Q3 2021 Blueprint Medicines Corp Earnings Call

Kristen: everyone that statements we make on this conference call will include forward-looking statements. However, 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 filing.

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 filings.

Jeff Albers: In addition, any forward-looking statement that we make on this call represents our views only as of today and should not be relied upon as representing our views as of any subsequent We specifically disclaim any obligation to update or revise any forward-looking statement. Now, here's our CEO, Jeff Albers. Thank you, Kristen, and good morning, everyone, and thanks for joining us today.

In addition, any forward looking statement made on this call represents our views only as of today and should not be relied upon as representing our views as of any subsequent date.

We specifically disclaim any obligation to update or revise any forward looking statements now here's our CEO Jeff Albers.

Kersten and good morning, everyone and thanks for joining us today.

Jeff Albers: In the third quarter, we made tremendous progress toward bringing our life-changing precision therapies to patients around the world. Today on the call, you'll hear about three areas of fundamental growth. The first is solid commercial performance anchored by Avicat's Advanced Systemic Massa Cytosis launch in the U.S. We're seeing broad demand for prescribers at both academic and community centers and across patients with different advanced SM subtypes. This momentum provides a foundation for continued leadership and growth for our SM franchise as we look to deliver top-line data from our pivotal pioneered study of aviakit in non-advanced systemic mastocytosis in mid-2020 and accelerate development of Blue 263, our next generation kit inhibitor.

In the third quarter, we made tremendous progress towards bringing our life changing precision therapies to patients around the world.

Today on our call Youll hear about three areas of fundamental growth.

The first is solid commercial performance.

<unk> by Eva Kit advanced systemic mastocytosis launch in the U S.

We're seeing broad demand for prescribers at both academic and community centers and across patients with different advanced SM subtypes.

This momentum provides a foundation for continued leadership and growth for our SME franchise as we look to deliver top line data from our pivotal pioneer study of Eva kit in non advanced systemic mastocytosis in mid 2022.

And accelerate development of Blu 263, our next generation kit inhibitor.

Jeff Albers: The second area of growth is based around the continued execution and expansion of our R&D vision, with a robust pipeline of innovative precision therapies advancing at all stages of development. As Fulad will describe, our next wave of clinical programs is progressing rapidly towards multiple proof of concept readouts. We've been encouraged by the widespread interest in our Symphony trial of Blue 945, and we're on track to initiate a phase one trial for Blue 701 in the fourth quarter.

The second area of growth is based around the continued execution and expansion of our R&D vision.

With a robust pipeline of innovative precision therapies advancing at all stages of development.

As Fouad will describe our next wave of clinical programs is progressing rapidly towards multiple proof of concept readouts.

We've been encouraged by widespread interest in our Symphony trial of Blu 945, and we're on track to initiate a phase one trial for Blu 701 in the fourth quarter.

Jeff Albers: Beyond our EGFR franchise, we continue to expect Blue 222, our CDK2 inhibitor, and Blue 852, our Map 4K1 inhibitor, to advance into clinical development next year. And a third area of strength is our current financial position, which, as Mike will describe in more detail, enables us to drive revenue growth across multiple domains, invest in a range of high-value R&D programs, and continue to build a world-class company with integrated global capabilities.

Beyond our Egfr franchise, we continue to expect Blue <unk> to our CDK <unk> inhibitor, and Blu 852, or <unk>, one inhibitor to advance into clinical development next year.

And a third area of strength is our current financial position, which as Mike will describe in more detail enables us to drive revenue growth across multiple domains <unk>.

We invest in a range of high value R&D programs and continue to build a world class company with integrated global capabilities.

Jeff Albers: For some time, we talked about the promise of diverse revenue streams across the strategic pillars of our business. This diversity is now truly coming into view as we're able to increase our full-year revenue guidance based on activity throughout our portfolio, both independently driven and through our strategic collaborations. Combining our prolific scientific platform and commercial execution with the financial and organizational strength to bring in external assets, we're well positioned for Blueprint to be the leading driver of innovation and precision medicine for years to come. With that, I'll turn the call over to Christy to discuss our commercial efforts. Christy?

For some time, we've talked about the promise of diverse revenue streams across the strategic pillars of our business.

This diversity is now truly coming into view.

As we are able to increase our full year revenue guidance based on activity throughout our portfolio.

Both independently driven and through our strategic collaborations.

Combining our prolific scientific platform and commercial execution with the financial and organizational strength to bring in external assets.

We are well positioned for blueprint to be the leading driver of innovation in precision medicine for years to come.

With that I'll turn the call over to Christie to discuss our commercial efforts Christy.

Christy: Thanks, Jeff. Good morning, everyone. Let me start by sharing our third quarter results. Our Avicat net product revenue was $17.3 million. Net end-user sales of Gavretto, as reported by Roche, were 5.5 million for the quarter.

Thanks, Jeff Good morning, everyone.

Let me start by sharing our third quarter results.

Our Ava kit net product revenue was $17 $3 million.

Net end user sales of CAD Red Arrow as reported by Roche for $5 5 million for the quarter.

Christy: As a reminder, the booking of Gavretto's sales shifted to Roche at the beginning of the quarter. Q3 was our first full quarter of the Avicate U.S. launch in advanced systemic mastocytosis, and the positive early trends we have been seeing reinforce our view that SM, across advanced and non-advanced forms of the disease, is the most significant near-term opportunity that we are pursuing at Blueprint Medicine As I reflect on the launch dynamics to date, a key theme that gives me confidence is the breadth, breadth of prescribers, accounts, and patient types.

As a reminder, the booking of <unk> sales shifted to Roche at the beginning of the quarter.

Q3 was our first full quarter of the Ava Kit U S launch and advanced systemic mastocytosis.

And the positive early trends, we have been seeing reinforce our view that SM across advanced and non advanced forms of the disease.

It's the most significant near term opportunity that we are pursuing at blueprint medicine.

As I reflect on the launch dynamics to date, a key theme that gives me confidence is breadth breadth of prescribers accounts and patient types.

Christy: Let's start with the breadth of prescriber and account activity. As I've shared previously, a key focus area for Blueprint has been engaging with SM Centers of Excellence and key accounts where patients are more concentrated. Over the first few months of the launch, our efforts to engage these centers have gained good traction, with approximately two-thirds of them now utilizing aviq commercially.

Let's start with the breadth of prescriber and account activity.

As I've shared previously our key focus area for blueprint has been engaging with SM centers of excellence and key accounts, where patients are more concentrated.

Over the first few months of the launch our efforts to engage these centers have gained good traction with approximately two thirds now utilizing <unk> commercially.

Christy: As we continue to focus here, we also know that many patients are cared for in a community setting, and that prescriber education and patient identification there will be critical to the long-term trajectory of the launch. With that in mind, I'm very encouraged that approximately half of our volume is coming from community prescribers and accounts. Overall, through the end of Q3, we have had more than 100 new prescribers or accounts utilize aviqate for the first time since our approval in Advanced FM.

As we continue to focus here. We also know that many patients are cared for in a community setting and that prescriber education and patient identification there will be critical to the long term trajectory of the launch.

With that in mind I am very encouraged that approximately half of our volume is coming from community prescribers and account.

Overall through the end of Q3, we have had more than 100, new prescribers or accounts utilizing Ava kit for the first time since our approval in advanced SM.

Christy: This prescriber breast will catalyze our ongoing efforts to identify more advanced SM patients and ensure they have access to avicate therapy. We are also seeing breadth of avicate utilization by patients across their advanced SM treatment journey. We continue to see a fairly even mix of patients switching from other therapies and those who have no indication of a prior advanced system therapy. We will gain additional insight into these patient dynamics as we move through the launch, but this early data suggests that Ava Kit is being used among the prevalent pool of diagnosed advanced SM patients, as well as newly diagnosed incident patients. Finally, we are pleased that the demand we are seeing has been supported by strong patient access to therapy and a rapid time to fill prescriptions.

This prescriber breadth will catalyze our ongoing effort to identify and more advanced SM patients and ensure they have access to <unk> therapy.

We are also seeing breadth of Eva kit utilization by patients across their advanced SM treatment journey.

We continue to see a fairly even mix of patients switching from other therapies and those who have no indication of a prior advanced SM therapy.

We will gain additional insight into these patient dynamics as we move through the launch but this early data suggests that <unk> is being used among the prevalent pool of diagnosed advanced SM patients as well as our newly diagnosed incident patients.

Finally, we are pleased that the demand. We are seeing has been supported by strong patient access to therapy in a rapid time to fill prescriptions.

Christy: In total, this combination of increasing prescriber and account for us, new patient starts, and the long durations of therapy we expect based on our clinical trial experience form a foundation for longer-term revenue growth. As we continue to execute on our launch and advanced SM, we are also focused on building our leadership position in SM more broadly. A key priority is increasing disease education and patient identification so that more patients who are suffering from SM can be diagnosed and offered appropriate treatment.

