Blueprint Medicines - Earnings Call - Q2 2021

Transcript

Speaker 0

Good morning, everyone. My name is Seb, and I will be your conference operator for today. At this time, I would like to welcome everyone to the Blueprint Medicines Second Quarter twenty twenty one Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session.

Thank you. I will now hand the floor to Kristin Hodus of Blueprint Medicines. Please go ahead.

Speaker 1

Thank you, operator. Good morning, everyone, and welcome to Blueprint Medicines second quarter twenty twenty one financial and operating results conference call. This morning, we issued a press release which outlines the topics we plan to discuss today. You can access the press release as well as the slides that we'll be reviewing today by going to the investors section of our website at www.blueprintmedicines.com. Today on our call, Jeff Albers, our chief executive officer, will discuss Blueprint Medicines second quarter twenty twenty one business highlights.

Christie Rossi, our chief commercial officer, will provide a commercial update. Becker Hughes, chief medical officer, will review our recent clinical progress. And Mike Landsittel, our Chief Financial Officer, will review our second quarter twenty twenty one financial results. Before we get started, I would like to remind everyone that statements we make on this conference call will include forward looking statements. Actual events or results could differ materially from those expressed or implied by any forward looking statements as a result of various risks, uncertainties and other factors, including those set forth in the Risk Factors section of our SEC filings.

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

Speaker 2

Thanks, Kristen, and good morning, everyone. Thanks for joining us today to review our second quarter performance. The progress made across our portfolio in the second quarter puts us in the strongest position we've ever been in as a company. In January, we laid out our strategic priorities for 2021, which were: one, to accelerate the global adoption of AYVAKIT and GAVRETO two, to advance the next wave of therapeutic candidates into the clinic and three, to further expand our precision therapy research pipeline. Underlying these three pillars is a single ambition: to build the world's leading precision medicine company and make real the promise of precision therapy to improve the lives of people with cancer and hematologic disorders.

In June, we received U. S. FDA approval of AYVAKIT for the treatment of advanced systemic mastocytosis or SM. This was a significant achievement for BLUEPRINT and the culmination of nearly a decade of hard work from our team in partnership with the medical and patient communities. Systemic mastocytosis is a classic example of a rare disease with a clear genetic driver that has been historically difficult to target.

With AYVAKIT's approval, we're ushering in a new era of care for these patients with advanced SM, offering them the first targeted therapy designed to potently and selectively inhibit D816V mutant KIT, the central driver of their disease. As Christy will review shortly, we're seeing very encouraging early momentum across all aspects of the launch as we work to drive patient identification and access to treatment. It's particularly rewarding to see the momentum and efficiencies being realized as we deliver AYVAKIT and GAVRETO to patients globally, both independently and through our partnerships. In parallel to the launch of avakitin Advance SM, we're making important progress across our clinical stage portfolio, as Becker will discuss later in the call. We now have six programs progressing through registration enabling trials or into proof of concept studies.

Our two product candidates for non advanced SM, two product candidates for treatment resistant EGFR driven non small cell lung cancer, BLU-two twenty two, our CDK2 inhibitor and BLU-eight fifty two, a MAP4K1 inhibitor developed under our cancer immunotherapy collaboration with Roche. What's exciting is that each of these programs could bring important innovation and improved outcomes for a large number of patients with significant medical need. Underpinning the promising scientific, clinical and commercial execution is a very strong financial position, as Mike will discuss. Through our product launches and a purposeful mix of collaborations, we've enabled a diversified revenue stream that will further strengthen BLUEPRINT and allow for meaningful improvement across our business and portfolio as we continue our efforts to deliver transformative benefit to patients. So with that, I'll turn the call over to Kristi to provide an update on our commercial efforts.

Kristi?

Speaker 3

Thank you, Jeff. Good morning, everyone. In the second quarter, we generated total net product revenue of $11,400,000 including $8,500,000 in sales of AYVAKIT and $2,900,000 in sales of GAVRETO. The second quarter marked a significant inflection point for BLUEPRINT, and we are now beginning to realize the enormous potential we see to change the lives of patients living with SM. The approval of AYVAKIT for advanced SM came just a few weeks ago, and we are already off to a strong start executing against our three launch priorities: identifying patients, providing disease and product education and ensuring best in class support.

