Q3 2020 Blueprint Medicines Corp Earnings Call

Operator: Standing by, and welcome to the Blueprint Medicine Third Quarter 2020 Earnings Conference Call. At this time, all participant lines are in a listen-only mode.

Standing by and welcome to the Blueprint medicines third quarter 2020 earnings conference call. At this time all participant lines are in a listen only mode. After the speakers presentation. There will be a question and answer session to ask a question during the session, we'll need to press star one on your telephone please be advised that todays conference is being real.

Operator: 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 one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to your speaker today, Kristen Hodas of Blueprint Medicine. Thank you.

Hoarded if you require any further assistance. Please press star zero I would now like to hand, the conference over to your speaker today, Kristen Potus, a blueprint medicine. Thank you. Please go ahead ma'am.

Kristen Hodas: Thank you, operator. Good morning, everyone, and welcome to Blueprint Medicine's third quarter 2020 Financial and Operating Results Conference call. This morning, we issued a press release that outlines the topics we plan to discuss today. You can access the press release as well as the slides that we'll be reviewing today by going to the investors and media section of our website at www.blueprintmedicines.com. Today on our call, Jeff Albers, our Chief Executive Officer, will discuss Blueprint Medicine's 3rd Quarter 2020 Business Highlights. Christy Rossi, our Chief Commercial Officer, will provide a commercial update, and Mike Landsittel, our Chief Financial Officer, will review our financial results.

Thank you operator, good morning, everyone and welcome to Blueprint medicines third quarter, 2020 financial and operating results conference call.

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

Today on our call Jeff hours, our Chief Executive Officer will discuss blueprint medicines third quarter 2020 business highlights.

Christy Rafi, our chief commercial officer will provide a commercial update and likely infertile, our chief Financial Officer will review our financial results Dr.

Kristen Hodas: Dr. Andy Burrell, our Chief Medical Officer, is also joining the call and will be available for Q&A. 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 most recent quarterly report on Form 10-2 filed with the SEC and any other filings that we may make with the SEC. 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.

Dr., Andy Brown, our Chief Medical Officer is also joining the call and will be available for QNX.

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 most recent quarterly report on form 10-Q.

Filed with the SEC and any other filings that we make with the SEC.

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.

Jeff Albers: Now, here's our CEO, Jeff Altman. Thanks, Kristen. And good morning, everyone. It's a pleasure to update you today on the significant progress we made this past quarter across our entire portfolio. As we've discussed previously, our key areas of strategic focus have been threefold. One, advancing our registrational programs in systemic mastocytosis. 2. Building our commercial expertise as we launch multiple new products, and three, continuing to strengthen our pipeline with new investigational medicines from our research platform. During the third quarter, and really the last month in particular, we made substantial progress across each of these focus areas, which highlights the strength of our portfolio as a whole and positions us well for continued growth opportunities ahead. Let me start with our focus on systemic mastocytosis, or SM.

Now here is our CEO, Jeff outburst.

Thanks, Christian and good morning, everyone. It's a pleasure to update you today on the significant progress we made this past quarter across our entire portfolio.

As we've discussed previously our key areas of strategic focus have been threefold, one advancing our registrational programs and systemic mastocytosis.

To building, our commercial expertise as we launch multiple new products and.

And three continuing to strengthen our pipeline with new investigational medicines from our research platform.

During the third quarter and really the last month in particular, we made substantial progress across each of these focus areas, which highlights the strength of our portfolio as a whole.

And positions us well for continued growth opportunities ahead.

Let me start with US is our focus on systemic mastocytosis or SM.

As a reminder, FM spans both advanced and non advanced forms of the disease and.

And the medical need across the entire spectrum is significant and urgent.

Jeff Albers: As a reminder, FM spans both advanced and non-advanced forms of the disease, and the medical need across the entire spectrum is significant. In September, we announced positive top-line results from our Explorer and Pathfinder clinical trials of AvaKit in patients with advanced SM. The data across both studies were consistent with previously reported results, showing profound reductions in mast cell burden, high overall response, and complete remission and Durable Clinical Benefit, including Prolonged Median Overall Survival.

Jeff Albers: Importantly, the data also showed an improved safety profile at the 200 mg once daily dose, validating our decision to capture additional data at this dose level. Collectively, the data underscore Ava Pritnick's transformative impact in these patients with advanced SM who are in urgent need of better treatment options. These data will comprise the foundation of our supplemental NDA filing with the FDA for Avapritinib and Advanced SM, which we are compiling rapidly and are on track to submit this quarter. Non-advanced or indolent SM remains a top priority for us based on the compelling Pioneer Part 1 data we presented earlier this year. They're again showing a high response rate and favorable safety profile at the 25 milligrams once per day dose. We continue to be encouraged to see acceleration of enrollment and expanding enthusiasm from existing investigators as well as from key opinion leaders more broadly. Turning to our commercial progress, in September, we received FDA approval of Gabaretto for the treatment of adult patients with metastatic RET fusion positive non-small cell lung cancer.

One data we presented earlier this year.

They are again, showing the high response rate and favorable safety profile at the 25 milligram once per day dose.

We continue to be encouraged to see acceleration of enrollment and expanding enthusiasm from existing investigators as well as from key opinion leaders more broadly.

Turning to our commercial progress in September we received FDA approval of GAAP rental.

For the treatment of adult patients with metastatic red fusion positive non small cell lung cancer.

A significant milestone for blueprint and for the lung cancer community.

This is our second precision medicine approval. This year following Eva kit for PDGF, our alpha driven just.

And solidifies blueprint medicines as a truly integrated biopharmaceutical company.

As Christie will discuss in a moment, we're ramping up the commercial launch of Gav Red Oak as we also leveraged the expertise of Roche with whom we signed a transformative collaboration for processing they have in the third quarter.

In addition, we look forward to the potential expansion of the GAAP write a label with an FDA decision anticipated by the first quarter of 2021 for Red altered thyroid cancers.

Finally, we continue to strengthen our pipeline with new programs emerging from our robust research platform.

As the virtual ESMO Congress in September we presented important preclinical data for Blue nine four or five our triple mutant inhibitor for treatment resistant SFR driven lung cancer.

Jeff Albers: A significant milestone for Blueprint and for the lung cancer community. This is our second Precision Medicine approval this year, following AvaKit for PDGFR-alpha-driven GIST, and solidifies Blueprint Medicines as a truly integrated biopharmaceutical company. As Christy will discuss in a moment, we're ramping up the commercial launch of Gavreto as we also leverage the expertise of Roche, with whom we signed a transformative collaboration for PralSetnib in the third quarter. In addition, we look forward to the potential expansion of the GEPRITO label with an FDA decision anticipated by the first quarter of 2021 for red altered thyroid cancer. Finally, we continue to strengthen our pipeline with new programs emerging from our robust research platform. For example, at the virtual ESMO Congress in September, we presented important preclinical data for Blue 945, our triple mutant inhibitor for treatment-resistant EGFR-driven lung cancer. Blue 945 was specifically designed to potently inhibit the most common on-target resistance mechanisms to osomertinib and first-generation EGFR inhibitors, importantly while retaining exquisite wild type and kinome selection.

Looking for five was specifically designed to Potently inhibit the most common on target resistance mechanisms to Opus Emerton and first generation EG fr inhibitors.

Importantly, while retaining exquisite wild type and timing and selectivity.

This is a product development from discovery through global registration.

This unified portfolio vision will be increasingly important as we advanced the next wave of investigational medicines into the clinic.

