Good afternoon. My name is Erica, and I will be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines conference call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press the pound key. Please, limit yourself to one question. Thank you. Kate Haviland with Blueprint Medicines, you may begin your conference. Thank you, operator. Good morning, everyone, and welcome to Blueprint Medicines' conference call to discuss the FDA approval of AYVAKIT and advanced SM. You can access the press release announcing the approval, as well as the slides that we'll be reviewing today, by going to the Investors and Media section of our website at www.blueprintmedicines.com. With me on the call today are Jeff Albers, our Chief Executive Officer, Becker Hewes, our Chief Medical Officer, and Christy Rossi, our Chief Commercial Officer. Before we get started, I would like to remind everyone that statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the Risk Factor section of our most recent quarterly report on Form 10-Q filed with the SEC and any other filings that we may make with the SEC. In addition, any forward-looking statement made on this call represents our views only as of today and should not be relied upon for representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statements. Now, here's our CEO, Jeff Albers. Thanks Kate. Good afternoon, everyone, thanks for joining us. Earlier today, the FDA approved AYVAKIT for the treatment of adults with advanced systemic mastocytosis. AYVAKIT is a truly novel medicine that provides remarkable clinical efficacy for advanced SM patients. Our team is already working with urgency to make sure AYVAKIT is made available to all advanced SM patients in the U.S. AYVAKIT was designed by our scientists to be a potent and selective inhibitor of the primary driver of systemic mastocytosis, KIT D816V. As many of you know, this approval in advanced SM is the culmination of years of hard work from our team in partnership with the medical and patient communities, as we have targeted SM from the early days of our company's founding. Systemic mastocytosis is a rare disease, like many other rare diseases, it's historically not been well-recognized and has been challenging to treat. With this approval, we can work with the SM community to fundamentally change the treatment paradigm for advanced SM and improve overall care and outcomes for patients. Today is truly the beginning of a new era of care for patients with advanced SM. Before digging into more details about the AYVAKIT ASM approval, let me remind everyone that Blueprint Medicines was built with the vision that a strong portfolio of targeted therapies would enable us to build a world-class biopharmaceutical company. With today's approval, our fifth across the U.S. or Europe in the past 18 months, we have further advanced that vision. We're proud of these recent accomplishments, but even more excited about what's to come as we build the world's leading precision therapy company. We believe AYVAKIT has the potential to be a transformative therapy for a broad range of systemic mastocytosis patients. This approval in advanced SM solidifies AYVAKIT's strong value proposition, upon which we will continue to build as we progress the development of AYVAKIT in non-advanced SM via our ongoing registrational Pioneer trial. Recently, we highlighted the continued flow of innovation from our research engine as we usher in the next wave of investigational drug candidates, each with the potential to address significant areas of patient need. With five promising development candidates nominated since the 4th quarter of 2019, we aim to carry forward our clinical development productivity and continue to work to translate our scientific innovation into tangible patient benefit and long-term growth. Combined with our established commercial footprint, the substantial collaborations we have in place, and a strong financial position that fortifies our ability to achieve our goals, the future is very bright for Blueprint Medicines. In many ways, our work is just getting started. I want to say for me personally, that this has to be one of the highlights of my career and one of the best days of my career. I reflect back when I joined Blueprint Medicines seven years ago, the very first meeting I was in was about systemic mastocytosis and the driver D816V, and I just am incredibly appreciative of all that I've learned along this journey from our investigators, from my colleagues, and most importantly, from the patients I've had the opportunity to meet that suffer from this severe disease. With that, I want to turn it over to Becker, who will walk us through the label, and then to Christy, who will discuss our launch plans. Becker. Thanks Jeff. Over the past 15 years, I've worked on multiple therapies for diseases without effective treatments. I came to Blueprint Medicines to be part of the cutting edge of precision medicine and participate in an approach that yields more victories than failures. What we're seeing here is the culmination of a six-year journey to demonstrate the power of a single compound designed specifically to tackle the aggressive tumor drivers KIT and PDGFR. Developing AYVAKIT