Q4 2023 Blueprint Medicines Corp Earnings Call

Drew: Good morning, my name is Drew, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines fourth quarter and full year 2023 financial results conference call. All lines have been placed on mute to prevent any background noise.

Good morning, My name is John and I'll be your conference operator today.

Speaker Change: Time, I would like to welcome everyone to the blueprint medicines fourth quarter and full year 2023 financial results 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.

Operator: After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press start, followed by the number one on your telephone keypad. If you would like to withdraw your question, press start, followed by the number zero.

Speaker Change: If you would like to withdraw your question press the star followed by the number Chase. Please plan to limit your questions to one. Thank you Jana Cohen you may begin your conference.

Operator: Please plan to limit your questions to one. Thank you. Jenna Cohen, you may begin your conference. Thank you, Drew, and good morning, everyone. Welcome to Blueprint Medicine's fourth quarter and full year 2023 Financial and Operating Results Conference call. This morning, we issued a press release that outlines the topics we plan to discuss today. You can access the press release as well as the slides that we'll be reviewing today by going to the investor section of our website at www.blueprintmedicines.com. Also joining me today are Kate Haviland, Chief Executive Officer, Helena Lee, Chief Commercial Officer, Fouad Namouni, President, Research and Development, and Mike Lancettle, Chief Financial Officer. Christy Rossi, Chief Operating Officer, and Becker Hughes, Chief Medical Officer, are also on the line and available during Q&A. Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements, as outlined on slide three, and are subject to a number of risks and uncertainties. These may cause our actual results to differ materially, including those described in our reports filed with the SEC.

Yeah.

Jana Cohen: Thank you Joe and good morning, everyone welcome to blueprint medicines fourth quarter and full year 2023 financial and operating results Conference call. This morning, we issued a press release, which outlines the topics. We plan to discuss today you can access the press release as well as the slides that we'll be reviewing today by going to the investors section of our website at www.

Dot blueprint medicines Dot com.

Jana Cohen: Joining me today are Kate Haviland, Chief Executive Officer, Alina, Lee Chief Commercial officer.

Speaker Change: I've been really President research and development and my glands that old Chief Financial Officer, Christy Rossi, Chief operating Officer, and Becker Hughes Chief Medical Officer are also on the line and available during Q&A.

Speaker Change: Before we begin I'd like to remind you that some of the statements made during the call. Today are forward looking statements is outlined on slide three and are subject to a number of risks and uncertainties may cause our actual results to differ materially including those described in our reports filed with the SEC you are cautioned not to place any undue reliance on these forward looking statements and blueprint.

Jenna Cohen: We are cautioned not to place any undue reliance on these forward-looking statements, and Blueprint disclaims any obligation to update such statements. And with that, I'll now hand the call over to Kate. Thank you, Jenna, and good morning, everyone.

Speaker Change: Claims any obligation to update such statements.

Speaker Change: I'll now hand, the call over to Kate Thank you, Jennifer and good morning, everyone.

Kate Haviland: 2023 was a pivotal year for Blueprint Medicines as we successfully brought AvaKit forward to become the first and only approved medicine for patients with indolent systemic mastocytosis, or ISF. As we enter 2024, AvaKit will continue to be the foundation of our thriving business, with our early launch momentum putting AvaKit firmly on the path to becoming a multi-billion dollar product. Our growing revenue also enables us to invest in additional compelling opportunities in our pipeline to drive longer-term growth and deliver even more transformational medicines in the future. To achieve our goals this year, we're focusing on three key aspects of the business.

Kate Haviland: 2023 with the pivotal year for blueprint medicines as we successfully brought forward either cat to become the first and only approved medicine for patients with indolent systemic mastocytosis or I get that.

As we enter 2024 Ava pet will continue to be the foundation of our thriving business without early launch momentum pretty Ava kit firmly on the path to becoming a multibillion dollar product.

Kate Haviland: Our growing revenue also enabled us to invest in additional compelling opportunities in our pipeline to drive longer term growth and deliver even more transformational medicines in the future.

Kate Haviland: To achieve our goals this year, we're focusing on three key aspects of the business.

Kate Haviland: Let's start with AvaKit's blockbuster potential and its ability to drive durable revenue growth for Blueprint well into the next decade. We know that the first few quarters of launch are critical in designing the sales trajectory for a product, and we have driven a very strong first six months of results in this ISM1. Establishing the Foundation for Future Growth

Kate Haviland: Let's start with either kept blockbuster potential and its ability to drive durable revenue growth will blueprint well into the next decade.

Kate Haviland: We know that the first two quarters of launch are critical in designing the Dell trajectory for our product and we have driven a very strong first six months of the results and the size and lunch.

Kate Haviland: Establishing the foundation for future growth.

Kate Haviland: We've clearly demonstrated our ability to reach patients and drive revenue, achieving $204 million in global advocate revenue in 2023, an 84% increase over 2022. This compelling growth was primarily driven by the uptake of patients with ISM, who comprise about 95% of all patients with SM, a sizable rare disease patient population that we estimate at 70,000 prevalent patients in the U.S. and Europe alone. Today, we are pleased to provide 2024 AvaKit revenue guidance of $350 million to $390 million, putting us on pace to nearly double our sales this year.

Kate Haviland: We have clearly demonstrated our ability to reach patients and drive revenue.

Kate Haviland: Keeping $204 million in global <unk> revenue in 2023, and 84% increase over 2022.

Kate Haviland: This compelling growth was primarily driven by the uptick in <unk>.

Kate Haviland: Patients with I S M.

Kate Haviland: Who comprise about 95% of all patients without them.

Sizable where does the patient population that we estimate at 70000 prevalent patients in the U S and Europe alone.

Kate Haviland: Today, we are pleased to provide 'twenty 'twenty four Ava kit revenue guidance of 350 million to $390 million, putting us on pace to nearly double our sales this year.

Kate Haviland: This revenue trajectory is very similar to other notable rare disease product launches, such as Solaris and Jakafi, with additional similarities being a compelling new first-in-class medicine approved to address a significant medical need and building a new multi-billion dollar market. These similar attributes, and importantly, similar sales trajectory, are why we believe the launch of AZKIT in MSM is one of the most exciting rare disease launches happening across the industry today. And we are just now scratching the surface.

Kate Haviland: This revenue trajectory is very similar to other notable rare disease product launches such as Solaris and geography.

Kate Haviland: With additional similarity being a compelling new first in class medicine approved to address a significant unmet medical need and building a new multibillion dollar market.

Kate Haviland: These similar attributes and importantly, similar sales trajectory.

Kate Haviland: Why do we believe the launch of is a kit and that's M is one of the most exciting where does he want to it's happening across the industry today.

Kate Haviland: And we are just now scratching the surface.

Kate Haviland: In 2024, our primary focus is on reaching more patients with SM in the U.S. and also now in Europe, with our EMA approval for ISM this past December. David Kitt's compelling Efficacy and Safety Profile, coupled with the chronic nature of ISM, mean that both new patient starts and the cumulative effect of patients staying on therapy for longer durations are important drivers of revenue this year and beyond. I will hand it over to Selina next on the call, and she'll go into more detail on AvaKick's performance in Q4, and why we expect our strong and steady growth to continue as we drive towards peak sales of greater than $2 billion. And yes, we are now pointing you all to a peak opportunity for advocates that is greater than $2 billion for the past 12 to 18 months, since before FDA approval for ISM. We have been citing a peace opportunity for AvaKit of greater than $1.5 billion.

Kate Haviland: In 2024, our primary focus is on reaching more patients without them in the U S. And also now in Europe, with our EMEA approval and I with them. This past December.

Kate Haviland: Neither kits compelling efficacy and safety profile coupled.

Kate Haviland: Coupled with the Qantas nature of I S M mean that.

Kate Haviland: Both new patient starts and the cumulative effect of patients staying on therapy for longer durations are important drivers of revenue this year and beyond.

Kate Haviland: I will hand, it over to Selina next on the call and she will go into more detail on it because the performance in Q4 and why we expect our strong and steady growth to continue as we drive towards peak sales of greater than $2 billion.

And yes, we are now pointing you to a peak opportunity for either kit that is greater than $2 billion.

For the past 12 to 18 months since before FDA approval and I S M.

Selina: We have been stating a piece of opportunity for Ava kit are greater than $1 5 billion.

Kate Haviland: Now, based on the strong underlying fundamentals that are driving our early sales trajectory and the rapid growth in diagnosis that has led to an expanding SM market, our conviction has grown that Avocate will be able to achieve peak global sales of greater than $2 billion. Now, let's turn to our second area of focus: Advancing Our Portfolio, Targeting Allergic Inflammatory Diseases Where Mass Cells Play a Central Role.

Selina: Now based on the strong underlying fundamentals that are driving our early sales trajectory and the rapid growth in diagnosis that has led to an expanding market.

Selina: Our conviction has grown ever kit will be able to achieve peak global sales of greater than $2 billion.

Selina: Okay.

Speaker Change: Now, let's turn to our second area of focus.

Speaker Change: Advancing our portfolio targeting allergic inflammatory diseases, where mast cells play a central role.

Kate Haviland: Last month, I shared how we are focusing our investment in our most exciting research and development program, with opportunities to address high medical needs in large patient populations and, importantly, in therapeutic areas that play to our strengths by leveraging our expertise and our infrastructure. A primary area of focus for us this year is to advance our portfolio of approved and investigational programs targeting mast cell-mediated diseases. Blueprint is uniquely positioned to drive novel science in this space because of our scientific leadership and targeting kit and our proprietary insights into mast cell biology, an important area of science that has been historically underappreciated. With AvaKit and LMF-MIB, we are fully covering mast cell diseases driven by mutated kits.

Last month I shared how we're focusing our investment and our most exciting research and development programs with opportunities to address high medical needs in large patient populations.

Speaker Change: And importantly in therapeutic areas that play to our strengths.

Speaker Change: Bridging our expertise and our infrastructure.

A primary area of focus for US this year is to advance our portfolio of approved and investigational programs targeting that cell mediated diseases.

Speaker Change: Blueprint is uniquely positioned to drive novel Science in this space.

Speaker Change: Cause of our scientific leadership in targeting kit and our proprietary insights into muscle biology, and important area of science that had been historically underappreciated.

Speaker Change: With <unk> and LMS and Ed we are fully covering muscle diseases, driven by mutated kicked.

Kate Haviland: And this year, we are expanding into a much larger opportunity driven by wild-type kids with Blue 808. We are particularly excited about the potential for Blue 808 to impact fundamental biology and a number of large diseases with significant medical needs, starting with chronic urticaria. We believe this program will move quickly, with a higher than typical probability of success at this stage, given our track record of translating our discovery expertise and targeting kits into clinical impact and now commercial success. Next week, we will have a huge presence at the American Academy of Allergy, Asthma, and Immunology meeting, often known as Quad AI, which is the largest allergy and immunology conference in the U.S. and taking place in Washington, D.

Speaker Change: And this year, we are expanding into a much larger opportunities driven by wild type kit, we blew it away.

Speaker Change: We are particularly excited about the potential for blue anyway to impact fundamental biology, and a number of large diseases with significant medical need starting to chronic urticaria.

Speaker Change: We believe this program will move quickly with a higher than typical probability of success at this stage given our track record of translating our discovery expertise and targeting kit into clinical impact and now commercial success.

