Q2 2024 Blueprint Medicines Corp Earnings Call

Bye-bye.

Unknown Executive: Hello, everyone.

Unknown Executive: At this time, I would like to welcome everyone to the Blueprint Medicines second quarter 2024 financial results conference call.

Operator: At this time, I'd like to welcome everyone to the Blueprint Medicines second quarter 2024 financial results conference call. All lines have been placed on mute to prevent any background noise.

Bruno: My name is Bruno, and I'll be operating your call today. All lines have been placed on mute to present any background noise.

Bruno: After the speaker's remarks, there will be a question-and-answer session. If you'd like to ask a question during this time, simply press star followed by one on your telephone keypad. If you'd like to withdraw your question, please press star followed by two. Please remember to limit yourself to one question.

Speaker Change: If you'd like to withdraw your question. Please press star followed by two.

Speaker Change: Please remember to limit yourself to one question.

Jenna Cohen: On our handover to your host, Jenna Cohen, please, you may begin your conference. Thank you, Bruno. Good morning, everyone, and welcome to Blueprint Medicines' second quarter 2024 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 by going to the Investors section of our website at www.blueprintmedicines.com.

Speaker Change: I'll now hand over to your host Khanna Cowen. Please you may begin your conference.

Khanna Cowen: Thank you Bruno good morning, everyone and welcome to Blueprint medicines second quarter 2024 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 by going to the investors section of our web.

Jenna Cohen: After the speaker's remarks, there will be a question and answer session. If you'd like to withdraw your question, please press the star followed by 2. Please remember to limit yourself to one question. Thank you, Bruno. Good morning, everyone, and welcome to the Blueprint Medicine second quarter 2024 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 by going to the investor section of our website at www.blueprintmedicines.com.

Speaker Change: Site at Www Dot blueprint medicines dotcom.

Jenna Cohen: Joining me today are Kate Haveland, Chief Executive Officer, Felina Lee, Chief Commercial Officer, Christy Rossi, Chief Operating Officer, and Mike Lancetel, Chief Financial Officer. Suad Nimuni, President, Research and Development, is also on the line and available during Q&A.

Joining me today are Kate Haviland, Chief Executive Officer.

Lina Li Chief Commercial Officer, Christy Rossi, Chief operating Officer, and Mike lands at all Chief Financial Officer.

Speaker Change: Pneumonia President research and development is also on the line and available during Q&A.

Unknown Executive: 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. Your caution not to place any undue reliance on these forward-looking statements, and Blueprint disclaims any obligation to update such statements.

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. These 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: 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, which 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 disclaims any obligation to update such statements. I'll now hand the call over to Katie.

Speaker Change: Claims any obligation to update such statements I'll now hand, the call over to Kate.

Kate Haviland: I'll now hand the call over to Kate. Thank you, Jenna, and good morning, everyone. This quarter marks a milestone, one full year since the U.S. approval of Ava Kit for indolent systemic massicitosis. At the beginning of the year, we laid out that our top priority as a company is Ava Kit's launch execution. And we have delivered yet another very strong quarter revenue, one that exceeded our own expectations as we continue to build this new world. This is one of the most exciting rare disease launches happening today, as each quarter makes Ava Kit's path to a greater than $2 billion peak revenue opportunity that much clearer.

Katie: Thank you, Jenna, and good morning, everyone. This is one of the most exciting rare disease launches happening today, as each quarter makes AvaKit's path to a greater than $2 billion peak revenue opportunity that much clearer. Avica offers a unique and multidimensional value proposition, a medicine that targets the source of SM, driving deep and durable benefits, while importantly, also being very well tolerated, enabling patients to stay on AvaKit over the long term, with a full year of launch now under our belts and our growing experience with the range of factors that drive our business, focused in Mass Cell Driven Disorders, where there is high medical need in large patient populations, and where we can leverage our expertise and infrastructure to drive the next phase of value inflection at Blueprint Medicines, and a financial profile anchored by sustainable top-line revenue growth.

Kate: Thank you Shannon and good morning, everyone.

Kate: This quarter marks a milestone.

Kate: One full year since the U S approval of a kit for indolent systemic mastocytosis.

Speaker Change: At the beginning of the year, we laid out that our top priority as a company, it's Eva kits launch execution.

Speaker Change: And we have delivered yet another very strong quarter of revenue.

Speaker Change: One that exceeded our own expectations as we continue to build this new rare disease market.

Speaker Change: This is one of the most exciting rare disease launches happening today as each quarter makes Ava kits path to a greater than $2 billion peak revenue opportunity that much clearer.

Kate Haviland: Our conviction in Ava Kit's multi-billion dollar market opportunity is based on the positive reception and adoption of Ava Kit. We are seen across physicians, patients, and payers, as we successfully changed the treatment paradigm for patients with SM. Ava Kit offers a unique and multi-dimensional value proposition: a medicine that targets the source of SM, driving deep and durable benefits, while importantly, also being very well-tolerated, enabling patients to stay on Ava Kit over the long term. As we increase the number of ISM patients on therapy, the cumulative effects of patients staying on therapy will be a significant driver of revenue this year and beyond.

Speaker Change: Our conviction and advocates multibillion dollar market opportunity is based on the positive reception and adoption of Ebix, yet we are seeing across physicians patients and payers.

Speaker Change: We successfully changed the treatment paradigm for patients with us up.

Speaker Change: <unk> offers a unique and multi dimensional value proposition.

Speaker Change: A medicine that targets the source of S M.

Speaker Change: Driving deep and durable benefits, while importantly, also been very well tolerated and.

Speaker Change: Enabling patients to stay on advocate over the long term.

Speaker Change: As we increase the number of ISR patients on therapy, the cumulative effects of patients staying on therapy will be a significant driver of revenue this year and beyond.

Kate Haviland: Today, we're raising revenue guidance based on our strong performance in the first half of this year. With a full year of launch now under our belts and our growing experience with the range of factors that drive our business, we have more confidence in this guidance and how we will end the year.

Speaker Change: Today, we're raising revenue guidance based on our strong performance in the first half of this year.

Speaker Change: With a full year of launch now under our belts and our growing experience with a range of factors that drive our business we.

Speaker Change: We have more confidence in this guidance and how we will end the year.

Speaker Change: Selina will discuss these factors driving commercial performance in more detail in a few minutes.

Selina: We have just started scratching the surface on reaching the patients with S M, who could potentially benefit from treatment with advocate.

Selina: And we expect that advocate will drive continued and sustainable revenue growth over the long term.

Kate Haviland: The sustainable revenue growth over the long term, enabling us to invest in our prioritized areas of research and development, focused in mass health-driven disorders, where there is high medical need and large patient populations, and where we can leverage our expertise and infrastructure to drive the next phase of value inflection of Blueprint Medicines.

Selina: Enabling us to invest in our prioritized areas of research and development.

Selina: Focused in mass cell driven disorders, where there is high medical need in large patient populations and where we can leverage our expertise and infrastructure to drive the next phase of value inflection of blueprint medicines.

Kate Haviland: We are pleased that received IND clearance for Blue 808, our wild-tip kit inhibitor, and we have initiated the Healthy Volunteer Study. We believe Blue 808 has the potential to impact core biology across a number of mass cell diseases by targeting Kit. Christie will review our progress to date across our entire portfolio later on the call. With a foundation of significant and growing revenue from Avicat, a next wave of therapies in our pipeline that address important medical needs and even larger-scale patient opportunities, and a financial profile anchored by sustainable top-line revenue growth, we have the financial flexibility to invest in innovation, and we have compelling opportunities in our portfolio that will drive the next wave of value creation as we continue building Blueprint Medicines.

Selina: We are pleased to have received I N D clearance for Blue 808 are wild type kit inhibitor and we have initiated the healthy volunteer study.

Selina: We believe Blue 808 has the potential to impact core biology across a number of Marcel diseases by targeting kit.

Selina: Christie will review our progress to date across our entire portfolio later on the call.

Speaker Change: With a foundation of significant and growing revenue from <unk> to cat.

Speaker Change: Our next wave of therapies in our pipeline that address important medical need an even larger scale patient opportunities.

Speaker Change: And our financial profile anchored by sustainable topline revenue growth.

Speaker Change: We have the financial flexibility to invest in innovation and we have compelling opportunities in our portfolio that will drive the next wave of value creation as we continue building blueprint medicines.

Kate Haviland: Mike will add more color to our financials to close us out.

Speaker Change: Mike will add more color to our financials to close us out.

Felina Lee: With that, I'll turn it over to Felina for more detail on our commercial performance. Thanks, Kate. In the second quarter, Avicat achieved $114.1 million in net product revenue, including $101.5 million in the US, and $12.7 million XUS. Avicat revenue has grown by more than 185 percent year over year, reflecting our strong execution as we capture this unique rare disease opportunity. Second quarter growth in the US was driven by continued positive trends across key business fundamentals, growth and patients on Avicat driven by new patient starts and low discontinuation rates, high compliance, and continued upside in our commercial versus free good mix.

Speaker Change: With that I'll turn it over to Philina for more detail on our commercial performance.

Philina: Thanks, Kate in the second quarter, Eva kit achieved $114 $1 million in net product revenue, including $101.5 million in the U S and $12 $7 million ex U S.

Philina: <unk> revenue has grown by more than 185% year over year, reflecting our strong execution as we capture the unique rare disease opportunity.

Katie: Second quarter growth in the U.S. was driven by continued positive trends across key business fundamentals, growth in patients on AvaKit, driven by new patient starts and low discontinuation rates, high compliance, and continued upside in our commercial versus free goods mix. We've seen a consistent pace of new patient starts over the first half of the year. Once patients start AvaKit, they stay on treatment. Patient compliance also remains strong, further reflecting how the compelling clinical profile and pioneering are playing out in the real world. Second,

Philina: Second quarter growth in the U S was driven by continued positive trends across key business fundamentals.

Philina: And patients on Eva kit, driven by new patient starts and low discontinuation rates high compliance and continued upside in our commercial versus free goods mix.

Felina Lee: And our international team had an exceptional quarter.

Philina: And our international team had an exceptional quarter.