has required collaboration with patients, regulators, and physicians to define multiple novel response evaluation criteria, optimize the dose for each indication, and include data across several clinical studies. Today's approval of AYVAKIT in advanced SM is certainly a proud moment for us as a team, and as Jeff said, the beginning of a new era of treatment and hope for patients with this disease. The FDA has granted full approval for AYVAKIT for the treatment of adult patients with advanced systemic mastocytosis. This includes patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. With this approval, AYVAKIT becomes the only therapy that precisely, potently, and selectively targets KIT D816V, the primary driver of this disease. Systemic mastocytosis is a clonal mast cell neoplasm characterized by hyperactivation and proliferation of mast cells. In advanced SM, mast cells also infiltrate vital organs, resulting in extensive, life-threatening damage. Patients with advanced SM typically live about three years from the time of diagnosis, and for patients diagnosed with the most aggressive subtype, mast cell leukemia, median survival is only about six months. The recommended dose of AYVAKIT for advanced SM is 200 milligrams taken orally once a day. The efficacy of AYVAKIT, as demonstrated across the Explorer and Pathfinder trial, was robust and consistent. The FDA utilized modified IWG, the most updated, clinically meaningful criteria to evaluate patient response. In patients receiving the recommended 200 milligram dose across both studies, the overall response rate was 57%. An additional 15% of patients had clinical improvement, which is another important category of response for patients. These results are consistent with the top-line data announced last fall, as well as those presented at medical conferences earlier this year. Safety was evaluated in 80 patients receiving a starting dose of 200 milligrams across both studies. Overall, AYVAKIT has been generally well-tolerated at this dose. There were no new safety signals identified, and there were no new warnings or precautions from the already approved PDGFRA GIST label. The most common adverse reactions occurring in at least 20% of patients are with the majority of adverse reactions being Grade one or two. AYVAKIT is not recommended for patients with a platelet count below 50,000, which is consistent with patient eligibility criteria in our clinical trials. The full prescribing information can be found on our product website, which is available at AYVAKIT.com. We're very pleased to see the transformative benefit that AYVAKIT brings for patients with advanced SM now reflected in our labeling. We look forward to generating additional data in non-advanced forms of the disease with the hope of impacting even more patients in the future. I'd like to thank the patients, families, clinicians, and advocacy groups who've all played a significant role in this approval. We're grateful for their support, and we join them in celebrating this achievement on behalf of all patients with advanced SM. I'll now turn the call over to Christy. Thanks Becker. Today is a truly important day for patients with advanced systemic mastocytosis and the culmination of many years of hard work by Blueprint, our investigators, and members of the SM community. As I've had the opportunity to interact with SM patients and the healthcare providers who care for them, I've been struck by the impact of this debilitating and, for many, life-threatening disease. The manifestations of SM can be severe and unpredictable, causing significant utilization of healthcare resources and profoundly impacting patients' quality of life. Today, patients with the advanced form of the disease, including those with all three of the subtypes that Becker described, have a powerful new therapeutic option that can truly transform their care. We've been eagerly anticipating today's approval for quite some time. Indeed, we built our commercial and medical affairs infrastructure with a view towards today's milestone, and we're ready to hit the ground running. Our launch efforts will be focused in three primary areas. The first is the identification of patients. Most advanced SM patients are diagnosed, and our work understanding treatment referral patterns has led us to target 70 hematology- oncology centers that treat around half of the estimated 2,000- 3,000 advanced SM patients in the U.S. As we've discussed previously, we will initially prioritize these centers while leveraging our portfolio-based approach to expand patient identification more broadly into the community setting over time. We also believe that the increased availability of highly sensitive blood-based tests for KIT D816V will increase the number of SM patients who are diagnosed and have access to treatment over time. Our second priority is focused on healthcare provider and patient education, disease state education, which will ensure patients are diagnosed more quickly and have access to appropriate care, as well as education on the compelling clinical value proposition of AYVAKIT. As Becker noted, AYVAKIT is the first and only therapy that effectively targets KIT D816V, the primary