Q1 2022 Blueprint Medicines Corp Earnings Call

Juan: Good morning, my name is Juan, and I will be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines Festival's 2022 Financial Results Conference call. All lines have been placed on mute to prevent any background noise.

Good morning, My name is one and I will be your conference operator today at this time I would like to welcome everyone to the blueprint medicines first quarter 2022 financial results Conference call. All lines have been placed on mute to prevent any background noise. After the.

Juan: After the speaker remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press a staff followed by number one on your telephone keypad. If you would like to withdraw your question, please press a staff followed by number two.

The speakers remarks, there will be a question and answer what Sachin if you would like to ask a question. During this time simply press the star followed by number one on your telephone keypad.

I would like to withdraw your question. Please press the star followed by number two please plan to limit yourself to one question. Thank you I would now like to turn the call over to your host Tina <unk> from Blueprint medicines Dana you may begin your conference.

Juan: Please plan to limit yourself to one question. Thank you. I would now like to turn the call over to your host, Gina Cohen, from Blueprint Medicines. Gina, you may begin your conference. Thank you, Juan.

Gina Cohen: Good morning, everyone, and welcome to Blueprint Medicine's first quarter 2022 Financial and Operating Results Conference call. This morning, we issued a press release that outlines the topics we plan to discuss today. You can access the press release, as well as the slides that we'll be reviewing today, by going to the Investors section of our website at www.blueprintmedicines.com. Today on our call, Kate Haviland, our Chief Executive Officer, will discuss Blueprint Medicines' Pillars for Growth through 2023.

Thank you Juan good morning, everyone and welcome to Blueprint medicines first quarter 2022 financial and operating results conference call.

Gina Cohen: Christy Rossi, our Chief Operating Officer, will provide an advanced FM launch update. Philina Lee, our Chief Commercial Officer, will provide a non-advanced FM market opportunity update. Becker Hughes, our Chief Medical Officer, will review our recent clinical progress and highlight upcoming milestones across our growing portfolio. And Mike Landsittel, our Chief Financial Officer, will review our first quarter 2022 financial results.

This morning, we issued a press release, which outlines the topics we plan to discuss today.

You can access the press release as well as the slides that we'll be reviewing today by going to the investors section of our website at Www Dot blueprint medicine Dot com.

Today on our call Kate Haviland, our Chief Executive Officer will discuss blueprint medicines pillars for growth through 2023.

Christy Rossi, our Chief operating officer will provide an advanced <unk> launch update.

Helena Lee our Chief commercial officer will provide a non advanced at that market opportunity update.

Becker Hughes Chief Medical Officer will review, our recent clinical progress and highlight.

Elsewhere across our growing portfolio and Mike lands at all our Chief Financial Officer will review, our first quarter 2022 financial results.

Percy Carter, our Chief Scientific Officer is also joining our call and will be available for Q&A.

Gina Cohen: Percy Carter, our Chief Scientific Officer, is also joining our call and will be available for Q&A. Before we get started, I would like to remind everyone that the statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factor section of SEC filings.

Before we get started I would like to remind everyone that statements. We make on this conference call will include forward looking statements.

Actual events or results could differ materially from those expressed or implied by any forward looking statements. As a result of various risks uncertainties and other factors, including those set forth in the risk factors section of <unk> SEC filings.

Kate Haviland: In addition, any forward-looking statement made on this call represents our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statement. Now here's our CEO, Kate Haviland. Thank you, Jenna, and good morning everyone. We appreciate you doing the call today. At Blueprint, we are clear in our goal to be the leading precision medicine company.

In addition, any forward looking statement made on this call represents our views only as of today and should not be relied upon as representing our views as of any subsequent date, we specifically disclaim any obligation to update or revise any forward looking statement.

Now here's our CEO Kate Haviland.

Okay.

Thank you Jennifer and good morning, everyone. We appreciate you joining the call today.

At Blueprint, we are clear in our goal to be the leading precision medicine company.

Kate Haviland: Building on this quarter's success, the next 12 to 18 months will be unprecedented for us as we execute on multiple milestones, driving value creation across all aspects of our business. Blueprint has an incredibly unique profile, with a diversity of significant growth drivers and a strong balance sheet that will enable us to outperform the sector over time as we expand global commercial execution, progress our clinical stage portfolio, and drive innovation through our leading precision medicine discovery platform.

Building on this quarter's success. The next 12 to 18 months will be unprecedented for us as we execute on multiple milestones driving value creation across all aspects of our business.

Blueprint has an incredibly unique profile with a diversity of significant growth drivers and a strong balance sheet that will enable us to outperform the sector over time.

As we expand global commercial execution.

Regress, our clinical stage portfolio and drive innovation through our leading precision medicine discovery platform.

Kate Haviland: The first quarter of this year was marked by a number of important milestones across We continue to solidify AvaKit as the standard of care in advanced systemic mesocytosis, or SM, in the U.S., and we close the quarter with the European Commission approval of AVICA and ADVANCE-SS. Our European launch is now underway.

The first quarter of this year was marked by a number of important milestones across our business we.

We continued to solidify <unk> as the standard of care and advanced systemic mastocytosis or S. M.

In the U S.

And we closed the quarter with the European Commission approvals advocate in advanced SM.

Our European launch is now underway.

Kate Haviland: The global launch of ADVOCATE and ADVANCE-SM is building a strong, real-world value proposition and an important foundation of relationships as we prepare for the top-line data from our registration-enabling Pioneer trial and non-ADVANCE-SM late in the summer. ADVOCATE has the potential to be the first and only treatment approved for non-advanced SS. With positive results from the Pioneer Study, we will have developed a comprehensive body of clinical evidence demonstrating the remarkable efficacy and profound benefits for SM patients across the spectrum of disease, while also driving significant near-term growth for Blueprint.

The global logic advocate in advanced SM is building a strong real world value proposition and an important foundation of relationships as we prepare for the topline data from our registration, enabling pioneer trial and not advanced SM late in the summer.

<unk> has the potential to be the first and only treatment approved for non advanced at that.

With positive results from the pioneer study, we will have developed a comprehensive body of clinical evidence demonstrating the remarkable efficacy and profound benefits to SM patients across the spectrum of disease.

Also driving significant near term growth for blueprint.

Kate Haviland: Another highlight from the first quarter was the data we presented at the AACR annual meeting across our EGFR and CDK2 franchises. It is early days for these programs, but there are many reasons for us to be encouraged about the differentiation of our investigational therapies and their prospects to address major medical needs and difficult-to-treat and prevalent cancers. As our strength this past quarter demonstrates, we are well on our way of delivering on the goals we have set for ourselves this year, while also building a foundation to drive value well beyond 2022. If you fast forward, for instance, to the end of 2023,

Another highlight from the first quarter, where the data we presented at the ACR annual meeting across our Egfr and CDK to franchises.

It is early days for these programs, but there are many reasons for us to be encouraged about the differentiation of our investigational therapies and their prospects to address major medical needs and difficult to treat and prevalent cancers.

As our strength this past quarter demonstrates we are well on our way of delivering on the goals. We have set for ourselves. This year, while also building a foundation to drive value value well beyond 2022.

If you fast forward for instance at the end of 2023, we.

Christy Rossi: We expect to be launching AvaKit in non-advanced FM, engaging Regulatory Authorities on Registration Plans for our EGFR and CDK2 Development Program, and expanding our pipeline with new programs in areas of significant medical need. With that, let me turn the call over to Christy to discuss the progress we have made on the AvaKit launch and Advanced SM.

We expect to be launching <unk> in non against them.

Engaging regulatory authorities on registration plans for our Egfr and <unk> development programs.

And expanding our pipeline with new programs in areas of significant medical need.

With that let me turn the call over to Christie to discuss the progress we have made on the Ava kit launch in against them.

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Christy Rossi: Thanks, Kate. Good morning, everyone. In the first quarter, we continued to build momentum in our ongoing launch of AvaKit and Advanced FM, generating net product revenue of $23.8 million. The Advanced SM Indication contributed the majority of this revenue, and we anticipate that it will be the primary driver of AVICT revenue growth over the course of the year. We are reaffirming our guidance of $115 to $130 million in advocate revenue in 2022, based on the strength of the ongoing U.S. launch, which I will speak about in a minute, and our recent approval in Europe, where we received a marketing authorization in advance of that on March 25th.

Thanks, Kay good morning, everyone.

In the first quarter, we continued to build momentum and our ongoing launch of <unk> and advanced at that.

Generating net product revenue of $23 $8 million.

The event that that indication contributed the majority of this revenue.

And we anticipate that it will be the primary driver of <unk> revenue growth over the course of the year.

We are reaffirming our guidance of $115 million to $130 million in.

Revenue in 2022 based on the strength of the ongoing U S launch, which I will speak about in a minute.

And our recent approval in Europe , where we received marketing authorization in advance that that on March 25.

Christy Rossi: BetaKit is now the first approved disease-modifying precision therapy in the European Union designed to selectively target Kit B816B, the primary driver of FM. Within one week of approval, the first patient was treated in Germany, where AvaKit is now reimbursed for its expanded indication. And we are looking forward to bringing AvaKit to patients in additional EU countries as we work through country-specific reimbursement processes. Now, let's turn to the U.S., which contributed $21.3 million in revenue this quarter.

<unk> is now the first approved disease modifying precision therapy in the European Union designed to selectively target <unk>.

<unk> being the primary driver back then.

Within one week of approval. The first patient was treated in Germany, where <unk> is now reimbursed for expanded indications.

And we are looking forward to bringing <unk> to patients in additional EU countries as we worked through country specific reimbursement processes.

Now, let's turn to the U S, which contributed $21 $3 million in revenue this quarter.

Christy Rossi: We expect revenue growth to continue through the year, driven by two key factors, increasing new patient starts as we reach more prescribers and support more patients, and extended durations of therapy as we impact patients earlier in their disease. Our continued launch execution is driving positive momentum across both of these important dimensions. The launch of AvaKit has fundamentally changed the treatment paradigm in advanced FM, driving significant market growth and setting a new standard of care.

We expect revenue growth to continue through the year driven by two key factors, increasing new patient starts as we reach more prescribers and support more patients.

And extended durations of therapy, as we impact patients earlier in their disease.

Our continued launch execution is driving positive momentum across both of these important dimension.

The London <unk> has fundamentally changed the treatment paradigm and advanced at that.

Driving significant market growth and setting a new standard of care.

