Q4 2020 Blueprint Medicines Corp Earnings Call

Okay.

Ladies and gentlemen, thank you for standing by and welcome to the Blueprint medicines fourth quarter 2020 earnings call. At this time, all participants are in a listen only mode.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Blueprint Medicines fourth quarter 2020 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0. I would now like to hand this conference over to your speaker today, Kristen Hodes of Blueprint Medicines. Thank you. Please go ahead, ma'am. Thank you, Operator.

After the speaker's presentation, there will be a question the answer session to ask the question. During the session you will need the press star one on your telephone. Please be advised that today's conference is being recorded if you quantified the assistance. Please press star zero.

I'd now like the hand off from what you're speaking of the day Christian photos of loop.

Print medicines. Thank you. Please go ahead ma'am.

Thank you operator.

Good morning, everyone and welcome to Blueprint medicines fourth quarter 2020 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.

Kristen Hodes: Good morning, everyone, and welcome to Blueprint Medicine's fourth quarter 2020 Financial and Operating Results Conference call. This morning, we issued a press release that outlines the topics we plan to discuss today. You can access the press release as well as the slides that we'll be reviewing today by going to the investor section of our website at www.blueprintmedicines.com. On today's call, Jeff Albers, our Chief Executive Officer, will discuss Blueprint Medicine's recent business highlights and 2021 corporate priorities.

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Today on our call, Jeff Albers, our Chief Executive Officer will discuss the blueprint medicines recent business highlights and 'twenty 'twenty, one corporate priorities Christy.

Christy Rossi, our chief commercial officer will provide of commercial update.

Kristen Hodes: Christy Rossi, our Chief Commercial Officer, will provide a commercial update, and Fouad Namouni, our President of Research and Development, will discuss our R&D efforts. And Mike Landsittel, our Chief Financial Officer, will review our financial results. Before we get started, I would like to remind everyone that the statements we make on this conference call will include forward-looking statements. Actual events or results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factors section of our most recent annual report on Form 10-K and any other filings that we have made or may make with the SEC.

Slide, namely our president of research and development will discuss our R&D efforts and Mike lands at all of our Chief Financial Officer will review our financial results.

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 most recent annual report on form <unk>.

10-K, and any other filings that we have made or may make with the SEC.

Kristen Hodes: In addition, any forward-looking statement made on this call represents our views only as of today and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update or revise any forward-looking statement. Now, here's our CEO, Jeff Albers.

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.

Jeff Albers: Thanks, Kristin, and good morning, everyone. We're happy to provide an update on recent progress and a look forward to our 2021 priorities and catalogs. I know our industry tends to use the word transformational quite a bit, but it really isn't hyperbole to say that 2020 was a transformational year for Blueprint Medicines. With four AvaKit and Gavretto regulatory approvals in the United States and Europe and a global collaboration signed with Roche, we're now a fully integrated global biopharmaceutical company, and we're exceptionally well positioned to drive our next As we progress into 2021, we're focused on three strategic pillars to build on our recent progress.

Okay.

Thanks, Christian and good morning, everyone. We're happy to provide an update on recent progress and I look forward to our 2021 priorities and catalysts.

I know all of our industry tends to use the word transformational quite a bit but it really isn't the hyperbole to say the 'twenty 'twenty was a transformational year for blueprint medicines.

With four eve of kit in GAAP right of regulatory approvals in the United States and Europe.

And the global collaboration signed with Roche, where now a fully integrated global biopharmaceutical company.

We're exceptionally well positioned to drive our next wave of growth.

As we progress into 'twenty 'twenty, one we're focused on three strategic pillars to build on our recent progress.

One to accelerate the global adoption of Eva kit and GAAP Righto.

Jeff Albers: One, to accelerate the global adoption of Avakit and Gavretto, to advance a new wave of therapeutic candidates to clinical proof of concept, and three, to further expand our precision therapy pipeline. The first, as Christy will discuss, is centered around the anticipated approval of AvaKit in advanced systemic massive cytosis and the acceleration of our Gabriel, with the advocate SNDA now accepted and a PDUFA date in the second quarter. We are on the verge of expanding into what we have long discussed as our most significant growth opportunity. Additionally, the development of AvaKit in non-advanced systemic mastocytosis is also progressing via the registration-enabling Pioneer trial.

Two to advance of new wave of therapeutic candidates the clinical proof of concept.

And three to further expand our precision therapy pipeline.

The first is Christie will discuss is centered around the anticipated approval of Eva kit in advanced systemic mastocytosis and the acceleration of our GAAP right of watch.

With the aim of Kid S. N D. A now accepted and the <unk> date in the second quarter.

We're on the verge of expanding into what we have long discussed is our most significant growth opportunity.

Additionally, the development of Eva kit and non advanced systemic mastocytosis is also progressing via the registration enabling pioneer trial.

This offers the potential to further expand our commercial efforts in the near future.

Jeff Albers: This offers the potential to further expand our commercial efforts in the near future. And for Gavretto, the expanded U.S. approval for forms of thyroid cancer in December positions us to continue to advance the launch in the U.S. while also focusing on applications in additional geographies. The second and third priorities, as Fouad will discuss, focus on advancing our new therapeutic candidates to clinical proof of concept and continuing to productively tap into our prolific research platform.

And forgive read of the expanded U S approval for forms of thyroid cancer in December.

Positions us to continue to advance the launch in the U S. While also focusing on applications in additional geographies.

The second and third priorities as Fouad will cover focus on advancing our new therapeutic candidates the clinical proof of concept.

And continuing to productively tap into our prolific research platform.

Jeff Albers: We expect to make significant progress on these fronts with several upcoming presentations of new preclinical data, including the first data for our latest and newly named development candidate, Blue 701, in double mutant EGFR-driven lung cancer. We also plan to initiate clinical trials for Blue 9-4-5 in EGFR-driven lung cancer and Blue 2-6-3 in non-advanced systemic mastocytosis. Finally, we're excited to announce a new research program focusing on CDK2, a compelling therapeutic target across multiple tumor types, as well as a mechanism of resistance in a subset of patients who progress on CDK4-6 therapy.

We expect to make significant progress on these fronts with several upcoming presentations of new preclinical data.

Including the first data for our latest of newly named development candidate Blu 701 in double mutant Egfr driven lung cancer.

We also plan to initiate clinical trials for Blu 945 in Egfr, driven lung cancer and Bluetooth fix three of non advanced systemic mastocytosis.

Finally, we're excited to announce the new research program, focusing on CDK to a compelling therapeutic target across multiple tumor types as well as the mechanism of resistance in a subset of patients who progress on CDK four six therapies.

Jeff Albers: I'm particularly excited to share more information about these research programs over the coming months given the quality of the science and the scope of their respective opportunities. All of this is further supported by our strong financial position, with more than $1.5 billion in cash at the end of 2020, which enables us to continue to invest in these programs and our research engines. While we also consider opportunities to bring in external innovation where there's a strategic fit. So with that introduction, I'll hand the call over to Christy to provide a commercial update. Christy

I'm, particularly excited to share more information about these research programs over the coming months, given the quality of the science and the scope of their respective opportunities.

All of this is further supported by our strong financial position.

With more than 1.5 billion in cash at the end of 2020.

Which enables us to continue to invest in these programs and our research engine. While we also consider opportunities to bring in external innovation, where there's a strategic fit.

So with that introduction I'll hand, the call over to Kristy to provide of commercial update Christy.

Thanks, Jeff and good morning, everyone.

Christina Rossi: This is Jeff. Good morning, everyone. In the fourth quarter, we continued to make progress toward our goal of delivering a portfolio of precision therapies to patients globally. With the FDA approval of Gabretto for Rett-altered thyroid cancer, the first European launch of AvaKit for PDGFR-alpha GIST in Germany, and most importantly, the submission of marketing applications for AvaKit for Advanced SM in the U.S. and now in Europe as well, we have set the foundation for 2021 to be a year of significant growth.

In the fourth quarter, we continue to make progress toward our goal of delivering our portfolio of precision therapies to patients globally.

With the FDA approval of God's Rado for Ret altered thyroid cancer. The first European launch of Eve of Cat for P. D. J F for Alpha just in Germany, and most importantly, the submission of marketing applications for Ava kit for advanced SM in the U S and now in Europe as well we have set the foundation.

