Q4 2019 Earnings Call

Ladies and gentlemen, thank you for standing by welcome to the fourth quarter two dozen in 19 Blueprint medicines conference call.

Operator: Ladies and gentlemen, thank you for standing by, and welcome to the 4th quarter 2019 Blueprint Medicines Conference call. At this time, all participants' lines are in a listen-only mode. After this 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. And I would now like to hand the conference over to your speaker today, Kristen Otis. Thank you. And please go ahead, ma'am.

At this time, all participants' lines are in listen only mode.

The speakers presentation, there will be a question and answers your.

A question during the session you need to press Star one wonder telephone.

If you acquire any further research. Please proceed or zero and I would now like to hand, the conference over to your speaker today Christian. Thank you. Please go ahead.

Kristen Otis: Thank you, Operator. Good morning, everyone.

Thank you operator.

Good morning, everyone. This is Chris in how to simply promotions and welcome to Blueprint medicine fourth quarter and full year 2019 financial and operating results conference call.

Kristen Hodes: This is Kristen Hodes of Blueprint Medicines, and welcome to Blueprint Medicines' fourth quarter and full year 2019 Financial and Operating Results Conference Call. This morning, we issued a press release that outlines the topics that 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 fourth quarter and full year 2019 business highlights. Dr. Andy Burrell, our Chief Medical Officer, will review our recent clinical progress. Christy Rossi, our Chief Commercial Officer, will provide an update on the initial launch of AvaKit, and Mike Landsittel, our Chief Financial Officer, will review our fourth quarter and full year 2019 financial report.

This morning, we issued a press release, which outweighed the topics that we plan to discuss today you can access the press release as well as the slides that will be reviewing today by going to the investor section of our website at www Dot blueprints medicines Dot com.

Today on our call just all burst, our chief Executive Officer will discuss blueprint medicine fourth quarter and full year 2019 business highlights.

Dr. Andy Brown, our Chief Medical Officer will review, our recent clinical progress.

Christy Rossi, our Chief commercial officer will provide an update on the initial launch of either kit.

And Mike Lansdell, our Chief Financial Officer overview, our fourth quarter and full year 2019 financial results.

Kristen Hodes: 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 statements as a result of various risks, uncertainties, and other factors, including those set forth in the risk factor section of our SEC filing. In addition, any forward-looking statements 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.

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 factor section of our SEC filings in it.

Addition, any forward looking statements 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 statement.

Now here's our CEO Jeff hours.

Jeff Albers: This morning, in addition to financial results for 2019, we'll highlight key value drivers for Blueprint Medicines in 2020, discuss top-line pralesentinib data in redfusion-positive lung cancer, and share initial insights on our early launch experience. 2020 is a pivotal year for Blueprint Medicines, as we complete our evolution into a fully integrated global biopharma. This transformation will be defined by three key themes.

Next question.

In addition to financial results for 2019 will highlight key value drivers for blueprint medicines in 2020.

Discuss topline profitably data in Red fusion pauses lung cancer.

And share initial insights on our early launch experience with eight again.

[noise] 2020 is a pivotal year for blueprint medicines as we complete our evolution into a fully integrated global biopharmaceutical company.

Its transformation will be defined by three key theme.

Jeff Albers: The first is an increasing focus on commercializing AvaPritinib and Pralsept. We were obviously excited to kick off the year with the FDA approval of AvaPritinib, which is now under the brand name AvaKit, for the treatment of patients with PDGFR-alpha exon 18 mutants, advocates the first precision medicine for GIST and the only highly effective treatment for patients with PDGFR-alpha meas With this launch, we're building the foundation and momentum for additional planned launches of AvaKit and PralSET-MIB across multiple indications and geographies. The second theme is an expanded strategic focus on systemic mastocytosis and other kit-driven mast cell diseases.

The first isn't increasing focus on commercializing even printed and processing.

We were obviously excited to kick off here with the FDA approval. The Britain NIM, which is now under the brand name Eva kit for the treatment of patients with PD do you have far Elfa Exxon 18, you and yes.

He became the first precision medicine for Jeff and the only highly effective treatment for patients with PDGF, Ralph and mutation.

With this launch we're building the foundation and momentum for additional planned launches of either kit and processing it across multiple indications on geography.

The second theme is expanded strategic focus on systemic mastocytosis and other kit driven mast cell disorders.

Jeff Albers: As we highlighted in our recent R&D day, we believe there is a tremendous medical need across a large systemic mastocytosis population, which includes up to 75,000 patients in major markets. We are uniquely positioned to address this need through Ava Pritnib's potent inhibition of DH16D mutant kit, which is the primary genetic driver in the vast majority of patients with systemic mastitis. This year, we'll continue to advance Ava Pritnip towards regulatory filings for Advanced FM in the second half of 2020 and then Indolent FM in 2021. Additionally, we'll initiate a Phase 1 healthy volunteer trial in the first half of this year for Blue263, which is our next generation kit inhibitor, with the goal of reaching even more patients with indolent SM, as well as other kit-driven mast cells.

As we highlighted our recent R&D day, we believe there's a tremendous medical need across a large systemic mastocytosis population, which includes up to 75000 patients in major markets.

We're uniquely positioned to address this need through either putting <unk>, oh inhibition of DHX TV Newton kit.

Which is the primary genetic driver in the vast majority of patients with systemic mastocytosis.

This year, we'll continue to advance Eva putting them towards regulatory filings for advanced FM in the second half a 2020, and then England S. M in 2021.

Additionally, we'll initiate a phase one healthy volunteer trial in the first half of this year for Bluetooth six three which is our next generation getting hibbett or with the goal of reaching even more patients with indolent S. M as well as other kept driven mast cell disorders.

Third the continued strengthening of our early stage research by boy.

Jeff Albers: Our third theme is the continued strengthening of our early-stage research pipeline. In January, we announced a first-in-class development candidate for triple mutant, EGFR-positive, non-small cell lung cancer. This program combines potent inhibition of treatment-resistant triple mutant EGFR with selectivity over the wild type, highlighting the strength of our scientific platform to pursue exceptionally challenging target product profiles. The Triple Mutant EGFR Program is just the first of up to three new development candidates we plan to nominate in 2020. So with these areas of focus, we aim to create substantial therapeutic value for patients and healthcare providers. The cadence of potential commercial launches could be as quick as one per quarter over the next year and a half. And importantly, with a strengthened balance sheet on the heels of our recent capital raise, we now have the runway to execute on our strategy as we begin to realize meaningful product revenue. This morning, we'll highlight several of the early 2020 milestones we've already achieved that are setting us off on a strong path forward. So Andy will start by reviewing the top-line pralsetnib data in RETFusion Positively. Are you ready?

In January we nominate a first in class development candidate for Triple meeting EG fr positive non small cell lung cancer.

[noise]. This program combined poking inhibition of treatment resistant triple mutiny jaafar.

With selectivity over the wild type kidney.

Highlighting the strength of our scientific platform to prosecute exceptionally challenging target product profile.

The Triple meeting Egypt far programs, just the first of up to three new development candidates, we plan to nominate and 2020.

So with these areas of focus we aim to create substantial therapeutic value for patients and health care providers.

The cadence the potential commercial launches could be as quick as one per quarter over the next year and a half.

And importantly, with a strengthened balance sheet on the heels of our recent capital raise we now have the runway to execute on our strategy as we begin to realize meaningful product revenue.

This morning, we'll highlight several the early 2020 milestones we've already achieved that are setting us off on a strong path forward.

Andy will start by reviewing the topline pro sudden of data in right fusion positive lung cancer handy.

Thanks, Jeff [laughter] and good morning, everyone.