Christy Rossi: AvaKit is now the treatment of choice for approximately 70% of all advanced SM patients starting on or switching to a new therapy. Since the launch of AvaKit, the percent of advanced FM patients who are being treated for their disease has grown by approximately 40% as healthcare providers are now choosing to intervene where, historically, they may have chosen to watch and wait. We know there is still significant room for growth as many patients remain untreated.

<unk> is now the treatment of choice for approximately 70% of all advanced SM patients starting on or switching to a new therapy.

Since the launch of <unk> the percent of advanced SM patients, who are being treated for their disease has grown by approximately 40%.

As health care providers are now choosing to intervene where historically they may have chosen to watch and wait.

We know there is still significant room for growth as many patients remain untreated.

Christy Rossi: At an upcoming medical meeting, we will be sharing new, real-world evidence supporting AvaKift's impact on overall survival and advanced SM, which we believe will further catalyze urgency to treat. The momentum we are seeing in new patient starts is driven by our growing prescriber base. In Q1, we activated approximately 65 new accounts, which is particularly impressive given the impact of Omicron early in the quarter.

At an upcoming medical meeting, we will be sharing new real world evidence.

<unk> indicates impact on overall survival in advanced SM.

Which we believe will further catalyze urgency to treat.

The momentum we are seeing in new patient starts is driven by our growing prescriber base.

In Q1, we activated approximately 65, new accounts, particularly impacted given the impact of omicron early in the quarter.

Christy Rossi: The strong base of AvaKid experience we are establishing is characterized by breadth in the community setting and depth in the academic setting. We have had strong penetration into academic centers of excellence. And as our prescriber base continues to broaden, the majority of new accounts are coming from the community, where half or more of advanced-system patients are cared for. This suggests that we are effectively reaching these patients where they are presenting for care, and also that providers who may historically have been less comfortable treating FM are now motivated to treat patients with AvaKit.

The strong base of advocate experience. We are establishing is characterized by breath in the community setting and death in the academic setting.

We have had strong penetration into academic centers of excellence.

And as our subscriber base continues to broaden the majority of new accounts are coming from the community where half or more of advanced SM patients are cared for.

This suggests that we are effectively reaching these patients where they are presenting for care.

And also that provider, who may historically have been less comfortable trading at that are now motivated to treat patients with advocate.

Christy Rossi: We are also seeing patients benefiting from extended treatment duration as we continue to progress the lung. Our estimated duration of therapy for AVACUTE and ADVANCED-SM is trending towards 18 months. In our clinical studies, patients stayed on therapy for an average of two or more years, some for far longer than that, and we expect duration of therapy to continue to extend as we are able to reach and impact patients earlier in the course of their disease when they can derive the most benefit from AvaKit.

We are also seeing patients benefiting from extended treatment duration as we continue to progress the launch.

Our estimated duration of therapy for <unk> in advanced SM is trending towards 18 months.

In our clinical studies patients stayed on therapy for an average of two or more years, some for far longer than that.

And we expect duration of therapy to continue to extend as we are able to reach and impact patients earlier in the course of their disease. When they can derive the most benefit from Eva cat.

Christy Rossi: This extended treatment duration we are seeing across academic and community settings in the real world also confirms that a broad range of prescribers are comfortable managing their patients with the Advocate. The insights that we are gaining throughout this launch cement my belief in the growing strength of our integrated organization and the power of the leadership position we have built in SF. With that, I'll turn the call over to Dr. Philina Lee, who was recently appointed as our Chief Commercial Officer and now oversees our Global Commercial Strategy and U.S. Commercial Organization, to discuss the medical need and market opportunity we see for non-advanced SM. Thanks, Christy, and hello everyone.

This extended treatment duration, we are seeing across academic and community settings in the real world.

Also confirmed that a broad range of prescribers are comfortable managing that patients will be like that.

The insights that we're gaining throughout this launch.

Belief in the growing strength of our integrated organization and the power of the leadership position, we have built and ask them.

With that I'll turn the call over to Dr. <unk> for Lina Li who was recently appointed as our Chief commercial officer, and now oversees our global commercial strategy and U S commercial organization.

Discuss the medical need and market opportunity, we see for non adapt desktop.

Thanks, Christie and Hello, everyone.

Philina Lee: I've been a part of AvaKit's development from discovery through commercialization. As I step into the role of CCO, I am honored to lead our team and deliver on the promise of this important therapy for patients living with FM. Our strong advanced SM launch trajectory, which Christy spoke about, and our growing understanding of the non-advanced SM market, reinforce our belief that SM is a potential blockbuster opportunity for AvaCare. Symptoms of non-advanced SM are debilitating and arise unpredictably, disrupting patients' ability to go to work and spend time with their families. Patients can experience a range of symptoms, such as uncontrolled anaphylaxis, extreme fatigue, diarrhea, skin lesions, and brain fog.

I've been a part of advocates development from discovery through commercialization.

As I step into the role of CCR.

I'm honored to lead our team and deliver on the promise of this important therapy for patients living with them.

Our strong advanced SM launch trajectory, which kristi spoke to and our growing understanding of the non advanced SM market reinforce our belief that SM is a potential blockbuster opportunity for Ava kit.

Symptoms of non advanced SM or debilitating and to rise unpredictably disrupting patients' ability to go to work and spend time with their families.

<unk> can experience a range of symptoms such as uncontrolled anaphylaxis extreme fatigue, diarrhea skin lesions and brain fog.

Philina Lee: Patients share that the symptom burden of non-advanced SM leaves them feeling depressed, isolated, and fearful that the disease will worsen. There are no approved therapies for non-advanced SM today. Current treatment options are inadequate and fail to address the underlying driver of The polypharmacy burden for non-advanced SM patients is significant. 75% of patients have reported taking at least four or more classes of therapies to manage their disease, and these interventions are woefully inadequate.

Patients share the symptom burden of non advanced SM leaves them, feeling depressed isolated and fearful that the disease will worsen.

There are no approved therapies for non advanced SM today.

Current treatment options are inadequate and failed to address the underlying driver of disease.

The polypharmacy burden for non advanced SM patients is significant.

<unk>, 5% of patients have reported taking at least four or more classes of therapies to manage their disease.

And these interventions are woefully inadequate.

Philina Lee: Greater than 80% of patients still report limitations in their work or daily activities, and 64% share that they avoid leaving their home due to their SM. Another study showed 83% of patients expressed frustration that current treatments do not address the root cause of the disease.

Greater than 80% of patients still report limitations in their work or daily activities and 64% share that they avoid leaving their homes due to the rest of them.

Another study showed 83% of patients express frustration, but current treatments do not address the root cause of disease.

Philina Lee: Together with the SM community, our efforts to raise disease awareness and accelerate time-to-diagnosis are yielding a tangible impact. A 54% growth in the number of SM patients observed in U.S. claims since the launch of AvaKit in January 2020. We now see more than 15,000 unique diagnosed SM patients in claims data.

Together with the SM community, our efforts to raise disease awareness and accelerate time to diagnosis are yielding a tangible impact of 54% growth in the number of SM patients observed in U S claims since the launch of <unk> in January 2020.

We now see more than 15000 unique diagnosed SM patients and claims data and most of these patients have not advanced SM.

Philina Lee: And most of these patients have non-advanced SM. We expect this population to continue to grow with our focus on disease education for health care providers, patients, and caregivers, and our emphasis on high-sensitivity blood-based testing for kit D816V. In March, we launched a new disease awareness campaign for patients with FM called It's Something. Within the first week of launch, the website had more than 6,000 unique visitors, including many undiagnosed patients seeking information and a path to diagnosis.

We expect this population to continue to grow with our focus on disease education for health care providers patients and caregivers and our emphasis on high sensitivity blood based testing for kit <unk> hundred <unk>.

In March we launched a new disease awareness campaign for patients with SM calls, it's something within the first week of launch the website had more than 6000 unique visitors, including many undiagnosed patients seeking information and a path to diagnosis.

Philina Lee: An educated patient is a catalyst for diagnosis and treatment. As we await the Pioneer data later this summer, we're confident there are many highly engaged SM patients, both diagnosed and not yet diagnosed, who are searching for better options to manage their disease. With that, I'll turn the call over to Becker to review our R&D progress. Thank you, Philina, and good morning, everyone. Today, I'll provide updates on two areas, expectations for Pioneer, our registrational study in non-advanced SM, and our anticipated clinical data milestones over the next year. Let's start with Pioneer, which has two parts.

And educated patient is a catalyst for diagnosis and treatment.

As we await the pioneer data later this summer we're confident there are many highly engaged SM patients both diagnosed and not yet diagnosed who are searching for better options to manage their disease.

With that I'll turn the call over to Becker to review to review our R&D progress.

Helena and good morning, everyone.

Today I'll provide updates in two areas expectations for pioneer our Registrational study in non advanced SM and our anticipated clinical data milestones over the next year.

Let's start with pioneer which has two parts part.

Becker Hughes: Part one was designed to select the optimal dose and demonstrate proof of concept to ensure a profound reduction of symptoms and show tolerability for long-term dosing. We saw that AvaKit demonstrated deep reductions of clinical symptoms at all doses, as well as a rapid reduction in mast cell burden, kit D816V allele burden, serum triptase, and positively impacted patient quality of life.

Part one was designed to select the optimal dose and demonstrate proof of concept to ensure a profound reduction of symptoms and sure tolerability for long term dosing.

We saw that <unk> demonstrated deep reductions of clinical symptoms at all doses, a rapid reduction in mast cell burden DP <unk> allele burden.

Serum tryptase and positively impacted patient quality of life.

Becker Hughes: These data from Part 1 were the basis for AvaKit's breakthrough therapy designation in non-advanced SM. Part 2 was designed to enable registration by demonstrating response rate superiority of AvaKit versus placebo, as assessed by Total Symptom Score (TSS). PFS is measured using the ISM Symptom Assessment Form or ISM-SAS.

These data from part one were the basis for <unk> breakthrough therapy designation and non advanced testing.

Part two was designed to enable registration by demonstrating response rates superiority of <unk> versus placebo as assessed by total symptom score or TSS.

First as measured using the <unk> symptom assessment form for <unk> Fas.

Becker Hughes: This is a patient-reported symptom assessment tool that we developed in collaboration with the SM community and regulatory authorities over the last six years. We believe that a roughly 30% difference in the proportion of responders with AvaKit versus placebo would be a clinically meaningful result that would be supportive of both regulatory filings and drive real-world utilization in non-advanced testing. We've also heard consistently from health care providers and patients that any reduction in symptom burden, including the most burdensome symptoms, will be viewed as clinically meaningful and potentially transformative for patients. We'll also be looking at a range of additional outcome measures, including mass flow burden and other measures of quality of life.