Immediately upon approval, we've seen a high level of engagement and interest from health care providers and patients. We received our first prescription request request just hours after announcing the approval. And over the past few weeks, we have already seen utilization of AYVAKIT by 40% of our 70 key target centers, which we believe treat about half of all SM patients in The United States. Importantly, we are seeing significant demand from community based physicians, including those who have no previous experience with AYVAKIT in the clinical setting. We've also been encouraged by feedback we've heard from health care providers on the differentiated profile and robust clinical data package supporting the launch.

We are hearing that AYVAKIT will set a new standard in the treatment of advanced SM, and healthcare providers are excited to have this option available for their patients. We were especially pleased to see AYVAKIT added to the NCCN guidelines as a preferred agent for the treatment of advanced SM. Our early data suggests that AYVAKIT is being used broadly across advanced SM patient types, including patients switching from other therapies such as Midostaurin and patients with no indication of a prior advanced SM therapy. These are promising indicators of the current breadth of demand and the potential for market growth over time. As more patients are treated, we will gain more insight into dynamics and the role that AYVAKIT is playing in revolutionizing the treatment paradigm.

We've also been encouraged by early indicators of strong patient access as well as the support we are offering to patients with advanced SM. Payer approval for our initial prescriptions have come fast, and initial payer policies appear to be in line with our label. Leveraging our expertise and existing infrastructure from previous launches, our goal remains to help every patient who is prescribed IVIKATE to start on therapy quickly and have continued access as long as it is clinically indicated. I'm thrilled to see our strong early execution in this area. While ADVANCE SM was a smaller part of our recognized revenue in Q2 because of the timing of the approval, I expect it to be the primary driver of AYVAKIT revenue growth going forward.

We view SM as a potential blockbuster opportunity, and I look forward to continuing to update you on our progress as we advance the launch. In PDGFRalpha GIST, we anticipate more incremental growth with additional launches outside over time. Let me turn now to GAVRETO. We continue to see good progress in growing our share of new patients who are starting on a selective RET inhibitor. Since launch, our share of new patient starts has steadily increased and now exceeds forty percent.

Growing the RET inhibitor market overall remains a key focus as well. We were encouraged to see an uptick in demand following ASCO this year, where we showcased updated data from the ARROW study that included an eighty eight percent overall response rate in the treatment naive setting. Continued multidisciplinary education on the compelling clinical data supporting GAVRETO aids our broader efforts to increase comprehensive and actionable biomarker testing rates at diagnosis. Importantly, we reached a milestone with our partners at Roche and Genentech at the end of Q2. Going forward, in The United States, Genentech will now be booking end user sales of GAVETO and as a result, will also assume responsibility for product distribution.

We are confident that our joint efforts will drive ongoing growth in the number of patients who are identified and treated in The United States, and we expect further revenue growth from ongoing launches outside of The U. S, driven by our partners Roche and SeaStone. Before I turn the call over to Becker, I wanted to come back to the opportunity in front of us to transform the treatment of all patients with SM, which starts with the launch of AYVAKIT and advanced SM and will expand through the ongoing development of AYVAKIT and BLU-two sixty three in non advanced disease. Earlier, I mentioned that we had our first ADVANCED SM prescriptions within a few hours of approval. As it happens, our first request came from a center that had Advanced SM patients identified, and the team there also told us that they had multiple non Advanced patients that they were interested in enrolling in PIONEER.

This demonstrates the power of the leadership position we have built in partnership with the SM community. The patient need across subtypes of SM is acute, and I could not be more excited about the opportunity we have to impact patients with a best in class portfolio of treatments for this debilitating disease. With that, I would now like to turn the call over to Becker to talk more about our clinical portfolio.

Speaker 4

Thank you, Christy, and good morning, everyone. Let's start with the PIONEER trial of AYVAKIT in non advanced disease. As we celebrate AYVAKIT's approval for advanced SM, we're eager to expand our impact to non advanced disease, which comprises the overwhelming majority of SM patients. PIONEER is the first large global registrational study ever conducted in non advanced SM and has required a complex operational effort, especially during this global pandemic. In Part two of the trial, we've activated nearly 40 sites across 12 countries and screened well over 200 patients.

