Blueprint Medicines Corp (BPMC) 2024 Q1 法說會逐字稿

Good morning. My name is Fate, and I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines first-quarter 2024 financial results conference call. (Operator instructions) Thank you. Jenna Cohen, you may begin your conference.

Thanks, Fate, and good morning, everyone. Welcome to Blueprint Medicines first-quarter 2024 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 section of our website at www.blueprintmedicines.com.

Joining me today are Kate Haviland, Chief Executive Officer; Philina Lee, Chief Commercial Officer; Fouad Namouni, President, Research and Development; and Mike Landsittel, Chief Financial Officer. Christy Rossi, Chief Operating Officer; and Becker Hewes, Chief Medical Officer, are also on the line and available during Q&A.

Before we begin, I'd like to remind you that some of the statements made during the call today are forward looking statements as outlined on slide 3 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. You are cautioned not to place any undue reliance on these forward-looking statements, and we print disclaims any obligation to update such statements.

I'll now hand the call over to Kate.

Thank you, Jenna, and good morning, everyone. We delivered another very strong quarter and our launch of AYVAKIT in indolent systemic mastocytosis. And we are entering 2024 in a position of strength. We have great momentum across all aspects of our business as we execute on our three priorities that we laid out in January.

Our first priority is the launch of AYVAKIT and indolent systemic mastocytosis. We have driven impressive revenue growth. And importantly, we are building the foundation for top line revenue growth well into the next decade. We are also making significant progress in advancing our pipeline of innovative programs that are focused in the most and our most compelling opportunities where we believe we have the greatest prospect of improving patient outcomes.

And third, we are maintaining a strong and durable financial position in a self-sustainable financial profile. I'll briefly touch on each of these. Starting with the exceptionally strong commercial performance we delivered in Q1, we achieved $92.5 million in AYVAKIT net product revenue for the quarter. This results surpassed external consensus as well as our own internal expectations.

Philina, will discuss in more detail the components of our continued commercial success, but I want to take a moment to say how incredibly proud I am of our hard-working and dedicated commercial and medical team members. Their commitment to delivering for patients with SM globally is resulting in this type of performance.

These results also reflect the profound impact to AYVAKIT is having on patients as well as our strong and growing prescriber base. Today, we're also increasing our AYVAKIT guidance for the year to $390 million to $410 million. Later on the call, Mike will share more of our thinking around today's AYVAKIT guidance increase, which is steadiest quarterly on a revenue trajectory to peak sales of greater than $2 billion globally.

This revenue trajectory makes AYVAKIT one of the most exciting rare disease launches happening right now and puts us on a similar path to other notable rare disease product launches of first-in-class medicines that built new multibillion-dollar markets. We are also strengthening our presence in allergy and inflammation with BLU-808 a while [AYVAKIT] inhibitor.

The BLU-808 program built on the significant insight we have data mast cell biology and targeting KIT, the master control switch mast cells, which we believe has the greatest prospect of improving outcomes for a large number of patients across allergic inflammatory diseases.

Our recent webinar entitled the powerful mast cell highlighted the scientific rationale for our aspiration to fundamentally shift the way many allergic inflammatory diseases are treated by targeting this primary effect to sell the mast cell with both mono and combination therapeutic approaches.

We are on track to file the IND for BLU-808 this quarter to enable initiation of a Phase 1 study in healthy volunteers. We've established a successful track record with AYVAKIT, and you can continue to expect blueprint to discover and develop potent and highly selective multiples and we expand our mast cell franchise behind systemic mastocytosis.

Turning now to the oncology side of our portfolio next month at ASCO will be presenting data, demonstrating that BLU-222 is the first CDK2 inhibitor to be well tolerated in combination with an approved CDK4/6 inhibitor. With this data, we now have the clinical evidence that BLU-222 is a differentiated best-in-class CDK2 inhibitor.

