Q1 2023 Blueprint Medicines Corp Earnings Call

Speaker 2: Good morning. My name is Kelly and I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines First Quarter 2023 Financial Results Conference Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a Q&A session.

Speaker 2: If you'd like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you'd like to withdraw your question, press star followed by the number two. Please plan to limit yourself to one question. Thank you. Jenna Cohen, please begin.

Speaker 3: Thank you and good morning, everyone. Welcome to the Blueprint Medicines first quarter 2023 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 by going to the investor section of our website at www.blueprintmedicines.com.

Speaker 3: for Q&A.

Speaker 3: Before we begin, I'd like to remind you that some of the statements made during the call today are forward-looking statements and are subject to a number of risks and uncertainties that may cause our actual results to differ materially, including those described in our reports filed with the SEC. I'll now hand the call over to Kate.

Speaker 4: Thanks, Jenna, and good morning, everyone.

Speaker 4: Last year, we introduced our 2027 Blueprint, a five-year growth strategy to achieve what we call precision at scale.

Speaker 4: What lies at the heart of that vision is our ability to scale our business operations as we execute on commercial launches, advance our clinical programs, and bring even more innovative compounds into the clinic.

Speaker 4: Our progress in the first quarter of 2023 has certainly shown that we are driving performance and are poised to deliver tremendous value in the years ahead.

Speaker 4: First, we delivered strong commercial performance in Q1.

Speaker 4: We achieved $39.1 million in AvaKit net product revenue for the quarter.

Speaker 4: driven by growth and demand, as well as by strong execution that resulted in favorable dynamics in the proportion of patients on commercial drugs.

Speaker 4: In a moment, Selena will discuss in more detail our continued success in driving ABICATE UPDAKING ADVANTS TESSA.

Speaker 4: Second, we continue to advance our pipeline.

Speaker 4: We are resuming the VELA trial of Blue 222 after working with the FDA to expeditiously resolve a partial clinical hold within weeks.

Speaker 4: Our team's fast progress and coordination with the FDA emphasize how well we collaborate with regulatory agencies in the face of an ever-evolving regulatory landscape.

Speaker 4: And the urgency with which we are working to bring our investigational medicines to patients in need.

Speaker 4: Third, we advance toward key data and suction points for our best-in-class, innovative, investigational medicines.

Speaker 4: We announced that next month at ASCO, we will present dose escalation data across three of our development programs.

Speaker 4: Better will share more about what you can expect at ASCO later on the call.

Speaker 4: Blueprint is distinguished by having a breadth of new product opportunities across our pipeline. And at the same time, we are heading into a major commercial launch with the expansion of our AVICT label.

Speaker 4: We are now a couple weeks out from our PDUFA date for AVICIT in Indolin SM.

Speaker 4: Our field teams are in the market delivering on pre-launch activities and are ready to support healthcare providers and patients upon approval.

Speaker 4: This approval will further solidify Blueprint's leadership in asset.

Speaker 4: As a cornerstone of our SM franchise, Avakit establishes the bar as both the first Invest in Class Therapy for ISM.

Speaker 4: enabling our team to accelerate the realization of what we are confident will be a greater than $1.5 billion market opportunity.

Speaker 4: Now let me turn it over to Felina to discuss our commercial progress with Avakit and the confidence we have in our go-to-market execution. Thanks, Kate. Good morning, everyone.

Speaker 5: We had a strong first quarter generating Avakit net product revenue of $39.1 million.

Speaker 5: including $34.9 million in the U.S.

Speaker 5: Let's look at the key sources of revenue growth in more detail.

Speaker 5: Half of this growth was due to greater demand and strength across several fundamentals in our AvaKit-based business.

Speaker 5: We grew the number of patients on therapy, exiting the quarter with approximately 520 patients on Avakit in the US.

Speaker 5: We added over 70 new accounts, increasing the breadth of prescribing to nearly 460 accounts with avicate experience.