And for 'twenty 'twenty, one to be a year of significant growth.

The two most important drivers of that growth will be our anticipated U S launch of Eva kit and advanced us on in the first half of the year as well as the ongoing launch of gift for auto in the U S.

Christina Rossi: The two most important drivers of that growth will be our anticipated U.S. launch of AvaKit and Advanced SM in the first half of the year, as well as the ongoing launch of Gavreto in the U.S. Before turning to SM, let me start with fourth-quarter results and the Gavreto launch. We had net product revenues of $6.7 million, bringing our total 2020 product revenue to $22.1 million.

Before turning to S. M. Let me start with fourth quarter of results and they gave read of lunch.

We had net product revenues of $6 7 million, bringing our total 'twenty 'twenty product revenue to $22 1 million.

Revenue for the quarter was primarily driven by $6 million in sales for Ava cat and.

We also recognized <unk> 7 million in revenue for GAAP read out.

Christina Rossi: Revenue for the quarter was primarily driven by $6 million in sales for AvaKit, and we also recognized $0.7 million in revenue for Gavretto. We were pleased to receive approval for thyroid cancer late in the fourth quarter, thereby enabling us to fully launch Gevretto across the set of indications we expect to have in the near term. In addition, two weeks ago, Gavreta was added to the NCCN treatment guidelines for medullary and papillary thyroid carcinoma, which should create further awareness of this indication.

We were pleased to receive approval in thyroid cancer late in the fourth quarter.

Thereby enabling us to fully launch GAAP write all across the set of indications we expect to have in the near term.

In addition, two weeks ago I've read of what's added to the N C. C N treatment guidelines from medullary and papillary thyroid carcinoma.

Which should create further awareness of the syndication.

Overall, we have seen thyroid cancer patients comprise approximately one third of the selective ret inhibitor market to date.

We are excited to have you have read of available for these patients.

As we continue to advance the launch of Caporetto, we are focusing with our partners at your non tech in two key areas.

Christina Rossi: Overall, we have seen thyroid cancer patients comprise approximately one-third of the selective RET inhibitor market to date, and we are excited to have Gavreto available for these patients. As we continue to advance the launch of Gabretto, we are focusing with our partners at Genentech on two key areas. The first is increasing our share of patients starting on a selective red inhibitor, where we have seen good progress since December. The second is growing the overall number of RET patients who are identified and treated with a selective RET inhibitor, which will be key to enable us to realize the longer-term potential of Gavreto.

The first is increasing our share of patients starting on a selective ret inhibitor, where we have seen good progress since December.

The second is growing the overall number of rat patients who are identified and treated with the selective ret inhibitor.

Which will be key to enable us to realize the longer term potential of GAAP right out.

Let me start with our share of new patient starts.

Following the give righto approval for thyroid cancer in December our share of new patients starting on a selective ret inhibitor ticked up to about 25 per cent.

We are seeing of generally balanced mix of academic and community prescribers and the majority of right of prescribers in the fourth quarter four of prescribing of selective ret inhibitor commercially for the first time.

Christina Rossi: Let me start with our share of new patients starting. Following the Govretto approval for thyroid cancer in December, our share of new patients starting on a selective red inhibitor kicked up to about 25 percent. We are seeing a generally balanced mix of academic and community prescribers, and the majority of Gavreto prescribers in the fourth quarter were prescribing a selective RET inhibitor commercially for the first time.

We will be focused on continuing to increase our share of new patient starts.

As this metric when combined with the prolonged duration of therapy, we expect based on our clinical studies.

Is the key leading indicator of revenue growth.

We continue to be very encouraged by feedback from health care providers and payers on GAAP Red Oak differentiated profile, which includes deep and durable responses are predictable and manageable safety profile and convenient once daily dosing.

Our second area of focus is on increasing the percent of ret positive patients who are identified and treated with the selective ret inhibitor, which we estimate right now is around 20%.

Christina Rossi: We will be focused on continuing to increase our share of new patient starts, as this metric, when combined with the prolonged duration of therapy we expect based on our clinical studies, is a key leading indicator of revenue growth. We continue to be very encouraged by feedback from health care providers and payers on Gavreto's Differentiated Profile, which includes deep and durable responses, a predictable and manageable safety profile, and convenient once-daily dosing.

There are two key drivers here.

Rebounding from the impact of Covid is having on cancer care in the U S.

As well as increasing comprehensive biomarker testing of all patients prior to the initiation of treatment.

Data in the public domain have shown that the overall volume of clinic visits as well as rates of biomarker testing for cancer patients have been impacted by Covid.

We see this in the rent market as the number of patients starting of selective ret inhibitor was approximately 25% lower in Q4 versus earlier in the year.

Christina Rossi: Our second area of focus is on increasing the percent of RET-positive patients who are identified and treated with a selective RET inhibitor, which we estimate right now is around 20%. There are two key drivers here, rebounding from the impact COVID is having on cancer care in the US, as well as increasing comprehensive biomarker testing of all patients prior to the initiation of treatment. Data in the public domain have shown that the overall volume of clinic visits, as well as rates of biomarker testing for cancer patients, have been impacted by COVID. We see this in the RET market, as the number of patients starting a selective RET inhibitor was approximately 25% lower in Q4 versus earlier in the year.

We expect that as we approach the second half of 'twenty 'twenty, one we will see these impacts subside and the number of newly diagnosed patients rebound.

Yeah.

In addition, as we have seen with other biomarkers the availability of a highly effective targeted therapy combined with educational efforts can rapidly increase the percent of patients who are identified and treated.

This is an area, where our partnership with Genentech plays a key role.

Their efforts driving testing and patient identification across their portfolio of targeted lung therapies complement and amplify the patient identification efforts of our team.

Overall, we anticipate that the total market opportunity for ret will expand which will be another significant driver of GAAP red oak growth.

Turning now to Ava Cat first in PT, Jeff for all suggest we've seen consistent new patient starts and total patients on therapy in the U S over the past few quarters.

Christina Rossi: We expect that as we approach the second half of 2021, we will see these impacts subside, and the number of newly diagnosed patients rebound. In addition, as we have seen with other biomarkers, the availability of highly effective, targeted therapy, combined with educational efforts, can rapidly increase the percent of patients who are identified and treated. This is an area where our partnership with Genentech plays a key role. Their efforts driving testing and patient identification across their portfolio of targeted lung therapies complement and amplify the patient identification efforts of our teams.

In Europe, we initiated our first country launch in Germany in the fourth quarter and consistent with our targeted approach, we anticipate seeing incremental growth over time with additional country launches.

Of course, our primary focus is on preparing for the anticipated U S launch and advanced systemic mastocytosis in the second quarter.

This will be a critical milestone for blueprint as we take the first steps towards realizing the commercial potential of the largest opportunity in our late stage portfolio.

While the advanced SM patients represent only about 5% to 10% of the overall S. On population. These patients tend to be treated at major centers.

This gives us an opportunity to focus the majority of our educational efforts on about 70 hematology centers that treat about half of all the advanced SM patients in the U S.

Christina Rossi: Overall, we anticipate that the total market opportunity for RET will expand, which will be another significant driver of Gavreto growth. Turning now to AvaKit, the first in PDGF for AlphaGIST, we've seen consistent new patient starts and total patients on therapy in the US over the past few quarters. In Europe, we initiated our first country launch in Germany in the fourth quarter, and consistent with our targeted approach, we anticipate seeing incremental growth over time with additional country launches.

As I've said previously we built our commercial organization with the portfolio in mind, So we will largely flex and adapt our existing infrastructure to meet the needs of the advanced S. M launch.

Including leveraging our portfolio footprint to identify patients who may be treated outside of these main centers.

We are also beginning to think forward two of potential 'twenty 'twenty two launch for Ava kit and the larger non advanced SM population.

Christina Rossi: Of course, our primary advocate focus is on preparing for the anticipated U.S. launch for advanced systemic mastocytosis in the second quarter. This will be a critical milestone for Blueprint as we take the first steps towards realizing the commercial potential of the largest opportunity in our late-stage portfolio. While advanced SM patients represent only about 5-10% of the overall SM population, these patients tend to be treated at major centers.

Our clear near term priority here is to increase patient identification with the accessible and actionable testing.