BLU-222 with the ability to combine with approved CDK4/6 inhibitors also position it to move quickly with the potential to also become the first in class CDK2 inhibitor approved for patients with hormone receptor positive HER2-negative breast cancer. I remain confident that we will execute a strategic partnership in the second half of this year to rapidly move BLU-222 forward into registration directed trials. Importantly, we are executing across the business while maintaining financial discipline.

Our total costs and operating expense continued to decline in was $735.6 million in cash on our balance sheet, we are in a strong and durable financial position. I am proud of the tremendous progress Blueprint have made in the first quarter of this year and continue to be impressed by the head down executional focus I see across all of our teams to make sure we're achieving our goals quarter after quarter.

Now let me turn it over to Philina to discuss this quarter's commercial performance. Philina?

Thanks, Kate, and good morning, everyone. We had an exceptional first quarter generating AYVAKIT net product revenue of $92.5 million, including $83.1 million in the US and $9.4 million ex US. AYVAKIT revenue has grown more than 135% year-over-year. We saw positive trends across all key business fundamentals, continued strong and steady growth in patients only AYVAKIT, reflecting a strong pace of new patient starts and low discontinuation rates. Our mix of commercial versus three goods also skewed more favorable than we anticipated. Comlines remains high our International ISM launch is off to robust start with Germany after the races.

Let's look at our key fundamentals in more detail, starting with growth in patients on AYVAKIT, we drove a really strong pace of new patient starts coming out of the holidays throughout the first quarter of the year. We continue to see low discontinuation rates driving positive trends in duration of therapy. For advanced SM patients duration of therapy is trending even longer than our last update now at an average of 25 months. And while it's still early days, duration of therapy in ISM patients is trending significantly longer. This is exactly what we expected based on AYVAKIT benefit risk profile.

Q1 tends to be a tough quarter in our industry with patients benefits reverifications, lower gross to net and impact on compliance. Our market access team did a great job managing through all the best. Our free goods share once again, has been a surprise to the upside and is now averaging about 20% since ISM launch.

The favorability in commercial versus free goods is really driven by two things. First, the payer mix of ISM patients skews more commercial, and we estimate that ISM patients now comprise the majority of patients on therapy.

Second, Medicare patients were able to access paid therapy as we saw last year. Importantly, unlike last year, we expect these patients will be able to stay on therapy for the rest of the year due to changes to the out-of-pocket cap as part of Medicare Part D benefits redesign in inflation reduction act. In this third full quarter of launch, we are seeing strong and steady performance against our key revenue drivers just as we expected.

The favorability in commercial mix exceeded our expectations and provides a tailwind for the remainder of the year. This, along with confidence in our strong continued execution is a key driver for our guidance update today, we'll continue to watch year, such as the ongoing pace of new patient starts, duration of therapy, compliance and free goods, as well as our ongoing European launch performance. Taken together, our first, our ISM first three launch quarters are showing a clear inflection point for AYVAKIT revenue growth.

Now let's talk about why we expect to sustain this growth for years to come. Our team is executing well against our commercial strategy, and we continue to make headway across multiple paths to drive sustained growth. We continue to grow breadth and depth in the AYVAKIT prescriber base across all specialties and settings. Prescriber breadth is one of the most important lead indicator through revenue growth. The number of new AYVAKIT prescribers continued to grow this quarter, including a growing number of allergists who have been activated to treat SM patients.

Overall prescribing is still split evenly across the academic and community setting. The chart on the left shows AYVAKIT adoption into the top 400 providers by SM patient volume. And as you can see, we're starting to see even more dense from repeat prescribing as positive first experiences lead providers to start their second, third or more patients on AYVAKIT.

Because the chronic burden of ISM is often underappreciated. A key part of ongoing execution is redefining what disease control means for providers and patients. And we continue to expand our direct to patient and provider educational initiatives to foster greater awareness of the burden of disease with the goal of activating patients to ask about AYVAKIT.

Moving with ISM can be very isolating. Establishing patient to patient connections is a critical part of the journey to treatment. In Q1, we launched a monthly educational series where patients can learn from the experiences of other patients who are taking AYVAKIT.