In total this combination of increasing prescriber and account breath, new patient starts and the long durations of therapy, we expect based on our clinical trial experience.

From a foundation for our longer term revenue growth.

As we continue to execute on our launch in advanced SM. We are also focused on building our leadership position in <unk> more broadly.

A key priority is increasing disease education and patient identification, so that more patients who are suffering from SM can be diagnosed and offered appropriate treatment.

Christy: I'm very excited about progress we've made in the third quarter to increase access to testing, which is critical to achieve this goal. We have initiated a partnership with Lab Corps to make highly sensitive blood-based kit D816B testing available for patients across the United States. Testing is now widely available and accessible through our sponsor testing program to qualifying patients where an SM diagnosis is suspected.

I'm very excited about progress we've made in the third quarter to increase access to testing, which is critical to achieving Paul.

We have initiated a partnership with Labcorp to make highly sensitive blood based kit the <unk> testing available for patients across the United States.

Testing is now widely available and accessible through our sponsor testing program to qualifying patients where in SM diagnosis is suspected.

Christy: We anticipate that the widespread availability of testing will help to improve the rate of diagnosis in the U.S. and facilitate improved access to care for patients. Overall, we've taken important steps this quarter towards realizing the potential we see to transform care for SM patients globally. I'm excited about the road ahead as we continue to execute on the U.S. launch and look to planned global launches in AdvancedS.M, the readout of Pioneer next year, and the opportunity for Ava Kid and non-Advanced SM, and, of course, our ongoing development of Blue 263. Let me now turn to Get Brito.

We anticipate that the widespread availability of testing will help to improve the rate of diagnosis in the U S and facilitate improved access to care for patients.

Overall, we've taken important steps this quarter towards realizing the potential we see to transform care for SM patients globally.

I'm excited about the road ahead as we continue to execute on the U S launch and look to planned global launches in advanced SM. The readout of pioneer next year and the opportunity for Ava kit and non advanced SM and of course, our ongoing development of Blu two fixed rate.

Let me now turn to gap right now.

Christy: As we've mentioned, a key strategic rationale for our collaboration with Roche and Genentech was that it enhanced our ability to reach more patients globally. We're excited to begin to see this come to fruition. In the U.S., we continue to focus our efforts on expanding the red inhibitor market through increasing comprehensive and actionable biomarker testing rates at diagnosis. We were pleased with the continued growth we saw during Q3, bolstered by strong momentum coming out of ASCO, where we shared updated data on treatment-naive patients from the Aero Studies. During the third quarter, we also received a positive CHMP opinion for Gavretto in a line agnostic non-small lung cancer setting. An approval in this indication would be a competitive advantage in the EU for Gavretto.

As we've mentioned a key strategic rationale for our collaboration with Roche and Genentech was that an enhanced our ability to reach more patients globally.

We're excited to begin to see this come to fruition.

In the U S. We continue to focus our efforts on expanding the ret inhibitor market through increasing comprehensive and actionable biomarker testing rates of diagnosis.

We were pleased with the continued growth we saw during Q3 bolstered by strong momentum coming out of Atco, where we shared updated data on treatment naive patients from the Arrow study.

During the third quarter. We also received a positive <unk> opinion for Gab, Brito and online agnostic non small cell lung cancer setting.

And approval in this indication would be a competitive advantage in the EU territory forgive Red Arrow.

Fulad: This, combined with the multiple-planned regulatory applications that Roche is pursuing in additional geographies and the ongoing strong launch of Gabretto in China by our partners at Seastone, provides a clear roadmap for global revenue growth. With that, I would now like to turn the call over to Fulad to review our clinical portfolio. Thanks, Christy, and good morning, everyone.

This combined with the multiple planned regulatory application that Roche is pursuing an additional geographies.

And the ongoing strong launch of <unk> in China by our partners at C. Stone provides a clear roadmap for global revenue growth.

With that I would now like to turn the call over to <unk> to review, our clinical portfolio. Thanks, Kristy and good morning, everyone.

Fulad: Earlier this year, I shared the broad R&D vision to position Blueprint Medicines as the world's leading precision therapy company. This included three areas of focus. Therapeutic Area Leadership in Precision, Oncology, and Hematology, with a near-term focus on systemic mastocytosis and one cancer. Innovative drug development, including the creative use of trial designs, translational data, and regulatory strategies to bring our therapies to patients faster, and continuous scientific leadership through the productivity and the expansion of our research platform.

Earlier this year I shared the broad R&D vision to position blueprint medicines as the worlds, leading precision therapy company.

This included three areas of focus.

Computer area leadership in precision oncology and hematology with a near term focus on systemic mastocytosis and one catcher.

Innovative drug development, including the creative use of trial designs conversational data and the regulatory strategies to bring our therapies to patients faster and continuous scientific leadership through the productivity and the expansion of our research platform.

Fulad: I'm excited to update you today on the very good progress that our R&D team has made towards realizing the vision across our portfolio. First, we continue to expand our leadership in systemic mastocytosis through robust execution of our kit programs. For AVEC, our registration-directed pioneer study in non-advanced SM is on track to deliver top-line results in the middle of next year. For Blue 263, our next generation kit inhibitor, the Phase 23 Harbor study, also in non-advanced systemic master status, is now underway.

I'm excited to update you today on the very good progress with our R&D team has made towards realizing the vision of course in our portfolio.

First we continue to expand our leadership in systemic mastocytosis through robust execution of our kit programs for Ava kit. Our registration directed pioneer study in non event for that Sam is on track to deliver topline results in the middle of next year.

For Blu 263, our next generation kit inhibitor phase II three Harbor study.

Also in non advanced systemic mastocytosis is now underway.

Fulad: In the third quarter, we began patient screening in the phase two portion of the study, carrying forward momentum as we wind down pioneer enrollment. As a reminder, Harbor is enrolling a broad population of patients with non-advanced SM, including patients with milder forms of the disease. Combined with the encouraging commercial launch of Avakit in Advanced SM, these studies position us to dramatically improve the standard of care across all forms of systemic master cytosis. Second, we have significantly advanced our clinical program in EGFR positive lung cancer.

In the third quarter, we began patient screening in the phase II portion of this study carrying forward momentum as we wind down pioneer enrollment.

As a reminder, harbor has been running the broad population of patients with nonsense at that time, including patients with milder forms of the disease.

Combined with the encouraging commercial launch of <unk> in advanced SM.

These studies position us to dramatically improve the standard of care across all forms of systemic mastocytosis.

Second we have significantly advanced our clinical program in Egfr positive lung cancer.

Fulad: For Blue 945, patient enrollment in the symphony trial is accelerating with significant and growing demand at multiple clinical sites. As the dose escalation phase of the study is moving rapidly, we are now planning combination expansion with third-generation EGFR inhibitors, such as Ocemercineb, next year. This approach will accelerate and expand our development effort across multiple patient populations. We are also happy to report that we have expanded the trials to a global scope with now a clinical trial agreement in place for Japan. This represents an important milestone towards building a robust trial footprint for our EGFR therapies in Asia.

For Blu 945 patient enrollment in the symphonia triangle is accelerating with significant and growing demand at multiple clinical sites.

As the dose escalation phase of the study is moving rapidly. We are now planning combination expansion with third generation Egfr inhibitors, such as all similar next year.

This approach will accelerate and expand our development effort across multiple patient populations.

We are also happy to report that we expanded the trials of global scope, we'd now in clinical trial agreement in place for Japan.

This represents an important milestone towards building a robust footprint for our Egfr therapies in Asia.

Fulad: For Blue 701, we have submitted an I&D application to the FDA, and we are on track to initiate a phase one-two study in the fourth quarter. Similar to the Symphony study, we plan to explore combination development early in this study, including with Blue 945. Furthermore, pre-clinical data continue to support our clinical development strategy. We have recently completed studies generating compelling data on the potential of a blue 945 and blue 701 combination, which we are submitting for presentation at a scientific meeting in early 2022.

For Blu 701, we have submitted an IND application to the FDA and we are on track to initiate a phase one two study in the fourth quarter.

Similar to the Symphony of study we plan to explore combination development early in this study, including with the balloon line four five.

Furthermore, preclinical data continue to support our clinical development strategy. We have recently completed studies generating compelling data on the potential of our Blue 94, five and Blu 701 combination, which we also have meeting for presentation at a scientific meeting in early 2022.

Fulad: Finally, our early stage research pipeline continues to flourish. In recent months, we have rapidly progressed Blue 222, our selective CDK2 inhibitor. Through IND-D enabling work, we now anticipate it will enter the clinic in the first quarter of 2022, earlier than previously expected. More broadly, we have also nominated multiple undisclosed research programs this year.

Finally, our early stage research pipeline continues to flourish in recent months, we have rapidly progressed blue.