Jeff Albers: This profile has the potential to provide benefit to patients with treatment-resistant disease, as well as a safety profile that may enable combination strategies in earlier treatment. As we announced last month, we plan to advance Blue 945 into the clinic in the first half of 2021. In parallel, we're planning to nominate a complementary double mutant EGFR development candidate by the end of this year. Together, the triple mutant and double mutant compounds have the potential to address a broad population of patients with on-target resistance to other therapies, as well as form the basis of a transformative wholly owned combination in early line treatment to prevent the emergence of resistance and enable more durable patient benefits.

Overall, the progress achieved last quarter significantly strengthens our portfolio across all three of our key areas of strategic focus.

Were now entering the back end of 2020 as a fully integrated company with a range of commercial development and research programs that leverage efficiencies balance risk and focus on truly transformative opportunities.

And with our strong financial position, we are well positioned to invest in our wholly owned research platform as well as external innovation that can enable sustained growth and diversification over the long term.

Now, let me turn the call over to Christie to discuss our commercial efforts Christie. Thank.

Thanks, Jeff Good morning, everyone.

In many ways our progress in Q3 highlights the incredible growth opportunity that is in front of us as we head into 2021.

Growth it will be driven by the ongoing launch of ghetto.

The expansion of the blueprint commercial footprint into new geographies.

And of course, most significantly by our efforts to bring Eva printed forward to patients suffering from systemic mastocytosis.

Through this lens our accomplishments in the quarter set the stage for the next phase of Blueprint medicines journey as a leading fully integrated global precision Medicine company.

Jeff Albers: Beyond our EGFR programs, we continue to make progress with additional wholly-owned programs, as well as through our cancer immunotherapy research collaboration with Roche, and we're excited about the strength of our platform and the opportunities for future growth being generated by our research and discovery team. On that front, this quarter, we welcome Dr. Fouad Namouni to Blueprint Medicines as President of Research and Development. Fouad is now leading the R&D organization, overseeing all phases of product development from discovery through global registration.

Let's start with revenue.

As Jeff mentioned with the U.S. approval of Ghetto, and the European Commission approval for Eva Kit in September we are now delivering a portfolio of precision therapies to patients globally.

Overall, we recognized $6.3 million of products revenue, driven primarily by U.S., Eva kit sales of $6.1 million.

Following FDA approval Gav retro became available to patients late in the quarter and early revenue primarily reflects initial ordering by our selects network of independent specialty pharmacies.

We look forward to sharing additional metrics from our first full quarter of launch at our Q4 update.

Although it is early over the past several weeks as we have had give red oak commercially available in the field.

Been pleased with the positive feedback we received from a variety of stakeholders.

Our differentiated clinical profile, which includes deep and durable responses.

Jeff Albers: This unified portfolio vision will be increasingly important as we advance the next wave of investigational medicines into the clinic. Overall, the progress achieved last quarter significantly strengthens our portfolio across all three of our key areas of strategic focus. We're now entering the back end of 2020 as a fully integrated company with a range of commercial development and research programs that leverage efficiencies, balanced risk, and focus on truly transformative opportunities. And with our strong financial position, we're well-positioned to invest in our wholly-owned research platform, as well as external innovation that can enable sustained growth and diversification over the long term. Now, let me turn the call over to Christy to discuss our commercial efforts. Okay, Christy?

A predictable and manageable safety profile and once daily dosing.

Has resonated well with health care providers.

We've seen early uptake in patients who are being treated with a selective ret inhibitor for the first time as.

As well as in patients, who have had safety or tolerability challenges on sulfur catnip.

We have also had very positive reaction to the value gap red oak bring to payers pharmacists and health system.

We've seen broad payer coverage with an average turnaround time from prescription to therapy start of four days on our initial prescription.

And it had some early formulary wins with large community practices.

We've also been working closely with our partners at Genentech as we ramp up the lunch.

Their field team, including sales are now fully trained and actively engaging in close collaboration with our team at a local and regional level to drive biomarker testing.

Then if I wrap patients.

Educate prescribers about gun Freddo and support scientific exchange.

The combined team is also ready for our anticipated launch of ghetto in Ret positive Cyberark cancer, which is currently under review by the FDA under the real time Oncology review program.

Turning to either kit, we're seeing consistent utilization driven by patients with PDGF Ralph adjust as.

Christina Rossi: Thanks, Jeff. Good morning, everyone. In many ways, our progress in Q3 highlights the incredible growth opportunity that is in front of us as we head into 2021, growth that will be driven by the ongoing launch of Gavretto. The Expansion of the Blueprint Commercial Footprint into New Geographies, and, of course, most significantly, our efforts to bring Ava Pritniv forward to patients suffering from systemic mastocytosis. Through this lens, our accomplishments in this quarter set the stage for the next phase of Blueprint Medicine's journey as a leading, fully integrated, global precision medicine company. Let's start with revenue.

As well as some unpromoted utilization in late line Jeff.

Importantly, we are encouraged to see real world duration continue to trend positively and exceed what we saw in clinical studies.

We were also thrilled to receive European Commission approval for Eva Cat for the treatment of adult patients with Unresectable metastatic chest harboring the PDGF for alpha the 40 to be mutation.

As we've discussed previously our focused commercial launch of Eva printing up in Europe, we'll take a rare disease approach targeting geographical centers of excellence, enabling a foundation for future commercial efforts, there, especially in systemic mastocytosis.

And finally as Jeff also mentioned we are truly excited about the top line data that we announced in September for Eva printed in advance of them.

As we deepened our understanding of the opportunity we see that approximately one third of the 75000 patients in major markets are already diagnosed with another one third identifiable but miss diagnosed.

These numbers coupled with a duration of response, we just shared in our topline advanced SM dataset.

Christina Rossi: As Jeff mentioned, with the U.S. approval of Gavreto and the European Commission approval for AvaKit in September, we are now delivering a portfolio of precision therapies to patients globally. Overall, we recognized $6.3 million of product revenue, driven primarily by U.S. AvaKit sales of $6.1 million. Following FDA approval, Gavretto became available to patients late in the quarter, and early revenue primarily reflects initial ordering by our select network of independent specialty pharmacies. We look forward to sharing additional metrics from our first full quarter of launch at our Q4 update. Although it is early, over the past several weeks since we have had Gavreto commercially available in the field, I've been pleased with the positive feedback we've received from a variety of stakeholders.

And the chronic treatment paradigm in non advance disease.

Make SM, a significant commercial opportunity for blueprint medicines.

I can't overstate, how great the treatment need is for these patients.

Who suffer from debilitating symptoms that significantly impact their lives.

We are working with urgency to make Ava <unk> viv available commercially to patients living with this devastating disease.

First in the U.S. and then globally.

As we move through Q4 and into 2021, we will continue to focus our efforts on these growth drivers that I've outlined.

We look forward to advancing the commercial launch of Gav righto in non small cell lung cancer and eagerly anticipate our approval in fibroid in collaboration with our colleagues at Genentech.

We've initiated the launch of advocate in Germany, and look forward to making even get commercially available in other countries in Europe.

And we'll continue our support of just patients in the U.S.

And finally and critically our team is ramping up our launch efforts in support of a partner for FM.

Which we hope will be available to patients in the U.S. next year.

The growth ahead of us is truly exciting.

Christina Rossi: Our differentiated clinical profile, which includes deep and durable responses, a predictable and manageable safety profile, and once-daily dosage, has resonated well with health care providers. We've seen early uptake in patients who are being treated with a selective red inhibitor for the first time, as well as inpatients who have had safety or tolerability challenges on sulpricat. We have also had very positive reactions to the value Gavreto brings to payers, pharmacists, and health systems.

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

Thanks Christie.

Earlier this morning, we reported.

Third quarter 2020 financial results in our press release.

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

We recognized total revenues of $745 million in the third quarter.