This is a patient reported symptom assessment tool that we developed in collaboration with the OSM community and regulatory authorities over the last six years.

We believe that a roughly 30% difference in the proportion of responders with <unk> versus placebo would be a clinically meaningful result that would be supportive of both regulatory filings and drive real world utilization can manage Vance peso.

We've also heard consistently from health care providers and patients with any reduction in symptom burden, including the most burdensome symptom will be viewed as clinically meaningful and potentially transformative for patients.

We'll also be looking at a range of additional outcome measures, including mass cell burden and other measures of quality of life.

Becker Hughes: Across this constellation of outcomes, we expect to see consistent impact with AvaKit treatment. We remain on track to report top-line data in late summer 2022, and pending results, we plan to submit an SNDA to the FDA by the end of 2022. Now, let's shift gears to talk about the additional clinical data milestones that will drive significant growth for Blueprint. Over the next year, Blueprint will be defining and executing registration-enabling strategies across its pipeline of investigational medicines.

Across this constellation of outcomes, we expect to see consistent impact with Veeva.

We remain on track to report topline data in late summer of 2022 and pending results. We plan to submit an SMB to the FDA by the end of 2022.

Now, let's shift gears to talk about the additional clinical data milestones that will drive significant growth for blueprint.

Over the next year, we will be defining and executing registration, enabling strategies across our pipeline of investigational medicines.

Becker Hughes: In addition to the pioneer top-line data in late summer of this year, we plan to report multiple clinical proof-of-concept datasets across our EGFR and CDK2 programs into early next year, including combination data that will enable us to expand into earlier lines of treatment and increasing numbers of patients. By the end of this year, we expect to have early clinical data for BLEU 9.4.5 in combination with Ossimertinib and initial data for BLEU 7.01 in EGFR meat and long, In addition, we expect to have initial clinical data for BLU451 in the first half of 2023 in EGFR Exon 20 Mutant 1, We will continue to initiate combination cohorts and progressively earlier lines of treatment and look forward to seeing early data from some of those cohorts in 2020.

In addition to the time of your topline data in late summer of this year. We plan to report multiple clinical proof of concept data sets across our Egfr and CDK two programs into early next year, including combination data that will enable us to expand into earlier lines of treatment and increasing numbers of patients.

By the end of this year, we expect to have early clinical data for Blu 945 in combination with <unk> and initial data for Blu 701, and Egfr mutant lung cancer.

In addition, we expect to have initial clinical data for Blu 451 in the first half of 2023 in Egfr exon 20 mutant lung cancer.

We will continue to initiate combination cohorts and progressively earlier lines of treatment and look forward to seeing early data from some of those cohorts in 2023.

Becker Hughes: I'm equally pleased about the speed with which we're advancing towards clinical proof of concept for Blue 2-2-2 and CDK2-vulnerable cancer, with our first clinical data expected in the first half of 2020. Importantly, we plan to explore both monotherapy and combination dose escalation in part one of Vela and accelerate development across multiple populations. This includes previously treated estrogen receptor positive breast cancer patients, as well as frontline patients in combination with other agents, including CDK4-6 inhibitors and hormonal therapy. Also, in patients with CCNA1 amplified tumors, including subsets of ovarian and endometrial cancer, where we plan to explore biomarker-driven strategies with our CDK2 inhibitor alone and in combination with standard of care.

I am equally pleased about the speed with which we are advancing towards clinical proof of concept for <unk> and CDK to vulnerable cancers.

With our first clinical data expected in the first half of 2023 importantly, we plan to explore both monotherapy and combination dose escalation in part one available.

And to accelerate development across multiple populations.

This includes previously treated estrogen receptor positive breast cancer patients as well as frontline patients in combination with other agents, including CDK four six inhibitors and hormonal therapy.

Also in patients with cc anyone amplified tumors, including subsets of ovarian and endometrial cancer, where we plan to explore biomarker driven strategies with our CDK inhibitor alone and in combination with standard of care.

Becker Hughes: As a leading precision medicine biotechnology company, we continue to build on our successful and strong R&D engine by bringing additional transformative opportunities to patients with severe diseases, including our targeted protein degradation work currently underway. We look forward to sharing more about our vision at our planned R&D day in the second half of the year. With that, I'll turn the call over to Mike to review our financial results. Thanks, Becker. 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. Total revenues were $62.7 million for the quarter, including $23.8 million in net product sales of AvaKit and $38.9 million in collaboration revenues.

As a leading precision medicine biotechnology company, we continue to build on our successful and strong R&D engine by bringing additional transformative opportunities to patients with severe diseases, including our targeted protein degradation work currently underway.

We look forward to sharing more on our vision at our planned R&D day in the second half of the year.

Mike Landsittel: This represents approximately 164% growth in AvaKit product sales from the same period last year. As Christy noted, we saw solid growth in Advanced SM, which is and will continue to be our major driver of Advocate product revenue, given our strong momentum with the U.S. launch and recent approval in Europe. In addition, in the first quarter, we recognized a $30 million development milestone payment from Clementia related to BLU782, our outlicensed ALK2 inhibitor in development for the rare bone disease fibrodysplasia ossificans progressiva. Turning to expenses, our total costs in operating expenses for the first quarter were $168.5 million.

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

Thanks Becker.

Mike Landsittel: Including $23.4 million of non-cash, stock-based compensation expense. This reflects moderate planned growth in R&D expenses related to the initiation of four new clinical trials across our EGFR and CDK2 programs. These new clinical programs will drive the next wave of value inflection points for Blueprint and highlight our ability to sustain meaningful innovation through our best-in-class discovery platform. As Christy noted, we are reiterating our previous revenue guidance for 2022. This includes $180 million to $200 million in total revenues and $115 million to $130 million in APICOT net product.

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.

Total revenues were $62 7 million for the quarter, including $23 8 million and net product sales of <unk> and $38 9 million in collaboration revenue.

This represents approximately 164% growth in EBIT net product sales from the same period last year.

As Christie noted we saw solid growth in advanced SM, which is and will continue to be a major driver of aggregate product revenue.

Given our strong momentum with the U S launch and recent approval in Europe .

In addition in the first quarter, we recognized a $30 million development milestone payment from <unk> related to Blu 708 to our out licensed our <unk> inhibitor in development for the rare Brian bone disease fiber dysplasia, Oxford <unk> progress either.

Turning to expenses, our total costs and operating expenses for the first quarter were $168 $5 million, including $23 4 million of noncash stock based compensation expense.

This reflects moderate planned growth in R&D expenses related to the initiation of four new clinical trials across our Egfr and CDK to programs.

These new clinical programs will drive the next wave of value inflection points for blueprint and highlight our ability to sustain meaningful innovation for our best in class discovery platform.

As Christie noted we are reiterating our previous revenue guidance for 'twenty. Two for 2022. This includes $180 million to $200 million in total revenues and $115 million to a $130 million in EBIT and net product revenues.

Mike Landsittel: In addition to our diverse revenue drivers, we are in an exceptionally strong position with nearly $900 million in cash on our balance sheet, and we are now entering a period where we expect our revenue growth rate to exceed our expense growth, moderating our cash burn and setting the stage for us to become a self-sustaining company. Earlier in the call, Kate and Becker outlined the significant potential we are unlocking as we invest in a breadth of exciting pipeline and discovery plans over the next 12 to 18, which we anticipate will lead to continued modest growth in R&D.

In addition to our diverse revenue drivers we are in an exceptionally strong position nearly $900 million in cash on our balance sheet.

And we are now entering a period, where we expect our revenue growth rate to exceed our expense growth moderating their cash burn and setting the stage for us to become a self sustaining company.

Earlier in the call Kate and Becker outlined the significant potential.

Unlocking as we invest in a breadth of exciting pipeline of discovery plans over the next 12 to 18 months, which.

Which we anticipate will lead to continued modest growth in R&D expenses.

Mike Landsittel: Our strong cash position and disciplined approach to capital allocation will ensure that we are well positioned to execute on these opportunities while driving towards a sustainable profile. With that, I'll now turn the call back over to the operator for any questions.

Our strong cash position and disciplined approach to capital allocation, we will ensure that we are well positioned to execute on these opportunities while driving towards sustainable profile.

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

Operator: Thank you. If you would like to ask a question at this point, please press star followed by 1 on your telephone keypad. And the first question comes from the line of Marc Frahm from Cohen. Please, Marc, your line is now open.

Thank you if you would like to ask a question at this point. Please press the star followed by one on your telephone keypad.

On your first question comes from the line of Mark from from Cowen. Please Mark Your line is now open.

Marc Frahm: Thank you for taking my question, and congratulations on a strong quarter. Becker, I think you discussed Part 1 results that showed a 60% response rate on the 25-milligram arm, and I was wondering if you could remind us what the rate was at the higher doses, the 50 and 100-milligram doses, and also looking forward to the Part 2 results beyond the response rate. Are there any components of the TSS that you think are important commercially and will drive patient use? Hi Marc.

For Mark.

Thank you for taking my question and congratulations from Florida.

Thank you.

Victor Thank you.

<unk> results showed a 60% response rate on the.

75 milligram arm on I was wondering if you could remind us what was the rate was higher.

Higher doses of <unk>.

Milligram doses.

And also looking forward to the.

Part two results beyond response rate are there any other.

Are there any components of the PSS that you're seeing already.

Commercially we will drive patient use.

Sure.

Hi, Mark.

Becker Hughes: So, with respect to the Part 1 data, we saw consistent response rates across all three arms. You'll remember it was 10 patients per arm. And we saw both consistent rates and depth of response across all three doses. With respect to Part 2, remember that the TSS score is not a clinical tool; this is a clinical trial tool, so it's not something that providers will be using in the field. However, what it does is it breaks down the patient's experience into a number of different measures of potential improvement.

So with respect to the part one data we saw consistent response rates across all three arms you remember it was 10 patients per arm and we saw both consistent rates and depth of response across all three doses.

With respect to part to remember the TSS score is not a clinical tool. This is a clinical trials tool does not not something that.

Providers will be using in the field. However, what it does is it breaks down the patient experience into a number of different measures of potential improvement. So patients tend to have a number of different organ systems, where the disease manifests so really really a myriad of symptoms with often one that's more.

Becker Hughes: So patients tend to have a number of different organ systems where the disease manifests, so really, a myriad of symptoms, with often one that's most bothersome, but it's rarely just one symptom, particularly at this moderate to severe level.