We believe that making blood based testing for Cat D 816 V. The SM driver mutation widely available will help remove barriers to diagnosis for non advanced SM patients.

Our precision medicine team has been working closely with testing providers and in part due to these efforts highly sensitive blood based testing is now commercially available in the United States.

Christina Rossi: This gives us an opportunity to focus the majority of our educational efforts on about 70 hematology centers that treat about half of all advanced SM patients in the U.S. As I've said previously, we built our commercial organization with the portfolio in mind, so we will largely flex and adapt our existing infrastructure to meet the needs of the advanced SM lots, including leveraging our portfolio footprint to identify patients who may be treated outside of these main centers. We are also beginning to think forward to a potential 2022 launch for AvaKit in the larger non-advanced SM population.

We expect the availability of testing to grow over the course of this year to labs, which cover about 80% of S. N patients in the U S.

We are confident that increased testing combined with disease education and other efforts will increase the number of S. N patients who are diagnosed and have access to treatment.

Over the course of 'twenty 'twenty, one I see the promise of the blueprint portfolio translating into accelerating commercial impact worldwide.

Anchored by the opportunity on S. M. We will significantly expand the value we are bringing to patients with our ongoing and planned near term launches while building. The foundation for the significant opportunities that are early stage portfolio is poised to address.

I'll now turn the call over to Phil <unk>, our President of research and development, who will provide more detail on our R&D efforts. So what.

Thanks, Christy and good morning, everyone. It's a pleasure to speak with you today.

Christina Rossi: Our clear near-term priority here is to increase patient identification with accessible and actionable testing. We believe that making blood-based testing for KIT-D816V, the SM driver mutation, widely available will help remove barriers to diagnosis for non-advanced SM patients. Our Precision Medicine team has been working closely with testing providers, and in part due to these efforts, highly sensitive blood-based testing is now commercially available in the United States. We expect availability of testing to grow over the course of this year to labs that cover about 80% of SM patients in the U.S. We are confident that increased testing, combined with disease education and other efforts, will increase the number of SM patients who are diagnosed and have access to treatment.

I was thrilled to join the blueprint in September to lead our research and development teams over the last six months I have had the opportunity to work closely with our scientists and clinical team as well as our executive team.

Charles the course for expanding our R&D vision.

It's important to begin by recognizing our future would be built on the foundation of scientific and clinical excellence.

Our research engine has been a profoundly productive with two novel drugs to the Scarborough and approve of in the first 10 years of blueprints existence. The claim we'd be the even though all of the companies you can meet.

We have also nominated for new development candidates since late 2019.

We now aim to build on this progress and become the worlds leading precision.

The content for us this means.

Strong scientific leadership in therapeutic innovation and the.

The focused R&D strategy in precision oncology and hematology.

And the expansive development portfolio combined with the commercial capability to deliver our medicines to patients globally.

Christina Rossi: Over the course of 2021, I see the promise of the Blueprint portfolio translating into accelerating commercial impact worldwide. Anchored by the opportunity in SM, we will significantly expand the value we are bringing to patients with our ongoing and planned near-term launches, while building the foundation for the significant opportunities that our early-stage portfolio is poised to address. I'll now turn the call over to Fouad, our President of Research and Development, who will provide more detail on our R&D efforts.

And being the partner of choice for stakeholders across of the drug development continuum.

To achieve this vision, we will if all of our R&D strategy in civil Oregon on ways.

First.

We will deepen the integration of our research and development teams to accelerate the innovation cycle and expand on what leadership and of course, the therapeutic areas, including systemic mastocytosis from lung cancer.

Fouad Namouni: Thanks, Christy, and good morning, everyone. It's a pleasure to speak with you today.

Second we will build on the productivity of our research engine by continuing to identify high unmet need targets and the rationally designed highly selective kinase inhibitors.

Fouad Namouni: I was thrilled to join Blueprint in September to lead our research and development team. Over the last six months, I have had the opportunity to work closely with our scientists and clinical team, as well as our executive team, to chart the course for expanding our R&D. It's important to begin by recognizing that our future will be built on a foundation of scientific and clinical excellence. Our research engine has been profoundly productive, with two novel drugs discovered and approved in the first 10 years of Blueprint's existence, a claim we believe no other company can make. We have also nominated four new development candidates since late 2019.

While exploring new modalities to expand our ability to address more targets in the fields of oncology and hematology.

Third we will operate at the forefront of drug development.

Expanding our use of the translational data.

The trial design and the regulatory strategies to bring our transformative of precision therapy to selected patient populations as quickly as possible.

Finally, our culture of scientific excellence and urgency to address patient needs will continue to be the core value as we grow and expand our portfolio.

Fouad Namouni: We now aim to build on this progress and become the world's leading precision therapy company. For us, this means strong scientific leadership and therapeutic innovation under a focused R&D strategy in precision oncology and hematology, an extensive development portfolio combined with the commercial capability to deliver our approved medicines to patients globally, and being the partner of choice for stakeholders across the drug development continuum. To achieve this vision, we will evolve our R&D strategy in several important ways.

I could not be more excited to work with our R&D teams as we disclose today, our newest neither of resource program C. D day too.

This program explores and the approach to target Cyclin E. An oncogenic driver by inhibiting its catalytic partner CDK to or cyclin dependent kinase two.

In subsets of patients with ovarian breast and other cancers amplification of Cyclin E drive of malignancy is associated with the poor clinical program doses, representing an area of significant patient need.

Fouad Namouni: We will deepen the integration of our research and development teams to accelerate the innovation cycle and expand our leadership in core therapeutic areas, including systemic mastocytosis and lung cancer. Second, we will build on the productivity of our research engine by continuing to identify high and met need targets and rationally design highly selective kinase inhibitors while exploring new modalities to expand our ability to address more targets in the field of oncology and hematology.

So I can eat amplification has also been the reported as of resistance mechanism to CDK four six agents and the hormone positive breast cancer.

We plan to share of preclinical data for our CDK cool program at the <unk>.

Yeah of annual meeting in April and then update on our progress towards selecting a development candidate.

At the ACR, we also plan to share a broad range of additional data.

Including preclinical data for our newly nominated.

Fouad Namouni: Third, we will operate at the forefront of drug development by expanding our use of translational data, innovative trial design, and regulatory strategies to bring our transformative precision therapy to selected patient populations as quickly as possible. Finally, our culture of scientific excellence and urgency to address patient needs will continue to be the core value as we grow and expand our portfolio. I could not be more excited to work with our R&D team as we disclose today our newest major research program, CDK2.

Double mutant Egfr inhibitor Blu seven of one.

Highlighting its potency high selectivity and the brain penetrant.

We will also reported the first clinical data from our phase one healthy volunteer study of Blu two six per week.

We anticipate key themes emerging from these presentations will include the clinical path to them all of our Egfr inhibitors.

The 94, five and Blu seven old ones to address on the target resistance with Egfr agents and most of them in non small cell lung cancer and the potential role of Blu 263 in the treatment of non advanced systemic mastocytosis.

Fouad Namouni: This program explores an approach to target cyclin E, an oncogenic driver, by inhibiting its catalytic partner CDK2 or cyclin-dependent kinase 2, in subsets of patients with ovarian, breast, and other cancers. Amplification of cyclin E drives malignancy and is associated with a poor clinical prognosis, representing an area of significant patient need. Cycline E amplification has also been reported as a resistance mechanism to CDK4-6 agents in hormone-positive breast cancer.

Beyond the ACR in.

In the coming months, we will be working closely with the FDA in EMEA on the reviews of our marketing applications for <unk>.

For advanced systemic mastocytosis.

With the goal of bringing this important from new therapy.

On the systemic most of this April just patients in the United States and in Europe as quickly as we can.

Fouad Namouni: We plan to share preclinical data for our CDK-II program at the AACR annual meeting in April and an update on our progress towards selecting a development candidate. At AACR, we also plan to share a broad range of additional data, including preclinical data for our newly nominated double mutant EGFR inhibitor, Blue 701. Highlighting its potent, high selectivity, and Brain Panel.

More broadly we are building the foundation for multiple clinical data Readouts in 2022.

Including data for Eva and on that math of systemic mastocytosis.

And the proof of concept of data sets across a range of the new programs.

It's an exciting time to be at the blueprint and I look forward to updating you on our progress over the course of the year.