As Christie mentioned, we are pleased to record $6.3 million of net product revenues, primarily driven by either kit sales.

We also recognized approximately $739 million in collaboration revenue, including the upfront payment equity purchase premium and milestone payments under our collaboration with Roche for consent.

Christina Rossi: We've seen broad payer coverage with an average turnaround time from prescription to therapy start of four days on our initial prescription, and we have had some early formulary wins with large community practices. We've also been working closely with our partners at Genentech as we ramp up the launch. Their field teams, including Salve, are now fully trained and actively engaging in close collaboration with our team at a local and regional level to drive biomarker testing, identify RET patients, educate prescribers about Gavreto, and support scientific exchange. The combined team is also ready for our anticipated launch of Gavreto in RET-positive thyroid cancer, which is currently under review by the FDA under the Real-Time Oncology Review Program. Turning to AvaKit, we are seeing consistent utilization, driven by patients with PDGFR-alpha GIST, as well as some unpromoted utilization in late line. Importantly, we are encouraged to see real-world durations continue to trend positively and exceed what we saw in clinical studies. We were also thrilled to receive European Commission approval for AvaKit for the treatment of adult patients with unresectable or metastatic gist harboring the PDGFR-alpha-D842V mutation.

Cost of sales remained low as we continue to work on commercial inventory that we expense pre approval.

Our total operating expenses decreased compared to the prior quarter.

Driven by global R&D cost sharing and us profit sharing under our collaboration with Roche.

Looking forward, we expect to see modest quarter over quarter operating expense growth as we continue to advance our investments in systemic mastocytosis psychosis with favorite Britain had been glued to Sixthree as.

As well as advanced our discovery portfolio, including our IGI apart programs towards the clinic.

We also anticipate significant increases in non cash stock based compensation expense for the foreseeable future.

With approximately $1.4 billion in cash on hand, we are in the strongest financial position that we have ever been as a company.

And looking over the long term our diverse portfolio and strategic collaborations have the potential to provide multiple meaningful revenue sources include.

Including product sales across multiple geographies and milestone and royalty payments under our four major partnerships with Roche Keystone and its and.

For example, we anticipate the total milestone and royalty payments from existing collaborations could average approximately $80 million per year over the next few years.

Christina Rossi: As we've discussed previously, our focused commercial launch of avipritinib in Europe will take a rare disease approach, targeting geographical centers of excellence, enabling a foundation for future commercial efforts there, especially in systemic mastocytosis. And finally, as Jeff also mentioned, we are truly excited about the top-line data that we announced in September for Ava Pritinib and Advanced FM. As we've deepened our understanding of the opportunity, we see that approximately one-third of the 75,000 patients in major markets are already diagnosed, with another one-third identifiable but misdiagnosed. These numbers, coupled with the duration of response we just shared in our Topline Advanced SM Dataset and the Chronic Treatment Paradigm in Non-Advanced Disease, make SM a significant commercial opportunity for Blueprint Medicines. I can't overstate how great the treatment need is for these patients, who suffer from debilitating symptoms that significantly impact their lives.

We are in a unique position for a company of our size and age and we look forward to sharing further updates with you as we continue to make progress across our portfolio.

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

As a reminder to ask a question you will need to press star one on your telephone to withdraw your question press. The pound key we ask that you. Please limit yourself to one question and one follow up question.

Please standby, while we compile the culinary roster.

Our first question comes on the line line of Marc Frahm from Cowen. Your line is now open.

We got into index and you can give us a status update and when do you expect to complete enrollment on there I know historically, you've talked about the end of this year being possible. But then also talked about Kobe, possibly slowing things down to discuss where are we there.

[music].

Sure. This is Jeff I'll take that so weve provided in the prepared statements in the release that will provide a more detailed update on enrollment at the beginning of 2021.

We had as we talked about previously it was certainly at the startup was slowed it.

Due to co vid.

Christina Rossi: We are working with urgency to make Avopretinib available commercially to patients living with this devastating disease, first in the U.S. and then globally. As we move through Q4 and into 2021, we will continue to focus our efforts on these growth drivers that I've outlined. We look forward to advancing the commercial launch of Gavreto in non-small cell lung cancer and eagerly anticipate our approval in thyroid in collaboration with our colleagues at Gene

And now we continue to add more sites and there is some critical sites that are coming on now in some cases, there in regions, where feed cases seem to be lower but in other cases. Some of the sites that you know work think of one site in particular about to come on where unfortunately cases seem to be spiking in that region as well. So we want to get a little more color.

On that.

But all the markers of engagement.

Oh patients' willingness to come in are there. So we need to be really optimistic we'll have a better sense of exact timing of when it will be fully enrolled.

At beginning of next year.

Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open.

Hi, everyone. Thanks for taking the question. This is Andrew on for Salveen, maybe just as a follow up to that would love to hear more about the cadence of other data read outs from SM portfolio, particularly when we might be able to see additional follow up for the Pathfinder trial, and then I have a follow up.

Christina Rossi: We've initiated the launch of AvaKit in Germany and look forward to making AvaKit commercially available in other countries in Europe, and we'll continue our support of GIST patients in the U.S. Finally, and critically, our team is ramping up our launch efforts in support of Ava Pritnick for SM, which we hope will be available to patients in the U.S. next year. The growth ahead of us is truly exciting I'll now turn the call over to Mike to discuss financial updates. Thanks, Christy.

Sure. So this is Jeff I'll start so we haven't guided to the next update obviously, we just provided the topline data for advance FM in September.

Obviously, we've we're in the process of first and foremost getting our SMB a file pulled together.

But we also.

Certainly intend to provide updates on on that data set in more fulsome nature at a medical conference, but we haven't guided to a specific timing.

Got it and then just with respect to the collaboration for 'em Kavita with Roche you've spoken about the potential to explore additional indications or combinations. Just wondering how you and Roche are thinking about this right now and when we might see advancement into into one of one of those programs.

Michael Landsittel: Earlier this morning, we reported detailed third quarter 2020 financial results in our press release. For today's call, I'll touch on a few financial highlights from the. We recognize total revenues of $745 million in the third quarter. As Christy mentioned, we are pleased to record $6.3 million of net product revenue, primarily driven by We also recognized approximately $739 million in collaboration, including the upfront payment, equity purchase premium, and milestone payments under our collaboration with Roche or Palsett. The cost of sales remains low as we continue to work off commercial inventory that we expensed pre-approval.

Yes, Andy I'll take that so yes. So we are we're working very closely with our colleagues overt Roche and it's been it's been a very.

Collegial relation.

Relationship where we are.

In the process of figuring out how to expand the excel and accelerate the development plan.

We are already pursuing the tumor agnostic indications in nonres.

Driven solid tumors that started out actually as an army Arris study and really now the focus is on how to move pressure NIM earlier into earlier lines of therapy, both as a single agent, but also importantly in combo with other medicines, including some of which would be in the Roche portfolio and so as we work through these details will I think we'll update in the future.

[music].

Great. Thanks, so much.

Okay.

Thank you. Our next question comes on the line all Ren Benjamin from JMP Securities. Your line is now open.

Michael Landsittel: Our total operating expenses decreased compared to the prior quarter, driven by global R&D cost sharing and U.S. profit sharing under our collaboration. Looking forward, we expect to see modest quarter-over-quarter operating expense growth as we continue to advance our investments in systemic mastocytosis with avipritinib and Blu263, as well as advance our discovery portfolio, including our EGFR programs, towards, We also anticipate significant increases in non-cash stock-based compensation expense for the foreseeable future. With approximately $1.4 billion in cash on hand, we are in the strongest financial position that we have ever been, and looking over the long term, our diverse portfolio and strategic collaboration, have the potential to provide multiple meaningful revenue, including product sales across multiple geographies and milestone and royalty payments under our four major partnerships with Roche, SkiStone, and, For example, we anticipate that total milestone and royalty payments from existing collaborations could average approximately $80 million per year over the next few years.

