Q2 2022 Blueprint Medicines Corp Earnings Call

Thank you.

[music].

Yes.

Good morning, my name is Charlie and I'll be your conference operator today.

Good morning, My name is Charlene I'll be conference operator today at this time I'd like to welcome everyone to the blueprint medicines second quarter 2020 financial results Conference call.

At this time, I'd like to welcome everyone to the Blueprint Medicines second quarter 2022 financial results conference call.

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All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there'll be a question and answer session. If you'd like to ask a question. During this time.

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Please plan to limit yourself to one question.

Thank you.

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

This morning, we issued a press release, which outlines the topics we plan to discuss today you can access the press release as well as the slides that we'll be reviewing today by going to the investors section of our website at Www Dot blueprint medicines dotcom joined.

Joining me on today's call are Kate Haviland, our Chief Executive Officer, who will discuss our successes in the second quarter and a look ahead to the second half of the year Selena Lee our Chief commercial officer, who will provide a commercial update becker.

Becker Hughes, Chief Medical Officer, who will provide a clinical update Christy.

Christy Rossi Chief operating Officer, who will review, our 2022 milestone progress in upcoming catalysts and Mike lands at all our Chief Financial Officer, who will review, our second quarter 2022 financial results.

Jenna Cohen, you may begin your conference.

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 our SEC filed.

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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, except as required by law, we specifically disclaim any obligation to update or revise any forward looking statements I'll now turn the call over to Kate Kate.

Thank you, Charlie.

Good morning, everyone, and welcome to Blueprint Medicine second quarter 2022 financial and operating results conference call.

Thanks, Gina and good morning, everyone. Thank you for joining the call today.

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 investor section of our website at www.blueprintmedicines.com.

At Blueprint, we continued to build one of the worlds, leading precision therapy companies with a diversity of growth drivers across all stages of our business.

Including two globally commercialized revenue generating medicines.

Joining me on today's call are Kate Haviland, our chief executive officer, who will discuss our successes in the second quarter and a look ahead to the second half of the year.

Multiple important clinical development programs across a range of prevalent and hard to treat cancers.

Our prolific early discovery engine and a strong cash position.

Felina Lee, our chief commercial officer, who will provide a commercial update.

Blueprint had a strong quarter with $36 5 million in total revenues, including $28 5 million in Ava kit net product revenues.

Becker Hughes, chief medical officer, who will provide a clinical update.

The 20% Eva kit quarter over quarter revenue growth underscores the strength of our ongoing commercial launch as we continue to solidify Ava kit as the standard of care for the treatment of advanced systemic mastocytosis.

Christy Rossi, chief operating officer, who will review our 2022 milestone progress and upcoming catalysts.

Our launch in advanced SM has demonstrated broad prescriber receptivity to advocates clinical profile.

Strong launch execution that has facilitated access and limited payer hurdles.

And an elevated patient awareness, leading to increase diagnosis and treatment rates.

It has also continued to improve our understanding of the non advanced at that market.

And a significant opportunity Ava kit has to meet the medical needs of these patients as we look toward registration, enabling pioneer part two topline data readout later this month.

Yeah.

We ended the quarter with the announcement of a transformative 1.25 billion non dilutive financing that ensures we have the resources and operational flexibility to dry blueprints long term growth, while maintaining our path to financial independence.

This financing enables acceleration of our broad pipeline and an ability to continue to explore opportunities for synergistic and strategic business development.

Business development has played a key role in blueprints value creation and long term portfolio growth and has allowed us to fully realize the value of our prolific discovery platform.

Today, we are happy to announce that we have out licensed our internally discovered kit exon 13 inhibitor to I D. Rx a newly launched clinical stage company.

Kristina will provide an overview of the transaction later during the call.

And finally, we plan to provide additional insights into our breadth of growth drivers at our Investor day, which will take place on November 1st of this year in New York City.

We look forward to sharing our strategic vision for blueprint with our near term focus on the important growth opportunity and S. M S.

As well as outlining how we are driving midterm value through to our Egfr mutant and CDK to vulnerable cancer development programs.

And how we're creating long term value through our research innovation and vision.

The depth and breadth of what we will cover at the Investor Day demonstrates our unique company profile and a strong position we have to continue to deliver significant value to patients and all of our other stakeholders.

And Mike Lansedal, our chief financial officer, who will review our second quarter 2022 financial results.

With that let me turn the call over to Selina to discuss our commercial updates cleanup.

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

Thank you Kate and good morning, everyone.

Reflecting on our first full year of launch with Eva Kit I am most proud of the strong commercial execution. Our team has demonstrated as we deliver for patients living with advanced S. M.

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.

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.

Except as required by law, we specifically disclaim any obligation to update or revise any forward-looking statements.

I'll now turn the call over to Kate.

We have established Ava kit as the standard of care in advanced SM secured a strong and growing prescriber base and enabled broad patient access with virtually no payer challenges.

We have driven four straight quarters of double digit revenue growth.

Kate?

In the second quarter, we continued to build on Ava kits launched momentum generating net product revenue of $28 $5 million.

Thanks, Jenna, and good morning, everyone.

Including $24.7 million in the U S.

And $3 $8 million ex U S.

Our launch in Germany is off to a strong start with early adoption mastocytosis centres of excellence as well as in the community setting.

We're in the midst of country specific reimbursement submissions in other key markets and anticipate launching in several more countries by the end of the year.

Turning to the U S.

Eva Kit is now the standard of care in patients being treated for their advanced SM with greater than 50% market share.

It's the treatment of choice for more than 70% of patients who are starting on or switching to a new therapy.

We expect both of these measures to continue growing.

We've now seen Eva kit prescriptions from nearly 300 accounts since the launch in advanced SM.

Our team activated 46 first time accounts in the second quarter, and we continue to drive breadth in the community setting and depth in the academic setting.

Yeah.

Duration of therapy continues to trend favorably at about 18 months overall, and we expect many patients to benefit from Eva kit for even longer periods of time.

The greatest opportunity, we see to drive continued growth is to increase the proportion of patients who are being treated for their advanced SM, particularly S. M. H N. The most common subtype.

Patients with S. M. H N have a poor prognosis with a median overall survival of around two years.

At <unk>, we presented a retrospective study comparing overall survival for Ava kit versus best available therapies.

Within S M. H N patients Ava kit demonstrated a median overall survival of 46.9 months versus 18.0 months for best available therapies.

These data should further catalyze the urgency to treat these patients.

Advanced Us EM represents just 5% to 10% of all S M and with our strong launch momentum we're only just getting started.

We see tremendous potential for Ava kit to benefit many more patients as we set our sights on the non advanced S M opportunity.

Non advanced SM leads to debilitating and potentially life, threatening symptoms, including uncontrolled anaphylaxis extreme fatigue, diarrhea skin lesions and brain fog.

Patients and caregivers undertake a significant burden to manage the disease, avoiding everyday triggers and coordinating complex therapy regimens that in most cases failed to control the disease.

There are no approved therapies today.

Our goal is to transform the lives of patients living with this debilitating disease.

Here's why we're excited about the opportunity.

First the number of diagnosed S. M patients is steadily growing.

We can see over 16000 unique diagnosed S M patients in U S claims data and most of these patients have not advanced SM.

This represents a remarkable 63% growth of the diagnosed patients in the U S. Since the initial launch of Eva Kit in January 2020.

Second.

Approximately 60% of non advanced SM patients in these claims take complex regimens of prescription medications.

Ticketing of moderate to severe disease burden.

These patients he was a cocktail of symptom directed therapies, including Epipen mast cell stabilizers, Teekay eyes, and cider reductive therapies.

These complex regimens of off label Polypharmacy highlight the serious medical needs these patients face.

Altogether the claims data combined with a breadth of patient and provider research indicates an addressable market opportunity of approximately 7500, not advanced SM patients with moderate to severe disease today, who may be candidates for Ava kit.

This represents a significant patient population, who have and will continue to actively seek treatment for their non advanced SM.

With a pricing strategy similar to rare disease analogues, such as hereditary angioedema.

We believe non advanced S. M may represent a multibillion dollar opportunity for Ava kit.

We expect the launch trajectory will follow other similar disease rare disease market.

We continue to advance our market development efforts working with the S M patient and provider community to accelerate the time to diagnosis and initiation of treatment.

We anticipate this will continue to increase the number of diagnosed patients towards the 32000 prevalent S M patients living in the U S.

On a personal note as I reach my eight fear at blueprint medicines, the non advanced SM opportunity has never felt so tangible.

We look forward to sharing more about this and how we will capture this opportunity at our Investor day in November .

With that I'll turn the call over to Becker to review our expectations for pioneer part two topline data.

Thank you Paulino and good morning, everybody.

Thank you for joining the call today.

As you know we plan to share topline results from our pivotal study of Eva Kit did.

At Blueprint, we continue to build one of the world's leading precision therapy companies with a diversity of growth drivers across all stages of our business, including two globally commercialized revenue-generating medicines, multiple important clinical development programs across a range of prevalent and hard-to-treat cancers, a prolific early discovery engine, and a strong cash position.

Non advanced SM later this month.

The first registration directed study in non advanced systemic mastocytosis.

In the year is on track to provide a wealth of data.

And confirm Ava kit potential to transform treatment of this more prevalent form of S. M.

In June we shared that the FDA requested we elevate mean changed in total symptom score or TSS, which was previously a key secondary endpoint to become the primary endpoint.

As we've seen with recent approvals from other medicines. This approach is increasingly becoming the FDA standard for randomized trials designed to assess patient reported outcomes because it considers the full range of benefit seen in each farm.

Let's review our primary endpoint the comparison of mean TSS reduction in each arm.

And a key secondary endpoint the proportion of patients who experienced a response defined as a 30% reduction in P. S F score.

These endpoints are correlated.

Illustrated by the part one data.

Our primary endpoint. The comparison of group means is a measure of how the population treated with Ava kit felt compared to those treated only with placebo plus best supportive care.

We'll refer to the control arm as placebo controlled for simplicity.

As was the case in pioneer part one patients in both arms continued to receive best supportive care before and during the study.