Felina Lee: Let's take a closer look at what drove our business this quarter and what we expected to see for the rest of the year. First, we continue to see strong and steady growth in patients on Avicat, driven by new patient starts and low discontinuation rates. We've seen a consistent pace as new patient starts over the first half of the year. These new patient starts are coming from an expanding Avicat prescriber base that continues to grow and breadth and depth. We continue to see low discontinuation rates consistent with a multi-year duration of therapy in ISM. Once patients start Avicat, they're staying on treatment.

Philina: Let's take a closer look at what drove our business this quarter and what we expect to see for the rest of the year.

Philina: First we continue to see strong and steady growth in patients on either kit driven by new patient starts and low discontinuation rates.

Philina: We've seen a consistent pace of new patient starts over the first half of the year.

Philina: These new patient starts are coming from and expanding Eva kit prescriber base that continues to grow in breadth and depth.

Philina: We continue to see low discontinuation rates consistent with our multi year duration of therapy and I S. M.

Philina: Once patients start either kit, they're staying on treatment.

Felina Lee: This will continue to drive our base of patients on therapy and be an increasingly important growth driver over time. Patient compliance also remains strong, further reflecting how the compelling clinical profile and pioneer is playing out in the real world. Second, free-good favorability was another source of strength this quarter, reaching an average free-good share of just below 20% since ISM launch. Our free-good share has been a significant source of strength in the first half of the year as the mix of patients on avicates skews increasingly towards ISM and as the IRA Part D redesign has enabled more patients to access paid therapy.

Philina: This will continue to drive our base of patients on therapy and be an increasingly important growth driver over time.

Philina: Patient compliance also remain strong further reflecting how the compelling clinical profile and pioneer is playing out in the real world.

Philina: Second.

Katie: Free Goods Favorability was another source of strength this quarter, reaching an average free goods share of just below 20% since ISM launched. Our free goods share has been a significant source of strength in the first half of the year as the mix of patients on AvaKit skews increasingly towards ISM, and as the IRA Part D redesign has enabled more patients to access paid therapy. Finally, the strong trends we have seen in our U.S. launch are playing out in our international business.

Philina: Free goods savvy ability with another source of strength this quarter, reaching an average free goods share of just below 20% since ISR launch.

Philina: Our free goods share has been a significant source of strength in the first half of the year as the mix of patients on either kit skews increasingly towards I S. M and is the IRA part D. Redesign has enabled more patients to access peds therapy.

Felina Lee: Finally, the strong trends we have seen in our US launch are playing out in our international business. Our international team is driving strong performance with the ISM launch underway in Germany, where the prescriber base is growing across both academic and community settings. And we are working to bring avicates to market for ISM in additional countries in 2025, both through our own global footprint and free distributors. We're just getting started and expect our international business to be an important contributor to our growth going forward.

Philina: Finally.

Philina: The strong trends, we've seen in our U S launch are playing out in our international business.

Katie: Our international team is driving strong performance with the ISM launch underway in Germany, where the prescriber base is growing across both academic and community settings. We're just getting started and expect our international business to be an important contributor to our growth going forward. As we enter the second half of the year, we expect continued strength across the business, and we're also keeping our eye on a few things, like seasonality, something common across our industry that we anticipate will impact the timing of patient start. The most important part of seasonality, now that we understand it better, is that we don't expect it will impact annual performance.

Philina: Our international team is driving strong performance with the ISR launch underway in Germany, where the prescriber base is growing across both academic and community settings.

Philina: And we're working to bring Ava kitson market for ice and in additional countries in 2025.

Philina: Both through our own global footprint and through distributors.

Philina: We're just getting started and expect our international business to be an important contributor to our growth going forward.

Felina Lee: Our year-to-date performance across key growth drivers has been strong, and our conviction in this blockbuster opportunity has never been stronger. As we enter the second half of the year, we expect continued strength across the business, and we're also keeping our eye on a few things like seasonality, something common across our industry that we anticipate will impact the timing of patient starts. Our share of free-good, which we believe has stabilized and will remain at a steady rate for the remainder of the year, and the revenue impact of German pricing negotiations, which would be finalized at the end of the year.

Philina: Our year to date performance across key growth drivers has been strong and our conviction in this blockbuster opportunity has never been stronger.

Philina: As we enter the second half of the year, we expect continued strength across the business and we're also keeping our eye on a few things like seasonality something common across our industry that we anticipate will impact the timing of patient starts.

Philina: Our share of free goods, which we believe has stabilized and will remain at a steady rate for the remainder of the year.

And the revenue impact of German pricing negotiations, which would be finalized at the end of the year.

Felina Lee: The most important part of seasonality, now that we understand it better, is that we don't expect it will impact annual performance. Patients are out there, and it's not a question of if, but when they'll start on avicates, and once they start, we know they'll stay on for a long time.

The most important part of seasonality now that we understand it better is that we don't expect it will and that will impact annual performance.

Speaker Change: Patients are out there and it's not a question of if but when they'll start on either kit and once they start we know they'll stay on for a long time.

Felina Lee: As we enter the second half of the year, we're focused on driving increased breadth and depth of prescribing and activating patients to seek treatment.

Philina: As we enter the second half of the year, we're focused on driving increased breadth and depth of prescribing and activating patients to seek treatment.

Katie: Let's look at these areas next. As I mentioned, we continue to expand the breadth and depth of the AvaKit prescriber base. Prescriber breath is growing steadily across all specialties, including allergy. Prescriber depth is growing as first positive experiences lead to repeat prescriptions. Long-term safety and efficacy data are highly motivating for providers and patients, which is why we continue to show that AvaKit's clinical profile is durable with long-term follow-up data. Oftentimes, they don't realize until after they've started AvaKit how good their lives can be again.

Felina Lee: Let's look at these areas next. As I mentioned, we continue to expand the breadth and depth of the Avicate prescriber base. Prescriber breadth is growing steadily across all specialties, including allergy. Prescriber depth is growing as first positive experiences lead to repeat prescriptions. For the first time, this quarter, we're seeing prescribers with more than 10 patients on therapy with avicates, and we see a clear trend of experienced prescribers broadening their view of who's an appropriate patient for avicates. Long-term safety and efficacy data are highly motivating for providers and patients, which is why we continue to show that Avicates clinical profile is durable with long-term follow-up data.

Philina: Let's look at these areas next.

Philina: As I mentioned, we continue to expand the breadth and depth of the Ava kept prescriber base.

Philina: Prescriber breadth is growing steadily across all specialties, including allergy.

Philina: [noise] prescriber depth is growing as first positive experiences lead to repeat prescriptions.

Philina: For the first time this quarter, we're seeing prescribers with more than 10 patients on therapy with Eva kit and we see a clear trend of experienced prescribers broadening their view of who is in appropriate patients for <unk>.

Philina: Long term safety and efficacy data are highly motivating for providers and patients which is why we continue to show that Eva kids clinical profile is durable with long term follow up data.

Felina Lee: This past quarter at the Iyaki conference in Spain, we showed that avicates leads to deep and sustained symptom alleviation and a well-tolerated safety profile, now over multiple years of treatment. The chronic burden of ISM is often underappreciated, and a key part of our ongoing strategy is redefining expectations for control with patients and providers. Trying a new treatment is a big step for patients who are accustomed to managing their disease by limiting their daily activities, taking symptom-directed medications, and avoiding triggers. Patients living with ISM have made a lot of compromises. Oftentimes, they don't realize until after they've started advocate how good their lives can be again, but they need to get ready to make that change.

Philina: This past quarter at the <unk> conference in Spain, we showed that Eva kit leads to deep and sustained symptom alleviation and a well tolerated safety profile now over multiple years of treatment.

Philina: The chronic burden of ice M is often underappreciated and a key part of our ongoing strategy is redefining expectations for control with patients and providers.

Philina: Triangle, new treatment is a big step for patients who are accustomed to managing their disease by limiting their daily activities, taking symptom directed medications and avoiding triggers.

Speaker Change: Patients living with ISN has made a lot of compromises.

Katie: But they need to get ready to make that change. This patient-to-patient dialogue is very powerful, and we're scaling several key initiatives to enable this further. Building on the success of our virtual patient educational series, we recently launched our first in-person patient ambassador program in conjunction with the Mass Cell Disease Society's Mass Cell Con last month. In closing, our first full year of launch has been highly successful and sets us firmly on the path to achieve a more than $2 billion opportunity for AvaKids.

Philina: Oftentimes they don't realize until after they've started David Kay how good their lives can be again.

Philina: But they need to get ready to make that change.

Felina Lee: What we've been hearing in this first year of launch is that we are beginning to change the experience of living with ISM. Patients are sharing that Advocate is life changing, enabling them to return to work, school, and family activities, reducing unpredictable symptoms layers and helping them feel better, and they're starting to tell each other about it. Patients to patient dialogue is very powerful, and we're scaling several key initiatives to enable this further.

Speaker Change: What we've been hearing in this first year of launch is that we were beginning to change the experience of living with I S. M pay.

Speaker Change: Patients are sharing that Eva kit is life changing enabling them to return to work school and family activities, reducing unpredictable symptom flares and helping them feel better.

Speaker Change: And they're starting to tell each other about it.

Speaker Change: This patient to patient dialogue is very powerful and we're scaling several key initiatives to enable this further.

Felina Lee: Building on the success of our virtual patient educational series, we recently launched our first in-person patient ambassador program in conjunction with the Mass Cell Disease Society's Mass CellCon last month. Throughout that meeting, it was incredible to see firsthand the impact of patients sharing experiences with other patients.

Speaker Change: Building on the success of our virtual patient educational theories. We recently launched our first in person patient Ambassador program in conjunction with the mast cell disease societies mast cell Con last month.

Speaker Change: Throughout that meeting it was incredible to see firsthand the impact of patients sharing experiences with other patients.

Speaker Change: In closing our first full year of launch has been highly successful and sets us firmly on the path to achieve a more than $2 billion opportunity for Ava kit.

Felina Lee: Our first full year of launch has been highly successful and sets us firmly on the path to achieve a more than $2 billion opportunity for Avicat. We are proud of the effort our commercial and medical teams have put forward. We understand every step of the patient journey and the education and support patients and providers need.

Katie: We are proud of the effort our commercial and medical teams have put forward, and we see a critical mass of both provider experience and patient activation that creates a nice compounding effect and bodes well for future growth. SM is a multi-billion dollar market opportunity, and we are committed to extending our leadership position and patient impact. In addition, today, I'm happy to share that we've reached an important milestone in our efforts to bring Blue 808, our wild-type kit inhibitor, to a broad range of patients suffering from allergic and inflammatory diseases.