Fouad Namouni: We will also report the first clinical data from our Phase 1 Healthy Volunteers Study of Blue 2638. We anticipate key themes emerging from these presentations will include the clinical path to develop our EGFR inhibitors. Blue 945 and Blue 701 to address on-target resistance to EGFR agents in non-small-cell lung cancer and the potential role of Blue 263 in the treatment of non-advanced systemic mastocytosis. Beyond AACR. In the coming months, we will be working closely with the FDA and MEA on the reviews of our marketing applications for AvaKit for advanced systemic mastocytosis, with the goal of bringing this important new therapy to systemic mastocytosis patients in the United States and in Europe as quickly as possible.

I now turn the call over to Mike to discuss the financial updates Mike.

Thanks Rod.

Earlier. This morning, we reported detailed fourth quarter and full year 2020 financial results in our press release.

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

Total revenues for the fourth quarter were $34 $1 million.

We recognized $27 $4 million in collaboration revenue during the quarter.

Primarily from our agreements with Roche and system.

For 'twenty 'twenty, one we anticipate achieving milestone payments from existing collaborations of approximately $80 million primarily towards the second half of the year.

As Christie mentioned, we recorded $6 7 million of net product revenue during the quarter.

Driven by a per kit sales.

With the launch of get rid of it in the early stages.

Fouad Namouni: More broadly, we are building the foundation for multiple clinical data readouts in 2022, including data for Avakid in non-advanced systemic musculoskeletal disease and proof-of-concept datasets across a range of new programs. It's an exciting time to be at the Blueprint and I look forward to updating you on our progress over the course of the year. I now turn the call over to Mike to discuss financial updates

Anticipated launch of Eve of kit and advanced systemic mastocytosis later this year.

Meaningful product revenue growth over the course of 2021.

Our total operating expenses increased compared to the third quarter of 2020, primarily driven by investments to advance our early discovery pipeline.

Looking forward, we expect to see increasing quarter over quarter operating expense growth driven by the next wave of research programs from our pipeline as they progress towards clinical development, including Bluetooth <unk> III are to Egfr programs.

Michael Landsittel: Thanks, Fouad. Earlier this morning, we reported detailed fourth quarter and full year 2020 financial results in our press release. For today's call, I'll touch on a few highlights from the quarter. Total revenues for the fourth quarter were $34.1 million. We recognized $27.4 million in collaboration revenue during the quarter, primarily from our agreements with Roche and Seastone. For 2021, we anticipate achieving milestone payments from existing collaborations of approximately $80 million, primarily towards the second half of. As Christy mentioned, we recorded $6.7 million of net product revenues during the quarter, driven by apricot sales.

Our newly announced CDK to program.

We also anticipate continued quarter over quarter increases in noncash stock based compensation expense throughout 2021.

Finally, we're entering 2021 in the strongest financial position we've ever been in as the company.

We ended 2020 with over $1 $5 billion in cash bolstered by product revenues milestone payments and proceeds from our ATM facility.

The strength provides us the ability to advance our robust pipeline of wholly owned drug candidates through development.

As well as the flexibility to prudently consider of strategic external innovation opportunities.

So with that I will now turn the call over to the operator for any questions operator.

Thank you as a reminder to ask the question you will need the press star one on your telephone.

Draw your question press the pound key.

We ask that you. Please limit yourself to one question you may re queue for any additional questions.

Michael Landsittel: With the launch of Gavreto in the early stages and an anticipated launch of AvaKit in advanced systemic mastocytosis later this year, we expect meaningful product revenue growth over the course of 2021. Our total operating expenses increased compared to the third quarter of 2020, primarily driven by investments to advance our early discovery pipeline. Looking forward, we expect to see increasing quarter-over-quarter operating expense growth driven by the next wave of research programs from our pipeline as they progress towards clinical development, including Blue263, our two EGFR programs, and our newly announced CDK2 program.

Our first question comes from solving Richter of Goldman Sachs. Your line is open.

Great. Thanks for taking the question. This is the Andrea on per stopping on Jeff.

Jeff maybe a question for you Big picture in terms of your your strategy for BD, just would love to hear what you're interested in bringing and.

As you think on on the Florida, what could what the complement your.

The current pipeline on portfolio. Thanks, so much.

Sure so focusing more on inbound business development has become a of.

The large priority for us.

Over the course of I'd say the last six months and is it the way. We think about is that we have built the capability to move precision therapies forward from.

Michael Landsittel: We also anticipate continued quarter-over-quarter increases in non-cash stock-based compensation expense throughout 2021. And, finally, we're entering 2021 in the strongest financial position we've ever been in as a company. We ended 2020 with over $1.5 billion in cash bolstered by product revenues, milestone payments, and proceeds from our ATM facility. This strength provides us the ability to advance our robust pipeline of wholly owned drug candidates through development, as well as the flexibility to prudently consider a strategic external innovation output. So with that, I will now turn the call over to the operator for any questions.

From the earliest stage of discovery all the way through the commercialization and I think that's it's certainly an underappreciated capability that the the have that team in place that is ready to execute on programs and when we think about very modalities, we've been focused exclusively on kinase molecules.

Holes, where our platform has and continues to identify really interesting new targets, but we know there's a lot more out there I mean, one of the cornerstones of our strategy has always been to think about the potential for a combination therapy, so bikes, creating select of molecules or the orthogonal mechanisms of action that could be complementary.

And rather than partnering those with other companies are there assets that we could go out and identify and bring in and develop our internally and so if we think about the core of precision therapy, but it's certainly beyond the kinase inhibitors and if I think of about five years out from now.

I think our our ongoing growth will be a blend a very natural blend of continued investment in our platform.

Operator: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. We ask that you please limit yourself to one question. You may recur for any additional questions. Our first question comes from Salveen Richter with Goldman Sachs. Your line is open.

But complemented by external opportunities.

Maybe foulard do you want to jump in and add anything to that.

Yes. Thank you Jeff one of the only thing I will add is obviously as Jeff said, we are blend and end to end the company with all of the capabilities that will allow us to of Redeveloping integrate additional godaddy means in terms of targeting more targets of new targets.

Andrea: This is Andrea on first salveen. Um, Jeff, maybe a question for you, the big picture in terms of your

One thing is there's going to be very important is to continue to look at the precision oncology and hematology always follow the science and follow the at the.

Andrea: for your strategy for BD. I just would love to hear.

Jeff Albers: I'd love to hear what you're interested in bringing in as you think forward about what could complement your current pipeline and portfolio. Thanks so much.

High unmet need for operations.

Thank you on next question comes from Marc Frahm with Cowen and company. Your line is open.

That's for <unk>.

Jeff Albers: Sure, so focusing more on inbound business development has become a large priority for us over the course, I'd say, of the last six months. And the way we think about it is that we have built the capability to move precision therapies forward from the earliest stage of discovery all the way through to commercialization. And I think that's certainly an underappreciated capability to have that team in place that is ready to execute on programs.

Maybe the other do you have.

All of our the vast majority of the preclinical data for your your double and Triple mutant Egfr inhibitors in place.

Maybe speak to kind of the dosing the therapeutically relevant doses. The the safety window that you have and maybe put it in the context of Goodbread OS early development and how quickly you think you can get into therapeutically relevant doses.

Or do you want to take that.

Thank you thanks, Mark for the question of <unk>.

So first let me say that our teams have been developing rationally how do you see that give highly potent egfr slope of generation Asians with the.

Jeff Albers: And when we think about varying modalities, we've been focused exclusively on kinase molecules where our platform has and continues to identify really interesting new targets, but we know there's a lot more out there. I mean, one of the cornerstones of our strategy has always been to think about the potential for combination therapy. So by creating selective molecules, are there orthogonal mechanisms of action that can be complementary? And rather than partner those with other companies, are there assets that we could go out and identify, bring in, and develop internally?

Idea of really tackling the resistance to Egfr treatments are in non small cell lung cancer.

The specific need to talk about your horse in the market can you start with seven of one seven and one is our doubling of <unk> has.

Has been developed with potency for the origin of the mutation on the CES of mutation selectivity of our lifetime.

And very importantly, brain tenants penetrance of.