As part of our ongoing community building efforts, we held a first-of-its-kind summit, bringing together patient AYVAKIT, patients and multidisciplinary thought leaders. Just this month, we launched an unbranded direct-to-patient campaign to drive further awareness of the total of living with ISM and the availability of a new treatment option. All of these efforts are yielding impressive results.

Unaided awareness among patients has grown nearly eight fold since approval, and we expect our expanding peer to peer and patient initiatives will continue to activate more patients and providers to drive AYVAKIT. In closing, the momentum we've shown in our first three quarters of launch make us incredibly confident about the path we're on to achieve a more than $2 billion peak opportunity with AYVAKIT.

We are building and shaping this market. We are growing the prescriber base. We are activating more patients to seek treatment were growing the number of diagnosed patients, and there is plenty of headroom to continue to grow. We knocked it out of the park this quarter, and we remain laser focused on our mission to help more patients in need.

With that, I'll hand it to Fouad who will share how we're expanding our efforts in mast cell disorders to help more patients with allergic and inflammatory conditions beyond SM.

Thanks Philina. Last week, Dr. [Maria Castel] the renowned research and clinical experts in mast cell diseases joined us for webinar titled The Powerful Mast Cell, a promising and yet under appreciated target for treating allergic and inflammatory diseases. There webinar was the first in a new series we have plan to keep you updated on how we are thinking about the evolving science behind the whole portfolio of R&D strategy.

If you haven't yet had a chance to listen to the discussion. I encourage you to check out the replay, which goes live on our website. The mast cell is a key driver cell responsible for the pathogenesis of a wide range of allergic and inflammatory conditions. Reserves into mast cell biology and its involvement in inflammatory diseases has recently increases with the goal to identify novel therapeutic targets in allergy and information. This webcast focused on the biology of mast cells, including there, especially roles of driver of and contributors to inflammatory responses.

Their core involvement in biological pathways are relevant to an array of allergic and inflammatory diseases. Blueprints approved to modulating mast cells and building a pipeline in allergic and inflammatory diseases. Blueprint has a long and proven track record of leadership in this space. As evidenced by the success of AYVAKIT and the ongoing development of [LM history]. And we have been what we believe is one of the most aggressive mast cell drug discovery capabilities in the industry.

BLU-808 is poised to help us beyond systemic mastocytosis. Secondly, the challenge of developing a potent, highly selective tunable, all wild-type good inhibitor is the logical evolution of our AYVAKIT capabilities in this space. And the opportunity we have ahead of us is significantly larger than any we've pursued in the past.

Our vision for scientific leadership in mast cell diseases is built on four key pillars. First level of deep understanding of the mast cell biology and to modulate activity. Second, to select the best targets modalities for monotherapy and combination strategies to achieve first and best in class positions. Third, establish a strong preclinical and early clinical POC, your approval process to do risk development.

And lastly, pursuit pipeline in a pill opportunities in major mast cell associated these orders where there is a medical need. We will continue to provide updates on our mast cell franchise throughout the course of the year, including BLU-808 IND submission on track for this quarter, which will enable us to initiate the healthy volunteer study. We will also initiate Part 2 of the harbor of trial in elenestinib in indolent systemic mastocytosis in the second part of this year.

As we expand our mast cell focus, we continue to drive innovation in systemic mastocytosis of our understanding of the spectrum of patients and the underlying biology of the disease evolves. Moving from allergy and inflammation to our oncology part of the portfolio. We are happy to report for the first time at the 2024 ASCO meeting, the safety and the single of early clinical activity of BLU-222 in combination with ribociclib and full restaurant in home and positive HER2-negative breast cancer patients.

We believe these data clearly demonstrate the first and best-in-class potential of BLU-222 become the combination partner of choice with CDK4/6 inhibitor in hormone positive HER2-negative breast cancer.

So this I will turn it over to Mike to discuss our financial results.