<unk>, our selective CDK <unk> inhibitor.

Through IND, enabling work and we now anticipate it will enter the clinic in the first quarter of 2022 earlier than previously expected.

More broadly we have also nominated multiple undisclosed with research programs this year.

Mike: These include a number of exciting targets with the potential to further extend our scientific leadership in precision oncology and hematology. As these programs progress through discovery research, we look forward to sharing more information on another wave of therapeutic candidates. I would now like to turn it over to Mike to discuss financial updates. Mike. Thanks, Ludd.

These include a number of exciting targets with the potential to further extend our scientific leadership in precision oncology and hematology.

As these programs progress through discovery research, we look forward to sharing more information on another wave of therapeutic candidates.

I would now like to turn it over to Mike to discuss financial updates Mike.

Thanks Rod.

Mike: Earlier this morning, we reported detailed third quarter financial results in our press release. On today's call, I'll touch on a few highlights from the quarter. But first, as we head into the fourth quarter, Blueprint continues to build on our strong financial foundation through a range of revenue sources. In addition to our growing base of global revenues from avocit and get-retto sales, progress across our multiple strategic collaborations is expected to meaningfully contribute to our fourth quarter revenues.

Earlier. This morning, we reported detailed third quarter financial results in our press release.

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

But first as we head into the fourth quarter Blueprint continues to build on our strong Foundation strong financial foundation through a range of revenue sources.

In addition to our growing base of global revenues from Eva kit and get better sales.

Progress across our multiple strategic collaborations is expected to meaningfully contribute to our fourth quarter revenues.

Mike: Based on increased anticipated milestone and other collaboration payments, including the acceleration of potential milestone achievements into the fourth quarter, we are raising our annual revenue guidance for 2021 to between $170 and $180 million. In the third quarter, total revenues were $24.2 million, including 17.3 million of net product revenues from sales of Avicat and $6.9 million in collaboration revenue.

Based on increased anticipated milestone and other collaboration payments, including the acceleration of potential milestone achievements into the fourth quarter. We are raising our annual revenue guidance for 2021 to between 170 and $180 million.

In the third quarter total revenues were $24 $2 million, including $17 3 million of net product revenues from sales of Eva kit.

And $6 9 million in collaboration revenue.

Mike: Collaboration revenue for the quarter was primarily driven by commercial supply shipments to our partners, Seastone and Roche, as well as royalty revenue for sales of Gavretto and Avicat by Seastone and China. As a reminder, U.S. Gavretto sales are now being booked by Roche, with our share of profit or loss appearing on our income statement. Our total operating expenses in the third quarter increased slightly compared to the second quarter of 2021, driven by continued growth in R&D expenses as we bring multiple programs into clinical development.

Collaboration revenue for the quarter was primarily driven by commercial supply shipments to our partners see stone and Roche as.

As well as royalty revenue for sales of <unk> and David Kit <unk> is done in China.

As a reminder, U S. GAAP retro sales are now being booked by Roche with our share of profit or loss, appearing on our income statement.

Our total operating expenses in the third quarter increased slightly compared to the second quarter of 2021, driven by continued growth in R&D expenses as we bring multiple programs into clinical development.

Mike: Over the next few quarters, we anticipate that investment in our promising early-stage programs, as well as our commercial efforts with the ongoing launch of aviacit in Advanced S.M., will continue quarter over quarter operating expense growth. Finally, we ended the third quarter with nearly $1.3 billion in cash on hand, ensuring that we have sufficient resources to invest in our pipeline.

Over the next few quarters, we anticipate that investment in a promising early stage programs as well as our commercial efforts with the ongoing launch of <unk> and advanced SM.

We will continue quarter over quarter operating expense growth.

Finally, we ended the third quarter with nearly $1 3 billion in cash on hand, ensuring that we have sufficient resources to invest in our pipeline.

Mike: Overall, this combination of growing product revenues and progress through our collaborations fortifies our exceptionally strong financial position, allowing us to focus on execution across our portfolio as we enter another transformative period of growth for the company. I would now like to turn the call over to the operator for questions. Operator?

Overall, this combination of growing product revenues and progress through our collaborations fortifies, our exceptionally strong financial position, allowing us to focus on execution across our portfolio as we enter another transformative period of growth for the company.

I would now like to turn the call over to the operator for questions operator.

Yeah.

Operator: At this time, I would like to remind everyone, in order to ask a question, please press the star followed by the number one on your telephone keypad. Please plan to limit yourself to one question. Our first question comes from Selveen Richter from Goldman Sachs. Your line is now open. Hi, everyone.

At this time I would like to remind everyone in order to ask a question. Please press <unk>.

<unk> for the site.

Number one on your telephone keypad, please limit yourself to one question.

Our first question comes from Salvino Victor from Goldman Sachs. Your line is now open.

Andrea: Thanks for taking the question. This is Andrea on behalf of Salvine. Congratulations on the quarter. Christy, there is a question for you. Just wondering if you could speak a bit more about your partnership with Lab Corps and how you expect this to expand the potential addressable population, and then very quickly, if you're seeing any utilization in non-advanced patients at these centers of excellence. Sure, so we're quite excited about the partnership with LabCore.

Hi, everyone. Thanks for taking the question. This is Andrew on for solving and congratulations on the quarter Christy maybe a question for you just wondering if you could speak a bit more on your partnership with Labcorp and how you expect this to expand the potential addressable population and then very quickly if youre seeing any utilization in non advanced patients at the centers of excellence.

Sure.

We're quite excited about the partnership with lab core throughout this year building capability and making highly sensitive blood based kit <unk> testing available in the U S has been a key strategic focus.

Andrea: Throughout this year, building capability and making highly sensitive blood-based kit B1816B testing available in the U.S. has been a key strategic focus of ours. And as I've discussed before, we believe blood-based testing will greatly facilitate access to diagnosis for patients, particularly for non-advanced SM patients where that diagnosis may be suspected.

Bars, and as I've discussed before we believe blood based testing will greatly facilitate access to diagnosis for patients, particularly for non advanced SM patients.

That diagnosis may be suspected and so the partnership with Labcorp Labcorp has this testing available commercially so that in of itself will be very helpful. For prescribers, who use lab core nationally we will have a we have a sponsor testing program that is available where if a patient is suspected of having an SM diagnosis.

Christy: And so the partnership with LabCore; LabCore has this testing available commercially, so that in of itself will be very helpful for, you know, prescribers who use LabCore nationally. We will have a sponsored testing program that is available where if a patient is suspected of having an SM diagnosis, they can receive access to testing through Blueprint. And so we believe that this will reduce the potential barriers and hurdles for patients to access testing and also ensure that if a provider suspects SM, they utilize the appropriate type of testing so that the results that they get can be trusted.

They can receive access to testing through blueprint and so.

We believe that this will reduce the potential barriers and hurdles for patients to access testing and also ensure that if a provider suspects at them. They utilize the appropriate type of testing so that the results that they get can be can be trusted and so we're really excited about this as a as a step forward.

Christy: And so we're really excited about this as a step forward. In terms of utilization of the AVA kit, our best understanding continues to be that, you know, patients who are being prescribed right now are advanced SM patients by and large. We, of course, don't have perfect visibility into everything.

In terms of utilization of Eva kit.

Our best understanding continues to be that patients who are being prescribed right now our advanced SM patients by and large we of course don't have perfect visibility into every patient and as I said before that the diagnosis and subtyping NSM is complex to say the least.

Christy: Every patient, and as I said before, the diagnosis and subtyping in SM is complex, to say the least. But certainly, that's our understanding based on the intelligence we have from speaking to health care providers. Great, thanks so much. Our next question is coming from Reni Benjamin from JNP Security. Your line is now open.

But certainly that that's our understanding based on the intelligence, we have from speaking to your health care providers.

Great. Thanks, so much.

Sure.

Yes.

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

Reni John Benjamin: Hey, thanks guys for taking the questions and congratulations on a great quarter. Can you just give us a breakdown of maybe Jess versus SM in terms of the end kit revenues? And can you just also give us an update on the tapestry study and whether pioneer enrollment is completed? Because I think to meet this deadline, at least by our calculations and the follow-up that's required, I would think enrollment had to be completed in the third quarter, but I'm not too sure I might have. Calculation off here.

Hey, Thanks, guys for taking my questions and congratulations on a great quarter.

Can you just give us a breakdown of maybe just versus <unk> in terms of the Rev.

Revenues.

<unk>.

Can you just also give us an update on on the tapestry study and if pioneer enrollment is completed.

I think to meet this deadline at least by our calculations and the follow up that's required.

I would think enrollment has been completed in the third quarter, but I'm not too sure I might have a calculation on here thanks very much.