And pioneer part one we observed a 16.5 point difference between the two groups, which was correlated with 60% of David kit treated patients experiencing a response something placebo was not able to achieve for any patient.

While this response striking we've received consistent feedback from practitioners that if at least one third of patients treated with either kit responded this would be highly important and practice changing.

Furthermore, both responders and those with less than a 30% reduction in total symptom score often experienced profound improvement in their most severe symptoms such as extensive rashes persistent diarrhea and brain fog.

Symptoms that make normal life, all but impossible.

These reductions in most severe symptoms can often be life changing for patients.

We are confident that pioneer part too.

Which is powered to measure a minimum difference of seven to 10 points between TSS reduction.

Half the difference observed in part one will provide robust practice changing results in all of these correlated measures of clinical benefit.

In addition to the primary and key secondary endpoint and similar to our prior topline data readout, We will report top line safety data.

This will serve as the foundation for global regulatory submissions.

It includes comparative safety from pioneer part two the first large placebo controlled safety dataset for Ava kit in systemic mastocytosis debate.

I'm extremely enthusiastic about the promise Ava kit provides for thousands of patients who have been suffering from non advanced SM for many years.

Now I'll turn the call over to Christie to review upcoming data milestones and catalysts.

Thanks Becker good morning, everyone.

We've made significant progress against our corporate goals in the first two quarters of 2022 and we are looking ahead to our breadth of value driving data catalysts plans for the second half of this year.

Within our S. M program, we plan to report pioneer apart to topline data later this month as Becker shared.

And initial clinical and safety data from the Harbor trial of Blu 263, and non advanced us them by the end of this year.

We are also making rapid progress across our programs and Egfr driven lung cancer, where we are working to generate datasets that inform further development and accelerate our path towards registration.

At ACR in April we presented early dose escalation and biomarker data for Blu 945 at once daily doses up to 200 milligrams.

These data show Tolerability and initial proof of concept consistent with Blu nine four fives preclinical profile.

Based on these data we initiated development of Blu 945 in combination with Aston Martin Ed in the second quarter.

We plan to report initial dose escalation data for the combination in the second half of the year with a focus on providing evidence that Blu 945, and <unk> can be combined safely.

As well as translational data highlighting the combinations broad coverage of primary and secondary Egfr mutation and early signs of clinical activity.

We also expect to report a recommended phase two dose for single agent Blu 945 by the end of this year.

More broadly and consistent with our prior guidance, we expect initial clinical data for Blu 701, and the second half of 2022 and for Blue for a five one in the first half of 2023.

Finally, we remain incredibly excited about Blu 222 or CK two program.

And its potential to impact many patients suffering from highly prevalent cancers.

And look forward to presenting initial clinical data in the first half of 2020 three.

As Kate previewed earlier, we are proud to announce that we have out licensed our internally discovered kit exon 13 inhibitor to I D. Rx to advance the program into the clinic a.

Evaluating it in combinations for patients with gist.

This represents our first development candidate F 2022.

And because we believe an idea or X is focused on the combinability of precision therapies.

We received a 15% series a preferred equity stake in exchange for our license grants.

We are also eligible to receive up to $217 million and potential regulatory and sales based milestones as.

As well as tiered royalties on net sales.

This transaction is another example of our commitment to ensuring that valuable scientific and medical innovation reaches patients regardless of the shifts in our portfolio priorities.

I'll now I'll turn the call over to Mike to review our financial updates.

Thanks Christy.

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 $36 $5 million for the quarter <unk>.

Blueprint had a strong quarter with $36.5 million in total revenues, including $28.5 million in AvaKit net product revenues.

Including $28 $5 million in net product revenues from sales of Eva kit and $8 million in collaboration revenues.

The 20% AvaKit quarter-over-quarter revenue growth underscores the strength of our ongoing commercial launch as we continue to solidify AvaKit as the standard of care for the treatment of advanced systemic mesocytosis.

Our launch in Advanced SM has demonstrated broad prescriber receptivity to AvaKit's clinical profile, strong launch execution that has facilitated access and limited payer hurdles, and an elevated patient awareness leading to increased diagnosis and treatment rates.

It has also continued to improve our understanding of the non-advanced SM model.

We are reiterating our previous revenue guidance for 2022 2022 of 180 million to $200 million in total revenues and $115 million to a $130 million and either kit net product revenues, putting us well on track to realizing the blockbuster potential for Africa.

Our R&D expenses for the second quarter were $128 $3 million, including approximately $10 million of noncash stock based compensation expense, reflecting planned growth in R&D expense related to the strong execution of our clinical trials.

Compared to the first quarter of this year R&D cost increased by approximately $25 million driven by accelerated timing of expenses related to the startup and supply activities are for new clinical trials across our Egfr and C. D K two programs.

Additionally, we saw increases driven by timing of certain early research activities.

These investments in new 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.

SG&A expenses for the second quarter were $58 $7 million, including approximately $15 million of noncash stock based compensation expense and were flat compared to Q1 of this year.

Looking forward, we expect that overall expenses will be flat or slightly lower in the second half of the year as we drive towards key data readouts.

We ended the quarter with the announcement of a transformative $1.25 billion non-dilutive, financing that ensures we have the resources and operational flexibility to drive Blueprint's long-term growth while maintaining our path to financial independence. This financing enables acceleration of our broad pipeline and an ability to continue to explore opportunities for synergistic and strategic business development.

Business development has played a key role in Blueprint's value creation and long-term portfolio growth and has allowed us to fully realize the value of our prolific discovery platform.

Finally, our June 30th announcement of a strategic non dilutive financing agreement with sixth Street and royalty pharma puts blueprint medicines in a strong financial position to drive rapid growth, while ensuring our path to profitability in the coming years.

Today, we are happy to announce that we have outlicensed our internally discovered kit Exxon-13 inhibitor to IDRX, a newly launched clinical stage company.

As of June 30th we had $947 million in cash on our balance sheet.

This balance includes $175 million upfront payment received under the royalty pharma agreement.

In addition in July we received an additional $400 million in gross proceeds related to our agreement with sixth Street, which will be recorded in our financial statements in the third quarter.

This quarter was marked by execution excellence across our commercial clinical and research organizations.

Christy will provide an overview of the transaction later during the call.

And finally, we plan to provide additional insights into our breadth of growth drivers at our investor day, which will take place on November 1st of this year in New York City.

We look forward to sharing our strategic vision for Blueprint with our near-term, focus on the important growth opportunity in SM, as well as outlining how we are driving mid-term value through our EGFR mutant and CDK2 vulnerable cancer development programs, and how we're creating long-term value through our research innovation and vision.

We continue to allocate resources towards R&D and core programs that are rapidly advancing towards value driving milestones.

The combination of our strong cash position with well over $1 billion on the balance sheet as of today mulch.

Multiple drivers of top line revenue and diversity are important pipeline programs uniquely positions us to continue building, a leading precision therapy company, bringing transformative medicines to patients worldwide and delivering value to our shareholders I'll now turn the call over to the operator for questions operator.

The depths and breadth of what we will cover at the investor day demonstrates our unique company profile and the strong position we have to continue to deliver significant value to patients and all of our other stakeholders.

With that, let me turn the call over to Felina to discuss our commercial updates.

Felina?

Thank you, Kate.

And good morning, everyone.

Thank you.

At this time with lots of remind everyone in order to ask a question. Please press star followed by one on your telephone Keypad Star followed by one on your telephone keypad now.

Reflecting on our first full year of launch, with AvaKit, I am most proud of the strong commercial execution our team has demonstrated as we deliver for patients living with advanced SM. We have established AvaKit as the standard of care in advanced SM, secured a strong and growing prescriber base, and enabled broad patient access with virtually no payer challenges. We have driven four straight quarters of double-digit revenue growth.

Our first question comes from Mark from Cowen and company. Your line is now open.

In the second quarter, we continued to build on AvaKit's launch momentum, generating net product revenue of $28.5 million, including $24.7 million in the U.S. and $3.8 million ex-U.S. Our launch in Germany is off to a strong start with early adoption at mastocytosis centers of excellence, as well as in the community setting.

We're in the midst of country-specific reimbursement submissions in other key markets and anticipate launching in several more countries by the end of the year.

Thank you for taking my question.

He goes for Mark.

On a great quarter or.

Two questions if I may Becker.

You mentioned reporting unit.

<unk> results for pioneer.

And I was wondering.

If you could tell us what level of grabbing a lot of good Ravi to you should we expect for the safety portion of why would you see us at an acceptable number of intracranial hemorrhage or a placebo adjusted neurocognitive.

We talked about at what level do you think this could significantly affect the adoption on a second question. If I may a four to six three.

What should we expect for the initial data disclosure at what level do you feel then how should we think.

How about the theater when comparing it to two probably over here. Thank.

Thank you.

Yeah. Thanks, Andy So Becker I think maybe you can start up with both and then if because here's what I want to add to the two 6 million common that'd be great.

Yeah. So for the topline data, we plan to present adverse events and serious adverse events comparing the two arms as we typically do with topline data when we first see the readout of these trials with respect to expected rates of.

Adverse events I hesitate to speculate on what we would see in the trial I think it's important to remember, though that these are patients receiving standard of care medications some of which have adverse.

Hence that overlap with the disease or even some that might overlap with some of the Ava kit adverse events. However, we're at 25 milligrams in part one we saw an extraordinarily good safety profile with very low rates of even grade one adverse events and really no grade three adverse events and we would expect the safety profile.

File in a part two to be very similar to what we saw in part one.

And then with respect to 263, we have part one of our study ongoing the first part is blinded and placebo controlled as was the case with pioneer part one. We also have some patients that are in a in an open label portion of that study, where we can look on in an ongoing matter of adverse.

And at a reduction in TSS score and we expect to present some preliminary data are about that.

That trial during the quarter before the end of the year and then we're looking at various opportunities to present, the randomized part one data.

Yeah. So if you want to add.

Yes.

Sure maybe just to add a couple of of that additional comments. There one just on the safety hurdle for for either Cat M. One thing that I think is really important for us to all keep in mind is that we have not actually seen a fully placebo controlled safety dataset for for Ava kit yet. So we are very much looking for it to have.