Speaker Change: Next week, we will have a huge presence at the American Academy of allergy asthma, and immunology meeting often under quite a I, which is the largest allergy immunology conference in the U S and taking place in Washington D. C. This year.

Kate Haviland: Later in the call, Fouad will go into more depth on what we will be showcasing at Quad AI, as well as provide an update on our development stage portfolio. The third area of focus for us is maintaining a strong and durable financial position. Cash management will continue to be a priority area for us to focus on in 2024.

Speaker Change: Later on the call, who I will go into more depth on what we will be showcasing at quanta I as well as provide an update on our development stage portfolio.

Speaker Change: The third area of focus for us is maintaining a strong and durable financial position.

Speaker Change: Cash management will continue to be a priority priority area for us to focus on it in 2024.

Kate Haviland: And as we sit here today, we see a clear path to profitability through the combination of strong revenue growth and disciplined operating expenses, which will result in a significant decrease in operating cash burn in 2024 and beyond. Mike will talk more about our financial results and our approach to balancing disciplined capital allocation and investing at the same time in our compelling near and long-term growth opportunities. Business development will also continue to be core to how we build and optimize our business in a sustainable way.

Speaker Change: And as we sit here today, we see a clear path to profitability through the combination of strong revenue ramp and disciplined operating expenses.

Speaker Change: Which will result in a significant decrease in operating cash burn in 2024 and beyond.

Speaker Change: Mike will talk more about our financial results and our approach to balancing disciplined capital allocation and investing at the same time, and our compelling near and long term growth opportunities.

Speaker Change: Business development will also continue to be core to how we build and optimize our business in a sustainable way.

Kate Haviland: To that end, I'm very pleased to say that we have made significant progress on a deal that will enable Gavretto to continue to be commercially available to patients in the U.S. while minimizing the financial impact of the deal. We look forward to updating you in the near future once that deal is finalized. Now I'll hand it over to Selena, who will go into more detail on our commercial performance. Selena?

Speaker Change: To that end I'm very pleased to say that we have made significant progress on a deal that will enable <unk> to continue to be commercially available to patients in the U S. While minimizing the financial impact of blueprint.

We look forward to updating you in the near future once that deal is finalized.

Cleanup: Now I'll hand, it over to cleanup who'll go into more detail on our collection performance Linux. Thanks Kate.

Selena: Thanks, Kate. AvaKit achieved $204.2 million in net product revenues in 2023, representing 84% revenue growth over the previous year. Fourth quarter revenues grew 30% quarter on quarter to $71 million, with $63.6 million in the U.S. This growth was driven by several key factors, including new patient starts, a decline in our share of free goods, low discontinuation rates, and high compliance. ISM is the clear growth driver, with the majority of new starts at the 25 MIG dose starting with patients on therapy. We hit a major milestone in January with approximately 1,000 patients on AvaKit in the U.S. We were looking to see if this would come in December or January and were encouraged by the strong demand we see coming into Q1. We're thrilled to hit this 1,000 patient milestone this early in the launch, and we're focused on driving continued growth.

Cleanup: They have a kid achieved $204 $2 million in net product revenues in 2023, representing 84% revenue growth over last year.

Cleanup: Fourth quarter revenues grew 30% quarter on quarter quarter on quarter to $71 million with $63 $6 million in the U S.

Cleanup: This growth was driven by several key factors new patient starts a decline in our share of free goods low discontinuation rates and high compliance.

Cleanup: I assume is the clear growth driver with the majority of new starts at 25 Meg dose.

Cleanup: Starting with patients on therapy.

Cleanup: A major milestone in January with approximately 1000 patients on either kits in the U S.

Cleanup: We're looking to see if this would come in December or January and we're encouraged by the strong demand we see coming into Q1, we're thrilled to hit this 1000 patient milestone. This early in the launch and we're focused on driving continued growth.

Selena: Today, we're setting revenue guidance that reflects the strong and steady continued growth we expect in 2024 as we get closer to realizing AvaKit's blockbuster potential. Our guidance range of $360 to $390 million assumes another year of more than 80% year-over-year revenue growth at the midpoint. We have good insight into the fundamentals driving our revenue, namely new patient starts, compliance, duration, free goods, and our international performance. This range reflects the inherent variability in those fundamentals.

Cleanup: Today, we are setting revenue guidance that reflects the strong and steady continued growth. We expect in 2024, as we get closer to realizing Ava kits blockbuster potential.

Cleanup: Our guidance range of $360 million to $390 million assumes another year of more than 80% year over year revenue growth at the midpoint.

Cleanup: We have good insight into the fundamentals driving our revenue, namely new patient starts compliance duration free goods and our international performance.

Cleanup: This range reflects the inherent variability in those fundamentals.

Selena: With guidance now in place, we're going to move away from providing a quarterly number of patients on therapy. However, we will continue to share commentary on how the launch is progressing. Looking next at persistent... We expected strong persistence in ISM based on Ava Kitt's clinical profile and the chronic nature of the disease. And even though it's early days, all signs point to extended durations of therapy with low discontinuation rates and high compliance launched to date. What's been a surprise upside is how quickly we've moved the needle on our free goods share, dropping to approximately 25% as we grow the number of ISM patients on therapy. We have just reported our second strong quarter of revenue from our ISM launch. Let me tell you why we expect to sustain this growth in 2024 and beyond. Our commercial strategy is grounded in strong continued execution across multiple paths that will drive sustained growth in this market. 1st

Cleanup: <unk> now in place, we're going to move away from providing a quarterly patients on therapy number we will continue to share commentary on how the launch is progressing.

Cleanup: Looking next at persistence.

Cleanup: We expected strong persistence and I affirm based on advocates clinical profile and the chronic nature of the disease.

Cleanup: And even though it's early days all signs point to extended durations of therapy with low discontinuation rates and high compliance launch to date.

Cleanup: It's been a surprise upside is how quickly we've moved the needle on our free goods share dropping to approximately 25% as we grow the number of <unk> patients on therapy.

Cleanup: We have just reported our second strong quarter of revenue from our ISR launch let me tell you why we expect to sustain this growth in 2024 and beyond.

Cleanup: Yeah.

Cleanup: Our commercial strategy is grounded in strong continued execution across multiple paths that will drive sustained growth in this market.

Cleanup: First.

Selena: We're ramping up our direct-to-patient marketing to further drive awareness and activate patients to seek treatment. The SM market is growing, and we've only captured a small fraction of it so far. Today, there are more than 20,000 diagnosed patients in the U.S. alone, and about half are not well-controlled on symptom-directed therapies. We know this is a chronic market where patient preference is sticky. Once patients start AvaKit, that positive clinical experience bodes well for chronic duration of therapy. Second, we're expanding AvaKit's prescriber base across all specialties and settings, and we're nowhere near saturation. We are seeing strong receptivity to Avakid's profile among both he-monks and allergists in academic and community settings.

Cleanup: We're ramping up our direct to patient marketing to further drive awareness and activating patients to seek treatment.

Cleanup: S M market is growing and we've only captured a small fraction of it so far.

Cleanup: Today, there are more than 20000 diagnosed patients in the U S alone and about half are not well controlled on symptom directed therapies.

Cleanup: We know this is a chronic market where patient preference is sticky.

Cleanup: Once the patients start either kit that positive clinical experience bodes well for chronic duration of therapy.

Cleanup: Second.

Cleanup: We're expanding Eva kits prescriber base across all specialties and settings, and we're nowhere near saturation.

Cleanup: We are seeing strong receptivity to either gets profile among both he marks an allergist in the academic and community settings.

Selena: The breadth of prescribing is happening exactly where we want it to, as we're motivating more allergists to prescribe AvaKit, and we're adding more prescribers at the top of the concentration curve. You can see this in the chart on the left, which shows early advocate adoption among the top 400 SM providers, who see about 4,300 unique SM patients. We continue to grow the breadth of prescribing here in light green, and we're also beginning to see depth of prescribing with providers who have already started two, three, or more patients on therapy in darker green. As we expected, the first positive experience is leading providers to recommend AvaKit to the next patients who are coming in for their scheduled appointment. Breath of prescribing is an important lead indicator for long-term growth.

Cleanup: Breadth of prescribing is happening exactly where we want and we're motivating more allergists to prescribe <unk> and.

Cleanup: And we're adding more prescribers at the top of the concentration curve.

Cleanup: You can see this in the chart on the left which shows early advocate adoption among the top 400 S. M providers, who see about 4300 unique S M patients.

Cleanup: We continue to grow the breadth of prescribing here in light Green and we're also beginning to see depth of prescribing with providers, who have already started to three or more patients on therapy and darker green.

Cleanup: As we expected the first positive experience is leading providers to recommend ever get to the next patients who are coming in for their scheduled appointments.

Cleanup: Breadth of prescribing is an important lead indicator for long term growth. We are highly encouraged to see prescriber breadth and early signs of prescriber depth at this point in the launch.

Selena: We are highly encouraged to see prescriber breaths and early signs of prescriber death at this point in the launch. Over time, we expect to see the cumulative impact of growing this motivated prescriber base, together with activating more patients to see what's possible with AvaKit. That's why I'm so confident about our ability to both grow and capture this market. We understand the FM market better than anyone else. What activates patients to move away from the symptom-directed polypharmacy they're habituated to and try therapy designed to address the underlying driver of disease? What drives providers' urgency to treat? What influences their prescribing behavior?

Cleanup: Overtime, we expect to see the cumulative impact of growing this motivated prescriber base together with activating more patients to seek what's possible with Eva kit.

Cleanup: That's why I'm, so confident about our ability to both grow and capture this market.

Cleanup: We understand BSM market better than anyone else.

Cleanup: What activates patients to move away from the symptom directed polypharmacy, there habituated to and try therapy designed to address the underlying driver of disease.

Cleanup: What drives providers urgency to treat what influences their prescribing behavior and how do we ensure that access is seamless for patients and providers.

Selena: And how to ensure that access is seamless for patients and providers? We're making great headway to disrupt entrenched attitudes and behaviors about disease control and treatment and to drive patients and providers to take action. With two quarters of strong performance and our guidance today, we are in the early innings of a pioneering rare disease launch. We're exactly where we thought we would be, and we're delivering what we said we would deliver, as we've seen from the launch trajectory of other rare disease blockbusters. We are right on track to capture AvaKit's peak opportunity of over $2 billion. With that, I'll hand it to Fouad to share what you can expect from Blueprint Medicines at Quad AI. Thank you, Kalima, with more than 10 years of experience in systemic mastocytosis.

Cleanup: We're making great headway to disrupt entrenched attitudes and behaviors about disease control and treatment and to drive patients and providers to take action.

Cleanup: With two quarters of strong performance and our guidance today, we are in the early innings of a pioneering rare disease launch.

Cleanup: We are exactly where we thought we would be and we're delivering what we said we would deliver.

Cleanup: As we've seen from the launch trajectory of other rare disease blockbusters, we're right on track to capture David its peak opportunity of over $2 billion.

Cleanup: With that I'll hand, it to flood to share what you can expect from blueprint medicines at Quad AI.

Thank you Celina.

Flood: With more than 10 years of experience in systemic mastocytosis, we have built an extensive repository of knowledge to uncover.