Thanks, Fouad. Earlier this morning, we reported detailed financial results in our press release. For today's call I'll touch on a few highlights. In the first quarter, total revenues were $96.1 million, including $92.5 million in net product revenues from sales of AYVAKIT and $3.6 million in collaboration and license revenues. As Philina discussed, AYVAKIT revenue was driven by strong -- continued strong and steady growth in patient starts, positive trends underlying extended duration of therapy and favorability in the mix of commercial patients.

Given the strength in Q1, we are raising our AYVAKIT product revenue guidance and now expect to achieve $390 million to $410 million in net product revenue in 2024. We've had a stronger than expected start to the year, and we are still learning about the seasonal trends and impacts in ISM as we make our way through the first year of launch. Our guidance philosophy is to provide our best understanding of where we may end the year, given the various puts and takes on revenue both in the US and EU each quarter.

This update relatively early in the year reflect that commitment. The increase in today's guidance reinforces that we are on our path to capturing AYVAKIT peak opportunity of greater than $2 billion. This revenue growth, coupled with expense discipline and focused investment is what continues to give us confidence in achieving a financially self sustaining profile.

Our total costs and operating expenses continued to decline and were $174.9 million for the first quarter. We anticipate that our research and development expenses will remain relatively flat for the remainder of the year with some quarter-to-quarter variability. We also expect our SG&A expenses to remain relatively stable as we continue to gain operating leverage from our commercial infrastructure.

We believe that the current full year sell-side consensus for total costs and expenses of approximately $715 million, which includes non-cash stock-based compensation expense, reflects an appropriate estimate for 2024. We remain in an exceptionally strong and durable financial position with $735.6 million in cash on hand.

AYVAKIT evenue performance in today's guidance increase, coupled with our continued focus on managing operating expenses, will result in our goal of further reducing our cash burn in 2024. Our solid financial profile drives our ability to generate long-term value as we invest in the commercial success of AYVAKIT in advanced and innovative portfolio of medicines.

With that, I'll now turn the call back over to the operator for questions. Operator?

(Operator Instructions)

Brad Canino, Stifel.

Thank you. Great quarter. KMR back at the quarter, meetin in February, you referenced a strong sense of via some awareness and the desire to treat patients in the company also had a strong presence of the meeting. So in your view, how much of that awareness momentum is based on the trajectory exiting the quarter? And what does the teams still sees headroom? Thank you.

Thanks for that question, Brad. And to your point, I think one of the things was very notable about Quad AI this year was just in comparison to the year previous where we are introducing Blueprint for the first time in showing the AYVAKIT pivotal data for the first time. And then here, we were sitting with a large group of now people that clinical the drug and we're treating patients, which was such a notable step change to your point.

So some equally, I'll talk a little bit about how our awareness ,the impact of awareness and healthcare providers are growing prescriber base and how that's really fueling our future growth this year and beyond.

Yeah. Thanks for the question, Brad. And tier point, quite AI certainly we could weaken our excitement was palpable from treaters across the academic and community setting. That said, I would still say we're just, we're still just getting started with significant headroom to grow. The team has the ongoing patent interactions of regional meetings, the cadence of congresses throughout the year. And I think as we really look at our lead indicators on the provider side with our breadth and depth of prescribing, this is a really strong foundation for continued growth and certainly leaves significant headroom for continued penetration, not just into the top 400 but well beyond that into the broader trading immunity.

And in addition, touching on some of the direct to consumer or initiatives are really excited to really be rolling out the next wave of engagements for patient activation and that also leaves significant headroom to grow in patient awareness and likely had to ask their provider those are the AYVAKIT. All of this, we think bodes exceptionally well on that. We are well on that path towards that over $2 billion peak opportunity for a AYVAKIT.

Marc Frahm, TD Cowen.

Hey, thanks for taking my questions and congrats on a quarter as well. Maybe following up on Brad's question is, how are you seeing maybe trends leading indicators to get into that bigger population that hasn't been well diagnose historically, things like testing rates and stuff like that to really access maybe the next curve, 10,000 patients that Kate you've talked about being out there that hasn't been care for historically.