Speaker Change: We are proud of the effort our commercial and medical teams have put forward we.

Speaker Change: We understand every step of the patient journey, and the education and support patients and providers need.

Christy Rossi: Our strategies are working, and Avicat is making a difference, and we see a critical mass of both provider experience and patient activation that creates a nice compounding effect and bodes well for future growth with that alternate over to Christie.

Speaker Change: Our strategies are working and advocate is making a difference.

Speaker Change: And we see a critical mass of both provider experience and patient activation that creates a nice compounding effect and bodes well for future growth.

Speaker Change: With that I'll turn it over to Christie.

Christie: Well enough.

Christy Rossi: In addition to the continued execution of the Avicat launch, we are focused on driving the next wave of innovation and growth at Blue Print Medicine. And today, I'd like to speak briefly about progress against our 2024 portfolio milestones.

Christie: In addition to the continued execution of the Ava Cat launch we are focused on driving the next wave of innovation and growth at blueprint medicines and today I'd like to speak briefly about progress against our 2024 portfolio milestones.

Christy Rossi: Let's start with the franchise we are building in mass cell disorders with Avicat, LNS to know and blue weight away. SM is a multi-billion dollar market opportunity, and we are committed to extending our leadership position and patient impact. Through our engagement with physicians and patients and the unparalleled depths of clinical data and real world experience we have amassed. We have unique insights into the biology of SM and the next frontiers of innovation that can move us further towards our goal of eradicating this disease. We have been advancing LNS to know our next generation kit date 16 V inhibitor to the registration directed part two of the Harbor study.

Christie: Let's start with the franchise, we are building in mast cell disorders, with Eva cat <unk> and blew it away.

Christie: S M as a multibillion dollar market opportunity and we are committed to extending our leadership position and patient impact.

Christie: Through our engagement with physicians and patients and the unparalleled depth of clinical data and real world experience. We have amassed we have unique insights into the biology of SM and the next frontier of innovation that can move us further towards our goal of eradicating the disease.

Christie: We have been advancing <unk>, our next generation kit the 16 D inhibitor to the registration directed part two of the Harbor study.

Christy Rossi: We are on track to initiate part two of Harbor by your end, and as we do, we will be sharing more details about our plans.

Christie: We are on track to initiate part two of Harper by year end and as we do we will be sharing more details about our plans.

Christy Rossi: In addition, today, I'm happy to share that we've reached an important milestone in our efforts to bring blue 808, our Wildtide kit inhibitor, to a broad range of patients suffering from allergic and inflammatory diseases. We've moved Lew-808 into the clinic with the initiation of our Healthy Volunteer Study, and we're eagerly anticipating initial data early next year. We believe this data has marked an important inflection point for the program, supporting our hypothesis that we can achieve tunable biological activity with a wide therapeutic window and enabling us to rapidly establish clinical proof of concept in a range of mass cell disorders, including and beyond urinary care.

Christie: In addition, today I'm happy to share that we've reached an important milestone in our efforts to bring Blue 808 are wild type kit inhibitor to a broad range of patients suffering from allergic and inflammatory diseases.

Katie: We've moved Lu808 into the clinic with the initiation of our Healthy Volunteer Study. Our goal is to raise the bar on what a disease-modifying treatment can offer, considering the full patient experience, efficacy, safety, and the burden associated with administration. The clinical data we are generating with Blue 222 is validating the importance of CDK2 as a target and gives us conviction that the next frontier in the treatment of breast cancer is the complete inhibition of the cell cycle achieved by targeting cell cycle regulators in combination.

Christie: We've moved blew it away into the clinic with the initiation of our healthy volunteer study.

Christie: And are eagerly anticipating initial data early next year.

Christie: We believe this data give mark an important inflection point for the program.

Christie: Supporting our hypothesis that we can achieve tunable biological activity with a wide therapeutic window and enabling us to rapidly establish clinical proof of concept in a range of mast cell disorders, including and beyond are to carry out.

Christy Rossi: Our goal is to raise the bar on what a disease-modifying treatment can offer, considering the full patient experience, efficacy, safety, and the burden associated with administration.

Christie: Our goal is to raise the bar on what a disease modifying treatment can offer.

Christy Rossi: And we will share more about our development strategy and the R&D strategy. In our second focus area of cell cycle inhibition, the clinical data we are generating with Blue-222 is validating the importance of CDK-2 as a target and gives us conviction that the next frontier in the treatment of breast cancer is the complete inhibition of the cell cycle achieved by targeting cell cycle regulators in combination. We believe that the optimal approach to bring Blue-222 forward to patients is in the context of a partnership to maximize the transformative potential of this target, and these discussions are ongoing.

Christy Rossi: We are also making significant progress advancing cell cycle degraders, which are poised to represent the first development candidates out of our targeted protein degradation platforms. This platform was established just a few years ago under Percy Carter's leadership and is already an integral part of our R&D engine across both allergy inflammation and oncology.

Philina Lee: This platform was established just a few years ago under Percy Carter's leadership and is already an integral part of our R&D engine across both allergy, inflammation, and oncology. As Philina noted earlier on the call, we are raising our APICOT product revenue guidance and now expect to achieve $435 to $450 million in net product revenue in 2024. This guidance update continues to reflect our evolving view of the fundamentals driving continued strength and compliance and duration of therapy and the potential impact of the ISM price negotiations in Germany.

Speaker Change: His leadership and is already an integral part of our R&D engine across both allergy inflammation and oncology.

Mike Lancetel: With that, I will turn it over to Mike. Thanks, Christie. Earlier this morning, we reported detailed financial results in our press release, and for today's poll, I'll touch on a few highlights from the quarter. In the second quarter, total revenues were $138.2 million, including $114.1 million in net product revenues from sales of Avakit and $24 million in collaboration license and other revenues. As Felina noted earlier on the call, we are raising our Avakit product revenue guidance and now expect to achieve $435 to $450 million in net product revenue in 2024. This guidance update continues to reflect our evolving view of the fundamentals driving the business.

Christie: With that I will turn it over to Mike.

Mike: Thanks Christy.

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

Mike: In the second quarter total revenues were $138 $2 million, including $114 1 million in net product revenues from sales of <unk> and $24 million in collaboration license and other revenues.

Mike: As Polina noted earlier on the call we are raising our Ava kit product revenue guidance and now expect to achieve $435 million to $450 million and net product revenue in 2024.

Polina: This guidance update continues to reflect our evolving view of the fundamentals driving the business.

Mike Lancetel: Patients on therapy, including a greater understanding of the role that seasonality plays in ISM, free goods favorability, and its impact on revenue growth in the second half compared to the first half of the year. Continued strength and compliance and duration of therapy and the potential impact of the ISM price negotiations in Germany. First half growth trajectory was influenced by stronger than expected performance, with upside across a combination of variables that drove results above the strong and steady growth that we have always expected. Throughout the year, we have talked about our philosophy in setting guidance and our goal of providing estimates that are relevant and reflective of our own expectations.

Polina: Patients on therapy, including a greater understanding of the role that seasonality plays an ASM.

Speaker Change: Pretty good favorability and its impact on revenue growth in the second half compared to the first half of the year.

Mike: Continued strength in compliance and duration of therapy.

Mike: And the potential impact of the ASM price negotiations in Germany.

Philina Lee: The first half growth trajectory was influenced by stronger than expected performance, with upside across a combination of variables that drove results above the strong and steady growth that we have always expected. Throughout the year, we have talked about our philosophy in setting guidance and our goal of providing estimates that are relevant and reflective of our own expectations. I'm thrilled that our performance year to date has enabled us to raise guidance twice, and we anticipate that both our research and development expenses and our SG&A expenses will remain relatively flat for the remainder of this year. We remain in a solid financial position with $868.5 million in cash on hand.

Mike Lancetel: Medicines Corp. Turning to expenses, total cost and operating expenses were relatively flat at $181.2 million for the second quarter. And we anticipate that both our research and development expenses and our SG&A expenses will remain relatively flat for the remainder of this year. We remain in a solid financial position with $868.5 million from cash on hand. And with the ongoing success of the advocate launch and our commitment to manage operating expenses, we are in a great position to continue to drive long-term shareholder value.

Katie: And with the ongoing success of the Avocat launch and our commitment to manage operating expenses, we are in a great position to continue to drive long-term shareholder value. With that, I'll now turn the call back over to the operator for questions. Operator? That's star one on your telephone keypad. To withdraw your question, press star followed by two.

Unknown Executive: With that, I'll now turn the call back over to the operator for questions. Operator? Thank you.

Unknown Executive: Ladies and gentlemen, if you'd like to ask a question, please press star one on your telephone keypad. To withdraw your question, press star followed by two. And please remember to unmute your microphone when it's your turn to speak.

Mike: Star followed by two.

Speaker Change: And please remember too and mutual microphone when it's your turn to speak.

Salveen Richter: Our first question comes from Savine Ritcher from Goldman Sachs. Savine, your line is now open. Good morning. Thank you for taking my question here.

Operator: Our first question comes from Salveen Richter from Goldman Sachs. Salveen, your line is now open. Good morning.

Richard <unk>: Our first question comes from Richard <unk> from Goldman Sachs.

Speaker Change: Your line is now open.

Richard <unk>: Good morning, Thank you for taking my question here.

Salveen Jaswal Richter: Thank you for taking my question here. With regard to the ISM launch here, now that you're a full year post approval, how are you thinking of, you know, quarterly dynamics here? And could you discuss any impact you've seen to date from the Part D redesign and how this might evolve? And for your well-type kit, when do you expect healthy volunteer data this year or early next year and how are you thinking about the importance of this data set as it relates to PK PD, such as potential for flexible dosing? Hi Salveen.

Salveen Richter: With regard to the ISM launch here, now that you're a full year post-approval, how are you thinking of quarterly dynamics here, and could you discuss any impact you've seen today from the Part D redesign and how this might be evolved?

Speaker Change: With regard to.

Speaker Change: The ASM.

Speaker Change: Sure now that you're a full year of post approval how are you thinking of.

Speaker Change: Quarterly dynamics here and could you discuss any impact you've seen to date from the part D redesign and how this might be evolved and for your wild type kit should we expect healthy volunteer data this year or early next year and how are you thinking about the importance of this data set as it relates to PK PD such as potential for flexible dosing.