Having that data and really understanding and contextualized thing what safety looks like and benefit risk in the context of a randomized study where we haven't seen that data before with regards to 263, you know with Becker said, we will have initial data prior to the end of the year at similar to what we saw from part one of.

Of pioneer and I think you know we're going to be looking at the data coming out of pioneer part two as well as this data to really understand how best to bring 263 forward to patients. We know that the the bar there is gonna be incredibly high and it's gonna be sat by what we anticipate will be you know really transformational data are that Eva kit.

Be demonstrating in this disease. So we really look forward to kind of put he knows those pieces together and then sharing more about how we see moving our best in class franchise for it from there.

Okay.

Perfect. Thank you. Our next question comes from Dane Leone of Raymond James Your line is now open. Please go ahead.

Alright, Thank you for taking the questions and congratulations on the quarter and all the progress.

Yes, too early a question for me just to clarify some of the commentary from your presentation.

That sparked some.

Some interest I guess for the investors on the call.

The first one would be in your slide around advance us Hum.

Turning to the U.S., AvaKit is now the standard of care in patients being treated for their advanced SM with greater than 50 percent market share. It's the treatment of choice for more than 70% of patients who are starting on or switching, to a new therapy. We expect both these measures to continue growing. We've now seen AvaKit prescriptions from nearly 300 accounts since the launch in Advanced, SM.

Your your update on the market our.

Our team activated 46 first-time accounts in the second quarter, and we continue to, drive breadth in the community setting and depth in the academic setting.

Duration of therapy continues to trend favorably at about 18 months overall, and we expect, many patients to benefit from AvaKit for even longer periods of time.

Penetration of Eva kit seems to imply that you have about 50% share in the U S. Now.

And I guess, maybe that's a bit below where.

We and others would think you'd be outright now given the revenue run rate. So if you could clarify I guess, what your U S expectations are for the opportunity and something that would be helpful.

Then secondly could you just clarify in terms of the pricing strategy you did.

As it relates to ISR mentioned, you thought had her.

Terry Angioedema could be.

But that's obviously incredibly highly priced drug do you.

I guess some of the questions there around use of Omalizumab and other.

Other interventions maybe off label for ISR.

Whereas the conviction that you can price that high and in the eyes.

With it because our 25 Meg to Dave of printing it. Thank you.

Yeah. Thanks, Dan So so pointed out maybe take both the first question being the 50% market share is still low relative to the revenue run rate.

And then you know talking about the pricing assumption itself.

Yeah. Thanks for the question Dane So first to your question about market share. So just first of all confirming them. The way we are defining market share is the proportion of patients who are currently receiving Ava kit out of the total portion of patients being treated with Teekay eyes and site, a reductive therapies and so we have seen.

The greatest opportunity we see to drive continued growth is to increase the proportion of patients, who are being treated for their Advanced SM, particularly SMAHN, the most common subtype. Patients with SMAHN have a poor prognosis with a median overall survival of around, 2 years.

The steadily growing and we're encouraged by this continued growth.

Today that number is over 50% and if anything we're excited about the substantial headroom that this represents for the market. Both in terms of the market share of treated patients.

But even more broadly we are continuing to grow the portion of the market that is actively being treated and that's where we see the greatest amount of continued headroom for the advanced SM patient opportunity.

And to your second question about pricing strategy. So I think that the intent was not to say that we were aiming for consistent or the same pricing as other hereditary angioedema therapies, but mainly to use that as a relevant analog for rare diseases, where the.

The underlying pathophysiology is known with high medical need where you have medications that can enable disease modification and truly transformative benefits for patients.

That is the type of transformative benefit that we anticipate for Ava kit you referenced Omalizumab and I think it's really important to them to understand that it's in spite of these cocktails of symptom directed medications.

Patients the vast majority of patients still have substantial medical need them. So we've talked before about patient and provider burden of disease studies that indicate the majority of patients still talk about having to avoid leaving their home because of S. M. So that's about two thirds of patients.

80% of patients you know despite taking these polypharmacy regimens are reporting serious limitations in their work or daily activities and so all of these mass cell mediated therapies are only symptom directed at the end of the day.

And we are really excited for the potential of Eva kit as a true targeted approach that addresses the underlying driver of disease to have disease modifying impact and from what we've seen over the many hundreds of patients that have been treated over the past seven years on an Eva kit is truly that ability.

<unk> decrease measures of mast cell burden improved symptoms as well as quality of life.

Perfect as a reminder, they won't complete plans to limit themselves to one question and that would be greatly appreciated. Thank you.

Our next question comes from <unk> Richter of Goldman Sachs solving Yolanda smart weapons.

Hey, everyone. Thanks for taking our questions. This is andrea on for solving may.

Maybe just one on the back of your data disclosures at Ehealth damaged are showing a benefit on overall survival. Just curious the feedback you've received there and how this is being marketed to physicians to drive further uptake. Thanks, so much.

At EHA, we presented a retrospective study comparing overall survival for AvaKit versus, best-available therapies. In SMAHN patients, AvaKit demonstrated a median overall survival of 46.9 months versus, 18.0 months for best-available therapies. These data should further catalyze the urgency to treat these patients.

Advanced SM represents just 5 to 10% of all SM, and with our strong launch momentum, we're, only just getting started.

We see tremendous potential for AvaKit to benefit many more patients as we set our sights, on the non-advanced SM opportunity. Non-advanced SM leads to debilitating and potentially life-threatening symptoms, including, uncontrolled anaphylaxis, extreme fatigue, diarrhea, skin lesions, and brain fog.

Yes, Becker do you want to start with with the data from Ehow and then others can chime in.

Patients and caregivers undertake a significant burden to manage the disease, avoiding everyday, triggers and coordinating complex therapy regimens that, in most cases, fail to control the disease.

Cleanup.

There are no approved therapies today.

Yeah, just to remind you of what we showed was and improved survival compared to standard of care treatment. So we looked at patients that had been treated with started reductive therapies and with my store and and we looked at their overall survival and then compared to that to what we saw in her exploring paths.

Finder studies, we saw a substantial improvement in overall survival.

Our goal is to transform the lives of patients living with this debilitating disease.

What this has done is it's really solidified the notion that by driving rapid deep responses in this aggressive malignancy, we're able to achieve a survival rates that have not been seen in this disease before and this is really in many ways woken up the community even further than the response rate.

Here's why we're excited about the opportunity.

First, the number of diagnosed SM patients is steadily growing. We can see over 16,000 unique diagnosed SM patients in U.S. claims data, and most of, these patients have non-advanced SM.

Have people think about their patients as being very ill because they are and they ended up in the hospital repeatedly and they are really quickly.

Quickly moving towards.

Rival event or or or potentially dying from the disease and so the ability for a practitioner to stop this and provide additional additional life and also to see it in the depth of the response has been one that's been really embraced if we shared these these data.

This represents a remarkable 63% growth of the diagnosed patients in the U.S. since the, initial launch of AvaKit in January 2020.

No.

Second, approximately 60% of non-advanced SM patients in these claims take complex regimens, of prescription medications, indicative of moderate to severe disease burden.

These patients use a cocktail of symptom-directed therapies, including epipens, mast cell stabilizers, TKIs, and cytoreductive therapies.

Yeah. This is celina I'd love to add them add onto becker's comment and share some of the sort of K O L and provider responses to this data.

These complex regimens of off-label polypharmacy highlight the serious medical needs these patients, face.

Altogether, the claims data combined with a breadth of patient and provider research, indicates an addressable market opportunity of approximately 7,500 non-advanced SM patients with moderate to severe disease today who may be candidates for AvaKit. This represents a significant patient population who have and will continue to actively seek, treatment for their non-advanced SM.

And so treating physicians are truly excited about this data they're talking about it as really first of its kind and practice changing as we have these discussions through medical interactions with the provider community. We're hearing feedback such as you know this illustrates we now have a treatment.

With a pricing strategy similar to rare disease analogs such as hereditary angioedema, we, believe non-advanced SM may represent a multibillion-dollar opportunity for AvaKit.

We expect the launch trajectory will follow other similar rare disease markets. We continue to advance our market development efforts, working with the SM patient and provider, community to accelerate the time to diagnosis and initiation of treatment.

We anticipate this will continue to increase the number of diagnosed patients towards the, 32,000 prevalent SM patients living in the U.S. On a personal note, as I reach my eighth year at Blueprint Medicines, the non-advanced, SM opportunity has never felt so tangible.

We look forward to sharing more about this and how we'll capture this opportunity at, our investor day in November.

Can truly obliterate the S. M. You know beyond the surrogate measures of mast cell burden, we're actually seeing prognostic improvement in overall survival of these patients I'm. A second piece is we think this is really important when it comes to that opportunity to increase the proportion of patients who are at.

<unk> being treated for their S. M I'm, the greatest subset being patients with S. M H N where some providers.

Had historically been used to prioritizing the H N.

Now, we're seeing the important efficacy and safety data for Ava kit, the tolerability profile as well as the emerging overall survival data at truly shifts the balance towards the urgency to treat the S. M.

With that, I'll turn the call over to Becker to review our expectations for Pioneer Part, 2 top-line data.

Yeah.

Thank you. Our next question comes from Peter Lawson of Barclays Pizza, you line, that's not what happened.

Great. Thanks for taking my questions.

And then just.

What's the proportion of patients you'll see in the naive to treatment versus already exposed to prior treatment and then proportion of revenues that you think are potentially off label and the ice in this space.

Thank you, Paulina, and good morning, everybody.

As you know, we plan to share top-line results from our pivotal study of AvaKit in non-advanced, SM later this month. As the first registration-directed study in non-advanced systemic mastocytosis, Pioneer, is on track to provide a wealth of data and confirm AvaKit's potential to transform treatment of this more prevalent form of SM. In June, we shared that the FDA requested we elevate mean change in total symptom score, or TSS, which was previously a key secondary endpoint, to become the primary endpoint.