Andrew Scott Berens: Thanks, Jeff, and good morning. In early January, we announced top-line data from our Phase I-II error trial at Prelstat in patients with RET fusion positive lung cancer, and we initiated a rolling NDA submission to the FDA. This morning, I want to take a few moments to share additional perspective on the highly encouraging top-line data. First, let me provide some background on why we think this data set is so strong and has the potential to position prosthetinib as a best-in-class retino The top-line Prosetinib data were centrally reviewed by blinded and independent radiologists, which is the standard required by FDA and EMA to support In addition, all patients were treated at the indicated dose of 400 milligrams once daily.

In early January we announced topline data from our phase one to ever trial that NIM in patients with reperfusion positive lung cancer and.

And we initiated a rolling NDA submission to the FDA.

This morning, I want to take a few moments to share additional perspective on the highly encouraging topline data.

First let me provide some background on why we think this dataset is so strong and that's a potential disposition process and it was a best in class written.

The topline press that enough data were centrally reviewed by blinded and independent radiologists, which is the standard required by the FDA, Andy I made a support approval.

In addition, all patients were treated the proposed indicated dose of 400 milligrams once daily.

Andrew Scott Berens: This is important because the data demonstrate both efficacy and safety at the dose expected to be used in the commercial setting. Top line results showed continued strengthening as we treated a broader population of patients for a longer duration. In patients previously treated with platinum-based chemotherapy, the objective response rate was 61%. In treatment-naive patients, the objective response rate was 73%. The data also showed a deepening of response that was striking. In treatment nave patients, 15 percent achieved complete resolution of measurable target tumors, and 12 percent achieved the even higher bar of complete response by RASIST 1.1. In addition, the median duration of response was not reached in patients treated with the 400 milligram dose, regardless of prior therapy. This evidence of prolonged durability is consistent with preclinical data we've long highlighted, showing that pralsetinib is uniquely equipotent against Rett gatekeeper mutations, predicted to be the most likely drivers of, Importantly, safety results were consistent with the previously reported data, and no new safety signals were observed. We're excited to see these data, which have further instilled in us a sense of urgency to deliver prosthetinib to patients as quickly as possible.

This is important because the data demonstrate both efficacy and safety that's a dose expected to be used in the commercial setting.

Topline results showed continued strengthening as we've treated a broader population of patients for longer duration.

Patients previously treated with platinum based chemotherapy you objective response rate was 61 person.

In treatment naive patients the objective response rate was 73%.

The data also showed a deepening of response that was striking in treatment naive patients, 15% achieved complete resolution is measurable target tumors and 12% achieved even higher bar a complete response by RECIST 1.1.

In addition, the median duration of response has not reached in patients treated with the 400 milligram dose regardless of prior therapy.

This evidence of prolong durability is consistent with preclinical data, we've long highlighted showing the pellets that name is uniquely equal potent against Rettke permutations predicted to be the most likely drivers of resistance.

Importantly safety results were consistent with the previously reported data and no new safety signals were observed.

We're excited to see these data, which a further instilled in us a sense of urgency to deliver process that and then to patients as quickly as possible.

Looking forward.

Andrew Scott Berens: And looking forward, we have several important clinical development milestones on the horizon. On March 14th, we'll present updated Part 1 data from the Pioneer Trial of avipritinib in patients with indolent systemic mastocytosis at the American Academy of Allergy, Asthma, and Immunology for the Quad AI Annual Meeting. In this presentation, we plan to share a robust data set, including patient-reported outcomes and quantitative measures of mass cell burden and safety, which we'll use to guide the registration-enabling Part 2 of the trial. Following that, we anticipate a decision from the FDA on our NDA for apopretinib for the fourth line in the second quarter. As expected, we received a three-month PDUFA date extension from the FDA last year. This will allow us to provide top-line data from the Phase 3 Voyager trial to the FDA early in the second quarter and enable the agency to take action on the fourth-line NDA by the May 14th PDUFA date. With that, I'll turn the call over to Christy to share an update on the commercial launch of AvaKit in PGFR AlphaGIST. Christy?

Several important clinical development milestones on the horizon.

On March 14, well present updated part one data from the pioneer trial of interpreting them in patients with the influence of stems Mr. mastocytosis at the American Academy of allergy asthma in immunology or the quality I annual meeting.

In this presentation, we plan to share a robust dataset, including patient reported outcomes quantitative measures of mass all burden.

Safety, which will use to guide the registration, enabling part two of the trial.

Following that we anticipated decision from the FDA owner in D.A. for April Britain NIM for Fortunately in just in the second quarter.

As expected you received a three month PDUFA date extension from the FTC last week.

This will allow us to provide topline data from the phase three Voyager trial to the FDA early in the second quarter and enable the agency to take action on the fourth line, just and D.A. by the May 14th due for gate.

With that I'll turn the call over to Christy to share an update on commercial launch of either Kid feature for Alpha just Christie.

Christina Rossi: Thanks, Andy. Good morning, everyone. It's a pleasure to be with all of you this morning to share initial insights on the launch of AvaKit for PDGFR-alpha-exon-18 mutant GIF. Of course, our approval occurred after the close of Q4, so we will not be reporting any sales results on today's call. Instead, we'll focus on some early accomplishments from the first few weeks of launch that highlight the urgency of our team, as well as the strong initial reception from healthcare providers and payers to the approval. On January 9th, we were thrilled to receive our first FDA approval for Avakid, five weeks ahead of the February 14th PDUFA date. At the time of approval, we were well-prepared to initiate our commercial launch, continuing the ongoing engagement and dialogue we've been having with the just- As we've previously shared, over the course of last year, we defined a nimble go-to-market strategy balancing a focus on the specific needs of patients with PDGFR-alpha exon 18 mutant GIF and an ability to scale over time with additional approval.

Thanks, Andy Good morning, everyone.

It's a pleasure to be with all of you. This morning to share initial insights on the launch of eight a cat for PDGF I Alpha Exxon 18 getting jets.

Of course, our approval occurred after the close of Q4, we will not be reporting any sales results on today's call.

Instead, we'll focus on some early accomplishments from the first few weeks of lunch, but highly urgency of our team as well. It's a strong initial reception from health care providers and payers to the approval.

On January nine we were thrilled to receive our first FTC approval of CAD five weeks ahead of the February 14th pretty funny.

At the time approval, we were well prepared to initiate our commercial launch continuing the ongoing engagement and dialogue, we've been having with the just community.

As we've previously shared over the course of last year, we defined and nimble go to market strategy balancing a focus on this specific needs of patients with P. Jaffer Alpha Exxon 18 meeting chest.

And an ability to scale over time with additional approvals.

Christina Rossi: With this approach, we built an integrated field team, including about 40 area business managers, as well as focus groups of precision medicine and market access experts. These teams are fully trained and actively engaging with health care providers and key accounts around the country. Within hours of the approval, our product website and initial marketing materials were available, and the Your Blueprint patient support program was open to receive patient and health care provider information. Within one week of the approval, our specialty pharmacies had the product on hand and had processed the first payable prescription.

With this approach, we built and integrated field team, including about 40 area business managers.

Well its focus groups, a precision medicine and market access experts.

These teams are fully trained and actively engaging with health care providers and key accounts around the country.

[noise] within hours of the approval our product website and initial marketing materials were available and they yard blueprint patient support program was open should we see patient and health care provider inquiries.

Within one week of the approval, our specialty pharmacies had product on hands and had process. The first payable prescription.

