Q1 2021 Blueprint Medicines Corp Earnings Call

Okay.

Ladies and gentlemen, thank you for standing by.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the Blueprint Medicines conference 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. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Ms. Kristin Hodes, with Blueprint Medicines. Thank you. Please go ahead, ma'am.

Welcome to the Blueprint medicines conference 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 the question during the session you will need.

The press Star one on your telephone.

If you require any further assistance please press star zero.

I'd now like to hand, the conference over to your speaker today, Ms. Christine hold it with the blueprint medicines. Thank you. Please go ahead ma'am.

Thank you operator, good morning, everyone. This is Christian how rest of blueprint medicines welcome to blueprint medicines first quarter 2021 financial and operating results conference call.

Kristin Hodes: Thank you, Operator. Good morning, everyone.

Kristin Hodes: This is Kristen Hodes of Blueprint Medicine. Welcome to Blueprint Medicine's first quarter 2021 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. Today on our call, Jeff Albers, our Chief Executive Officer, will discuss Blueprint Medicine's first quarter 2021 business highlights.

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

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

Today on our call, Jeff Albers, our Chief Executive Officer will discuss blueprint medicines first quarter 2021 business highlights.

Kristin Hodes: Christy Rossi, our Chief Commercial Officer, will provide a commercial update. Becker-Hewes, our Chief Medical Officer, will review our clinical progress and highlight upcoming milestones across our growing pipeline, and Mike Landsittel, our Chief Financial Officer, will review our first quarter 2021 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. However, actual events or results could differ materially from those expressed or implied by any forward-looking statement as a result of various risks, uncertainties, and other factors, including those set forth in the risk factor section of our SEC filing.

Christy Rossi, our Chief commercial officer, who will provide a commercial update.

Becker Hughes, our Chief Medical Officer will review, our clinical progress and highlight upcoming milestones across our growing pipeline.

And Mike Lee and stone, our Chief Financial Officer will review, our first quarter 2021 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.

Against the 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 on the risk factors section of our SEC filings.

In addition, any forward looking statement made on this call represent 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.

Kristin 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.

Jeff Albers: Good morning. 2021 is off to a productive start, and I'm pleased to provide an update on recent progress across our growing portfolio. As we outlined on our year-end call, our 2021 efforts are centered around three strategic pillars. First, Accelerating the global adoption of AvaKit and Gavretto. Second, advancing the next wave of therapeutic candidates to clinical proof of concept, and third, further expanding our precision therapy research pipeline. Just a few months into the year, we've already made significant progress against each of these goals.

Thanks, Christian and good morning, everyone.

2021 is off to a productive start and I'm pleased to provide an update on recent price.

Progress across our growing portfolio.

As we outlined on our year end call our 2021 of efforts are centered around three strategic pillars.

First accelerating the global adoption of the kit and GAAP of Idaho.

Second advancing our next wave of therapeutic candidates to clinical proof of concept.

And third further expanding our precision therapy research pipeline.

Just a few months into the year, we've already made significant progress against each of these goals.

Jeff Albers: As Christy will discuss in a moment, we continue to advance the commercial launches of AvaKit and Gavrato. In parallel, we're preparing for the anticipated approval of AvaKit in advanced systemic mastocytosis. As we near our PDUFA date in the U.S., and with the Type 2 Variation MAA under review with the EMA,

As Christie will discuss in a moment, we continue to advance the commercial launches of Eva kit and gave her Idaho.

In parallel we're preparing for the anticipated approval of Eva kit in advanced systemic mastocytosis as.

As we near of Purdue date in the U S and with the type two variation MAA under review with the EMA.

Jeff Albers: We're moving forward with urgency to provide a therapeutic option for as many patients as possible fighting this disease. At the ACR Annual Meeting earlier this month, we presented registrational data from our Phase II Pathfinder Trial and Advanced Estimates, which demonstrated a confirmed overall response rate of 75%, with responses occurring rapidly and continuing to deepen over time. In addition, new patient-reported data showed that treatment with AvaKit significantly reduced disease symptoms and improved quality of life. We believe these results reinforce the potential of AvaKit to fundamentally change the outlook for patients with advanced systemic mastectomy.

We're moving forward with urgency to provide of therapeutic option for as many patients as possible fighting this disease.

At the ACR annual meeting earlier this month, we presented Registrational data from our phase II Pathfinder trial in advanced SM.

Which demonstrated the confirmed overall response rate of 75%.

With responses occurring rapidly and continuing to deepen over time.

In addition, new patient reported data showed that treatment with eight of a kit significantly reduce disease symptoms and improve quality of life.

We believe these results reinforced the potential of Eva kit to fundamentally change the outlook for patients with advanced systemic mastocytosis.

We also shared new data at ACR from several of investigational medicines in our portfolio that comprised our next wave of therapeutic candidates.

Jeff Albers: We also shared new data at AACR from several investigational medicines in our portfolio that comprise our next wave of therapeutic candidates, including Blue 263, our next generation kit DH16V inhibitor. Blue 701 and Blue 945 are two EGFR development candidates, and our newest programs, Blue 222 targeting CDK2, and Blue 852 targeting MAP4K1. Collectively, these programs have the potential to dramatically expand our ability to reach patients on a global basis. In fact, each of these markets targeted by these new programs is forecast to more than double in size over the next five years, underscoring the opportunity for us to bring innovation to areas of significant medical need. Since our founding 10 years ago, we've worked hard to integrate our discovery, development, and commercialization efforts in order to maximize innovation and efficiency.

<unk> Blu 263, our next generation kit D. H 16 V inhibitor.

Blu 701, and Blu nine four of five or two egfr of development candidates.

And our newest programs Blu 222 targeting CDK too and.

And Blue 852 targeting map for K one.

Collectively these programs have the potential to dramatically expand our ability to reach patients on a global basis.

In fact, each of these markets targeted by these new programs is forecast of more than double in size over the next five years.

Underscoring the opportunity for us to bring innovation to areas of significant medical need.

Since our founding 10 years ago, we've worked hard to integrate our discovery development and commercialization efforts in order to maximize innovation and efficiency.

We've already demonstrated the productivity of this approach having successfully discovered and developed two approved medicines.

Jeff Albers: We've already demonstrated the productivity of this approach, having successfully discovered and developed two approved medicines. In the past year and a half alone, we've expanded our pipeline with five additional development candidates. All of which we intend to advance with the same sense. To that end, and as Becker will describe in a few minutes, we remain on track to initiate multiple clinical trials in the months ahead, positioning us to generate several significant proof-of-concept data sets in the near future.

In the past year and a half alone we've expanded our pipeline with five additional development candidates.

All of which we intend to advance with the same sense of urgency.

To that end and as Becker will describe in a few minutes, we remain on track to initiate multiple clinical trials in the months ahead positioning us to generate several significant proof of concept data sets in the near future.

Jeff Albers: Importantly, we continue to operate from a position of tremendous financial strength, with the resources to invest in our commercial efforts, our pipeline programs, and our research end, as we aim to make real the promise of precision therapy for as many people with cancer and hematologic disorders as possible. With that, I'll now turn the call over to Christy to discuss our commercial efforts.

Importantly, we continue to operate from a position of tremendous financial strength with the resources to invest in our commercial efforts our pipeline programs and our research engine.

As we aim to make real the promise of precision therapy for as many people with cancer and hematologic disorders as possible.

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

Christina Rossi: Thanks, Jeff, and good morning, everyone. I'm pleased to share our first quarter results as we continue to progress the launches of AvaKit and Gavreta. In Q1, we generated net product revenue of $9 million, including $7.1 million in sales of AvaKit and $1.8 million in sales of Gavreta. Let me start with Gavreta.

Thanks, Jeff and good morning, everyone.

I'm pleased to share our first quarter results as we continue to progress the launches of Eva kit and GAAP read out.

In Q1, we generated net product revenue of $9 million, including $7 1 million in sales of eight of cat and 1.8 million on sales of gas read out.

Let me start with GAAP Ralph.

Christina Rossi: As I shared on our Q4 call, we are focused, with our partners at Genentech, on two key priorities for the launch. The first is growing our share of new patients who are starting on a selective red inhibitor. And the second is increasing the percent of RET-positive patients who are identified and treated with a targeted therapy. We've seen good progress against our first priority.

As I shared on our Q4 call. We are focused with our partners at Genentech on two key priorities for the lunch.