Christy: Thanks very much. Yes, Chris, you want you to take the first half, and Becker will take the second half. So in terms of revenue, you know, we obviously did not provide a formal breakdown in terms of indication split, but as you've seen, if you kind of look historically, and as we've discussed, it just has been, I would say, a relatively consistent revenue stream for Blueprint at this point. And so when we look at quarter-on-quarter growth, it's really coming from Advanced S.M. primarily, as well as a But Advanced S.M. is really the key driver if you look at quarter on quarter growth.

Yeah, So Chris do you want to take the first half and Becker take the second half.

So in terms of of revenue.

We obviously did not provide a formal breakdown in terms of indication splits, but as as you've seen if you kind of look historically and as we've discussed just has been I would say relatively consistent revenue stream for for blueprint at this point and so when.

When we look at quarter on quarter growth, it's really coming from advanced SM, primarily as long as a little bit of of international as well, but <unk> is really the key driver if you look on quarter on quarter growth.

Christy: And then with respect to the two trials you mentioned, tapestry, again, we're transitioning to Roche, and there continues to be enthusiastic interest in getting multiple tumor types into this study. With respect to Pioneer, we have, as I mentioned on the last call, The process is to screen patients and make sure that the patients with the right PSS score, severity, and disease are enrolled in the study. We've actually stopped the pre-screening, and so we have filled our screening group of patients, and we're converting those into patients enrolled in the study, and we're looking forward to revealing top-line data in the middle of next year.

And then with respect to the two trials you mentioned tapestry again, we're transitioning to erosion there continues to be enthusiastic.

Interest in getting multiple tumor types in the study with respect to pioneer we have as I mentioned on the last call.

The process is to screen patients and make sure that the patients with the right PFS score severity of disease are enrolled in the study we actually stopped the.

Pre screening and so we filled our screening.

A group of patients and we're converting those into patients enrolled in the study and we're looking forward to reviewing topline data in the middle of next year.

Christy: Thanks for taking the question. I also mentioned that we're taking that momentum, and we're shifting it over to Bluetooth 63. You know, the Harbor trial has an even more extensive site list.

Got it thanks for taking the question.

I also mentioned that we're taking that momentum and we're shifting inevitably to six three.

The Harbor trial has been even more extensive list, we discovered a lot more interest and.

Christy: We discovered a lot more interest and were really enthusiastic about this next-generation kit and head that are moving into the treatment. Great, thank you. Our next question comes from Dane Leon from Raymond James. Please proceed with your question. Hi, thank you for taking the questions. I'll keep it to two for me.

Really enthusiastic about this next generation kit inhibitor moving into.

The treatment.

Great. Thank you.

And our next question comes from Dane Leone from Raymond James. Please proceed with your question.

Alright, Thank you for taking the questions.

I'll keep it to two for me Firstly could you comment at all in terms of that.

Dane Vincent Leone: Firstly, could you comment at all on the progress with the Blue 945, phase one, enrollment, and treatment anecdotal evidence that I think most of those 15 at this point just suggest you're getting a mix of patients that do and do not have a T-790M mutation. So, I'd be curious about your thoughts around the complexion of the patients getting treated in that dose-ascending study and the kind of implications for the evaluation of the therapeutic index and what's going to be effective for those patients with T790M.

With the Blue <unk> five phase, one enrollment and treatment anecdotal evidence that I think most of those 15 at this point does suggest you are getting a mix of patients that do and do not have achieved 790.

Mutation, so I'd be curious about your thoughts around the complexion of the patients getting treated in that dose ascending study in kind of the implications for evaluation of the <unk>.

Therapeutic index, and what's going to be effective for those patients with <unk> hundred 90 <unk>.

Dane Vincent Leone: And then secondly, for me, could you just maybe comment a little bit more in terms of the treatment center utilization around ASM now for those treatment centers that are open? Where do you think the percentage of doctors and patients being treated now that would qualify for Ava-Pritinib are getting the drug, and just some of the hurdles that your team's trying to get over now to increase that utilization rate heading into 2022? Thank you. All right, so Fouad, why don't you take the 945 study question, and Becker can add color as necessary? Thank you, Dean.

And then secondly for me could you.

Just maybe comment a little bit more in terms of the treatment center utilization around ASM now.

For those treatment centers open where do you think the percentage of docs and patients being treated now.

That would qualify for <unk>.

Our getting the drug and just some of the hurdles that your teams.

Trying to get over now to increase that utilization rate.

Heading into 2022, thank you.

Alright, so provide why don't you take the $9 five study question Becker can add color as necessary.

Fulad: For 945 in this... the dose escalation phase, and we have, you know, four months in phase one, we have seen really good momentum. We are also very happy that our use by the investigator of tumor and CT DNA is able to pick up a variety of mutations, TM mutation, CS mutation, double mutation, and triple mutation. All this information, and with the profile of 945, would allow us, you know, in the next months to have a much better understanding of the safety profile and also be able to see detection of clinical signals. We will be sharing data next year on the first part of 945. I think Christi wants to take a breakdown of where we're seeing activity in AFM.

Thank you Dean.

My amplify in this.

The dose escalation phase.

Four months into phase one we have seen really good momentum.

We're also very happy that our used by the investigator of tumor and CPE DNA is able really to pick on.

Royalty of mutation TM mutation cys mutations double mutation and Triple mutation all this information and with the profile of my five would allow us in the next months to have a much better understanding of the safety profile and also be able to see detection of clinical signals, we will be.

Sharing data next year on the first part of 945.

Alright, Christy wanted to take the breakdown of where we're seeing activity in ASM yeah. So.

Christy: Yeah, so I think your question sort of speaks to, I think, what the opportunity is going forward in terms of, you know, additional opportunities at centers as well as beyond that. So, as I said, we're pleased to see that we've had engagement and utilization by two-thirds of sort of the accounts that we consider to be, you know, key accounts and centers of excellence, which is great. But I'm also very happy that we've got a significant amount of utilization coming outside of those accounts in the community. I think there is additional opportunity within key accounts. You know, I think what's interesting about SM is that it is still an immature market in many ways.

And I think your question sort of speak to I think what the opportunity is going forward in terms of additional.

Opportunity at centers as well as beyond that so as I said.

To see that we've had engagement and utilization by two thirds of sort of the accounts that we consider to be key accounts in centers of excellence.

Which is great, but I'm also very happy that we've got a significant.

A significant amount of utilization coming outside of those accounts and the community.

There is additional opportunity within key accounts.

I think what's interesting about <unk> is that it is still an immature market and in many ways and so unlike other diseases, where you may have one specialist at a center that tends to have every patient funnel to that person what we see in advance. This time is that these patients at a center may be seen by multiple providers and so.

Christy: And so unlike other diseases where you may have, you know, one specialist at a center that tends to have every patient funneled to that person, what we see in AdvancedSM is that these patients at a center may be seen by multiple providers. And so one trend that I've been watching and interested to see is that we're starting to see more than one prescriber at a given account utilizing Ava Kidd.

One trend that I've been watching and interested to hear is that we're starting to see more than one prescriber at a given account utilizing ava kit and that deepening within accounts is something that we're going to continue to focus on as we go forward.

Christy: And that deepening within accounts is something that, you know, we're going to continue to focus on as we go forward. But long term, I think the key driver for us of, you know, additional patient identification and growth will also be really getting out into the community where we have that, you know, tail of patients that are presenting. And, again, you know, really happy with what we're seeing. I'm certainly looking forward to, you know, having additional catalysts going forward as our data gets out and we continue to educate and identify more patients there. Thank you. Our next question comes from Mark from Karen. Your line is now open.

But long term I think the key driver for us of additional patient identification and growth will be also really getting out into the community, where we have that tail of patients that are presenting and again really happy with what we're seeing certainly looking forward to having.

Additional catalyst going forward as as our data gets out and we continue to educate and identify more patients there.

Thank you.

Our next question comes from Mark from from Cowen. Your line is now open.

Mark: Thanks for taking my questions and congrats on the quarter. Christy, just to follow up on the last points about physician use and who they are. When you are seeing the use in the community, is that still just with community-based oncologists, or are you seeing some use in, you know, other things like places like allergist offices and things like that that may have broader populations than just ASM within their practice? And then also, to follow up on Dane's question on the different types of patients enrolling in 945, would you expect to ultimately have expansion cohorts that are broader than just Sure, I can start with your first question.

Hi, Thanks for taking my question.

That's on the quarter Christy.

Christi.

Follow up on that.

Last point about <unk>.

Physician use and who they.

Are you seeing the using the community is that.

Just with community based oncologists or are you seeing some use in other places like Allergist's office.

Like that that may have broader population to adjust ASM within their practice.

Christy: So in terms of the mix of prescriber types that we're seeing, the vast majority of utilization right now is coming from hematology, whether that's at a center of excellence or in the community. We have seen some utilization by allergy. I think what's important to keep in mind is that allergies play a role in the management of advanced thromboembolic disorders in some patients and certainly are a critical point in the pathway to diagnosis for many of these patients, and will often be involved in co-managing patients with hematomies.