Speaker 5: And we continue to capture more than 75% of new patient starts and switches.

Speaker 5: The remaining half of this growth we saw this quarter was driven by a reduction in the percent of patients on free drug, as some patients were instead able to receive avicate commercially.

Speaker 5: we expect this benefit to be temporary and the proportion of patients on free drug to return to more typical levels by the end of Q2. We've also completed the hiring and training of our expanded field team members who have been activated and engaging customers since the end of the quarter.

Speaker 5: With the full force of our highly experienced team in place, we expect to drive continued growth in Advanced SM, and we are ready for ISM.

Speaker 5: The year is off to a strong start, giving us great momentum as we head into the ISM launch. We have never been so ready to unlock the opportunity and deliver for many more patients living with SM. Let's look to that next.

Speaker 5: We are just 18 days from our Padoopa Day in IFM and the energy at Blueprint Medicines is U-loop- U-led- ?????ory.

Speaker 5: Our team is ready, the market is ready, and patients are waiting for Avakit.

Speaker 5: We have shared previously the three pillars of our launch strategy.

Speaker 5: healthcare provider engagement, patient activation, and patient access.

Speaker 5: We have consolidated our ISM launch preparations across each of these three areas.

Speaker 5: First, provider engagement.

Speaker 5: Among hemox and allergist immunologists managing patients with ISM, we have grown unated awareness of AVAKIT to approximately 40% or double what you would expect from industry benchmarks. Our field teams have profiled and built relationships with hundreds of high-volume healthcare providers to identify patients in need who are most likely to initiate AVAKIT.

Speaker 5: Second, patient activation.

Speaker 5: It's something our unbranded disease awareness campaign is drawing thousands of people who are signed up to receive more information about SM and AvAKit upon approval.

Speaker 5: And third, access. Our patient support program, Your Blueprint, continues to secure industry-leading times to fill. And the 25-meg dosage strength is already in the channel with broad payer coverage. These three strategic pillars also frame the performance metrics that we'll focus on.

Speaker 5: to frame our launch progress post-approval. For provider engagement and patient activation, our goal is to drive to a decision to treat with AVICAT.

Speaker 5: And to measure our progress, we'll look at prescriber breaths, particularly in allergist immunologists.

Speaker 5: as well as growth in the number of patients in therapy.

Speaker 5: In a chronic disease like ISM, growth in patients on therapy is an important lead indicator of continued revenue growth.

Speaker 5: We'll also be looking to maintain strong patient access for avocate and will track pay your coverage relative to label through the ISM launch.

As I shared with our team at our National Field Meeting last month, the FM story is a blueprint story. We are the pioneers. The opportunity is there and we're ready to deliver for patients.

We have the right medicine, the right team, and we are ready to launch.

And with that, I'll hand it over to Becker, who will share progress across our burdening portfolio as we prepare for ASCO. Thanks, Volina. Good morning, everyone.

far and other.

We operate on the premise that if the preclinical profiles of our compounds are born out in the clinic

Multiple blueprint medicines could become future cornstones of treatment.

We continue to make progress towards that goal, and last week we announced the acceptance of data presentations at ASCO that will provide an update on dose escalation as we work towards defining recommended doses across three of our phase one, two programs.

First, we have our initial clinical data for BLU222, our selective CDK2 inhibitor focused on advancing treatment of breast cancer and other CDK2 vulnerable cancers.

The data at ASCO will demonstrate evidence of monotherapy safety and pathway modulation.

The safety profile is particularly important here, as we anticipate that the maximum benefit of Blue 222 will be in combination with other agents such as CDK46 inhibitors like ribocycline.

Following ASCO, we will continue enrollment in Mono Therapy cohorts and in parallel, continue dose escalation of the combination of ribosype glybine breast cancer patients. Second, we have our initial clinical data disclosure for Blue 451.

in EGFR exon 20 mutant non-small cell lung cancer. These data will show safety in early clinical activity, including evidence of CNS activity.

that reinforce best-in-class potential for BLE451.