Michael Landsittel: We've been very pleased with the initial receptivity of health care providers to the approval, and we are encouraged to see prescribing interest beyond our trial investigators. In addition, our market access team has been out in the field meeting with commercial and government payers to secure appropriate coverage for AvaKit. These early discussions have gone well, and we're confident we'll achieve broad coverage for AvaKids. As we reported last week, we were pleased to learn that the National Comprehensive Cancer Network, or NCCN, has added AvaKit to its clinical practice guidelines for soft tissue sarcoma. The updated guidelines now include AvaKit as a front-line treatment for patients with PDGFR-alpha-exon-18 mutant GIF, as well as a treatment for patients with fourth-line gist. For both indications, AvaKit is recommended as a Category 2 agency, which indicates uniform consensus that an intervention is appropriate among a committee of expert physicians from leading U.S. cancer centers. This is a very positive step forward and provides additional support for the adoption of AvaKit in clinical practice, as well as payer coverage. Over the course of 2020, we look forward to sharing additional details on the launch as we gain more experience and insight. I'll now turn the call over to Mike to review our financial results for the quarter.

We've been very pleased with the initial receptivity of health care providers to the approval and we are encouraged to see prescribing interest beyond our trial investigators.

In addition, our market access team has been out in the field meeting with commercial and government Harris to secure appropriate coverage for Eva cat.

East early discussions have gone well and we're confident we'll achieve broad coverage for efficacy.

[noise] actually reported last week, we were pleased to learn that the national comprehensive cancer network or NCCN has added advocate to its clinical practice guidelines for soft tissue sarcoma.

The updated guidelines now include Eva kit and they frontline treatment for patients with PDGF or alpha eggs on 18 years, and just as well as a treatment for patients with fourth line just.

For both indications either kit is recommended as a category to entry.

Which indicates uniform consensus that an intervention is appropriate among a committee of experts physician from leading U.S. cancer centers.

It's a very positive step forward and provides additional support for the adoption of efficacy in clinical practice as well as payer coverage.

Over the course of 2020, we look forward to sharing additional color on the watch as we gain more experience and insight.

I'll now turn the call over to Mike to review, our financial results for the quarter.

Michael Landsittel: Thanks, Christy. So earlier this morning, we announced detailed fourth quarter and full year 2019 financial results in our press release. For today's call, I'm just going to touch on a few financial highlights from the quarter as well. First, we're entering 2020 in a very strong financial position, which enables us to focus on the execution of our strategy ahead of critical milestones across our portfolio, including multiple planned commercial launches. We ended 2019 with $548 million in cash, and in January 2020, we closed a public offering resulting in net proceeds of approximately $308 million. Based on our current plans, we believe we have sufficient capital to fund our operations into the second half of 2020. Importantly, as Jeff mentioned earlier, this runway extends into a time frame in which we expect to achieve meaningful commercial revenue.

Thanks Christy.

Earlier. This morning, we reported detailed fourth quarter and full year 2019 financial results in a press release.

For today's call I'm, just going to touch on a few financial highlights from the quarter as well as the year.

First we're entering 2020 in a very strong financial position, which enables us to focus on the execution of our strategy out of critical milestones across our portfolio, including multiple planned commercial launches.

We ended 2019 with $548 million in cash ended January 2020, we closed the public offering resulting in net proceeds of approximately $308 million.

Based on our current plans, we believe we have sufficient capital to fund our operations into the second half of 2022.

Importantly, as Jeff mentioned earlier this runway extends into a timeframe in which we expect to achieve meaningful commercial revenues.

Second collaboration revenues increased in the fourth quarter to 66, and a half million dollars, primarily due to revenue recognized under our license agreement with Clemente a pharmaceuticals, a subsidiary subsidiary of Gibson for the development and commercialization of Blue 72 for fiber dysplasia Ossificans Progressiva.

Michael Landsittel: Second, collaboration revenues increased in the fourth quarter to $66.5 million, primarily due to revenue recognized under our license agreement with Clementia Pharmaceuticals, a subsidiary of Ipsen, for the development and commercialization of Blu782 for fibrodysplasia ossificans progressiva. The revenue recognized includes a $25 million upfront payment as well as an additional $20 million payment that is due in the third quarter of 2020. Third, there was an increase in total operating expenses in the fourth quarter of 2019 compared to the prior quarter. This was due to investments in our global commercial infrastructure as we prepared for the potential launches of AvaKit and Pralsat, as well as the acceleration of clinical development activities, including preparation for the Phase 3 Accelerate Trial of pralsetinib in front-line laboratories. We expect to see continued moderate increases in quarter-over-quarter expenses consistent with the long-term growth rate that we've seen over the past several quarters. With that, I'll now turn the call over to the operator for questions.

The revenue recognized includes a 25 million dollar upfront payment as well that's an additional 20 million dollar payment that it's due in the third quarter of 2020.

Third there was an increase in total operating expenses in the fourth quarter of 29 team compared to the prior quarter due to investments in our global commercial infrastructure as we prepared for the potential launches of advocate and process.

As well as the acceleration of clinical development activities, including preparation for the phase three accelerant trial of processing. It in first line lung cancer.

We expect to see continued moderate increases in quarter over quarter expenses consistent with a long term growth rate that we've seen over the past several quarters.

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

Thank you.

And as a reminder to ask a question do we need to press star one on your telephone to withdraw your question. Please press the pound key.

Operator: Operator. Thank you. And as a reminder to ask a question, you will need to press star one on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. And our first question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Please stand by what we completed the culinary roster.

And our first question comes from a line of Salveen Richter with Goldman Sachs, Let us know.

Good morning, Thanks for taking my question. So I think about the upcoming quite a meeting [laughter] then what data will be in what is meaningful to move forward to part two of the pioneer study and then secondly.

Salveen Richter: Good morning, thanks for taking my questions. So as we think about the upcoming Quad AI meeting, we have to understand what data will be and what is meaningful to move forward with Part 2 of the Pioneer Study. And then, secondly, we need to speak to the ongoing AvaKit launch and initial learning feedback from prescribing physicians and also the inclusion of AvaKit in the NCCN guidelines for fourth-line GIST.

So to speak to the ongoing either kit launch and initial learnings feedback from prescribing physicians and so with inclusion of either cut in the NCCN guidelines for fourth line just [laughter], how should we think about pricing for the drugs igniting Lincolnshire. Thank you.

[noise] think salveen. So this is Jeff I'll take the first part of the question maybe have add de add some color if necessary I think Christy why don't you take the launch it NCCN.

Jeff Albers: How should we...

Jeff Albers: How should we think about pricing for drugs in that indication? Thank you.

Jeff Albers: Thanks, Salveen. So, this is Jeff. I'll take the first part of the question and maybe I will have Andy add some color if necessary. And then, Christy, why don't you take the launch and NTCN questions? So first off, given that quad AI is upcoming, we're not going to address specific data questions. But as a reminder, the purpose of Part 1 is to guide the registration-enabling Part 2. So what we'll be looking for to inform the study will be things like dose selection, sample size, and duration for the second part of the trial. And then we'll watch for results that are consistent with those that we've seen previously in indolent SM patients treated with avipritinib from the EXPLORER trial. And I think Andy then highlighted some of the components of that. I don't know if it's worth repeating. Yeah, maybe just to say that, of course, we'll be looking at objective measures of reduction in mast cell burden. We've shown a little bit of that at ASH.

Question, Bob So first off given that quite a guy is upcoming we're not going to address specific data question, but as a reminder of the purpose of part one is the guide the registration enabling part too. So what will be looking for arch informed <unk> study will be things like dose selection sample size and duration for the second part of the trial.

Ill and will then we'll watch for results that are consistent with those what we've seen previously and indolent SM patients treated with Eva bread.

Britain it from the explore trial and I think Andy then highlighted some of the components of that I don't know if it's worth repeating yeah, maybe I'd just to say that then of course will be looking at objective measures of mass reduction in metal burden Weve shoe showed up a little bit of that at ash, but those are things that we should things that we've shown before like trip taste bone marrow mass cells.