driver of this disease, and it has the potential to be transformative for many advanced SM patients. AYVAKIT has generated deep and durable responses, which have translated into extended treatment duration in a patient population that unfortunately has a life expectancy on the order of months to a few years. Its clinical efficacy profile, coupled with a favorable safety profile and a convenient one tablet a day dosing regimen, can meaningfully benefit patients. Third, we will strive to provide best-in-class access and support for patients by leveraging our expertise and infrastructure from our previous launches of AYVAKIT and GAVRETO, while also meeting the unique needs of advanced SM patients. The YourBlueprint Patient Support Program offers financial assistance and tailored support to patients throughout their treatment journey, including copay assistance, no-cost medication to patients who qualify, and other programs. Our goal is to help every patient who is prescribed AYVAKIT to start on therapy quickly and have continued access to therapy as long as it is clinically indicated. Ensuring access for patients also includes providing significant value to payers. The value proposition for AYVAKIT in advanced SM is primarily built on the transformational clinical outcomes we have seen in a rare patient population with significant medical needs due to a disease that drives significant morbidity and mortality. Our commitment to SM patients does not stop with today's approval. We are working to develop treatments for every patient suffering from SM, as evidenced by our development programs for both AYVAKIT and BLU-263. AYVAKIT is already available for patients with PDGFRα GIST in multiple dose formats, 300, 200, and 100 milligrams, and we will be adding 2 more, 50 milligrams and 25 milligrams. We will be maintaining our flat pricing model, which provides predictability to payers and healthcare providers. This approach provides pricing predictability and transparency, and our range of dosage strengths gives healthcare providers and patients the ability to easily adjust those based on individual patient needs. We anticipate our new dose strengths will be available within approximately one week through our established network of specialty pharmacies and specialty distributors. We've been thoughtful about our distribution approach to ensure convenience and to best support the needs of patients. When I initially joined Blueprint and worked with our team to develop our strategy and organizational approach, it was with today's milestone in mind. We have experienced teams in place across our commercial and medical affairs organization. With today's approval, we could not be more excited to deliver this transformative therapy to patients. We also look forward to building on this foundation with the continued development of AYVAKIT and BLU-263, as well as the progression of our other promising candidates in development across our portfolio to be able to positively impact the lives of an increasing number of patients in the years to come. With that, I would now like to turn the call over to the operator for any questions. Operator? Your first question comes from the line of Salveen Richter with Goldman Sachs. Good question. This is Andrew on for Salveen. Congratulations on the approval here. Maybe one question for Becker or Jeff. Just wondering if you could speak to the evolving response to AYVAKIT that you're observing here in patients as it looks like the ORR decreased from the top line read, but your CR has increased. Sure. I'll take that. This is Becker. As we said in the announcement, the way the FDA looks at the response criteria is to remove the clinical improvement, which is why there's an apparent decrease. It's not actually a decrease. The other thing that we've spoken to a number of times is that the responses do deepen over time. We've seen this over many months and years of therapy that patients at all doses will continue to get into complete response from partial response and go into partial response from that clinical improvement area of response. Perfect. Thanks so much for the clarification. Your next question comes from the line of Marc Frahm with Cowen and Company. Thanks for taking my questions. Let me start by offering my congratulations to the whole team. For Christy, just with the patient population, can you lay out where they're located? I think when you got the approval for GIST, you gave some guidance on kind of patient mix in terms of the payers that would be supporting them. Are there any differences we should be thinking about here? I guess related to that is should the person at profile stay roughly the same as where it's been? Yeah. This patient population actually looks very similar to GIST in terms of the age distribution, and our expectation is that the payer mix is likely to look similar as what we've been seeing with AYVAKIT. We wouldn't expect major differences in terms of course, path utilization, et cetera. That'll be something we'll continue to monitor, and we do look forward to a potential approval in non-advanced forms of the disease down the road that would potentially be a younger patient population. There could be