The first is growing our share of new patients who are starting on a selective ret inhibitor.

And the second is increasing the percent of ret positive patients who are identified and treated with a targeted therapy.

We think good progress against our first priority on.

Christina Rossi: Our share of new patient starts continued to increase over the course of Q1, exceeding 35% by the end of the quarter. An increasing number of new patients starting on Gavreto is a key driver of future revenue growth based on the favorable duration of treatment we expect from our clinical data. And in March, we had our highest number of new patients starting on therapy since launch. The number of Gavreto prescribers is continuing to grow, and we've started to see stronger uptake among physicians in the community setting, many of whom are prescribing a selective red inhibitor for the first time. We continue to receive positive feedback on the deep and durable responses, predictable and manageable safety profile, and once-daily dosing with Gavreto, which makes it well-suited to broad use in the community setting.

The share of new patient starts continue to increase over the course of Q1 exceeding 35% by the end of the quarter.

An increasing number of new patients starting on GAAP read out is the key driver of future revenue growth based on the favorable duration of treatment, we expect from our clinical data.

And in March we had our highest number of new patients starting on therapy since launch.

The number of guests Red Oak prescribers is continuing to grow and we started to see stronger uptake among physicians in the community setting.

Many of whom are prescribing of selective ret inhibitor for the first time.

We continue to receive positive feedback on the deep and durable responses predictable and manageable safety profile and once daily dosing with GAAP read out, which makes it well suited to broad use in the community setting.

We see great potential to further grow the ret inhibitor of market overall as fewer than half of rat patients are being tested for Iraq, and then being given the opportunity to be treated with the targeted therapy.

Christina Rossi: We see great potential to further grow the Rett inhibitor market overall, as fewer than half of Rett patients are being tested for Rett and then being given the opportunity to be treated with a targeted therapy. We are working with our partners at Genentech to impact this through Continued Multidisciplinary Education to increase comprehensive biomarker testing and ensure that it is appropriately acted upon. As we've seen with other targeted therapy launches, we expect ongoing growth in the number of identified patients driven by these efforts, by the availability of highly effective therapy, and by the waning impact of COVID in the U.S. as we approach the second half of the year.

We are working with our partners at Genentech to impact. This through continued multi disciplinary education to increase comprehensive biomarker testing and ensure that it is appropriately acted upon.

As we've seen with other targeted therapy launches, we expect ongoing growth in the number of identified patients driven by these efforts by the availability of highly effective therapy.

And by the waning impacts of COVID-19 in the U S. As we approach the second half of the year.

Finally, we are excited about the progress we've made with our partners to bring of Red oak to patients around the world.

Christina Rossi: Finally, we are excited about the progress we've made with our partners to bring Gevretto to patients around the world. A few weeks ago, Seastone Pharmaceuticals received NMPA approval in China for Gavretto in RET fusion positive non-small cell lung cancer, making it the first approved selective RET inhibitor in the market. We are also looking forward to the anticipated approval and launch of Gavreto in Europe by our partner Roche. We expect these global launches to be additional drivers of revenue growth in the future. Now, let's turn to AvaKip.

A few weeks ago ceased on pharmaceuticals received an M. P. A approval in China forgive Red Oak in Ret fusion positive non small cell lung cancer, making it the first approved selective ret inhibitor in the market.

We are also looking forward to the anticipated approval and launch of Red Oak in Europe by our partner Roche.

We expect these global launches to be additional drivers of revenue growth in the future.

Now, let's turn to Ava cat.

And P D. Jeff for Alpha just we've seen consistent new patient starts quarter over quarter in the U S.

Christina Rossi: In PDGF or AlphaGIST, we've seen consistent new patient starts quarter over quarter in the U.S., and we are progressing our first EU launch in Germany. Our partner, Seastone, also recently secured an MPA approval of AvaKit, making it the first approved precision therapy for patients with PDGFR-alpha exon 18 mutant gist in China. We anticipate seeing incremental growth in GIST revenue over time with additional country launches.

And are progressing our first EU lunch in Germany.

Our partners. The stone also recently secured an M. P. A approval of Eva cat, making it the first approved precision therapy for patients with PD, Jeff for Alpha Exon 18 mutant Gist in China.

We anticipate seeing incremental growth in just revenue overtime with additional country launches.

Of course, our primary focus with Eva cash continues to be preparing for our anticipated approval and launch in advanced systemic mastocytosis in the U S. This quarter.

Christina Rossi: Of course, our primary focus with AvaKit continues to be preparing for our anticipated approval and launch in advanced systemic mastocytosis in the U.S. this quarter. As I've described before, advanced SM represents about 5-10% of the overall SM population, or about 2,000 to 3,000 patients in the U.S., many of whom are treated at major centers. We plan to initially focus the majority of our educational efforts on about 70 hematology oncology centers that treat about half of all advanced SM patients in the U.S. Our existing commercial and medical affairs infrastructure allows us to prioritize these key centers, while using our portfolio footprint to increase patient identification in the community over time.

As I've described before advanced S. M represents about 5% to 10% of the overall S. M population or about 2000 to 3000 patients in the U S.

Many of whom are treated at major centers.

We plan to initially focus the majority of our educational efforts on about 70, hematology oncology centers that treat about half of all advanced SM patients in the U S.

Our existing commercial and medical affairs infrastructure allows us to prioritize these key centers, while using our portfolio footprint to increase patient identification and the community overtime.

As we begin to realize the tremendous impact that Eva kit can bring to patients with S. M. We are focused in three key areas.

Christina Rossi: As we begin to realize the tremendous impact that AvaKit can bring to patients with SM, we are focused on three key areas. First, on driving patient identification and appropriate diagnosis, which includes understanding current treatment and referral patterns to key centers.

First on driving patient identification and appropriate diagnosis.

Which includes understanding current treatment and referral patterns to key centers.

We believe that upon approval initial utilization of a the cat will be driven by already diagnosed prevalent patients who may be currently treated with might've store N. Other tyrosine kinase inhibitors or side of reductive agents.

Becker Hewes: We believe that upon approval, initial utilization of AvaKit will be driven by already diagnosed prevalent patients who may be currently being treated with mitostaurin, other tyrosine kinase inhibitors, or cytoreductive agents. Over time, we expect to see increasing utilization from newly diagnosed patients. We also believe that making blood-based testing for KIT-D816V, the SM driver mutation, widely available will help remove barriers to diagnosis for both advanced and non-advanced SM patients. In our fourth-quarter call, we announced that highly sensitive blood-based tests for KIT-D816b are now commercially available in the U.S., and we expect that over the course of 2021, testing availability will grow to cover about 80% of SM patients in the U.S. We are confident that this, combined with disease education and other efforts, will translate into an increased number of identified SM patients who are diagnosed and have access to treatment.

Overtime, we expect to see increasing utilization from newly diagnosed patients.

We also believe that making blood based testing for kit. The 816 P. The S M driver mutation.

Idly available will help remove barriers to diagnosis for both advanced and non advanced SM patients.

And our fourth quarter call, we announced that highly sensitive blood based tests for kit. The 16 D are now commercially available in the U S and we expect that over the course of 2020, one testing availability will grow to cover about 80% of SM patients in the U S.

We are confident that this combined with the the disease education and other efforts will translate into an increased number of identified S. M patients.

Who are diagnosed and have access to treatment.

Our second priority is educating health care providers patients and other stakeholders on the differentiated and compelling value proposition of Eva Cat NSM.

Becker Hewes: Our second priority is educating healthcare providers, patients, and other stakeholders on the differentiated and compelling value proposition of AvaKit and SM. We believe AvaKit is a transformative, precision therapy solution that will profoundly change the way patients are treated and meaningfully improve their lives, and we will work to ensure healthcare providers are fully educated on the clinical data supporting its use quickly upon approval. Finally, and most importantly, we are committed to providing best-in-class access and support for patients.

We believe the kit at the transformative precision therapy solution that will profoundly change the way patients are treated and meaningfully improve their lives and we will work to ensure the health care providers are fully educated on the clinical data supporting its use quickly upon approval.

Finally, and most importantly, we are committed to providing best in class access and support for patients.

Becker Hewes: Consistent with our approach to our launch of AvaKid and GIST, as well as Gavreto, we will focus on meeting the unique needs of SM patients, facilitating access to therapy, and providing best-in-class financial assistance and support through the Your Blueprint Patient Support Program. As we look ahead to the launch of AvaKit and Advanced SM and continue to progress development in non-advanced forms of the disease. We are excited to build on our leadership position with the goal of meeting the unique needs of all SM patients.