We've also worked carefully with sites to transition patients with consistently evaluable moderate to severe disease into the treatment phase of the study. As the trial's momentum has increased and with AYVAKIT's recent approval for advanced disease, the investigator and patient enthusiasm has reinforced for us the breadth of need in this population. Now, as we begin to plan the wind down of screening and enrollment efforts at clinical sites, we're focused on driving toward top line data, which we're looking forward to reporting in mid-twenty twenty two with potential regulatory filings following thereafter. Importantly, we're also applying the learnings and deep learnings in carrying this trial momentum to BLU-two sixty three, our next generation KIT D816V inhibitor. Recently, we initiated the HARBOR study, which is evaluating BLU-two sixty three in non advanced SM, including in patients with milder disease, with the goal of expanding our reach to an even broader SM population.

As PIONEER winds down, we expect HARBER to ramp up and benefit from our expertise and deep engagement with the global SM community. We look forward to providing updates on the HARVOR trial next year. Shifting to EGFR mutant lung cancer. In the second quarter, we initiated the Phase III trial of BLU-nine forty five, a triple mutant inhibitor. This study includes escalation portion in patients with EGFR mutant non small cell lung cancer who previously received at least one prior EGFR targeted tyrosine kinase inhibitor, followed by expansion in groups of patients with tumors harboring specific mutation profiles.

Later this year, we plan to bring BLU-seven zero one, our double mutant inhibitor, into the clinic as well. For both programs, we'll rapidly evaluate both single agent activity and both agents in combination with each other and other EGFR targeted therapies. In addition, we continue to advance our newest development candidate, BLU-two twenty two, CDK2 inhibitor targeting cyclin E aberrant cancers. This is expected to enter the clinic in the first half of next year. Yesterday, we announced a strategic research collaboration with MD Anderson, well known for their expertise in translational medicine.

The collaboration is designed to enhance the program by identifying novel methods to select tumors likely to be responsive to selective CDK2 inhibitor as both mono and combination therapy. With this robust list of drug candidates advancing toward proof of concept data, all homegrown from our prolific and proven scientific engine, we're excited to keep you updated on our progress in the months ahead. I'd now like to turn it over to Mike to discuss financial updates.

Speaker 5

Thanks, Becker. Earlier this morning, we reported detailed second quarter financial results in our press release. And for today's call, I'll just touch on a few highlights from the quarter. Total revenues for the quarter were $27,300,000 highlighting our growing diversity of global revenue of our global revenue base and positioning us for strong future growth. This included $11,400,000 in net product revenues, as Kristi discussed, and $15,900,000 in collaboration revenue.

Collaboration revenue was primarily driven by commercial supply shipments to our partners, SeaStone and Roche, to support our broadening geographic approvals. Collaboration revenue also included royalty revenue for sales of AYVAKIT and GAVRETO by SeaStone in Greater China. Our total costs and operating expenses in the second quarter increased moderately compared to the first quarter of twenty twenty one. We saw an increase in cost of sales related to drug product shipments to our partners. In addition, SG and A expenses increased, driven by our commercial infrastructure expansion.

As we increase investment in our promising early stage programs over the next few quarters and expand our commercial efforts with the launch of AYVAKIT in Advanced SM, we expect to see continued increases in future quarter over quarter R and D and SG and A operating expenses. We ended the second quarter with nearly $1,400,000,000 in cash on hand, ensuring that we have sufficient resources to invest in our growing pipeline of wholly owned drug candidates. Overall, with the recent approval of AYVAKIT and Advanced SM, strong collaboration execution and a deepening pipeline, we have a solid foundation from which to drive future revenue growth. Anchored by sales of AYVAKIT and the potential for several meaningful collaboration milestones, we anticipate that our second half revenue will more than double over the first half, which positions us to meet our 2021 revenue guidance of $150,000,000 for the full year. This second half financial momentum will then set us up for a series of important clinical catalysts in 2022 as we continue to build the world's leading precision medicine company.

So with that, I'd now like to turn the call over to the operator for questions. Operator?