Jeff Albers: And so if we think about the core is precision therapy, but it's certainly beyond kinase inhibitors. And if I think about five years out from now, I think our ongoing growth will be a blend, a very natural blend of continued investment. Maybe Fouad, do you want to jump in and add anything to that?

This gives an opportunity for this patient seven of one to really go on to tackle the resistance to also the Merck and he'd be in second line non small cell lung cancer, but of course will become a strong candidate for combinations with our own mine four of five and the other Egfr of T. J is.

From a 945 perspective, we call it the triple mutant.

Fouad Namouni: Yeah, thank you, Jeff. One thing I will add is, obviously, as Jeff said, we are a blend and end-to-end company with all the capabilities that will allow us to really develop and integrate additional modalities in terms of targeting more targets and new targets. One thing that is gonna be very important is to continue to look at precision oncology and hematology, always follow the science, and meet the high and met needs of patients.

Because it covers all of the origin of the mutation the C. S mutation and the T. M. A piece of a 98 mutations altogether.

It is important to highlight from the line four of five but it has been developed weighted.

A very very selective wild type Egfr window, which is about 900 fold selectivity over egfr.

Not only the this compound has the opportunity to be double up in high end met need triple the music tumor patients but has clear.

Operator: Thank you. Our next question comes from Marc Frahm with Cowen & Company. Your line is open.

Opportunity to be a combination of partner given its clinical profile and given its ability to combine the only with our own egfr agents and <unk>.

Marc Alan Frahm: Thanks for attending. Perhaps you know that you have all or the vast majority of the preclinical data for your double and triple mutant EGFR inhibitors in place. Could you maybe speak to kind of the dosing, the therapeutically relevant doses, the safety window that you have, and maybe put it in the context of Govretto's early development and how quickly you think you can get into therapeutically relevant doses?

So with all of the agents all in on when we look beyond the single agents of the volatile I think combining both agents together has the opportunity to cover the majority of the resistance mutation in Egfr and move.

Already of lines, while also thinking about expanding the opportunity to additional combination in the space of lung cancer.

Fouad Namouni: Fouad, do you want to take this?

Fouad Namouni: Thank you. Thanks, Marc, for the question. So first, let me say that our teams have been developing rationally, highly selective, highly potent EGFR fourth-generation agents with the idea of really targeting the resistance to EGFR treatments in non-small cell lung cancer. Specifically, to talk about your question, Marc, let me start with 701. 701 is our W, and has been developed with potency for the original mutation and the CS mutation, selectivity of our wild type, and, very importantly, brain penetration.

We are moving both of them very quickly so the agent on line four five.

We're getting in the R&D.

Is sort of half of year end stop in right way a day.

As of <unk> for mine four of five we are targeting before the end of this year or second half of this year before 701 will be developing the monotherapy and combination of.

Both agents and with all of our agents with the sense of urgency because we believe that is of high unmet need in Egfr mutant population of patients that we can meet with our.

Fouad Namouni: This gives an opportunity for this agent, 701, to really go and tackle the resistance to osteoamerican hip and second Y non-small cell lung cancer but also become a strong candidate for combinations with our own 945 and other EGFR TKIs. From a 9-4-5 perspective, we call it the triple mutant because it covers all of the original mutation, the CS mutation and the TM or T790M mutations altogether. It is important to highlight for 9.4.5 that it has been developed with a very, very selective wild-type EGFR window, which is about 900 fold selectivity over EGFR.

With our Egfr pipeline.

Thank you. Our next question comes from Dane Leone with Raymond James Your line is open.

Thank you for taking the questions and congratulations on all of the updates.

So maybe two things for me one could you maybe provide a little bit more color in terms of how you see the.

Is M launch going into the back half of the year.

You gave us some good color in terms of how you're targeting different centers, but.

How long do you think it's going to take to get access for all of these docs and patients.

How much can you leverage the utilization of light of store and currently to do so.

Fouad Namouni: Not only does this compound have the opportunity to be developed in high-end triple mutant tumor patients but it also has the clear opportunity to be a combination partner given its clinical profile and given its... Ability to combine not only with our own NGFR agents but also with other agents. All in all, when we look beyond the single-agent development, I think combining both agents together has the opportunity to cover the majority of the resistance mutation in EGFR and move earlier lines, while also thinking about expanding the opportunity to additional combinations in this space of one cancer.

And then my second question is more of the preclinical questions on your CDK to.

Program, historically and classically the issue of targeting CDK too has been on cell activity.

From what you've seen the darn sick with the Dodgers sick lived on others.

Obviously, the odds of a high interest area of Pfizer is working on the exploration programs as well.

Where do you think your angle is there do you think you can just actually dial and selectivity of did not hit the other CDK is or is there. Another kind of is that your team is working on thank you.

Thanks, Dan So Christy why don't you take the first question and Foulard will pass over to you for the second question.

Fouad Namouni: We are moving both of them very quickly. So the first agent 945 will, we are targeting an IND in the first half of the year and starting right away the phase one trials for 9-4-5. We are targeting the end of this year or the second half of this year the IND for 7-1-1. We will be developing monotherapies in combination with both agents and with other agents with a sense of urgency because we believe there is a high level of need in the EGFR mutant population of patients that we can meet with our EGFR pipeline.

Sure so.

As I said, we're we're excited about the prospect of an approval and launch in the second quarter and the teams are engaging now and and ready to go out of four that's you know I think whats interesting about this is that obviously advocate isn't approved therapy. So you know I think upon the indication approval in advanced of.

Some are you know we are I think we will be ready to go very quickly on our commercial infrastructure is out of engaging with these key centers.

Actually we're just looking at some data yesterday, even looking at overlap with our just utilization for eight of Cat M. The centers that are of treating most of advanced SM patients theres quite a high degree of overlap with where we already see the kit uptake for jest.

Operator: Thank you. Our next question comes from Dane Leone with Raymond James. Your line is open.

So you know I think we have a good sense of of you know who the prescribers are where these patients are certainly we have a sense of where might've started as used although as I said before you know I would say motto is underutilized in advanced SM, just given the limitations of the product's profile and so you know we will be looking.

Dane Vincent Leone: Thank you for taking the questions and congratulations on all the updates. So maybe two things for me.

Dane Vincent Leone: One, could you maybe provide a little bit more color in terms of how you see the ASM launch going in the back half of the year? You gave us some good color in terms of how you're targeting different centers, but how long do you think it's going to take to get access for these docs and patients? How much can you leverage the utilization of Mitostorin currently to do so? And then my second question is more of a preclinical question about your CDK2.

Certainly you know expand the opportunity for Ava kept behind where where mitel was used and the feedback we've gotten from <unk>.

Prescribers health care providers Kols is that they really see the Ava kept profile as being best in class I'm for it for these patients. So you know I think upon approval, we'll be looking to go out very quickly and focus on education and I would imagine that access you know should be relatively smooth. The given again you know the the drug is out of.

Dane Vincent Leone: Program. Historically and classically, the issue with targeting CDK2 has been selectivity, for what you see with DymesticLib, FadristicLib, and others. Obviously, you know, it's a highly interesting area. Pfizer is working on next-generation programs as well.

There and available.

Alright, and then maybe you can talk about the CDK to the target product profile and the focusing on selectivity.

Dane Vincent Leone: Where do you think your angle is there? Do you think you can just actually dial in selectivity to not hit the other CDKs, or is there another premise that your team is working on?

Thanks, Jeff and day into your question. So first let me say a one on one of the of programs that they were really excited about when I was joined the blueprint calls the CDK to our program and that's for a key of reasons.

Dane Vincent Leone: ...

Christina Rossi: Thanks, Dane. So, Christy, why don't you take the first question, and then Fouad, we'll pass over to you for the second question.

Christina Rossi: Sure. As I said, we're excited about the prospect of approval and launch in the second quarter, and the teams are, you know, engaging now and ready to go for that. You know, I think what's interesting about this is that, obviously, AvaKit is an approved therapy. So, you know, I think upon indication approval and advanced SM, we are, I think we'll be ready to go very quickly. Our commercial infrastructure is out engaging with these key centers.

The reasons one blueprint.

Blueprint is redeployed their expertise in making very rational and designed molecules to be highly selective. This program is focused on the high selectivity high potency of course, CDK too and the selectivity has over other CDK.

Kind of is this including CDK one than the others.