a difference there. For now, I think it'll be consistent. Okay. Thank you. I'll come back in a bit. Your next question comes from the line of Dane Leone with Raymond James. Hi. Thank you. Congratulations on the approval and the well-written, clean label that everyone was hoping for. For me, just a question, how you guys are going to handle commercial pricing across the different dosages, given there will be some dose titration until strengths available. Sure, I can take that. As you know, we currently take a flat pricing model, so the price is the same regardless of dose strength, and we are continuing that approach with the 50 and 25 milligram. It's something that's worked well. We've gotten positive feedback from a variety of stakeholders in the community around that, and so we will be using a consistent approach. Your next question is from David Lebowitz with Morgan Stanley. Thank you very much for taking our questions. Do you expect that some doctors might consider off-label use in indolent populations, given that there is dosing for a 25 mg formulation available, and so they would be able to use a considerably lower dose in such patients? I can take it as Christy. When we think about this indication, we start again from a perspective of the disease state overall, which as we know, the patients across the spectrum with SM and subtyping patients accurately is not always clear. We saw that in our own studies where we saw patients in our advanced SM studies who were eventually readjudicated as actually having indolent disease. I don't have an expectation that we would be seeing a lot of utilization necessarily in patients who are truly due to be indolent. I do think you may see patients who have very symptomatic disease where the classification may not be completely clear. Our expectation is that prescribers who are prescribing the drug initially are doing it because they feel that the patient fits the clinical criteria for the drug. That having a 50 and a 25 milligram strength available really helps to ensure that providers can dose adjust in line with the guidance that's in the label to really appropriately manage patients and help support them on therapy over the long term. Thanks. Thanks for the question. Your next question is from Joel Beatty with Baird. Hi, thanks for taking the question and congrats on the approval. Can you help us set expectations for use in patients that are not at those 70 hem-onc docs that the sales force will be initially focused on? Do you expect any use of the drug in patients at those other docs? Can you tell us about the support services that would be available for those docs and those patients? Absolutely. We are focused on 70 key centers because we know that they have capability and capacity to treat advanced SM. We also know that, as you say, patients are treated in the community, we do have a commercial and medical affairs team that's already engaging in the community to support GAVRETO as well as AYVAKIT. We will be focused there to provide education, help facilitate patient diagnosis, whether the patient would be treated there or referred would be up to the prescribing physician. We are 100% there to support appropriate patient ID and treatment in the community as well. Great. Thank you. Your next question is from Michael Schmidt with Guggenheim Securities. Good afternoon, everyone. This is Charles Zhu on for Michael Schmidt. Congrats on the approval with the tuned label. Thanks for taking the questions. If I may impose on you for a couple of them. First, as a follow-up to Dane's earlier question, could you just elaborate a little bit upon how flat pricing could potentially impact the dose strength that will potentially be used for the ISM future opportunity? Is it fair to assume that that strength will, that 25 mgs will be 1/4? It sounded like you said it was going to go flat across the board. As a second question, a bit more commercially based. Could you just remind us very quickly what proportion of patients are currently being identified and treated amongst the indolent population? How should we think about how this potentially impacts launch dynamics both in the U.S. and abroad? I guess as a last follow-up, what proportion of these patients have this baseline thrombocytopenia? Thank you. Hopefully, I will get through hit all of those points. To start, again, just to clarify on pricing. With this launch, we are making 50 milligram and 25 milligram strengths available. Those are strengths that are indicated in the PI. Healthcare providers will have the ability to utilize those strengths as appropriate to individualize patient management and care. We will be taking a flat pricing approach across all of the strengths that we have. How that evolves as we get towards a potential ISM approval down the road is something that we'll continue to evaluate and engage with the community. We will take a very similar approach in terms of thinking about pricing, which is centered on 1 way to deliver value to the system and to patients, and 2, really ensuring that we support patient access. More to come as we get towards the potential approval there. In terms of the proportion of patients. Again, we estimate about 2 to 