As we've seen with recent approvals of other medicines, this approach is increasingly becoming, the FDA's standard for randomized trials designed to assess patient-reported outcomes because it considers the full range of benefits seen in each arm.

Do you want to take both of those.

Let's review our primary endpoint, the comparison of mean TSS reduction in each arm, and a key, secondary endpoint, the proportion of patients who experience a response defined as a 30% reduction in TSS score. These endpoints are correlated, as illustrated by the Part 1 data. Our primary endpoint, the comparison of group means, is a measure of how the population, treated with AvaKit felt compared to those treated only with placebo plus best supportive Care.

Yeah happy to thank you for those questions. So we haven't provided specifics on the breakdown of patients.

Who are naive treatment naive them versus them switching from another therapy. However, I would say, we do continue to see adoption across both of these patient populations and importantly, we are seeing 70% of new therapy patient starts going to Ava kit.

As well as 70% of switching from preexisting therapies, such as such as Might've story.

And so when you you know we're highly encouraged to see that data and that essentially puts us towards a trajectory towards the market chair of 70% or above.

Your question about off label treatment. So certainly we don't promote to that and I would also say we are seeing a proportion of Ah adoption coming from the non advanced.

Patient community, which is a reflection of of the medical need that we see there.

And maybe just to just to add onto that on that a little bit of additional clarity. So so its planed upsetting a we we we don't break down specifically, but I will say the majority of our starts are first of all coming from what we would consider to be previously diagnosed <unk> patients and we still see a lot of headroom actually on both of those friends. So you know a lot of opportunity.

You increased penetration of what we would consider to be prevalent patients as well as to continue to see adoption for <unk> for newly diagnosed patients and we have seen that increase and we expect that to continue to increase and for non advanced us and as we've previously shared and it's fully not just shared we have seen them from physician reports some utilization with those patients.

It's very small in terms of the proportion of our overall revenue. So certainly you know the vast majority of Eva kit revenue currently is coming from utilization and advanced at them I do think though it's encouraging that we've seen prescriptions go through and be paid for for non advanced patients as well, which I think speaks to some of the earlier questions around access.

And pricing.

Thank you. Our next question comes from Reni Benjamin of JMP Securities. Your line is now open.

Great. Thanks for taking the questions and congrats on the quarter.

Sticking with with pioneer when you once you have the results we've had and we've submitted do you expect to have full approval from the FDA does this get a standard review or priority and then kind of just as you think about the landscape upon something like a full approval.

Fast followers need to run a study against Iva kit or.

You know as this disease indication one way or you can run all their placebo controlled trials and if so are there strategies that you have to keep the competitors kind of a thing.

Thanks.

So becker, maybe take that take the first part and and I'm happy to weigh in on the second part of it and we can take care of as well.

Hi, Yeah, so with respect to what we would expect from this randomized placebo controlled trial as we would expect this to be a full approval again. This is a supplemental NDA and we do expect.

Rapid review of the of the dossier.

With respect to what would be required for follow on compounds I think and we've thought about this quite a bit with a 263, we think that the bar is going to be extraordinarily high with the Eva kit data.

Particularly given the clean safety profile in the high efficacy that we saw in part one I hesitate to speculate on what the FDA will require but we do think that that coming behind it.

In indolent and non advanced SM is gonna be a difficult lift for any compound.

And just just to add is it's tobaccos point I think when you think about that care standards as well you know we have cases, where you know drugs with a similar mechanism or you know.

Our approved within a few months of each other that's very different than when theres, a multiple year gap right and so I think that is another kind of context to consider is just a temporal nature and what does a fastball or really mean.

Thank you.

Okay.

Thank you. Our next question comes from young of Jefferies. Your line is now open.

Thank you one other question on pioneer study expectation. So in part to one you showed a 16.5 point difference Ah with about 60% patients are responding and in part two it's a larger number of a patient population.

We'll refer to the control arm as placebo-controlled for simplicity, but as was the case in Pioneer, Part 1, patients in both arms continued to receive best supportive care before and during the study. In Pioneer Part 1, we observed a 16.5 point difference between the two groups, which was correlated with 60% of AvaKit-treated patients experiencing a response, something placebo was not able to achieve for any patient.

So how do you think about the changes in FX size. They usually you know in the larger trial at the size of tends to decrease so can you kind of talk about.

In this particular indication or whether you.

We expect <unk> to shrink because even if it can play or do you expect it's going to be kind of a similar to the.

The data in party.

Thank you.

Yeah, Beth you want to weigh in on them.

Yeah. So thank you for the question and I appreciate the historical referenced two phase III trials generally having a less.

While this response was striking, we've received consistent feedback from practitioners that if at least one-third of patients treated with AvaKit responded, this would be highly important and practice-changing.

Therapeutic impact in what you might see in some early trials. However in this case.

I still expect very robust results in part of the reason is that as investigators have learned about the patients about the benefit of putting up and about how to identify patients with very severe and moderate disease. We would expect the results to be relatively similar between part one and part.

Just another thing to remember about historical references is often people will change their design, even slightly between the phase two and then the pivotal study in this case, we've screened patients the same way. We've we've applied the same type of a statistical analysis. So part one and part two are really quite mirror images of.

Each other with just a broader investigator base and patient base, we expect the results to be quite robust and similar.

Yeah.

Thank you.

Question comes from Brett <unk> of Stifel. Your line is now open.

Good morning, and thanks for the refresher on market share versus market penetration. So quickly just like that do you have an estimate on the U S penetration rate of disease modifying therapies in a S. M. And then a follow up on <unk> question for ISR.

Do you expect the degree of benefit in pioneer from the new endpoint to impact physician utilization. If the difference was 10 points between Avi kit and placebo would you expect uptake to be significantly different than if it was a 15 point difference. Thank you.

So it made for me do you want to take the first part of that question around market penetration and then Becker if you want to weigh in on the second piece and and you know of course, you can also add some color there yeah. Thanks spread.

So starting off I think we shared in our last call that one of the things. We're highly encouraged by is that the.

The share of patients who are actively being treated for their therapy has grown substantially since the beginning of Eva kit launch it's grown by about 40%.

Now an important point to the heart of your question is this is still a minority of patients with advanced SM today and that flips into the opportunity, where we see significant headroom to continue to increase the size of the announced S M opportunity.

In fact, there maybe talk at going to the kind of a minimal clinical important difference in how you want to think about that relative to practice changing impact on patients.

Yeah, let's talk a little bit about the endpoint. The endpoint switching then how investigators and prescribing physicians are seeing it. So as we mentioned previously the design of the pioneer and the <unk> S. A S. R products with many years of collaboration with the FDA under the breakthrough therapy designation and both the F D. A.

And we've kind of committed to measuring clinically meaningful benefit for patients in pioneer part too and it's just a reminder, the FDA requested the change in endpoint elevating mean change to become our primary endpoint.

A little bit about the various end points you have to remember that there are many ways to measure clinical meaningful mess in systemic mastocytosis for patients. It's a return to a new normal after years of suffering from extensive rashes and diarrhea, and pervasive rainfall golfman preventing them from going to work for.

Furthermore, both responders and those with less than a 30% reduction in total symptom score often experience profound improvement in their most severe symptoms, such as extensive rashes, persistent diarrhea, and brain fog, all symptoms that make normal life all but impossible. These reductions in most severe symptoms can often be life-changing for patients.

Providers. It also includes objective evidence that the disease burden is substantially reduced.

So as we've spoken to investigators and prescribers about this they look at the totality of the data.

So looking at in.

Patient responses the proportion of patients that have different.

Depth of response, the proportion of patients with resolution of each type of symptom. So when their patient comes into the office. They can consider all of those.

The benefits of Eva kit and consider what's right for their patient.

Think about the they'll look at their trip if you look at the allele burden they'll look at the most bothersome or most severe symptom and they'll go look at the results from pioneer part two to understand what their patients could benefit their patients could it be.

We are, confident that Pioneer Part 2, which is powered to measure a minimum difference of 7 to 10 points between TSS reduction, half the difference observed in Part 1, will provide robust, practice-changing results in all of these correlated measures of clinical benefit.

In addition to the primary and this key secondary endpoint, and similar to our prior top-line data readouts, we will report top-line safety data. This will serve as the foundation for global regulatory submissions. It includes comparative safety from Pioneer Part 2, the first large placebo-controlled, safety data set for AvaKit in systemic mastocytosis to date.

Yeah.

Yeah, and I think you know.

I think just to add to that you know as as we know that patient for patients and it struck me as we've talked to patients.

I'm extremely enthusiastic about the promise AvaKit provides for thousands of patients who've been suffering from non-advanced SM for many years.

Idly over the last number of months that we noted a meaningful change for a patient is one that really reduces the symptoms and often the most bothersome symptom that has changed their quality of life are the ability to to work or to participate and kind of what we all take for granted it's just normal activities of daily living and and what we saw in part one.

Is that if a guy had a profound impact on the ability of patients to restore their quality of life to get back to work to build to do the things that take vacation and things they hadn't done for for years.

And so tobacco point you know it's of course, you know, we we know that the seven to 10 point change as we look at the part one data provides us type of meaningful benefit to patients. We are confident in that and everything we've heard from both patients and providers reinforce that confidence that this will change the prognosis for these patients and change the.

And not address at that.

Okay.

Our next question comes from David Newman can auction of Wedbush Securities. David Your line is not what happened.

I'll now turn the call over to Christy to review upcoming data milestones, and catalysts.

Thanks, Becker.

Hey, Thanks for taking my question most of them have been asked but I was curious.

You mentioned a high bar for Blu 263 development you know assuming pioneer is positive I mean is there a scenario where you have discontinued development or would you consider or is there a role for something like a molecule like <unk> hundred 63.

Maybe less severe indolent mastocytosis.

The mild or moderate version I suppose or is there you.

Not a good way to swap out it.

Good morning, everyone.

We've made significant progress against our corporate, goals in the first two quarters of 2022, and we are looking ahead to a breadth-of-value driving data catalyst planned for the second half of this year.

Yes, Dave Thanks for the question I'll start and Tim can add in but I mean, we were an incredibly strong position with two best in class assets that have slightly different profiles that we believe will both have our position both in U S M as well as when we think about logistics area and other mass cell driven disorders, and so you know the the <unk>.