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

Thats on all the progress can you just I know, it's early for good Red Oak, but.

As we follow the trajectory of.

Loxo drugs should we be thinking about this ramp kind of like neck and neck with that or are there differences that we need to be.

Considering as we as we think about the commercialization of this product and then maybe just related to what's happening in the E. U you mentioned, Germany I jumped on the call a little late and so I just wanted to get a sense as to how the other country specific discussions are emerging and how we should view that.

Thank you.

Sure I have this is Christie I cannot I can take that so and as I said, we're really excited about the progress that we're seeing with the got ready to launch we've had a lot of you know great reception to the data as well as the approach that we're taking you know if I think about what we've seen from Lilly you know I think the biggest thing that we can.

Take from from that so far is that the opportunity is as attractive right. I mean, we clearly know that there is a lot of rep patients out there and we expect that that opportunity will continue to grow is as more and more patients are identified a you know I think the biggest difference is that now there that.

Center available as opposed to one so you know you can't extrapolate obviously the ramp up of an agent when it's the only agent on the market, but we are certainly going to continue to look to new patient starts first in lung and then you know anticipating as I write approval on the heels of that and as we continue to ramp new patient starts we'll see that flow through.

So look forward to having kind of more of that data to share as we provide to keep our IP.

And then on Europe to address that question as well so at where we were thrilled to have that approval and have you know blueprint really emerge as a global commercial company and now the German launches is underway, Germany is usually the first market out of the gate as as I know I'm sure everyone's aware just given the reimbursement dynamics.

Michael Landsittel: We are in a unique position for a company of our size and age, and we look forward to sharing further updates with you as we continue to make progress across our portfolio. With that, I would now like to turn the call over to the operator. Operator. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key.

And we would expect other countries to come online over time clearly the biggest hurdle is as I think everyone's aware is really securing pricing and reimbursement in the timelines around that are different by market. So we will we are actively engaged in those discussions and look forward to having Eva cat commercially available for PDF, Ralph added 40 to be mutant patients in Europe.

Operator: We ask that you please limit yourself to one question and one follow-up question. Please stand by while we compile the Q&A roster. Our first question comes from the line of Marc Frahm from Cowan. Your line is now open. Maybe on indolent SM, can you kind of give us a status update? And when do you expect a complete enrollment there?

In the coming in coming months.

Thank you. Our next question comes the line of Andrew Barron's from SVB Leerink. Your line is now open.

Hi, Thanks.

I wanted to ask you guys a question regarding the regulatory process.

Which you are about to summit I.

Jeff Albers: I know, historically, you've talked about the end of this year being possible, but then you also talked about COVID possibly slowing things down. So, just kind of where are we? Sure, this is Jeff. I'll take that.

No we probably visited this in the past, but I was wondering how you think the FDA, we'll look at your submission, which will have two studies, they're both non control versus minus store, which has a full approval based on a controlled trial.

Jeff Albers: Yeah, so we provided in the prepared statements and release that will provide a more detailed update on enrollment at the beginning of 2021. As we talked about previously, it certainly was the startup that was slowed due to COVID. And now, you know, we continue to add more sites. And there are some critical sites that are coming on now. In some cases, they're in regions where cases seem to be lower.

Hey, it's Andy I'll take that yes, I know, we think the the data with even in advance as Sam has really transformative for patients and pretty dramatically different than what's been seen with might historian.

So yes. So we are actually very confident in the data set based on both exploring Pathfinder studies, it's consistent with discussions we've had with the FDA and where are you on track to submit that.

Make that in the SSD submission in the fourth quarter end.

And are confident that we will be well received I actually want to point out that while made a store and had a randomized study in leukemia with single arm data in the densest now.

Jeff Albers: But in other cases, some of the sites that, you know, I can think of one site in particular about to come on where, you know, unfortunately, the cases seem to be spiking in that region as well. So we want to get a little more color on that. But you know, all the markers of engagement of patients' willingness to come in are there. So we continue to be really optimistic, but we'll have a better sense of the exact timing of when it will be fully enrolled at the beginning of next year. Thank you. Our next question comes from the line of Salveen Richter from Goldman Sachs. Your line is now open. Hi everyone.

I got their approval.

Okay. Okay.

Okay. Thanks for clarifying that appreciate it.

Thank you. Our next question comes from the line of Peter Lawson from Barclays. Your line is now open.

Hey, Thanks for taking my question just on Bloom Lake for five against the Triple in the double digit phone.

Drugs, how should we think about trial design wins.

When should we be thinking about initial data from this growth.

Sure Andy why don't you take that yes. So so if you could just remind everyone that fleet grew nine four or five which is our triple meeting each of our inhibitor was specifically designed to potently inhibit the most common on target resistance mutations to both customers and the first generation Jeff are inhibitors.

Well not inhibiting the wild type kind nieces delta kinase and really we think this profile has the opportunity to provide.

Operator: Thanks for taking the question. This is Andrea on behalf of Salveen. Maybe just as a follow-up to that, we'd love to hear more about the cadence of other data readouts from the SM portfolio, particularly when we might be able to see additional follow-up for the Pathfinder trial. And then I have a follow-up. Sure. So this is Jeff.

We are very important benefit to patients both with true with treatment resistance with treatment resistant disease, but also in combination with other EG far directed agents and I think as you know we're also developing a double mutant inhibitor, which is really focused on the resistance situation following frontline awesome.

Martin and then really the.

Jeff Albers: I'll start. So we haven't been guided to the next update. Obviously, we just provided the top line data for ADVANCE-SM in September. Obviously, we've, you know, we're in the process of, first and foremost, getting our SNDA file pulled together. But we also, you know, certainly intend to provide updates on that data set in a more fulsome nature at a medical conference, but we haven't guided to a specific timing. Got it.

The what is truly exciting about this program is the up the opportunity to combine these two medicines is they'll both be wild type sparing in the frontline setting where we can really provide high response rates per lung disease control we think.

By preventing the emergence of resistance really potentially of all of the known on target HFR resistance mechanisms. So we are planning to advance nine for five into the clinic in the first half of <unk>.

2021, and we expect to nominate a double mutant inhibitor by the end of the year.

Unknown Speaker: And then just with respect to the collaboration for Gavreto with Roche, you've spoken about the potential to explore additional indications or combinations. Just wondering how you and Roche are thinking about this right now and when we might see advancement into one of those programs. Hi Sandy, I'll take that.

And this is Jeff just to underscore that yes.

Yes, it's been interesting as we shared data asset virtual mean ESMO just the engagement from investigators and Kayla has has really been exciting on this program and that I think Andy summarized that well, it's first establishing single agent the single agent opportunity, but the ability to combine.

Buying these two therapies based on the profile that any just laid out and the potential from a safety perspective to move into early lines and really present prevent resistance and then maximize durability is something that internally. There is just growing enthusiasm to move those programs as a fee.

Unknown Speaker: So yeah, we're working very closely with our colleagues over at Roche, and it's been a very collegial relationship where we are in the process of figuring out how to expand and accelerate the development plan. We are already pursuing the tumor agnostic indication in rectal driven solid tumors that started out actually as an arm in the arrow study, and really now the focus is on how to move pralsetinib into earlier lines of therapy, both as a single agent and also importantly in combination with other medicines, including some of which would be in the Roche portfolio. And so as we work through these details, I think we'll update them in the future. Thank you. Our next question comes from the line of Ren Benjamin from JMP Securities. Your line is now open. Hey, good morning, guys.

Recently and effectively it forward as possible.