3,000 patients in the U.S., of which the majority are diagnosed, about half of which are treated at these key centers. That's where we will focus initially, but we'll also be in the community to really facilitate patient ID, et cetera. The dynamics outside the U.S. differ country to country. One aspect in Europe is certainly they have an organized approach to SM treatment through the ECNM in many countries. In most countries, there's also a center-based approach to the management of advanced SM patients. You had 1/3, the last question, which I'm sorry. Yeah, what percent of patients will have- Oh, thrombocytopenia. Yeah. We estimate about 10%-15% of advanced SM patients may fall below that criteria of 50,000. Understood. Thanks. Your next question is from Arlinda Lee with Canaccord Genuity. Hi, guys. Congratulations on the SM approval. Can you talk a little bit more about the label population? What proportion is treated at the 70 centers you're initially targeting, and can you talk about how that compares to what you think are the addressable SM population? Lastly, can you provide an enrollment update on PIONEER? Again, we think that the majority of the advanced SM patient population is diagnosed in the U.S. and about half would be treated at these key centers. We believe that most patients are potentially addressable. Obviously, the appropriateness of any therapy in a given patient is going to depend on a lot of factors and how that healthcare provider is approaching that patient's treatment plan. Of course, we have the limitation of use where we will want to ensure that healthcare providers understand how to use AYVAKIT and would not use it in a patient that's thrombocytopenic. That will be a key point that we'll be educating on. This is a patient population with a really significant medical need, and AYVAKIT is a really transformational new therapeutic option that we think will be impactful for many of these patients. With respect to PIONEER enrollment, overall, we're on track. We continue to see enthusiasm and demand for the study, both from investigators from Part 1 and new investigators. Recently, we've seen a doubling in the screening rate. We anticipate with today's approval and strong label that there'll be further awareness of AYVAKIT and expect even additional momentum on our enrollment rate. Early in the study, we were really focused on opening clinical sites, particularly with COVID. We reached a critical mass with the majority of sites activated this spring. This is including some high-priority sites in Europe where there are large patient populations identified. Since then, we've started to shift our focus to driving a pull-through from patient screening to enrollment. That's a key metric that we're following internally. We anticipate sharing additional updates on this trial as we continue to make progress in the future. Thank you. Your next question is from Peter Lawson with Barclays. Thanks. Thanks for my question. Congratulations to the team. I guess first question or first and sole question would be just around the label population, how that was selected by you or the FDA in the sense of how you got to the 53 from the EXPLORER plus PATHFINDER study. Yeah. The discussions with the FDA were focused around the 200 milligram dose, and we had a few patients in the EXPLORER study and all the patients in the PATHFINDER study that were at that 200 milligram dose. The safety and efficacy is based on that, which is the label dose. The piece of the IWG at baseline dropped some of the 200s down because I think they were looking for total safety. The criteria where the patients had to start at 200 milligrams, they had to be IWG evaluable from baseline. That creates the crosswalk, which we shared, in fact, I think it was at ASH 2020. Yeah, maybe. Two years ago. Perfect. Thank you so much. I think more broadly, one of the things why today is so rewarding is this is a complex response criteria. Early on, we knew we had a very active molecule, and we're incredibly encouraged how we've seen deepening of responses in a consistent manner and more broadly, just clinical benefit in these patients. Working through to the evaluable patient when you're looking across two studies, when it's in an open label trial with different doses, it definitely took a lot of work by a lot of folks within Blueprint, from our investigators, from the regulatory authorities, and really felt like we landed at a very consistent spot with this label to the way we've presented data previously. I think for me personally, that's incredibly rewarding. There are no further questions at this time. Mr. Albers, I'll turn the call back over to you. On short notice, thanks, everyone. It's always interesting when you're pushing up right to the PDUFA date. We appreciate all the patience that you've all shown. We're excited to get moving. As I said in the opening remarks, in a lot of ways, we feel like we're just getting started and look forward to continuing to work with the SM community, the physicians, the patients, to make avapritinib available to as many patients as possible. Everyone, have a great evening. Bye-bye. This concludes today's conference call. You may now disconnect.