Fouad Namouni: We have built an extensive repository of knowledge to uncover insights into SM disease biology, our patients' journey, and our prescriber management of the disease spectrum from ISM to ASM. Blueprint Medicines, we are redefining how SM is treated across a broad network of academic leaders and prescribers with whom we are not only expanding the frontiers of innovation in SM but also in many other mass-set driven disciplines. With two oral presentations and seven posters, Blueprint will lead SM science and medicine at the 2024 Quad II Conference. The long-term efficacy and safety data from Pioneer will continue to establish AvaKit as the standard of care and the only available option to treat the root cause of systemic mastocytosis.

Flood: Gets into Smbs view biology, our patient's journey.

Flood: Fiber management of the disease spectrum from ISI.

Flood: Awesome.

Flood: <unk> medicines, we are redefining how smbs to.

Flood: Of course, a broad network of academic leaders and prescribers with whom we are not only expanding the frontier innovation E. S them, but also in many other math so driven diseases.

Flood: With two oral presentations and seven posters blueprint, we'd need some science and medicine of the 2024.

Flood: Yeah.

Flood: The long term efficacy and safety data from pioneer we continue to establish Ava gets out of the standard of care and the only available option to treat the root cause of systemic mastocytosis.

Fouad Namouni: Additional data will include health outcomes measures and reduction in polypharmacy. Turning now to our pipeline, the extensive data we generated from PIONEER and from real-world evidence in ESSEM, coupled with the regulatory experience we gained with AVACID development, are enabling us to build a robust, differentiated development path for an understanding of why our next generation D8 vaccine being inhibited.

Flood: Additional data will include has outcomes measures and reduction in polypharmacy.

Flood: Turning now to our pipeline.

Flood: The extensive data we generated from pioneer and from real World evidence and SM, coupled with the regulatory experience regained with Eva could development.

Enabling us to build a robust differentiate it development path for <unk>.

Flood: Our next generation <unk> inhibitor.

Fouad Namouni: We very recently presented data showing an unestimated, rival clinically meaningful symptom improvement across those levels with well-tolerated safety profiles. We see a lot of potential within this estimate as the core part of expanding our SM front. Mast cells are well-established key drivers for many allergic and inflammatory diseases where there is still a high medical need.

Flood: We did recently presented data showing that in this data right with clinically meaningful symptom improvement across dose levels with a well tolerated safety profile.

We see a lot of potential with an interest in it.

Flood: The core part of expanding our S M franchise.

Milestones are well established with key drivers for many allergic and inflammatory diseases, where there is a still a high medical need.

Fouad Namouni: However, their role as therapeutic targets for inflammation has often been underappreciated in our industry. At Blueprint Medicines, we are building on our expertise in mast cell biology to identify targets and develop therapies for a variety of mast cell-driven inflammatory diseases. Last month, we presented for the first time more detail on the preclinical profile of Blue 808, a profile that met or exceeded all our key criteria. It is potent in wild-type kits, highly selective, and it has drug properties compatible with one's daily oral administration.

However, their role as therapeutic targets for inflammation has often been underappreciated in our industry.

Flood: At Blueprint Medicine, we are building on our expertise in mass everybody already to identify targets and develop therapies for a variety of mast cell driven inflammatory disease.

Flood: Last month, we presented for the first time more detail on the preclinical profile of Blue 808.

Flood: The profile of the Smith well.

Flood: We exceeded all our key criteria. It is potent Walmart target highly selective and it has drug properties compatible with once daily oral administration.

Fouad Namouni: Next week, we will also share compelling in vivo activity of Blue808 in models of mast cell activation and asthma that support our development strategy into these diseases and beyond. We are on track to submit an IND in the second quarter of this year, and then we will initiate the SADMAD study. Finally, on the solid tumor part of our body, we are advancing our CDK2 inhibitor, BLEU222, one of the most exciting programs that we have in clinical development. Bluetooth 2.2 is an important value driver for Blueprint Medicine and one that we are looking to move forward in the context of a partnership. CDK2 is a clinically validated cell target with the potential to impact a large patient population with hormone-positive, HER2-negative breast cancer.

Flood: Next week, we will also share component in vivo activity of Blue.

Flood: Oh wait in models of mass excavation and asthma that supports our development strategy into these diseases and we are on track to submit an IND in the second quarter of this year and then we will initiate the sad Mad study.

Flood: Finally on the solid tumor part of our pipeline we are advancing our CDK inhibitor grew two two to one of the most exciting programs that we have entered clinical development.

Flood: Bluetooth is an important value driver for blueprint medicine, and one that we are looking to move forward in the context of a partnership.

CDK too is a clinically validated target.

Flood: With the potential to impact a large patient population with hormone positive <unk> negative breast cancer.

Fouad Namouni: Blu222 has a very encouraging profile with a broad therapeutic window and best-in-class selectivity. Our goal is to pursue it in combination with approved CDK-4.6 medicines to prolong breast cancer patients' survival. We have had significant engagement on this program with a range of potential partners, and those conversations continue very productively. With that, I will turn the call over to Mike to review our financial updates. Thanks, Fouad. Earlier this morning, we reported detailed financial results in our press release. For today's call, I'll touch on a few... For the full year, total revenues were $249.4 million, including $204.2 million in net product revenues from sales of AvaKit and $45.2 million in collaboration and license revenues. Of these full-year revenues, $71 billion of AVICID net product revenues were recorded in the fourth quarter.

Flood: <unk> has a very encouraging profile with a broad therapeutic window and best in class selectivity.

Flood: Our goal is to pursue in combination with a proven CDK four six medicines, a prolonged breast cancer patient survival.

Flood: We have had significant engagement on this program with a range of potential partners and those conversations continue very productively.

Flood: With that I will turn the call over to Mike to review our financial updates.

Mike: Thanks Rod earlier.

Mike: Earlier. This morning, we reported detailed financial results in our press release for today's call I'll touch on a few highlights.

Mike: For the full year total revenues were $249 $4 million, including $204 2 million in net product revenues from sales of advocate and $45 $2 million in collaboration and license revenues.

Mike: These full year revenues $71 billion of advocate net product revenues were recorded in the fourth quarter.

Mike: In 2024, we anticipate that we will achieve $360 to $390 million in APICOT net product revenue. We expect that the U.S.-ex-U.S. APICIT revenue split in 2024 will be approximately consistent with what we observed in 2023, as we launch first in Germany before expanding to other countries as pricing and reimbursement are negotiated. Today's guidance illustrates we are on the path to capturing AvaKit's peak opportunity of $2 billion. This revenue growth, coupled with expense discipline and focused investment, is what is accelerating our path to profitability. We do not anticipate any material collaboration revenue from existing collaborations in 2024.

Mike: In 2024, we anticipate that we will achieve $360 million to $390 million and <unk> net product revenues.

Mike: We expect that the U S ex U S. <unk> revenue split in 2024 will be approximately consistent with what we observed in 2023 as we launch first in Germany before expanding to other countries as pricing and reimbursement that's negotiated.

Today's guidance illustrates we are on the path to capturing advocates peak opportunity of $2 billion.

Mike: This revenue growth coupled with expense discipline and focused investment is what is accelerating our path to profitability.

Mike: We do not anticipate any material collaboration revenue from existing collaborations in 2024.

Mike: We are nearing a path forward for Gabretto in the U.S. and plan to provide an update next week to coincide with the termination date for our existing agreement with Roche. We continue to expect that the wind-down of the Roche Collaboration for Gabretto will result in significantly lower year-over-year operating expenses related to Gabretto and will have no material impact on our overall expense plans in 2020. Our total costs and operating expenses continue to decline and were $735.7 million for the full year and $177.1 million for the fourth quarter.

Mike: We are nearing a path forward forget retro in the U S and plan to provide an update next week to coincide with the termination date for our existing agreement with Roche.

Mike: We continue to expect that the wind down of the Roche collaboration forget Rado will result in significantly lower year over year operating expenses related to get Red Oak and we will have no material impact to our overall expense plans in 2024.

Mike: Our total costs and operating expenses continue to decline and was $735 7 million for the full year and $177 1 million for the fourth quarter.

Mike: We anticipate our R&D expenses will continue to decline in 2024 as we wind down our early stage EGFR clinical program, partially offset by increased investments in our programs for mass cell-mediated diseases, specifically Blue 808. We expect only a small increase in SG&A expenses as we gain operating leverage from our commercial infrastructure and continue to drive significant increases in revenue. Last month, Kate shared our vision for maintaining financial strength at Blueprint. We have a focused spending plan that allows for continued reduction in operating expenses while also investing in opportunities for longer-term growth. We have prioritized capital allocation towards a portfolio built around mast cell-mediated disease, solid tumors implicated by cyclin-dependent kinase biology, and ongoing early research efforts, as we believe that these areas provide the best opportunity to drive long-term value.

Mike: We anticipate our R&D expenses will continue to decline in 2024, as we wind down our early stage Egfr clinical programs.

Mike: We offset by increased investments in our programs for mast cell mediated diseases, specifically blue eight alright.

Mike: We expect only a small increase in SG&A expense as we gain operating leverage from our commercial infrastructure and continue to drive significant increases in revenues.

Mike: Last month, Kate shared our vision for maintaining financial strength that blueprint.

Mike: We have a focused spending plan that allows for continued reduction in operating expenses, while also investing in opportunities for longer term growth.

Mike: We have prioritized capital allocation towards the portfolio built around mass cell mediated diseases solid tumors implicated by cyclin dependent kinase biology.

Mike: And ongoing early research efforts as we believe that these areas provide the best opportunity to drive long term value.

Mike: Entering 2024, we are in an exceptionally strong and durable financial position with $767.2 million in cash. We are commercializing AvaKit globally, a first and best-in-class medicine that is growing revenues on the way to blockbuster status. We expect our operating cash burn to further decline in 2024 even as we advance our portfolio of high-potential medicines like Blue Atoid. Our pathway to profitability is becoming clearer, solidifying our financial profile and our ability to generate long-term benefits. With that, I'll now turn the call back over to the operator for any questions. Operator.

Mike: Entering 2024, we are in an exceptionally strong and durable financial position with $767 $2 million in cash.

We are commercializing <unk> globally.

Mike: First and best in class Medicine that is growing revenues on the way to blockbuster status.

Mike: We expect our operating cash burn to further decline in 2024, even as we advance our portfolio of high potential medicines like Blue anyway.

Mike: Our pathway to profitability is becoming clearer solidifying our financial profile and our ability to generate long term value.

Speaker Change: With that I'll now turn the call back over to the operator for any questions operator.

Operator: Thank you. At this time, I would like to remind everyone, in order to ask a question, press star, then the number one on your telephone keypad. We'll pause for just a moment to compile the Q&A. Our first question today comes from Brad Canino from Stiefel. Your line is now open.

Speaker Change: Thank you at this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad, we'll pause for just a moment to compile the Q&A roster.

Speaker Change: Our first question today comes from Brad <unk> from Stifel. Your line is now open. Please go ahead.

Brad Canino: Please go ahead. Good morning, and congratulations on the quarter. It would be great to hear a description of how the team viewed its overall approach coming into guidance here and then what you believe this guidance now represents about the opportunity. And then I've got a follow-up. Thank you, Brad, very much. We really appreciate that. Chrissy, do you want to take the question on guidance? Sure, Brad.