De CIX TV, a little burden and of course will be tying that together with the.

<unk>.

Results from the patient board outcome to all that are part of the the into and study.

And I can comment on that the launch and how we're thinking about fourth line. So you know I'm very pleased with how things have been going over the last several weeks you know we had built a very strong relationship with the just community over many years and I think this lunch and certainly a month or the committee that's been helping to support the development of either.

Andrew Scott Berens: But those are things that we've shown before, like tryptase, bone marrow mass cells, and V16 V allele burden. And, of course, we'll be tying that together with the results from the patient-reported outcome tool that is part of the indolence study.

Christina Rossi: And I can comment on the launch and how we're thinking about FourthLine. So, you know, I'm very pleased with how things have been going over the last several weeks. You know, we've built a very strong relationship with the GIST community over many years, and I think this launch, certainly amongst the community that's been helping to support the development of AvaKit, there was just a real sense of pride and excitement about having a highly effective, innovative agent available for the first time in many years to treat these patients. I think for, you know, investigators that are experienced, they were certainly very excited. But for me, you know, I think the thing that I've been most excited to see personally is the interest outside of our investigators in prescribing AvaKit and the breadth of prescribing that we're already starting to see. So that's been really gratifying.

There was just a real sense of I've tried and excitement about having a highly effective innovative at age and available for the first time in many years to treat these patients.

I think very you know investigators that are experience. There were certainly very excited but for me you know I think the thing that I've been most excited to see personally as the interest outside of our investigators and prescribing and in a cat and the breadth of prescribing never we're already starting to see so that's that's been really gratifying.

The thing about fourth line you know as I said when we let me set the initial price right in a cat we were thinking about the transformational benefit I'm in a targeted patient population ingest I anticipate that that that strategy will continue to hold as we think about and to provide fourth line, where again there are no currently approved an effective therapies and the unmet need is.

It's very significant so were looking for it to ft action and the second quarter.

Thanks [laughter].

Thank you and our next question comes from them on a b.

Raymond James Your line is now.

Christina Rossi: In terms of thinking about FourthLine, you know, as I said, when we set the initial price for AvaKit, we were thinking about the transformational benefit in a targeted patient population in GIST. I anticipate that that strategy will continue to hold as we think about an approval in FourthLine, where, again, there are no currently approved effective therapies, and the unmet need is very significant. So we're looking forward to FDA action in the second quarter.

Hi, Thank you for taking my question Congrats update so maybe on a the Twosix degree highlight that you will be in a healthy volunteer study in the first half of this year do you have any further thoughts and the cadence for that program or where are you hope to get it too by the ended the year.

Yeah. So so again, we've you will be starting that we'll be starting that study. This year as we've described and again importantly, that's a [laughter] he said to healthy volunteer study.

Operator: Thanks, Chris. Thank you. And our next question comes from the line of Dane Leone with Raymond James.

It really to identify the easy appropriate starting dose in.

Dane Vincent Leone: Your line is now open. Hi, thank you for taking the question and congrats on the update. So maybe on the 263 highlight that you will be in a healthy volunteer study in the first half of this year. Do you have any further thoughts in terms of the pace of that program or where you hope to get it to by the end of the year?

Systemic mastocytosis patients indolent systemic mostly just patients in particular.

And you haven't speculated on on the on the subsequent timing of that's how do you think well as we get started we'll update.

And maybe this is Jeff I'll just added as we've talked about a frequently is we see systemic mastocytosis as the cornerstone opportunity of of our commercial build over time and and when we think about that we want a fortified our leadership position within this disease area. So we think the.

Andrew Scott Berens: Yes, so again, we've... We'll be starting that study this year, as we've described. And again, importantly, that's, as you said, a healthy volunteer study, really, to identify the appropriate starting dose for systemic mastocytosis patients, indolent systemic mastocytosis patients in particular. And we haven't speculated on the subsequent timing of that study. I think we'll, as we get started, we'll update you.

Complimentary nature of April Britney have focused on advancing samik mastocytosis patients and those with moderate to severe indolent systemic mastocytosis align that with blue to six three where we'll be initially starting patients with <unk>, maybe more mild to moderate indolent systemic mastocytosis will put us in a really strong.

Jeff Albers: Eun Yang

Jeff Albers: And this is Jeff. I'll just add, as we've talked about frequently, that we see systemic mastocytosis as the cornerstone opportunity of our commercial build over time.

Position over the long term.

Great and maybe one follow up on Red I think everyone has been really pleased with how the lung datas matured.

Jeff Albers: [inaudible]

Jeff Albers: When we think about that, we want to fortify our leadership position within this disease area. So we think the complementary nature of avipritinib focus on advanced systemic mastocytosis patients and those with moderate to severe indolent systemic mastocytosis, aligned then with Blu263, where we'll be initially starting patients with maybe more mild to moderate indolent systemic mastocytosis, will put us in a really strong position over the long term.

With.

With the right data.

Where can you give us kind of a sense of the scale and scope of the thyroid data that we expect to see around the filing.

Probably the second quarter is here.

So so yeah, no we're incredibly thrilled with the evolution the data from the Arrow study.

That we that we recently presented so if that rate data is coming together. We will you know we're on track to Britain to file the registration data from that study in the second quarter. I mean, it is a yeah, we'll be a robust insufficient dataset to support and application for accelerated approval in sort.

Andrew Scott Berens: Great, and maybe one follow-up on Rhett. I think everyone's been really pleased with how the lung data has matured with the RET data. Where can you give us kind of a sense of the scale and scope of the thyroid data that we expect to see around the filing in the probably second quarter of this year?

Yes, we you know we feel we will at a medical meeting present those data.

Okay, great. Thank you.

Thank you.

Our next question comes from the line of Joe told me with Cowen and company. Your line is now [laughter] are there and thank you for taking my question, maybe just on the alternative.

Small cell lung cancer filing what is.

Andrew Scott Berens: So, yeah, we're incredibly thrilled with the evolution of the data from the ARO study, you know, the lung data that we recently presented. And so the thyroid data is coming together. We will, you know, we're on track to file the registration data from that study in the second quarter. It will be a robust and sufficient data set to support an application for an accelerated approval. And certainly, as we, you know, we will at a medical meeting present.

Remaining in order to complete the rolling submission there and then one on on even Britain had been a third line [laughter] that can help and now have you had the last events of the third line study and you're just waiting for data cleaning or patients are used the waiting on additional follow up from patient [laughter].

Do you want to start with threat, yeah, I get it shows so yes, so that as we announced we you know we initiated the rolling submission for profit and had been in Red driven non small cell lung cancer. We are on track to complete that this quarter and its you know we it.

Andrew Scott Berens: Okay, great, thank you. Thank you.

Joe Tomei: And our next question comes from the line of Joe Tomei with Cowen and Company. Your line is now open. Hi there, and thank you for taking my questions. Maybe just on the process.

Where we we.

Filed the materials as they become complete didn't become available, but there's no we're completely on track to complete the full submission.

Joe Tomei: Sutton of Non-Small Cell Lung Cancer filing: What is remaining?

Joe Tomei: remaining in order to complete the rolling submission there.

Joe Tomei: and then one on avipritinib on the third line.

And then on Voyager, where they were still waiting on events and still on track that.

Andrew Scott Berens: Where does that trial stand now? Have you kind of had the last events of the third line study and you're just waiting for data cleaning, or are patients still waiting? Andy, do you want to start with the RET? Yeah, I guess so.

We'll be able to see that data early in second quarter and have time to turn it around quickly to provide top line data to F.D.A. to take action by the May 14th up with you today.

Great. Thank you.