Salveen Richter: And for your wild-type kit, should we expect healthy volunteer data this year or early next year? And how are you thinking about the importance of this data set as it relates to PKPDs such as potential for flexible dosing? Thank you.

Speaker Change: Thank you.

Unknown Executive: Thank you, Savine, for the question.

Speaker Change: Thank you. So let me answer the question why don't you talk a little bit more about those quarterly dynamics and how where we're seeing some of the part D reform impacting that and then what if you can talk a little bit more about the wild type kit healthy volunteer data that would be great.

Felina Lee: Solina, why don't you talk a little bit more about those quarterly dynamics and how we're seeing some of the Part D reform impacting that?

Felina Lee: And then, if you can talk a little bit more about the wild-type kit, healthy volunteer data, that'd be great. Hi, Solina. First off, I think we're just really pleased with yet another strong quarter in our launch, and this is strength in our conviction to the greatest degree we've ever had, really to see the degree of provider feedback, the growing prescriber base, and how activated patients are coming. These are the factors that will really portend towards the peak potential of a baby kit. Speaking to the quarterly dynamics, I think as we dig in and learn more about this chronic rare disease opportunity, one of the things that we're learning is to expect some seasonal dynamics, right?

Katie: First off, I think we're just really pleased with yet another strong quarter in our launch, and this has strengthened our conviction to the greatest degree I think we've ever had. Really, to see the degree of provider feedback, the growing prescriber base, and how activated patients are coming on board. These are the factors that will really portend towards the peak potential of AvaKit. Speaking to the quarterly dynamics, I think as we dig in and learn more about this chronic rare disease opportunity, one of the things that we're learning is to expect some seasonal dynamics, right? And so for patients with a chronic rare disease, trying something new is really a big step. And they may be more hesitant to do that around times of vacations and holidays.

Felina Lee: And so patients with the chronic rare disease, trying something new is really a big step, and they may be more hesitant to do that around times of vacations and holidays. We saw some of this dynamic last year around Q4, but more importantly, it is to note that the opportunity is absolutely there. The patient funnel is strong. There are a number of patients in need who are not well controlled, and it's not a question of type of if, but when they go on therapy. The timing of when they start depends on a few things. We talked about seasonal impacts.

Katie: We saw some of this dynamic last year around Q4. But more importantly, it's absolutely there. The patient funnel is strong. There are a number of patients in need who are not well controlled, and it's not a question of time, of if, but when they go on therapy. The timing of when they start depends on a few things.

Felina Lee: We talked about the timing of when they happen to have patient visits. Another component that's important is how they're feeling when they show up at that visit, which impacts the provider's ability to recognize their disease burden. And so importantly, the opportunity is absolutely there. It's not a question of if, but when. If a patient doesn't start in August, they will likely start at a subsequent visit. And when they start, we know they'll stay on the kit. These are the most important factors that give us confidence in that peak opportunity. So your question about Part D redesign, you know, we've highlighted the proportion of free goods as one of the important fundamentals in our launch, and that with the strong execution of our team, we've been able to convert a number of patients over to access commercial therapy.

Katie: We talked about seasonal impacts. We talked about the timing of when they happen to have patient visits. Another component that's important is how they feel when they show up at that visit, which impacts the provider's ability to recognize the disease burden. And so importantly, the opportunity is absolutely there. It's not a question of if, but when.

Katie: If a patient doesn't start in August, they will likely start at a subsequent visit. And when they start, we know they'll stay on AvaKit. These are the most important factors that give us confidence in that peak opportunity. Thank you and a nice quarter where there is good advocate experience. And what is your vision for where this eligibility number will go long term? Thank you, Thank you, Brad, for that question. And it's a great question, as we really do see this as a growing overall pie. Philina, do you want to talk a little bit more about that?

Speaker Change: Houston of our team, we've been able to convert a number of patients over to access commercial therapy.

Felina Lee: We believe at this point that the proportion of free goods has stabilized; we've reached just under 20% on average launch to date, and we expect this to remain relatively stable for the rest of the year. Maybe what just one thing, Dad, on that, Salveen, is that we think about ISM, really, you know, this is much more of an I and I type of footprint in terms of payermakes. These patients tend to skew younger, have more commercial payers, and so that's obviously part of the favorability that we're seeing as well.

Speaker Change: We believe at this point that the proportion of free goods has stabilized we've reached just under 20% on average launch to date.

Speaker Change: And we expect us to remain relatively stable for the rest of the year.

Speaker Change: Maybe one just one thing to add on that Sylvain is that as we think about ISR I'm really you know this this is much more of a ini type of footprint in terms of the payer mix.

Speaker Change: <unk> tend to skew younger and have more commercial payer and so that that's obviously part of the favorability that we're seeing as well.

Felina Lee: So, do you want to move on to it, Bluey, to eight? Thank you, Salveen. So, I'm very, very happy that the year view process I and E was very smooth, and now the Healthy Volunteers study is up and running.

Speaker Change: Move onto it blew it away. Thank you salvi.

Speaker Change: I'm really very happy that the.

Speaker Change: The review process was very smooth.

Speaker Change: No.

Speaker Change: This study is up and running we expect the sad and mad data to be available 30.

Felina Lee: We expect the sad math data to be available early in 2025, and it is an important milestone, an important inflection point for us to show the PK, the PD, and the safety data in healthy volunteers. Because we all know why type kit as a target in chronic spontaneous or TKR CSU, now in cold and used TKR has been already demonstrated. So, showing the good profilers consistent with our expectations from 808 will be really a major inflection point for us, so that data will be very important early next year.

Brett Canino: Our next question comes from Brett, can you know, from Typhoon? Brett, your lens is now open. Thank you, a nice quarter.

Brett Canino: You know, one of the main discussions I still have is around how to think about the right eligibility proportion for advocate, and there is this thesis, and you even talked about this, that this number is likely dynamic over time, where you might see that the threshold for use around disease severity declines with physician experience. So, I'm looking at this, and you now have initial practices that have been installed for a year. You're highlighting that many of the practices have up to 10 or more patients on therapy. So, I want to ask, what is your initial read?

Brett Canino: You know, what are you seeing on the ground of the type of patient that's starting therapy today at those legacy practices where there is good advocate experience? And what is your vision for where this eligibility number goes long term? Thank you.

Felina Lee: Thank you, Brad, for that question, and it's a great question as we really do see this as a growing overall pie.

Felina Lee: Selena, do you want to talk a little bit more about that? Yeah, thanks, Brett. I think your hypothesis is really on point, and we really do see a trend towards providers, you know, with that first positive experience on Advocate, where they're likely to select, you know, the one or two. More, most symptomatic patients within their practice. We are really seeing a trend towards them broadening the lens on who's inappropriate patient for advocate towards patients who may have, you know, one or two predominant symptoms that are significantly impacting their quality of life. You know, having interacted with a number of these providers firsthand into our field intelligence, we see multiple signs of that deepening, and we also see it reflected in our claims data as we look at the degree of symptom burden, ER visits, and other measures of disease severity.

Philina Lee: Yeah, thanks, Brad. I think your hypothesis is really on point. And we really do see a trend among providers, you know, with that first positive experience with AvaKit, where they're likely to select, you know, the one or two most symptomatic patients within their practice. And we are really seeing a trend toward them broadening the lens on who's an appropriate patient for AvaKit, toward patients who may have, you know, one or two predominant symptoms that are significantly impacting their quality of life You know, having interacted with a number of these providers firsthand in our field intelligence, we see multiple signs of that deepening, and we also see it reflected in our claims data.

Philina Lee: As we look at the degree of symptom burden, ER visits, and other measures of disease severity, what we're starting to see is a real trend towards that broadening lens of providers opening their minds to who's eligible for AvaKit. And so we think that portends very well toward us achieving the peak opportunity. Our next question comes from Marc Frahm from TD Cohen. (inaudible) Thanks for taking my questions and congratulations on another strong quarter for ABA Kit. Maybe over the last year or so, ABA Kit's been growing like 15, 20 million a quarter at least.

Felina Lee: What we're starting to see is a real trend towards that broadening lens of providers opening their minds to who's eligible for advocate. And so we think that pertains very well towards us achieving the peak opportunity.

Speaker Change: Opening their minds to who's eligible for advocate and so we think that portends very well towards us achieving the peak opportunity.

Kate Haviland: Yeah, and maybe just to add on to that, Brad, a couple of things, you know, one, Toflina's point, really almost every ex-m patient in the United States is eligible for Advocate. And, you know, we have such a broad, a broad label. And I think Toflina's point, what we're seeing is that both prescribers and patients are widening their lens on the benefits of treatment, which, you know, increasingly we're beginning to understand, go beyond just sort of resolution of symptoms, but really addressing some of the underlying drivers of the disease that we think could have, you know, longer-term implications for these patients.

Speaker Change: And maybe just to add onto that Brad a couple of things you know one to clean his point really.

Brad: Really almost every S M patient in the United States is eligible for Ava Cat and I. You know, we have such a broad a broad label and I think to Flenaise point and what we're seeing is that both prescribers and patients are widening their lens them on the benefits of treatment, which you know increasingly we're beginning to understand and go beyond just sort of resolution of <unk>.

Brad: But really addressing some of the underlying drivers of the disease that we think could have longer term implications for these patients. The other really interesting aspect of this market is sort of our increasing understanding that the prevalence may actually be underestimated and maybe growing right. So we know that the number of diagnosed patients has been growing over time.

Kate Haviland: The other really interesting aspect of this market is sort of our increasing understanding that the prevalence may actually be underestimated and may be growing, right? So we know that the number of diagnosed patients has been growing over time. There's also increasingly data out there that suggests that the true prevalence of the disease could be, you know, twice what we thought it was. So I think the dynamics are really interesting and how they will play out to drive what ultimately could be a peak potential that's even greater than what we've estimated to date.

Brad: There is also increasingly data out there that suggest that the true prevalence of the disease disease could be twice, what we thought it was so I think the dynamics are really interesting and how they will play out to drive, but ultimately it could be a peak potential that's even greater than what we've estimated to date.

Mark: Our next question comes from Mark from TD Cohen. Mark, your lens. Oh, thanks for taking my questions, and congrats on another strong quarter for Advocate. Maybe over the last few quarters, the last year or so, it could have been growing like 15, 20 million a quarter at least.