Good morning, and congrats on the quarter.

Brad: It'd be great to hear a description of how the team viewed its overall approach coming into guidance here and then what you believe this guide now represents about the opportunity and then I've got a follow up thank you.

Speaker Change: Thank you bad very much I really appreciate that cause you to want to take the question on guidance sure Brad.

Chrissy: So, as Kate said, we now have two full quarters of experience under our belts with AvaKit, and those two quarters have set an incredibly strong foundation for the trajectory that we see for this product. We also have a sense now, based on those two quarters, of what some of the key drivers are of revenue performance, and Felina walked through those, you know, things like new patient starts, duration of therapy, which, increasingly, in a chronic market like this is becoming a very important driver of revenue growth as we have a strong and growing base of patients on therapy, and then factors like compliance, et cetera, free drug rates And so, as we've understood those variables and we understand what reasonable ranges are around those variables, that's really informed our guide, which, you know, like other external milestones, et cetera, that we communicate, we're really putting out so that we can help everyone understand what we think is a reasonable expectation for revenue this year. You know, one important factor is that we are not even 12 months into this launch, and so one of the things that we're understanding as we go through are some of the quarter-on-quarter dynamics and how those things will play out. Felina talked about, for example, seasonality in Q4.

Speaker Change: So as Kate said you know, we now have two full quarters of experience under our belts with either cat and those two quarters have sat an incredibly strong foundation for the trajectory that we see for that product.

Speaker Change: We also have a sense now based on those two quarters of what some of the key drivers are of revenue performance and Selena walked through those.

Speaker Change: You know things like new patients starts duration of therapy, which increasingly in a chronic market. Like this is becoming a very important driver of revenue growth as we have a strong and growing base of patients on therapy, and then factors like compliance etcetera, I afraid drive rates and so as we've understood those variables and we understand.

Speaker Change: And what reasonable ranges are around those variables, that's really informed our guide which you.

Speaker Change: You know like other external milestones et cetera that we communicate we're really putting out so that we can help everyone understand what we think is a reasonable expectation for revenue this year.

You know one important factor is that we are not even 12 months into this launch and so one of the things that we're understanding as we go through or some of the quarter on quarter dynamics and how those things will play an absolutely I talked about for example seasonality in Q4, and we know that Q1 is often a quarter you know and many and pharma generally where you see impact.

Chrissy: We know that Q1 is often a quarter, and pharma generally, where you see impacts around compliance, growth in that, et cetera. So we're understanding how those factors will also play in as we think about the quarter-on-quarter ramp through the year. I think the important thing, if we pull back, is that this guide represents more than 80% year-on-year growth again for AvaKit. And it is very, very clear, if you look at the revenue trajectory that we are on, that we are very much marching down that road toward a $2 billion peak. The trajectory is very much aligned with what we've seen with other compelling rare disease launches. And so we feel like we're in an incredibly strong place and very much demonstrating, with each quarter, the opportunity that we've been seeing in SM.

Around compliance starts to that et cetera. So we're understanding how those factors will also play and as we think about the quarter on quarter, our ramp through the year.

Speaker Change: I think the important thing that would be pulled back is that that's guide represents more than 80% year on year growth again for Ava cats and it is very very clear. If you look at the revenue trajectory that we're on that we are very much marching down that road towards a 2 billion dollar peak.

Speaker Change: The trajectory is very much aligned with what we've seen with other compelling rare disease launch it and so we feel like we're in an incredibly strong place and very much demonstrating with each quarter the opportunity that we've been saying is there an S M.

Chrissy: And then I want to ask, on slide seven, which was a very helpful visualization of the proportion of practices where only one or two patients have started AvaKit, but what were the key execution steps that got that disclosed minority of activated accounts to three to ten patients, and how are you going to replicate that in the remaining majority that are at one to two? Thanks, Brad. Bruna, do you want to talk more about that dynamic?

Speaker Change: Great and then I want to ask on slide seven which was a very helpful visualization of the proportion of practices, where only one or two patients have started Ava kit.

Salveen Richter: But what were the key execution steps that got that disclosed minority of activated accounts to three to 10 patients.

Salveen Richter: How are you going to replicate that in the remaining <unk>.

Speaker Change: Jordan that are at one to two thank you.

Thanks, Bob.

Speaker Change: More about that dynamic yes, thanks for the question Brad.

Bruna: Yeah, thanks for the question, Brad. You know, we're really encouraged this early in the launch to see strong signs of growing prescriber breadth across all specialties and settings. So HEMOC, AI, and an even split across academic and community.

Jordan: Encourage this early in the launch to see both strong signs of growing prescriber breadth across all specialties and setting so seamark AI and an even split across academic and community.

Bruna: That therein represents how well that real world experience with Avikit's strong profile is playing out and the receptivity, you know, to the point where what's leading providers with their first experience to put on two or more patients, you know, it's really as simple as they start using Avikit and can see that positive benefit. It brings it to life in these providers of what's possible with patients. And that is leading to further repeat prescribing and deepening of these accounts. You know, from an executional standpoint, I would highlight the efforts of our team that have the greatest amount of promotional focus on the providers who are seeing the greatest number of SM patients, and it's really the strength of both our data analytics that inform that targeting, as well as the strong relationships that our team has forged with these top volume prescribers on the ground. Thanks and congrats again. Our next question today comes from Salveen Richter of Goldman Sachs. Your line is now open; please go ahead.

That theyre in represents how well that real world experience with advocates strong profile is playing out and the receptivity.

Jordan: To the point of what's leading providers with their first experience to put on two or more patients.

Jordan: It's really as simple as they start Ava kit and can see that positive benefit it brings it to life in these providers of what's possible with patients.

Jordan: That is leading to further repeat prescribing and deepening in these accounts.

Jordan: From an execution standpoint, I would highlight the efforts of our team that are that have the greatest amount of promotional focus on the providers, who are seeing the greatest number of SM patients and it's really the strength of both our data analytics that inform that targeting as well as the strong relationships that our team has.

Jordan: Forged with these top volume prescribers on the ground.

Jordan: Yeah.

Speaker Change: Thanks, and congrats again.

Speaker Change: Okay.

Speaker Change: Our next question today comes from Zach Salvia Ritchie from Goldman Sachs. Your line is now attendant. Please go ahead.

Salveen Richter: Good morning, and thanks for taking my question here. Two on the pipeline. For BLU-263, following positive data from the Part 1 portion of the Phase 2-3 trial, in ISM, the next key event is in the Part 2 trial. How will you demonstrate the differentiation of this asset relative to AvaKit in that portion? And then separately on the CDK-2 program, we are going to see that in the first half. Just walk us through your expectations, what you have presented, and the benchmarks here for success and differentiation versus the other CDK-2 inhibitors. Thank you. Yeah, thank you for the question, Salveen. And, you know, I'll hand it over to Fouad.

Speaker Change: Good morning, and thanks for taking my question here too on the pipeline for Blu 263, following positive data from the part one portion of the phase III <unk> III trial.

Speaker Change: The next key events in the part two trial, how would you demonstrate that differentiation of this asset relative to a vacant in that portion and then separately on the CDK to program, we are going to see.

Speaker Change: Data in the first half just walk us through your expectations, what you present in.

Speaker Change: And the benchmarks here for success and differentiation versus the other CDK <unk> inhibitors. Thank you.

Speaker Change: Yeah. Thank you for the question and solving and.

Kate Haviland: But, you know, we look at LMS as being a really core part of how we're going to maximize the long-term performance of our overall SM franchise. And as we've said before, AvaKit sets a very, very high bar. So I'll hand it over to Fouad to talk about how we're going to be able to bring LMS forward in an innovative way. Thank you, Salveen, for the question. We presented at ASH a few weeks ago very robust data on the activity of the validated TSS tool put in an estimate in patients with invalid and systemic mastocytosis. We also showed very good safety and tolerability profiles.

Speaker Change: I'll hand, it over to <unk>, but we look at all of them, that's where there's been a really core part of how we're going to maximize the long term performance of our overall SM franchise.

Speaker Change: And as we've said before your Ava kits at the very very high bar. So I'll hit it where there's a lot to talk about how we're going to have we're going to be able to bring all of that's important and innovative way.

Speaker Change: Okay. So the real question that we presented at Ash few weeks ago very robust data on the activity in terms of improving the symptoms with a validated T S has to food.

Speaker Change: And then in patients with indolent systemic mastocytosis. We also showed very good safety and Tolerability profile. So.

Fouad Namouni: So the Phase 2 POC is very solid there. We are, and we continue to gain scientific information from Pioneer. We will show some of it at this upcoming Quad AI meeting. We have information from real-world evidence.

Speaker Change: Phase II POC is very solid there.

Speaker Change: We are and we continue to gain scientific information from pioneer we show some of this.

Speaker Change: This upcoming what AI a meeting.

Speaker Change: We have information from real World evidence. We also gained a very robust experience from a regulatory perspective, not only in the United States, but also in Europe. So all these items are being put together to really put together a differentiation strategy to develop I understand and for what we believe ISN.

Fouad Namouni: We also gained very robust experience from a regulatory perspective, not only in the United States but also in Europe and elsewhere. So all these things are being put together to really put together a differentiated strategy to develop an estimate for what we believe ISM patients will be in a few years from now, not what they were back in 2016. And I think you will see this reflected in our development strategy as we start the registration trial. For the CDK2 question, I think we're happy that the study is continuing with the dose escalation in phase one. We're mostly focused on the combination, as I mentioned in my prepared notes, on the combination with CDK4-6 medicines. We will be presenting early safety data from the combination of ribociclib and Blu222, all with the characteristics and profile of this combination together.

Speaker Change: Patients will be in a few years from now multiple b, where back in 2016 2017, and I think you will see this reflected in our development strategy as we start the <unk>.

Speaker Change: Additional trials.

Speaker Change: For the CDK to question.

Speaker Change: I think we're happy that the study is continuing the dose escalation in the phase one.

Speaker Change: Mostly focus on the combination as I mentioned in my prepared notes on the combination with CDK four six medicines.

Speaker Change: We will be presenting the early safety data from the combination of <unk> and Bluetooth to all would be characteristic and the profile of this combination together. The goal. There is really to show that as we go to hormone positive <unk> negative breast cancer or the goal is to show that we can.

Fouad Namouni: The goal there is really to show that as we go to hormone-positive, HER2, and negative breast cancer, the goal is to show that we can combine safely, and that safe combination will drive efficacy in the short and the long term. So, stay tuned for data coming from the Velaster. Our next question comes from Marc Frahm from T.D. Cohen.

Speaker Change: Combined safely and that's safe combination will drive the efficacy in the short and the long term so stay tuned for data coming from the Valor study.

Thank you.

Speaker Change: Our next question comes from Marc Frahm from T. D. Cohen. Your line is now could you. Please go ahead.

Marc Frahm: Your line is now open. Please go ahead. Hey, thanks for taking my questions and congrats on all the growth in the quarter. Maybe going to that slide of the patient per prescriber, can you maybe give a sense of, kind of, what's the opportunity from the breadth side, right, of just deepening at those existing kind of 400 treaters, you know, versus the depth of, sorry, the depth of that, but then what's the opportunity more of expanding out to many more Guidance implies, at the midpoint, maybe like 100, 25, 150 patients per quarter kind of being added to the franchise versus the recent trend of more like 200. So, I guess, maybe you can kind of square that? Yeah, thanks, Marc. I'm going to hand it over to Selena.