Bob in some but it's rarely just one symptom, particularly with moderate to severe level and so I think that people will pay attention both to the overall score, but there'll be particularly interested depending on the types of patients that they're treating on specific domain you can imagine a patient who's got 20% to 30 episodes of diarrhea database being particularly.

Becker Hughes: And so I think that people will pay attention both to the overall score, but they'll be particularly interested, depending on the types of patients that they're treating, in specific areas. For example, you can imagine a patient who's got 20 to 30 episodes of diarrhea a day being particularly interested in those patients that have diarrhea and the improvement there. And then patients who have a more global manifestation, where they're just not able to get out of bed, go to work, or they're really worried about recurrent anaphylaxis, looking at the skin score and the fatigue and the ability to alter a number of different symptoms and decrease frequency of a number of different types of manifestations would speak to those providers and patients as well. Thank you, that's very helpful.

Interested in those patients that have diarrhea, and the improvement there and then patients who have a more global manifestation, where they're just not able to get out of bed to go to work or they're really worried about recurrent anaphylaxis looking.

Looking at the skin score and the fatigue and the ability to alter a number of different symptoms and decreased frequency of a number of different types of manifestations will speak to those providers and patients as well.

Christy Rossi: If I can, one more question for Christy, I think you mentioned the 20% market share for the new prescriptions. I was wondering what market share EvaKill has captured for the overall advances in market share? Sure.

Thank you that's very helpful.

One more question for Christie.

Can you you mentioned the.

7%.

Marketing for the new prescriptions I was wondering.

I appreciate it.

Q capture for the overall.

Advances in that market.

Sure.

Yes.

Christy Rossi: So, you know, as I said, we're really pleased to see AvaKit very quickly, you know, through this launch becoming the standard of care for treatment. And there are really two aspects to the kind of overall treatment rates that we look at. So one is market growth, right?

Sure so as.

As I said, we're really pleased with.

B very quickly through the slides, becoming the standard of care for treatment and it was really Q2 aspects to kind of overall treatment rates that we look at the one is <unk>.

Market growth rates. So this is a market where historically a lot of patients. Unfortunately have not received <unk> directed therapy for the launch of a Mccann is growing the market for by about 40% and then we're looking at of course, how many patients are actually being treated with <unk> as opposed to the other.

Christy Rossi: So this is a market where, unfortunately, a lot of patients, unfortunately, have not received SM-directed therapy. So the launch of AvaKit has grown the market by about 40%. And then we're looking, of course, how many patients are actually being treated with AvaKit as opposed to other therapies. And that's where we're seeing now 70% of all new initiations going on AvaKit. Our overall share is trailing that, you know, given where we are in the launch. And actually, you know, that's a good thing when your new start share is above your total share. It's a signal that, you know, you're growing up.

Our other therapies and that's where we're seeing now 70% of all new initiations I'm going on Ava cat <unk> trailing map.

Given where we are in the launch and actually.

That's a good thing when your new your new start share is above your total Sarah to signal that youre growing as bill are continuing to see Eva very rapidly I think we're kind of close to 50% of all patients now behind the curtain, we expect that that number to continue to grow with your progress of the launch.

Christy Rossi: And so we're continuing to see Ava very rapidly. I think we're kind of close to 50% of all patients now on AvaKit, and we expect that number to continue to grow as we progress with the launch.

Christy Rossi: Thank you. I appreciate that. And congratulations again.

Okay. Thank you I appreciate that and congratulations I guess.

Operator: Thank you. Our next question comes from the line of Dane Leone from Raymond James. Please, Dane, your line is now open.

Thank you. Our next question comes from the line of Dane Leone from Raymond James Please.

<unk> is now open.

Dane Leone: Hi, thank you for taking the questions and congratulations on all the progress made over the course of the quarter. Two for me, if I may, firstly, could you maybe provide a little bit more commentary about some questions then around, what you said about 18 months of treatment duration, could you maybe contextualize that, given that the drug hasn't been commercially launched for 18 months now, just kind of how you're doing that math and what you're seeing play out in the clinic? And then could you maybe comment on what you're seeing in the second quarter?

Alright, Thank you for taking my questions and congratulations on all the progress over the course of the quarter.

Two for me if I may.

Firstly could you maybe provide a little bit more commentary about some questions then around.

What you said around 18 months expected treatment duration.

Could you maybe contextualize that given that the drug hasnt been commercially launch for for 18 months now just kind of how youre doing that math and what youre seeing play out in the clinic.

<unk>.

And then could you maybe comment on.

What youre seeing in the second quarter I think everyone expected.

Dane Leone: I think everyone expected the launch in ASM to experience the normal issues that most drug companies have in the first quarter of the year. But any commentary on maybe how things are now progressing, you know, April to May on some of the key metrics that you talked about would be super helpful. And then finally, could you just maybe set expectations for the clinical updates for the back half of the year for 945701451?

The launch an ASM.

Experienced the normal issues that most drug companies out in the first quarter of the year, but.

But any commentary on maybe how things are now progressing April to May.

Some of the key metrics that you talked about would be Super helpful. And then finally could you just maybe level set expectations for the clinical update for the back half of the year for $95 700, 151, I think investors are always trying to figure out for these early data set because it's really an or our data set where we're going to establish something like an <unk> or are we going to be.

Dane Leone: I think investors are always trying to figure out in these early data sets, is this really an ORR data set where we're going to establish something like an RP2D? Or are we going to be looking more for the safety signals and emerging signs of clinical effect at the doses reported? Thank you. Thanks, Dane.

Looking more for the safety signals and emerging.

Lines of clinical exact doses reported thank you.

Christy Rossi: So, Christy, do you want to take the 18 months and talk a little bit about the quarter-over-quarter growth, and Becker, will you take the clinical updates and what to expect? Sure. So thanks for the question, Dane.

Okay. Thanks, Dana So Christie do you want to take the 18 months and talk a little bit about the you've had a quarter over quarter growth in Becker will you pick that.

Clinical updates and what to expect.

Christy Rossi: So duration is obviously one of the two key sort of, you know, drivers that we're watching very closely in terms of, you know, the trajectory of the overall launch. And, you know, the context here is that we know that AvaCat patients can have quite long treatment durations and advanced FM. In our clinical studies, we saw treatment durations of two plus years. And so our expectation is that over time, as we continue to find patients closer to a point of diagnosis, we'll continue to extend those treatment durations in a real-world setting. You're absolutely right. We have not been on the market for, you know, 18 months.

Sure.

So.

Thanks for the question Dan So duration is obviously one of the few key.

The drivers.

Drivers that we're watching very closely in terms of the trajectory of the overall launch.

And.

Is the context here is that we know that <unk> patients can have quite long treatment durations and adapt them and our clinical studies, we saw treatment durations of two plus years and so our expectation is that over time as we continue to find patients closer to a point of diagnosis.

We'll continue to extend those treatment durations that a railroad setting youre absolutely right. We have not been on the market for 18 months and so at this point, we are essentially looking occur and comparing sort of the <unk>.

Christy Rossi: And so at this point, we are, you know, essentially looking at curves and comparing sort of the curves that we see around duration of therapy in the real world to what we see in our clinical studies. And so we're estimating how we're trending in terms of the median duration of therapy. We'll continue to take a look at that over time. One positive note there is that we're even seeing that patients who have started more recently in the launch seem to be trending even more favorably.

<unk> that we see around duration of therapy in the real world to what we saw in our clinical studies and so we're estimating how were trending in terms of the median of duration of therapy. We will continue to take a look at that over time one positive.

Note. There is that we're even seeing that patients who have started more recently on the lines seem to be trending even more favorably and I think again that reinforces this expectation that we have around being able to impact patient who are not as sick as they move through that launch and see the durations extend.

Christy Rossi: And I think, again, that reinforces this expectation that we have around being able to impact patients who are not as sick as we move through the launch and see those durations extend. Regarding the quarter-over-quarter dynamics, you know, this is our first SM for Q1 that we've gone through, and we had an expectation that we would see many of the dynamics that, you know, certainly other oncology products and, more broadly, we see in pharma around Q1 in the U.S. where revenue can be impacted by factors around growth to net compliance, as well as some other factors.

Regarding the quarter over quarter dynamics, we certainly this is our first.

For Q1 that we've gone through and had an expectation that we would see many of the dynamics that you know.

Certainly other oncology products and more broadly we see it.

<unk> Q1 in the U S where revenue can be impacted by factors around crested at compliance as well as some other factors.

Christy Rossi: We were, you know, pleased to see really not a lot of impact through the quarter there. Certainly, we had some minimal impact on growth to net because of co-pays, et cetera. But some of the other factors that often impact the first quarter did not impact the advocate as much as we thought they might have.

We were pleased to see.

Not a lot of impact through the quarter. There certainly had some minimal impact on gross to net because of co pays et cetera.

Some of the other factors that often impacts the first quarter.

Christy Rossi: And I attribute, you know, some of our excellent patient support services and distribution programs to meeting that impact. So as we go into Q2, we continue to be really happy with the trends around new patient starts and treatment duration. And we expect really more steady growth as we go through the year in line with the overall revenue guidance that we get, and Becker is the one that takes the questions, yeah.

It did not impact the <unk> as much as we thought they may.

It should be.

Some of our excellent patient support services and distribution program to mute that impact so it would be.

We go into Q2.

We continue to be really happy with the trends around new patient starts and treatment duration and we expect really more steady growth as we go through the year in line with the overall revenue guidance that we gave.

In fact, our kinase and Bachelor and I'll take that question yeah.

Christy Rossi: Yeah, so then with respect to our EGFR Meat and Lung Cancer Program, just a reminder that what we're trying to do is make sure that we bring everyone along with us on this journey to understand our compounds better and the disease better. EGFR Meat and Lung Cancer has become a disease of combinations. As is often the case, as we get better and better at treating these tumors, these tumors find more mechanisms of resistance, and finding the right combination partners is really important.

Yes.

Then with respect to our Egfr mutant lung cancer program, just a reminder.

That what we are what we're trying to do is make sure that we bring everyone along with US on this journey to understand our compounds better and the disease better.

Egfr mutant lung cancer has become a disease of combinations as is often the case as we get better and better at treating these tumors. These tumors.

More more mechanisms of resistance and finding the right combination partners is really important.