We're continuing to work through dose escalation cohorts to optimize a dose and a regimen, and at ASCO we'll show progress to date.

Third, we will present updated dose escalation data on Blue 945, both as monotherapy and in combination with awesome magnet in a heavily pre-treated EGFR mutant patient population.

A key focus of this presentation will be the safety and tolerability of blue 945 in combination with Austin Mertonib. This tolerability is remarkable given the failure of previous EGFR-targeted combinations.

with other EGFR inhibitors and awesome magnet due to additive wild type EGFR toxicity.

We are on track for our other important pipeline milestones as well, including nomination of a development candidate targeting wild-type kit for chronic urticaria in the middle of this year.

We look forward to sharing more data next month as we reach these milestones and make progress towards our 2027 blueprint.

With that, I'll turn the call over to Mike to review our financial updates.

Thanks, Becker. Earlier this morning, we reported detailed financial results in our press release, and for a second I'll touch on a few highlights from the quarter. In the first quarter, total revenues were $63.3 million, including $39.1 million in net product revenues from sales of advocate.

and $24.2 million in collaboration and license revenues.

As Feline noted, we saw continued growth in advocate demand that helped drive quarter on quarter revenue growth, as well as one time free goods' favorability that we expect to unwind in Q2.

We are pleased with our progress early this year and are now updating our advocate net product revenue guidance for 2023 to reflect the patient-mixed favorability that we observed in the first quarter.

We now anticipate approximately $135 to $145 million for our currently approved indications of advanced S.M. and GIST.

Based on our pedophadate, Q1 is our last full quarter of revenue prior to our anticipated ISM launch.

As we have noted, we do not plan to issue guidance including ISM this year, as it will be too early in the launch to do so.

We expect to see continued growth in advanced SM through this year driven by patient demand. Our anticipated label expansion into ISM will be the main driver of evicate growth in the second half of the year.

Turning now to expenses are total costs in operating expenses where $187.5 million for the first quarter.

Financial discipline remains a priority for Blueprint, and we saw that play out as we showed quarter-over-quarter operating expenses decline for the third consecutive quarter.

Similar to our expense guidance from last quarter, we expect a slight increase in operating expenses in the first half of the year related to launch preparations and clinical pipeline investments.

and then expect a quarter on quarter opex to be relatively flat for the remainder of the year.

In February , we announced that we are in the process of regaining development and commercialization rights for Guevretto from Roche.

We do not anticipate any incremental op-x impact related in 2023 related to this transition.

We have initiated a process to repartner Gevredo as we believe that this is the best model to drive value going forward as we prioritize our focus on SM.

We are in a unique position in that avocate is a breakthrough medicine that has been significantly de-risked, and blueprint medicines has a clean growth story as we continue to generate commercial revenue and make progress on multiple assets across our clinical pipeline.

We remain in an exceptionally strong financial position with nearly a billion dollars in cash and a planned reduction in our annual operating cash burn, a trend that we expect will continue as we grow revenues and remain disciplined around operating expenses. This continued financial strength will help fuel our 2027 Blueprint.

to achieve precision at scale and create transformative value for patients and shareholders. With that, I'll now turn the call over to the Operator for Questions.

Thank you. At this time, I would like to remind everyone in order to ask a question, press start, then the number one on your cell phone keypad. Thank you. The first question comes from Yang of Jeffries. Please go ahead.

And that's the same. Could you talk about what really what?

Types of patients in advance, the same population actually drove increase uptake and based on why you so quarter of a quarter. Do you think a third quarter last year is kind of a normally kind of seasonality that you might expect?