Marc Frahm: Hey, guys. Thanks for taking my questions and congrats on all the growth in the quarter.

Marc Frahm: Maybe going to that slide of the patients per prescriber can you maybe give a sense of kind of what's the opportunity from the breast side, Brian just deepening at those existing 400 treaters.

Marc Frahm: Versus the depth of the.

Marc Frahm: The depth of that but then what's the opportunity more expanding out to mine more.

Marc Frahm: <unk> prescribers and kind of related to that guidance.

Marc Frahm: Implies at the midpoint, maybe like 120 550 patients per quarter kind of being added to the franchise versus the recent trend has been more like 200. So I guess, maybe can you kind of square those.

Yeah. Thanks Mark.

Selena I also just wanted to reiterate the point that Chris made by the guidance I know you know we are we are six months into a launch we have not had an opportunity to see a full year of <unk> revenue and were continuing to get a sense of some of the seasonal dynamics and we're incredibly excited that the guidance puts us on the trend line.

Selena: I also just wanted to reiterate some of the points that Christy made about the guidance, right? You know, we are six months into a launch. We have not had an opportunity to see a full year of ISM revenue, and we're, you know, continuing to get a sense of some of the seasonal dynamics. And we're incredibly excited that this guidance puts us on the trend line for kind of comparable rare disease products that have just created really compelling markets. But Selena, do you want to talk about some of the specifics? Yeah, hey, Marc.

Marc Frahm: <unk> four kind of comparable where do these products that have just created a really compelling markets, but can you talk about the specifics.

Selena: Yeah, Hey, Mark so to your question about sort of the opportunity that this represents when we look at the top 400 treaters by S. M patient volume collectively they're seeing about 4300 already diagnosed <unk> patients today.

Selena: So to your question about sort of the opportunity that this represents, you know, when we look at the top 400 treaters by SM patient volume, collectively, they're seeing about 4,300 already diagnosed SM patients today. There's substantial headroom to grow both in breadth as well as depth just within these top 400. So when we look at penetration, only about 20% of these top 400 have yet prescribed AvaKit, and we see this growing steadily in that sort of light, clean curve on the top. You also see that substantial opportunity for deepening. And we sort of talked about how the first positive experience leads to repeat prescribing, and that's both recognition of the clinical benefit, which is leading providers to think of AvaKit for a broader range of their patients. You know, they typically start with a more severe symptomatic type of patient, and they're broadening that lens over time.

Selena: There is substantial headroom to grow both in breadth as well as depth just within these top four hundreds so when we look at the penetration only about 20% of these top 400 have yet prescribed Ava kit and we see this growing steadily and that sort of light light green curve on the top.

Selena: You will also see that substantial opportunity for it for deepening.

Selena: Talked about how the first positive experience leads to repeat prescribing and Thats. Both recognition of the clinical benefit which is leading providers to think of Eva kit for a broader range of their patients. They typically start with a more severe symptomatic type of patient and they are broadening that lens overtime.

Selena: You know, it's also exciting to see the growth in allergy penetration within and beyond this segment as patients become familiar with AvaKit, accustomed to the access process, and then, again, are sort of fishing and identifying those next patients as they're coming in for treatment. And so I think that the take-home message there is, you know, we see significant potential for growth as this continues to accumulate over time, both breadth and depth. To the second part of your question, pardon me; you know, this is not a sort of 125 to 150 per quarter story alone. You know, I think that the limitations of patients on therapy at the end of every quarter just don't tell you when those new patient starts are happening, what the duration of therapy is for these patients, and we've highlighted how much more important duration will be as a contributor going forward in this launch. You know, it's a rare disease.

Selena: It's also exciting to see the growth in allergy penetration within and beyond the segment as they become familiar with Eva kit.

Selena: And through the access process.

Selena: And then again, our sort of fishing and identifying those next patients as they're coming in for treatment.

Selena: And so I think the take home there is we see significant potential for growth as this continues to accumulate over time, both breadth and depth.

Speaker Change: To the second part of your question.

Speaker Change: Pardon me this.

Speaker Change: This is this is not a sort of a 125 to 150 per quarter.

Speaker Change: Story alone you know I think that the limitations of patients on therapy at the end of every quarter. You know just it doesn't tell you.

When those new patient starts are happening what the duration of therapy is for these patients and we've highlighted how much more important duration will be as a contributor going forward.

Speaker Change: In this launch.

Speaker Change: It's a rare disease, where early theres theres variability month over month as Keith alluded to were learning those quarterly dynamics and so I think a better lens to take is probably that moving average.

Selena: We're early. There's variability month over month, as Kate alluded to. We're learning those quarterly dynamics, and so I think a better lens to take is probably that moving average, as well as a breadth of factors that are contributing to that revenue guidance that Christy just highlighted. You know, I think taken together, we're really pleased with the first two quarters, and when we look at the other blockbuster opportunity comparators that Kate mentioned, we're well within the pack of the trajectory that they've been on toward Okay, thank you. Our next question comes from Wren Benjamin from Citizens JMP. Your line is now open.

Speaker Change: As well as our breath of factors that are contributing to that revenue guidance that Christy just just.

Speaker Change: Just highlighted you know I think taken together, we're really pleased with the first two quarters.

Speaker Change: And when we look at the other blockbuster opportunity competitors that Kate mentioned like we're well within the pack of the trajectory that they've been on towards realizing that blockbuster opportunity for advocate.

Speaker Change: Yeah.

Speaker Change: Okay. Thank you.

Our next question comes from Ren Benjamin from citizens JMP. Your line is now open.

Ren: Hey, good morning. Thanks for taking the questions. Congratulations on a great quarter and an even more impressive guide. Can you talk a little bit about the trajectory in Europe and, maybe, what contribution the guide is coming from Europe? I know you mentioned in the prepared remarks that the launch will start in Germany, but can you maybe just talk us through the cadence of how the country's coming online and who's doing the actual selling? And just as a follow-up, you talked about the $2 billion, you know, peak revenues. How do you think about, you know, how long it might take to get there?

Ren Benjamin: Hey, good morning, Thanks for taking the questions congratulations on a great quarter and are even more impressive guide.

Ren Benjamin: Can you talk a little bit about the trajectory in Europe, and maybe what contribution of the guidance is coming from Europe. I know you mentioned in the prepared remarks, the launch will start in Germany, but can you maybe just talk us through the cadence of the countries come online and who's doing the actual selling and just as a follow up you've talked to.

Ren Benjamin: How about the 2 billion dollar peak revenues.

Ren Benjamin: Do you think about how long it might take to get to peak revenues.

Christy: Yeah, Ren, thank you for both those questions. Christy, do you want to talk about Europe in the peak, actually? Sure. Thanks, Jen. So we were pleased to see the European approval come through before the end of last year, as I think everyone knows. And even more pleased to see that we saw ISM patients being treated in Germany even before the holidays, which was great to see. So we're out of the gates in Europe and ISM. Germany is really going to be the primary market that's driving ISM this year due to the cadence of pricing and reimbursement. So other, other markets will start to come online. But I would expect that more towards the kind of end of this year and early next year.

Ren Benjamin: Yeah.

Speaker Change: Yeah, and thank you for both those questions because if you want to talk about about European but actually I'm. So sorry, thanks Dan.

Speaker Change: So we were pleased to see the European approval come through before the end of last year is as I think everyone knows and I'm, even more pleased to see that we saw ISN patients being treated in Germany, even before the holidays, and which was which was great to see so well out of the gates are in Europe, and I asked them, Germany is real.

We are going to be the primary market, that's driving I S. M. This year due to the cadence of pricing and reimbursement. So other other markets will start to come online, but I would expect that more towards kind of end of this year into next year and I think the important thing is if we're thinking about from a revenue protect that certainly our guide does encompass international.

Christy: I think the important thing is that, from a revenue perspective, certainly, our guide does encompass international markets. And that's yet another variable, actually, as we think about sort of the, you know, the guidance range as that launch gets underway. My general expectation is that if you look at the percent of revenue that the international business contributed to avocate, say, in twenty twenty three, it's probably going to be roughly in the same range as the U.S. continues to grow very robustly. So, you know, 10 ish percent plus or minus is, you know, probably not a bad assumption there to think about Europe.

Speaker Change: That's yet another variable actually as we think about sort of the you know the guidance range.

Speaker Change: That launch gets underway and my general expectation is that if you look at the percent of revenue that the international business contributed two eight a cat in 2023 and.

Speaker Change: It's probably going to be roughly in the same range as the U S continues to grow very robustly. So.

Speaker Change: You know 10 ish percent plus or minus is as you know.

Speaker Change: Probably not a bad bad assumption there to think about Europe.

Christy: In terms of the peak, you know, I think, again, Kate mentioned, we're on a very clear trajectory that I think looks a lot like other rare disease launches. The time to peak in those launches, you know, it varies. Right. These are never markets that are sort of up to saturation within two or three years and then flattening.

Speaker Change: In terms of the peak you know I think again Kate mentioned you know we're on a very clear trajectory that I think looks a lot like other rare disease launches the time to peak in those launches.

Speaker Change: It varies right. These are never markets that are sort of uptick saturation within two or three years, and then flattening I expect either cat revenue to drive growth for blueprint for several years to come at you know one thing that I think is often interesting about time to peak is that there is often a positive relationship between times.

Christy: I expect to advocate revenue to, you know, drive growth for the blueprint for for several years to come. You know, one thing that I think is often interesting about time to peak is that there is often a positive relationship between time to peak and what the peak is. So, you know, we just talked about our view of the peak kind of coming up to two billion dollars. If you look at, you know, markets like H.A.E., if you look at even Jacobi or Solaris, those drugs have continued to grow. And the peak opportunity has also continued to grow because the market grows underneath the drug launch. And so, you know, we'll see what happens. It wouldn't surprise me if our view of the peak continues to evolve as we move through this launch. Our next question comes from Michael Schmidt from Guggenheim. Your line is now open.

Speaker Change: Peak and what the peak, yes. So you know we just talked about our view of the P kind of coming up to $2 billion.

Speaker Change: If you look at you know markets like a J. If you look at even jakafi or Solaris and those drugs have continued to grow and the peak opportunity has also continued to grow because the market grows underneath the drug launch and so you know, we'll see what happens it wouldn't surprise me if our view of the peak continues to evolve as we.

Speaker Change: As we move through this watch.

Speaker Change: Our next question comes from Michael Schmidt from Guggenheim. Your line is now open. Please go ahead.

Michael Schmidt: Please go ahead. Hey, guys, good morning. Thanks for taking my question. I had one on blue 808.

Michael Schmidt: Hey, guys. Good morning, Thanks for taking my question I had one on Blue 808.

Michael Schmidt: You know, as we sort of head towards quad AI next week, how do you think about the overall development opportunity for this oral wild type kit inhibitor and talk a bit about how you see potential for differentiation from biologics that are in development for wild, Thanks so much. Thank you, Michael. We're really excited about Blue 808.

Michael Schmidt: As we head towards Quad AI next week.

Michael Schmidt: How do you think about the overall development opportunity for this or wild type kit inhibitor and <unk>.