Consistent with our approach to our launch of Eva Kid ingest as well as Gathright Oh, we will focus on meeting the unique needs of SM patients facilitating access to therapy, and providing best in class financial assistance and support through the Euro blueprint patient support program.

As we look ahead to the launch of Eva kit in advanced SM and continue to progress development and non advanced forms of the disease.

We are excited to build on our leadership position with the goal of meeting the unique needs of all of S. M patients.

Eva kept will play a key role as the cornerstone of our portfolio and we look forward to further extending and expanding the impact we can have on the S. M with the development of Blue cheese sticks story as we initiate the harbor study this year.

Becker Hewes: AvaKit will play a key role as the cornerstone of our portfolio, and we look forward to further extending and expanding the impact we can have on SM with the development of Blue263 as we initiate the Harbor Study this year. With that, I would now like to turn the call over to Becker to discuss our clinical portfolio.

With that I would now like to turn the call over to Becker to review our clinical portfolio.

Becker Hewes: Thanks, Christy. And good morning, everyone.

Thanks, Christy and good morning, everyone.

Becker Hewes: As we discussed a couple of weeks ago on our AACR call, we're in the midst of a period of robust research productivity, having nominated five new development candidates in the past 18 months. Of those programs, BLU263 and BLU945 are anticipated to begin clinical development in the next few months. Let me start with BLU263 and continue Christy's discussion of our groundbreaking kit franchise.

We discussed a couple of weeks ago on our ACR call. We're in the midst of a period of robust research productivity, having nominated five new development candidates in the past 18 months.

Two of those programs Blu 263, and Blue 94 of five are anticipated to begin clinical development in the next few months let.

Let me start with Bluetooth six three and continued Christie's discussion of our groundbreaking kit franchise boot.

Becker Hewes: Blu263 is a non-brain penetrant kit D816V inhibitor with similar potency to avian. We presented Phase 1 data at AACR that showed Blue263 was well-tolerated at all doses tested in healthy volunteers. Pharmacokinetics were linear and dose dependent with a half-life supporting once daily dose.

Bluetooth fixed three of the non brain penetrant.

The 816 V inhibitor with similar potency to either kit we.

We presented phase one data at ACR that showed Bluetooth six three was well tolerated at all doses tested in healthy volunteers pharmacokinetics were linear and dose dependent with the half life supporting once daily dosing.

Based on these data we plan to initiate the phase two three harbor trial later this year.

Becker Hewes: Based on these data, we plan to initiate the Phase 2-3 HARBOR trial later this year. Similar to the ongoing Pioneer trial for AvaKit in non-advanced SM, we will evaluate a range of doses, quantifying the impact on disease symptoms and safety. This will include a multiple-dose Part 1 to determine the optimal dose, followed by a randomized placebo-controlled Part 2, evaluating reduction in total symptom score as the primary answer.

Similar to the ongoing pioneer trial for Ava kit and non advanced S. M. We will evaluate a range of doses quantifying the impact on disease symptoms and safety.

This will include a multiple dose part one to determine the optimal dose followed by a randomized placebo controlled part two evaluating reduction in total symptom score as the primary endpoint.

Becker Hewes: One novel aspect of the HARBOR trial will be enrolling patients with a broader eligibility criteria, including patients with a lower baseline total symptom score. This provides the potential to extend our reach to a broader population of patients with non-advanced systemic mastocytosis, a central goal of the Blue 263 program. In addition, we plan to include an exploratory cohort in Part 2 of the trial for patients with monoclonal mast cell activation syndrome, also driven by the KIT D816V mutation.

One novel aspect of the harbor trial will be enrolling patients with the broader eligibility criteria, including patients with the lower baseline total symptom score.

This provides the potential to extend our reach to a broader population of patients with non advanced systemic mastocytosis.

Central goal of the Bluetooth <unk> III program.

In addition, we plan to include an exploratory cohort in part two of the trial for patients with monoclonal mast cell activation syndrome also driven by the kit the 816 V mutation.

Becker Hewes: Turning now to our EGFR program. During our AACR call, we outlined how our EGFR inhibitors are designed to address important unmet medical needs by providing comprehensive coverage of activating and on-target resistant mutations. They have optimized selectivity profiles, enabling combination strategies and high CNS activity to treat or prevent brain maturation. At AACR, we presented for the first time foundational preclinical data for BLU701, our potent wild-type selective brain penetrant double mutant EGFR inhibitor.

Turning now to our Egfr programs.

During AC or.

Our ACR call, we outlined how our Egfr inhibitors are designed to address important unmet medical needs by providing comprehensive coverage of activating and on target resistant mutations.

We have optimized flow activity profiles, enabling combination strategies and high see enough activity to treat or prevent brain metastases.

At ACR, we presented for the first time foundational preclinical data for Blu 701, our potent wild type selective brain penetrant double mutant Egfr inhibitor. We also presented additional preclinical data for Blu 945 of Triple mutant Egfr inhibitor.

Becker Hewes: We also presented additional preclinical data for BLU945, a triple mutant EGFR. As monotherapies and combination therapies, these rationally designed investigational candidates have the potential to address patient needs across all lines of care. This quarter, we will initiate the clinical trial of Blue 945, and later this year, we plan to initiate a similar trial for Blue 701. The BLUE-945 trial will include a dose escalation portion in patients with EGFR mutant non-small cell lung cancer who have previously received at least one prior EGFR-targeted tyrosine kinase inhibitor, followed by expansions in cohorts of patients with tumors harboring specific mutation profiles.

As monotherapy and combination therapies. These rationally designed investigational candidates have the potential to address patient needs across all lines of therapy.

This quarter, we will initiate the clinical trial of Blu nine four of five and later this year, we plan to initiate a similar trial for Blu 701.

The Blue 945 trial will include a dose escalation portion in patients with Egfr mutant non small cell lung cancer, who have previously received at least one prior egfr targeted tyrosine kinase inhibitor followed by expansion in cohorts of patients with tumors harboring specific mutation profiles, while our initial focus.

Becker Hewes: While our initial focus will be to rapidly demonstrate single-agent activity, we plan to quickly advance the development of both of these agents into combinations with each other and other EGFR-targeted therapies, a strategy that offers multiple shots. With the initiation of these trials across our clinical portfolio, we are well positioned for numerous milestones in the quarters ahead. At ASCO in June, we will present updated clinical data for Gevretto from the ARO trial in patients with non-small cell lung cancer, as well as in patients with solid tumors driven by Rett oncogenesis.

It will be to rapidly demonstrate single agent activity, we plan to quickly advance development of both of these agents into combinations with each other and other egfr targeted therapies. The strategy that offers multiple shots on goal.

With the initiation of these trials across our clinical portfolio, we are well positioned for numerous milestones in the quarters ahead.

I'd ask on June we will present updated clinical data forgive read out from the arrow trial in patients with non small cell lung cancer as well as in patients with solid tumors driven by the Rep oncogene.

Becker Hewes: We also anticipate presenting preclinical combination data for blue 701 and blue 945 in the second half. In 2022, we plan to bring our two newest development candidates to the clinic, Blue 2-2-2, a potent and highly selective CDK2 inhibitor targeting Cycline E aberrant cancers, and Blue 8-5-2, a potential best-in-class MAP4K1 inhibitor developed under our immunotherapy collaboration with ROSA.

We also anticipate presenting preclinical combination data for Blu 701, and Blue 94, five in the second half of the year.

In 2022, we plan to bring our two newest development candidates through the clinic Blu 222 of potent and highly selective CDK <unk> inhibitor targeting cyclin E aberrant cancers, and blue eight five to a potential best in class Mt. Four K, one inhibitor developed under our immunotherapy collaboration with Roche, we look forward to prove.

Becker Hewes: We look forward to providing further updates on these programs as they move into the clinic. I'd now like to turn it over to Mike to discuss financial issues... Thanks Becker.

Riding further updates on these programs as they move into the clinic I'd now like to turn it over to Mike to discuss financial updates.

Thanks Becker earlier. This morning, we reported detailed first quarter financial results in our press release.