Mark: Your guidance seems to assume quite a significant slowdown from that. I guess, and then all the commentary around, you know, huge patient population still to access and everything would be kind of pointing to the opposite. I guess there's some sort of dynamic beyond just maybe people pushing out a month or two start because of summer vacations that is driving that with there's some sort of stocking impact in Q2 or something else.

Marc Alan Frahm: Your guidance seems to assume quite a significant slowdown from that, I guess. And then all the commentary around, you know, huge patient populations still to access, and everything would be kind of pointing to the opposite. I guess there is some sort of dynamic beyond just maybe people pushing out a month or two start because of summer vacations that is driving that? Was there some sort of stocking impact in Q2 or something else we should be thinking about?

Mark: We should be thinking about. And then maybe longer term, you know, to the last point of Christie, is that maybe this opportunity is even bigger than 2 billion. I guess what, what do you need to see to what needs to happen to kind of give you confidence that it is 2 and a half or 3 or something bigger than 2.

Marc Alan Frahm: And then maybe, longer term, you know, to the last point, Christie, that maybe this opportunity is even bigger than two billion. I guess what do you need to see to give you confidence that it is two and a half or three billion? Yeah, thank you, Marc, for the question. Philina, do you want to talk a little bit about how we've considered the range of variables that inform guidance? I mean, maybe I'll just clarify very quickly: there is no stocking.

Mike Lancetel: Yeah, thank you, Mark, for the question. We do want to talk a little bit about how we've considered the range of variables that the informed guidance. I mean, maybe I'll just clarify very quickly.

Felina Lee: There is no stocking impact mark. We actually, like we've mentioned this on other calls, where we actually have kind of guidance and in contract with guidelines within our channel that it doesn't allow for that. But basically, you can talk a little bit more about how we're thinking about guidance and those range of variables. Yeah. And I think maybe, first off, Mark, hear a question about what do we need to see? I think it's exactly what we're seeing, which is giving us that conviction in the peak opportunity and that we're marching along the path to achieve that peak.

Philina Lee: In fact, Marc, we actually, like we've mentioned this on other calls, where we actually have kind of guidance and contractual guidelines within our channel that doesn't allow for that. But maybe, Philina, you can talk a little bit more about how we're thinking about guidance and those range of variables. Yeah, and I think, first off, Marc, to your question about what we need to see, I think it's exactly what we're seeing, which is giving us that conviction in the peak opportunity and that we're marching along the path to achieve that peak.

Felina Lee: You know, I think it's valuable to sort of look to where we started this year and where we are now at the midpoint, where our updated guidance represents, you know, a more than doubling of our revenue over last year. So your question is more about the dynamics and the growth rate. So certainly, I think the guidance provides the best signpost for the continued growth. As I've alluded to, this represents substantial revenue growth year over year. The guidance factors in a number of variables. And so we've talked about how it's patients on therapy, which is a function both of new patient starts and discontinuation rates, which have been very low for tending, you know, chronic durations of therapy.

Philina Lee: You know, I think it's valuable to sort of look at where we started this year and where we are now at the midpoint, where our updated guidance represents, you know, a more than doubling of our revenue over last year. To your question more about the dynamics and the growth rate. So certainly, I think the guidance provides the best signpost for continued growth. As I've alluded to, this represents substantial revenue growth year over year. The guidance factored in a number of variables.

Philina Lee: And so we've talked about how patients are on therapy, which is a function both of new patient starts and discontinuation rates, which have been very low, portending, you know, chronic durations of therapy. I think we've spoken a couple of times about the potential for seasonal impacts, which we wouldn't be surprised to see around the times of the holidays. But, you know, importantly, even if quarter over quarter is variable, it's the year over year that remains strong and puts us marching towards that impact. Other factors that are important, we talked about the proportion of free goods, compliance, and international, where we certainly see potential growth and contribution there from our expanding geographic contribution. Yeah, thanks, Marc.

Felina Lee: I think we've spoken a couple times to the potential for seasonal impacts, which we wouldn't be surprised to see around the times of the holidays. But, you know, importantly, is that even if quarter over quarter is variable, it's the year over year that remains strong and puts us marching towards that impact. Other factors that are important: we talked about the proportion of free goods, compliance, and international, where we certainly see, you know, potential growth and contribution there from our expanding geographic contribution. Yeah, thanks, Mark.

Brad: We certainly see.

Brad: Potential growth and contribution there from our expanding geographic contribution.

Philina Lee: I, you know, just to reiterate what Salina said, first of all, just on the sort of dynamics. I think we've had these conversations as we've talked about guidance for the year and how we think about, you know, quarter on quarter dynamics. This launch is not about sort of one quarter versus the next. It's about sort of the journey that we're on towards this incredible peak opportunity, and I think what this year has demonstrated is that we are, that opportunity is absolutely there. We are We are capturing it.

Brad: Yeah.

Mark: Thanks, Mark I, you know just to reiterate what between US that first of all just on the sort of dynamics I think we've had these conversations as we've talked about guidance for the year and how we think about you know a quarter on quarter dynamics.

Kate Haviland: Just to reiterate what Flina said, first of all, just on the sort of dynamics. I think we've had these conversations as we've talked about guidance for the year and how we think about quarter-on-quarter dynamics. This launch is not about sort of one quarter versus the next; it's about sort of the journey that we're on towards this incredible key opportunity. And I think what this year has demonstrated is that that opportunity is absolutely there. We are capturing it in big picture. We're in a place where we started the year with a guide of 360 to 390, and we've raised that substantially.

Speaker Change: This launch is not about sort of one quarter versus the next its about sort of the journey that we're on towards this incredible peak opportunity I think what this year has demonstrated is that we are that opportunity is absolutely. There. We are at we are capturing it.

Speaker Change: Big picture, we're in a place where you know we started the year with a guide of $3 60 to 390, and we've raised that substantially right. So we really are very pleased with where we are right now and what that portends for future growth.

Philina Lee: You know, in the big picture, we're in a place where, you know, we started the year with a guide of 360 to 390, and we've raised that substantially, right? So we are really very pleased with where we are right now and what that portends for future growth. In terms of what we need to see to raise the peak, you know, we have been strong in our conviction. I mean, I have seen this as a blockbuster opportunity going back to 2019.

Kate Haviland: So we really are very pleased with where we are right now and what that port ends for future growth. In terms of what we need to see to raise the peak, we have been strong in our conviction. I mean, I've seen this as a blockbuster opportunity going back to 2019. I think we have been on a journey building a market that from scratch really. And so I think we're bringing everybody along with us as we demonstrate that a market opportunity is really there. We'll raise the peak as we feel it is meaningful to kind of bring everybody along.

Speaker Change: In terms of what we need to see to raise the peak you know we have been strong in our conviction.

Speaker Change: I've seen this as a blockbuster opportunity going back to 2019, I think we have been on a journey.

Speaker Change: Building, a market and that you know.

Speaker Change: From scratch really and so I think we're bringing everybody along with us as we demonstrate that that market opportunity is really there well raise the peak.

Philina Lee: I think we have been on a journey, building a market from scratch, really. And so I think we're bringing everybody along with us as we demonstrate that that market opportunity is really there. We'll raise the peak, you know, as we feel it is meaningful to kind of bring everybody along and as we continue to execute the launch and really show that that opportunity is there. But some of the things we're going to be looking at are exactly the dynamics that Felina said, right?

Kate Haviland: And as we continue to execute the launch and really show that that opportunity is there. But some of the things we're going to be looking at are exactly the dynamics that Flina said, right? That broadening of the lens on who may be an appropriate patient to treat. They continued growth and diagnosed patients were suddenly we're seeing, you know, the number of diagnosed patients in the United States approach our initial estimates of what the actual prevalence of the disease is. It would not surprise me to be in a place where we could see more patients diagnosed and, you know, the 32,000 estimate that we had at launch.

Kate Haviland: And so I think you know we'll continue to look at those dynamics. But you know, this is really one of the most exciting launch opportunities that I've had a chance to experience in my career, where you have the first disease on a fine therapy and a really serious prevalence rare disease.

Michael Schmidt: Our next question comes from Michael Schmidt from Guggenheim. Michael, your lunch is now open. Yeah, hey guys, good morning, congrats for me as well on a great continuous avocade launch here. Just one more on that, so you mentioned obviously treatment duration being one very important growth driver here.

Philina Lee: That broadening of the lens on who may be an appropriate patient to treat. Michael, your line is now open. What are you seeing in terms of patients that are using the drug continuously versus perhaps in a more intermittent way? And what are you seeing for the refill rate and how you're thinking about that?

Michael Schmidt: And you know, when you think about patients, what do you see in terms of patients that are using the drug continuously versus perhaps in a more intermittent way, and what are you seeing for refill rate and how you're thinking about that dynamic longer term ultimately. Definitely, do you want to talk a little more about compliance and how we're seeing patients, you know, continuing therapy here.

Christy Rossi: Yeah, thanks for the question, Michael. We're really pleased to see that that strong profile of avocate from Pioneer is playing out exactly as we hope in the real world. You know, I think we've shared earlier that advanced SM duration of therapy is now trending to 25 months and longer. If we look at our ISM trends relative to that patients who have started on therapy, are trending towards an even longer duration of therapy with very few discontinuations, consistent with a multi-year chronic duration of therapy in the real world. To your question on compliance, again, I think really pleased to see how high compliance remains in the real world, certainly towards the upper bound of analogs that we have seen.

Christy Rossi: And we're really pleased to see all of these impacts. We think, as Kate alluded to, this is going to become an increasingly important contribution to our growth as we march towards that peak opportunity.

Unknown Executive: Thank you.

Operator: Our next question comes from Ren Benjamin from Citizen JM. Hey, friend, your line is now open. You know, kind of a strategy to also start expanding beyond the original number of targeted physicians as you go through the And Mike, do you want to talk a little bit about Wild Type Kit? Yes, and then just with respect to kind of our financial guidance, so to answer your question, Laura, yes, like the development plan for Wild Type Kit is baked into our guidance that we give about our confidence to be able to get to a self-sustaining financial profile.

Ren Benjamin: Our next question comes from Ren Benjamin from Citizen JMP. Ren, Berlin is now open. Good morning, guys. Thanks for taking the questions, and congratulations on an amazing quarter and the opening of guidance. Maybe for us, the top 400 or 450 docks that you're originally targeting, how many are prescribing, and it's the idea to get all of them to 10 plus patients, or is there a strategy to also start expanding beyond the original number of targeted physicians as you go through this launch?