Becker Hughes: 945 is our inhibitor that has a very high window to wild type, so we see it as a backbone for future treatment. It has activity not only in preclinical models where there's T790M, but also in the LR mutant population of cells, so we have presented at ACR initial data showing that this compound behaves exactly as we expected it would, with very little toxicity, really not even much of a hint of EGFR wild-type toxicity and a rapid reduction in the circulating tumor DNA alleles that it's supposed to be. It's designed to inhibit

<unk> five is our <unk> inhibitor that has a very high window to wild type. So we see it as a backbone for future treatment. It has activity not only in in preclinical models, where there is 279 yen, but also in the <unk> mutant.

Population of cells. So we have presented at ACR initial data showing that this compound behaves exactly as we expected it would with very little toxicity really not even much of a hint of Egfr wild type toxicity, and so rapid reductions in the.

Circulating tumor DNA allele that is designed to inhibit as we move into the next phase of this study we start combining with <unk>. This is a strategy to cover a more heterogeneous tumor population and and drive deeper remissions, we will be in the dose finding phase of this customer in a combination.

Becker Hughes: As we move into the next phase of this study, we will start combining it with Osimertinib. This is a strategy to target a more heterogeneous tumor population and drive deeper remissions. We will be in the dose finding phase of this Osimertinib combination over the next portion of the study, and similar to what we did at ACR, we expect to continue to update the community on both the combination and the single agent activity. With respect to 701, which is a brain penetrant inhibitor, this one has really high potency on the driver mutation, and then activity in the central nervous system; it is really class-defining with respect to penetration of the central nervous system.

The next portion of the study and similar to what we did at ACR or we expect to continue to update the community on both the combination and the single agent activity.

With respect to 701, which is our brain penetrant.

Inhibitor <unk> has really high potency on the driver mutation and then.

Activity in central nervous system. It really is class defining with respect to penetration of the central nervous system.

Becker Hughes: We are in escalation right now, and we, similar to the way that we presented data for 945, plan to bring people along and help you understand circulating tumor DNA and the early evidence of activity. And then we will have our strategy and early data as we combine in 2023, both with 945 and with Austin Merton and the NAP program. And then BLU451 is a more straightforward biology where the tumors are driven by a single driver mutation, the exon 20 mutation.

We are in escalation right now and we similar to the way that we presented data for 945 planned to bring people along and help you understand circulating tumor DNA in the early evidence of activity and then our strategy and early data as we combined in 2023.

Both with 945, and we've also Martin under that program.

And then maybe 451 is a more straightforward biology, where the tumors are driven by single driver mutation in exon 20 mutation.

Becker Hughes: We are in escalation now, and we expect to be in escalation for most of the rest of the year. But in that case, we might expect more straightforward evidence of response, as we've seen with some of the other EGFR20 inhibitors in the clinic. And so, as soon as we have a good body of data, that's what we'll be updating in that program. Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Please, Salveen, your line is now open. Hey, good morning, and thanks for taking our question. This is Elizabeth on behalf of Salveen.

We are an escalation now and we expect to be an escalation for for most of the rest of the year.

But in that case, we might expect a more straightforward.

Evidence of responses, we've seen with some of the other Egfr inhibitors.

<unk> inhibitors in the clinic and so as we have a good body of data that's what we'll be updating in that program.

Thank you. Our next question comes from the line of <unk> Richter from Goldman Sachs. Please <unk>. Your line is now open.

Elizabeth: Just maybe if you could provide some color on the sustainability of the growth drivers underpinning the AvaKit sales this year and then look forward. Thank you. Christina, do you want to take it off?

Hey, good morning, and thanks for taking our question. This is Elizabeth on for solving this maybe if you could provide some color on the sustainability of the growth the growth drivers underpinning the Ava kit sales. This year and then looking forward. Thank you.

Thank you and take care of those.

Christy Rossi: Yeah, thanks for the question. So, you know, as we shared, we're really looking at, at a very simple level, kind of two key drivers around the AvaKit launch, new patient starts and duration of therapy. And, you know, I think that both of those are trending in a way that really sets us up nicely for steady growth as we go through the year. On the new patient start front, as we mentioned, we continue to have a lot of headroom; many, a dense population of some patients, are not receiving any therapy for their disease.

Yes.

Thanks for the question. So as we shared we're really looking at it a very simple level kind of two key drivers around the <unk> launch.

New patient starts and duration of therapy, and I think that both of those.

Are trending in a way that really sets us up nicely for a steady growth as we go go through the year.

On the new patient start fan as he mentioned, we continue to have a lot of headroom.

Many advanced SM patients are not receiving a therapy for their disease and <unk> has very quickly grown to become the standard of care as new patients are initiating therapy and so we're continuing to focus on broadening our base of prescribers going out and identifying patients closer to diagnosis.

Christy Rossi: And AvaKit has very quickly grown to become the standard of care as new patients are initiating therapy. And so we're continuing to focus on broadening our base of prescribers, going out and identifying patients closer to diagnosis, and we continue to see a lot of room to grow. And then, as I mentioned, we're pleased to see the trends and duration that we're seeing already. I think we have some room to continue to improve there as we go through the year, but in general, for extended periods of time.

Then and continue to see a lot of room to grow.

And then as I mentioned, we're pleased to see that.

Trends in duration that we're seeing already.

We have some room to continue to improve there as they go through the year, but in general extended periods of time and as they move through the year that will help US also drive outgoing revenue growth. So we're reiterating.

Kate Haviland: And as we move through the year, that will help us also drive ongoing revenue growth. So, for reiterating, you know, these, The overall guidance, and we are looking to see, you know, more steady quarter on quarter growth as we go through the year. And just to add to that, one thought to that is that, you know, this, as Chrissy mentioned, you mentioned in her prepared remarks, I mean, SM has been a condition where physicians have been really in a wait and watch mode for quite a bit of time, right? They just haven't had directed therapies that have been, you know, very impactful to patients.

The overall guidance and are looking to see more steady quarter on quarter growth as we go through there.

Yeah.

And just to add one thought to that is that this is Christian.

You mentioned in your prepared remarks.

John has been a condition, where physicians have been really in a wait and watch for quite a bit of time, rather than just haven't had directed therapies that have been very impactful to patients and so I think the enthusiasm. We're also getting from from our dispositions that were talking to you about the clinical aspects.

Kate Haviland: And so I think the enthusiasm we're also getting from the physicians that we're talking to about the clinical aspects of AvaKit, their early experiences with AvaKit, have been really, you know, really promising. As you mentioned, you know, we at a near-type of upcoming medical conference, we plan to also present data based on some real-world evidence showing improved survival in patients who are receiving AvaKit relative to standard of care and other therapies, which I think is going to be incredibly compelling.

Their early experiences with advocate has been really.

Really promising and as Christian mentioned as well we are.

Near kind of upcoming medical conference, we plan to present data based on some real world evidence on showing improved survival in patients who are receiving indicate relative to standard of care and other therapies, which I think is it going to be incredibly compelling and so.

Kate Haviland: And so, you know, you add kind of the early experience plus this kind of additional data as we see the benefits of AvaKit, you know, really a life-extending type of therapy, I think will very much continue to catalyze physicians out of this wait and watch kind of attitude they've been in. Thank you. The next question comes from the line of Reni Benjamin. Thanks for taking the questions and congratulations on the quarter. Can we get a little bit more color on the European launch?

You add kind of the early experience plus just kind of additional data as we see the benefits that we have a cat.

Turning to real life extending type of therapy.

Very much connected to catalyze physicians out of just wait and watch.

Attitude they've been in previously.

Thank you. The next question comes from the line of Ren Benjamin.

Reni Benjamin: I guess in particular, you know, how that's going to build out over time? And should we be thinking about, you know, maybe a year from now, the revenues or the uptake, kind of mirroring what's happening here in the US? And then, just kind of related to that, I'm pretty intrigued by the U.S. claims data that you guys are showing. How much granularity do you have with that data, and do you know which sites, per se, might be, you know, having a lot of advanced FM patients so that once the launch takes place, you can actively target those sites? Thank you. Thanks, Reni, for the question. Chrissy, if you could take the question on the EU launch dynamics, and then Philina can answer the question about the claims data. Great.

Thanks for taking the questions and congrats on the quarter.

So it's a little bit more color on the European launch.

I guess in particular.

How that's going to build out over time and should we be thinking about.

Maybe a year from now.

Revenues or the uptake kind of mirroring what's happening here in the U S.

And then just kind of related to that.

Yes, I'm pretty intrigued by the U S claims data that you guys are showing how much granularity do you have with that.

And you know which sites per se might be having.

A lot of the amount of the foundation for that one.

The launch takes place you can you can.

<unk> target groups.

Thank you.

Thanks for any further questions Christy.

Could take the question on the EU launch dynamics and then Selina can answer the question about the claims data.

Christy Rossi: So we were really pleased to see the European approval come through several weeks ago, and, you know, as I mentioned on the call, we have already launched in Germany and see, you know, a lot of interest coming from German health care providers and patients right out of the gate, which is really encouraging. The overall dynamics in Europe, I think, will be very similar to the US.

Great.

So we were really pleased to see the European approval come through several weeks ago.

As I mentioned on the call have have already launched in Germany and see.

A lot of interest coming from German health care providers and patients all right out of the gate, which is which is really encouraging.

All dynamics in Europe , I think will be very similar to the U S. Certainly the epidemiology is similar and in fact I would argue that some of the European market and Germany is one of them.

Christy Rossi: Certainly, the epidemiology is similar. And, you know, in fact, I would argue that some European markets, and Germany is one of them, may be a bit more organized in their treatment of SM patients through the efforts of the European cooperative network around treatment of SM or ECNM. So we're excited to see this roll out. You know, we expect in terms of the cadence of the launch, Germany is obviously often the first market out of the gate in Europe, given the reimbursement dynamics, and because we already have a reimbursed price there, we expect Europe or Germany to really be kind of the primary driver in the immediate term.

It may be a bit more organized and their treatment of of SM patients through the Africa, the European cooperative that workarounds treatment <unk> our ECM.

We're excited to see this rollout we expect in terms of the cadence of the launch Germany is obviously often the first market out of the gate in Europe , given the reimbursement dynamics because they already have a reimbursed price there we expect to Europe , Germany to really be kind of as the primary driver in the immediate term we will have additional European markets.

Christy Rossi: We will have additional European markets coming online as we move through the year and then certainly into next year as we work through those reimbursement processes. But, generally speaking, I would expect kind of the overall cadence of the launch to not look very different and, you know, expect EvaKit to become the standard of care for treatment of advanced SM in Europe over time as well, and speaking to the U.S. plane. Absolutely, Christie.

Online as we move through the year and then certainly into next year as the rest of it is reimbursement processes, but.