<unk>, that's part of you know the the Ava kit in the clinical profile. They are a kit and not and advanced that Sam as well as what we anticipate coming out of pioneer not advance. The S. M is how we talk about that's going be a very high bar for and we're going to think about how Bluetooth how to move Blu six three forward, but there are gonna be patience, whether that'd be less severely affected patients.

Within our SM program, we plan to report Pioneer Part 2 top-line data later this month, as Becker shared, and initial clinical and safety data from the HARBOR trial of Blue263 in non-advanced SM by the end of this year.

We are also making rapid progress across our programs in EGFR-driven lung cancer, where we are working to generate data sets that inform further development and accelerate our path toward registration.

At AACR in April, we presented early dose escalation and biomarker data for Blue945s at once daily doses up to 200 milligrams. These data show tolerability and initial proof of concept consistent with Blue945's preclinical, profile. Based on these data, we initiated development of BLEU-945 in combination with osimertinib, in the second quarter.

We plan to report initial dose escalation data for the combination in the second half, of the year, with a focus on providing evidence that BLEU-945 and osimertinib can be combined safely, as well as translational data highlighting the combination's broad coverage of primary and secondary EGFR mutations and early signs of clinical activity.

Thanks, Christy.

We also expect to report a recommended phase 2 dose for single-agent BLEU-945 by the end, of this year.

Earlier this morning, we reported detailed financial results in our press release.

More broadly and consistent with our prior guidance, we expect initial clinical data, for BLEU-701 in the second half of 2022 and for BLEU-451 in the first half of 2023.

Finally, we remain incredibly excited about BLEU-222, our CDK2 program, and its potential, to impact many patients suffering from highly prevalent cancers, and look forward to presenting initial clinical data in the first half of 2023.

As Kate previewed earlier, we are proud to announce that we have outlicensed our internally, discovered KIT Exon-13 inhibitor to IDRX to advance the program into the clinic, evaluating it in combinations for patients with GIST. This represents our first development candidate of 2022.

And because we believe in IDRX's focus on the combinability of precision therapies, we received a 15% Series A preferred equity stake in exchange for our license grant. We are also eligible to receive up to $217 million in potential regulatory and sales-based, milestones, as well as tiered royalties on net sales.

This transaction is another example of our commitment to ensuring that valuable scientific, and medical innovation reaches patients regardless of the shifts in our portfolio priorities.

I'll now turn the call over to Mike to review our financial updates.

Or you know patients where the profile of Bluetooth six three is most appropriate and important and the position. We are in is to be able to strategically develop the clinical evidence in those patient populations as it makes the most sense. When we see you know the full set of clinical data out of pioneer and so we have a first in class and best in class.

Franchise, and systemic mastocytosis and you know feel I'm very excited about the opportunity to have a blueprint solution for all patients with systemic mastocytosis regardless of what.

What former subtype or clinical presentation they have.

Yeah.

For today's call, I'll touch on a few highlights from the quarter.

Yes.

Total revenues were $36.5 million for the quarter, including $28.5 million in net product, revenues from sales of AvaKIT and $8 million in collaboration revenues.

Yes.

Our next question comes from Michael <unk> of Morgan Stanley Michael Your line is not open. Please go ahead.

We are reiterating our previous revenue guidance for 2020-2022 of $180 million to $200 million, in total revenues and $115 million to $130 million in AvaKIT net product revenues, putting us well on track to realizing the blockbuster potential for AvaKIT.

Our R&D expenses for the second quarter were $128.3 million, including approximately $10, million of non-cash, stock-based compensation expense, reflecting planned growth in R&D expense related to the strong execution of our clinical trials.

These investments in new 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.

Prior to the first quarter of this year, R&D cost increased by approximately $25 million, driven by accelerated timing of expenses related to the startup and supply activities of four new clinical trials across our EGFR and CDK2 trials. Additionally, we saw increases driven by timing of certain early research activities.

SG&A expenses for the second quarter were $58.7 million, including approximately $15, million of non-cash, stock-based compensation expense, and were flat compared to Q1 of this year.

Yeah.

Hey, guys. Thanks for taking the question maybe a clarifying question first just for the pioneer topline results should we expect both TSS score and responder analysis.

Looking forward, we expect that overall expenses will be flat or slightly lower in the second, half of the year as we drive towards key data readouts.

Finally, our June 30th announcement of a strategic, non-dilutive financing agreement with Sixth, Street and Royalty Pharma puts Blueprint Medicines in a strong financial position to drive rapid growth while ensuring our path to profitability in the coming years. As of June 30th, we had $947 million in cash on our balance sheet. This balance includes a $175 million upfront payment received under the Royalty Pharma, agreement. In addition, in July, we received an additional $400 million in gross proceeds related to, our agreement with Sixth Street, which will be recorded in our financial statements in the third quarter.

This quarter was marked by executional excellence across our commercial, clinical, and research, organizations.

We continue to allocate resources towards R&D and core programs that are rapidly advancing, towards value-driving milestones.

The combination of our strong cash position, with well over a billion dollars on the balance, sheet as of today, multiple drivers of top-line revenue, and diversity of important pipeline programs uniquely positions us to continue building a leading precision therapy company, bringing transformative medicines to patients worldwide, and delivering value to our shareholders.

And then secondly, just a follow up to some of the earlier discussion on sort of what's meaningful.

With respect to TSS you mentioned.

Having a reduction in the most sort of severe symptom is there a particular reduction in terms of points on TSS.

That physicians would be looking for you know for example is a one point change enough or do you need to have a couple of point change there.

Sure.

So maybe I'll just start with the first one is easy question and I'll, let Becker answered the second but you can expect both the mean change in TSS as well as the responder analysis and she has asked that topline and Becker do you want to weigh in on that that you know any specific domain point change.

Yeah. So.

When you look at a patient with a most severe symptom it depends on where they are starting there can be one to two point changes that are extraordinarily meaningful for patients and when you think about single digit changes a seven point change in something that scored on a scale of one to 10 can be really substantial or.

Even the disappearance of that symptom. So if you can imagine a patient whose brain fog has been an eight and that goes down by even three or four points that can be a substantial change in their ability to function on a daily basis and go to work for a rash having it go from something that's very itchy and all over their body, which might be seven or eight and then dropped.

A few points on that single score that can really be life changing for patients. So will illustrate a lot of those scenarios as we get deeper into the data of pioneer part two but I think it's going to be transformative in so many different ways for different patients.

Got it. Thank you and we look forward to presenting those those broader dataset that medical meetings coming up and we're really I mean, it's as we as Becker mentioned in the prepared remarks. It was pioneer study is going to give us just a breadth and depth of data in this population that you know that is kind of unprecedented and we're gonna be able to really start elucidated all all the dynamics.

Within that dataset over overtime.

Yeah.

Thank you next question comes from Michael Schmidt with Guggenheim Michael Your line is now open.

I'll now turn the call over to the operator for questions.

Operator?

Thank you.

At this time, I'd like to remind everyone, in order to ask a question, please press star, followed by one on your telephone keypad.

Hey, this is Paul on for Michael Thanks for taking my questions. Just had a quick follow up on the is end market supermarket penetration for new patient starts you mentioned about 70% share currently and how much further room do you expect for gross peak and poor treatment duration on 18 months are trending towards that direction.

That's star followed by one on your telephone keypad now.

Our first question comes from Mark Frum of Cohen & Company.

Your current full year guidance for indicate incorporate any range of anticipated longer treatment duration.

Please point that when you take that yeah. Thanks for the questions Paul and so to your question about the I actually would you could would you mind repeating just the first part of your question one more time please.

Mark, your line is now open.

Thank you for taking a question.

This is Ernie Rodriguez for Mark.

Yeah, just on the market penetration for new patients and ASM.

About 70% share currently.

Yeah. Thanks for that question. So, yes, we do see Eva kit selected 70% of the time for new patients and we do continue to see a significant amount of upside to grow the treatment of these new patients as Christie alluded to them.

Congratulations on a great quarter.

I have two questions, if I may.

Becker, you mentioned reporting the safety results for Pioneer, and I was wondering if, you could tell us what level of granularity should we expect for the safety portion, and what would you see as an unacceptable number of intracranial hemorrhage or placebo-adjusted neurocognitive AEs?

Basically, at what level do you think these AEs could significantly affect adoption?

And a second question, if I may.

An important point is when we look at the market of treated actively treated advanced SM patients today, we can see that over the past few years or so about it's only on the order of about a thousand.

Who have received active treatment with Teekay is insider reductive therapies.

And so when you combine that with our understanding of the prevalent patient population on the order of about sort of.

Mid 1600, two or 3000 or so patients prevalent you can see that substantial upside in the need to grow the proportion of patients who today has not yet been treated so that new patient share is an important source of growth and ongoing focus for our team.

For 263, what should we expect for the initial data disclosure?

What level of detail?

Your second question was around duration of therapy, and we're highly encouraged as we continue along the launch trajectory of Eva kit to continue seeing.

And how should we think about this data when comparing it to Pioneer?

Significant durations of therapies in in our patient trends. So as I mentioned, we're trending towards 18 months and we're seeing this consistently across both the academic and the community setting which indicates a degree of physician comfort in managing patients across both settings.

And can I, just thought I'll chime in a little bit to add some color there as well so to the first question is ethylene at you know nicely summarized we're thrilled to see you know really dominant market share that's playing right. So either kit has clearly established as the best in class therapy amongst treated patients that can that can increase above 70%. We know that not every single patient will be a candidate for Ava.

Thank you.

Right, certainly patients with low platelets et cetera, and so as we look at the opportunity to grow you know, we see room to grow market share, but significant room to grow the size of the overall treated market and is as I'm. You know fellaini was saying some of the new data from <unk> et cetera, we think it can be really instrumental and driving that growth and there is a lot of opportunity to continue to.

With respect to duration you know, we're very happy to see where we are trends and duration are not going to be as relevant for guidance. This year, they're certainly going to be important as we think about the overall opportunity going forward and so we're really we're really excited because these long treatment durations and should enable revenue accelerates.