Christy: And so we've seen some utilization coming from allergy, but again, the vast majority coming from hematology. And for your second question, Mark, for 945, our triple-m mutant agent covers, you know, the drivers, but also T-790M and C-797-S. The way the Symphony Phase 1 trial was designed was to expand to all subgroups of mutations.

The way the Symphony Phase one trial is designed is to expand in all subgroups of mutation. So it will be expanding in triple mutations will be expanding also in C. S double mutation and in TM double mutation. So it will have really a very good understanding across the broad spectrum of these combinations of mutations.

Fulad: So we'll be expanding in triple mutations; we'll also be expanding in CS double mutations and in TM double mutations. So we'll have really a very good understanding across the broad spectrum of these combinations of mutations. I just wanted to add one thing. The 945 compound is optimized to hit the triple mutation, but it is a compound with a really large winded, wild type.

I just wanted to add one thing.

The nonprofit compound is optimized to hit the triple mutation, but it is a compound with a really large wind at a wild type. So we expect extraordinary safety.

Becker Hewes: So we expect extraordinary safety. That really plays into our plan to combine these molecules and move to earlier lines of therapy. And we're really open to all levels of activity for this compound, just given how safe we expect it to be. Okay, thanks, very helpful. Our next question comes from Andrew Behrens from SVB. Lee Rink. Your line is now open.

That really plays into our plan to combine these molecules and move to earlier lines of therapy.

And we're really open to all levels of activity for this compound just given how how safe we expect it to be.

Okay. Thanks very helpful.

Our next question comes from Andrew Barron from SBB Leerink. Your line is now open.

Andrew Scott Berens: Thanks. Let me also have my congratulations on the advocate execution this quarter. Just a few for me.

Let me also add my congratulations.

Execution this quarter.

Just a few for me I'm trying to get a sense of how excited we should be about these results.

Christy: I'm trying to get a sense for how excited we should be about these results being sustainable. For example, were there a meaningful percentage of patients using abacit this quarter from the expanded access program? Do you guys have any color on how many lines of therapy they've seen previously on the average or how long the patients have been diagnosed? And then, on the Good Letter for Christie, I didn't hear you give a percentage of new patient starts like in previous quarters and just wanted to see if I had missed that.

Annabelle.

Was there a meaningful percentage of patients.

Using a big hit this quarter from the expanded access program.

You guys have any color on how many lines of therapy.

They had been previously on the average or how long patients have been diagnosed.

And then a question and good router for Christie I didn't hear you give a percentage of new patient starts like in prior quarters and I just wanted to see if I had missed that and I'm wondering why the 40% you saw in Q2 and the 25% in Q1.

Christy: And again, wondering why the 40% you saw in Q2 and the 25% in Q1 doesn't seem to be translating to revenues. Really, just the rep market is not that large. So I think all of those are for me. So happy to start with the SM color.

Can be translated through revenues is it really just the rep market is not that large.

So I think I'll go over for me.

Let me just start with that that would be some color. So in terms of patient dynamics in the quarter.

Christy: So in terms of, you know, patient dynamics in the quarter, we did have some patients who were on access programs prior, but it's the minority, certainly, of the patients that we saw coming on to aviakit through the quarter. I think your question sort of speaks a little bit to you about this Ebola.

We did have some patients who were on access programs. Prior is the minority certainly of the patients that we saw coming onto <unk> through the quarter I think your patient your question so to speak a little bit too.

Christy: And, you know, I think what we've seen, certainly, is that there were patients who, you know, know, we're frankly waiting for aviate approval. There was a lot of excitement from the centers that, you know, know the aviqa kit well and have experience waiting for the drugs to become available commercially. So certainly, you know, we're pleased that we were able to pull those patients on and offer them treatment upon approval. But what we now see and what I think will be sort of offsetting that and continuing to drive growth is the rate of new prescribers and accounts that continue to come on board. And so, you know, I'm really excited.

And I think what we've seen certainly is that there were patients too.

We're frankly waiting for approval there was a lot of excitement from the centers that you now know Eva kit, well and have experienced waiting for the jersey become available commercially. So certainly we're pleased that we were able to pull those patients on alpha them treatment. Upon approval, what we now see and what I think will be sort of offsetting that and continuing to do.

Drive growth.

Is the.

The rate of new prescribers and accounts that continue to come onboard and so I'm really excited about just the breath again of prescribing I see that as a critical indicator of long term growth potential and pleased to see that we've continued to really add new prescribers and accounts.

Christy: About just the breadth, again, of prescribing. I see that as a critical indicator of long-term growth potential. And, you know, pleased to see that we've continued to really add new prescribers in accounts at a very steady rate as we've moved through the quarter. In terms of lines of therapy, as I said, our best data right now suggests that we're seeing a pretty even split in terms of patients who have been on a prior therapy versus those who say that they do not have any indication of a prior therapy. Our visibility into that right now is limited.

A very steady clip as they can Mr hu through the quarter.

Of lines of therapy as I said, our best data right now suggests that we're seeing a pretty even split in terms of patients who've been on prior therapy versus those who say that they do not have indication of a prior therapy or visibility into that right. Now is limited and as we start to CRM patients through claims data, we will have a better sense frankly.

Christy: And as we start to see our own patients through claims data, we'll have a better sense, frankly, of exactly what we think that mix looks like. And so I would say that we'll gain insight into that as we continue to move toward the launch. In terms of Gavretto, you know, the question about sort of how do we think about new starts and then, you know, kind of moving through to revenue.

Of of exactly what we think that mix looks like and so I would say that well gain insight to that as we as we continue to move through the launch.

In terms of <unk>.

The question about sort of how do we think about new starts and then and then kind of moving through to revenue. So.

Christy: So, you know, with the transition to Genentech, our level of sort of individual patient visibility is simply different. They have a different distribution model than we do, and so really, we're looking at prescriber level demands now as kind of the best indicator of growth and had our strongest quarter to date, essentially, in Q3. And so we're excited about that.

With the transition to Gen manpack, our level of sort of individual patient visibility is simply different they have a different distribution model than we do and so really we're looking at prescriber level demands now is kind of the best indicator of growth and had our strongest quarter.

Today, it essentially in Q3, and so we're excited about that.

And that speaks to I think the ongoing growth of the market, which we're seeing across both blueprint and Lilly.

Christy: And that, you know, speaks to, I think, the ongoing growth of the market, which we're seeing across both Blueprint and Lilly. It will take time, as I've said before, between, you know, new products, new patients starting or transitioning into revenue. You know, new share is a leading indicator of total share, which then will translate into revenue over time.

It will take time as I said before between new product, new patient starts or translation transitioning into revenue.

Sure.

Christy: And, of course, you know, our quarter-on-quarter revenue growth continues to be really strong. Okay, thank you. Our next question comes from Avatar Jones from Morgan Stanley. Your line is now open. Thank you for taking my question. Many have already been answered, but I will have one question on advocates.

<unk> is a leading indicator of total chair, which then will translate into revenue over time and of course, you know our quarter on quarter revenue growth continues to be really strong.

Okay. Thank you.

Our next question comes from Avatar James from Morgan Stanley. Your line is now open.

Thank you for taking my questions. Many have been answered, but I had one question on Eva kit.

Avatar Jones: Do you have any visibility into the average duration of therapy to date? And moving forward, how do you suspect this will evolve? Sure, so duration of therapy is one of the aspects of, you know, the advocate opportunity in Advanced System that I think is most exciting and certainly will be a critical driver of growth, particularly as we get further into the launch and, you know, can see patients, you know, sort of accumulating because they can stay on therapy.

Do you have any visibility into the average duration of therapy to date and moving forward. How would you suspect this will evolve. Thank you.

Sure. So in duration of therapy is is one of the aspects of the <unk> opportunity in advanced I found that I think is most exciting and certainly will be a critical driver of growth, particularly as we get further into the launch and you know can see patients.

Sort of accumulating because they can stay on therapy. I also think it's exciting because we have the potential I think to really impact.

Avatar Jones: I also think it's exciting because, you know, we have the potential, I think, to really impact how long patients are living well with Advanced Thesson, which I think is a really exciting clinical opportunity. At this point in the launch, it is just, it's too early to really have any meaningful insight into duration of therapy, right? We're a couple, you know, a few months into the market at this point.

How long patients are living well with a desk with them, which I think is a really exciting clinical opportunity at this point in the launch and it's just it's too early to really have any meaningful insight into duration of therapy right, where a couple of you know a few months onto the market at this point certainly our clinical data suggest that patients may be on for years and so you know I think we'll have better.