So thank you, Yun. So I think what you're asking is, we lost the first part of your question, but I believe what you're asking is what was the mix of kind of the base growth in terms of advanced SM patients and then just the dynamic quarter over quarter. And, you know, I think we've, you know, what we've mentioned before is that, you know, advanced SM is very much a rare disease, and we're going to see lumpiness quarter over quarter. It's really kind of what we see over the course of a year that's going to be important there. And, you know, where.

happy to see the dynamics that happened here in Q1 and to build a radar guidance to 135 to 145. But, did you want to talk about the mix in the against SM growth? Yeah, thanks you. So, starting with the mix, we were really pleased to see growth across many subtypes of advanced SM, especially in the subset of patients who have SM-HN, which is the most common subtype.

where we saw a 15% growth in the market share of AvaKit into patients with SM-AHN. To your question about quarter-over-quarter growth, again, I'd say we were extremely encouraged to see 30% growth in Q1 coming out of Q4. As we've talked about, growth in advanced SM is something that we continue to see, albeit at a more measured pace than in the earlier stages of the year.

label from the FDA? I don't know if you want to make a comment as we get so close to the FDA action date, but is that still what you are expecting, broader label for ISM?

So, hey, you and this is Kate. I don't think we've talked really about what we expect from a label perspective on ISM. And as you said, you know, just close the action date. We don't really, you know, talk about the kind of the discussions we're having with the regulatory agencies. Things are on track. We're having a good collaborative discussion. And you know...

plan to limit yourself to one question. Thank you.

This question comes from Salfine Richard of Goldman Sachs. Please go ahead.

Thank you for taking our question. Just one on the guidance. Are there any other underlying assumptions outside of patient mix that's driving the raise? And then just quickly on the ISM launch, could you just walk us through how you're planning to target the physicians that have the patients that are adequately controlled?

composition of two different dynamics. One is the increase in the base business, which Felina mentioned in her prepared remarks. And the other was a shift in the free goods, the number of patients on free goods, which is a temporary shift. The team did a great job to find a way for the patients who would have traditionally been on free goods in Q1 to get into paid therapy.

how we thought about our previous guidance. We know you're going to have to buy us some. Yeah, so I think I heard your second question is really around how are we targeting providers who have patients in need and what are we doing to activate that urgency to treat and sort of move from symptom directed polypharmacy alone to treatment with AVA kit.

And so really a key focus of our strategy is to target the highest volume AIs and heat mocks. The top 350 is we've talked about our treating approximately 1,500 already diagnosed moderate to severe ISM patients, who today are actively engaging with the healthcare system seeing their provider on average a couple of times a year.

In addition to that, we have a substantial armamentarium of tools, right? So every territory is not created equal. And so where there are those high-volume centers, our ABMs are targeting them. They also have extremely powerful data capabilities, as we've talked about, in terms of patient journeys that are now

kind of had to drive that switching. I might reframe that actually as sort of activating for the urgency to treat with Avokit. And again, I think that's really a combination of conveying the burden of disease with providers, and there's substantial literature on that front.

Secondly, really engaging with patients and caregivers to activate them and let them know when a new treatment option becomes available.

engaging with patients and caregivers to activate them and let them know when a new treatment option becomes available.

Thank you. Our next question comes from Ren Benjamin of GMP Securities. Please go ahead. Can you talk just maybe quantify a little bit of the provider engagement stats that you mentioned. And you know, you talked about growing.

unaided awareness growing to 40%. Is that 40% of the top 350? I mean, what's the denominator that we should be thinking about? And I guess ultimately, as you get closer to launch, is this something that can go even higher to 60% to 80%? Or do you think this is kind of plateauing here?

And just as a follow-up, can you just give us an update as to how peer discussions are progressing? Thank you. Thanks for that question, Ron. And then I, you know.