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

Thank you very much for taking my question.

When you look at the initial the rental launch.

It would be the recent entry of the Roche partnership.

Would you say the commercialization effort is fully ramped up.

To steady state at this point given how close to the partnership was entered or do you expect it will evolve more in the coming months.

Sure Yeah. So as I said, you know there the Roche and Genentech teams have been trained and they are out engaging and were certainly working at a local level to collaborate on specific engagements and of course at a national level as well to make sure that were fully utilizing the capabilities of both partners. So.

Operator: Thanks for taking the questions and congrats on all the progress. Can you just, I know it's early for Govretto, but, you know, as we follow the trajectory of the Loxodrug, should we be thinking about this rant kind of like neck and neck with that? Or are there differences that we need to be considering as we think about the commercialization of this product? And then, maybe just related to what's happening in the EU, you mentioned Germany.

I would say the effort is is ramped up and of course as you go through Alliance you know one of the critical things is to be nimble and flexible and to adapt and as you learn more information. So I'm sure. We will do that like we would do with any product that we've got both teams are fully engaged and we're really excited about that.

Hey, Jeff maybe I'd just add on there that need obviously, it's going to be a continued evolution to because we've got the additional fibroid indication coming and then ultimately where we really think that the value from these two teams working together is going to be realizes and patient identification. So that will be more of a sort of a gradual realism.

Christina Rossi: I joined the call a little late, and so I just wanted to get a sense as to how the other countries' specific discussions are emerging and how we should view that. Thank you. Sure, this is Christy.

Nation of maximizing that opportunity.

With that in mind.

Understanding that since it is a red targeted therapy and yes. The approval at this point is non small cell and then mtc could come in first quarter.

Christina Rossi: I can take that. So, as I said, we're really excited about the progress that we're seeing with the Gavretto launch. We've had a lot of, you know, great reception for the data, as well as the approach that we're taking. You know, if I think about what we've seen from Lilly, I think the biggest thing that we can take from that so far is that the opportunity is attractive, right?

How do you expect.

Physicians will.

I guess deal with.

People that come up testing positive for for rent fusions and red alterations in other indications at this point.

So our focus right now is certainly on really driving education around non small cell lung and then obviously preparing for thyroid, which we're hopeful we'll be in the near future and that approval. So we're ready to go there.

Christina Rossi: I mean, we clearly know that there are a lot of RET patients out there, and we expect that that opportunity will continue to grow as more and more patients are identified. You know, I think the biggest difference is that now there are two patients that are available as opposed to one. So, you can't extrapolate, obviously, the ramp of an agent when it's the only agent on the market.

You know, we certainly do see you know rat alterations in other indications as well that's you know not a commercial focus we certainly share some clinical data in that respect and I think you know we may see utilization there.

We would anticipate that but that's not a place that we would be primarily focus from a commercial perspective sure sure and then last question certainly the operating expenditures.

Christina Rossi: But we are certainly going to continue to look to new patient starts, first in lung cancer, and then, you know, anticipating a thyroid approval on the heels of that. And as we continue to ramp up new patient starts, we'll see that flow through. So, I look forward to having kind of more of that data to share as we provide a Q4 update. And then on Europe, to address that question as well, so we were thrilled to have that approval and have Blueprint really emerge as a global commercial company now. The German launch is underway.

Dropped.

Oh quite a bit from the second quarter in both R&D and as teenagers.

With the first quarter kind of being in the middle given the recent partnership how should we think of.

Which we should think of as the right run rate as far as spend level going forward or would it be closer to the first quarter second quarter or third.

Yeah, Mike do you want to take that one.

Yes. Thanks. This is Mike Yeah. So I think what you saw in the third quarter was the impact.

The global R&D cost sharing as well as the U.S. cost sharing profit sharing from the Roche collaboration and so that caused a reset of clinical or operating expenses are for Q3, but going forward. We think we will see modest quarter over quarter increases maybe not unlike I don't want to point to a specific quarter, but the trend that we.

Christina Rossi: Germany is usually the first market out of the gate, as I know, I'm sure everyone is aware, just given the reimbursement dynamics. We would expect other countries to come online over time. Clearly, the biggest hurdle, as I think everyone is aware, is really securing pricing and reimbursement, and the timelines around that are different by market. So we are actively engaged in those discussions and look forward to having AvaKit commercially available for PDGF-4-Alpha, D842V mutant patients in Europe in the coming months. Thank you. The next question comes from the line of Andrew Berens from SVB Larynx. Your line is now open.

We saw over the.

The past year or so on quarter on quarter growth. It just will be resetting from a lower level since we have the impact of the cost and profit sharing.

Thank you very much for that very helpful.

Yes.

Thank you our.

Our next question comes from the line of Chris Raymond from Piper Sandler. Your line is now open.

Good morning, and thanks for taking the question. This is Nicole good Brzeski on for Chris. So maybe just one on the pipeline I'm following up with some of the other questions. So I know you guys have talked about disclosing up to three new development candidate this year and I know one of those is two nights were five in the second will be the IGI affordable meeting candidate but.

Operator: Hi, thanks. I wanted to ask you guys a question regarding the ASM regulatory process, which you're about to submit. I know we've probably discussed this in the past, but I was wondering how the FDA will look at your submission, which, while you'll have two studies, they're both non-controlled versus mitostorin, which has a full approval based on a controlled trial. Hey, it's Andy.

I guess I'm just curious is there a certain venue, where we can expect to hear more about the affordable yet.

Candidate as well as a potentially more detail around a potential third development candidate. Thanks.

Andrew Scott Berens: I'll take that. Yes, I know we think the data with Ava Pritnib in advanced SM is really transformative for patients and pretty dramatically different from what's been seen with mitostaurin. So, you know, we're actually very confident in the data set based on both the Explorer and Pathfinder studies. It's consistent with discussions we've had with FDA, and we're on track to make that SNDA submission in the fourth quarter and are confident that we'll be well-received. I actually want to point out that while mitostaurin had a randomized study in leukemia, it was single-arm data. Okay. Oh, okay.

Sure This is Jeff.

I'll take that so in terms of venue, we haven't guided to where we'll provide.

Preclinical data I think it's safe to assume that's going to happen.

For the double meeting program in 2021, and we'll sort of reset.

Goals and guidance early in Q1 as we do every year in terms of a venue for that third development candidate I think there to sort of.

The team is is pulling all that together will likely happen.

During the quarter. So I think early Q1 is what we where we would announce what that program is.

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

Hi, Thanks for taking my questions here.

So I guess I'll just jam two together here firstly.

Andrew Scott Berens: Yeah. Thanks for clarifying that. I appreciate it.

When you're thinking about the market opportunity for imprinted and.

Operator: Thank you. Our next question comes from the line of Peter Lawson from Barclays. Your line is now open. Hey, thanks for taking my question. Just on Blue 945, I guess the triple and the double EGFR mutant drugs. How should we think about trial designs and when should we be thinking about initial data for both those?

Yes, and I asked them in the 75000 patients.

This is the market opportunity how are you thinking about incremental opportunity with Bluetooth Sixthree is that more on my cell activation syndromes like hereditary outlets septicemia syndrome, or perhaps as it's called.

And then secondly.

Sorry, Blue nine four or five maybe you could put some more contact in terms of.

The murder to moving now into adds event and how you would think about running the study and then just basically what's the checklist to do to actually get that study started in the first half the year from a regulatory and clinical site standpoint. Thank you.