Michael Schmidt: Talk a bit about how you see potential for differentiation from biologics that are in development for wild type kit. Thanks, so much.

Speaker Change: Thank you Michael we're really excited about the way the way forward.

Kate Haviland: Fouad, you want to talk a little bit more about that? Thank you. Thank you, Michael. So, lots of questions. First, I have to say I'm very happy today to see that Proof of Concept has been achieved by inhibiting wild type kit with... strategy using monoclonal antibodies.

Speaker Change: Talk a little bit more about that in episodic.

Speaker Change: Thank you thank you Michael.

Speaker Change: So.

Speaker Change: What's your question first.

Speaker Change: I have to say I'm very happy to be able to see that.

Speaker Change: Proof of concept.

Speaker Change: Have been achieving.

Speaker Change: In inhibited by inhibiting Wild type group.

Speaker Change: Our strategy of using monoclonal antibodies. So we will see you there.

Fouad Namouni: So the POC is there. Now, Blue 808 is a small molecule decay inhibitor that is highly polymorphic. Eric Selekti will have a promising safety profile as we run the SADMAP studies. It is a very flexible way to administer a drug, and it will be very simple to compare it to all the strategies. The most important thing that, in my opinion, will be a key inflection point for us in Group 808 is the safety and pharmacology data that we will gather from the SADMAP. After that, I think the POC of Y-type could be a superior strategy of inhibition, and CSU has already been shown in some Phase II data. Beyond CSU or chronic spontaneous urticaria, there is cold-induced urticaria, as we all know, but overall, mast cells, as I mentioned in my earlier remarks, have been a really underappreciated target in type 2 inflammation.

Speaker Change: No.

Speaker Change: <unk> is a small molecule inhibitor that is highly vulnerable type kit.

Speaker Change: As elective.

Speaker Change: It would have a promising safety profile as we have won the sad Mad studies IBD.

Speaker Change: It is very flexible way to administer the drug and it will be very simple to give compared to all the strategy is the most important thing in my opinion will be a key inflection point for US. We grew eight away is the safety and pharmacology data that we gather from the sad and Mad after that I think the POC.

Speaker Change: A wild type could be in a superior strategy of inhibition in CSU has already been shown in some phase II data.

Speaker Change: Beyond CSU or chronic continues RT carrier there is cold and use of the Arctic area as we all know.

Speaker Change: But overall mast out as I mentioned in my earlier remarks has been the leading under appreciated targeted type two inflammation and now that we started this in our industry IBD the opportunity to leverage blow it away then.

Fouad Namouni: And now that we have started knowing this in our industry, I believe the opportunity to leverage blow-weight weight and wild-type inhibition overall in the number of inflammatory disorders, such as type 2 asthma or MCAS and others, will be very important. I think patients would, at the end of the day, like an oral agent that we can dial up and down depending on the need for their disease. Yeah. And thanks, Fouad. I just wanted to add one thing. This is Becker.

Speaker Change: One side because inhibition overall in a number of inflammatory disorders, such as type two asthma.

Speaker Change: Or M cash.

Speaker Change: Others.

Speaker Change: We will be very important I think patients will at the end of the day like some oral agent that we can dial up and down depending on the need for the diseases.

Speaker Change: Yeah. Thanks, Rob I just wanted to add one thing. This is Becker I get the question a lot about how.

Becker: I get asked a lot about how a wild-type kit inhibitor might compare with what is currently being developed. And I think one thing to remember is we're talking about a very wide spectrum of disease with different manifestations in different tissues and different levels of severity. And using a blunt instrument like an antibody that might eliminate a number of mast cells isn't where you want to go with a lot of these diseases. And so we think that a tunable solution that we can titrate to what each patient or patient population needs is the right thing in this population or in these diseases. The other thing to remember is that most of these approaches, whether it's BTK or antibodies, don't directly address the true driver of the mast cell, which is kit. BTK inhibits activation and degranulation but really doesn't address the biology of the mast cells.

Becker Hughes: <unk> inhibitor, what might compare with what is currently being developed and I think one thing to remember is we're talking about a very wide spectrum of disease with different manifestations in different tissues and different levels of severity and using a blunt instrument like an antibody that either that might eliminate a number of mast cells.

Isn't exact isn't where you want to go with a lot of these diseases and so we think that a tunable <unk>.

Becker Hughes: Solution that is we can we can titrate to what each patient in patient population needs is the right things in this population or in this in these diseases. The other thing to remember is that most of these approaches whether it's PTK or antibodies don't directly address the true driver of the mast cell which is kick.

Becker Hughes: V Teekay inhibits activation and degranulation, but really doesn't address the biology of the mast cells and even the antibodies that are active in asthma really an orthogonal approach to the disease methodologies. So really kit is the achilles' heel of these diseases.

Becker: And even the antibodies that are active in asthma are really an orthogonal approach to the disease methodology. So really, kit is the Achilles heel of these diseases. Our next question today comes from Derek Archilla from Wells Fargo. Your line is now open, please go ahead.

Speaker Change: Thank you.

Our next question today comes from Derek <unk> Chiller from Wells Fargo. Your line is now I'd say that please go ahead.

Derek Archilla: Hey, good morning, and congrats on the results here. We have just two questions from us. You know, you talked about kind of an increasing rate of diagnosis for ISM. So I guess I'm just curious, do you think, you know, current estimates might still be too low for the number of patients out there? And I guess, what inning do you think we are in terms of the increasing diagnosis rate? And then, just as a follow-up, any additional kind of quantitative color on the current discontinuation rate you're seeing? Thanks. Thank you, Derek, for those questions. Maybe I should start with the epidemiology.

Derek Chiller: Hey, good morning, and congrats on the results here just two questions from us.

Derek Chiller: You talked about kind of an increasing rate of diagnosis for ISN. So I guess I'm. Just curious do you think current estimate there might be still slow for the number of patients out there and I guess what inning do you think we are in terms of the increasing diagnosis rates and then just as a follow up.

Derek Chiller: Additional kind of quantitative color on the current discontinuation rate you're seeing thanks.

Speaker Change: Thank you Dan Good question as well, maybe just starting with the epidemiology and maybe updated epidemiology of JP Morgan, we've seen really nice growth in the diagnosis of us and that is predominantly I affirm that cause of death in patients R. R.

Kate Haviland: I mean, we updated epidemiology at J.P. Morgan. We've seen really nice growth in the diagnosis of SM, and that is predominantly ISM because advanced SM patients have a smaller or less intense diagnostic odyssey, just given the manifestations of that disease.

A smaller or less intense diagnostic odyssey, just given the manifestations of that disease and we're in very early innings on understanding the size of this market and we anticipate it will continue to grow very substantially over the next set of years, if it's because he talked about what we've seen in other rare disease launches.

Kate Haviland: And, you know, we're in the very early innings of understanding the size of this market, and we anticipate it will continue to grow very substantially over the next set of years, just as Christy talked about what we've seen in other rare disease launches. So, do you want to talk a little bit about, you know, the durability we're seeing and how that forms such a big part of the kind of future value prospect of AvaKit? Yeah, sure.

Speaker Change: We'll talk to you about the durability, we're saying and and and how how that because it's a big part of that future value prospect of eight again, yes sure Derik, we've been really pleased to see the clinical profile of Eva can't really playing out positively in terms of real world experience.

Selena: Derek, we've been really pleased to see, you know, the clinical profile of AvaKit really playing out positively in terms of real-world experience. Compliance has been really high, and while we're really early in the launch, but very low discontinuation rates, which bode well for chronic durations of therapy with AvaKit. And, you know, at this point in the launch, as we continue to add more patients, that duration and the cumulative impact of adding more patients and more patients staying in the clinic is going to continue to grow. And, you know, adding more patients staying on therapy is going to be, you know, a substantial contributor to revenue growth going forward. understood.

Speaker Change: Clients has been really high and while we're really early in the launch, but very low discontinuation rates, which bode well for chronic durations of therapy with <unk> and you know at this point in the launch as we continued to add more patients that duration and the cumulative impact of adding more patients and more patients staying.

Speaker Change: On therapy is going to be a substantial contributor to the revenue growth going forward.

Selena: Thank you. Our next question comes from Laura Prendergast from Raymond James. Your line is now open.

Understood. Thank you.

Speaker Change: Our next question comes from Laura <unk> from Raymond James Your line is now open.

Laura Prendergast: Hey guys, congrats on the big beat today. Very exciting to see. Just two questions for me.

Laura: Hey, guys. Congrats on the congrats on the beat today very exciting to see.

Laura: Just two questions from me first of all what is driving these new patient starts do you think that's more so from the patient awareness.

Laura Prendergast: First, what is driving these new patient starts? Do you think it's more from the patient awareness side or education from providers during routine visits? And then my second question is, as you guys think about the CDK2 partnerships, is this focusing on just partnering the Blue 222 asset, or are you more thinking about partnering the whole CDK2 franchise, the NextGen, and the Degrader you guys brought up at JPMorgan? Yeah, thank you, Laura, for those questions.

Laura: [noise] side or education can provide everything you're doing routine visits and then my second question is are you guys think about that P. D. K two partnerships that's focusing on just partnering the blue to two two at that or are you more thinking about partnering the hull CDK to franchise in action and integrator you guys brought up with JP Morgan. Thanks.

Speaker Change: Yeah, there's a lot more questions, but please do you want to talk a little bit about how we see the drivers of new patient starts and Christopher I'll hand, it over to you to talk about this development electrification yeah. Thanks for the question. Laura. So you know we entered the launch already with strong awareness among our targeted he marks in AI.

Flea: Flea, do you want to talk a little bit about how we see the drivers when a patient starts? Then, Christy, we'll hand it over to you to talk about this development around CBKT. Yeah, thanks for the question, Laura. So, you know, we entered the launch already with strong awareness among our targeted hemocs and AIs. You know, initially, the drivers, obviously, some of the hemocs were coming in with experience with AvaKit from Advanced SM. That was what we shared in some of our very earliest adoptions. But, you know, what's really exciting to see is an expansion in the breadth of new prescribing in hematology oncology as well. You know, they're motivated.

Initially the drivers obviously some of the Haemonchus, we're coming in with experience with they they get from.

Christopher: From advanced Us and that was what we shared in some of our very earliest adoptions, but you know it's honestly been really exciting to see is an expansion in the breadth of new prescribing.

Christopher: In hematology oncology as well you know they're motivated they're so much more excited about I S M.

Flea: They're so much more excited about ISM and the opportunity and the need here, as well as an increasing proportion of allergy and immunology doctors who are prescribing. So, significant growth to date there, and significant headroom to grow, as we've said. To date, you know, the majority of that growth has been driven by provider engagement. We've talked about how, out of the gate, we have made available a lot of really patient-facing initiatives. And, you know, JPMorgan, we shared that we almost doubled patient awareness of AvaKit, which activates patients to speak to their providers about it. But I would say with patient activation, that's early days. And that's, you know, even more headroom to grow on that front.

Christopher: And the opportunity and the need here.

Christopher: As well as an increasing proportion of allergy immunology, who are prescribing <unk>.

Christopher: Significant growth to date, there is significant headroom to grow as we said today. The majority of that growth has been driven by provider engagement.

Christopher: We've talked about how out of the gate.

Speaker Change: We have.

Made available a lot of really patient facing initiatives and.

Speaker Change: J P. Morgan we shared that we.