Speaker 0

Thank Our first question comes from the line of Salveen Richter from Goldman Sachs. Please go ahead.

Speaker 1

Good morning. Congratulations on the launch. What are your thoughts here on the trajectory of the ADVANCE SM launch? Is there an initial bolus given the demand you mentioned? And then at the 70 hematological centers, what is the overlap there with the non advanced SM total opportunity?

And then separately, if you could just comment on the accounting mechanics for next quarter when Roche takes over booking GIVRATO sales. Thank you.

Speaker 3

Great. I can start. This is Kristie, and then I'll let Mike chime in on the accounting. So we've been really excited to see the initial feedback and interest we're seeing around the ADVANCE SM launch. I think what the thing that is particularly notable has been that, yes, we're seeing interest certainly among those 70 key centers, but also seeing a lot of organic interest in the community setting, which I think is a really good indicator of the potential for future growth.

It's early, obviously, so understanding exactly the dynamics around bolus versus not, etcetera, are I think we'll have more clarity on that as we emerge over time. But I'm excited about the potential for ongoing growth here given that we are seeing broad interest. And in my experience, the breadth of interest and breadth of prescribing is often really a key driver of ongoing demand growth over time. We're also seeing utilization, you know, amongst patients that look like they've been previously diagnosed and treated, but also some uptake amongst patients with no indicators at least of another advanced system therapy in their history, which suggests that we're seeing prevalent patients, but potentially some newly diagnosed patients coming on to therapy over time. We look forward to seeing how that continues to emerge as we go forward from here.

The overlap amongst the centers, I mean, the 70 centers are critical for treatment of advanced system patients. Certainly, we get into the non advanced setting, we will be broadening out into the allergy setting to a greater extent. But those centers are going to be critical for both indications. You know, as I've said before, SM is very much one disease with a common driver, a common mutation. And hematology can play a critical role in the diagnosis of non advanced patients as well.

So certainly getting established with advanced disease in these centers is going to be a critical part of setting us up for the non advanced indication that we expect to receive over time. Maybe I'll let Mike comment on the accounting.

Speaker 5

Yes. So for the accounting, just as a reminder, in Q2, we recognized end user sales of GAVRETO's product revenue and then there was a true up to the profit sharing for The U. S. That flowed through SG and A. Starting in Q3, as Christy mentioned, Roche will be booking end user sales under the collaboration.

And what we'll do is we'll record our share of the collaboration profit or loss as one line item on our income statement. It will either show up as in the revenue section if the collaboration is profitable or in the expenses if the collaboration is in a loss position. We're also intending to continue to provide transparency on our global product sales at the end user level going forward.

Speaker 6

Thank you.

Speaker 0

Our next question comes from the line of Mark Fram from Cowen. Please go ahead.

Speaker 7

Hi, thanks for taking my questions. One on to start with AYVAKIT. Just was there any kind of stocking impact from the launch of the new dose strength in the quarter or is that kind of all demand?

Speaker 3

Yes. So very minimal. We the ADVANCE system dose, as you know, starting dose is two hundred and we already had three hundred, two hundred, one hundred milligram dose in the channel. So there's minimal twenty five and fifty in the channel, obviously, to be available if patients need it as part of their ongoing treatment, but we haven't seen a lot of utilization of those strengths. That wasn't a huge driver of what we saw in Q2.

Speaker 7

Okay. Thanks. That's helpful. And then maybe looking to the pipeline, just for RET, you were able to kind of report initial data about a year after initiating the trial. You think that's still a reasonable expectation for nine forty five monotherapy data?

Or do you think we should maybe expect you to wait a little bit longer for maybe combo data to kind of mature before you start reporting data out of the EGFR program?

Speaker 2

So as we do every year, the beginning of twenty twenty two, we'll lay out guidance in terms of sharing data and expectations, more specifically around timing. As Becker highlighted, we think we're really well positioned now with this wave of new programs having either recently entered a clinic or soon to enter the clinic. And so to me, the company fundamentally feels different now than it did, say, a year ago. Getting the breadth of development candidates that we got had pulled through and the quality of those candidates late last year, early this year, This advanced SM approval in the early indications, as Christy has highlighted, that we're seeing in terms of uptake and giving us a better sense of the magnitude of that opportunity. Thought Mike said it well with the we'll ride the launch into next year, but then we're looking to sort of weigh out a series of clinical updates across these programs.