And then related to some of that, just with the top line, really taking off here, very Kate in by talk about because the goal of getting to profitability. How important is that for the company, particularly as you start thinking about things like 808 coming in that could have a very broad to development program on there ultimately.

Thanks for the questions, Marc. Maybe we'll start with talking about how we see, where we are building a brand new market here with AYVAKIT and SM and how we think about the different avenues of growth of billing that market that some of the things you mentioned already, which is the increasing rate of diagnosis, which is a critical part, but also the fact that we know that there's a number of patients who are diagnosed and that we are just kind of starting to penetrate. We have a lot of room there as well. So if we know how do you think about both penetrate in the currently diagnosed group versus the opportunities to continue to grow the overall size of the market?

Yeah, I would say, thanks for the question, Marc. First and foremost, if we just look at the patients who are already diagnosed, which continues to steadily increase, penetration into that patient population already represents an over $1 billion opportunity. And that's where like hearing now primary focuses is dedicated. And you spoke to sort of what there are multiple prongs for continued growth and you spoke specifically to continued growth in diagnosis.

There, we are really focused on continuing to drive initiatives like the high sensitivity kit testing, the disease awareness and the sponsor testing from Blueprint and we're really encouraged to see significant increases in volumes of high sensitivity kit testing, especially in the allergy segment, where that's really important. And even beyond that, we know there are further levers for growth for AYVAKIT, and that's adoption into broader range of patients initiative, widening that line of who is seen as not well controlled as well as expansion into further geographies. And we're seeing, as I said, in a really strong initial performance in our international launches, all this bodes really well towards that peak opportunity.

Yeah, one thing maybe to add there, is still very similar to other rare disease launches. We've seen where the epidemiology and these disease states tend to be dated and very small studies to inform that and what we're seeing is even at our sponsored testing patients coming out of other pools of patients with the M cast or others that I think have been very much underrepresented. And that current epidemiology, though, it will be providing more views on that and it comes. But our view is this market has a long way to go in terms of continued to grow the number patients on therapy as well as the number patients are diagnosed with this disease.

May be now turning to your question about the importance of profitability. And how we think about that [Michael, your turn].

Yeah, I'll start. I think, Mark, I think the key is we're trying to build a sustainable business for the long-term. And so part of that is making sure that we stay laser focused on our top priority investment areas such as BLU-808, which is upcoming, and that requires financial discipline and focus. But like long-term, we're looking to find these key value drivers where we can add long-term value to the company. And that's a long-term goal.

Yeah. Just add on that. I completely agree. And I think one of the things we've been known for a Blueprint Medicines as our research and development capabilities. And we have had just tremendous opportunity to continue to drive innovation and to make really meaningful impact on patients. I think BLU-808 is certainly on everyone's radar, but we have some of our favorite programs. We haven't had a chance to talk to anybody about yet. And so we know we're looking forward to talking about our continued innovation in this spare part.

Okay. Thank you.

Michael Schmidt, Guggenheim.

Good morning. This is Paul on for Michael. Thanks for taking our question and congrats on the quarter. Month on AYVAKIT for the ex US opportunity. I know you mentioned Germany drive the European sales this year, or do you still see a roughly 10% contribution to this year's full-year sales? And then how are you currently thinking about the longer-term trajectory in Europe perhaps beyond this year? And then maybe just squeeze in one of the CDK2 on any update on the call or the tenor of the progress of your partnership discussions for that? And are these exclusively on BLU-222 or perhaps more broadly for the city of franchise?

Thank you, Michael, thank you for your question. That I think one thing is the European team has done a tremendous job out of the gates with ISM approval at the end of December with Germany really coming on strong in terms of getting patients under therapy. And so they've done a tremendous job there because you how do you think about the overall contribution for Europe in its growth trajectory. And maybe also, could you take that the BLU-222 the questions as well?