Speaker Change: We almost doubled patient awareness of Eva kit, which activates them to speak to their provider about it but I would say with the with the patient activation. That's early days and that's even more headroom to grow on that front. We know patients are a critical stakeholder in this type of chronic disease, where there are key.

Flea: We know patients are a critical stakeholder in this type of chronic disease where they're a key part of that shared decision-making with their providers. And so, this year, we're really embarking on deeper direct-to-patient initiatives to promote, increase the awareness of AvaKit, and really encourage patients to seek options that can give them better disease control. And we're excited to share more about that. And we're also doing that, I should say, in a very resource-effective way based on our deep knowledge of where these patients are going to look for information, learn about the disease, and engage with providers. And one thing I'd just add to that is, you know, nothing is as impactful to patients as hearing from other patients who've been on the therapy.

Speaker Change: Part of that shared decision, making with their providers and so this year, we're really embarking on deeper direct to patient.

Speaker Change: <unk> to promote increase the awareness of Eva kit and really encourage them to seek options that can give them better disease control.

Speaker Change: And we're excited to share more about that and we're also doing that I should say in a very resource effective way.

Speaker Change: Based on our deep knowledge of where these patients are going to look for information and learn about the disease and engage with providers and one thing I would just add to that is you know.

Speaker Change: Nothing is is as impactful to patients is hearing from other patients who've been on the therapy and now as we sit here today, where we're over 1000 patients at the 8000 patients in the U S and we see patients who are on therapy sharing those experiences in chat rooms, and online and we also have some more formalized programming around that where we can connect patients to who.

Flea: And now, as we see here today, we're over 1,000 patients, estimated to be 1,000 patients in the U.S. And we see, you know, patients who are on therapy sharing those experiences in chat rooms and online. And we also have some more formalized programming around that where we can connect patients who are on AvaKit with patients who are considering it as therapy, which I think is going to be very impactful this year. Christy, do you want to talk about the CDK2? Sure.

Speaker Change: <unk> with patients who are considering it as a therapy, which I think is gonna be very impactful. This year could you do you want to talk about other CDK to so as he said you know we have a significant amount of strategic interest in that target right. I think the target is clearly now on that's going to be incredibly inquiries and see what any company that wants to be a player in the bus cancer market going forward.

Christy: So, as you said, we have a significant amount of strategic interest in the target, right? I think the target is clearly now one that's going to be incredibly important to any company that wants to be a player in the breast cancer market going forward. You know, the focus of conversations from a BD perspective has been on, you know, 222. We have a next-generation asset that, you know, could be a part of those conversations.

Speaker Change: Or are the focus of conversations on BD perspective had.

Speaker Change: <unk> had been a you know TQ too certainly and we have a next generation at that that you know could be a part of those conversations for exploring and open to different different possibilities there.

Christy: We're exploring and open to different possibilities there, but, you know, I think there's also a lot of interest in our degrader platform broadly. And, you know, we really look at that as, you know, essentially a different modality and approach to addressing this target.

Speaker Change: You know I think there's also a lot of interest in our Degrader a platform broadly.

Speaker Change: And you know, we really look at that as you know essentially a different modality and approach to addressing that target. So you know, we'll see how these conversations evolve.

Christy: So, you know, we'll see how these conversations evolve. We are certainly open to different collaboration structures, but our overall goal is really maximizing the value of the franchise in totality. Thank you.

Speaker Change: I'm certainly open to different collaborations structures, but our overall goal of maximizing the value of the franchise in totality.

Speaker Change: Great. Thank you and just what can we expect to see more and more information on this the greater platform.

Fouad Namouni: And just when can we expect to see more, you know, more information on this, the greater plot? Do you want to talk a little bit more about that? We are very happy with the rapid progress that we have made on our degrader platform.

Speaker Change: Before I do want to talk a little bit more about that.

Speaker Change: We are very very happy with the rapid progress that we made on all of them to grow their platform. As you may remember, we started there's a little bit more than two years ago and today, we have a number of the grid and development, we mentioned CDK to the graders and decide independent kinase space, but this is only the tip of the iceberg that we end up.

Fouad Namouni: As you may remember, we started this a little bit more than two years ago, and today we have a number of degraders in development. We mentioned CDK2 degraders in the psyche-independent kinase space, but this is only the tip of the iceberg that we and Medicaid shared at the JPMorgan conference. I think down the road, you will see some good degraders, CDK2 clearly.

Speaker Change: Kate shared at the Jpmorgan conference.

Speaker Change: I think down the road you will see.

Speaker Change: Some would be greater CDK to clearly although targets on our key targets in the treatment of cancer.

Fouad Namouni: Other targets are key targets in the treatment of cancer, and we will really give more timeline and guidance as we get closer and ready to share that type of information. And I think one other thing to mention, too, and I know we said it in our press release, I mean, we're also doing quite a bit of work in the mast cell, looking at other mast cell-driven targets as well. And so stay tuned on that as we move forward. Our next question today comes from Mike Earls from Morgan Stanley. Your line is now open; go ahead. Hi, good morning. This is Rohit on for Mike.

Speaker Change: We will really give more timeline in guidance or we get closer and ready to show that type of information.

Speaker Change: And I think one other thing dimension to it and I know, we said in our press release, I mean, where were also doing quite a bit of work in the Marcellus and looking at other mass all different targets as well and so stay tuned on that as well.

Speaker Change: Mood Board.

Speaker Change: Our next question today comes from Mike <unk> from Morgan Stanley. Your line is now I can go ahead.

Speaker Change: Hi, Good morning. This is Ryan on for Mike. Thanks for taking our questions can you just talk about the breakdown of your 2024 guidance how much do you attribute to <unk> versus <unk>.

Rohit: Thanks for taking our questions. Can you just talk about the breakdown of your 2024 guidance? How much do you attribute to ASM versus ISM?

Christy: And then can you talk about any trends you're seeing thus far for 2024? Yeah, Christy, do you want to take the guidance? I mean, one thing I'll say about 2024 is that, you know, we're a few weeks in, and this is our first experience with the Q1 dynamics that Christy mentioned that you see often in pharma with ISM. So we're just, you know, teams working through that; we'll have to see how that plays out.

Ryan: And then can you talk about any trends youre seeing thus far for 2024. Thank you.

Ryan: Chris do you want to take the guidance I mean, the one thing I'll say about 'twenty 'twenty four is that it's we're a few weeks in here, where you know this is our first experience with the Q1 dynamics. The Christie mentioned you see often in pharma with ISI am. So we're just you know it seems working through that we'll just see how that plays out but you know really the underlying demand from both new and existing patients appears very strong as you are in very early days.

Kate Haviland: But, you know, really, the underlying demand from both new and existing patients appears very strong this year and in these early days. Christy, do you want to talk about the guidance? Sure.

Ryan: Chris do you want to talk about guidance to ourselves.

Christy: So, as you all have heard us say many times, we don't, we don't break out revenue by indication. However, ISM is clearly driving our revenue growth, right? You know, you've seen that clear inflection during the first two quarters of launch.

You all have heard US say many times, we don't we don't breakout revenue by indication. However, I S. M is clearly driving our revenue growth rate up.

Chris: Being that clear inflection up high in the first two quarters of of watch and I think if you look at the revenue trajectory. We're on it. It's obviously that growth is coming from Sam I'm going to share that you know more than 70% of our new starts are coming at the 25 milligram dose, which is an imperfect you you know sort of way of looking at that I think is relevant.

Christy: And I think if you look at the revenue trajectory we're on, it's obviously where that growth is coming from. From ISM. Felina shared that, you know, more than 70% of our new starts are coming at the 25 milligram dose, which isn't the imperfect, you know, sort of way I'm looking at ISM, but I think it's a relevant data point that, again, just highlights that we're really seeing growth coming from ISM and would expect that to continue well into the future as we, as we capitalize on this, you know, $2 billion opportunity As Kate said, we are early in Q1.

Chris: Data point that again just highlights that.

Chris: Seeing the growth coming from from ISR and would expect that to continue well into the future as we as we capitalize on that as you know $2 billion opportunity for advocate.

Speaker Change: As Keith said, we are early in Q1 as you know the one thing I would highlight is we were really pleased to hit the 1000 patient Mark in January right. So I think that speaks to certainly the continued demand that we're seeing in terms of new patient starts et cetera that that we're seeing there's other dynamics in Q1 that you know I wouldnt be surprised.

Christy: You know, the one thing I would highlight is that we were really pleased to hit the 1,000 patient mark in January, right? So I think that speaks to certainly the continued demand that we're seeing in terms of, you know, the new patient starts, et cetera, that we're seeing. There are other dynamics in Q1 that, you know, I wouldn't be surprised if we faced our first quarter of launch. Certainly, in my previous experience, especially in these types of chronic immunology markets, you do often see hits around compliance, growth to net, and co-pay dynamics, et cetera. So we're only part of the way through the quarter. Obviously, we'll, we'll, we'll see how that all plays out, but Q1 is often more of a challenging one. Just if you look at the quarter on quarter dynamics of the year. Our next question comes from Matt Beigler from Oppenheimer. Your line is now open. Please go ahead. Hey guys, congrats from us as well.

Speaker Change: If we face that first quarter of of lunch and certainly in my previous experience, especially in these types of you know chronic immunology markets.

Speaker Change: Do you often see hits around compliance.

Speaker Change: Can add and co pay dynamics et cetera. So we're only partway through the quarter, obviously, we'll see how that all plays out but Q1 is often more of a challenging one just if you look at quarter on quarter dynamics. It together.

Speaker Change: Our next question comes from Matt Biegler from Oppenheimer. Your line is now I tend to Chase go ahead.

Matt Biegler: Hey, guys congrats from us as well can you give us more granularity on the prescriber of minutes I think last quarter, we saw around 25% of new scripts from allergists have that figure continues to increase and also what's the contribution of dermatologists and Gi docs as well thanks.

Matt Beigler: Can you give us more granularity on the prescriber mix? I think last quarter we saw around 25% of new scripts from allergists. Like, has that figure continued to increase? And also, what's the contribution of dermatologists and GI docs as well? Yeah, thanks, Nat.

Speaker Change: Yeah. Thanks, Dan I don't have that that's something that I mean, we've been really pleased to see that that that contribution of allergists immunology, which are a key prescribers target for US has continued to grow when they're going to talk more about that.

Felina: I mean, we've been really pleased to see that the contribution from allergist immunology, which is a key prescriber target for us, has continued to grow. Salina, do you want to talk more about that? Yeah, thanks for the question, Matt. We do continue to see the allergist contribution grow. It's now over 30 percent, probably in the mid-30s.

Speaker Change: Yeah. Thanks for the question, Matt We do continue to see the allergist contribution grow it's now over 30% probably in the mid Thirty's I think we had talked about 2025% previously we're really excited to be motivating. This prescriber base. Among allergists also adoption among the academic as well as the community setting.

Felina: I think we talked about 20, 25 percent previously. We're really excited to be motivating this prescriber base. Among allergists, there is also adoption among the academic setting, as well as the community setting. They're finding Avikit easy.

Speaker Change: Theyre finding advocate easy, they're obviously very attuned to the symptom management and the quality of life impact of I S. M. On these patients and are motivated to try a disease modifying option.