Thank you and our next question comes on line of Michael Schmidt with Guggenheim Securities. Your line is now open.

Andrew Scott Berens: So yeah, as we announced, we initiated the rolling submission for palatinate in RET-driven non-small cell lung cancer. We are on track to complete that this quarter, and it's, you know, we file the materials as they become completed and become available, but there's no, we're completely on track for full submission.

Hi, guys. This is Charles <unk> on for Michael Schmidt, Thanks for taking the questions and congrats again on the quarter.

Want one quick follow up on D. applaud the.

Due to on dental into some but just one quick clarification or would there be potential differences.

Andrew Scott Berens: And then on Voyager, we're still waiting for events, and we're still on track that we'll be able to see that data early in the second quarter and have time to turn it around quickly to provide top-line data to FDA to take action by the May 14th PDUFA date. Great, thank you.

Between the information released the abstract fixed on the week of the 24th versus the actual presentation at the conference.

So yes, there will be up so we know we always strive to present the most current update at the time that conference and we will certainly be probably more information than the abstract then isn't the abstract and perhaps even more so in this case given that the unblinding of the that occurred after the abstracts are really good [laughter].

Michael Werner Schmidt: Thank you. And our next question comes from the line of Michael Schmidt with Guggenheim Security. Your line is now open. Good morning, guys. This is Charles Zhu Han from Michael Schmidt.

Charles Zhu Han: Thanks for taking the questions, and congrats again on the quarter. One quick follow-up on the Quad AI data on indolent SM. Just one quick clarification. Would there be potential differences between the information released in the abstract text the week of the 24th versus the actual presentation at the conference?

Got it makes sense, thanks for that clarification into another follow up on Red.

I'm wondering if you could provide any color around the drivers of the a hard complete response rates over time as it is it I guess the true response [laughter] overtime, New response was occurring or you know potential differences between independent versus Central review on these pieces.

Andrew Scott Berens: So yes, there will be. We always strive to present the most current update at the time of the conference, and we'll certainly be providing more information than is in the abstract.

Yeah. So zandi, we've been really thrilled to see the evolution of the lung cancer data with Eutelsat NIM and in particular is very deep robust.

Andrew Scott Berens: and perhaps even more so in this case given that the unblinding of the data occurred after the abstract.

Andrew Scott Berens: Hey! Got it. Makes sense. Thanks for that clarification. And another follow-up on RET, I'm kind of wondering if you could provide any color around the drivers of the higher complete response rates over time. Is it, is it, I guess, a true response deepening over time, new responses occurring, or, you know, potential differences between independent versus central review on these patients?

Responses that we think really are unique for lung cancer, you just not seen ambitious lung cancer.

So this is Joe this is and this is evolution of of the responses over time, we certainly see deepening is as we've shown.

And I think it's always hard to know what drives that but we but I think usually that's due to good access of the tumor tissue by by the medicine and I think profit and it was just shown to.

Andrew Scott Berens: So yes, this is Andy. We've been really thrilled to see the evolution of the lung cancer data with Pralfet-Nib and, in particular, these very deep, robust responses that we think really are unique for lung cancer, just not seen in patients with lung cancer. So this is the evolution of the responses over time. We certainly see deepening, as we've shown. And I think it's always hard to know what drives that, but I think it's usually due to good access to the tumor tissue by the medicine. And I think Pralfet-Nib is just shown to achieve very highly effective concentrations in the tumor tissue itself, something we don't typically have a way of measuring in patients.

It's probably it's probably achieving very highly effective concentrations in the tumor tissue itself something we don't typically I believe measuring in patients.

Understood. Thanks for that colored and congrats again, thanks for taking the questions.

Thank you and our next question comes some amount of Union with Jefferies. Your line is nope.

If your line is you. Please I'm you know thank you [laughter] couple of questions and of course that tenants. So first so please let me first line not [laughter] comment on how the study.

Andrew Scott Berens: Understood. Thanks for that color.

Eun Yang: And congratulations again. Thanks for taking the question. Thank you. And our next question comes from the line of Eun Yang with Jefferies. Your line is now open. If your line is on mute, please unmute it. Thank you. I have a couple of questions in perspective.

Oh, Yeah, I'm, sorry, I'm kind of a PFS compare you [laughter] Dublin within without Pembro I know so previously you've mentioned Uh Huh [laughter] two combo study [laughter], so [laughter] easier Uh huh.

Andrew Scott Berens: So first, the phase three, first line, not with a lung cancer trial that just was started. Can you comment on the power for the primary and prone of a PFS compared to platinum doublet with or without PEMBRO? And also, previously, you mentioned a phase two combo study with cabiriso in treatment-resistant EGFR mutant non-small cell lung cancer. Can you give us an update on that trial? Thank you.

Nice most in lung cancer can you give us enough data on that trial. Thank you.

[laughter] is this is Andy again, so the phase three first line lung cancer study the what we call the accelerant to study. So there we are comparing.

Probably <unk> NIPT, you platinum doublet therapy, with or without with or without a checkpoint inhibitor that's up to the treating physician.

Andrew Scott Berens: This is Andy again. So the Phase III Frontline Lung Cancer Study, what we call the Accelerate Study, so there we are comparing pralsetinib to platinum doublet therapy with or without a checkpoint inhibitor. That's up to the treating physician. The study is well-powered to achieve the primary endpoint of progression-free survival. We've based the design on, you know, there's plenty of available data with in-lung cancer, frontline lung cancer with platinum doublets, with the triplet, with Checkpoint Inhibitors. Based on those data and the data that we've seen from the ARO study, we have a well-powered and well-controlled study to, I think, In terms of the osmertinib-prosetinib combination, we have not kicked off a specific study with that combination yet. We do have some cases that we've actually reported in the literature, and we are still working on deciding the best time and mechanism to do a study like that. Part of it is really understanding how to find the patients who have EGFR mutant disease that actually relapses due to a RET fusion. So we continue to work on that project.

This study is is well powered to achieve the primary endpoint of progression free survival. We've we base. The design on you know there's plenty of available data.

In lung cancer from line lung cancer with button doublets with the triplett with.

With.

Checkpoint inhibitors based on those days.

Data that we've seen from the Arrow study, we have a well powered and well controlled study to I think show benefit in front line.

In terms of the I see the <unk> combination data, we have not kicked off a specific study with a combination yet we do have some some cases have we <unk> that we've actually recorded in the literature and are still working on 'em deciding to best time in Mexico.

To sum to do a study like that and talk to you know part of its really understanding how to find the patients where there who have you Jeff or disease that actually relax is do you do erect fusion and so we continue where we continue to work on that project.

Thank you.

Andrew Scott Berens: Thank you. Thank you. And our next question comes from the line of David Lebowitz with Morgan Stanley. Your line is now open. www.microsoft.com.au. If your line is on mute, please unmute it. And our next question comes from the line of Andrew Berens with SBB Lyric. Your line is now open. Thanks a lot, guys. Appreciate you taking the questions. I also have a couple for Andy on the pipe. Just wanted to get your thoughts on the initial data that Lilly and LOXA recently published on the resistance that they're seeing for speltrocatinib. And then I guess, you know, primarily, what do you think the primary liability for that drug will be, and how do you think speltrocatinib's profile could differ? And then I also have one on the EGFR program.

Thank you and our next question comes on line of D.V.

<unk> with Morgan Stanley Your line is no.

[noise] if your line is on mute who's on mute.

[noise] and our next question comes from them on the Andrew parents with STB Leerink. Your line is now.

Thanks. Good luck guys. Appreciate you taking the questions I'm also have a couple of branded.

[noise] from a pipe she wanted to get your thoughts on the initial data that will we unlock so recently published resistance was there soon personal per cabinet.