Michael Landsittel: Earlier this morning, we reported detailed first quarter financial results in our press release. For today's call, I'll touch on a few highlights from the quarter. Total revenues for the first quarter were $21.6 million. This included $9 million in net product sales, as Christy mentioned, and $12.6 million in collaboration revenue. Primarily from our agreements with Roche and Seastone. Our total operating expenses increased moderately compared to the fourth quarter of 2020, primarily driven by costs associated with advancing our early-stage pipeline towards the, offset by cost-sharing from our agreement with Roche on GetREDA.

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

Total revenues for the first quarter were $21 $6 million. This included $9 million of net product sales as kristie mentioned and $12 $6 million in collaboration revenue, primarily from our agreements with Roche and system.

Our total operating expenses increased moderately compared to the fourth quarter of 2020, primarily driven by costs associated with advancing our early stage pipeline towards the clinic.

Offset by cost sharing from our agreement with Roche on GAAP read on.

As we expand investment in our promising early stage programs as they enter the clinic over the next few quarters, we expect to see continued increases in quarter over quarter operating expense growth.

Michael Landsittel: As we expand investment in our promising early-stage programs as they enter the clinic over the next few quarters, we expect to see continued increases in quarter-over-quarter operating expenses. We ended the first quarter with $1.4 billion in cash, ensuring that we have sufficient resources to invest in our growing pipeline of wholly owned drug cannabis. As we look forward to the second half of 2021, we are uniquely positioned to drive revenue growth through a variety of sources, including direct product sales of AvaKit in multiple geographies.

We ended the first quarter with $1.4 billion in cash ensuring that we have sufficient resources to invest in our growing pipeline of wholly owned drug candidates.

As we look forward to the second half of 2021, we are uniquely positioned to drive revenue growth through a variety of sources.

Including direct product sales of Eva kit in multiple geographies.

Michael Landsittel: Royalties on both AvaKit and Gevretto outside the U.S., profit sharing on Gevretto Sales in the U.S., and milestone payments from our various collaborations. Based on our projected growth across these revenue sources, and driven largely by the planned launch of AvaKit and Advanced SM, the global expansion of indications for both AvaKit and Gavretto, and anticipated milestone payments in the third and fourth quarter We continue to be comfortable with the current total revenue expectations for 2021 of approximately $150 million.

Royalties on both the Ava kit and get rid of outside the U S.

Profit sharing on GAAP router sales in the U S.

And milestone payments from our various collaborations.

Based on our projected growth across these revenue sources and driven largely by the planned launch of Eva kit in advanced SM global expansion of indications for both the eve of kit and get Red Oak and anticipated milestone payments in the third and fourth quarters, we continue to be comfortable with the current total revenue expectations for 2021 of.

Of approximately $150 million.

This revenue growth will build on the strong financial position that we're in today and help solidify our path to becoming a self sustaining biopharmaceutical company.

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

Thank you.

Michael Landsittel: This revenue growth will build on the strong financial position that we are in today and help solidify our path to becoming a self-sustaining biopharmaceutical company. I would now like to turn the call over to the operator for questions. Operator.

Reminder, to ask a question press star one on your telephone.

Draw your question. Please press the pound key.

These limit yourself to one question each and we will now start the Q&A with.

The <unk> Richter with Goldman Sachs.

Operator: Thank you. As a reminder, to ask a question, press star 1 on your telephone. To withdraw your question, please press the pound key. Please limit yourself to one question each, and we will now start the Q&A with Salveen Richter of Goldman Sachs.

Good morning, Thanks for taking my question on maybe with regard to Rod pumps and identification of diagnostics, you've given us some sense of how that was tracking I think last quarter could you just talk about the trends in one two and on how you're thinking about the cadence moving forward.

Sure. So you know as I said, there's there's really Q2 key levers that we are focused on so one is is our share of of the rat market. But then the second as he mentioned is increasing the number of patients who are identified and treated and I spoke about this and in Q4 and said that you know of something like maybe 20.

Christina Rossi: Sure. So, you know, as I said, there are really two, you know, two key levers that we are focused on. So one is our share of the RET market, but then the second, as you mentioned, is increasing the number of patients who are identified and treated. And I spoke about this in Q4 and said that, you know, something like maybe 20 percent of patients, if you look at testing, as well as then the opportunity to be treated with a selective RET inhibitor, are having that opportunity at this point.

The percent of patients if you look at testing as well as that of the opportunity to be treated them with the selective ret inhibitor.

We are having that opportunity at this point. So there's still I think substantial room for growth and you know I will say, we haven't seen as much growth quarter over quarter as I'd like to see I think that's you know partially driven by the impact of COVID-19, which we know has really you know had it had an impact on patient identification of tap.

Christina Rossi: So there's still, I think, substantial room for growth. You know, I will say we haven't seen as much growth quarter over quarter as I'd like to see. I think that's, you know, partially driven by the impact of COVID, which has really, you know, had an impact on patient identification, testing, et cetera. But I'm optimistic that as we go into the second half of this year and then go forward from there, we will see that grow.

Staying et cetera, but I'm optimistic that as we go on to the second half of this year and then and then go forward from there we will see that grow them and certainly we've seen with other targeted therapies that you know the advent of effective treatment is in itself of primary catalyst. We saw that with you know Alex we saw that with Ross and I think we'll see it.

Christina Rossi: And certainly, we've seen with other targeted therapies that, you know, the advent of effective treatment is in itself a primary catalyst. We saw that with, you know, ELK. We saw that with ROS, and I think we'll see it here as well. So we'll look to see that number grow, and clearly that's, you know, in the best interest of patient care. So we're working actively with our partners at Genentech to really make that happen.

Here as well and so we'll look to see that number of growl and clearly that's the now in the best interest of patient care. So we're working actively with with our partners of Genentech to to really make that happen.

Your next question comes from the line of Mark from with Cowen and company.

Operator: Your next question comes from the line of Marc Frahm with Cohen & Company.

Christina Rossi: Hi, thanks for taking my question. I'm speaking with Christy. Just with the guidance on the patient numbers for ASM, can you kind of detail the, as we've seen in the clinical trials, right? The definition of a patient between ISM and ASM is very gray. And can you kind of detail how strict you're being in your definitions when you're kind of making those splits in your guidance and then kind of along those lines? Would you expect some of those patients that are under your guidance in the ISM population to actually, you know, be able to gain access to the drug once you're approved in ASM?

Hi, Thanks for taking my question.

Sticking with Christy.

What's the guidance on the patient numbers.

The detail the as we've seen in the.

Cool.

Trials like the definition of a patient screen I assume this is very great.

The.

How strict you're being in your definitions when you're kind of making the splits on your guidance and then kind of along those lines would you expect some of those patients that are in your guidance on the ISO on population to actually.

The gain access to the drugs once you're approved in Arizona.

Operator: Yeah, so you're right on. We've seen that in our clinical studies. I think we see it in clinical practice. It can be challenging to accurately subtype patients. The world's leading KOLs may struggle to do it at times, and certainly patient typing can evolve even in a given patient over the course of their disease. Where I think we see the most potential sort of gray or overlap is between patients with aggressive advanced SM or ASM and patients who may have ISM that's more severe.

Yeah, So you're right on and we've seen that on a clinical study is I think we see it in clinical practice. It can be it can be challenging to accurately subtype patients the worlds leading kols.

All of the do it at times and certainly of patient typing can evolve even in a given patient over the course of their their disease, where I think we see most potential of sort of gray our overlap is between patients with aggressive Ah advanced us the Amor a S M and patients who may have you know I assume that's more of more severe and.

Operator: And so the patient estimates that I gave of two to 3,000, approximately, those reflect that uncertainty, right? I think that as we get into the market, we'll have a better sense of how healthcare providers are subtyping patients. Fundamentally, I think the diagnosis codes, et cetera, are overlapping in this disease, and we've seen that it's not a space that payers tend to manage closely. So our assumption is that our initial utilization will be driven by patients for whom the healthcare provider believes that they have advanced SM. And we are optimistic that we will have good access for those patients given the really compelling value proposition that AvaKit will have for that patient population.

So you know the patient the patient and the estimates that I gave of two to 3000 approximately those reflect that uncertainty right. I think that's you know as we get into the market well, we'll have a better sense of how health care providers are our subtyping patients.

Fundamentally I think you know the the diagnosis codes et cetera are overlapping I'm in this disease and we've seen that it's not a space that payers tend to manage closely. So our assumption is that our initial utilization will be driven by patients for whom the health care provider of believes that they have adapted S. M. A.