Andrew Scott Berens: Andy, why don't you take this? Yes, So, you know, just remind everyone that Blue 945, which is our triple mutant EGFR inhibitor, was specifically designed to potently inhibit the most common on-target resistance mutations to both osimertinib and the first-generation EGFR inhibitors while not inhibiting the wild-type kinases. And really, we think this profile has the opportunity to provide a very important benefit to patients, both with treatment-resistant disease but also in combination with other EGFR-directed agents. And I think, as you know, we're also developing a double mutant inhibitor that is really focused on the resistance situation following frontline osomertinib. And really, what's truly exciting about this program is the opportunity to combine these two medicines, since they'll both be wild-type sparing in the frontline setting, where we can really provide high response rates and prolonged disease control, we think, by preventing the emergence of resistance, really, potentially, to all of the known on-target EGFR resistance mechanisms.

So Chris you want to take the first question enough I pass it over to Andy for the second question sure. So you know we are.

Moving even print no forward, obviously very rapidly in I asked them and we're very excited about the data that's emerging there and pioneer Lucy six three you know I think about really as a you know an opportunity to sort of solidify and expand our emerging franchise and myself.

Saunders am I thinking about that first for iOS them as well and there you know I think the potential is you know as the profile emerge as to really optimize labeling dosing and maybe to be able to penetrate even more broadly into the indolent opportunity and so we're excited about that and then we are also investigating flew to sixthree.

As I said before in an other national disorders, and really feel like we can optimize the profile there for.

You know a group of diseases that really require a chronic lifelong treatment. So we'll be moving both of those for it and I will turn it to Andy Hersey. So maybe I'll take your second first steps to getting nine for five into the clinic. It's we're just working on the components.

Andrew Scott Berens: And so, we are planning to advance 945 into the clinic in the first half of 2021, and this is Jeff, just to underscore that, you know, it's been interesting as we shared data at the virtual meeting in Esmo, just the engagement from investigators and KOLs has really been exciting on this program. And I think Andy summarized that well as first establishing single agent, the single agent opportunity, but the ability to combine these two therapies based on the profile that Andy just laid out, and the potential from a safety perspective, to move into early lines and really prevent resistance and then maximize durability is something that internally, there's just growing enthusiasm to move those programs as efficiently and effectively forward as possible. Thank you. Our next question comes from David Lebowitz from Morgan Stanley. Your line is now open. Thank you very much for...

And final.

Nonclinical Tox and other work necessary for the R&D and <unk>.

And of course, we will submit the idea and be on track to begin that study in the first half of next year I think theres nothing specific or unusual that's that's going on there and osmer and moving it has been I think is actually I think offers a pretty interesting opportunity in fact nine for five years as we talk to you.

Some of the argue on the lung cancer experts that we interact with there's definitely thinking that as as assay goes to address and in those patients when they as they progress.

Operator: When you look at the initial Govretto launch, would you say the commercialization effort is fully ramped up to steady state at this point, given how closely the partnership was entered into, or do you expect that it will evolve? Sure. Yeah, so as I said, the Roche and Genentech teams have been trained, they are out engaging, and we're certainly working at a local level to collaborate on specific engagements, and, of course, at a national level as well to make sure that we're fully utilizing the capabilities of both partners. So, you know, I would say the effort is ramped up. Of course, as you go through a launch, you know, one of the critical things is to be nimble and flexible and to adapt as you learn more information. So I'm sure we will do that. Like we would do with any product, we've got both teams fully engaged, and we're really excited about that.

An advanced form of the disease gives us a really strong starting point and then we made investments in 263 to round out from a position of strength and so there was still be patients where there is need whether it be X.

Christina Rossi: This is Jeff. I just want to add that obviously, it's going to be a continued evolution too because we've got the additional thyroid indication coming, and then ultimately, where we really think that the value from these two teams working together is going to be realized is in patient identification. So that will be more of a sort of gradual realization of maximizing that opportunity. Um, with that in mind, um... Understanding that since it is a retargeted therapy, and yes, the approval at this point is non-small cell, and then MTC could come in the first quarter. How do you expect physicians will deal with patients that come up testing positive for RET fusions and RET alters, and other indications?

Expanding is Christie said, indolent SM or another Marcel diseases, but.

If you think about how a portfolio evolves over time.

All of that is at play here and with the strong financial position allows us to continue to invest in the opportunities.

That provide the greatest potential patient benefit.

Thank you.

Next question comes from the line of Ireland in the front Canaccord. Your line is now open.

Hi, guys. Thanks for taking my question.

A couple of one and it's M filing.

I'm curious with getting for that.

And then until three.

And you said you were planning to initiate.

Trial.

Also can you please talk about and.

<unk> you mentioned that was not bringing penetrant can you can you also talk about the other design elements that money to 263.

Christina Rossi: So, our focus right now is certainly on really driving education around non-small cell lung cancer and then obviously preparing for thyroid, which, you know, we're hopeful will be in the near future, that approval, and so we're ready to go there. You know, we certainly do see RET alterations in other indications as well. That's, you know, not a commercial focus; we certainly shared some clinical data in that respect, and I think, you know, we may see utilization there; we would anticipate that, but that's not a place that we would be primarily focused from a commercial perspective. Transcripts provided by Transcription Outsourcing, LLC. And then last question, certainly operating expenditures dropped quite a bit from the second quarter, both R&D and SG&A, with the first quarter kind of being in the middle.

Okay.

Sure and did you want us to go so the filing an advance SM and then characteristics of two 600.

So in terms of in terms of what's gaming for some filing it's just now getting the documents together.

Really fair better writing to do and that kind of thing, but all that we have all the data in hand, and so we're just doing the final through.

Through the final.

Parts of the process to get the filing together and again that will go in this year.

263 so.

So the.

In terms of the trial, we're we're very happy to get that healthy volunteer study started in the first half of the year on track. Despite COVID-19, and it remains on track to provide the the key data by the end of this year, which is really is really dose determining data for what the Ah.

Appropriate dose or dose range would be for patients with ism's for the first time. Some study we haven't specifically guided to win that first Ism's study will start, but obviously, that's a high priority for us and elegant as you mentioned, we designed which is six three very specifically not across the board room.

Operator: Given the recent partnership, what should we think of as the right run rate as far as spend levels going forward would be closer to the first quarter, second, and Mike, do you want to take that one? Yeah, thanks. This is Mike.

[noise] barrier and that's an important.

Michael Landsittel: Yeah, so I think what you saw in the third quarter was the impact of the global R&D cost sharing, as well as the US cost sharing profit sharing from the Roche collaboration. And so that caused a reset of kind of where operating expenses were for Q3. I think going forward, we think we will see modest quarter-over-quarter increases, maybe not unlike I don't want to point to a specific quarter, but the trend that we saw, you know, over, Page PAGE of NUMPAGES www.verbalink.com Page PAGE of NUMPAGES, Thank you. Our next question comes from the line of Chris Raymond from Piper Sandler. Your line is now open. Good morning, and thanks for taking the question. This is Nicole Gabreski on for Chris.

Distinction from a nib. It also has a bit more selectivity on a couple of other fronts.

On on a few other enzymes, where we think are potentially.

For potential benefit, but some of that some hypothetical.

Thank you Alright next question goes online no Michael Schmidt some Guggenheim Your line is now open.

Hey, guys. Thanks for taking my questions Uhm I just had one on Eva kit Uhm your sales in the third quarter suggest about 100 patients treated can you confirm that and I think you mentioned some non promotive use could you maybe quantify that little bit how much of that is in.

Just more broadly versus potentially in as a patient already at this point.

Sure I'll I'll take that so I'm not going to get into details on exactly how many patients. They have treated obviously then that there is is complex if that patient continuing to sky.

Operator: So, maybe just one on the pipeline, following up with some of the other questions. So, I know you guys have talked about disclosing up to three new development candidates this year, and I know one of those is Blue 945, and the second will be the EGFR double mutant candidate. But I guess I'm just curious, is there a certain venue where we can expect to hear more about the EGFR double mutant candidate, as well as potentially more detail around a potential third development? This is Jeff.