The other thing that excites me about this program at the blueprint is the scope of the opportunity and the ability to help many patients with cancer.

Christina Rossi: In fact, we were just looking at some data yesterday, even looking at overlap with our JIST utilization for AvaKit. The centers that are treating most advanced SM patients, there's quite a high degree of overlap with where we already see AvaKit uptake for JIST. So, you know, I think we have a good sense of who the prescribers are, where these patients are. Certainly, we have a sense of where Midostorin is used, although, as I said before, I would say Mito is underutilized in advanced SM, just given the limitations of the product profile.

You can think of and cancer, where the development of the CDK to would be.

On the therapy for tumors addicted to the pathway you can think about opportunities for combining with other agents like CDK four six in the form of therapy in cancer like breast cancer all of the way from resistant tumors to liberty or sort of every airlines. So this I believe this will be the best and has the potential of it used to be.

Christina Rossi: And so, you know, we will be looking to certainly, you know, expand the opportunity for AvaKit beyond where Mito is used. And the feedback we've gotten from prescribers, healthcare providers, and key opinion leaders is that they really see the AvaKit profile as being best in class for these patients. So, I think upon approval, we'll be looking to go out very quickly and focus on education. And I would imagine that access, you know, should be relatively smooth given, again, you know, that the drug is out there and available.

The best in class CDK to in the space and I a force that the.

Data that we just show.

As you all will be very compelling to you.

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

Hey, Good morning, guys. This is Charles Zhu on for Michael Schmidt, Thanks for taking the questions.

Dropped off low materially there. So I don't know if this was already asked but I'm kind of wondering on how our GAAP net of sales tracking relative to your initial launch expectations in the blood of really sort of fourth quarter performance with low I do understand you know some of the color that you've already provided during the prepared remarks, but just kind of on.

Fouad Namouni: All right, and then, Fouad, maybe you can talk about CDK2, the target product profile, and the focus on selectivity.

Fouad Namouni: Thanks, Jeff and Dane, for your question. So first, let me say one of the programs that I was really excited about when I was joining Blueprint was the CDK2 program, and that's for a couple of reasons. One, Blueprint has really deployed their expertise in making very rational and designed molecules to be highly selective. This program is focused on high selectivity and high potency for CDK2, and the selectivity is over other CDK kinases, including CDK1 and others. The other thing that excites me is...

On the sea.

Forward end of the 25% of share of new patients that youre picking up from I was wondering how that breaks down between the lung and thyroid and how you see the building out thanks.

Sure So I'll take that one.

So you know as I said that the share of new starts is really the the sort of the primary indicator that we are looking at to understand the health of the lunch along with as I mentioned kind of the overall size of the opportunity of those are really the two key variables that we'd be looking at evolving over the course of of the year.

Fouad Namouni: The other thing that excites me about this program at Blueprint is

Fouad Namouni: Cancer. You can think of cancer where the development of CDK2 would be as monotherapy for tumors that are addicted to the pathway. You can think about opportunities for combining it with other agents like CDK4-6 and hormone therapy in cancers like breast cancer all the way from resistant tumors to earlier lines. So I believe this will be the best and has the potential actually to be the best in class CDK2 inhibitor in the space, and I trust that the data that we show at AACR will be very compelling.

Given that we essentially got the full label of six months behind Lilly you know we.

We were pleased to get to 25 per cent by the end of this year or last year, and we're hoping that that will continue to grow and evolve certainly the feedback we're getting from prescribers has been very positive and I think you know the fact that we're seeing utilization of GAAP red oak coming from new to market prescribers is I think of really key insight that speak.

Just sort of the opportunity for growth here overall right. So we know that the majority of patients are not being treated.

The ret inhibitor right now and that's that's not a good thing for patients and certainly that's the focus that we will have.

Operator: Thank you. Our next question comes from Michael Schmidt with Guggenheim. Your line is open.

The kind of grow that pie and core of that opportunity through the course of the year, which will then give us an opportunity to grow get rid of utilization as well.

Charles Yuan: Hey, good morning, guys. This is Charles Yuan from Michael Schmidt. Thanks for taking the questions. I dropped off momentarily there. So I don't know if this has already been asked, but I'm kind of wondering, how are Gabretto sales tracking relative to your initial launch expectations and in light of Willie's fourth quarter performance with Rura Tevmo? I do understand, you know, some of the color that you already provided during the prepared remarks, but just kind of wanted to see, you know, forward, and the 25% share of new patients that you're

You know I mentioned here is the question regarding thyroid certainly we view thyroid is a very important component of the overall rat opportunity you know in total it looks like its about a third of prescriptions coming forward, it's been less than that for us, but quickly catching up right. So obviously, we just got the thyroid indication at the end of.

Of last year. So we've only had that for several weeks now at this point, but we've seen utilization of thyroid and you know we we believe our day to there is very strong and certainly you know the duration that those patients may be treated with can be quite long as well. So thyroid will be an important part of our focus is as we go forward.

Charles Yuan: That breaks down between the lung and thyroid and how you see that building out. Thanks.

Thank you. Our next question comes from David Lebowitz with Morgan Stanley. Your line is open.

Christina Rossi: Sure, so I'll take that one. So, as I said, the share of new starts is really the sort of primary indicator that we are looking at to understand the health of the launch, along with, as I mentioned, kind of the overall size of the opportunity. Those are really the two key variables that we'll be looking at, you know, evolving over the course of the year. You know, given that we essentially got the full label six months behind Lilly, we were pleased to get to 25% by the end of this year or last year, and we're hoping that that will continue to grow and evolve.

Thank you very much for taking my question.

With respect to the printing and submission per advanced systemic mastocytosis number one do you expect it will go to panel and the number two.

One of the.

FTA be looking also at the data from the Indolent population and I guess do you expect you might get some commentary on that as well from the agency and insight on their view on how they look at the dataset.

Sure.

Do you want to start with that the path for review for Ava printing of in advance of S. M.

Thank you Geoff and thanks, David.

Christina Rossi: Certainly, the feedback we're getting from prescribers has been very positive. And I think, you know, the fact that we're seeing utilization of Gevretto coming from new-to-market prescribers is, I think, a really key insight that speaks to sort of the opportunity for growth here overall, right? So we know that the majority of Rett patients are not being treated with a Rett inhibitor right now, and that's not a good thing for patients. And certainly, that's a focus that we will have to kind of grow that pie and grow that opportunity through the course of the year, which will then give us an opportunity to grow Gevretto utilization as well.

After you have submitted what we believe is a robust package of data for the advanced systemic mastocytosis indication to the FDA and the review of started.

We believe we are ready to handle the review questions and we also will.

We'll be ready to handle any advisory committee.

On a maze of OCA.

Well of one but so far we believe that's all of our data are robust and can be too.

The approval.

In terms of the data from non advanced systemic mastocytosis indolent systemic mastocytosis I think the total.

Christina Rossi: You know, I mentioned the question regarding thyroid. Certainly, we view thyroid as a very important component of the overall Rett opportunity. You know, in total, it looks like about a third of prescriptions are coming forward. It's been less than that for us, but we're quickly catching up, right? So obviously, we just got the thyroid indication at the end of last year, so we've only had that for, you know, several weeks now at this point.

80 of the data we have submitted on advanced systemic mastocytosis is sufficient on all of opinion and make a compelling case for the approval of this indication in systemic.

Systemic mastocytosis would be a separate indication we will be happy to submit these data when they are available the laser for this indication in 2022% of the SBA, but we do not see an interaction between the pioneer data and the approval of <unk>.

Christina Rossi: But we've seen utilization in thyroid, and you know, we believe our data there is very strong, and certainly, you know, the duration that those patients may be treated with can be quite long as well. So thyroid will be an important part of our focus as we go forward.

On advanced it just didn't mess of the St. Louis.

Yeah.

Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.

Operator: Thank you. Our next question comes from David Lebowitz of Morgan Stanley. Your line is open.

Hey, Thanks for taking the question.

Just to more of a modeling question on anything else just for from Mike around how we should be thinking about SG&A and R&D for 2021.

David Neil Lebowitz: Thank you very much for taking my question. With respect to the Abercrinton Submission for Advanced Systematic Master's Psychosis, number one, do you expect it will go to panel? And number two, will the FDA also be looking at data from the indolent population? And I guess you expect you might get some commentary on that as well from the agency and insight into their view and how they look at that data set?