And we are optimistic that you know we will have good access for those patients given the really compelling value proposition that aim of cat will have them in that patient population.

The next question comes from the line of Dane Leone with Raymond James.

Operator: The next question comes from the line of Dane Leone with Raymond James.

Jeff Albers: Thank you for taking the questions and congratulations on the start of the year and thanks for the guidance. There may be two questions for me, one in terms of guidance on the SM launch. Could you maybe provide more color in terms of how many patients are currently treated with Mido? And do you know what the patient population and opportunity would be for other switch therapies beyond Mido that you think docs would be willing to try?

Thank you for taking the questions and congrats on the sorts of the year and thanks for the the guidance of.

The maybe two questions from me one in terms of guidance on the us on watch.

Could you maybe provide more color on in terms of how many patients are currently treated with <unk> and you know what the patient population and opportunity it would be for other switch therapies beyond <unk> that you think docs would be willing.

Jeff Albers: to cross over to Ava Prydneb once approved. And then, second question, do you think it would be interesting to perhaps partner with AstraZeneca and add an adaptive arm to the ORCHARD study? Thank you. Alright, so Christy, why don't you take the ADVANCE-SM question and Becker take that 9-4-5 question around combinations.

The crossover to a blueprint nib once approved.

And then second question would be in terms of thinking about the.

The development of of 945.

Do you think it would be interesting to perhaps partner with Astrazeneca in an odd and adopted the arm into the Orchard study.

Thank you.

So Chris do you want to take the advantage of some question of in Becker and take the 945 question or on combinations.

Sure. So you know as as I mentioned in the prepared remarks, we would assume that you know upon approval, where we would expect to see initial utilization would be on patients who are diagnosed and currently being treated and we know that those patients can be treated with might've store and they may be treated off label with other teekay is cladribine them etcetera.

Christina Rossi: Sure. As I mentioned in the prepared remarks, we would assume that, upon approval, where we would expect to see initial utilization would be in patients who are, you know, diagnosed and currently being treated. And we know that those patients can be treated with Midostorin. They may be treated off-label with other TKIs, Cladribine, et cetera.

The utilization of Might've store and we don't have perfect insight into health care providers will report that maybe 30% of advanced SM patients are treated with might of storing the data would suggest it's probably less than that and I think a driver of the difference. There is that patients have a hard time staying on them and so what we hear.

Christina Rossi: We don't have perfect insight into the utilization of Midostorin. However, healthcare providers will report that maybe 30% of advanced SM patients are treated with Midostorin. The data would suggest it's probably less than that, and I think a driver of the difference there is that patients have a hard time staying on. And so what we hear is that, you know, duration of therapy in advanced SM with Midostorin is unfortunately suboptimal and can be well less than a year in many patients.

That you know duration of therapy and advanced of them with with Midas Doron is unfortunately, suboptimal and can be well less than a year and many patients and so are you know we are feeling confident certainly amongst the a S. M kols and people who are very comfortable managing this day.

He is that they understand you know sort of the value proposition that Eva kit will have in and would expect to see an uptake. There quickly. However, you know we'll go broader than the kols and get into the community and expect to see that patient identification grow overtime and have that be sort of the driver of of longer term growth.

Christina Rossi: And so, you know, we are feeling confident certainly amongst the SM, you know, KOLs, and people who are very comfortable managing this disease that they understand, you know, sort of the value proposition that AvaKit will have and would expect to see uptake there quickly. However, you know, we'll go broader than KOLs and get into the community and would expect to see patient identification grow over time and have that be sort of the driver of longer-term growth along with treatment of newly diagnosed patients, which again would happen over time. [inaudible]

Along with treatment of newly diagnosed patients, which again what happened over time.

And with respect to the ninth of five program. Our strategy is within our studies to really look at the combinations closely of Blue 94 of five as you May remember is is a compound with an extremely high window over while the types of very little inhibition of wild type of Eugene.

F R, which makes it a great combination partner for a number of different agents will be looking at combinations of drugs site costs of Martin Nib, and Blu 701 and in the future even drugs that address different mechanisms of resistance like Mac inhibitors. So we're going to take it on within our trials initially to us.

Becker Hewes: And with respect to the 945 program, our strategy is, within our studies, to really look at the combinations closely. Blue 945, as you may remember, is a compound with an extremely high window over wild-type, so very little inhibition of wild-type EGFR, which makes it a great combination partner for a number of different agents. We'll be looking at combinations of drugs like Osamartinib and Blue 701 and, in the future, even drugs that address different mechanisms of resistance, like MAT inhibitors. So, we're going to take them on within our trials initially to understand the tolerability of the combinations and look for preliminary activity.

To understand the tolerability of the combinations and looked for a preliminary activity.

At this point.

Your next question comes from the line of Michael Schmidt with Guggenheim.

Hey, guys. Good morning, Thanks for taking my questions I had one on labeling of considerations in the land as and you know my my first questions will.

Would you potentially pursue different brands on label for ease of Prisma.

Hum versus just and then you know thinking further upon potential approval in you know advanced or England as M with different dosing I guess, how would that potentially affect labeling given that the side effects and the other factors from my potentially defer given the.

Operator: Your next question comes from the line of Michael Schmidt with Guggenheim.

Operator: Hey guys, good morning. Thanks for taking my questions. I had one on labeling considerations in Indolent SM, and, you know, my first question was, will, would you potentially pursue a different brand or label for Avapritinib in SM versus GIST, and then, you know, thinking further upon potential approval in Advanced or Indolent SM with different dosing. I guess, how would that potentially affect labeling given that side effects and other factors might potentially differ given the different doses used in those two subtypes of SM?

The different doses used from those two subtypes of with them.

Chris you want to take the Yep share and so you know we are eagerly and urgently working to make a of a kit available first in advanced us on them and then in non advanced forms of the disease and our you know obviously working actively to finish enrollment of pioneer we are excited about the profile of Eva.

And and non advanced forms of the disease and so we don't anticipate making of different different brand available. We know that the benefit risk of Eva cat just like in many other you know with many other therapies that are approved of different doses for different indications is.

Christina Rossi: Christy, would you like to take it? Sure. So, you know, we are eagerly and urgently working to make AvaKit available first in advanced SM and then in non-advanced forms of the disease and are, you know, obviously working actively to finish enrollment in Pioneer. We are excited about the profile of Ava in non-advanced forms of the disease and don't anticipate making a different brand available.

Going to look different and so for for non advanced S. M. A you know the preliminary data we have seen at the 25 milligram dose them out of part one of pioneer of it makes us feel really confident that we're going to have a very favorable benefit risk profile and allows us to impact many patients with non advanced forms of the disease.

Christina Rossi: We know that the benefit-risk profile of AvaKit, just like many other, you know, with many other therapies that are approved at different doses for different indications, is going to look different. And so for non-advanced SM, you know, the preliminary data we've seen at the 25 milligram dose in part one of Pioneer makes us feel really confident that we're going to have a very favorable benefit-risk profile and allow us to impact many patients with non-advanced forms of the disease.

Of course, we're also excited about Bluetooth six three as you know our our share of next generation kit inhibitor and its backers said, we anticipate that that could potentially broaden even further the number of non advanced Ah patients that that we can impact them. So you know in terms of the dosing again, you know there's plenty.

He of precedent and labeling to be able to differentiate them, what the benefit risk profile and safety and efficacy look like on both across different indications as well as a different dose profile.

Christina Rossi: Of course, we're also excited about Bluetooth 6.3 as, you know, our sort of next generation kit inhibitor. And as Becker said, we anticipate that that could potentially broaden even further the number of non-advanced patients that we can impact. So, you know, in terms of dosing, again, there's plenty of precedent in labeling to be able to differentiate what a benefit-risk profile and safety and efficacy look like, both across different indications as well as at different levels.

Your next question comes from the line of David Lebowitz with Morgan Stanley.

The days of this morning, two questions from us the first on good Friday. So in the early launch stage what is the initial feedback from physicians on how the ret inhibitor may be used.

Versus staying with tableau you know are there specific types of patients are linked to one therapy versus the other.

Second question is on EBIT.

Operator: The next question comes from the line David Lebowitz with Morgan Stanley.

So in the review of the.

Of the registration by the F D a.

Operator: for David this morning. Two questions from us. The first on good

The question has been focused on how should we expect the labeling smoke in regards to the safety given the patient deaths on the phone.

Operator: So, at the early launch stage, what is the initial feedback from customers?