Generally speaking, we would expect kind of the overall cadence of the launch to not look very different and expect <unk> to become the standard of care for treatment of advanced spend in Europe over time as well.

And speaking of the U S.

Okay.

Philina Lee: So, Reni, regarding U.S. claims data, we have visibility into a number of factors in our patients and provider claims. We can see that the majority, in fact, of these patients have non-advanced SM, and in fact, these patients, we think, are on the more moderate to severe spectrum of disease in terms of how they're engaging with the healthcare system. We have visibility into the fact that it's mostly medical oncologist and allergist immunologists who are the most involved in the diagnosis and overall management of these patients, with other specialties, such as dermatology and GI, more focused on the symptom management of these patients.

Absolutely Christy so reni.

Regarding the U S claims data, we have visibility into a number of factors in our patient and provider claims.

We can see that the majority in fact of these patients have not advanced SM and in fact these patients. We think are on the more moderate to severe spectrum of disease in terms of how they're engaging with the health care system.

We have visibility into the fact that it's mostly medical oncologists and allergists and Immunologists, who are the most involved in the diagnosis and overall management of these patients with other specialties, such as dermatology and Gi more focused on the symptom management of these patients and to your question.

We do have some visibility into who is treating and managing these patients and are very focused on efforts to raise disease awareness among these providers.

Perfect. Thanks for taking the questions.

Philina Lee: And to your question, we do have some visibility into who is treating and managing these patients and are very focused on efforts to raise disease awareness among these providers. Terrific, thanks for taking the question. Thank you. Our next question comes from the line of Brad Canino from Stifel. Please, Brad, your line is now open. Good morning, and congratulations on the quarter.

Thank you. Our next question comes from the line of Brett <unk> from Stifel. Please <unk>. Your line is now open.

Brad Canino: Now that we're closer to the ISM readout, can you outline the degree of data disclosure you expect to put in the top-line press release versus what data points you might save for a medical conference? And then, on the 945 plus OC combination, specifically where you're focused on the LR subgroup, what doses are you going to start at? And based on your 945 PK PD analysis, will those doses already provide predicted therapeutic coverage of all the potential compound and single EGFR mutation combination clones for those LR patients in the trial? Thank you. Thanks, Brad. This is Kate.

Good morning, and congrats on the quarter.

Now that we're closer to the Io. Some readout can you outline the degree of data disclosure you expected.

Top line press release versus what data points, you might save for a medical conference.

And then I wanted to ask on the $9 five OCI combination, specifically, where you're focused on the LR subgroup. What doses are you going to start out and based on your nine five PK PD analysis, where those doses already provide predicted therapeutic coverage of all the potential compound in single Egfr mutation combination.

Clones for those <unk> patients in the trial. Thank you.

Kate Haviland: I'll take the first and hand it over to Becker for the second part of your question. In terms of expectations and top-line data, this is going to be very similar to what we've done in the past with Gavreto and with AvaKid in the advanced setting and PTFR alpha-driven GIST. So we will plan to put out, you know, particularly the results on the primary endpoint, and a safety overview as the primary kind of anchors to that communication.

Thanks, Brad This is Kate I'll take the first one and hand over to Becker forgot the second part of your question.

In terms of expectations on top line data. This is going to be very similar to what we what we've done in the past with <unk> and the advanced setting in <unk> Alpha driven just so we will we will plan to put out, particularly the results on the primary endpoint of safety overview.

As the primary kind of anchors to that communication, we will save the majority of that data for you.

Kate Haviland: We will save the majority of that data for, you know, presentation at a medical meeting. So we will certainly talk about the overall results of the study and what are the critical pieces for, you know, pursuing FNDA. So that's what you can expect there.

Presentation at a medical meeting so so we will certainly talk about the overall results of the study and what is what are the critical pieces for.

Pursuing F&B. So that's what you can expect <unk> and Becker talk yes.

Becker Hughes: And then, Becker, do you want to talk about that? Yeah. So, Brad, with respect to the combination of Osimertinib and Blu945, we'll be starting Blu945 at 200 milligrams. This is a dose that begins to approach the LR coverage in the blood, but it's important to remember that we're really trying to get deeply into tumors in patients with very bulky disease in some cases. We have a number of different – and we'll start with full-dose Osimertinib.

So Brad with respect to the combination of <unk> and Blu 945 will be starting to 95 200 milligrams.

Is it does that begins to approach the LR coverage in the blood, but it's important to remember that we're really trying to get deeply into tumors in patients with very bulky disease in some cases.

We have a number of different and we'll start with full dose <unk>. We have a number of different combination doses to test during this escalation period to get the right balance between the two we don't expect there to be additional toxicity by adding benign because it doesn't hit the wild type egfr until very high doses, but nonetheless.

Becker Hughes: We have a number of different combination doses to test during this escalation period to get the right balance between the two. We don't expect there to be additional toxicity by adding Blu945 because it doesn't hit the wild-type EGFR until very high doses.

Operator: Thank you. Our next question comes from the line of Michael Schmidt from Guggenheim Securities. Please, Michael, your line is now open. Hi, good morning. This is Yigal for Michael.

Thank you. Our next question comes from the line of Michael Smith from Guggenheim Securities. Please Michael Your line is now open.

Hi, Good morning, this is eating out for them.

Michael Thanks for taking our questions one on the long term strategy for CDK to program, you've spoken about potential combinations with CDK <unk> inhibitors.

Yigal Nochomovitz: Thanks for taking our question, one on the long-term strategy for your CDK-2 program. You've spoken about potential combinations with CDK-4-6 inhibitors. How should we think about that combination from a safety perspective and in terms of sequencing therapy? And how would it be positioned relative to Pfizer's CDK-2-4-6 inhibitor in any read-through from their initial data in San Antonio? Thank you very much. Yeah, so, with respect to CDK2 inhibitors, particularly our CDK2 inhibitors, we don't expect overlapping toxicity. But certainly, we need to look at single-agent data before we know that for sure.

How should we think about that combination from a safety perspective and in terms of sequencing therapy.

And how would it be positioned relative to Pfizer CDK <unk> inhibitor and any read through from there should be that San Antonio. Thank you very much.

Yes.

So with respect to CDK too.

Inhibitors, particularly our CDK <unk> inhibitors, we don't expect overlapping toxicity, certainly we need to look at the single agent <unk>.

Data before we know that for sure.

Becker Hughes: But based on our preclinical data, we expect these to be complementary to CDK4-6 inhibitors. We looked at a number of different combinations with chemotherapy and CDK4-6 inhibitors. And so we look at Pfizer's data, and we're pleased by the fact that they're seeing activity. However, I think that it's been mentioned both by us and them multiple times that being able to control CDK2 versus 4-6 is going to be important to both manage potential toxicity and make sure that we are in different lines of therapy addressing either the initial driver or the resistance mechanism or both at the same time.

So but based on our preclinical data we expect these to be complementary to CDK <unk> inhibitors, we've looked at a number of different combinations with chemotherapy pre clinically.

<unk> six inhibitors and so we look at Pfizer's data and we're pleased by the fact that they are seeing activity. However, I think that as I mentioned, both by us and them multiple times, but being able to control CDK two versus four six is going to be important to both manage potential toxicity and made.

Sure that we are in the different lines of therapy addressing the either the initial driver or the resistance mechanism or both at the same time.

Becker Hughes: With respect to the Pfizer compounds, both their selective CDK2 inhibitor and the 2, 4, 6 inhibitor, we see this compound is highly competitive. It's a very selective CDK2 inhibitor, and we see it as having potential to combine with a number of different Cdk4, 6 inhibitors. Multiple lines of therapy in hormone-resistant breast cancer.

With respect to the Pfizer compounds.

Our selective <unk> inhibitor and the <unk>.

The 246 inhibitor, we see this compound is highly <unk>.

Competitive it's a very selective CDK <unk> inhibitor, and we see it as having potential to combine with a number of different CDK four six inhibitors.

Multiple lines of therapy in hormone resistant breast cancer.

Becker Hughes: That's helpful. Thank you. Thank you. Our next question comes from the line of Andrew Berens from SVB Securities. Please, Andrew, your line is now open.

That's helpful. Thank you.

Yes.

Thank you. Our next question comes from the line of Andrew Burns from a fee based securities. This Andrew Your line is now open.

Andrew Berens: Hi, thanks. Can you give some additional details on the development and plan for the combo of 945 plus to Grisso? Sounds like you're initially going to go after the L858R subgroup.

Hi, Thanks can you give some additional detail on the development plan for the combo of non core book to grow so it sounds like initially youre going to go out for the OE part of it also group has developed for seven months of <unk> point mutation to grips, though do you expect that could be an accelerated pathway and then.

Andrew Berens: We've developed the 797S point mutation to Grisso. Do you expect that to be an accelerated pathway? And then what are the plans to penetrate the first line?

What are the plans to penetrate the first one are you kind of the two drugs small molecule conoco.

Andrew Berens: Are you going to test the two-drug small molecule cocktail or the MET inhibitor, either a small molecule or a large molecule? So let me address those individually. So with respect to the combination, again, as I mentioned, the reason for the combination is twofold. One is to hit the driver mutation as hard as possible.

But are there a small molecule or large molecule.

So let me address those individually so with respect to the combination again as I mentioned.

The reason for the combination is twofold, one is to hit the driver mutation as hard as possible.

Becker Hughes: So the combination of either osomatinib or blue 701 plus blue 945 would be expected to do that, but also in the resistance setting to address heterogeneous tumors and in the frontline setting to prevent the emergence of resistance. Our goal in the front line setting is to really shut down the EGFR signaling pathway, and it's been shown multiple times in hematologic tumors that when you can do this, you get longer durations of response and, eventually, longer overall survival.

So the combination of either <unk> or Blu 701, plus 395 would be expected to do that but also too in the resistant setting to address heterogeneous tumors and in the frontline setting to prevent the emergence of resistance. Our goal in the frontline setting is to really shutdown the egfr signaling.

Pathway and it's been shown in multiple times in hematologic tumors that when you can do this you get longer durations of response and eventually longer overall survival.

Becker Hughes: With respect to pathways to approval in the relapsed refractory setting, even in second-line chemotherapy that's showing activity at this point, and so we do think that there are potential rapid pathways to approval, either for the single agents or in combination with standard of care that would then be followed up with randomized trials to confirm the clinical benefit of that combination. So we will look early in our study of 945 plus osimartinib for evidence of activity in the relapsed refractory setting... to show that we can achieve rapid, deep responses with that combination.