Christy: Certainly, our clinical data suggests that patients may be on for years. And so, you know, I think we'll have better insight as we go through the next year or two to really understand what we're seeing in terms of what that looks like. Okay, thank you. Our next question comes from Linda Lee from Canacord. Your line is now open. Please proceed with your question. Hi guys, congratulations on the quarter end along.

Right as we go through over the next you know year to to really understand what we're seeing in terms of what that looks like.

Okay. Thank you.

Our next question comes from Arlinda Lee from Canaccord. Your line is now open. Please proceed with your question.

Hi, guys, congratulations on the quarter and a lunch.

Philina Lee: I had maybe an additional follow-up on additional color that you might be able to provide on the breakdown of newly diagnosed patients versus those that were already known. And if you could maybe talk a little bit about the turn-around time for the lab core test and what kinds of, you said that it would be available to patients that were eligible to provide additional information on who might be an available safe. Sure, so again, in terms of the split of patients that we're seeing, right now, we're really relying on the feedback we hear from patients and prescribers directly, which is how we understand that mix of, you know, about half saying they do not have prior therapy versus half, you know, saying they come from a variety of other therapies that are being used. No indication of prior therapy does not necessarily mean that they're newly diagnosed.

I had a maybe an additional follow up on.

Additional color that you might be able to provide on the breakdown of newly diagnosed patients.

Versus those that were already known and if you can maybe talk a little bit about the turnaround time for the lab core tests and what kinds of you said that it would be available to patients that were eligible could you provide additional information on who might be available.

Sure. So again in terms of the split of patients that we're seeing right now we're really relying on the feedback we hear from patients and prescribers directly which is how we understand that mix of you know about half, saying they did not have prior therapy versus half you know think coming from a variety of of.

Other therapies that are being used.

One indication of prior therapy does not necessarily mean that they're newly diagnosed and so we will continue to gain insight to that as I said as we start to you know kind of thing.

Christy: And so we will, you know, continue to gain insight into that, as I said, as we start to, you know, kind of see claims data and other sources that will help inform our understanding. You know, our expectation, certainly, is that as we move through the launch, we will shift from being utilized primarily by patients who are already diagnosed to newly diagnosed incident patients. And so that's a dynamic I would anticipate we will see.

He claims data and other sources that will help inform our understanding of XP.

Expectation certainly is that as we move through the launch we will shift from.

Being utilized primarily in prevalent patients who are already diagnosed to newly diagnosed incident incident patients and so that's a dynamic I would anticipate we will see but again, it's just too early to really know.

Christy: But, again, it's just too early to really know what we're seeing. In terms of the lab core test, the turnaround time is fairly quick. I believe it's something on the order of, you know, less than a week.

What we're seeing in terms of the lab core task. The turnaround time is is fairly quick I believe it's something on the order of less than a week and the eligibility criteria essentially we ask physicians to.

Christy: And the eligibility criteria, essentially, we ask physicians to fill out a form where they have to specify one or two of a couple of different symptoms that are often hallmarks of a potential SM diagnosis. So essentially, what we're looking for is suspicion, clinical suspicion of SM in order to be eligible for the test. Great, thank you, and congratulations to Dems. The next question comes from Michael Schmidt from Guggenheim. Your line is now open. Please go ahead. Hi, this is Paul on behalf of Michael.

Fill out a form or they have to specify.

One or two of a couple of different symptoms.

Symptoms that often hallmarks of a potential SM diagnosis, so essentially what we're looking for a suspicion clinical suspicion of S. M.

In order to be eligible for the death.

Great. Thank you and congratulations again.

The next question comes from Michael Schmidt from Guggenheim. Your line is now open. Please go ahead.

Hi, This is Paul on for Michael Thanks for taking our question just one from us on the CDK program.

Paul: Thanks for taking our question. Just one from us on the CDK2 program. Can you provide your thoughts on how 2-2 potentially compares to other CDK2 coaches in development? For instance, molecular glue and triple-un edition of CDK-24 and 6 are being explored. I'm just hoping to see your early read there on the landscape. So if you want, maybe Becker can add color if needed.

Can you provide your thoughts on how Q2 to potentially compares with other CDK two approaches in development for instance, like losing Triple inhibition is getting hit 2.6 are being explored just hoping to see your early beat there on bundled landscape.

Once you started maybe becker can add color if needed.

Fulad: Thank you. Our CDK2 inhibitor that is answering the clinic early next year, as I mentioned earlier, is a selective one. It has been developed as a validated target, a regulatory partner of CCNE1, with particular selectivity over CDK1, CDK4, CDK6, and others. This allows our CDK2 inhibitor to be selective, leading to efficacy and potentially very favorable safety.

<unk>.

Our CDK <unk> inhibitor that.

Entering the clinic early next year as I mentioned earlier.

Selected one it has been <unk> as a validated targets every collutory partner, obviously see any one.

Particular selectivity over CDK, one CDK four CDK six on the others.

Along with our CDK <unk> inhibitor to be selective leading to efficacy and potentially in Gerry.

Fulad: When you look at the entire landscape, one of the challenges the landscape faces in developing CDK2 inhibitors is selectivity not only over CDK1, but also over CDK6. So we do believe that our CDK2, with its very selective profile, is also a very good partner for combination with CDK4-6s. We believe the strategy of developing a selective sole CDK2 inhibitor is a good strategy that gives us the ability to combine different doses with CDK

A favorable safety profile.

When you look at the entire landscape one of the challenges that landscape faces in developing CDK inhibitor.

Its selectivity over CDK one.

So over CDK six so.

We do believe that our CDK to wood.

Selective profile is also a very good partner for combination with CDK. Four six is we really have this strategy of developing a selective so CDK <unk> inhibitor is good.

Good strategy that gives us the ability to combine a different doses with CDK for success.

Fulad: Our development strategy targets two major areas. CC&E-driven cancers, where we believe that tumors are addicted to the pathway; ovarian cancer, and rheumaterial cancer, where CDK2 would be developed, in combination with standard of care and disease. The other part of the development of CDK2 will focus on the emerging issue of resistance to CDK4s in breast cancer. We know today that CCNU1 over expression is behind the resistance to CDK-4-6 in breast cancer.

Development strategy targets two major area.

<unk>, driven cancers, and where we believe the tumors addicted to the pathway ovarian cancer endometrial cancer CDK to would be demo.

In combination with standard of care in their diseases.

The other part of the development of CDK to we focus on the emerging issue of resistance to CDK four system in breast cancer.

We know today that you see anyone over expression is behind the resistance to CDK four six in breast cancer. So we wouldn't be looking to really contribute to reverse this resistance.

Fulad: So we'd be looking to really contribute to reverse this resistance, not only in the late stage by combining CDK-4-6 in breast cancer but also in the early stage. Okay, thank you. Our next question comes from Joel B2 from Bird. Your line is now open.

The late stage by combining CDK four six in breast cancer, but also in the early stage.

Great. Thank you.

Okay.

Our next question comes from Joe <unk> from Baird. Your line is now open.

Joel Lawrence Beatty: Hello, this is Benjamin Pallumper, Joel. I have two questions for you, one on Ava Kid and one on the pipeline. As far as Avaacid, do you get a sense, I'm not sure if I missed it or not, but the number of repeat descriptions. And then on the pipeline, I'm just curious if you could maybe put in the context of the relative risk of the different plan initiations for 701, 222, and 8.5D.C.1 is more highly risky or less risky than the others. Thank you. Sure, so good, this is Christy. I can take the first one on a repeat prescription.

Hello, This is Andrew on for Joel.

Two questions for US one on <unk> and then one on the pipeline as far as <unk>, because you have a sense I'm not sure if I missed it or not but the number of repeat.

Prescriptions.

And then on the pipeline I'm just curious if you could maybe put in put in context, the relative risk of the different.

Planned initiatives for 701 <unk> two <unk> one is more highly risky you are less risky than the others. Thank you.

Sure.

Christy I can take the first one on repeat prescriptions so again.

Christy: So, again, we're, you know, early on in the launch, and we've seen nothing that would be any different than what we would expect, which is in terms of, you know, we expect patients will be refilling. Certainly, we do know that often if patients are going to find their right dose, that is the dynamic that happens early on, and so dose modifications, et cetera, tend to occur in the first few months. Our strategy around flat pricing, et cetera, really mitigates a lot of the impact that we would expect to see from that. But that's, you know, a trend we will continue to watch.

Early on in the launch we have seen nothing that would be any different than what we would expect switches in terms of it. We expect patients will be will be refilling certainly we do know that often if patients are going to find the right dose that is the dynamic that happens early on and so dose modifications et cetera tend to be occurring in the first few months.

Our strategy around flat pricing et cetera.

Really mitigates a lot of the impact that we would expect to see from that but that's a trend we'll continue to watch, but so far we're seeing everything essentially in line with what we would expect.