Christina Rossi: the initial feedback from physicians on how the RET inhibitor may be used versus, say, Ritevimol. Are there specific types of patients that lend to one therapy versus the other?

Nickel trials.

Maybe I'll start with the second question first and then I'll have Christy talk about the differentiation components from a physician perspective with GAAP Rado, So obviously, where we're in the middle of of our review and as we highlighted last quarter that given that that timing in the given the the active progress that we're making.

Operator: And our second question is on Avacad. So in the review of the registration by the FDA, where have questions been focused?

Jeff Albers: How should we expect the labeling to look in regards to safety given the patient death? A clinical trial. Maybe I'll start with the second question first, and then I'll have Christy talk about the differentiation components from a physician perspective with Gavreto. So obviously, we're in the middle of our review, and as we highlighted last quarter, given that timing and given the active progress that we're making, we're not going to comment on the back and forth.

We're not going to comment on the on the back and forth I mean questions change day to day and I can tell you, we're making nice progress on the agencies.

Very engaged.

And and going through the the data and understanding of the disease, but in terms of the specifics.

We're not wouldnt dig into that level of detail.

And then regarding I've read I wouldn't read has now and how you know the feedback. We're hearing are you know we we certainly hear that there are points of differentiation I'm you know certainly the the breadth of efficacy and the the consistently a deep and durable responses across patient types I think of something that's been compelling.

Jeff Albers: I mean, questions change day to day, and I can tell you we're making nice progress. The agency is very engaged in going through the data and understanding the disease, but in terms of the specifics, we wouldn't go into that level of detail.

On the teeth physicians about got right out of it and then of course as I've mentioned before there are differences in safety as well as the administration that can be kind of important then I think more important even as you get into the community setting and then certainly you know of Qt prolongation and not having that with GAAP right out of it has been an important point as well as once daily dosing the bigger picture, though with this.

Christina Rossi: And then regarding Gavreto and Retevmo and how, you know, the feedback we're hearing, we certainly hear that there are points of differentiation. You know, certainly the breadth of efficacy and the consistently deep and durable responses across patient types is something that's been compelling to physicians about Gavreto. And then, of course, as I've mentioned before, there are differences in safety as well as administration that can become important and, I think, more important even as you get into a community setting.

Is that you know are there are some physicians who have used both what we are seeing is that you know we are still at the beginning stages of really developing this overall market and so you know we're continuing to really add new prescribers and the majority of the prescribers were seeing for gut read all of our new two barquette prescribers, so their prescribing of Radnet.

Christina Rossi: And certainly, you know, QT prolongation and not having that with Gavreto has been an important point as well as once daily dosing. The bigger picture, though, with this is that, you know, there are some physicians who have used both. What we are seeing is that, you know, we are still at the beginning stages of really developing this overall market, and so, you know, we're continuing to really add new prescribers, and the majority of the prescribers we're seeing for Gavreto are new to market prescribers.

For the first time and what that tells me is that you know the opportunity here really is to go out and educate new prescribers and help them identify new about patience and there's still a ton of potential to do that because we know that the majority of our patients are not are not getting the opportunity to go on either one of these drugs.

Your next question comes from the line of Chris Raymond with Piper Sandler.

Christina Rossi: So, they're prescribing an RET inhibitor for the first time, and what that tells me is that, you know, the opportunity here really is to go out and educate new prescribers and help them identify new RET patients, and there's still a ton of potential to do that because we know that the majority of RET patients are not getting the opportunity to go on either one of these drugs.

Hey, Thanks, I'm, just kind of question on the EGF or molecules. So just just going through the preclinical data you guys have published on these it looks like Youre able to reach of therapeutically active dose with seven of them one at much lower doses than the 94 five.

So obviously, there's differences in underlying mutations, but just kind of curious around you know how do you think about but above that translate into the clinic and you know sort of the.

Operator: Your next question comes from the line of Chris Raymond with Piper Sandler.

All of the efforts here to find out of a therapeutic index.

Operator: Hey, thanks. I've got a question about the EGFR molecules. So just going through the preclinical data you guys have published on these, it looks like you're able to reach a therapeutically active dose with 701, at much lower doses than 9-4-5. So obviously, there are differences in underlying mutations. But just kind of curious around, you know, how do you think about that translating to the clinic and sort of the efforts here to find a treatment? Sure.

The second you want take that sure.

So.

The preclinical data as a guide to where we're going to start the study is really how how I look at preclinical data on dosing.

There obviously are differences between animals and humans with respect to exposure in metabolism. So we've got a starting dose for 94, five and we're working towards that for 701, we have some predictions about where we will see activity and get full coverage of the egfr molecule for the full.

Becker Hewes: So taking preclinical data as a guide to where we're going to start the study is really how I look at preclinical data on dosing. There obviously are differences between animals and humans with respect to exposure and metabolism. So we've got a starting dose for 9-4-5, and we're working towards that for 7-0-1. We have some predictions about where we will see activity and get full coverage of the EGFR molecule for the full day.

The day both of them, we expect to be amenable to once daily dosing and then as we combine them, we expect them to combine very easily because they both have a huge window of of wild type.

So we'll have to get into the clinic to really get more specifics about that.

The programs are not separated in time substantially so we do expect seven O one to potentially catch up with 94 of five which is which is great. Because then we can look at the combination of the two in real time as we.

Becker Hewes: Both of them we expect to be amenable to once-daily dosing, and then as we combine them, we expect them to combine very easily because they both have a huge window over wild type. So we'll have to get into the clinic to really get more specifics about that. The programs are not separated in time substantially. So we do expect 7-0-1 to potentially catch up with 9-4-5, which is great because then we can look at the combination of the two in real time as we dose escalate and really get MTDs for single agents and combinations in about the same timeframe, and, as I mentioned earlier, also combination dosing with other molecules such as osmertinib.

As we dose escalate.

And really get Mtge's for single agent in combination in about the same timeframe and as I mentioned earlier also combination dosing with either molecules such as customer nib.

Your next question comes from the line of Randy.

The Benjamin with JMP Securities.

Hey, good morning, guys. Thanks for taking the questions maybe.

Maybe just on the Blue to six three can you I think you mentioned here that there is an exploratory arm.

Monoclonal mast cell activation can you just remind us what are the various types of non advanced SM patients that you will be enrolling in the study and the the Registrational part.

Operator: Your next question comes from the line of Reni Benjamin with JMP Securities.

Operator: Hey, good morning guys. Thanks for taking the questions. Maybe just on Blue 263, can you, I think you mentioned here that there's an exploratory arm in monoclonal mast cell activation. Can you just remind us what are the various types of non-advanced SM patients that you'll be enrolling in the study in the registrational part? And you know, will it be evenly split?

Will it be will it be evenly split and it's this.

<unk> already been discussed with the with the FDA that you know.

It could ultimately lead to a registrational purposes or is it kind of solely based on the data.

So the foundation of our program is in patients in the this is the advocate program is in patients with the higher TFS score or symptom score and so we have that cohort in part one of our study. We're also going to be looking in part one it at the effect.

Becker Hewes: And is this already being discussed with the FDA that could ultimately lead to registration purposes, or is it, you know, kind of solely the So the foundation of our program is in patients, and this is the advocate program in patients with a higher TSS score or symptom score. And so we have that cohort in part one of our study. We're also going to be looking in part one at the effect on patients with a lower symptom score.

On patients with the lower symptom score the part of the reason that we have this two part program is to allow us to optimally set up our Registrational study. The plan right now is to look at both groups of of patients in that Registrational study.

Becker Hewes: The part of the reason that we have this two-part program is to allow us to optimally set up our registrational study. The plan right now is to look at both groups of patients in that registrational study, the obvious one being those with a higher symptom score. So there will be an opportunity to refine the registrational portion of the study as we move forward. We have had discussions about the general design of our program with the agency, but we're really going to let the data drive how we ultimately design the registrational part.

On the obvious one being those with the higher symptom score so the there'll be an opportunity to refine the registrational portion of the study as we move forward.

We have had discussions about the the general design of our program with the agency, but we're really going to let the data drive how we ultimately designed the registration of part of the study.

Operator: Your next question comes from the line of David Niren-Garden with Wetbush Securities. Hey, thanks for taking the question.

Your next question comes from the line of David Nearing Garden with Wedbush Securities.