And as we get into your you know sort of further years of a lunch and we start to see patients new patients sort of stacking on top of patients who've been on therapy for it you know potentially I'm quite quite significant length of time.

Thank you. Our next question comes from David Lebowitz with Citi. David Your line is now open.

Well. Thank you very much for taking my question.

Out of curiosity when you when you look at the TSS score I would assume that from the patient and physician perspective not all.

The symptoms are created.

Created equal as far as their impact on their treatment direction.

Which of the symptoms as most are most typically cited as driving the treatment decision for these patients.

Becker do you want to weigh in there and also if you have any color from the interaction partially.

Yes, David.

That's a good question and I had the same one when I first looked at the data and I expected that maybe there would be a specific domain or specific symptom that was driving a lot of the TSS reduction or maybe even more meaningful to patients, but I really discovered the opposite.

If you are a patient with brain fog and you have been a practicing attorney in and can't go to work anymore and can't function and then improving that brain fog is life changing an extraordinarily meaningful for you if you have diarrhea.

Many times a day and you can't see your family. Your friends you can't don't have a social life and improving the diarrhea can be really profound and you know I've heard similar stories for each of the domains in each of the symptoms. The skin rashes, one obviously that can be disfiguring and extraordinarily bothersome, it's very periodic I think we've all.

Had allergic reactions when we understand how how life changing that can be even for a day much less day. After day. So we will certainly dive more deeply into the various symptoms and the impact on TSS score.

In the rich dataset that we're gonna see from pioneer, but I've really been.

Extraordinarily convinced that all of the symptoms individually and combined can be tremendous.

Life, changing and the disappearance thereof will really return these patients to what I've started to call. The new normal you hear so many stories about people, saying I've never felt this good before it because they've been living with this disease for so long.

Thank you for taking my question.

Yeah.

Thank you. Our next question comes from Joel Beatty of Bad joke, Yolanda Smart weapon.

Alright, Thanks for taking the question for the topline pioneer readout. Later this month do you anticipate breaking out results by each of the components of the TSS score.

And then I'll go to the last point or it sounds like patients are often able to reengage with.

Daily living and daily activities are the measures that you're collecting that you've made but it sure at some point.

So I'll start and then Becker please weighing on if I can so for topline data, Delaware, where it'll be it'll be very much. The top line. So that the kind of endpoints that we've highlighted them as well as that topline safety perspective, we will be planning to present this data at a medical conference and more.

Detailed likely a few medical conferences in more detail in the near term after the topline data and Becker would you want to weigh in on the second part of Jeff's question Yeah.

So Joel we have multiple measures of quality of life that we will be digging deeply into during the filing and in subsequently to show various ways of looking at the benefit not only the measurable symptoms, but also the the level of functioning and just the general quality of life of patients have.

Great. Thank you.

Yeah.

Thank you Joe and our final question for today comes from Matthew Biegler with Oppenheimer. Matthew Your line is now open.

Oh, Hey, guys. Thanks for squeezing me in.

Maybe it is maybe it's controversial question, but given all the debate about the euro Euro end points I'm, just wondering if there's a scenario where you could leverage the breakthrough therapy designation.

Its file for accelerated approval based on improvements and objective endpoints and I'm I'm really thinking back to GBT story here.

And their development.

Element of ox brighter, where they where they essentially shelved the bureau altogether and just filed based on the objective improvement so.

That would be an interesting case, but I'm curious to hear your thoughts. Thanks.

Yeah. Thanks for the question Matthew I mean really.

Really simply I mean, we don't anticipate that that scenario for us at all I mean this is a well designed registration directed global placebo controlled study and you know I you know our our belief will be that we have a dataset that speaks for itself that is going to be registration directed both here and in and globally.

And they will be looking for full approval.

Okay.

Uh huh.

Yeah.

Yeah, thanks, Ernie.

Thank you there are no further questions at this time Ms Harper loans, that's on the call back over to you.

So, Becker, I think maybe you can start off with both, and then if Christina or Flora, want to add to the 263.

Thank you operator, and thanks, everybody for joining us today as we discuss today you know Apple print medicines, we are building a strong and resilient organization that will continue to drive value and growth delivering transformative new medicines to patients around the world.

Our ongoing global commercial launch success, the breadth and depth of our upcoming milestones and data catalysts.

Fortified cash position.

Has that has oh, sorry, no uniquely and exceptionally exceptionally strong profile as we head into the second half of the year.

We look forward to discussing the pioneer part two topline data with all of you later this month. So thank you for your time today and for your continued support of blueprint medicines.

For the top line data, we plan to present adverse events and serious adverse events, comparing the two arms, as we typically do with top line data when we first see the readout of these trials.

With respect to expected rates of adverse events, I hesitate to speculate on what we would see in the trial. I think it's important to remember, though, that these are patients receiving standard of care medications, some of which have adverse events that overlap with the disease or even some that might overlap with some of the AvaKit adverse events.

However, at 25 milligrams in Part 1, we saw an extraordinarily good safety profile with, very low rates of even Grade 1 adverse events and really no Grade 3 adverse events. And we would expect the safety profile in Part 2 to be very similar to what we saw in Part 1.

And then, with respect to 263, we have Part 1 of our study ongoing.

The first part, is blinded and placebo-controlled, as was the case with Pioneer Part 1.

Thanks for taking, our questions.

We also have some patients that are in an open-label portion of that study where we can look in an ongoing matter at adverse events and at reduction in PSS score.

This is Andrea for Salveen.

And we expect to present some preliminary data about that trial during the quarter, before the end of the year.

Maybe just one on the back of your data disclosures at EHA are showing the benefit on overall survival.

And then we're looking at various opportunities to present the randomized Part 1 data.

Just curious the feedback you've received there and how this is being marketed to physicians to drive further uptake.

Yeah, thanks.

Thanks so much.

Maybe you want to add to that?

Yeah, Becker, do you want to start with the data from EHA and then others can chime in? Yeah, just to remind you, at EHA what we showed was an improved survival compared to, standard of care treatment. We looked at patients that had been treated with cytoreductive therapies with mitostaurin. We looked at their overall survival and then compared to that to what we saw in our Explore and Pathfinder studies. We saw a substantial improvement in overall survival.

Sure.

Ladies and gentlemen, this concludes today's conference call.

What this has done is it's really solidified the notion that by driving rapid, deep responses in this aggressive malignancy, we're able to achieve survival rates that have not been seen in this disease before.

Maybe just to add a couple of additional comments there.

This has really, in many ways, woken up the community even further than the response rate has.

One, just on the safety hurdle, for AvaKit, one thing that I think is really important for us to all keep in mind is that we have not actually seen a fully placebo-controlled safety data set for AvaKit yet.

People think about their patients as being very ill, because they are, and they end up in the hospital repeatedly. They are really quickly moving towards a survival event or potentially dying from the disease.

So, we are very much looking forward to having that data and really understanding and contextualizing what safety looks like and benefit-risk in the context of a randomized study where we haven't seen that data before.

The ability for a practitioner to stop this and provide additional life and also to see it in, the depth of the response has been one that's been really embraced as we share these data.

With regards to 263, as Becker said, we will have initial data prior to the end of the year, similar to what we saw from Part 1 of Pioneer.

Yeah.

And I think we're going to be looking at the data coming out of Pioneer Part 2, as well as this, data, to really understand how best to bring 263 forward to patients.

This is Felina.

We know that the bar there is going to be incredibly high, and it's going to be set by what we anticipate will be really transformational data that AvaKit will be demonstrating in this disease.

Uh huh.

I'd love to add on to Becker's comment and share some of the, KOL and provider responses to this data.

So, we really look forward to putting those pieces together and then sharing more about, how we see moving our best-in-class franchise forward from there.

Treating physicians are truly excited about this data.

Uh huh.

Perfect.

They're talking about it as really first of its kind and practice changing.

Thank you.

Uh huh.

As we have these, discussions through medical interactions with the provider community, we are hearing feedback such as this illustrates we now have a treatment that can truly obliterate the SM.

Our next question comes from Dane Leone of Raymond Chains.

Beyond the surrogate measures of mast cell burden, we're actually seeing prognostic improvement in overall survival of these patients.

Dane, your, line is now open.

A second piece is we think this is really important when it comes to that opportunity to increase the proportion of patients who are actively being treated for their SM.

Please go ahead.

Hum.

The greatest subset being patients with SM-AHN, where some providers had historically been used to prioritizing the AHN. Now, seeing the important efficacy and safety data for AvaKit, the tolerability profile, as well as this emerging overall survival data, it truly shifts the balance towards the urgency to treat the SM.

Hi.

Thank you.

Thank you for taking the questions, and congratulations on the quarter and all the, progress.

Our next question comes from Peter Lawson of Barclays.

I guess two related questions from me, just to clarify some of the commentary from your presentation that sparked some interest, I guess, from the investors on the call.

Peter, your line is now, open.

The first one would be, in your slide around Advanced SM, there's a lot of information Your update on the market penetration of AvaKit, seems to imply that you have about 50% share in the U.S. now.

Yeah.

Great.

And I guess maybe that's a bit below where, we and others would think you'd be at right now given the revenue run rate.

Thanks for taking my questions.

So if you could clarify, I guess, what your U.S. expectations are for the opportunity in ASM, that would be helpful.

In ASM, what's the proportion of patients you're seeing that are naive to treatment versus already exposed to prior treatments?

And then secondly, could you just clarify, in terms of pricing strategy?

And then proportion of revenues that you think are potentially off-label in the ISM space?

You did, as it relates to ASM, mention you thought hereditary angioedema could be a comp, but that's obviously an incredibly highly priced drug.

Yes.

Philina, do you want to take both of those?

And I guess some of the questions there, around use of omalizumab and other interventions may be off-label for ASM.

Yeah, happy to.

Where's the conviction that you can price that high in ASM, with AvaKit or 25 meg QDA AvaPrintNib?

Thank you for those questions.

Thank you.

We haven't provided specifics on the breakdown of patients who are treatment-naive versus, switching from another therapy. However, I would say we do continue to see adoption across both of these patient populations.