With respect to pathways to approval in the relapsed refractory setting.

Even in the second line chemotherapy, that's showing activity at this point and so we do think that there are potential rapid pathways to approval either for the single agents or a combination with standard of care.

That would then be followed up.

But with randomized trial to confirm that that clinical benefit of that combination. So we will look early in our.

Study of <unk>, plus <unk> four activity evidence of activity in the relapsed refractory setting line to show that we can achieve rapid deep responses with that combination.

Becker Hughes: With respect to MET inhibitors, MET is an important but certainly not overly dominant mechanism of resistance. I think that it is important. It's important to remember that some of these other non-EGFR-mediated mechanisms of resistance are really the drivers of early resistance, where patients that have been on ophthalmertin for a longer period of time will have higher rates of on-target or EGFR mutations driving the resistance.

With respect to met inhibitors, Matt is an important but certainly not overly dominant mechanism of resistance I think that.

It is important.

Important to remember that some of these other non egfr mediated mechanisms of resistance are really the drivers of early resistance, where patients that had been on <unk> for a longer period of time, we'll have higher rates have on charter or egfr mutations driving the resistance. So.

Becker Hughes: So we will, using 9-4-5, start to explore combinations with a number of these, or maybe in early relapse patients, it will be something that we'll be determining over the next year to 15 months. Okay, thank you very much. Our next question. Our next question comes from Mike Ulz from Morgan Stanley. Please, Mike, your line is now open.

We will using 95 start to explore combinations with <unk> or maybe in early relapse patients will be something that will be determining over the next year to 15 months.

Okay. Thank you for them our next question.

Our next question comes from the Mike <unk> from Morgan Stanley . Please Mike Your line is now open.

Mike Ulz: Good morning and thanks for taking the question. Maybe just to follow up on an earlier question related to the claims data and the diagnosis rate. It looks like you're still getting some nice traction there.

Good morning, and thanks for taking the question maybe just a follow up on an earlier question related to the claims data and the diagnosis rate it looks like you're still getting some nice traction there just curious Pete you ultimately expect the majority of SM patients to be diagnosed or.

For some reason.

So that could that number be lower and maybe it's because you're not capturing mild patients. For example, and then secondly, just can you remind us what the current diagnosis rates in Europe . Thanks.

Mike Ulz: Just curious, at peak, you ultimately expect the majority of SM patients to be diagnosed, or for some reason, could that number be lower, and maybe it's because you're not capturing mild patients, for example? And then, secondly, just can you remind us what the current diagnosis rate is? Christy, can you take that?

Christine can you take that.

Yeah.

Christy Rossi: Sure. So we are really excited to see kind of the ongoing growth in diagnosed patients. You know, I know many of you remember a couple of years ago when we started talking about non-advanced SM and sort of more detail. And at that point in time, maybe 10,000 patients were diagnosed in the U.S., and now we're close to half that number. So, you know, our expectation is that the majority of SM patients will be diagnosed as we approach the launch and then move through the launch with our ongoing efforts and our focus. And, you know, we're kind of close to that point now.

Sure. So we are really excited to see kind of the ongoing growth and diagnose patients I know many of you remember a couple of years ago. When we started talking about none of that is sort of more detail and at that point in time, maybe 10000 patients are diagnosed in the U S and now we're close to half so.

Vacation is that the majority of S&P options will be diagnosed as we approach. The answer then move through to the other launch there are ongoing efforts and our focus and we're kind of <unk>.

To that point now.

Christy Rossi: We also think that moderate to severe patients, because of their symptomatology, are on the margin more likely to find their way to a diagnosis versus patients who may be milder. So we will continue to really be making an effort against that. In Europe, you know, we are building that picture market by market.

So think that moderate to severe patients because of their symptomatology are on the margin more likely to find their way to a diagnosis versus patients who may be milder. So we will continue to vary be putting effort against that.

In Europe , we are building that picture market by market I can say that we were able to get.

Christy Rossi: I can say that, you know, we were able to get a look at sort of analogous claims data in Germany, and it painted a very similar picture to what we see in the U.S., which was really encouraging because I think it validates the idea that these patients are definitely out there, they're being diagnosed, and we're continuing to see that growth, you know, both through our efforts as well as, I think, just the efforts of And just to add one other element to that, too, for Chrissy, is that I think one of the things we've seen in other similar launches, whether that be at Jackify or others, is that, you know, we expect a very compelling risk-benefit profile coming out of the Pioneer study in the non-advanced setting.

Look at <unk> and now I guess claims like data in Germany and Canada.

And in a very similar picture to what we see in the U S.

Which was really encouraging because I think it is a validated the idea that these patients are definitely out there they're being diagnosed.

And we're continuing to see that that growth.

Through our efforts as well as I think just the efforts of the above.

<unk> community and the patients who are just so motivated to really seek seek diagnosis and treatment.

Yeah.

And just to add one element to that too. So quickly is that I think one of the things <unk> seen in other kind of similar launches whether that be of jakafi or others does that.

We expect a very compelling risk benefit profile coming out of the pioneer study and I'm not against that.

Christy Rossi: And as physicians start treating and get comfortable, we certainly see that less symptomatic patients start to be, you know, more included in those treatment paradigms. So I think, you know, upon the Pioneer study and our launch in the non-advanced setting, we would expect that patients with less symptomatology would start to be included again as physicians gain that experience. Thank you. Our next question comes from the line. First, on non-advanced FM, you indicated that 70% of new patients start where we're going to advocate.

As physicians start treating and get comfort, we certainly see that lesson JAK patient start to be more.

<unk> in the industry in that part of it. So I think upon the pioneer study and are launching and the non event setting we would expect that.

Patients with lesser dermatology would start to be included.

As physicians gain that experience and comfort.

Thank you. Our next question comes from the line first on non advance their firm you had indicated that 70% of new patient starts were going to either kit.

Christy Rossi: I guess, how can we look at the growth trajectory going forward as it seems that it's going to be shifting less, more from new patients to duration over the long haul. How does that affect the run rate?

How can we look at the growth curve.

Directory going forward as it sees that it's going to be shifting.

More from I guess, new patients to duration over the long haul how does it affect the run rate.

Yeah.

David Lebowitz: For Chrissy, I think David, I think you're saying that in the advanced setting, 70% of new patients start, but Chrissy, do you want to, do you want to answer the question? Yes. Right. So, as I said, there are really two kinds of factors to think about when we're thinking about kind of new patients starting in advance of them. So one is just the overall rates of treatment for this indication. And despite the fact that it is such a severe disease with, you know, a very limited life expectancy, we know that many patients have not been treated.

Sure Christy I think David I figured that.

The advanced setting that 70% of new patient starts, but Chris you're doing.

Yes, yes.

Christy Rossi: Providers have taken more of a watch and wait approach, I think largely because the available therapies simply haven't been, you know, very effective at treating the disease. So, the fact that we've seen 40% growth in the number of patients being treated, which is sort of the overall market since AvaKit launched, really speaks to that. But the majority of patients are still not being treated, and so there is a lot of room to continue to grow the overall size of the market.

Right. So so.

As I said it tends to be like Q2 kind of factors to think about with when they could give up kind of new patients starting in advance of that so one is just the overall rates of treatment in this indication and despite the fact that it is such a severe disease with <unk>.

Very limited life expectancy.

No that many patients have not been treated providers have taken more of a watch and wait approach I think largely because the available therapies simply haven't been.

Very effective.

Actually the disease so.

The fact that we've seen 40% growth and the number of patients being treated so just sort of the overall market. Since <unk> has launched I think really speak to that but.

But the majority of patients are still not being treated and so there is a lot of.

To continue to grow the overall size of the market and with Eva getting about 70% of those new starts I think we're very well positioned as the market continues to grow to continue to drive new patients back on either cat. So I continue to see both new starts as well as treatment duration to be very.

Christy Rossi: And with AvaKit getting about 70% of those new starts, I think we're very well positioned, if the market continues to grow, to continue to drive new patient starts on AvaKit. So I continue to see both new starts as well as treatment duration to be, you know, very important drivers for our ongoing growth. And in fact, in the near term, you know, I think new starts will probably be the more important of the two of them.

Important drivers for our ongoing growth and in fact in the near term I think new starts there'll be it will be probably the more part of the two of them and that we continue to see.

A lot of help there expanding prescriber base continuing theory of in the last few months since in Q1, and so I think we're well set up as it did this year after the steady growth that we expect.

Christy Rossi: And we continue to see a lot of health there, expanding the prescriber base, continuing through even the last few months of Q1. And then, you know, so I think we're well set up as we move through this year for the steady growth that we expect. Sure, thank you for that. And looking at the claims data regarding systemic mastocytosis as a whole, how are those numbers actually determined? What factors go into determining and differentiating one patient versus another, given that polypharmacy is a substantial issue, which could hamper such analysis? Many of the drugs often used are antihistamines, things that actually don't require prescriptions.

Sure. Thank you for that and we're looking at the claims data regarding <unk>.

Systemic mastocytosis as a whole.

Are those numbers actually determined.

Factors that goes into determining.

Differentiating one patient versus another given that polypharmacy is substantial issue, which which could hamper such analysis. Many of the drugs often use or anti histamines things that don't require prescriptions.

unknown: How do we break those numbers down? We know. Can you keep that?

How do you break those numbers down.

Philina Lee: Sure. So, thank you. Oh, sorry, you guys, we're coordinating remotely, but Philina, maybe you could take a stab, and Christy, please add color.

Can you keep that share.

Okay.

Oh, sorry, you guys were anywhere close to even remotely, but maybe if you could take a stab and Christy. Please I'd call. It I'm happy to start yes. So thanks for that question. So first off I would say we're fairly confident that these are indeed unique patients that we're looking at as we're able to follow their journey through initial diagnosis and their health care.

Philina Lee: I'm happy to start, yeah, so thanks for that question. So first off, I would say we're fairly confident that these are indeed unique patients that we're looking at, as we're able to follow their journey through initial diagnosis and their healthcare utilization, which includes things like the treatments that they may use as well as the different physician specialties that they're interacting with both for chronic care as well as sort of the features that we're able to see are both the initial diagnosis of SM as well as the I got it.

unknown: And the last question is, uh, the denominator of those, uh, the questions on the left is slide six, six patients on polypharmacy. Is that the claims data, or are there differences in the sample? Yeah, that's a great question.

Utilization.

And which includes things like the treatments that they need.

Use as well as the different physician to physician specialties that theyre interacting with.

Both of our chronic care as well as sort of the features that we're able to see our both the initial diagnosis of FM as well as the SM diagnosis code associated with all of these care interactions along that journey.