Hey, Thanks for taking the question I just had a quick one on diagnosing mastocytosis patients you mentioned the blood test can you just remind us you know.

Christina Rossi: Question. I just had a quick one on diagnosing massive cytosis patients. You mentioned the blood test. Can you just remind us, you know? Currently, we require, as I recall, a bone marrow aspirate to confirm the diagnosis. Would this replace that, or would patients still, you know, be going in for a confirmatory or, you know, other testing? Maybe just, you know, walk us through how you see testing becoming a little bit more patient-friendly in the future? Thanks. Sure.

Currently the require as I recall on a bone bone marrow aspirate two confirmed diagnosis of this replace that or would patients still be going on for a confirmatory or other testing maybe just walk us through how you see you know testing, becoming a little bit more patient.

Friendly in the future.

Sure. So yeah, you're right. The the diagnosis of of S. M. You know power of criteria of it does require a bone marrow biopsy. That's you know recommended for for every S. N. Patient. However, you know we know that for some patients that is a hurdle and then certainly for some you know non advanced patients that are being treated by <unk>.

Christina Rossi: Sure. So yeah, you're right. The diagnosis of SM, you know, per criteria does require a bone marrow biopsy. That's, you know, recommended for every SM patient. However, you know, we know that for some patients, that is a hurdle. And certainly, for some, you know, non-advanced patients that are being treated by allergists, that can be a hurdle. And, you know, at times, patients are treated based on suspicion versus actually going through the process of getting a bone marrow biopsy.

Allergists that can be of her at all and and you know of times patients are treated based on suspicion versus actually going through the process of getting out of bone marrow biopsy for advanced SM patients. You know, we would certainly expect that of bone marrow biopsy. Because you know continues to be a very important part of diagnosis and management.

Christina Rossi: For advanced SM patients, you know, we would certainly expect that a bone marrow biopsy will continue to be a very important part of diagnosis and management over time. For non-advanced patients, you know, I think that blood-based testing can become a really important way of identifying potential patients in a much easier and simpler way that can be managed by allergists more broadly. And so the key to that is really making highly sensitive blood-based testing available.

The overtime for non events patients you know I think that blood based testing can become a really important way of identifying potential patients I'm in a much easier and simpler a way that can be managed by allergists more broadly.

And so the key to that is really making highly sensitive blood based testing available. So you know there is kept day at 16 V testing that's available now, but we know from our own data that you can miss patients I'm. If if you know you're not using the right approach in terms of sensitivity and specificity. So that's really our you know one of our very key pillar.

Christina Rossi: So, you know, there is D816V testing that's available now, but we know from our own data that you can miss patients if, you know, you're not using the right approach in terms of sensitivity and specificity. So that's really our, you know, one of our very key pillars over the next few years is to increase the number of patients who are tested. Certainly, once a patient, you know, tests positive, they may still require a bone marrow workup to further understand their disease and pathology. But I think that blood-based testing will be a very critical lever to enable more patients to get access to the right diagnosis more quickly.

Over the next few years is to increase the number of patients who are tested certainly once the patient has positive. They may still require of bone marrow work up to further understand a their disease and pathology, but I think that blood based testing will be a very critical lever to enabling more patients to get access to the right diagnosis.

The more quickly.

Your next question comes from the line of June Yang with Jefferies.

This is Sarah on for Ian.

On a couple of questions first on the Egfr of program, where do you think that the combination of nine four of five and 701 with differentiate in first line therapy versus off the Martin and <unk>.

Operator: Your next question comes from the line of Eun Yang with Jeffreys.

And then when do you think you would expect to start the first line trial.

Operator: This is Sarah. I'm here for you. I just have a couple of questions.

Is there potential to run that trial and of partnership and then just a quick one on the small cell activation syndrome exploratory cohort how many patients do you think there are with the diagnosis in the U S. Currently thank you.

Operator: I just have a couple of questions. First, on the EGFR program, where do you think that the combination of 945 and 701 would differentiate in first-line therapy versus osimertinib? And then when do you think you would expect to start the first line trial? Is there potential to run that trial in partnership? And then just a quick one on this mast cell activation syndrome exploratory cohort: how many patients do you think there are with that diagnosis in the U.S. currently? Thank you.

That's the.

So I'll start with the question of about 701 of 945, just remembering how patients present and why they are treated with <unk>. They have been the first line. They don't have to 79 of them at the beginning they have the driver mutation and the anti <unk> 790 activity of awesome or any of its important to prevent the emergence of.

Of that driver Awesome Martin I've also has a very high potency over that driver of dose driver mutations. So the combination of blue shoving on one in Blue 945, do those things plus additional activity. So 701 has better penetration of the central nervous system.

Becker Hewes: So, I'll start with the question about 701 and 945. Just remember how patients present and why they're treated with Osimertinib in the first line. They don't have T790M at the beginning.

Any compound.

Caleb or or in development that we're aware of and so treating patients initially with the driver mutation both in the periphery and in the central nervous system will serve to treat small ah well existing central nervous system disease, and any non measurable central nervous system disease, but also prevent the.

Becker Hewes: They have the driver mutation, and the anti-T790M activity of Osimertinib is important to prevent the emergence of that driver. Osimertinib also has very high potency over those driver mutations So, blue 701 and blue 945 do those things plus additional activities. As a result, 701 has better penetration of the central nervous system than any compound available or in development that we're aware of. And so, treating patients initially with the driver mutation both in the periphery and in the central nervous system will serve to treat small, well-established central nervous system diseases and any non-measurable central nervous system diseases but also prevent the disease from going to the central nervous system, which is often less well-penetrated than the blood is.

The disease from going to the central nervous system, which is often a less well penetrated than the blood is so we get amazing coverage throughout the body of Blu 701, and that context Blu nine four of five would be pregnant to prevent the emergence of a T. Seven nine a M. So here we've got.

A all oral regimen that would treat the entire body and treat all of the resistant mutations that we know all of that can emerge and so what we would expect there is an enhanced treatment of patients with CNS disease, as well as longer progression free survival.

Becker Hewes: So, we get amazing coverage throughout the body with blue 701. In that context, blue 945 would be present to prevent the emergence of T790M. So, here we've got an all-oral regimen that would treat the entire body and treat all of the resistant mutations that we know of that can emerge. And so, what we'd expect there is an enhanced treatment of patients with CNS disease as well as longer progression-free survival. With respect to a frontline study, clearly, we will look at a number of different patient populations during our first two studies and determine the activity there, and then look to develop it in the frontline in parallel with the other studies that we're doing to develop resistant mutations.

With respect to of a frontline study clearly we will look at a number of different patient populations. During our first two studies and determined the activity there and then look to develop it in the frontline in parallel with the other studies that we're doing to develop.

And resistant mutations.

Your next question comes from the line of Peter Lawson with Barclays.

Thanks for taking the questions just the I guess the.

A follow up around the Egfr.

When could we see the initial.

Clinical data and Egfr mutant patients then as we kind of think about ways to kind of break into the loop.

Market all of the.

The.

Areas that you think of kind of loans.

Operator: Your next question comes from the line of Peter Lawson with Barclays.

The fruit essentially or is it you.

Operator: Thanks for taking my questions. Just, I guess, a follow up on the EGFR data. When will we see the initial clinical data in EGFR mutant patients? And then, as we kind of think about ways to kind of break into that post-emergent market, are there areas that you think of as kind of low, low-lying fruit essentially, or do you need to be in combination with additional agents whether it's a med to hit med?

We need to be in combination with additional agents, whether it's a bad debt.

So.

True.

So maybe I'll take the first part of that and then Becker Ken can talk about the development plan. So in terms of when we'd see data.

As Becker just laid out.

Our design with each of these trials of similar to what we've done with with of course, if a kid and GAAP righto of of starting up getting finding the optimal dose and then expanding through various arm exploratory arms to the best understand the potential activity of a molecule both as the single agent <unk>.

Operator: The HITMATS, ALCS, etc.

Jeff Albers: So maybe I'll take the first part of that, and then Becker can talk about the development plan. So in terms of when we see data, as Becker just laid out. Our design with these trials is similar to what we did with both AvaKit and Gavretto of starting up, finding the optimal dose, and then expanding through various exploratory arms to best understand the potential activity of a molecule, both as a single agent or in combination.

Or in combination.

And so we want to get those trials up and running before we guide to when we'd be sharing data, but I think it's a safe assumption would be similar to the timeframe of how and when we share data from Eva kit or GAAP right, though.