We are really pleased with where we sit today and the receptivity of both the data coming out quite AI And just as as William mentioned about how physicians are aware of This innovative medicine that is possibly coming to them But you want to talk about some of the details on that. Yeah, so I think the first part of your question was around the awareness mattress

the top 350 providers. We saw a strong bump in this awareness coming out of Qwaiai, especially among the allergist immunologists. And in addition to that, the aided awareness of avicate is well above 60 percent at this point. So I would say it's certainly not plateauing. There's further work to do as we get into sort of lower

and sort of the current performance of what we see, we anticipate and will be really focused on maintaining strong patient access post-approval. You know, all five doses of Avakit are on the market, including the 25 milligrams.

And we are certainly seeing strong reimbursement. There's one code for SM as well. So for the small proportion of scripts with ISM that we are seeing today, we are seeing those getting good coverage as well. Thank you. Our next question comes from

ISM treatment durations may shape up in the real world. I particularly get questions on the 40% of trial patients that received less than a 30% symptom reduction after a year and if that cohort in the real world may be at risk for shorter durations. Thank you.

So, Brad, thanks for your question, and, Becker, can you weigh in on that? Yeah. I think it's important to remember that TSS score is not a binary measure. Patients derive benefit on their most bothersome symptom. Sometimes that includes the total TSS score going down. Sometimes it doesn't.

But for most of the patients on the study derived benefit, and what's really important is that patients at all TSS levels have remained on drugs for a very long time in the study, including the patients from part one that remain on after many years. So...

I don't think we're in a position yet to say what the duration is going to be. This is going to be lifelong treatment, I believe, for many patients. And then we're going to continue to learn of all the ways that A.O.K. benefits patients beyond what's measured by the T.S.S.

And I would just add, Brad, I mean, we've said this before, is that when you see the 96% of patients who are on AVA in Part 2 roll over into Part 3 and continue on therapy in the context of a clinical trial, you know, with having to be part of a protocol, I mean, I think that's really a testament and patients really vote with their feet.

We've also mentioned that as we've gone out broadly with this data, the response rate criteria that we put in place is really not relevant to the AI community. It's certainly something that hematologist oncologists are familiar with, and we certainly have strong data there that we can discuss with them, but AIs don't really think about that response rate as a metric by which they think about patient benefit.

Thank you. Our next question comes from Mac Fran of TD Cohen. Please go ahead.

Good morning, this is Ernie, and you guys are March. Congratulations on the quarter. Thank you for taking my questions. We just have a couple on the Iva-Kubit and the guidance.

So you mentioned some of the growth came from a reduction in the percentage of patients on free drugs. And we're wondering what exactly drove that and why do you think it would be temporary? So how does it push everything about it going forward? And then also wondering if you...

So any off label use of the drug, given that we're getting so close to, you know, the expected data approval in ISM. And then a second question on guidance. Have you guys determined how you plan to address, I reckon guidance once the label is expanded? Thank you.

Thanks for those questions and appreciate that everyone has a lot of questions. We're going to try to keep this just given the queue. So maybe I'll answer your last two questions quickly Ernie and then we can get, have Felina weigh in on how we thought about the growth. So no, we do not anticipate providing any additional guidance upon the ISM approval.

It's going to be early days and a launch, the first therapy ever approved in this disease state, so we will not be issuing guidance. And then we've had very little off-label usage at all, so that remains the same as it was last quarter. We have a few patients, but not many. So maybe, Felina, can you weigh in on how we've thought about the kind of growth and what happened with the free goods patients? Yeah. So what we saw this quarter is that half of the growth that we saw was due to a shift to a greater proportion.

to help in re-verifying patient status. In some cases, patients may qualify for additional sources of financial assistance, such as third-party charitable foundations. And if they're able to go on to this, then they're able to move off of free drug and onto commercial therapy. The resources available here are finite. And so for that reason, we expect this to be.

That's helpful. Thank you. Thank you. Our next question comes from Dane Leon of Raymond Jeans. Please go ahead.