So I don't think we're at the point where we'll specifically guide to any one of those. But the breadth of those launches or of those clinical trials is what for me is really exciting.

Speaker 8

Okay. Thank you.

Speaker 0

Our next question is from Dane Leone from Raymond James. Please go ahead.

Speaker 4

Hi.

Speaker 8

Congratulations on all the updates and launch in ASM. Just one question for me following up on the EGFR question Mark asked. Could you just maybe elaborate a

Speaker 9

little bit more in terms of

Speaker 8

the clinical strategy here? What you need to see out of the Phase I to then move into combination studies, which I think a lot of us think is the end game here? And again, you know, as much as I can push you to give some idea of timelines on that effort, it would be appreciated. Thank you.

Speaker 4

Yeah. First, Becca, I'll take that. With respect to the overall strategy, you hit the nail on the head. The combinations are the key to providing the most benefit with these compounds to patients. We are going to explore, as I said, single agent activity of both, and we will start combinations before we finish exploring single agent activity.

Combinations both with BLU-nine forty five and seven zero one together and then with each of those with other third generation tyrosine kinase inhibitors for EGFR mutant lung cancer. So I think what you'll see is a number of different experiments going on simultaneously in different patient populations. We're also learning more about the mutation profile of the patients, how they present either alone or in combination, that is the mutation. And so we'll refine our strategy as we understand the biology more and our ability to combine these compounds during the trials. With respect to timing, as we've previously reported, we started the nine forty five dose escalation recently and we expect to enter BLU-seven zero one by the end of this year.

And the extent to which the as Jeff said, rather than releasing data piecemeal, we have so much data coming out next year that there will be periodic updates. But I hesitate to speculate or guide about any specific thing individually.

Speaker 2

This is Jeff. Maybe just combining the comments from Mark and Dane and comparing them to RET. All of us, when you're looking to think about forward looking statements are speculating on when we'll have data, how quickly you'll move through the dose escalation to get to an effective dose. As Becker just highlighted, understanding the biology and where there's likely to be the greatest benefit. Early signs are encouraging on this end.

The fact that with the first couple of sites activated, we're already seeing patients lined up with some of those sites, patients willing to travel. So the first marker is, are the patients there? Can you identify them? And we're moving through that nicely. And then for 07/2001, as Becker said, we're looking to move into the clinic by the end of this year.

The enthusiasm from investigators and potential investigators there to get that up and running is just one more of those markets. And tied together is why I think we're collectively so optimistic about those two programs together.

Speaker 0

The next question comes from Rene Benjamin from JMP Securities. Congratulations

Speaker 9

as well. This is one question on Gabretto regarding, can you just give us a status update of what's happening with the application there? And kind of importantly, what's the rest of world filing strategy for 2021 in terms of other geographies to look at? And just as a follow-up, I know, Christy, you talked about patient identification. And I thought in the past we we talked about digital PCR, NGS, and then, you know, your own sort of test.

I think CStone is coming up with their own test as well. Can you just give us an update as to what's happening with your own testing product?

Speaker 2

Becker, you take the first part of that with Roche's efforts outside The U. S. And then Christy talking a little bit about patient identification.

Speaker 4

Yeah. So as you'll remember, Govetta outside The US is owned by Roche, and they're leading the filing. We've guided to having filed that, and that's well under review right now. With respect to the strategy in other regions, they have a number

Speaker 2

of other regions lined up

Speaker 4

to shortly follow the European evaluation of the dossier.

Speaker 3

And then I can pick up the thread on patient identification and ready. I think you might have been asking around advanced SM, but let me know if I'm picking in a different direction than what you were asking.

Speaker 2

I thought it was GAVRETO.

Speaker 3

Are you asking about GAVRETO? Or

Speaker 9

No. No. No. Advanced. Yeah.

Switch. Switched on you.

Speaker 3

Yeah. Okay. So so yeah. So, you know, the the most important one of the most important patient ID levers across, you know, advanced and non advanced disease, frankly, is testing for KITV816V. In advanced disease, you know, where I would say that becomes most important is in SMAHN, where you're really trying to, you know, identify the SM component.