And then I guess, you know primarily what what do you think primary liability for the drug and how do you think trial setting its profile could differ that I also have one on the easier bar program.

Andrew Scott Berens: Okay, so I'll say, yes, Lilly recently published, I guess, a paper with a couple of case reports showing solvent front mutations as mechanisms of resistance to cell procatinib. I think that wasn't surprising to us based on what we know about the compound and potential mechanisms of resistance for the RET kinase. We continue to look carefully at mechanisms of resistance with procatinib. For example, we are measuring circulating tumor DNA at baseline and over the course of treatment.

Okay. So.

Yeah. So the literally recently published I guess, there's a couple of people with a couple of kids report showing a so solvent front mutations as mechanisms of resistance to.

To sell for Catnip, I think that would be that wasn't surprising to us based on what we know about the compound and and potential mechanisms of resistance for for the Red kinase.

We continue to to look carefully at mechanisms of resistance with pro sat NAV, we are measuring I'm circulating tumor DNA a baseline in over the course of treatment. So far we've been pleased with what we've seen we've seen really.

Andrew Scott Berens: So far, we've been pleased with what we've seen. Really on-target RET resistance mechanisms have been relatively rare. We haven't yet seen a gatekeeper-mediated resistance mechanism. We have actually also seen this solvent front mutation, which we would have expected, but at this point, we don't have a sense that it's a major mechanism of resistance. And I think that's still to be understood.

On target right Museum right on target resistance mechanisms has been has been relatively rare we haven't yet seen a gatekeeper mediated resistance mechanism. We have actually also seen this solvent front mutation, which we would have expected but at this point.

It would have a sense that it's a major mechanism of resistance and I think that's still to be to be understood.

I'm sorry, what was the second half half nasty, Oh, even if somebody's liver [laughter] yeah about that leads you up our program I guess I'd, just there seems to be a little bit of confusion behind the rationale for having a triple mutation drug and a double mutation is something just walk us through the rationale there and then also.

Andrew Scott Berens: He hasn't asked yet. Oh, he hasn't asked. He hasn't asked.

Andrew Scott Berens: So far,

Andrew Scott Berens: Yeah, about the EGFR program, I guess I just, there seems to be a little bit of confusion behind the rationale for having a triple mutation drug and a double mutation. So can you just walk us through the rationale there? And then also, if you have any idea, I know it's probably early days, but what percentage of Tegressa failures could you potentially address with either of these drugs?

You have any I'd be I know, it's probably early days, but what percentage of tagrisso failures 'cause could you potentially do absolutely eagerly needs rather than usual.

So <unk> so yes, so I'm in terms of the of the you know the rationale. So we think this this combination two new programs is is actually a very rich next step in developing our lung cancer portfolio, Yeah, we know that.

Jeff Albers: So, in terms of the rationale, we think this combination of two new programs is actually a very important next step in developing our lung cancer portfolio. We know that around the world, the use of osmertin or Tregriso is really kind of varied. It started out as a second-line EGFR inhibitor in the U.S. and globally, and while it's moving into front line in the U.S., it remains a standard second-line therapy in many parts of the world. And the first, you know, the lead program of our two programs, which is looking at what we call the triple mutation, which inhibits the EGFR kinase in the setting of the driver mutation, plus the T790M mutation, plus the C797S resistance to osmertin mutation, is what we expect to see in the setting of osmertinib as a second-line agent.

That around the world the use of.

Martin victory Bristow is really kind of very.

It's it's a started out as a second line you, Jeff our inhibitor in the U.S. and globally and in many wallets moving into frontline in in the U.S., but it's it remains a second line standards like mine therapy in many parts of the world and the the first you know the the lead pro.

Gram of our two programs, which is looking at we call the triple mutation, which inhibits the Egypt or.

Chinese setting of the driver mutation plus the T. 790, M. mutation plus the season 797, S. resistance to Somerton mutation is what we expect to see in the signing of Abbas Summer NIM as a second line agency you get the sub 90 m. from something like a lot NIM and then you got to see.

Jeff Albers: So, you get the T790M from something like erlotinib, and then you get C797S as the mechanism of resistance to osmertinib. We think that will continue to be a very important group of sorts of resistance for many patients globally. Now, of course, with the shift of osmertinib earlier to front-line therapy, then that raises the possibility of seeing the C797S mutation in the absence of the T790M, and that's the whole rationale for the second program that we're working on, and see that as, you know, a very complementary opportunity as osmertinib starts to move to the front line in the U. But again, I think that it's going to take much longer elsewhere.

Nine seven assets in mechanism of resistance to Osimertinib, we think that we'll continue to be a very important a group of sorts of resistance for many patients globally.

We now of course with their shift of customer.

Earlier in the frontline therapy, then that raises the possibility of seeing the said she 797 mutation in the absence of the G 790, M. and that's the whole rationale for the for the second program that were that we're working on and see that as you know you know as a very complimentary opportunity.

As I said Merton it starts to move frontline the U.S., but again I think that's going to take much longer elsewhere.

And so the Jeff maybe I'll, just add that Dave it at a higher level much as we see blue to Sixthree is early complementary to what we're doing with Eva preventive and systemic mastocytosis in terms of building out a franchise here with with this blend the VGF our programs, we find that they're incredibly complimentary to the work that we're doing with problems that now then.

Jeff Albers: Maybe I would just add that at a higher level, much as we see Blu263 as really complementary to what we're doing with avipritinib and systemic mastocytosis in terms of building out a franchise, here with this blend of EGFR programs, we find that they're incredibly complementary to the work that we're doing with pralsetinib. And more broadly, if you think about it, that if treatment paradigms remain where osmertinib is still globally used off the second line, our triple mutation molecule is the most frequent on-target mutation that should occur. And as that paradigm shifts, particularly in the U.S. and many countries in Europe, where osmertinib is the first line, our double mutant would be the most likely on-target resistant mutation that would emerge. So, we think it's complementary to what we have with pralsetinib, and it will serve what is going to be an evolving need within patients with EGFR.

You know more probably if you think about it that if if treatment paradigms remain where a customer it is still globally use off in second line.

Triple mutation a molecule is the most frequent on target a mutation that that should occur and as that paradigm shifts pretty late in the U.S. and in many countries in Europe, where early summer in its first line our double mutant would be the most likely on target resistance mutation a that.

I would emerge so it's we think it's it's it's complementary to what we have with prell setting it and it will serve a what it's going to be an evolving a need within patients that would EG, if our driven disease.

Andrew Scott Berens: Okay.

Andrew Scott Berens: Epidemiology

Is there any epidemiology.

Andrew Scott Berens: to predict the percentage of progressive failures to get the 797 mutation.

Predict the percentage of progress as opposed to get the 797 pension.

Yeah, we think it should be the most common on target mutation I think the actual epidemiology did are evolving.

Andrew Scott Berens: You know, we think it should be the most common on-target mutation, but I think the actual epidemiology data are evolving.

Okay.

Andrew Scott Berens: Okay, thanks a lot. Thank you. And our next question comes from the line of Ren Benjamin with JMP Securities. Your line is now open. Hi, good morning. Thanks for taking the questions and congratulations on the quarter. Maybe just starting off with Christy, can you talk a little bit about your, you know, the sequencing campaign? And I know it's only been a month, but, you know, do you have any sort of a sense as to whether, you know, that's working well? Are the scripts coming in from the front line, or, you know, are they primarily being used? Fourth line, just any sort of trend you can provide for us.

Thanks, a lot.

Thank you and our next question comes from them on of Ren Benjamin with JMP Securities. Your line is now.

Hi, good morning, Thanks for taking the questions and congratulations on the quarter, maybe just starting off of Christy can you talk a little bit about your you know the sequencing campaign and I know, it's only been a month, but you know do you have any sort of a sense as to whether that's that's working well our though.