Thanks for finally getting me connected here. So just two for me.

clarifying that actually the last point that was made there. I think people are just trying to understand the cadence going into the second quarter where obviously you're going to get approval this month. What we should expect with ASM. So to frame it more broadly, you raise your guidance.

obviously you feel confident coming out of the first quarter that things are going well, you're picking up momentum in ASM. On the commentary that there's going to be some shift back to patients on pre-drug. Can you maybe just help us frame it a little bit so we're all kind of more dialed in to what we should expect maybe the second quarter Q on Q to look like for ASM with all those moving pieces.

And then could you just frame quickly for us to your expectations for the 945 plus those Merton and first data will see at ASCO. Obviously, that seems to be a curtain razor for the L. A, 5, 8, our patient population that we'll get later on the year. But, you know, we would expect to see maybe some initial signs of advocacy between that combination just based on the mechanism of action. So anything there could be helpful as well. Thank you.

of the free goods impact that we mentioned. And you can think about it almost as, you know, so we've increased our guidance by $5 million. That's approximately what the impact of the free goods was. And so you can almost think about the base to grow revenue off of for Q2 as being like closer to 34 million. And we still expect to see moderate growth off of that going forward, consistent with what Polina said. And that is consistent with our.

the 945 question for you. So, Dane, thanks for mentioning the 945-plus-osse combination. That is a combination we're very excited about. This is an update on our phase 1 part of the study. As you know, patients in phase 1 are heavily pretreated and have quite complex tumors.

What we're looking at here is really safety and tolerability of this combination. This is really the first time that full doses of 2 eGFR inhibitors with different side effect profiles are being combined. We look to the activity data to validate that the compounds hit the mutations that they're expected to. These types of Wei cabin

shared some of that data in the past. And so that's really the expectation with respect to efficacy in a heavily appreciated patient population. But the safety is what we are focusing on at ASCO.

Great, thank you guys. Congrats. Thank you. Our next question comes from Michael Schmite of Guggenheim. Please go ahead.

Hey, this is Paul on Michael. Thanks for taking the question. I have 1 on on blue 451 data at. So I just wanted you could set some expectations. How are you thinking about the bar for next gen exon 20, chocolate therapy to sort of shift the treatment practice in the 2nd line plus setting.

And then maybe if I could squeeze a quick one in on GitHub Red O, anything you can share on those policies that you've initiated to a reporter and sort of how your confidence is in filing a new partner in the year term, that'd be super helpful. Thank you.

So thank you for the question. Becker can take the 451, but maybe I'll just address Gabretto first. So from a Gabretto perspective, we are very confident that we will be able to find a great partner for this product. It is an important medicine that has a tremendous impact on patients with red driven cancers. And we've got a lot of...

So to spare patients the toxicity of what we've seen with some of the other compounds and then to be able to address the most common area for relapse, which is the central nervous system.

So we're in dose escalation right now, still escalating. So I'm not, don't expect an ORR from this early study. But what we are anticipating showing is the level of activity that we've seen. We've already shared that we've seen activity at all of the dose levels. So this will be an update on this.

and Central Nervous System Activity as we continue to escalate the compound.

system activity as we continue to escalate the compound. Thank you.

Thank you. Next question comes from Joe Betty of Bright. Please go ahead.

Hello, this is Benjamin Poulouccion for Joel. Thanks for taking our question. I just had a clarifying question. What's driving the team percent growth in SMAHN? And then would you expect that to continue? Thank you. Sure, hopefully, do you want to talk about the SMAHN and the work we've been doing there?

Yes, thanks for that question. So as you mentioned, we were really encouraged to see 15% growth in the market share into SMHN. I think just for contacts into the overall advanced SM market, it's still a relatively small proportion of the patients who are being treated.

for their SM. And the dynamic there is that most of these patients have SM-AHN and really the education there is focused on the awareness of the SM and the urgency to treat the SM, where providers, heMOX, have traditionally been attuned more to treating the AHN.