The shorter durations only be late Lang catcher then just patients on therapy, we I think quite long durations when you see PDGF wrath of patients.

But overall, we're pleased to continue to see revenue growth and jazz and.

Very happy to have that option.

Available for for patients and entered the quantifying the exact Max as I said before it's challenging to do that.

We can try to make estimates felt we're relying primarily on.

Feedback, we may get from from prescribers and patience the coding for these patients says the same and so.

Jeff Albers: I'll take that. So in terms of venue, we haven't decided where we'll provide preclinical data. I think you could safely assume that's going to happen for the Double Mutant program in 2021, and we'll sort of reset goals and guidance early in Q1, as we do every year. In terms of a venue for the third development candidate, I think they're two sort of. The team is pulling all that together. It will likely happen later in the quarter.

We're not in a position to be able to stay with certainty. We just know that we continue to see utilization clearly have guidelines listing in late lines, yet and we know that the unmet need patience.

Patience is still very high.

Understood and then a kristy with Gov, rather on on the market.

The only been a few weeks, but just wondering what the initial of feedback has been from lung cancer for sessions.

And.

With two T. K I is now available and maybe what has feedbag been around some of the differentiating side effects of those two drugs specifically the absence of Q T. C. Prolongation and then some of the potential differences in efficacy and dosing frequencies.

Jeff Albers: So I think early Q1 is where we would announce what that program is. Thank you. Our next question comes from the line of Dane Leone from Raymond James. Your line is now open.

Sure and yeah. So I think the feedback has been at that very very positive ink first of all the community thrilled to have effective therapies available for the patients right that if not had treatment available today.

Operator: Hi, thanks for taking the questions here. So, I guess I'll just jam two together here. Firstly, when you're thinking about the market opportunity for ibuprofen and ASM and ISM and the 75,000 patients you listed as the market opportunity, how are you thinking about the incremental opportunity with flu 263? Is that more in mast cell activation syndromes like hereditary alpha tryptosemia syndrome or HATs, as it's called?

I think we're going to see utilization of of both agents I think.

Right. It was for you to be very highly effective I think certainly the safety as you mentioned is probably where you see maybe more difference and again.

Again, I think the idea of sinus.

Side effects that are sort of in though we all house of prescribing oncologists.

Christina Rossi: And then secondly, regarding Blue 945, maybe to put some more context in terms of isomertinib moving now into adjuvant therapy and how you would think about running the study? And then, just basically, what's the checklist to do to actually get that study started in the first half of the year from a regulatory and clinical site standpoint? Thank you. So, Christy, why don't you take the first question and then I'll pass it over to Andy for the second question.

Thing that I think is is comforting versus some things that maintenance requires some some different management approach. My <unk> is one hypersensitivity is another again and I think we've continued to hear about in the real world and it's early days I think with both of these agents is that I think what we have to remember is that the clinical profile will continue to emerge over time, both from an <unk>.

<unk> at the end of safety perspective, as you start to get that railroad utilization.

Last piece I think that we've been very happy to to get feedback around is is sort of the <unk>.

Non clinical aspects of the profile that are also very important right. So once daily dosing, which again oncologists like everybody else that in fact, we had one one person's data oncologist, but I still would like to get a call back around issues and so it's simplicity is important and the approach that we've taken which is really again prioritized.

Christina Rossi: Sure. So, you know, we are, you know, moving, if I put it forward, obviously, very rapidly in ISM, and we're, you know, very excited about the data that's emerging there in Pioneer. Blue 263, I think about really as an opportunity to sort of solidify and expand our emerging franchise in mast cell disorders. We're thinking about that first for ISM as well.

Practices and dispensing pharmacy is being able to you know.

Retain control and treatment of their patients has been very well received.

Thank you.

Our next question comes from the line of David near in General from Wedbush Securities. Your line is now open.

Alright, Thanks Sofa the interpretation of the name.

Christina Rossi: And there, you know, I think the potential is, you know, as the profile emerges, to really optimize labeling, dosing, and maybe to be able to penetrate even more broadly into the indolent opportunity. And so we're excited about that. And then we are also investigating Blue 263, as we said before, and other mast cell disorders, and really feel like we can optimize the profile there for, you know, a group of diseases that really require chronic, lifelong treatment. So we'll be moving both of those forward, and I will turn it to Andy first. So maybe I'll take your second one first.

Oh, just one question you mentioned a couple of formulary wins I believe I'm a prepared remarks I was curious so the dynamics on formularies employers are the uhm, preferring one agent over the other the sorry. This is regarding Deborah or is it equal or.

Exactly that's what are there is there a preference for one over the other on the formularies or Trinity College friends.

Sure.

It's interesting when you when you say the word formulary in the space that can have many different connotations right. There's different aspects of formulary choice that appear level, but also certainly at health system levels within community group practices et cetera that will drive.

<unk> chiffon therapy or another.

<unk>, what we've seen is <unk>.

Broad access.

I think both agents frankly, we will be covered by most by most payers that's what we would expect.

Andrew Scott Berens: So it's steps to getting 945 into the clinic. You know, we're just working on the components and final nonclinical talks and other work necessary for the IND. And, of course, we'll submit the IND and be on track to begin that study in the first half of next year. I think there's nothing specific or unusual that's going on there.

And certainly we support that we want patients have access to both therapies.

I think at at practice level.

And given some of the dynamics and and certainly more of a focus on <unk>.

Quality and cost measures that are now becoming very important in oncology.

Pricing strategy that we've taken I think has been incredibly well received and there's clear value. There that may drive preferential utilization of of gap Rado and again the approach around distribution and.

Andrew Scott Berens: Some of the lung cancer experts that we interact with think that as ASCII goes to adjuvant in those patients, when they progress, for their initial metastatic progression, a lot of people will go back now to use a first-generation EGFR inhibitor. And so that gets you actually back to the triple mutant again, just with the drugs in the opposite order. So we think that could be an opportunity for Blue 945 in the study. And maybe then I'll merge those two questions together, sort of at 30,000 feet.

Et cetera that really again allows.

Pharmacies that are integrated into community practices, who want to be able to care for their patients and often are fighting broader healthcare system dynamics that prevent them from being able to do that have been very happy with the person that we've taken so that is another place where we're seeing some <unk>.

Preference being driven.

Thank you at this time I am showing no further questions I would like to turn the call back over to Jeff Albers for closing remarks.

Jeff Albers: Early on, when we were building Blueprint Medicines, we often talked about playing to where the puck will go rather than where it is currently. And I think that really underscores why we're so confident today in our position: if you look at how the year has unfolded, as we get into the back half of this year, you know, on the Osa-Merton piece of moving into earlier lines, the evolution of the treatment paradigm for EGFR-driven lung cancer, the building out of two different programs that will be effective or provide an opportunity regardless of when and how patients are treated in Similarly, following that playbook of Osimertinib moving into the adjuvant setting could impact how we think about future RET development for Pral-Setinib within our Roche collaboration.

Thanks, operator, and thanks again for everyone for taking time with us in their continued support if we print medicines.

Obviously this is a really rewarding quarter to reflect on and.

I'm appreciative to all the employees at blueprint medicines and the focus they've kept during this difficult time and I.

I also been thinking about looking forward in a lotta ways. We feel like we're just getting started wearing a really strong position now we know we have to continue to execute over the remainder of the year and then we continued to be really encouraged by the setup as we look forward and based on the investigational medicine that we continue to work on preclinical.

<unk> the.

The regulatory feed.

Feedback and processes that we're undertaking as well as now adding in the commercial components. So.