And then with respect to showing activity in breaking into as you described of the awesome nib.

Jeff Albers: And so we want to get those trials up and running before we guide when we'd be sharing data. But I think a safe assumption would be similar to the timeframe of how and when we share data from AvaKit or Gavretto.

Market the the way I like to think about this is in three different buckets. The first is patients who have been through a first generation <unk> inhibitor like the rest of our Tarceva and then moved on to off the Merck Nib and we'll develop either on an on target mutation, which often will be the the six 787 asked mutation in combination with the driver.

Becker Hewes: And then with respect to showing activity and breaking into, as you described, the osomertinib market, the way I like to think about this is in three different buckets. The first is patients who have been through a first-generation inhibitor like erythrotarceva and then moved on to osomertinib and will develop either an on-target mutation, which often will be the C797F mutation in combination with the driver And then patients who have the driver mutation will develop another mechanism of resistance like metamplification.

<unk> 79, a M or the triple mutant patients and then patients who have the driver mutation.

And we'll develop another mechanism of resistance like like met amplification.

In both cases, you still need to inhibit Egfr and so blue 94, five is it will look for activity in as the single agent and those patients that are have their disease driven by a subsequent mutation of Egfr and then eventually in our program. We may need to as you mentioned look at other types of cars.

Becker Hewes: So in both cases, you still need to inhibit EGFR, and so BLU945 will look for activity as a single agent in those patients that have their disease driven by a subsequent mutation of EGFR. And then eventually, in our program, we may need to, as you mentioned, look at other types of combinations with other tyrosine kinase inhibitors or other modalities to address the additional mechanisms of resistance in that really third-line patient population.

Combinations with other parts.

<unk> kinase inhibitors or other modalities to address the additional mechanisms of resistance and that really third line pay.

Patient population the other bucket I think of as patients failing on our or of patients whose disease is progressing following off the Merck nib in that case Blu 701 is a the the molecule that we expect to show activity very early in that resistant population.

Becker Hewes: The other bucket I think of is patients failing or whose disease is progressing following osomertinib. In that case, BLU701 is the molecule that we expect to show activity very early in that resistant population. Again, there may be a rationale to combine with other agents, including osomertinib, to continue to keep the pressure on all forms of the mutation and then to prevent subsequent emergent of point mutations. And then with respect to breaking into the larger part of the osomertinib treatment landscape, it's really looking at either our own proprietary combinations or adding our drugs to an existing treatment with an EGFR inhibitor to allow longer progression-free survival and really kind of mirror the way that osomertinib marched from laetal lines into the front line.

There there may be of rationale to combine with other agents, including awesome partner to continue to keep the pressure on all forms of the mutation and then to prevent subsequent emergence of a point mutations and then with respect to breaking into the larger part of the customer and the treatment landscape.

Chip, it's really looking at either our own proprietary of combinations or adding on our drugs to an existing treatment with an egfr inhibitor.

Inhibitor to allow longer progression free survival, and really kind of mirror the way that off the Merck nib marched from later lines into the frontline of Egfr mutant lung cancer.

Your next question comes from the line of Brad Canino with credit Suisse.

Operator: Your next question comes from the line of Brad Canino with Credit Suisse.

Operator: Good morning. Just some clarification on the comments you made about flu 945 in Phase 1. You mentioned that the dose expansion will be in patients with specific mutations, and I assume that will include 2790M and C797S, but are you planning to enroll any other mutations? And if so, could you outline the reason why you're doing that?

Good morning, just some clarity on the comments you made about Blue 94 of five phase. One you mentioned of the dose expansion will be in patients with specific mutations and I assume that will include $2 792 seven.

797 assets are you planning to enroll any other mutations and if so could you outline the reason why youre doing that thank you.

Becker Hewes: So with respect to other mutations, if you're asking about other EGFR mutations, we're currently pre-clinically profiling both of the compounds further to identify the full spectrum of mutations against which they are active. During escalation, we have the ability to expand while we're expanding, and so we expect to get early information about where the compound is active so that we can tailor our expansion cohorts to fit these mutation profiles. With respect to other mutations like met amplification, that would be a later part of phase one where we would need to determine the optimal compounds to combine with, and then we could look at a combination of EGFR inhibition plus another modality of inhibiting the resistant pathway.

So with respect to other mutations if you're asking about other egfr mutations. We're currently pre clinically profiling. The both of the compounds further to identify the full spectrum of mutations against which they are active in.

During escalation, we have the ability to expand while were escalating and so we expect to get early.

Information about where the compound as active so that we can tailor our expansion cohorts to fit the mutation profiles.

With respect to other mutations like met amplification that would be in a later part of the the phase one where we would need to determine the optimal compounds to two combined with and then we could look at a combination of Egfr inhibition plus another modality of inhibiting the.

Resistance pathway.

And there are no further questions at this time I will now turn the call back over to Jeff Albers for closing remarks.

Operator: And there are no further questions at this time. I will now turn the call back over to Jeff Albers for closing remarks.

Jeff Albers: Thank you, Operator. So I'll wrap up with where we started, given the strong position we find ourselves in on this quarterly call. Around our strategic imperatives, we spent less time talking about our early research pipeline today, but under the leadership of Fouad Namouni, our president of R&D, we continue to identify new opportunities and new targets to focus on to further expand our portfolio. Becker walked us through the next wave of therapeutic candidates, really anchored around these five recent development candidates that show exceptional promise.

Thank you operator, so I'll I'll wrap up with where we started.

The strong position, we find ourself in a at this quarterly call around our strategic imperatives. We spent the last time talking about our early research pipeline today, but under the leadership of flow out in the Mooney, our president of R&D, we continue to identify new opportunities and new targets to focus on.

On to further expand our portfolio of Becker walked us through the next wave of therapeutic candidate is really anchored around these five recent development candidates that that show exceptional promise and then as Christy you walked through the the the acceleration of our commercial efforts with <unk>.

Jeff Albers: And then Christy walked through the acceleration of our commercial efforts with AvaKit and Gavreto, and really our focus on ensuring that we're prepared to bring AvaKit to patients in advanced systemic mass cytosis, potentially this quarter with the targeted pedophidate in mid-June. And all that's really underscored by the strong financial position that we're in. And Mike walked us through the financials, really focusing on the gap financials. The way I look at it is probably a bit more broadly, and I tend to anchor in on end-user sales and think about how we bring these medicines to patients, both directly in sales that we book, as well as through our various collaborations. And in the case of Genentech, with a profit share, but then with Genentech, Ipsen, and Seastone, you also see royalty potential as well as milestones.

Of the kit and get Red, Oh, and and really our focus on ensuring.

That we are prepared to bring Ava kit the patients in advanced systemic mastocytosis potentially this quarter with the with the targeted produce the date in in mid June and all of that's really underscored by the strong financial position that we're in the end and Mike walked us through the financials really focusing on.

And on the GAAP financials of the way I look at it it's probably a bit more broadly as I tend of anchor in on end user sales and thinking about how we bring these medicines to patients both directly and sales that we book as well as through our various collaborations in the in the case of.

Of Genentech with a profit share.

But then with Genentech Gibson C stone.

You also see royalty potential as well as milestones and when we take all of that together.

Operator: And when we take all of that together, the growth potential, as Mike highlighted, going into the second half of the year, is becoming increasingly clear to us and should position us to further expand our portfolio over time. And so, with that, we know we have a lot of work to do. It's nice we're actually doing this call from a room together in our office for the first time in over a year.

On the growth potential and as Mike highlighted going into the second half of the year.

Becoming increasingly clear to us and should position us to be even further.

Expand our portfolio over time, and so with that we know we have a lot of work to do yeah. It's nice we're actually doing this call from a room together in our office for the first time in over a year and so we continue to be optimistic about.

Operator: And so we continue to be optimistic about, certainly in the U.S., the ability for business to accelerate as we come out of the backside of this pandemic. And so we look forward to continuing to update all of you and calling you again in the near future. Bye-bye.

You know certainly in the U S. The ability for business to accelerate as we come on to the back side of of this pandemic.

And so we look forward to continuing to update all of you and and calls again in the near future with that thank you for taking the time of day Bye bye.

Operator: Ladies and gentlemen, this concludes today's conference call. We thank you for your participation, and you may now disconnect.

Ladies and gentlemen, this concludes today's conference call. We thank you for your participation and you may now disconnect.

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