I think to answer your question, primarily there's still a lot of headspace because it is still on the order of just a minority of overall patients who are being treated for their SM.

Thank you. Our next question comes from Matt Biegler of Oppenheiger. Please go ahead. Oh, hey, good morning. Thanks for the question. So I guess

separate J code for ISM and is that needed to be able to provide concrete guidance? Thanks. So, thanks for the question. So, what we've talked about before is that the code for ISM is actually the same. So, we will not be breaking out ISM versus Advanced SM.

We certainly have a certain level of insight into that dynamic, but we do not have full visibility just based on the channels through which the product flows. We will be making sure we've talked about some of the KPIs will be using around launch and how to help you all think about the impact of the launch. That's going to include putting out new patient starts, which we started last quarter. We've updated here.

looking at the breadth of prescribers and the activation of new accounts. So those are the types of metrics we'd suggest that people look towards as we think about the health of the ISM launch. Felina, do you want to add to that? Yeah, just to jump in and clarify, completely agree with what Kate said. Just to clarify, the one point is it's not the new patient starts, but the total patients on therapy with AvaKIT that we'll report going forward.

Thank you. Our next questions come from Amy Savia of Meha. Please forehead. Hi, good morning. Thanks for taking my question. Can you talk about some of the physicians that you identified that are already physical? Yes.

describing Avikit and you know if you can give us some color on how many ISM patients are under their care and maybe at least qualitatively how quickly do you see them describing Avikit to their ISM patients.

Thank you. Thanks, Ami. So, I think what you're kind of asking about is how do we think about the dynamics early in launch? Who will be those early adopters? And are the physicians who have some current experience, we expect that to be one of those groups. But, Felina, do you want to weigh in on that? Yes, so to the first part of your question, as we've talked about, there's around 460 accounts, so really good breadth of prescribing for AvaKit for the current indications.

which is a great foundation heading into the ISM launch. We estimate that the current prescriber base is managing around 400 already diagnosed moderate to severe ISM patients. The second part of your question was really around the speed of the ramp. We expect that to come both from existing prescribers as well.

is going to be hard to predict, right? So these are early quarters in a first to market new therapy. And so it's always harder to predict those early quarters until we have a couple under our belt. And again, that's why those KPIs that Kate alluded to are going to be so important in tracking the trajectory of our early launch.

So out of these four and 50 accounts, are all of them mostly sort of oncologists? Have you been, you know, presumably prescribing advocates to ASN patients?

Are they predominantly, you know? Yes. So the answer to your question is yes, because the current indications are primarily managed by oncology. Anyway,okay,we are from Fort Olforum

Thank you. Our next question comes from Andrew Baron of SBB. Security, please go ahead. Hi, thanks. Two questions for me. Maybe the first one is from Mike. I know you said the Integrated and the Curved Router Program wouldn't impact expenses in 2023 and you're trying to reach out.

to add to the trial protocol to have the clinical holder move? So maybe starting with Gavrado, Mike, do you want to weigh in on how we're thinking about any additional expenditure and just our discipline around our view on that? And then, Becker, we can go to 222. Yeah, I think, yeah, so Andy, like as we mentioned, we're in

into the process of re-partner gap rate or now. We feel very confident about how that is going, and that leads to our belief that we will not see any operating expense, incremental operating expense impact this year or in future years beyond what we've planned. If anything, we could possibly see if benefit going forward. So we feel very confident about that position. We don't anticipate any impact on how we guide to our long-term sustainability. And I'll just add to that, Andy, you know, this is an area that we have a lot of control over. As we think about our operating expenses, access, uh, across, and still teams are bigger ?'ass, uh, and it's…so? ?? investir whats'watchra pearls capra satisfied.

We added baseline ophthalmologic exams for patients, and then if patients had symptoms, they'll get a follow-up. But that was that and the FDA toxicity criteria or the only real addition to the protocol.