Felina Lee: Yeah, thanks for that question, Ren, and hopefully you don't want to talk a little bit more about the strength we've seen in the breadth and depth here in physicians adopting data. Yeah, Ren, maybe just to be clear, our adoption and our breadth has been tremendous launch to date and continues to grow. It's certainly not limited towards just the top 400 providers by volume.

Felina Lee: That top 400 snapshot, I think, is most important to illustrate the dynamics of deepening that we've talked about, and we're really pleased to see that there are now providers who are treating more than 10 ISM patients. I think we would expect to continue to see deepening among those top 400, but importantly, the breadth and depth that we're seeing is far more expansive beyond this. We see a growing number of hematologists, oncologists, allergists in the academic and community settings who are adopting Avakit, and in fact, we also see these dynamics of deepening happening across that entire tranche of providers who are prescribing, which I think just really reflects, again, the strength of the profile in the real world and how providers can become comfortable with Avakit and putting those repeat patients on therapy over time.

Speaker Change: World and how providers can become comfortable.

Speaker Change: With Eva kit and putting those repeat patients on therapy over time.

Laura Prendergast: Our next question comes from Laura Prendergast from Raymond James.

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

Laura Prendergast: Laura, your lines are not open. Hey guys, we're off on the great quarter. Two quick ones for me. First, I know they're obviously low, but what are the real, real discontinuation rates of Avakit shaking out to be? And then, for 808, how much of this clinical development is big into your financial and your guidance for financial self-sustainability? You know, assuming once you have the healthy volume to your data, you'll probably want to move pretty rapidly into a phase two for CFU and possibly other indications. Thanks.

Laura Prendergast: Hey, guys. Congrats on the great quarter, two quick ones for me.

Laura Prendergast: What I know of there, obviously low but what are the railroad of continuation rates of music has shaking out to be and then for <unk> how much of a clinical development is baked into your financial and your guidance or financial self sustainability, assuming once you have the healthy volunteer data, you'll probably want to move pretty rapidly into phase two into phase two for <unk> and parcel.

Speaker Change: Other indications thanks.

Laura Prendergast: Thanks for that question, Laura. Maybe so you can just comment on the discontinuation, and then, Michael, you take the question about how much we have allocated to wild type kids. So, Laura, I think, as we've alluded to, the, you know, in the real world, the discontinuation rates that we're seeing are very low, right? So once patients start on therapy, they're staying on therapy; they're doing that in a highly compliant way. You know, these are patients who have a very, you know, sticky preference. I think when it comes to really balancing all of the things that they're doing in their lives to gain control over their disease, which includes sort of both the behaviors that they're taking to avoid triggers, as well as how they're taking medications.

Laura Prendergast: Yeah. Thanks for that question Laura maybe.

Michael: Can you just comment on the discontinuation and then Michael you take that question about how much we have allocated to wild type kit. So yes.

Christy Rossi: Turns out this is an extremely compliant patient population. And so, you know, mapping that over to some of the data I alluded to in Yaki, where we presented, you know, just strong and sustained symptom alleviation, sustained QOL benefit, as well as a very well-tolerated safety profile. That was seen over a median of two years, and with patients on therapy as long as four years and ongoing. And so, we absolutely expect this profile to be playing out in the real world as well.

Mike Lancetel: Mike, can I talk a little bit about wild-type kit? Yes, and then just with respect to kind of our financial guidance. So, to answer your question, Laura, yes. Like the development plan for wild-type kit is baked into our guidance that we give about our confidence to be able to get to a self-sustaining financial profile.

Mike Lancetel: You know, our priorities, you know, as we look beyond Advocate, are to continue to allocate capital to high-value R and D opportunities, like Blu-Edoi, that are going to drive our long-term growth rate. And so that is factored in. And obviously, we'll share more color on specific financial guidance, you know, as we get into that trial and see how the data plays out. And to your point, Laura, I mean, you know, with the really strong proof of concept, the targeting kit impacts core biology of disease that we've seen. And that we believe it's really potentially the most promising way to improve patient symptoms and outcomes across a range of diseases.

Operator: You know, our priorities, as we look beyond AvaKit, are to continue to allocate capital to high-value R&D opportunities like Blue 808 that are going to drive our long-term growth rate. And so that is factored in.

Mike: And obviously, we'll share more color on specific financial guidance as we get into that trial and see how the data plays out. And to your point, Laura, I mean, you know, with the really strong proof of concept that Targeting Kit impacts core biology of disease that we've seen, and that we believe it's really potentially the most promising way to improve patient symptoms and outcomes across a range of diseases, we're very excited about this Blue 808 program.

Mike: And as we said, I think this healthy volunteer data will be a significant inflection point for us that will help us think about, you know, how broad do we think this molecule could go. And that, you know, we're certainly going to look at that data to define, you know, we have it as an absolute priority for investment, as Mike said, and we will, you know, consider even going beyond that as we anticipate this data to be very strong. Our next question comes from Mike Ulz from Morgan Stanley. Mike, your line is now open. Yeah, thanks, Mike.

Mike Lancetel: We're very excited about this Blu-Edo8 program. And as we said, you know, I think this healthy volunteer data will be a significant inflection point for us that will help us think about, you know, how broad do we think this molecule could go? And that, you know, we're certainly going to look at that data to define, you know, we have, we have it as an absolute priority for investment, as Mike said. And we will, you know, consider even going beyond that as we anticipate this data to be very strong.

Mike: Our next question comes from Mike, both from Morgan Stanley. Mike, your lines are now open.

Mike: Hi, this is a road on from Mike. Thanks for taking our questions on the XUS front. You mentioned expanding Advocate to additional countries in 2025. Can you just talk about the opportunity and expectations there?

Christy Rossi: Yeah, I think Mike, Kristi, you want to talk about our international expansion? Yeah, so, you know, we are really pleased with what we're seeing from our international business. We had a great quarter this quarter. And, you know, importantly, we're really in the beginning stages of bringing an advocate to patients globally and expect us to be, you know, a continued driver of top line revenue growth as we go forward from here. You know, the nature of the business outside the US is that often pricing reimbursement is sort of a gating factor. And so launches tend to lag what we see in the United States.

Christina Rossi: Christina, do you want to talk about our international expansions? Yeah, so, you know, we are really pleased with what we're seeing from our international business. We had a great quarter this quarter.

Christina Rossi: And, you know, importantly, we're really in the beginning stages of bringing AvaKit to patients globally and expect this to be, you know, a continued driver of top-line revenue growth as we go forward from here. But, the nature of the business outside the US is that often pricing reimbursement is sort of a gating factor, and so launches tend to lag what we see in the United States.

Christina Rossi: So what we're seeing right now is, you know, primarily Germany launching an ISM, but a number of other markets continuing to launch advanced ISMs. You know, we have a footprint throughout Europe; we also bring AvaKit to patients through distributors in Eastern Europe and other geographies. And so, you know, we're, we have a great opportunity to continue to expand our revenue base. I'd expect ISM launches to start coming online next year, primarily in some of the other major markets beyond Germany, where, you know, we're actively engaged in pricing reimbursement procedures and sort of walking, walking through that process now.

Christy Rossi: So what we're seeing right now is, you know, primarily Germany launching an ISM, but a number of other markets continuing to launch an advanced FM. You know, we have a footprint throughout Europe. We also bring advocate to patients through distributors in Eastern Europe and other geographies. And so, you know, we have a great opportunity to continue to expand our revenue base. I'd expect ISM launches to start to come online next year, primarily in some of the other major markets beyond Germany, where, you know, we're actively engaged in pricing, reimbursement procedures and sort of walking through that process now.

Operator: So we would expect, you know, as those come online, we'll be able to start to commercialize them in a larger ISM opportunity. So the bottom line is, continue to expect that to be an important driver of growth, and it's certainly, you know, a contributor to that peak potential that we see for AvaKit globally. Our next question comes from Ami Fadia from NIDA, in terms of sort of that, you know, decreasing the sort of threshold for treatment, you know, you've, So you've sort of done your patient activation efforts and gotten feedback from physicians. What's your current thinking around that? Oh, it sounds good.

Christy Rossi: So we would expect, you know, as those come online, we'll be able to start to commercialize in the larger ISM opportunity. So bottom line is continue to expect, you know, that to be an important driver of growth. And, certainly, you know, a contributor to that peak potential that we see for an advocate globally.

Amir Fadia: Thank you. Our next question comes from Amir Fedia from Needham. Amir, you're not open. Thanks, good morning. Thanks for taking my question.

Felina Lee: I have two questions: one for Lena and just a follow-up to Brad's question from earlier. Can you talk through the spectrum of severity of patients across, you know, the 32,000 South patients? And is it a way to, in some way, objectively quantifying Matthew's patients in terms of sort of that, you know, decreasing sort of thresholds for treatment, you know, you've sort of done your patient activation efforts and gotten feedback from physicians, you know, what sort of your current thinking around that.

Fouad Namouni: And then I have another one for Becker. Please, please go ahead. Up, we have your second question on me, because we'll shut the line after. So, sounds good. Just with regards to Blue Edo 8, and you know, if there's some sort of a biomarker of metrics that we should be looking for in order to understand the breadth of application of the data from the Healthy Volunteer Study that will read out next year. Thanks.

Fouad Namouni: Just with regard to Blue 808. You know, is there some sort of biomarker or metric that we should be looking for in order to understand the breadth of application of the data from the Healthy Volunteers study that we'll read out next year? Maybe just to add one thing on me is, at the beginning of this year, we did kind of, as we looked at claims data, which Christy already kind of talked through how we believe that that is likely an undercall of what the overall disease prevalence is. But we said there's just about, you know, a little under 10,000 patients who would qualify as moderate to severe.

Fouad Namouni: Thanks, Amy.

Felina Lee: So, Lena, I think the first question around the spectrum of kind of disease burden that we're seeing as patients are coming on, Avicant, and how we think about that.