But clearly, most advanced patients are diagnosed with something. In non advanced disease, you know, driving accessibility to, you know, highly sensitive blood based testing is really critical. And there, I think we've made a lot of progress. So the goal is it's not so much our own assay. What we're trying to do is really enable capability amongst labs broadly in markets that we're going to be commercializing in to have that available so that physicians and patients can access testing easily.

Over the last six to nine months, I would say there's been good progress in terms of the number of commercially available highly sensitive tests in The United States. And then we are working as well with a few large lab partners to further develop that capability and make sure that it's accessible and available to patients. And I'm expecting ongoing progress against that even as we go through the remainder of this year. So I would say, generally speaking, we're in a much better spot even now than we were twelve months ago and would expect to see ongoing developments there from here.

Speaker 9

Great. Thanks for taking the questions and congrats.

Speaker 0

The next question is from Peter Lawson at Barclays. Please go ahead.

Speaker 10

Hi. Thanks for taking the questions and thanks for the update. Just on the preclinical update for September and 07/2001, just, if you could kind of perhaps walk through what we should expect to see and the potential venue for that in the second half?

Speaker 4

So, I assume what you're talking about is the, combination of 07/2001 and September in preclinical models. We haven't decided on a specific venue, but we are working on generating that data. Identifying the proper models and animal models for these complex mutation profiles is is where we've gone. We are partnering in. We have internal models.

So, you should just look forward later this year for a couple of different looks at that.

Speaker 10

Gotcha. Thank you so much.

Speaker 0

The next question is from David Lebowitz from Morgan Stanley. Please go ahead.

Speaker 11

Thank you very much for taking my question. In the early run of the IVIGAT launch in

Speaker 9

ASM, there's certainly been sounds like there's been a lot

Speaker 11

of inquiries about patients with ISM that you end up referring to the PIONEER trial. Are any of the physicians actually trying to take these ISM patients and, put them on drug now at this point or certainly inquiring as to ways they might be able to get patients on drug? As as you have elaborated on in the past, it is overall considered one disease.

Speaker 3

Sure. So, you know, the data that we have right now suggests that the patients are being prescribed AYVAKIT or against the same patients as diagnosed by their health care provider. Certainly, as, you know, I mentioned anecdotally, and that's not the only site, I will say, where we have seen, you know, both advanced and non advanced patients being treated and interest in PIONEER, also potentially interest in HARBOR down the road. So I think it just highlights, you know, again, the synergy that we're seeing in our engagement with this community. You're right.

SM is absolutely one disease. Subtyping is complicated. So I think we may see over time, utilization. But I think what we've heard is that, you know, early on, we expect utilization to be in advanced with some patients, and we have no data to suggest anything differently, from what we're seeing.

Speaker 11

Thanks for taking my question.

Speaker 0

The next question is from Benjamin Pollock from Baird. Please go ahead.

Speaker 11

Hello. This is Benjamin on for Joel Beatty. Just a few questions for us, mainly on AYVAKIT. I'm just wondering if there's a sense of the number of repeat scripts potentially and the number of new prescribers. And then I was wondering if you also could comment more on the demand from community physicians.

Is it more demand? Or is there interest? Or is there maybe specific examples you might be able to point to to kind of provide a little bit of clarity on that? Thank you so much.

Speaker 3

Sure. So, you know, we are, I guess, this point, like five weeks in or so, right? So we are most I mean, the majority of this band that I've been commenting on is new patients, where we would certainly expect with an indication like this and given, you know, the incredible duration of therapy that we see with AYVAKIT, which is, you know, I think one of the ways that it's really transforming care for these patients, we would expect long duration over time. And so certainly seeing that revenue build as we see refills as well as, new patients coming in. But based on where we are in the calendar, we've barely even gotten to the point where you would see your first refill starting to come through.

In terms of the community, again, it's early days, but I think the market for us was that we saw interest really almost immediately coming from a broad number of stakeholders. And I would say a significant percent of our utilization already is coming from the community, which I think is a really good indicator. And I will likely be sharing more about that as we progress through the launch and continue to build that data. But, you know, this is a rare disease. And to me, what this suggests is, you know, we are often the launch of a transformational therapy catalyzes, you know, changes in the treatment paradigm as well.