Got it.

And the last question is.

The denominator of those.

Questions on the left of slide six.

Patients on polypharmacy.

Is the claims data or are there differences in the sample.

Philina Lee: There are actually a number of different publications on this topic. And so some of these facts that we're showing on Slide 6 come from a touchstone survey that was done with both patients living with non-advanced SM as well as the allergy immunologists and hematology oncologists that are managing these patients, patient, and provider healthcare populations. Thank you very much for taking my question. Thank you. Our next question comes from the line of Eun Yang from Jefferies. Please, Eun, your line is now open.

Yes, that's a great question they are actually a number of different publications.

On this topic and so some of these facts that we're showing on.

On slide six.

From a touchstone survey that has been done with both patients living with non advanced FM as well as the allergist immunologist and hematology oncologists that are managing these patients patient and provider health care populations.

Yes.

Thank you very much for taking my questions.

Thank you. Our next question comes from the line of young from Jefferies. Please go.

He is now open.

Eun Yang: Thank you. I have a question on non-advanced SN. Previously, you mentioned about 70,000 patients in major global markets. And based on the Phase 2 entry criteria, what percent of patients do you think would be realistic candidates for AVAPretinib? And if you are targeting the majority of 70,000 patients, what do you think would be a reasonable price for rapid adoption? And the second question is, what percent of a target patient population in ISM would be treated with a hematologist versus an allergy specialist?

Thank you I have a question on non of advanced SM.

Previously you mentioned about 70000 patients in major global markets and based on Q2 criteria what percent of a patient do you think could be really.

Realistically tended to for <unk> printing it.

And if you are targeting majorities over 70000 patients but is included in the original pricing for.

Rapid adoption and the second question is what percent of a target patient population.

Sam.

Would it be treated with hematology is diversity.

Specialist thank you.

Yeah.

Eun Yang: So, Philina, again, we'll take some of the first part of that question, just around the addressable patient population, and then, Christy, if you could weigh in on the pricing, that would be great. Yeah, thanks for that question, Yoon.

So we again will take some of the first part of that question just around the addressable patient population and then Christi, if you could weigh in on the pricing that'd be great.

Philina Lee: So just to kick it off, as we look across multiple data points, the study suggests that 60% or more patients may ultimately be candidates for disease-modifying therapy. So we've talked about the vast majority of these patients receiving polypharmacy and, despite this, still reporting significant impacts on their quality of life. For example, we hear that up to 50% of patients are reporting potentially life-threatening anaphylaxis, and we've heard an example of a patient who keeps an EpiPen in every room of her house.

Yes. Thanks for that question, Yeah, So just to kick it off and as we look across multiple data points.

Just that 60% or more of patients may ultimately be candidates for disease modifying therapy. So we've talked about the vast majority of these patients receiving polypharmacy and despite this still reporting significant impact on their quality of life.

For example, we hear that up to 50% of patients are reporting potentially life threatening anaphylaxis.

And we've heard an example of a patient who keeps in epipen in every room of her house.

Philina Lee: As we speak to allergists and hematologists and oncologists, they also share with us that 60% to 80% of their patients are moderate to severe and really not well-controlled on symptom-directed therapies. Great. And Chris, do you want to weigh in on the pricing question from your perspective?

As we speak to an allergist and Hematologists oncologists. They also share with us that they see 60% approximately of their patients being moderate to severe and really not well controlled on symptom directed therapies.

Yeah.

Greg and Christa you wanted to do in a way and on the pricing question from you.

Yes.

Christy Rossi: Absolutely. So, you know, the context that Philina just shared about this disease is important when we think about pricing. So non-advanced SNARV is clearly a much bigger indication versus advanced. However, it is still very much a rare disease.

Absolutely. So you know the comps.

Separately as I stare at about the disease I think is important when we think about pricing and <unk> currently got much bigger indication versus advance. However, it is still very much a rare disease.

Christy Rossi: And it's a rare disease where patients are suffering from very severe morbidity, impact on ability to work, quality of life along the lines of cancer patients, etc. You know, as we've engaged with payers, they very much understand that context. And, you know, in fact, through our experience with the launch of ADVOCATE so far, we've had really no barriers to access from a payer perspective, a very rapid time to fill, and we've seen some reimbursements, in fact, in the non-advanced setting as well.

And it's a rare disease, where patients are suffering from a very severe morbidity impact on ability to work quality of life, along the lives of cancer patients et cetera.

As we've engaged with payers they very much understand that context and in fact through our experience with the launch of David hit So far we've had really no barriers to access from a payer perspective, I'm very rapid time to fill and we've seen some reimbursements and factor in the amount of that setting as well.

Christy Rossi: And so, you know, our expectation is to go forward. ADVOCATE, you know, we're on the market for price, certainly in the U.S. at all doses, and would expect to be able to continue to ensure patient access as we go forward into the non-advanced launch. And so I don't really see price as being kind of a major driver of that launch.

And so.

Our expectation as we go forward the indicate.

We're on the market and price certainly in the U S at all doses.

And I would expect.

To be able to continue to ensure patient access as we go forward into the non against launches. So I don't I don't really see prices being kind of a major driver of that law and so I think it's going to be much more about our continued engagement with health care providers and patients.

Christy Rossi: I think it's going to be much more about our continued engagement with healthcare providers and patients, education around, you know, patient identification and testing, and, of course, the very positive benefit-risk profile that we're expecting to see from ADVOCATE and this syndication, particularly at the doses for non-advanced SM based on the data that we've seen so far from Pioneer in Part 1, and Becker Yelts Other population?

Education around patient identification.

<unk> testing and of course, the very positive benefit risk profile that we're expecting to see from from advocate and Thats indication, particularly at the doses were not adapted them based on the data that we've seen so far from my side.

In part one.

Thank you Alan.

Becker Hughes: Thank you. Sure. Go ahead. Go ahead. I'm sorry, Eun. What was it? Oh, yeah.

Yeah.

As the population okay.

Go ahead go ahead I'm sorry.

Eun Yang: Oh, I'm sorry. I missed the last part. I apologize, hematologist versus allergist. Yes.

Oh I see.

Nonetheless, I apologize yes.

Christy Rossi: So what we see is that non-advanced patients generally are, you know, managed by allergy; primarily, hematology is often involved in co-managing these patients. And so we expect that, you know, our efforts will be primarily focused on allergies, as well as on the hematology call points that were already focused on for the advanced. Can I ask you one more question about that then? Do you have to, would you need to add sales reps to target allergy specialists?

Hematologists versus allergist, yes.

So what we see is that non advanced patients generally are met.

Managed by allergy, primarily hematology is often involved in co managing these patients and so we expect that our efforts will be primarily focused in an allergy.

As well as in the hematology compounds that were already focused on floor for the advanced patients.

Well can I ask you one more question to that then do you have to would you needed to add sales reps to target allergy specialist.

Okay.

Christy Rossi: So our expectation is that we may, okay, go ahead, go ahead, Christie. Our expectation is that we may modify our commercial footprint as we go forward towards that non-advanced approval to make sure that we are really adequately directing resources into the allergy space, but we don't expect those changes to be significant.

So, yes, I already expectation of that we made.

Go ahead. Please go ahead, Greg go ahead Christie.

Yes.

Our expectation is that we may modify our commercial footprint as we go forward towards that not advanced approval to make sure that we are really adequately directing resources into the allergy space.

But we don't expect those changes to be significant thats at the very tractable call points for a specialty commercial organization and kind of the context of a biotech company and we are already quite adapted snowfall at utilizing some of the claims data that we've already been talking about to make sure that we're directing our efforts in a very efficient way.

Christy Rossi: This is a very tractable call point for a specialty commercial organization in the context of a biotech company. We are already quite adept and skillful at utilizing some of the claims data that we've already been talking about to make sure that we're directing our efforts in a really efficient way. Thank you very much. Thank you. This is Becker.

Thank you very much.

Becker Hughes: I just wanted to make a point about the first part of your question. I think we need to think of these patients as having a chronic disease that progresses over time. The story that we've heard from patients has been that they start out, may start out with mild symptoms, but that they tend to get worse and worse over time and become more and more debilitating.

Jake This is better I just wanted to make a point about the first part of your question.

I think we need to think of these patients as having a a chronic disease that does progress over time.

The story that we've heard from patients has been that they start out and they started out with mild symptoms, but they tend to get worse and worse over time and become more and more debilitating.

Becker Hughes: To date, we haven't had an option for these patients, so I think that what we're going to see is providers looking to understand the depth of the disease sometimes by trying the treatment that we know wipes out the clone that causes the disease. And also start to work with the community to understand the value of preventing the progression of this disease, even in the non-advanced setting. So I wouldn't think of patients as showing up at a certain level of severity and simply staying there for good.

We haven't had an option for these patients so I think that.

What we're going to see is providers looking to understand the depth of the disease, sometimes by trying the treatment that we know wipes out the clone that causes the disease and also starting to work with the community to understand the value of preventing the progression of this disease, even in the non event setting so.

I wouldn't think of patients is showing up.

There's a certain level of severity and simply staying there for good.

Operator: Thank you. At this time, we have run out of time for further questions, so I will turn the call over to Katie Haviland for any final remarks. Thank you, Operator. Our strong performance in Q1 sets the foundation for us to achieve the priorities we've laid out as a company this year. AvaKit, as we just talked about, is off to a very strong start in its first full year of launch, with the opportunity to expand to the non-advanced SM right around the corner.

Thank you at this time, we have run out of time for further questions. So I will turn the call back to Katie have land for any final remarks.

Thank you operator, our strong performance in Q1 sets the foundation for us to achieve the priorities we laid out at the company this year.

Advocate as we just talked about is off to a very strong start in its first full year of launch with the opportunity to expand into non advanced SM right around the corner.

Operator: We are also maintaining our growth momentum with the execution of our pipeline through key data milestones this year and next. We look forward to talking with all of you about this continued progress very soon. So, thank you for taking the time to join us today, and thank you for your continued support of Blueprint Medicines. This concludes today's conference call. Thank you so much for joining us. You may now disconnect your lines. [music]

We are also maintaining our growth momentum with the execution of our pipeline to key data milestones. This year and next we look forward to talking with all of you I'm. Just continued progress very soon so thank you for taking the time to join US join US today and thank you for your continued support of blueprint medicines.

This concludes today's conference call. Thank you so much for joining domain now disconnect your lines.

Okay.

Sure.

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Okay.

Yes.

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Yes.

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