or by the NCI investigators that led the Phase II trial. We think that will provide additional lens on the activity and tolerability profile of Nirogacestat over a longer term, as you alluded to in your question. That said, until the abstracts are public, we obviously can't get into any of the specific data that are gonna be part of that presentation, but we think it's gonna be quite informative as it relates to long-term dosing dynamics in these patients. Gotcha. Thank you. Final follow-up, just what percentage of these women were enrolled in this trial? We haven't disclosed that type of demographic data. Mary, I don't know if there's any color you wanna share. I would just say that it's consistent with what we would expect from the majority of desmoid patients being women. It's representative of the patient population. Perfect. Thank you so much. Our next question comes from Corinne Jenkins with Goldman Sachs. Good morning, I'd add my congratulations on the data. Given where we were with respect to the number of events, kind of as you approach the triggering of the analysis, is it fair to assume that you haven't reached a median progression-free survival in the treatment arm? I think it's premature to reach that conclusion. I think what we saw in Phase I and Phase II is that we did not reach median progression-free survival in either arms there, which were treatment arms. I think it's until we share the full data set, Corinne, it's hard for us to get more specific, but it wouldn't be an unreasonable place for you to be to assume that there's a strong benefit and certainly a difference between treatment and placebo here. Obviously, you see the hazard. I think I can- You do the hazard ratio of 0.29, right? Right. Can you just remind us as you approach a filing in the second half of this year where you stand with respect to some of the CMC preparations? Yeah. I think we're in actually very good stead, and I think part of this is driven by our preparations through the pandemic of being multi-source from, you know, an API, drug substance, that product standpoint. And also what we have to do to be ready to make sure that there's enough available in the BCMA context as well for our partners. I think we're in a very good position, you know, with small molecule manufacturing, but with a very clear understanding of what is required from a manufacturing standpoint for us to be ready for a commercial launch next year. I think this is a situation where given the fact that we're using Nirogacestat in these different settings has allowed us to be quite prepared for a launch here for desmoid tumors. Great. Thank you. Thank you. Our next question is a follow-up question from Peter Lawson with Barclays. Hey, thank you. Just as we think about cash runway and kind of build out of the sales, how should we be thinking about that and kind of where can the cash runway get you? Well, we said that our, you know, our cash, we talked about having over $380 million as of the last quarter. That gets us into 2024 comfortably. We think we've got pretty significant flexibility and multiple data readouts, you know, starting with more information at ASCO, our R&D day, and more with MEK and more of our combinations, well before we actually are in a position to need cash. I think we're in a very good spot as it relates to cash. Thank you. Just as we think about safety and read through to the BCMA combinations, is there anything else we should be thinking about, beyond the ovarian insufficiency that was called out in the press release? I think the ovarian insufficiency, as we said, it's consistent with what we've seen before, and ovarian dysfunction, I think, is the umbrella term here. I, you know, I think you're not gonna have to wait long, Peter, for the data from ASCO to actually reveal itself. We feel quite good, as we felt quite good going into top-line data, notwithstanding some skepticism, we feel quite good going into ASCO. The safety profile you've seen kind of is consistent with what you've seen in the past Phase I, Phase II, so there's nothing that surprised you in that phase III data set? It is, as we said, it is consistent. Perfect. Thanks so much. congratulation. Thank you. This concludes our call for today. Thank you for joining. You may now disconnect.