Felina: They're obviously very attuned to the symptom management and the quality of life impacts of ISM on these patients and are motivated to try a disease-modifying option. Among DERM and GI, in our experience, DERM and GI are really much more of a referring specialty, whereas allergists, immunologists, and hematologist oncologists are the primary prescribing specialties. That really has been our focus to date from a promotional standpoint. For example, when you look at the top 400 players, that is completely dominated by HEMOC and AI. That continues to be our primary focus to drive adoption where we're most likely to see repeat prescribing. When it comes to DERM and GI, I would say they do play an important role in diagnosis and multidisciplinary care.

Speaker Change: Among German G I and our experienced derm and Gi is really much more of a referring.

Speaker Change: Specialty, whereas allergist immunologist and Hematologists oncologists are the primary prescribing.

Speaker Change:

Speaker Change: Specialties and that really has been our focus to date from a promotional standpoint for example, when you look at the top 400 treaters that is.

Speaker Change: We dominated by a behemoth nai and that continues to be our primary focus to drive the adoption, where we're most likely to see repeat prescribing.

Speaker Change: When it comes to Derm and GI would say they do play an important role in in diagnosis and multidisciplinary care.

Felina: We do have other arms of education to help these specialties identify patients. And just to add to that, you know, our medical team has done a really great job here, actually, and they've been focusing on some of these other specialties to this point, but making sure we're finding kind of the right medical dermatologists who actually have an interest in SM, see SM patients, and tend to be kind of part of those patients' journeys, and so it's, you know, it's a full 2012 University of Georgia College of Agricultural and Environmental Sciences UGA Extension Office of Communications and Creative Services. Our next question comes from Armie Fadia from Needham.

So we do have other sort of arms of of educating too to help these specialties identified patients and just to add to that I know our medical team has done a really great job here actually in and they've been focusing on some of these other specialties to point his point, but making sure we're finding the right medical dermatologist, who.

Speaker Change: Who actually have an interest in S. M. S N patients and tend to be kind of part of that those patients journeys and so if you know what the full full group effort here and and but is it the allergy immunology and hematology oncology are going to be the drivers of this opportunity for the foreseeable future.

Speaker Change: Thanks again.

Speaker Change: Our next question comes from Amit <unk> from Needham. Your line is now open. Please go ahead.

Armie Fadia: Your line is now open. Please go ahead. Thank you. Let me add my congratulations on the strong quarter and guidance, but I had a follow-up on guidance, and I'm trying to square away what some of the variables are as I think about what the guidance implies. It seems to be that in the fourth quarter, you had added more than 200 patients, and guidance implies roughly a little over 100 patients asked per quarter. So, what are some of the other variables we should be thinking about? What's your assumption with regard to discontinuation of patients from the 1,000 patients that you had in January? And then how should we think about duration of treatment? And is there any other sort of important variable we should be thinking about?

Amit: Thank you let me add my congratulations on the strong quarter and guidance.

Amit: But I had a follow up on guidance and I'm trying to square away.

Amit: What are some of the variables as I think about what the guidance implies it seems to be that in the fourth quarter. You had added more than 200 patients and guidance implies roughly a little over 100 patients per quarter. So what are some of the other variables, we should be thinking about what's your.

The tech ops to discontinuation of patients from me.

Amit: Housing patients that you have had in January and then how should we think about duration of treatment and is there any other sort of unveiled what we should be thinking about.

Ami: Thank you. Yeah, thanks, Ami. Christy, do you want to dive into guidance a bit? Sure. So, you know, Ami, I would say the guidance does not imply that. And, you know, I know Marc asked a similar question earlier.

Amit: <unk>.

Speaker Change: Yeah, I mean, Chris do you want to dive into guidance, but sure. So you know I mean, I would say the guidance does not imply that and you know I would I know Mark asked at similar question earlier Theres a range of assumptions on each of these variables that you can kind of think about to get into that guidance range. We're obviously thinking about it.

Christy: There's a range of assumptions on each of these variables that you can kind of think about to get into that guidance range. We're obviously thinking about a number of inputs here, right? So new patients prescribed, discontinuation rates, both of those things kind of impacting that patient as a whole quarter. Factors like compliance, what our percent of free drug looks like, etc.

Speaker Change: <unk> of inputs.

Speaker Change: Inputs here right, so new patients prescribed discontinuation rates both of those things kind of impact net patient adds on a on a quota.

Speaker Change: There's like compliance what our percentage of free drug looks like et cetera, and then we talked about the international lifestyle. You know you could probably get to more than 1000 scenarios that can play with those variable depending on the assumptions and I think there's some people blueprint that I've, probably done that but you know what safe to say is that our first couple.

Christy: And then we talked about the international launch. So, you know, you could probably get to more than a thousand scenarios if you played with those variables, depending on the assumptions. And I think there are some people at Blueprint that have probably done that.

Christy: But, you know, what's safe to say is that our first couple of quarters of launch and our experience there really set the foundation for sort of what are the key assumptions that we're taking forward. And certainly one of those is that we're going to continue to have very steady, consistent new patient starts and, you know, discontinuation rates that are very much in line with what we've been seeing, which, you know, support extended durations of therapy that we think could be a good thing. And so, you know, that is sort of the foundation of our assumptions based on the last two quarters of experience. That was where we started. And then you kind of think about reasonable ranges and assumptions around each of those things.

Speaker Change: All corners of lunch and our experience there really set the foundation for sort of what are the key assumptions that where we're taking forward and certainly one of those is that we're continuing we're going to continue to have very steady and consistent a new patient starts and you know discontinuation rates that are.

Speaker Change: That are very much in line with what we've been seeing which you know support extended durations of therapy that we think could be multiple years.

Speaker Change: So that you know that is sorry that forms the foundation of our assumptions based on the last few quarters of experience that was where we started and then you kind of think about reasonable ranges and assumptions around each of those things are not really as far as how they got to that guidance range.

Christy: And that really informed how we got to the guidance. Our next question comes from Peter Lawson from Barclays. Your line is now open. Great. Thanks for the update, Scott. The view that she has today is the same record. Thanks, Peter, for that for that question. I mean, the answer is no, but Floyd, I don't know if you have any more color. I mean, we've been very just as consistent. I mean, we have fed them for maybe 18 months now, and that just contributes about $8 million a quarter.

Speaker Change: Our next question comes from Peter Lawson from Barclays. Your line is not like that.

Peter Lawson: Great. Thanks for the update guidance all the details.

Peter Lawson: Yeah.

Peter Lawson: Anything that happened during Q2 that kind of changes to the.

Use it yesterday or same revenues essentially before 24.

Thanks, Peter for that for that question I mean, the answer is no, but I know if you have any more color I mean, we've been very consistent consistent I mean, we have said for maybe 18 months now that just contributes about $8 million a quarter that is steady Eddie.

Peter Lawson: That is steady, Eddie. That is, you've been very, very consistent quarter over quarter for a long period of time now. The FSM continues to have growth, and it's just not the same growth rate as ISM. Yeah, the short answer, Peter, is no. The launch is not flattening.

That has been very very consistent quarter over quarter for a long period of time now. It does have some continues to have growth and it's just not the same growth rate as I said I don't want to talk about that yeah. The short answer Peter is no. The launches not flattening I think that our guidance guidance is the clearest signal of that with over 80%.

Floyd: I think that our guidance is the clearest signal of that, you know, with over 80% of growth at the midpoint and all leading indicators being very positive. Our next question comes from Kaleem Koozie from BARD. Your line is now open. Please go ahead.

Peter Lawson: Growth at the midpoint, and all leading indicators being very positive.

Peter Lawson: Okay.

Peter Lawson: Our next question comes from clean Crazy from Barclays. Your line is now open. Please go ahead.

Kaleem Koozie: Great, thanks, good morning, congrats on all the progress and thanks for taking the time. So I think you talked about 20% of the top 400 docs based on volume prescribing Avikit. So in those 80% of docs that haven't, can you explain what's been the hurdle for them and what might convince them to start prescribing? Yeah. So, Felina, you should dive in here.

Great. Thanks, Good morning, Congrats on the progress and thanks for taking our question, but I think you've talked about 20% of the top 400 docs think about volume of prescribed to either can't so 80% of docs that haven't can you explain.

Crazy: But the hurdle for them and what Mike and suddenly start prescribing and kits.

Yeah, So what you're saying that you should dive in here just to be clear. That's that's been Cynthia I S. M approval, just speak lease or where we're trying to track here like physician to see and then generally but we're looking at the we cant as Christiana said you know we're in Florida, we can't really distinguish between advanced that's M&A or some other time different diagnosis codes, we do look.

Felina: Just to be clear, that's been since the ISM approval. Just to be clear, you know, we're trying to track here, like, Physician 2C, SM generally, but we're looking at the, we can't, as Christy has said, you know, and Felina, we can't really distinguish between advanced SM and ISM all the time based on diagnosis codes. We do look at the dosage, 25 milligrams, as an imperfect proxy for that. So, this is really looking at physicians, the physicians who have been prescribing since, you know, Q3 and Q4, right? So, I don't know, Felina, if you want to talk about that.

Crazy: The dosage 25 milligram as an imperfect proxy for that so this is really looking at you know physicians the physicians who have been prescribing since Q.

Crazy: Q3, and Q4 right. So I don't know if when if you want to talk.

Speaker Change: Yeah. Thanks for the question. This is a market where the the cadence the timing of patient visits is a really critical factor in when they are able to engage and have that conversation.

Kate Haviland: Okay. Yeah, thanks for the question. You know, this is a market where the cadence, the timing of patient visits is a really critical factor, and when they're able to engage and have that conversation about Indolent SM with their providers. And so, you know, I would say at this point, this early in the launch, we're actually really excited to have penetrated 20% of this group, with room to grow the adoption both within that group, as well as broadening beyond those who haven't. I would say awareness among this group is very strong. They are all, you know, having personally engaged a number of these providers. They are all motivated, they are excited about AvaKit's benefit-risk profile, and they're waiting for those next patients to come in and have that conversation.

Speaker Change: 'bout indolent SM with their providers and so you know I would I would say at this point. This early in the launch we're actually really excited to.

Speaker Change: You have had penetration into 20% of this group with room to grow the adoption both within that group as well as broadening.

Speaker Change: Beyond to those you Havent you know I would say awareness. Among this group is very strong that they are all having personally engaged a number of these providers.

Speaker Change: They're all motivated they are excited about Eva kits benefit risk profile and they are waiting for those next patients to come in and have that conversation.

Felina: We are coming up on the hour and going to end the call. Miss Haviland, I turn the call back over to you. Thank you, Operator, and I want to thank you all for taking the time to join us today and thank you for your questions. And, you know, we look forward to seeing you in the near term here, many of you, at Quad AI in Washington, D.C. So, have a great day, and we'll see you soon. That concludes today's call. You may now disconnect your line. www.microsoft.com

Speaker Change: That's helpful. Thank you.

Speaker Change: We are coming up on the guidance and the cool metabolite and hand, the call back over to you.

Speaker Change: Thank you operator, and I want to thank you all for taking the time to join US today and thank you for your questions and we look forward to seeing you in the near term here. Many of you at Quad AI in Washington D C and so.

Speaker Change: Have a great day, and we'll see you soon.

Speaker Change: That concludes today's call you may now disconnect your line.

Speaker Change: [music].