Felina Lee: And then for Blue Edo 8, Fouad, we want to talk a little bit about how we're going to be looking at target engagement and the Healthy Volunteer Study. Yeah, thanks for the question, Amy. I think it is Christy alluded to given the breadth of the label, you know, virtually all patients who are adults living with ISM are eligible for Avicant. And certainly, I think the dynamic we're seeing playing out in our launch to date is really starting with patients who tend to be on the more, you know, severe end of symptomology, but broadening towards an ever-widening lens on who is an appropriate patient.

Felina Lee: And we're seeing that, I think, both on the provider side as they gain experience, as well as on the patient side, as patients who are on that step of considering Avicant are encountering more of their providers gaining that experience, having comfort managing Avicant and identifying, you know, I have an opportunity to address these one or two symptoms that are really impacting my quality of life. I think importantly, you know, just if the way we think about ISM 2 is really it's not it's not just a static disease, it's not necessarily even just treating the symptoms that's important.

Felina Lee: This is a disease where you have too many mass cells, too many abnormal or mutated mass cells in the bone marrow and other organs of the body. That's leading to worsening of symptoms over time. That's leading progressively to impacts on bone health and other elements of the biology that's leading to potential for progression. And so I think one piece we're also seeing on the leading edge with key opinion leaders is really that urgency to treat ISM in an attempt to improve that natural history of the disease. Maybe just to add one thing on me is at the beginning of this year, we did could have as we look at claims data, which Christie already could have talked through how we believe that that's likely an under call of what the overall disease prevalence is, but we said there's just about, you know, a little under 10,000 patients who call by moderate to severe.

Speaker Change: Too many mass cells to any abnormal or mutated mast cells in the bone marrow and other organs of the body, that's leading to worsening of symptoms over time, that's leading progressively to impacts on bone health and other elements of the biology, that's leading to the potential for a progression and so I think one piece. We're also seeing on the leading edge with.

Michael: Key opinion leaders is really that urgency to treat.

Michael: ASM and in an attempt to improve that natural history of the disease.

Fouad Namouni: So those are patients that are kind of right in line with, you know, our pioneer clinical trial. And so, if you think about 10,000 there, plus this broadening aperture, really, we are just scratching the surface of this opportunity. And there are thousands of patients who could potentially benefit from AvaKit, which, again, leads to our, you know, conviction about this peak opportunity. Fouad, do you want to talk a little bit about Blue 808 and its pharmacodynamics?

Speaker Change: Maybe just to add one thing on me is at the beginning of this year, we did kind of as we look at at claims data, which Christy Arty you kind of talk through how we believe that that is likely in under call of of what the overall disease prevalence as but we said it was just about a little under 10000 patients who would qualify as moderate to severe. So those are patients that are kind of right in line with.

Felina Lee: So those are patients that are kind of right in line with, you know, our pioneer clinical trial and so. So if you think about 10,000 there, plus this broadening aperture, really we are just scratching the surface of this opportunity, and there are thousands of patients who can possibly benefit from a kit, which again leads to our conviction on this peak opportunity.

Fouad Namouni: What do you want to talk a little bit about blue weight weight and the data that we'll see from healthy volunteers will cover obviously the safe use is important, but also the pharmacology. The pharmacodynamics will look at the wide number of pharmacodynamic markers in the healthy volunteer study as we all know when we talked about it at our, you know, past webinar and you want to go and wild type kit as a target is really an ideal target to tackle type 2 inflammation or inflammatory diseases and the range of applicability is a pretty broad. The way we are thinking about it or the way we are tackling that and increasing our confidence in the opportunity for blue weight weight is really not only looking at biomarker but rapidly looking at clinical multiple clinical proof of concept as we finish the execution of the very early study that we just started that will give us even an idea on the breath of the diseases with type to inflammation diseases that we will go to with the blue a to weight.

Fouad Namouni: I mean, Blue 808 and the data that we see from healthy volunteers cover, obviously, safety, which is important, but also pharmacology, and pharmacodynamics, and we're looking at a wide number of pharmacodynamic markers in the healthy volunteer study. As we all know, and we talked about it at our past webinar a few months ago, wild type NK cells as a target is really an ideal target to tackle type 2 inflammation or inflammatory diseases, and the range of applicability is pretty broad.

Fouad Namouni: The way we are thinking about it or the way we are tackling that and increasing our confidence in the opportunity for Blue 808 is really not only looking at biomarkers but rapidly looking at clinical, multiple clinical proof of concept as we finish the execution of the very early study that we just started. That will give us even an idea of the breadth of the diseases with type 2 inflammation that we will go to with Blue 808. Our next question comes from Matt Biegler from Oppenheimer. Matt, your line is now open.

Unknown Executive: Great.

Matthew Biegler: Next question comes from Matt Biegler from Oppenheimer. Matt, your line is now open. Hey, good morning guys. Congrats on the front from us as well. Can you comment on whether there's been any net pricing increases quarter and quarter, and if so, could you break down revenue growth by price versus bonds? Is a question that you investors have asked us. Thanks. Thanks for the question, Matt. I think that's an easy one I can just take that, but no, we have not had any quarter of a quarter net pricing increases, so that's not one of the contributing factors.

Matthew Cornell Biegler: Hey, good morning, guys. Congratulations on the print from us as well. Um, can you comment on whether there were any net pricing increases quarter over quarter? And if so, could you break down revenue growth by price versus volume?

David: Thank you. Our next question comes from David, the bot from CT. David, the line is now open. Hi, John on for David. Thanks for taking our question. On advocate, can you contextualize some of the trends you're seeing for prescribers at academic centers versus community centers? And in the slides, it appears that the relative proportion of community docs has ticked slightly down from a lot of quarters, so just any color there would be helpful. Thanks. Yeah, John, thanks for the question. I think one of the things that we've been really pleased about is the participation of the community so early, even in the first quarter of our launch.

Operator: This is a question that a few investors have asked us. Thank you. Our next question comes from David Lebot from Connecticut. David, your lines are now open. On the slides, it appears that the relative proportion of community docs has ticked slightly downward from the last quarter. So just, you know, any color there would be helpful.

Felina Lee: But definitely, did you want to talk a bit more about that split? Yeah, sure. As Kate alluded to, I think really the breadth of prescribing is one of the most important lead indicators in a chronic rare disease launch like this one. We see that as a great sort of lead for continued growth and prescribing. The trends that you're speaking to in terms of academic and community, so in things first off, we've just been pleased to see broad adoption across all specialties as well as settings, academic and community, hematology oncology, as well as an increasing number of allergists.

Felina Lee: The trend that we're seeing this quarter, I think, probably speaks more to the extent of deepening that we're seeing, which is likely occurring more within those centers of excellence.

Felina Lee: But as I alluded to before, we're really seeing deepening along that entire curve of providers who have adopted, David, and so we expect both continued breadth as well as continued depth across all specialties and settings over time.

Peter Lawson: Our next question comes from Peter Lawson from Barclays.

Alex: Peter, your line is now open. Hey, good morning. This is Alex on for Peter at Barclays. Thank you for taking our question.

David Neil Lebowitz: Thanks. Hey, good morning. This is Alex Onfura, Peter from Barclays.

Christy Rossi: Just on LNS to NIB, just wondering if you could remind us how that molecule differentiates or improves on the profile of Advocate, and then how should we think about the time needed to complete that pivotal study? Thank you.

Christy Rossi: Thanks, Alex, for the question. Christy, do you want to talk about LNS good? Sure. So we're, you know, moving out on this new forward. It's our next generation, Kiti at 16D inhibitor. As you know, we've said before, it's another very potent selective molecule. You know, the primary point of differentiation is around brain penetrance, although increasingly, we know we don't think that's necessarily relevant in ISM. So, you know, our strategy is really to bring this forward in a way where we can really clinically differentiate and address, you know, where the disease is going in ISM. So we, you know, we now understand the biology of the disease, the spectrum of the disease in a much deeper way than we did, you know, 10 years ago, at Blueprint Medicines.

Alex Onfura: Thank you for taking our question. Just on LNS-DNIB, I was wondering if you could remind us how that molecule differentiates or improves on the profile of AvaKit, and then how should we think about the time needed to complete that pivotal study? Thank you. Thanks, Alex, for the question. Christy, do you want to talk about L-Nested? Sure. So we're, you know, moving L-Nested forward.

Christy: It's our next generation KIT-C816B inhibitor. As we've said before, it's another very potent, selective molecule. The primary point of differentiation is around brain penetrance, although increasingly we don't think that's necessarily relevant in ISM.

Christy: So, you know, our strategy is really to bring this forward in a way where we can really clinically differentiate and address where the disease is going in ISM. So we now understand the biology of the disease, and the spectrum of the disease in a much deeper way than we did, you know, 10 years ago at Blueprint Medicines. And I think the frontier has really moved in terms of what the expectations are for treating patients and really moving towards that goal of really eradicating what is a very serious chronic disease in this patient setting.

Speaker Change: Much deeper way than we did you know 10 years ago at blueprint medicines and I think the frontier has really moved in terms of what the expectations are for treating patients and really moving towards back all of of really eradicating what is a very serious chronic disease in that patient setting and so when we think about part two of harbor them, we're really being thoughtful.

Christy Rossi: And I think the frontier is really moved in terms of what the expectations are for treating patients, and really moving towards that goal of really eradicating what is a very serious chronic disease in this patient setting.

Christy: And so when we think about Part 2 of HARBOR, we're really being thoughtful in terms of how we bring L-Nested forward to really demonstrate that differentiated clinical impact on ISM. And again, we'll be sharing more about that as we head into the end of the year. Hi, thanks, and congrats on the numbers. Any questions from you?

Christy Rossi: And so when we think about part two of Harbor, we're really being thoughtful in terms of how we bring LNS to NIB forward to really demonstrate that differentiated clinical impact on ISM. And again, we'll be sharing more about that as we head into the end of the year.

Speaker Change: In terms of how how we bring all of that for too to really demonstrate that differentiated clinical impact them on an ISR and again will be will be sharing more about that as we as we head into the AR at the end of the year.

Okay.

Speaker Change: Yeah.

Unknown Executive: Thank you.

Speaker Change: Our next question comes from Andy Berens from Leerink your.

Unknown Executive: Our next question comes from Andy Berens from Learing. Andy, your line's not open. Thanks and congrats on the numbers. Two questions from you. I was wondering if you could give us some insight into the 20% free drug number. I recall in Q1 of last year, because it's a bit over 5 million of the ASM revenues were from free drug, purchased by charitable organizations. You give us the number this quarter, because these patients have their drug purchased by charitable organizations; all they ultimately converted to paying patients, just trying to get a sense whether they're expected to grow as the patient numbers increase in order to maintain the sub 20%.