Yeah, thanks, Dane.

Okay.

And importantly, we are seeing 70% of new therapy patient starts going to AvaKit, as well as 70% of switching from pre-existing therapies, such as Midostorin.

So Philina, maybe take both.

And so we're highly encouraged to see that data, and that essentially puts us towards, a trajectory towards a market share of 70% or above.

The first question being the 50% market share, feels low relative to the revenue run rate.

Your question about off-label treatment, so certainly we don't promote to that.

And then talking about the pricing assumption, so.

And, I would also say we are seeing a proportion of adoption coming from the non-advanced patient community, which is a reflection of the medical need that we see there. Maybe just to add on to that, a little bit of additional clarity.

Yeah, thanks for the question, Dane.

So, as Philina said, we don't break down specifically, but I will say the majority of our starts are, first of all, coming from what we would consider to be previously diagnosed patients.

So first to your question about market share.

Yeah.

And we still see a lot of headroom, actually, on both of those fronts. So, a lot of opportunity to increase penetration of what we would consider to be prevalent patients, as well as to continue to see adoption for newly diagnosed patients. And we have seen that increase, and we expect that to continue to increase.

So just first of all, confirming, the way we are defining market share is the proportion of patients who are currently receiving AvaKit out of the total portion of patients being treated with TKIs and cytoreductive therapies.

For non-advanced SM, as we've previously shared and as Philina just shared, we have seen from physician reports, some utilization with those patients.

And so we have seen this steadily growing, and we're encouraged by this continued growth.

Yeah.

It's very small in terms of the proportion of our overall revenue. So, certainly, the, vast majority of AvaKit revenue currently is coming from utilization in advanced SM.

Today, that number is over 50%. And if anything, we're excited about the substantial headroom, that this represents for the market, both in terms of the market share of treated patients, but even more broadly, we are continuing to grow the portion of the market that is actively being treated.

Yeah.

I do think, though, it's encouraging that we've seen prescriptions go through and be, paid for for non-advanced patients, as well, which I think speaks to some of the earlier questions around access and pricing.

And that's where we see the greatest amount, of continued headroom for the advanced SM patient opportunity.

Thank you.

And to your second question about pricing strategy.

Our next question comes from Rene Benjamin of JMP Securities.

So I think that the intent was not to say, that we were aiming for consistent or the same pricing as other hereditary angioedema therapies, but mainly to use that as a relevant analog for rare diseases where the underlying pathophysiology is known with high medical need, where you have medications that can enable disease modification and truly transformative benefits for patients. That is the type of transformative benefit, that we anticipate for AvaKit.

Rene, your line is now open.

You referenced omalizumab, and I think it's really important to understand that it's in spite of these cocktails of symptom-directed medications, patients, the vast majority of patients still have substantial medical need.

Great.

So we've talked before about patient, and provider burden of disease studies that indicate the majority of patients still talk about having to avoid leaving their home because of SM.

Thanks for taking the questions, and congrats on the quarter.

So that's about two thirds of patients.

Just sticking with Pioneer, once you have the results in hand and you've submitted, do you expect a full approval from the FDA?

80% of patients, despite taking these polypharmacy regimens are reporting serious limitations in their work or daily activities.

Does this get a standard review or priority?

And so all of these mast cell mediated therapies, are only symptom-directed at the end of the day.

And, kind of, just as you think about the landscape upon something like a full approval, do fast followers need to run a study against AvaKit, or, you know, is this disease indication one where you can run, you know, other placebo control trials?

And we are really excited for the potential of AvaKit, as a true targeted approach that addresses the underlying driver of disease to have disease modifying impact.

And, if so, are there strategies that you have to keep the competitors, kind of, at bay?

And from what we've seen over the many hundreds of patients, that have been treated over the past seven years on AvaKit is truly that ability to decrease measures of mast cell burden, improve symptoms as well as quality of life.

Thanks.

Life.

So, Becker, maybe take the first part, and I'm happy to weigh in on the second part, and the team can as well.

Perfect.

Hi.

As a reminder, if everyone can please plan to limit themselves to one, question, that would be greatly appreciated.

Yeah.

Thank you.

So, with respect to what we would expect from this randomized placebo-controlled trial is, we would expect this to be a full approval.

Our next question comes from Salveen Richter of Goldman Sachs.

Again, this is a supplemental NDA, and we do expect a rapid review of the dossier.

Salveen, your line is now open.

With respect to what would be required for follow-on compounds, I think that, and we've, thought about this quite a bit with Blue 263, we think that the bar is going to be extraordinarily high with the AvaKit data, particularly given the clean safety profile and the high efficacy that we saw in Part 1.

Hey, everyone.

I hesitate to speculate on what the FDA will require, but we do think that coming behind, AvaPritinib in indolent and non-advanced SM is going to be a difficult lift for any compound.

And just to add, to Becker's point, I think when you think about care standards as well, we have cases where drugs with a similar mechanism are approved within a few months of each other.

That's very different than when there's a multiple-year gap, right?

And so, I think that is another kind of context to consider is just the temporal nature and, what does a fast follow-up really mean.

Thank you.

Our next question comes from Yoon Yang of Jeffries.

Yoon, your line is now open.

Thank you.

Another question on pioneer study expectations.

So, in Part 1, you showed a 16.5-point difference with about 60 percent patients responding.

And in Part 2, it's a larger number of patient populations.

So, how do you think about the changes in effect size?

Usually, you know, in the larger trial, effect size tends to decrease.

So, can you kind of talk about, in this particular indication, whether you expect effect size, to shrink significantly or do you expect it's going to be kind of similar to the data in, Part A?

Thank you.

Yeah.

Becker, do you want to weigh in on that?

Yeah.

So, thank you for the question.

I appreciate the historical reference to Phase 3 trials generally having less therapeutic, impact than what you might see in some early trials.

However, in this case, I still expect very robust results. And part of the reason is that as investigators have learned about the patients, about the, benefit of avipritinib, and about how to identify patients with severe and moderate disease, we would expect the results to be relatively similar between Part 1 and Part 2.

Just another thing to remember about historical references is often people will change their, design even slightly between the Phase 2 and then the pivotal study.

In this case, we've screened patients the same way.

We've applied the same type of statistical analysis.

So, Part 1 and Part 2 are really quite mirror images of each other with just a broader investigator, base and patient base.

So, we expect the results to be quite robust and similar.

Thank you.

Our next question comes from Brad Sineno of Stiefel.

Brad, your line is now open.

Good morning and thanks for the refresher on market share versus market penetration.

So quickly, I'd just like to ask, do you have an estimate on the U.S. penetration rate of disease modifying therapies in ASM?

And then a follow-up on Yoon's question for ISM, do you expect a degree of benefit in Pioneer from the new endpoint to impact physician utilization?

You know, if the difference was 10 points between Avikit and placebo, would you expect uptake to be significantly different than if it was a 15-point difference?

Thank you.

So, maybe, Philina, you want to take the first part of the question around market penetration, and then, Becker, if you want to weigh in on the second piece, and Christy can also add some color there.

Yeah, thanks, Brad.

So, starting off, I think we shared in our last call that one of the things we're highly encouraged by is that the, share of patients who are actively being treated for their therapy has grown substantially since the beginning of Avikit launch. It's grown by about 40 percent.

Now, an important point to the heart of your question is this is still a minority of patients with advanced SM today, and that flips into the opportunity where we see significant headroom to continue to increase the size of the advanced SM opportunity.

And, Becker, maybe going to the kind of minimal clinical important difference and how you want to think about that relative to practice changing impact on patients.

Yeah, let's talk a little bit about the endpoint, the endpoint switch, and then how investigators and prescribing physicians are seeing it.

So, as we mentioned previously, the design of the Pioneer and the ISM-SAS are the product of many years of collaboration with the FDA under the breakthrough therapy designation, and both the FDA and Blueprint are committed to measuring clinically meaningful benefit for patients in Pioneer Part 2.

And, just a reminder, the FDA requested the change in endpoint elevating mean change to become our primary endpoint.

Now, just a little bit about the various endpoints.

You have to remember that there are many ways to measure clinical meaningfulness in systemic mastocytosis.

For patients, it's a return to a new normal after years of suffering from extensive rashes and, diarrhea and pervasive brain fog, often preventing them from going to work.

And, for providers, it also includes objective evidence that the disease burden is substantially reduced.

So, as we've spoken to investigators and prescribers about this, they look at the, totality of the data. So, looking at individual patient responses, the proportion of patients that have different depth of response, the proportion of patients with resolution of each type of symptom.

So, when their patient comes into the office, they can consider all of those the benefits of Aviket and consider what's right for their patient.

They'll think about the, they'll look at the trip days, look at the allele burden, they'll look at the most bothersome or most severe symptom, and they'll go look at the results from Pioneer Part 2 to understand what their patients could, what benefit their patients could, Yeah, and I think, you know, so I think just to add to that, you know, as as we know that patient for patients, and it struck me as we've talked to patients, kind of widely over the last, you know, number of months that we know that a meaningful change for a patient is one that really reduces the symptoms and often the most bothersome symptom that has changed their quality of life or their ability to to work or to participate in kind of what we all take for granted as just normal activities of daily living.

And, and what we saw in part one is that AvaCat had a profound impact on the ability of patients to restore their quality of life to get back to work to be able to do the things that take vacation things they hadn't done for for years.

And so to Becker's point, you know, it's, of course, you know, we we we know that the seven to 10 point change as we look at the part one data provides this type of meaningful benefit to patients.

We are confident in that. And everything we've heard from both patients and providers reinforce that confidence that this will change the prognosis for these patients and change the practice in non-advanced SM.

Our next question comes from David Nearingotton of Wedbush Securities.

David, your line is, now open.

Thanks for taking my question.

Most of them have been asked, but I was curious, you mentioned, a high bar for blue 263 development, you know, assuming Pioneer is positive.

I mean, is there a scenario where you discontinue development or would you consider is there a role for something like a molecule like 263 and maybe less severe indolent mastocytosis of the mild or the moderate version, I suppose?