And how we should be thinking about if there's any changes give rest of 2021.

The sense of total revenues and payments of the Roche et cetera, how that should be accounted for of the P&L.

Yeah. Thanks, Peter So I think in terms of.

Operating expenses, what we've guided to is that we expect to start to see.

Fouad Namouni: Sure. Fouad, do you want to start with that, the path for review for Ava Prime and Advanced SM?

Increasing quarter over quarter operating expense growth through the year and this will primarily be driven by our R&D investments and investments in our early stage pipeline as we move of $90 five and $2 six three further into the clinic.

Fouad Namouni: Thank you, Jeff, and thanks, David. We actually have submitted what we believe is a robust package of data for the advanced systemic mastocytosis indication to the FDA, and the review has started. We believe we are ready to handle the review questions, and we also will be ready to handle any advisory committee if we are aware of one. So far, we believe that our data are robust and can lead to approval. In terms of the data from non-advanced systemic mastocytosis or indolent systemic mastocytosis, I think the totality of the data we have submitted on advanced systemic mastocytosis is sufficient, in our opinion, and makes a compelling case for the approval of this indication.

As for SG&A, we built out our commercial infrastructure of last year. So I think there will still be some incremental growth as we approach the advanced SM launch, but R&D will be one of the key drivers for that going forward in terms of milestone payments for the year, what we've guided to is that we anticipate approximately.

Up to 80.

$80 million in potential collaboration revenue to come in in 2021, we think that's going to be weighted towards the back half of the year kind of middle of back half of the year.

Fouad Namouni: Indolent systemic mastocytosis would be a separate indication. We'll be happy to submit this data when they are available later for this indication in 2022 to the FDA, but we do not see any interaction between the pioneer data and the approval of advanced systemic mastocytosis.

And that will be that revenue will be accounted for as collaboration revenue as it comes in.

Thank you. Our next question comes from Arlinda Lee with Canaccord. Your line is open.

Hi, guys. Thanks for taking my questions I have two one day alluded to the 91 and 94 of five combination of frontline analyst, whether the preclinical data would be at ACR or would that be sometime.

Operator: Thank you. The next question comes from Peter Lawson with Barclays. Your line is open. Hey, thanks for taking the question. Just more of a modeling question than anything else, just for Mike around how we should be thinking about SG&A and R&D for 2021 and how we should be thinking about if there are any changes for Gavretto in 2021 in the sense of total revenues and payments, Roche, etc., how that should be accounted for in the P&L.

This year and then secondly as.

As you prepare for launch this year and more into it because he's next.

Our channel checks indicate that in light of storm sales could be up to half of current sales. So I'm wondering how that might affect your regulatory process and I'm here on the launch preparation.

So thank you or Linda on the first question I'll take that in terms of the timing of that as sort of a.

Michael Landsittel: Yeah, thanks, Peter. So I think in terms of operating expenses, what we've guided to is that we expect to start to see increasing quarter-over-quarter operating expense growth through the year. And this will primarily be driven by our R&D investments in our early stage pipeline as we move 9.4.5 and 2.6.3 further into the clinic. In terms of milestone payments for the year, what we've guided to is that we anticipate approximately $80 million in potential collaboration revenue to come in in 2021. We think that's going to be weighted towards the back half of the year, kind of the middle back half of the year. And that revenue will be accounted for as collaboration revenue as it comes in.

<unk> is going to be a busy conference for us is foulard laid out with updates across a range of preclinical programs as well as clinical programs with respect to Egfr of what we've guided to is we'll have preclinical single agent data for seven O. One and then we'll look to share.

Share additional data for both of the Egfr programs over the course of the year, but our guidance has been the combination data towards in the second half of of this year.

On the second question I'm not sure I completely got it but I think.

I wasn't sure of the reference to.

Might of store in sales and how that impacts of the regulatory process is that what your question was.

From sales really are.

Of the happens.

Sales of minus two one is from indolent disease.

Michael Landsittel: Thank you. Our next question comes from Arlinda Lee with Canaccord. Your line is open. Hi guys, thanks for taking my questions. I have two.

Even though they only had some label I'm wondering how that might affect your regulatory and launch preparation.

Okay Chris.

Christi.

So we know that might've store and is certainly used in S. M broadly, including in non advanced forms of the disease I think that speaks to you know to two issues. One is that as I touch you know previously S. M really is one disease, where the single driver and you know of differentiating exactly how these pace.

Operator: One, you guys alluded to the 901 and 945 combination in the front line. I missed whether the preclinical data would be at AACR or would that be sometime later this year? And then secondly, as you prepare for ASM launch this year and more into what's to be next, you know, our channel checks indicate that mitostaurin sales could be up to half of current sales. So I'm wondering how that might affect your regulatory process and your launch preparation. Thank you.

<unk> may be categorized as challenging even for the you know most knowledgeable kols across the across the world. Let alone for you know a hematologist that may see these patients less frequently.

I think it also speaks to just a very significant unmet need that we see across the spectrum of of SM. I'm. You know our data would suggest that you know use of motto of non event says, it's probably less than half I mean, I think of it you know, but you may be looking at different at different data I think overall utilization of might've starring as limited as I said just.

Philina Lee: So, thank you, Arlinda. On the first question, I'll take that in terms of the timing of data. ACR is going to be a busy conference for us, as Fouad laid out with updates across a range of preclinical programs as well as clinical programs. With respect to EGFR, what we've guided to is we'll have preclinical single-agent data for 701 and then we'll look to share additional data for both of the EGFR programs over the course of the year, but our guidance has been for the combination data towards the second half of this year.

The both of the efficacy and sort of safety tolerability profile of of that therapy and as Phil said earlier, you know our our we are filing for indications in advanced of Sam That's our assumption.

How the kit is used in the real World I think you know will be driven by both of the factors that I just mentioned, but certainly we would imagine that initial utilization will be in patients who.

Philina Lee: And the second question, I'm not sure I completely understood it, but I think... I wasn't sure of the reference to... might a store be in sales and how that impacts the regulatory process. Is that what your question was?

Have more significant disease and you know over time, we're looking forward to filing and the non advanced from sort of the disease and having the indication there as well and we'll be engaging with hematologists as well as allergists and others, who may see these patients to ensure that they are being identified and appropriately diagnose and that's really going on.

Jeff Albers: Current sales really are, up to half of the current sales of Midastorin are from indolent diseases, even though they only have an ASM label. I'm wondering how that might affect your regulatory and launch preparation. Okay.

Christina Rossi: Okay, Christy.

Christina Rossi: So we know that Mitostaurin is certainly used in SM. But broadly, including in non-advanced forms of the disease, I think that speaks to, you know, two issues. One is that, as we've talked about previously, SM really is one disease with a single driver, and, you know, differentiating exactly how these patients may be categorized is challenging even for the most knowledgeable KOLs across the world, let alone for hematologists that may see these patients less frequently.

Yes.

Thank you. Our next question comes from the Union with Jefferies. Your line is open.

Thank you.

For the Egfr program.

The frequency of of six 797 as the mutation.

The post the first of all line with him more Canadian non small cell lung cancer.

The debt after the second line use.

So maybe I'll start and then I'll have jumped at it jump in as well.

Christina Rossi: I think it also speaks to just a very significant unmet need that we see across the spectrum of SM. You know, our data would suggest that, you know, the use of MITO in non-advanced is probably less than half. I mean, I think, you know, but you may be looking at different data.

And all of a backup it actually think about the development of these two program. So our triple mutant program of or Blue 94, five is what I talked about.

Really developed early on when there was a more traditional path of a first generation Egfr inhibitors, then followed Bios Emerton day of once the T 790 M mutation of emerge and then the.

Christina Rossi: I think overall utilization of Midasdorin is limited, as I said, just by the – both the efficacy and sort of safety tolerability profile of that therapy. As Fouad said earlier, you know, we are filing for indications in advanced SM. That's our assumption. How AvaKit is used in the real world, I think, you know, will be driven by both of the factors that I just mentioned, but certainly, we would imagine that initial utilization will be in patients who, you know, have more significant diseases, and, you know, over time, we're looking forward to filing for it in the non-advanced forms of the disease and having the indication there as well. And we'll be, you know, engaging with hematologists as well as allergists and others who may see these patients to ensure that they are being identified and appropriately diagnosed. And that's really going to be our focus.