And you don't anticipate that will change anything around the cadence of enrollment or anything like that? No, there's no change expected for a patient.

And you don't anticipate that will change anything around the cadence of enrollment or anything like that. No, there's no change in expected for patients. Thanks.

Thank you. Our next question comes from David of City. Please go ahead. Thank you very much for taking my question. Regarding the change in guidance for Ava, can we assume that the incremental increase is primarily from the one time charge in the quarter? Yes, that's the one time charge, the one time benefit.

One time benefit, that's exactly what we expect to be the same. And on the ISM launch, when you look forward, I understand you're not going to be able to give any guidance or anything like that, but when you look forward to the launch, what dynamics and you're not going to be able to give any guidance or anything like that, but when you look forward to the launch, what dynamics

should we be attuned for, given the differences between the ASM and ISM population in terms of potential cadence, how long it takes to get a patient from prescription to being on therapy and other such items.

So, Selena's mentioned or talked a little bit on the call today already about how to think about that ramp cadence and the KPIs. Selena, do you want to reiterate that? Yeah. I mean, I would start with, I think, the biggest difference is really the number of prevalent patients who have already been diagnosed and are really actively seeking treatment.

is driving that urgency to treat, right? You know, while these patients have significant need and are taking polypharmacy and are still facing limitations on their activities of daily living, their ability to work or participate in family activities, it still is a behavior switch for these patients to move from symptom directed therapy to being...

times a year and so this education is really important to maximize you know the urgency to treat and the decision to treat with AvaKIT at these visits.

Thank you. Any questions come from Pepper Larson of Lortoise. Please go ahead.

Hi, this is Cheyenne for Peter. Thanks so much for taking our question. So it sounds like there was two key dynamics here for the bump and product revenue, both with the free drug dynamics and also some growth in ASM. Could you add a little more color on how much was really driven by organic growth in the ASM market and maybe what we could be thinking about for growth trajectory there for ASM?

Thanks for the question.

Thank you. Our next question comes from Xi Xiong Xu of Berenborg. Please go ahead. You Alright?

Good morning. Thanks for taking the questions. First one I want to ask Kate, the earlier comment you made around 25 mg dose strength is already in the channel. I wonder if you can talk about the significance of that both in terms of the

launch red in this as well as the importance of that metric for you internally and if we're able to track the use of describing in the high-sm patient population. And then the second question is around the CDK2, Bluetooth 2.

as well as the importance of that metric for you internally and if we're analysts to track the use of describing in the ISM patient population. And then the second question is around the CDK-2, our newdies2 program.

Can you talk about the safety matrix that we're going to see at the ASCA and also around the pathway modulation signal you were referring to? Thanks very much. Thank you for those questions. Starting with the 25-meg question, I think one thing that's really unique about this launch and this opportunity is the fact that Avakit is available in all doses strengths.

there would be additional lag time needed, right, upon the label coming in and getting that product into the channel. And that doesn't exist for the situation that we are in. So that's a great strength that we have coming into this launch. And then, Becker, do you want to talk a little bit about Blue222 and what to expect from a safety, what are you looking for from a safety perspective?

Yeah, so just a reminder, Bluetooth 2.2 was designed and selected to be highly selective such that it hits CDK2, but does not hit CDK1. And when you hit CDK1, you can get hematologic and gastrointestinal toxicity. So really showing that we're in an active range without seeing that type of side effects going to be important. Both is a single agent and...

Thank you. There are no further questions at this point. Ms. Hevelin, I'll turn the call over back to you.

Thanks, operator, and thank you all for taking the time to join us today and for your continued support of Blueprint Medicines. It is going to be an exciting month for us, and we really look forward to talking to all of you again soon. And given that it's May 4th, I'd be remiss to not end the call by saying May the 4th be with you for all the Star Wars fans out there. So again, look forward to talking to you all hopefully in a couple weeks.

Thank you. This concludes today's conference call. You may now disconnect.