Or is there, you know, not a good way to slot that in?

Yes, Dave, thanks for the question.

I'll start and the team can add in.

But I mean, we we, are an incredibly strong position with two best in class assets that have slightly different profiles that we believe will both have a position both in SM as well as we think about blue 263 and other mast cell driven disorders.

And so, you know, the data sets, you know, the advocate and the clinical profile advocate and not in advanced SM as well as what we anticipate coming out of Pioneer and non-advanced SM is how we talk about that's going to be a very high bar for and we're going to have to think about how to move blue 263 forward.

But there are going to be patients, whether that be less severely affected patients or, you know, patients where the profile of blue 263 is most appropriate and important.

And the position we are in is to be able to strategically develop the clinical evidence in those patient populations, as makes the most sense when we see, you know, the full set of clinical data out of Pioneer.

And so, you know, we have a first in class and best in class franchise in systemic mastocytosis and, you know, feel very excited about the opportunity to have a blueprint solution for all patients with systemic mastocytosis regardless of what form or subtype or clinical presentation they have.

Thanks.

Thank you.

Our next question comes from Michael Oles of Morgan Stanley.

Michael, your line, is now open.

Please go ahead.

Hey guys, thanks for taking the question.

Maybe a clarifying question first, just for the Pioneer top line results, should we expect, both TSS score and responder analysis?

And then secondly, just to follow up to some of the earlier discussion on sort of what's, meaningful with respect to TSS, you mentioned, you know, having a reduction in the most sort of severe symptom.

Is there a particular reduction in terms of points on TSS, you know, that physicians, would be looking for?

You know, for example, is a one point change enough, or do you need to have a couple point, change there?

Thanks.

So, maybe I'll just start with the first one, it's an easy question, and I'll let Becker, answer the second.

But you can expect both the mean change in TSS as well as the responder analysis in TSS, at top line.

And Becker, do you want to weigh in on the, you know, any specific domain point change?

Yeah.

So, when you look at a patient with a most severe symptom, it depends on where they're, starting.

There can be one to two point changes that are extraordinarily meaningful for patients.

And when you think about single digit changes, a seven point change in something that's scored, on a scale of one to ten can be really substantial or even be disappearance of that symptom. So, if you can imagine a patient whose brain fog has been an eight, and that goes down, by even three or four points, that could be a substantial change in their ability to function on a daily basis and go to work.

For a rash, having it go from something that's very itchy and all over their body, which, might be a seven or eight, and then dropping a few points on that single score, that can really be life changing for a patient.

So, we'll illustrate a lot of those scenarios as we get deeper into the data of Pioneer, Part 2.

But I think it's going to be transformative in so many different ways for different patients.

Got it.

Thank you.

And we will look forward to presenting those broader data sets at medical meetings coming, up. And we'll really... As Becker mentioned in the prepared remarks, this Pioneer study is going to give us just, a breadth and depth of data in this population that is kind of unprecedented, and we're going to be able to really start elucidating all the dynamics within that data set over time.

Thank you.

Our next question comes from Michael Schmidt of Guggenheim.

Michael, your line is now open.

Hey, this is Paul.

I'm for Michael.

Thanks for taking our questions.

Just had a quick follow-up on the ASM market.

So, for market penetration for new patient starts, you mentioned about 70% share currently.

How much further room do you expect for growth at peak?

And for treatment duration on 18 months trending towards that direction, does your current, four-year guidance for etiquette incorporate any range of anticipated longer treatment duration?

Thank you.

Please, Flynn, I want you to take those.

Yep.

Thanks for the questions, Paul.

And so, to your question about the... Actually, would you mind repeating just the first part of your question one more time, please?

Yeah.

Just on the market penetration for new patients in ASM, you mentioned about 70%.

Yeah.

That's shared currently.

Yeah.

Thanks for that question.

So, yes.

We do see advocates selected 70% of the time for new patients.

And we do continue to see a significant amount of upside to grow the treatment of these new, patients, as Christy alluded to.

An important point is when we look at the market of treated, actively treated advanced, And who have received active treatment with TKIs and cytoreductive therapies.

And so when you combine that with our understanding of the prevalent patient population on the, order of about sort of, you know, mid 1600 to 3000 or so patients prevalent, you can see that substantial upside in the need to grow the proportion of patients who today had not yet been treated.

So that new patient share is an important source of growth and ongoing focus for our, team.

Your second question was around duration of therapy.

And we're highly encouraged as we continue along the launch trajectory of AvaKit to, continue seeing significant durations of therapies in our patient trends. So, as I mentioned, we're trending towards 18 months and we're seeing this consistently, across both the academic and the community setting, which indicates a degree of physician comfort in managing patients across both settings.

And can I just add, I'll chime in a little bit to add some color there as well.

So to the first question, as Philina nicely summarized, we're thrilled to see, you know, really dominant market share at this point.

Right.

So AvaKit is clearly established as the best in class therapy amongst treated, patients.

That can increase above 70 percent.

We know that not every single patient will be a candidate for AvaKit, right? Certainly patients with low platelets, etc.

So as we look at the opportunity to grow, you know, we see room to grow market share, but, significant room to grow the size of the overall treated market.

And as, you know, Philina was saying, some of the new data from EHA, etc., we think is, going to be really instrumental in driving that growth.

And there is a lot of opportunity to continue to grow.

With respect to duration, you know, we're very happy to see where we are.

Trends and duration are not going to be as relevant for guidance this year.

They're certainly going to be important as we think about the overall opportunity going, forward. And so we're really excited because these long treatment durations should enable revenue acceleration as we get into, you know, sort of further years of a launch and we start to see patients, you know, new patients sort of stacking on top of patients who have been on therapy for, you know, potentially quite significant lengths of time.

Thank you.

Our next question comes from David Lebowitz of Citi.

David, your line is now open.

Thank you very much for taking my question.

Out of curiosity, when you look at the TSS score, I would assume that from the patient, and physician perspective, not all of the symptoms are created equal as far as their impact on their treatment direction.

Which of the symptoms is most are most typically cited as driving the treatment decision, for these patients?

Zachary, do you want to weigh in there and also if you have any color from the, interactions commercially?

Yeah, David, that's a good question.

And I had the same one when I first looked at the data and I expected that maybe there, would be a specific domain or specific symptom that was driving a lot of the TSS reduction or maybe even more meaningful to patients.

But I really discovered the opposite.

I really started to say people thank you for this treatment.

I'm also grateful for these instances where not only I might have succeeded at doing, something versus not even knowing what I could do most efficiently.

If you are a patient with brain fog and you have been a practicing attorney and can't go to work anymore and can't function, then improving that brain fog is life-changing and extraordinarily meaningful for you.

If you have diarrhea 20 times a day and you can't see your family, your friends, you don't have a social life, then improving the diarrhea can be really profound.

I've heard similar stories for each of the domains and each of the symptoms.

The skin rash is one, obviously, that can be disfiguring and extraordinarily bothersome. It's very periodic.

I think we've all had allergic reactions and we understand how life-changing that can be, even for a day, much less day after day.

We'll certainly dive more deeply into the various symptoms and the impact on PFS score in the rich data set that we're going to see from Pioneer, but I've really been extraordinarily convinced that all of these symptoms, individually and combined, can be tremendously life-changing and the disappearance thereof will really return these patients to what I've started to call the new normal.

You hear so many stories about people saying, I've never felt this good before because they've been living with this disease for so long.

Thank you for taking my question.

Thank you.

Our next question comes from Joel Beattie of Baird.

Joel, your line is now open.

Hi, thanks for taking my question.

For the Top Line Pioneer readout later this month, do you anticipate breaking out results by each of the components of the TSS score?

Also, to the last point, it sounds like patients are often able to reengage with daily living and daily activities.

Are there measures of that that you're collecting that you may be able to share at some point?

I'll start, and then, Becker, please weigh in on the second.

For top-line data, Joel, it will be very much the top line.

The endpoints that we've highlighted, as well as that top-line safety perspective, we will be planning to present this data at a medical conference in more detail, likely a few medical conferences in more detail, in the near term after the top-line data.

Becker, do you want to weigh in on the second part of Joel's question?

Yes.

Joel, we have multiple measures of quality of life that we will be digging deeply into during the filing and, subsequently, to show various ways of looking at the benefit, not only the measurable symptoms, but also the level of functioning and just the general, Great.

Thank you.

Thank you, Joel.

And our final question of the day comes from Matthew Beigler of Oppenheimer.

Matthew, your line is now open.

Hey, guys.

Thanks for screening me in.

This may be a controversial question, but given all the debate about the PRO endpoints, I'm just wondering if there's a scenario where you could let us know what you think of the PRO endpoints.

I'm just wondering if there's a scenario where you could leverage the breakthrough therapy designation to file for accelerated approval based just on improvements and objective endpoints.

And I'm really thinking back to GBT's story here in their development of Oxbright, where they were able to get the breakthrough therapy designation to file for accelerated approval based just on improvements and objective endpoints.

And I'm really thinking back to GBT's story here in their development of Oxbright, where they essentially shelved the PRO altogether and just filed based on those objective improvements.

So, that would be an interesting case, but I'm curious to hear your thoughts.

Thanks.

Thanks for the question, Matthew.

I mean, really simply, we don't anticipate that scenario, for us at all.

This is a well-designed, registration-directed, global, placebo-controlled study, and our belief will be that we have a data set that speaks for itself, that is going to be registration-directed both here and globally, and that we'll be looking for full approval.

Thank you.

There are no further questions at this time.

Ms. Haviland, I turn the call back over to you.

Thank you, Operator, and thanks, everybody, for joining us today.

As we discussed today, you know, at Blueprint Medicines, we are building a strong and resilient organization that will continue to drive value and growth, delivering transformative new medicines to patients around the world.

Our ongoing global commercial launch success, the breadth and depth of our upcoming milestones and data catalysts, and our fortified cash position has a uniquely and exceptionally strong profile as we head into the second half of the year.

We look forward to discussing the Pioneer Part 2 top-line data with all of you later this month, so thank you for taking your time today and your continued support of Blueprint Medicines.