Look forward to providing a future update thanks, a lot have a great day.

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

[music].

Jeff Albers: And then, as you think about systemic mastocytosis, we had clearly articulated that as a priority, and we took the time to really understand and characterize avopritinib, and so seeing the activity we have at 200 mg in the advanced form of the disease as well as 25 mg in the non-advanced form of the disease gives us a really strong starting point. And then we made investments in 2-6-3 to round out from a position of strength, and so there will still be patients where there's need, whether it be expanding, as Christy said, in indolent SM or in other mast cell diseases. But if you think about how a portfolio evolves over time, all of that is at play here, and our strong financial position allows us to continue to invest in the opportunities that provide the greatest potential patient benefit. Thank you. Our next question comes from the line of Arlinda Lee from Canaccord. Your line is now open. Hi guys, thanks for taking my question. I have a couple.

Operator: One, on the ASM filing for, I'm curious what's skating for that, and then on 263, I missed when you said you were. Also, can you briefly talk about, and you mentioned it was not brain penetrant, but can you also talk about the other design? Sure. Andy, do you want to take those?

Andrew Scott Berens: So first, the filing on advanced SM and then characteristics of 263. Yeah. So in terms of what's gained for the ISM filing, it's just now getting the documents together. There's actually a fair bit of writing to do and that kind of thing, but we have all the data in hand. And so we're just doing the final, through the final Hearts of the Process to get the filing together. And again, that'll, you know, go in this year too. 263.

[music].

Andrew Scott Berens: So, um, so, in terms of the trial, we're, we're very happy to get that Healthy Volunteer study started in the first half of the year on track, despite COVID-19. It remains on track to provide the key data by the end of this year, which is really, is really dose determining data for what the appropriate dose or dose range would be for patients with ISM in the first ISM study. We haven't specifically been guided as to when that first ISM study will start, but obviously, that's a high priority for us. And, um, Arlinda, as you mentioned, we designed Blue 263 very specifically not to cross the blood-brain barrier. And that's an important distinction from avipritinib. It also has a bit more selectivity on a couple of other fronts.

Andrew Scott Berens: It's, you know, on a few other enzymes where we think they potentially offer potential benefits, but some of that's hyperbole. Thank you. Our next question comes from the line of Michael Schmidt from Guggenheim. Your line is now open. Hey guys, thanks for taking my questions. I just had one on AvaKit.

Operator: Your sales in the third quarter suggest about 100 patients have been treated. Can you confirm that? And I think you mentioned some non-promoted use. Could you maybe quantify that a little bit? How much of that is just more broadly versus potentially in ASM patients already at this point? I'll take that. So, you know, I'm not going to get into details on exactly how many patients we've treated. Obviously, the math there is

Christina Rossi: You've got patients continuing to start. We have, you know, shorter durations when we see late-line, kit-driven GIST patients on therapy. We are seeing quite long durations when you see PDGF for alpha patients. But, you know, overall, we're pleased to continue to see revenue growth in GIST and, you know, very happy to have that option available for patients. In terms of quantifying the exact, you know, mix, as I said before, it's challenging to do that.

Christina Rossi: You know, we can try to make estimates, but we're relying primarily on feedback we may get from prescribers and patients. The coding for these patients is the same, and so we're not in a position to be able to say with certainty.

Christina Rossi: We just know that we continue to see utilization. Clearly, we have a guidelines listing for late-line GIST, and we know that the unmet need in those patients is still very high.

Operator: And then, Christy, with Gavreto now on the market, I realize it's only been a few weeks, but I was just wondering what the initial feedback has been from lung cancer physicians and, you know, the two TKIs now available, and maybe, you know, what the feedback has been around some of the differentiating side effects of those two drugs, specifically the absence of QTC. Sure. Yeah, so, you know, I think the feedback has been, as I said, very, very positive. I think, first of all, the community is thrilled to have effective therapies available for these patients, right, that have not had treatments available to date. I think, you know, we're going to see the utilization of both agents. I think, you know, Gavreto is viewed to be very highly effective. I think certainly safety, as you mentioned, is probably where you will see maybe more difference.

Christina Rossi: And, you know, again, I think the idea of side effects that are sort of in the wheelhouse of prescribing oncologists is something that I think is comforting versus some things that may just require some different management approaches. I mean, QTC is one, hypersensitivity is another, again, that I think we've continued to hear about in the real world. And, you know, it's early days, I think, with both of these agents.

Christina Rossi: And so, I think what we have to remember is that the clinical profile will continue to emerge over time, both from an efficacy and a safety perspective, as you start to get that real-world utilization. And the last piece, I think, that we've been very happy to get feedback on is sort of the non-clinical aspects of the profile that are also very important, right? So, once daily dosing, which, you know, again, oncologists like everybody else. In fact, we had one person say to us, "I'm an oncologist, but I still don't like to get called back for issues." And so, simplicity is important.

Christina Rossi: And the approach that we've taken, which is really, again, prioritized practices and dispensing pharmacies being able to retain control and treatment of their patients has gone very well. Thank you. Our next question comes from the line of David Nirenjeren from Woodbush Securities. Your line is now open. Hey, thanks. That's a new interpretation of the name.

[music].

Operator: Oh, just one question. You mentioned a couple of formulary wins, I believe, in the prepared remarks. I was curious, as to the dynamics of formularies and payers, are they preferring one agent over the other? Sorry, this is regarding Gavreto. Or is it equal, or, Basically, that's it. Is there a preference for one over the other on the formularies, or are they treated equally?

Christina Rossi: Sure. So you know, it's interesting when you say the word formulary in this space. It can have many different connotations, right? There are different aspects of formulary choice at a payer level, but also certainly at health system levels within community group practices, etc., that will drive selection of one therapy over another. You know, with payers, what we've seen is, you know, broad access. I think both agents, frankly, will be covered by most payers.

Christina Rossi: That's what we would expect, and certainly we support that we want patients to have access to both therapies, I think, at a practice level. And, you know, given some of the dynamics and certainly more of a focus on quality and cost measures that are now becoming very important in oncology, the pricing strategy that we've taken, I think, has been incredibly well received, and there's clear value there that may drive preferential utilization of Gavreto.

Christina Rossi: And again, the approach around, you know, distribution and etc., that really, again, allows pharmacies that are integrated into community practices who want to be able to care for their patients and often are fighting broader healthcare system dynamics that prevent them from being able to do that, have been very happy with the approach that we've taken. So that is another place where we're preferencing. Thank you. At this time, I am showing no further questions. I would like to turn the call back over to Jeff Albers for his closing remarks.

Jeff Albers: Thanks, Operator, and thanks again to everyone for taking the time with us and their continued support of Blueprint Medicines. Obviously, this is a really rewarding quarter to reflect on, and I'm appreciative of all the employees at Blueprint Medicines and the focus they've kept during this difficult time. And I also have been thinking about looking ahead. In a lot of ways, we feel like we're just getting started. We're in a really strong position now.

Jeff Albers: We know we have to continue to execute over the remainder of the year, and then we continue to be really encouraged by the setup as we look forward and based on the investigational medicines we continue to work on preclinically, the regulatory feedback and processes that we're undertaking, as well as now adding in the commercial components. So, I look forward to providing future updates. Thanks a lot. Have a great day. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? [inaudible] Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music, ?? ?? ?? ?? ?? ?? ?? Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music, ??? ??? ??? ??? Music Music Music Music Music Music Music Music Music, ?? ?? ?? ?? www.cdc.gov.au www.cdc.gov.au www.cdc.gov.au www.cdc.gov.au www.cdc.gov.au www.cdc.gov.au www.cdc.gov.au www.cdc.gov.au

[music].