ER scripts coming in from the front line or you know they primarily being use fourth line just any sort of trend you can provide force.

Christina Rossi: Sure, just so I'm answering the question correctly, when you say sequencing campaign, are you talking about driving mutational testing and sort of what line of therapy we're seeing AvaKit being used for PDGF or Alpha mutant patients? Correct, correct. Okay, great, yeah.

Sure I, just just so I I'm answering the question in the right way are you I. When you say sequencing campaign are you talking about driving mutational testing answer to that where what line of therapy were seeing if it kept being used for and teach out for alpha mutant patients correct correct. Okay. Great. Yeah. So yeah, we've we do.

Christina Rossi: So, you know, we do have a team of precision medicine focused diagnostic experts who have come from a variety of backgrounds and have been focused in this area. Where we think we'll get the most leverage is really by trying to influence behavior at a national account level. So, there's, you know, there's a lot that we can do in terms of making sure that, for example, PDGF or Alpha mutations are reflexed every time AvaKit is negative, making sure that as results are reported, AvaKit is flagged as the appropriate therapeutic intervention in those cases, and we've started to see early wins there already. You know, we know that mutational testing in the community, certainly well less than 50% of patients are receiving it.

You have a team of precision medicine, and focus that really diagnostic experts who have come from a variety of ads backgrounds and I've been focused in this in this area, where we think we'll get the most leverage is really by trying to influence behavior at a national account level. So there is you know there's a lot that we can do in terms of making.

Sure that for example, PDGF Ralph.

Patients are reflects every time kid is negative and making sure that as results are reported as a kid is flagged as at the appropriate therapeutic intervention in those cases, and we started to see early wins. There already you know we know that mutational testing in the community certainly well less than 50% of patients are receiving at.

Christina Rossi: And there's been good reason for that. But we've had a lot of success, you know, even in the early days when we had those discussions with prescribers because now they have a therapeutic intervention that is very meaningful to them. And so, you know, we expect this will take some time to evolve. Certainly, we'll see PDGF or Alpha patients who have been on numerous other therapies because they just, you know, they haven't had other options until now. But I think over time we'll start to see AvaKit being used more and more in early stages of therapy.

And there has been good reason for that at that we've had a lot of success you know even in early days and having those discussions Adam with prescribers because now they have a therapeutic intervention that it's very meaningful to them. So you know we expect that's well we'll take some time to evolve and certainly you know, we'll see PDGF Ralph a patients you had been on numerous other therapies because.

They just you know they haven't had other options until now, but I think over time look back at the end, a cat and being used more and more in earlier lines of therapy.

Got it and just maybe one frenzy regarding Voyager study are you sequencing the patients tumors now.

Andrew Scott Berens: And then just maybe one question for Andy regarding the Voyager study: are you sequencing patients' tumors now and trying to get a sense as to whether patients are being stratified based on mutations, in the case of EGRF-alpha regions?

[laughter] trying to get a sense as to you know outlines because her patients being stratified based on mutations in the kids can you hear about [noise].

So so we we do do baseline ctdna and archival tumor assessment of mutations and on study. We do we follow evolution mutations actually by circulating tumor DNA sequencing, especially in the large study, it's pretty hard to get more tumor tissue.

Andrew Scott Berens: So, we do baseline ctDNA and archival tumor, you know, assessment of mutations, and in the study we do, we follow evolution mutations actually by circulating tumor DNA sequencing. Especially in a large study, it's pretty hard to get more tumor tissue, but the study does stratify patients based on their status if they have PGFR-alpha or KIT-based mutations for the randomization. And we think...

But study does stratify patients based on their status within feature for Alpha or kit. This mutation for the randomization.

And then we think more bought that's gonna be it very important because it'll be an incredibly rich data source and it's our view that overtime that patients are going to be treed.

Andrew Scott Berens: I think more broadly that's going to be very important because it is our view that over time, patients are going to be treated with the right therapy for the right patient based on that mutational status, and this will give us a really rich data set to think about where patients are most likely to see optimal benefit from avopretinib.

Treated with the right therapy for the right patient based on that mutational status and this will give us a really rich data sets to think about where which patients are most likely to see optimal benefit from either putting them.

Andrew Scott Berens: Got it. And then just regarding the... Fourth Line Indication and FDA review and what exactly they might be looking for. Is it the crossover arm, you know, that has now moved on past Regorafinib, that is now getting AVA, and are technically fourth line patients? Is it that data set that goes on to the FDA for review prior to the May 14th production?

Got it and just regarding the the fourth line indication in Ft. A review what exactly that they might be looking for.

Is it the is it the crossover arm you know that have that have now moved on past programs that are now getting Eva.

Okay technically fourth line patients because if that dataset that goes on to the F.D.A. for for review prior to that May 14th.

Andrew Scott Berens: No, you know, I think it's way simpler than that. They're just looking for the top-line, I think primarily efficacy data, meaning the primary PFS assessment from the, you know, the primary study, the phase 3 comparator of AVA versus Reg ARAF. And as part of the top-line data, of course, they also see the summary safety data. I think they really just want to know whether the study is going to be possible.

No I think it's it's way simpler than that fair just looking for the top line I think primarily efficacy data, meaning the primary PFS assessment from the you know the primary study the phase three compared or of of even versus right graph and had been as part of the topline data of course, they also see that the.

Summary safety data I think they really just want to know the that the studies can be positive.

Andrew Scott Berens: Great, thank you very much, and good luck. Thank you. And our next question comes from the line of Arlinda Lee with Canaccord. Your line is now open. If your phone is on mute, please unmute it.

Great. Thank you very much and good luck [laughter].

Thank you and our next question comes from in London, Arlinda, Lee with Canaccord. Your line is no.

[noise] [laughter].

If your phone is on mute please a muted.

Sorry about that I was curious about the.

Philina Lee: Sorry

Philina Lee: I was curious about the lung cancer Rett data set. Can you provide additional detail on the scope of the clinical data we should expect?

Lung cancer Ret dataset and can you provide additional detail on what the scope of the clinical data we should expect.

Andrew Scott Berens: Transcripts provided by Transcription Outsourcing, LLC.

Similarly.

Thank you for mutations or patients.

Transcription Outsourcing, LLC.: And then, on the SM data at Quad AI, what would you consider?

And then on some data equity I, what would you consider clinically meaningful and are you still planning to start the need to either.

Andrew Scott Berens: Are you still planning to start the Phase II Ava Pritchard ISM-SSM expansion cohort this year?

It's an FSRU Sanchez cohort this here thanks.

Andrew Scott Berens: Sure, so maybe I'll start with those, and Andy can add color. So our RET data set in lung cancer, we'll be presenting that at a medical meeting, and that will obviously be a robust update. That'll be the centrally reviewed full data set that we're submitting to FDA, and so there'll be a variety of...

Sure. So maybe I'll start with those now you can add color, so or our red data set in lung cancer will be presented at a medical meeting and that will obviously be a robust update that that that will be the the centrally reviewed full data set that that were submitting to the FDA and.

So there will be all it'll be a variety of.

Andrew Scott Berens: Efficacy, safety, and certainly we'll break down subsets of information that we think are impactful. For Quad AI, again, given the proximity to the conference, we're not going to get into the details beyond what Andy's already highlighted, but that too will be a meaningful update. It will pull together the unblinded data at the various doses, and the whole purpose of Part 1 is to inform Part 2, and so that very much is still on track, that we'll be looking to select the dose and move forward based on feedback from investigators, based on a blend of efficacy and safety.

Efficacy safety and certainly we'll break down subsets of of information that we think our impactful for quality I again, given the proximity to copper and we're not going to get into the details beyond what and he's already already highlighted but.