And so, you know, I would not be surprised to see that here and to see EVOCAT really enabling broader care of advanced system patients both in centers as well as in community practices.

Speaker 11

Great. Thank you. And then if I could squeeze more one more quick follow-up. On the underutilization of the twenty five and fifty milligram dose, any thoughts there? Is that kind of surprising or does that speak more to like your comments earlier about that early in the launch?

Speaker 3

Yes, absolutely. So it's certainly not being underutilized in terms of what we would expect, right? I mean, the starting dose for Advancius in patients is two hundred milligrams. We know we expect the majority of patients to be treated at two hundred milligrams, maybe one hundred milligrams, twenty seven fifty or there, certainly to enable appropriate dose adjustments and care on an individualized basis based on, you know, a patient and a provider. But I wouldn't expect to see broad use of those dose strengths in advance of that.

So we're at there's nothing that I've seen so far that is different than what we would have expected.

Speaker 11

Got it. Thank you so much.

Speaker 0

The next question is from Michael Schmidt at Guggenheim Partners. Please go ahead.

Speaker 4

Hey, guys. Thanks for taking my question, and congrats on on the progress as well. I had a couple on your CDK two inhibitor program. Just, help us understand how your, collaboration with MD Anderson actually accelerates development as you mentioned? And then secondly, just mechanistically, how should we think about BLU-two 22 activity perhaps in EPNE amplified or Cyclin E, you know, amplified cancers relative to other potential mechanisms that include, for example, v one inhibition or PKY PKNY p one inhibition in the same setting?

Thanks so much. Thanks, Michael. Let me start with MD Anderson. So I think as everyone knows, Anderson is really a powerhouse with respect to translational research. Just identifying a selective CDK2 inhibitor is really just the beginning of the journey.

You've seen in CDK4six development that identifying signals often requires combinations, sophisticated preclinical models to understand how and when to use these drugs together. And in this case, we're looking at foursix inhibitors combined with two inhibitors and a number of other mechanisms, including those that you just mentioned, where novel combinations may really uncover amazing therapeutic advantage in different patient populations. The other place that they have quite an angle on the science is that there are so many patients that go through MD Anderson. So their ability to query tumor banks and really deeply understand the biology of the indications such as ovarian and breast cancer and endometrial and beyond that we have identified and then pulling additional tumors off the shelf to understand where there's a vulnerability that might allow us to either use BLU-two twenty two or a combination that either we or they identify is really unprecedented when you look at the breadth of the tumor banks they have and the investigators that are involved. So we expect, to enhance our understanding of activity where we expect it.

And what I'm really excited about is what we don't expect. This is what happened with Pfizer and CDK foursix where UCLA identified a signal that really transformed breast cancer. So this collaboration is one of the ones that I'm most excited about in my entire career. With respect to the other modalities, it's really too soon to speculate about how the relative activity will compare. We're looking at cyclin amplified cancers, expecting that a subset of these malignancies will be so dependent on the CDK2 pathway that we can see some apoptosis when we inhibit CDK2.

The extent to which that's achievable through these other mechanisms, we're going to have to see. But as I said, as we go into novel parts of this tumor's biology, understanding how to combine, novel compounds, and the more standard of care compounds is going to be something that we're really focused on. Great. Thank you.

Speaker 0

The next question is from Andrew Berens from SVB Leerink. Please go ahead.

Speaker 12

Hi. Thanks, guys. A couple of questions for me on RET and then one I was wondering if you give us some color on the RET market. If you guys are getting forty five percent of new patient starts, and I think previously, you said it was around twenty five percent in Q1, but we haven't seen that translated to the P and L yet.

Is that because of sampling in the new patients? Or is it just not as many new patients as we had anticipated? And then what percentage of diagnosed patients are actually being treated with any RET inhibitor? And are you seeing any frontline usage or is usage predominantly after Retevmo? And then just a question on the ASM launch.

Should we expect to see any change in the gross genetic adjustments now that you're expanding into a larger opportunity?