Andy Berens: Your line is now open.

Andy Berens: Alright, thanks, and congrats on the numbers.

Operator: I was wondering if you could give us some insight into the 20% free drug number. I recall in Q1 of last year, you told us that a bit over 5 million of the ASM revenues were from free drugs. Charitable Organizations Ultimately Converted to Paying Pays, trying to get a sense whether it is expected to grow as the patient numbers increase in order to maintain the sub 20. And then the second question would be, what percentage of the ISM patients escalate to 50 milligrams or higher?

Andy Berens: And then the second question would be, what percentage of the ASM patients escalate to 50 milligrams or higher? Thanks. Thanks for the questions, Andy.

Christy Rossi: Kristi, do you want to take both of those? Sure.

Christy Rossi: Nice to hear from you, Andy. We are, as you said, really happy to see kind of the dynamics that we're seeing with free drug in this launch. And you know, a lot of the evolution comes from the underlying dynamics in the patient population, right? So in case said, we are launching really more into a chronic immunology space with ISM patients, you younger the pair mixes different. So we see more commercial patients, and that naturally will help start to reduce our exposure to free drug. In addition, you know, we see some benefit this year from the IRA redesign, which has limited patient out-of-pocket and basically means that more patients can afford to access paid therapy, whether that's on their own or with the addition of external sources of support that patients may find on their own.

Speaker Change: External sources of support that patients may find on their own and this dynamic is very different than what we saw last year that you are alluding to the reason why we quantified and were able to quantify that dynamic last year was because it was in the setting of advanced us out and we knew that that that sort of tailwind was temporary and would unwind right.

Christy Rossi: And this dynamic is very different than what we saw last year. That you're alluding to the reason why we quantified and were able to quantify that dynamic last year was because it was in the setting of advanced exam. And we knew that that sort of tailwind was temporary and would unwind, right? So we knew that we had a proportion of patients who would access free drug, but unfortunately, or paid therapy, but would have to move back to free drug. And in this case, what we're seeing is that patients who access commercial therapy, we expect that to be a permanent situation for as long as they're, you know, clinically, you know, indicated to be on treatment, which again, an ISM tends to be for long, long periods of time.

Andy Berens: So we knew that we had a proportion of patients who would access free drug, but unfortunately are paid their people, but would have to move back to free drug in this case, what we're seeing is that patients who access commercial therapy, we expect that to be a permanent situation for as long as they're you know clinically.

Andy Berens: [noise] indicated to be an on treatment, what you get and I found tends to be for for a long long periods of time.

Christy Rossi: So we expect that that benefit to continue as Selena said, you know, we think that the rate of free drug overall has reached a relatively steady state. So, as we think about guidance going forward, we wouldn't expect that to be a big driver one way or the other.

Felipe: So we expect that that benefit to continue as Felipe said you know, we think that the rate of free drug overall has reached a relatively steady state. So as we think about our guidance going forward, we wouldn't expect that to be a big driver one way or the other.

Christy Rossi: We want to talk a little bit about the what we're seeing in terms of the 50 milligram usage. Yes. So, you know, we continue to report patients, you know, starting at 25 milligrams, being the vast majority of patients we're seeing across that. And we really don't see a lot of utilization of 50 milligrams, where we've seen it tends to primarily be utilized in centers of excellence, where they're really treating the full spectrum of patients. And we know it's a spectrum, right? We see patients from, you know, advanced to indolence; it's a very clinically, you know, heterogeneous patient population, and that, you know, each patient need is unique.

Christy Rossi: And so the fact that we have a range of safe and effective doses available for patients that prescribers can easily access is a huge strength of this profile. You know, one thing we've learned about SM is that it's not a one-size-fits-all disease. It's not a one dose fits all patients' disease, but for the vast majority of ISM patients, 25 milligrams is the right dose. And that's certainly what we're continuing to see in the real world.

Sudan Loganathan: I'm next question, and last question comes from Sudan Loganathan from Stevens. Sudan, your lens now open. Hi everyone, good morning, and congratulations again on your great quarter.

Kate Haviland: My first question is more big picture on your views on business development. With the growing task position and ongoing acceleration of ABKIT launch, do you have the appetite for both on deals to bring in earlier late-stage clinical assets into the mix that may benefit from the groundwork that ABKIT assets, or is the focus still on developing the pipeline from this average age kind of endeavors akin to what you're doing with the targeted protein degradation portfolio.

Fouad Namouni: And then secondly, on Harbor studies, do you anticipate there being any challenges with enrolling for ISM patients? For the study, would be effective ABKIT on the market for the same indication? Will there be any patients enrolled in this program that may actually be refactoring ABKIT with that profile set, you know, to test out there?

Speaker Change: Burst study.

Operator: Do you anticipate there will be any challenges with enrolling ISN patients for the study with the effective advocate on the market for the same? We currently have no further questions, so I would like to turn the call back to the CEO, Kate Haviland, for closing remarks. Please go ahead. Thank you, Operator, and as we cross into the second half of 2022, we are in a tremendously strong position, thanks to our people who are driving the success of Blueprint Medicines.

Speaker Change: Do you anticipate there being any challenges with enrolling for ISR patients for the study would be effective advocate on the market for the same indication would there be any patients enrolled in this program that may actually be refractory to because you know what.

Speaker Change: That profile upset.

Andy Berens: You know to test out there.

Kate Haviland: Thank you, Sudan, for the questions and welcome. We really appreciate your kind of joining the Blueprint coverage team here.

Speaker Change: Hey, Thank you sit on for it for the questions and welcome way I really appreciate your kind of joining join that blueprint coverage came here so and in terms of those questions. Yeah, maybe Chris they can start would be D. And then why do you want talk about hardware, but I think I hit on one of the things that I think has been a strength of blueprint medicines and almost nine years that I've been here is that we.

Christy Rossi: So, in terms of those questions, you know, maybe Kristi can start with BD, and then Fouad, you want to talk about Harbor. But thanks to one of the things that I think has been a strength of Blueprint Medicine in the almost, you know, nine years that I've been here, is that we consistently think about business development, both on the buy side and sell side, as a ways of achieving and optimizing our corporate goals and optimizing our business. But me, Kristi, do you want to talk a bit more specifically on how we're thinking about BD? Yeah.

Christy Rossi: So, in case that, I mean, this is two-assisted strategic leverage to optimize the portfolio in terms of both inbound and outbound business development. We are constantly, you know, sort of engaged on that front, you know, scanning kind of the external environment, looking for things that, you know, could be a fit, talking to strategic companies, you know, again, both from an inbound and outbound business development perspective. We are very clear about what our priorities are, right? So we've been very clear in terms of capital allocation, you know, our time and attention and effort. It's very much from a clinical and commercial perspective, particularly focused on advancing our muscle disorder franchise.

Christy Rossi: And that's really around continuing to execute the avicates launch as well as the avicates, you know, clinical development program, which continues to be prolific and generate a lot of important data, bringing out an SNF forward. And then, you know, very importantly, Blue 8-8-8, which, you know, as we said on this call, you know, we are, you know, really moving towards, we think an inflection point here as we get that phase one data and believe that we could advance, you know, across a number of fronts to bring this forward to patients, suffering from muscle disorder. So that is our focus and, you know, nothing from a beauty perspective is distracting from that focus.

Christy Rossi: And, but of course, we're going to continue to look and, you know, other things that makes sense strategically, both from an inbound and outbound perspective.

Christy Rossi: And then you just add one other thing is that, you know, we have been, you know, we would be remiss not to talk about the fact that our discovery team has been prolific in driving innovation at Blueprint Medicines. I mean, I think we're now at 17 development candidates that come out of our labs. I think we're the only company that brought two candidates from our lab, two FDA approvals in less than 10 years. You know, our research and development teams are just absolutely top-notch, top quality. And that just gives us an incredible opportunity to have that internal innovation engine that really enables us to keep a high bar.

Christy Rossi: We think about external innovation.

Fouad Namouni: Flood, do you want to talk about Harper? Yeah. I mean, I'm going to begin the innovation teams now. Okay. To really say that our teams continue to innovate, to really design a structural strategy for Harper that will differentiate Alenestinib from Ava, get an answer to her to Christie's earlier point, major questions that will be we are needed to be answered in many years from now. In terms of execution of Alenestinib and the availability of Ava as a standard of care today, we don't expect major challenges in terms of recruiting patients. First, because institutions that do clinical trials that really have that skill set and that performance aspect of at the same time doing clinical trials but also treating patients, and they know how to do this.

Christy Arty: It's not a strategy for a hot about that will differentiate an interest in it from from from a bucket and the answer to her to christy's every appoint major questions that will be needed to be answered in many years from now in terms of execution and the availability of Eva as the standard of care today, we don't expect major.

Speaker Change: The challenges in terms of recruiting patients first become institutions do clinical trials to really have.

Speaker Change: That skill set in that.

Fouad Namouni: Also, I mean, the study will open in the US, and as we did with Pioneer, the study will also open in a number of international sites to support the recruitment and to also help patients from other countries to get access to Alenestinib trials. So we are very confident about our ability to execute Alenestinib Harbour Part 2.

Kate Haviland: We currently have no further questions, so I'd like to turn the call back to the CEO, Kate Haviland, for closing remarks. Please go ahead. Thank you, operator, and as we cross into the second half of 2022, we are in a tremendously strong position thanks to our people who are driving the success of Blueprint Medicines.

Operator: I'm extremely proud of the hard work, contributions, and dedication of our entire team at Blueprint Medicines as we deliver on our commitment to patients with systemic mesocytosis and beyond. Thank you all for taking the time to join us today, and we thank you for your continued support of Blueprint Medicines. Ladies and gentlemen, this concludes today's call. Thank you for joining us. You may now disconnect your lines. Thank you.

Kate Haviland: I'm extremely proud of the hard work, contributions, and dedication of our entire team at Blueprint Medicines, as we deliver on our commitment to patients with systemic mesocytosis and beyond.

Kate Haviland: Thank you all for taking the time to join us today, and we thank you for your continued support of Blueprint Medicines.

Unknown Executive: Ladies and gentlemen, this concludes today's call. Thank you for joining. You may not disconnect your lines. Thank you.