Christy: But so far, we're seeing, you know, everything essentially in line with what we would expect. Sure, then in terms of the relative risk, maybe I'll have you start, but yeah, I think it's a question we look at all of our programs in terms of going after known oncogenic drivers of disease where there should be a higher probability of success in cases where we can get to clinical proof of concept as quickly as possible remains a hallmark of our portfolio selection priority or process. We do always take into account, though, the size of the opportunity or the relative opportunity. So right before you enter the clinic, it's almost an impossible exercise, but who cares?

Sure and then in terms of the relative risk maybe a fool I don't have you start but I think it's a question we look at all of our programs in terms of.

Going after known oncogenic drivers of disease.

Where there should be a higher probably of success.

Pieces, where we can get to clinical proof of concept as quickly.

Possible remains a hallmark of our portfolio selection priority.

Process, we do always taken into account as well, although the size of the opportunity as the relative opportunity. So.

Yes.

Great before you enter the clinic, it's almost impossible exercise, but foulard tab.

Pam.

The only thing I would add Jeff.

Jeff Albers: The only thing I would add, Jeff, to your answer is Blueprint, the leading precision medicine company, has really, you know, one of the strongest expertise in rationally designing molecules that are selective against targets that we would like to use as treatment. To Jeff's point, these targets are well validated and are important for the treatment of cancer. It's now taken the blueprint to the next level of targets with a broader scope of the opportunity.

To your answer is blue blueprint, leading precision medicine company.

Really one of the strongest expertise in rationally designing molecules that are selective.

Against the targets that we would like to.

To use his treatment.

To Jeff's point these targets, whether validated and are important for the treatment of cancer.

It's now taken blueprint to a next level of targets with a broader scope of the opportunity. What do you think about it from an egfr mutated lung cancer or breast cancer resistance of CDK four as an example for CDK to all.

Jeff Albers: Whether you think about it from the EGFR mutated Lyme cancer or breast cancer resistant to CDK as an example for CDK2, obviously, these studies are either in phase one or entering phase one clinical trials in the next weeks or months.

Obviously these studies are either in phase one or entering the phase one clinical trials in the next weeks or months. So we will have more information to determine really the profile of these agents.

Fulad: So we would have more information to determine the profile of these patients. But I think with the responder hypothesis as a part of the development, with selectivity, with windows of therapy, or wood therapeutic indexes in the development of this compound, I'm confident that we will run these compounds very efficiently, and the data will tell us when we see it from phase one. Maybe I'll circle back.

Think with responder hypothesis.

Part of the development, we've seen activity with windows.

Or would therapeutic indexes in the development of this compound.

Confident that we will.

This compound is very efficiently and the data will tell us what what.

When we see it from the phase one.

Maybe I'll circle back it's interesting Kate Haviland, our chief operating officer, often talks about the idea that how.

Jeff Albers: It's interesting. Kate Havlin, our chief operating officer, often talks about the idea of how we get better with subsequent programs over our first wave of programs, and it has always been a cornerstone of our strategy to develop molecules that can be combined with other effective therapies if we really want to change the course of disease. And so, as Becker noted earlier on 945, that was part of the target product profile, that to reach the full potential, it was to focus on that the window over wild type so that you could see various combinations, expanding the opportunity over time.

How do we get better with subsequent programs over our first wave of programs and it has always been a cornerstone of our strategy to develop molecules that can be combined with other effective therapies. If we really wanted to change that.

Course of disease, and so as Becker noted earlier 94 five.

It was part of the target product profile that to reach the full potential was to focus on that that the window over wild type. So that you could see various combinations expanding the opportunity over time, Similarly, I would say.

Jeff Albers: Similarly, I'd say that's true for Blue 222, our CDK2 program, that we will certainly be looking for single agent activity, but the true opportunity comes in how you combine them over time. And so that selectivity that Fulaw talked about with respect to Blue 2212 is really critical to what we hope to see as we move into the clinic.

That's true for Bluetooth to our CDK to program that.

We will certainly be looking for single agent activity, but the true opportunity comes in how do you combine.

Over time, and so that sort of activity that <unk> talked about with respect to Blue 222 is really critical to what we hope to see.

We move into <unk> into the clinic.

Peter Richard Lawson: Thank you so much for those insights. The next question comes from Peter Lawson from Barclays. Your line is now open.

Got it. Thank you so much for those.

The next question comes from Peter Lawson from Barclays. Your line is now open.

Peter Richard Lawson: Great, thanks so much for seeing the question. Just kind of thinking about the gist and the AFM revenues underlying this. Is there any way, or would you kind of break out those revenues at any point, or would you kind of break out when GIST, or rather, ASM, kind of exceeds the GIST revenues? Just, just your thoughts there and if that happened this quarter.

Great. Thanks, so much for taking the question.

Just kind of thinking about the just the NSM revenues underlying this is there any way.

Is there any point, where you break out those revenues and.

Or would you kind of break out win.

Yes.

Robert Sam kind of exceeds the just revenues just just your thoughts there if that happen this quarter and then the second question for Mike just on the breakup fee.

Mike: And then the second question for Mike, just sort of break out of the guidance, you know, how much is that milestone driven? Should we think about the milestone number is, you know, 75 million or a 50 million dollar number? Thank you. Maybe I'll start.

Guidance, how much of that milestone driven.

Should we think about it most of that number is.

75 million or $50 million.

Thank you.

So maybe I'll start.

Jeff Albers: We don't have perfect visibility into every patient, so the effort of trying to break out exactly where each of them sits will probably be difficult, so I don't think it'll be a focus. I mean, based on the data we see, as Christy has already highlighted, the growth is clearly coming from ASM, but exactly where that line is. I don't think we have that degree of detail, and then maybe Mike you. Yeah, so just a little bit.

We don't have perfect visibility into every patient so the the effort of trying to break out exactly where each of them fits.

We'll probably be difficult.

I don't think it'll be a focus I think based on the data we see that as Christine has already highlighted the growth is clearly coming from ASM.

Exactly where that line is.

I don't think we have that degree of detail and then maybe Mike you.

Mike: more color on the revenue guidance. I think maybe backtracking a little bit, like early in the year we guided to the fact that we might have $80 million in potential milestone payments. What we've seen, we've recognized a little bit of that today, but what we've seen is primarily a lot of potential milestones are now concentrated in Q4. And that also includes the acceleration of potential milestones that were originally, I'd say, forecast for 2022.

So just a little bit more color on the revenue guidance I think maybe backtracking a little bit like early in the year, we guided to the fact that we might have $80 million in potential milestone payments, what we've seen we've recognized a little bit of that today, but what we've seen is primarily a lot of potential milestones are now concentrating in Q4 and that also includes the <unk>.

<unk> of potential milestones that were originally forecast for 2022, so as those come together and come to fruition in Q4, the bulk of the revenue guidance range that we're seeing is driven by milestone revenue that we anticipated as well as other other collaboration payments supply payments and royalty payments.

Mike: So as those come together and come to fruition in Q4, the bulk of the revenue guidance raise that we're seeing is driven by milestone revenue that we anticipate as well as other collaboration payments, supply payments, and royalty payments. Yeah, and maybe I'll add to that.

And maybe I'll add I mean thats.

Think that the overall under appreciated aspect of.

Jeff Albers: I think that's an overall underappreciated aspect of our current position is that we've always focused on retaining meaningful commercial rights and bringing therapies to patients on our own. But we also have looked at collaborations as an opportunity to either accelerate or expand our reach. And the breadth of collaborations we now have in place is truly differentiating our revenue streams. What's in exactly quarter over quarter, maybe a little lumpier than revenue growth, end user revenue growth, but we're seeing a mix of milestone payments, royalties, and other payments from partners that is going to continue on as we go forward.

<unk>.

Our current position is that we've always focused on retaining meaningful commercial REIT and bringing therapies to patients patients on our own but we also have looked at collaborations as an opportunity to either accelerate or expand our reach and the breadth of collaborations we now have.

In place is is it truly.

Truly differentiating our revenue streams at what then exactly quarter over quarter, maybe a little lumpier than revenue growth.

Our user revenue growth, but we're seeing a mix of milestone payments royalties.

Another.

Payments from partners that is going to continue on as we go forward. So.

Jeff Albers: So I would say from my seat, I don't really care where the revenue comes from; it's meaningful, and it allows us to continue to invest in our research platform, which is the way we're going to drive long-term shareholder value. Thank you. Just a follow-up on Chris's comments about ASM. Are the majority of patients going to come from the heen or the allergy side for ASM? Yeah. Advanced systems certainly will be a majority hematologists, because, you know, that's the specialty that tends to primarily manage. As I said, allergies certainly can be involved.

I would say is in my seat.

I don't really care, where the revenue comes from it's meaningful and it allows us to continue to invest in our research platform, which is the way we're going to drive long term shareholder value.

Could you just.

Just a follow up.

Scott.