With that it will be a meaningful update that it will pull together the unblinded data at the various doses and the whole purpose. Apart one is to inform part two and so that very much still is on track.

That will be looking to select the dose and can move forward with based on feedback from my with investigators based on a blend of the efficacy and safety.

George Farmer: Thank you, and our next question comes from the line of George Farmer with BMO Capital Markets. Your line is now open. Good morning, guys. Regarding the Voyager trial, for top-line analysis, do you talk about course-line prediction?

Thank you. Thank you.

Thank you in our next question comes on line of George Farm with BMO capital markets. Your line is open.

Good morning.

[laughter].

[laughter].

Regarding.

Uh huh.

Sure.

Yes.

[laughter].

George Farmer: [inaudible] Video.

Right.

<unk>.

George Farmer: All right.

George Farmer: I have the same question regarding the 10-year trial Part 2. You know, you mentioned two CK3 migraines in breast cancer patients. I guess, do you plan to select or stratify these Part 2 patients by symptom test?

Uh huh.

My question.

Wow.

No you mentioned.

And I.

I guess.

Hi.

<unk>.

Yes, so I think there's three questions. There. The first one that I think is Ah. So I've started how do you thought you were up breaking up a little bit I think it's the first question is on Voyager carving a fourth line I can be I guess, but yes, yes. It on the first so the topline results for for Voyager again, you know.

Andrew Scott Berens: Yeah, so I think there are three questions, and the first one, I think, so I'm sorry you said you were breaking up a little bit, but I think the first question is about Voyager.

Andrew Scott Berens: So the top-line results for Voyager, again, FDA is looking for the global top-line results of the study, which includes everyone who's enrolled, which is a mix of third and fourth-line patients. It is primarily a third-line study, actually, and it's pretty typical for confirmatory studies in oncology to be performed in earlier indications. So the top line data will include the mix of primarily third-line patients, but also including some fourth-line patients. They are, randomization is stratified for those two groups, so the total PFS assessment, and, of course, the high level safety assessment. And importantly, I think your question about third-line approval is actually a really important one. So no, the May 14th PDUFA date is in order for FDA to make an assessment of the fourth-line NDA submission that we've already submitted.

This is a after is looking for the global topline results for the study not you know, which which includes everyone who's enrolled which is it's a mix of third and fourth line patients. It is primarily a third line study actually and it's pretty typical for confirmatory studies in oncology to be performed in earlier.

Indications so it'll be the it'll be the topline it'll include the the mix of primarily third but also including some fourth line patients. They are randomization stratified for those two groups. So that the total PFS assessment and of course high level safety assessments and importantly, I think you're.

About third line approvals actually really important one so no. We the may 14th PDUFA date is in order for a few to make an assessment of the force line and de submission that we've already submitted the third line review and approval assuming this study is positive.

Andrew Scott Berens: The third line review and approval, assuming the study is positive, would be based on complete submission of the full NDA later in the year and subsequent completion. I wasn't quite sure if I, you broke up a little bit on the Part 2 Pioneer, I think you were asking if we're stratifying by symptom score. And, you know, the study is designed such that patients, to be eligible, have to achieve a minimum symptom score on the PRO. And by doing that, we address the question of whether there is heterogeneity of symptoms. So that's, I don't, you know, we don't see that as an issue. But at the same time, we will look very carefully at the Part 1 data, and we will use those data to help optimize the design of Part 2.

Based on completes submission of the full in D.A. later in the year.

Subsequent to complete review.

Yeah, the I wasn't quite sure if I if I you broke up a little bit on the part to pioneer <unk> I think you're asking for stratifying by symptom score.

And your the this study is the study its design such that patients to be eligible have to achieve a minimum symptom score on the bureau and done by doing that we I think address the question of is there a heterogeneous heterogeneity of symptoms. So that's why don't you know, we don't see that as as an issue but.

But.

At the same in this you know at same time, we will look very carefully at the part one data and we will I'm use those data to help them optimize design part two.

Christopher Joseph Raymond: Thank you. And our last question comes from the line of Chris Raymond with Piper Sandler. Your line is now open. Hey, thanks. Just a couple of ones.

Thank you I know last question comes from them on of Chris Raymond with Piper Sandler Your line is an open.

Thanks, just a couple ones I'm. So I noticed I know that you guys have talked about see stone doing bridging work in China.

Christopher Joseph Raymond: So I noticed, I know that you guys have talked about Seastone doing bridging work in China with Aviprinib and GIST, but we just noticed on ClinTrials that last week, I think it was posted, that there was actually a dose-ranging study, and I think it looks like it's starting at a lower dose than that that was approved in the U.S. Just curious if you have any color there. Was this a requirement from Chinese regulators, or why is there a need, I guess, to run a... A dose-ranging study given full approval in the U.S.

With that upfront they've been Jeff just but we just noticed on Clin trials.

Last week I think it was posted this is actually a dose ranging study.

I think it looks like it starting at a lower dose and that there was approved in the U.S. Just curious if you could do you have any color. There was this a requirement from Chinese regulators or why what's the need I guess to run a.

A dose ranging study with given the full approval.

Andrew Scott Berens: Yes, this is Andy. I'll take it.

They would have really.

Andrew Scott Berens: Yeah, this is just a standard requirement from the Chinese CDE that they require that the PK, safety, and activity be re-established in a Chinese population in a small group, not at a statistical scale. Signature level, and you need to start at a lower dose, just in case exposure in Chinese patients is higher than in Western patients.

Yes, Dan Delta Yeah. This is just standard requirement from the Chinese C. D E that they require that that the PK and safety and activity be reestablishing the Chinese population in small group not as a statistically significant level and you need to start at a lower dose just in case exposure.

In Chinese patients is higher than in western patients.

Jeff Albers: And then just, I know a lot of questions have been asked, file, but I guess I'll just ask one question we've gotten a lot from investors: Have you guys considered what happens if repretinib is granted accelerated approval before the FDA sort of makes a call on avipretinib in the broader fourth-line setting? That is, you know, I think from my understanding your ability to get accelerated approval when another drug has an approval, there might be some question there. Can you maybe talk about that scenario?

And then.

I know that a lot of questions have been asked on the broader fourth line fine, but I guess like.

One question, we've gotten a lot from some investors is.

Have you guys consider what happens if repression of is granted accelerated approval before.

If you sort of makes a call on on ever printed in getting the broader fourth line setting that is.

Yeah, I think from from my understanding your ability to get accelerated approval when another drug has an approval.

No that there might be some question. There can you maybe talk about that scenario.

Jeff Albers: Yeah, so that's not correct. There are multiple examples where there are multiple accelerated approvals, so it should have zero effect.

Yeah, so that that's not correct that there's multiple examples where there are multiple accelerated approval. So it should have material effect.

Jeff Albers: Thank you, and this includes today's question and answer session. I would now like to turn the call back to Jeff Albers for closing remarks.

Okay.

[noise]. Thank you.

This concludes today's question and answer session I would now like to turn the calls back to Jeff hours for closing remarks.

Jeff Albers: Thanks, Operator. And again, thanks, everyone, for taking the time to join us tomorrow. I know it's a busy time of the year and for your continued support of Blueprint Medicines. And, importantly, we look forward to seeing all of you in a few weeks at Quad AI as we provide an update on the Indolent SM dataset. Thanks a lot. Bye-bye.

Thanks, operator, and again, thanks, everyone for taking time to join US Tomorrow I know, it's a busy time of the year and for your continued support a blueprint medicines.

And importantly, we look forward to seen to all of you in a few weeks at quite a high as we provide an update on the indolent SM data set thanks, a lot so by.

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

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

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