Speaker 3

Great. Those are all for me. So I can start with Rhett. And actually the questions that you asked are all related. So the way that we think about this market is new patient starts being sort of the first indicator, total patient share then following over time and total patient share as total share approaches new share more quickly, obviously the faster the market grows.

And so we know that Lilly had a bit of a time advantage on us in terms of being the only game in town for six months prior to having both indications available. And so as we've gained new patient share, we're seeing our total patient share grow, but it will take time for our total share to catch up to where we see those new starts coming. So it's essentially thinking about like NRx versus TRx and it's an indicator of revenue growth. And I think we've seen that. I mean, we're continuing to see really robust revenue growth relative to what we've seen from certainly Retevro over the last period of time.

I think we would like to see the market growing more and growing faster to your point. And I think that's really where we're spending a lot of time focusing with Genentech. Our best estimate right now is that it's maybe twenty percent of maybe a little bit more than that of potential RET patients are being diagnosed and then treated with a selective RET inhibitor. And so there's certainly a lot of opportunity we think to continue to really grow patient ID and that the rebound post COVID is happening in terms of testing, etcetera. So we're excited to see that pull through and we're seeing use across lines of therapy right now, but certainly there's opportunity to get to patients earlier upon diagnosis.

And so that's something that, again, we're focused on. From a post to net perspective, I wouldn't expect dramatic changes from where we were with AYVAKIT. Certainly the strategy that we've been using to distribute the product in United States is consistent and our broad access strategy is consistent there. So would not expect dramatic changes with Advanced Systems.

Speaker 12

Okay. Thanks, Chris. We appreciate it.

Speaker 0

Our next question comes from Arlinda Lee at Canaccord. Please go ahead.

Speaker 6

Great. Thanks for taking my question. I was interested in the overlap of in ISM versus ASM. You mentioned, how much you've been able to get into the key ASM centers. I'm I'm wondering how much overlap do you think there is with, the PIONEER and the harbor ISM populations?

And then if you can maybe talk a little bit about your GC's education efforts. Have you been, is there any inbounds on ISM? And if you can maybe discuss if you've been seeing increases in D816V testing. Thank you.

Speaker 3

Sure. So as I said earlier, the 70 key centers are certainly where we see we think a lot of advanced SM patients being treated, about half in The United States. They also play a key role for non advanced patients. And I think that, again, as I shared, we're seeing that in real time as we're out engaging with sites where we're seeing advances in patients being identified, but then also sites flagging non advanced patients who are interested in treatment. Certainly, goal at this point is to facilitate enrollment in clinical studies for those patients, whether that be PIONEER or eventually HARBOR.

So we're going to be following up on that interest. And then as we get into the ISM market more generally, allergy, as I said, becomes a broader a more important call point. But I think these 70 centers still will help really you know, they play a role in diagnosis certainly of many patients and I think will be a good sort of foothold for us as we broaden on into the non advanced market. Great. And then is there a way

Speaker 6

for you guys to track the d eight sixteen v testing that's kind of you mentioned that that was a bottleneck or one of the main levers for patient identification.

Speaker 3

Yeah. So this is something we will be looking at over time. I mean, the difference, you know, I think a subtle difference here, if I even compare to, say, GABRITO, right, where we're, you know, the the I think the goal there is to get patients who are being diagnosed with lung cancer appropriately tested for a mutation. Here, you know, our label is obviously not specific to a mutation, but we really see the testing as being kind of the key to facilitating increased diagnosis, particularly for non advanced patients. So it's obviously early.

We're just in the market commercially. So I think something we'll certainly have a sense of over time. And the way I think we'll see that play out is growth in the number of non advanced patients that we can really identify and see. And so that's a place that we will continue to focus in terms of disease education, market development, etcetera, you know, between now and when we have a updated approval there.

Speaker 6

Great. Thank you very much.

Speaker 0

There are no further questions at this time. So I'll hand the call back to Mr. Albers.

Speaker 2

Thanks, operator, and thank you all for taking time to join us today and for your continued support of Blueprint Medicines. And look forward to updating you again soon. Have a great day. Bye bye. This

Speaker 0

concludes today's conference call. Thank you all for joining. You may now disconnect.