And that of see 797 S mutation was the most frequent on mutations thereafter.

On the target product profile of of course, it's very challenging when you have to hit that range of mutations while also.

The molecule that the wild type of sparing and brain penetrant. So it's a very classically blueprint molecule of of a select our discrete patient population. Blu 701 to me is much more interesting because that was a program that was started based on on understanding of wear resistance.

Would go over time.

And that was watching the landscape change no somerton, they've moved to first line and based on preclinical models determining that the C. 797 S mutation of wood would likely appear earlier and so that's that's our evolving landscape were definitely seen it emerge the.

Operator: Thank you. Our next question comes from Eun Yang with Jefferies. Your line is open. Thank you. For the EGFR program, is the frequency of a C797S mutation post the first line or C-multinib in non-small cell lung cancer similar to death after the second line?

Interest from Kols is significant for that program you know, there's a lot of ways, we see that blues.

<unk> 701 could be the awesome.

Awesome and it was to the the first generation of Egfr of molecules.

So the the range to date is perhaps a little bit lower than that debt sort of 10 per cent range, maybe up to 20% of patients develop that form of resistance, but again most of them or NAV.

Eun Yang: after the second line use.

Jeff Albers: So maybe I'll start, and then I'll have Fouad jump in as well. And I'll back up and actually think about the development of these two programs. So our triple mutant program, or BLU945, as Fouad talked about, was really developed early on when there was a more traditional path of first-generation EGFR inhibitors, then followed by o-submertinib once a T790M mutation emerged, and then the recognition that a C797S mutation was the most frequent on-track mutation thereafter.

Is that debt to continue to evolve.

Importantly, with the profile of Foulard hit on is the fact that we've created a very selective molecule.

Wild type sparing molecule in the brain penetrant molecule and so as you think about the evolving landscape, we see seven of one could potentially serving as an anchor to any treatment of egfr patients and bean is.

Set up well to combine with other therapies, including 94 of five or other so.

Jeff Albers: The target product profile, of course, is very challenging when you have to hit that range of mutations while also creating a molecule that's wild-type sparing and brain penetrant. Blue 701, to me, is much more interesting because that was a program that was started based on an understanding of where resistance would go over time. And that was watching the landscape change, and Osimertin had moved to the first line, and based on preclinical models, determining that the C797S mutation would likely appear earlier. And so that's an evolving landscape. We're definitely seeing it emerge. The interest from KOLs is significant for that program.

We're prepared to watch the landscape continue to evolve, but with the two molecules. We think we can cover the vast majority of patients at some time on along their treatment journey.

Thank you. Our next question comes from Michael <unk> with Baird Capital. Your line is open.

Hey, guys. Thanks for taking the question just sort of follow up on the CDK to program on a real realize youre still in preclinical development there, but just curious if you of a sense of what indications you might plan to target.

Obviously, it'll be driven by some data and then also.

How does that relate to sort of going after the the resistant mutations for the CDK four six inhibitors.

Thanks, Mike a lot of pool or do you want to take that.

Yes, Thank you Jeff.

The CDK to program.

Jeff Albers: In a lot of ways, we see that Blue 701 could be to Osimertin what Osimertin was to the first generation of EGFR molecules. So the range to date is perhaps a little bit lower in that that... 10% range, maybe up to 20% of patients develop that form of resistance. But again, osomerdib, that data continued to evolve. Importantly, with the profile as Fouad hit on, is the fact that we've created a very selective molecule, a wild-type sparing molecule, and a brain penetrant molecule.

I mentioned earlier is there any of them Devil really.

The two <unk>.

Solid parts of the program high selectivity and high potency of engage the CDK to as as a target.

And when we look at the cancer and the role of CDK too and it sort of got off to where your partner Chiesi and E.

We can see a broad range of cancer, where these agents could be double.

Monotherapy or in combination with other agents.

We give you a few examples of cancer, where we know CDK to NCC of knee on a major of player.

Jeff Albers: And so, as you think about the evolving landscape, we see 701 potentially serving as an anchor for any treatment for EGFR patients and being set up well to combine with other therapies, including 945 or others. So, we're prepared to watch the landscape continue to evolve, but with the two molecules, we think we can cover the vast majority of patients at some time along their treatment journey.

If you think about ovarian cancer.

On that cancer.

He is an addiction to this pathway in ovarian cancer. If you think about other accounts sort of like the breast cancer. There is really the opportunity not only to devil of this agent in patients resistance to CDK. Four six is that we have in the treatment of hormone positive breast cancer today, but also in combination with <unk>.

Operator: Thank you. Our next question comes from Michael Ulz with Barrett Capital. Your line is open.

Michael Eric Ulz: Hey guys, thanks for taking the question. I just had a follow-up on the CDK2 program, and I realize you're still in preclinical development there, but just curious if you have a sense of what indications you might might plan to target. Obviously, it'll be driven by some data, and then also you know how that relates to sort of going after the resistant mutations for the CDK4-6 inhibitors. Thanks.

CDK four cities on hormone therapy in breast cancer of moving to.

The year lines, there on a number of other cancers, such as gastric and esophageal cancer would be exploring but I mean, if I step back a little bit I would say with such an agent. The scope of the opportunity is really broad. It will include a variety of the development strategies all the way from monotherapy to combination agents.

Jeff Albers: Thanks Michael. Fouad, do you want to take that?

Fouad Namouni: Yes, thank you, Jeff. So the CDK2 program, as I mentioned earlier, is really developed with really two solid parts of the program, high selectivity and high potency against CDK2 as a target. And when we look at cancer and the role of CDK2 and its regulatory partner, CCNH,

And will include a variety of.

So types in combination. So we're very very excited them I'm, particularly excited about this CDK to program we are announcing today.

Thank you and I'm currently showing no further questions at this time of like to turn the call back over to Jeff Albers for closing remarks.

Fouad Namouni: me.

Fouad Namouni: We can see a broad range of cancers where this agent could be developed either as monotherapy or in combination with other agents. I will give a few examples of cancers where we know CDK2 and CCNE are major players. If you think about ovarian cancer, there is an addiction to this pathway in ovarian cancer. If you think about other cancers like breast cancer, there is really the opportunity not only to develop this agent in patients resistant to CDK4-6s that we have in the treatment of hormone-positive breast cancer today but also in combination with CDK4-6s and hormone therapy in breast cancer moving to earlier lines.

Thank you operator, so I started off the call of talking about how 2020 was a transformational year for blueprint medicines and hopefully you've got a sense of the setup. We feel like we have for 2021 really is a year of of execution across that fully integrated business and starting with the.

The potential approval in advanced SM for any of the printing of in the second quarter.

There's just a flurry of progress from our discovery efforts and upcoming preclinical data.

Fouad Namouni: There are a number of other cancers, gastric and esophageal cancer, that we will be exploring. But I mean, if I step back a little bit, I would say with such an agent, the scope of the opportunity is really broad. It will include a variety of development strategies all the way from monotherapy to combination agents and will include a variety of cancer types and combinations. So we are very, very excited. I'm particularly very excited about this CDK2 program we are announcing today.

The opportunities at various conferences, both in the first half and second half and then it continued clinical execution.

All of your across multiple programs all under of underscored by a strong financial position. So.

As always we appreciate your taking the time of.

This morning, the spend it with us and look forward to further updates over the coming months have a good day bye bye.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.

Operator: Thank you, and I'm currently showing no further questions at this time. I'd like to turn the call back over to Jeff Albers for closing remarks.

[music].

Jeff Albers: Thank you, operator. So I started off the call talking about how 2020 will be a transformational year for Blueprint Medicines. And hopefully, you've got a sense of the setup we feel like we have for 2021 really as a year of execution across that fully integrated business and starting with the potential approval of advanced SM for Ava Pritnev in the second quarter. There's a flurry of progress from our discovery efforts and upcoming pre-clinical data opportunities at various conferences, both in the first half and second half. And then it continued clinical execution across multiple programs, all underscored by strong financial positions.

True.

On the data.

[music].

Jeff Albers: So, as always, we appreciate you taking the time this morning to spend it with us and look forward to further updates over the coming months. Have a good day. Bye bye.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.

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