But the majority of patients going to come from the heme unless you sell it for is it.

Eventually.

One advanced SM, certainly will be majority hematologists that.

The specialty that tends to primarily manage as I said allergy certainly can be involve some times. They are involved in co management, but we expect hematology to continue to be the primary driver for advanced SM.

Christy: Sometimes they're involved in co-management, but we expect hemetology to continue to be the primary driver for advanced systems. Brilliant, okay, thanks so much. Our next question comes from David Nearingarten from Wedbush. Your line is now open. Hey, thanks for taking a question. I'll skip any commercial questions.

Okay. Thanks, so much.

Our next question comes from David Mann gotten from Wedbush. Your line is now open.

Hey, Thanks for taking the question I'll skip any commercial questions that often.

David Neil Lebowitz: They both have been beaten to death. On the pipeline for 701 and 945, maybe if you could help us out with the ultimate goal, is it to have a combination therapy with 701 and 945 in that setting? And, you know, say, second line mutated, you know, UTFR mutated lung cancer. And then, you know, if that's the ultimate goal, what do we need to see from these single agent studies to accelerate your entry into the clinic with a combo? Thank you, David.

The death.

On the pipeline for 701 and 94 five maybe if you could help us out with the ultimate goal is it to have a combination therapy with southern water.

Byron.

In that setting in second line.

David.

CFR mutated lung cancer.

And then.

If that's the ultimate goal, what do we need to see some mid single agent studies too.

Accelerate your entry into the clinic with the combo.

Thank you David.

Fulad: 945 and 701, our fourth agent of EGFR, a fourth generation EGFR agent, have been developed with combination in mind and have been designed with combination in mind. So very quickly, 945, as Becker mentioned earlier, has one of the widest selectivity profiles over wide type EGFR. And that allows this compound not only to be developed as the same agent but also to be developed in combination with other agents. As I mentioned earlier, it will be started next year in combination with third-generation EGFR and 945.

Nine for five and 701, our footage of Egfr.

For generation Egfr agents have been developed with combination in mind have been designed with the combination in mind. So very quickly and 94 five as Becker mentioned earlier has one of the widest selectivity profiles over wild type Egfr and.

And that's what allows this compound not only to be developed for the same reason, but also to be developed in combination with other agents as I mentioned earlier, we will be starting next year combination with third generation Egfr is a nine profile.

Fulad: 7-1 has also been developed as a single agent, highly potent on CS mutations and on driver mutations, more importantly, highly brain-penetrant, but also developed towards combinations with other agents. So for the on-target combination strategy, we would like to see each agent developed as a single agent and in combination in the late stage, but our ultimate goal is to move these two agents together to the frontline treatment of each agent in GFR positive lung cancer

701 has been also demo.

As a single agent is highly potent.

<unk> mutation on driver mutations more importantly, highly brain penetrant, but also develop towards combinations with other agents. So for the on target combination strategy, we would like to see each agent developed as a single and in combination in the late stage, but our ultimate goal is to move.

These two agents together to the frontline treatment of Egfr positive non small cell.

Lung cancer, and that's because of the profile of both agents the potential synergy and combinability.

Fulad: And that's because of the profile of both agents, the potential synergy and combinability in terms of being able to replace and do better than standard of care. We will also be looking, in addition to the combination of 701 when it's ready at 945, to combine with other agents. I talked about DGF FART third generations, such as OC MERDNN, but we will also be looking at combinations with off-target agents just given the profile and the selectivity of these compounds. Off-target agents can include a variety of things.

In terms of being able to displace and do better than standard of care. We will also be looking in addition to the combination of 701, when it's ready in line four five.

The combination with other agents I talked about Egfr third generation, such as long simmering, but we would also be looking at combination with targeted agents just given the profile and the selectivity of these compounds off target agents can include a variety of things could.

Fulad: It could be a med inhibitor, could be res, could be chemotherapy, and others. I do believe that these four-generation agents developed together could become transformational in the treatment of EGFR mutant, non-smouse lung cancer. Thanks, and maybe just a quick follow-up on the, you know, other potentially off-target agents. You know, again, I guess I'm curious how far you might look into those before, you know, again, focusing on 945-701, or is it going to be, you know, just a broader basket study and open to, you know, just interpreting the results as they come. Thanks. So this is Becker.

Could be met inhibitor could be <unk> could be chemotherapy and havas.

Do believe that this full generation agents developed together could become transformational in the treatment of Egfr mutant non small cell lung cancer.

Thanks, and maybe just a quick follow up on the other potentially off target.

Again, I guess I'm curious.

<unk> you might look into those before again focusing on.

900, <unk> 701 or is it going to be just a bra.

<unk> basket study and open to just interpreting the results.

Thanks.

Sure. So this is becker and I'll take that with respect to combining with.

Becker Hewes: I'll take that. With respect to combining with agents that have other mechanisms of action and address resistance or potential resistance from other targets, such as Matt or RAS inhibitors, initially, we need to get the tolerability and dosing information for our single agents, but I don't see it as a sequential development. We tend to do these things in parallel.

<unk> agents that have other mechanisms of action and address resistance or a.

Potential resistance from are there targets such as not a RAF inhibitors.

Initially we need to get the Tolerability and dosing information for a single agent, but I don't see it as a sequential development. We tend to do these things in parallel we're quickly adding combinations to our ongoing studies and.

Becker Hewes: We're quickly adding combinations to our ongoing studies, and we will let the pre-clinical data guide us to an extent, but emerging data on resistance and trying to get in front of resistance is really where we're going with this program in a broad fashion. Got it, thanks. Our final question for today comes from Brad Canino from Stiffel. Your line is now open.

Well, let the preclinical data guidance to an extent, but emerging data on resistance and trying to get in front of resistance is really where we're going with this program in a broad fashion.

Got it thanks.

Our final question for today comes from Brad <unk> from Stifel. Your line is now open.

Bradley Patrick Canino: Great, thanks for fitting me in and for the great launch execution here. I mean, just one more from me on the EGFR trial. And again, specifically in that cohort that's T790M, but not C797S, it looks like, per the protocol, they're going to go first gen to Aussie to 945.

Great. Thanks for fitting me in and been great launch execution here.

One more from me on the Egfr trial, and again, specifically on that cohort. The two 790, <unk>, but not see 790 <unk>. It looks like per the protocol Theyre going to go first Gen to Aussie to 94, five and like we talked about previously on the call likely cancer. There is driven by something other than <unk> 790 <unk> like.

Bradley Patrick Canino: And like we talked about previously on the call, the likely cancer there is driven by something other than T790M, like Matt. So are you expecting to see and should we be looking for monotherapy 945? efficacy in this specific cohort because you've been talking about the higher therapeutic window and wild types bearing, or is this really the focus safety in this cohort? Thank you. This is Becker.

So are you expecting to see and should we be looking for monotherapy <unk> 945 efficacy in this specific cohort because <unk> been talking about the higher therapeutic window and wild type sparing or is this really the focus safety on this cohort.

Good morning.

This is becker.

Becker Hewes: I mean, obviously, phase 160 is the initial focus and the main focus of this study. However, just a reminder, 945 will strongly inhibit any protein that has the T790M mutation on it. We are trying to understand better the heterogeneity of this cancer. There are patients where we believe that the EGFR mutations or the EGFR proteins are still the primary driver, and the more we look, the more patients that seem to be the case.

I mean, obviously in phase one safety is the initial focus and the main focus of this study. However, just a reminder, 945 will inhibit very strongly any any protein that has 3700 90 <unk> mutation on it.

We are trying to understand better the heterogeneity of this cancer.

There are patients, where we believe that there is the egfr mutations or the Egfr protein is still the primary driver and the more we look the more patients that seems to be the case.

Becker Hewes: There are other patients where it's more heterogeneous, and you have multiple populations of cells or even multiple drivers within a single cell. And so as we understand the biology, we'll have a better sense of where to expect single-cell age and activity.

Other patients, where it's more heterogeneous and you have multiple populations of cells or even multiple drivers within a single cell and so as we understand the biology, we'll have a better sense of where to expect single agent activity. So that's an emerging story that will.

Becker Hewes: So that's an emerging story that we'll speak to later when we have more data. Thank you. All right. Thank you, Operator, and thanks to all of you for taking the time to join us today and for your continued support of Blueprint Medicines. And we look forward to updating you again soon and hope you all stay well. Goodbye. Ladies and gentlemen, this concludes today's call. Thank you for joining us. You may now disconnect your lines.

I'll speak to later, we have more data.

Alright.

Call back to Mr. Albert <unk> for closing remarks.

Thank you operator, and thanks to all of you for taking time to join US today and for your continued support of blueprint medicines and we look forward to updating you again soon and hope you all stay well goodbye.

Ladies and gentlemen. This concludes today's call. Thank you for joining you may now disconnect your lines.

Okay.

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