Sure. Thanks, Paul. And yeah, we're really pleased with the performance of the international team. As Kate said, they're very much of the races. And I think it's been particularly encouraging to see that some of the underlying dynamics in the German launched early on have looked very similar to the United States, including [elenestinib] prescribing, et cetera, lots of that patient demand. So really encouraging to see. And of course, there's other dynamics in Europe that are different from the United States than.

And most notably, that would be price negotiations. System of those cars will start flipping this year and then into next year as well. So what I think about the overall opportunity in Europe, it's certainly significant. It's going to be a contributor to our overall top line and that for this year that's adding to that 10% to 15% of revenue as a rough estimate is probably not a bad place to be.

This, frankly, is one of the levers that we think about when we're trying to set guidance ranges, right? I mean, this is a variable that informs how we make may perform over there. But I think tenants [18%] is probably a good estimate. And then at peak in markets like that, we'll see how things evolve in the coming years as we continue to grow the opportunity but you often, let's see the US still representing certainly the majority of the dollar value of the SM opportunity and as Philina said, and it's very easy math math to get to a multi-billion dollar opportunity just in the US based on what we are, what we are seeing.

In terms of CDK2, I think that in the prepared remarks, very excited about the data set that we're going to be sharing at ASCO. And we really see this as the first the data that will be showing that you can safely combine CDK2 and inhibitor with a 406. And our partnership discussions are progressing well. We've always been very clear that in a second half of this year is when it makes sense to have a partner on board strategically based on where the program will be heading as we exit this year and into next.

And certainly, you know, as we think about the tenor of those conversations, our focus is on CDK2, that's where having a BLU-222 having a partner on board to advance the program makes the most sense. Of course, there's a lot of innovation in our pipeline that. Partners may be interested and excited by we always have those conversations and will continue to do that.

Laura Prendergast, Raymond James.

Hey, guys, congrats on the Blueprint today. Another one on CDK2 thinking about how the costs of CDK2 impacts your OpEx costs throughout the year. I mean, I'm assuming you guys are looking to out-license and not cause share and [EBITDA] from adding any input here about how you're thinking about CDK2 moving forward.

Yeah. Thank you, Laura. [Becker] Christina do you start with just strategically how you're thinking about BT? And then, Mike, maybe you can weigh in on just how you feel any kind of impact on what it's like year, yeah?

So from a strategy perspective, we've always been very intentional easing business development to advance programs and really complements and what our own capabilities and our own internal priorities may look like.

And certainly at this stage and as we said, we are very focused on continuing to really add develop a broad portfolio and myself driven disorders and certainly executing the ongoing launch of AYVAKIT, we've the L&S Nov and BLU-808 coming behind that. And CDK2 is a very significant commercial opportunity. And one that because it's primarily in breast cancer, is obviously in a somewhat different space. And so that's really the driver behind as having these conversations will be open as we go through, in terms of what the exact structure will look like.

But we have a part we are on board because we think the capabilities that partner brands are relevant to how we advanced that. I always think about having at co-development, co-commercialization makes sense in places where you're trying to build and leverage scale. In the short-term, that breast is not a place where we're trying to build and leverage scale. So again, we'll consider to that those conversations and as they make sense. But we have a very clear idea strategically of what where trying to accomplish.

(multiple speakers) I just I think with respect to the financials, there's those we obviously don't comment specifically on our partnership structures are financials at this point. It's too early. But for 2024, we're continuing to execute on our Phase 1 study that's baked into all of the financial guidance that we've given. We feel very confident about that. And then longer-term, as Christy mentioned, strategically, it makes a lot of sense to bring in a big partner on. And part of that is driven by the fact that these studies to move forward in breast cancer going to be very expensive. And we want to partner to both strategically as well as financially help support us there.

Thank you.

Salveen Richter, Goldman Sachs.

Alright. Thanks. I think my own personal view on BLU-808 could you talk about your strategy for determining which indications to expand into after competition from establishing cronacutic earning? Thank you so much.

[Michael] want to start and talk about 808?

Thank you. Yeah, I mean, for BLU-808 and I actually would, of course, you and others to really go back and listen to the live replay of our powerful mast cell for mast, we got really treated this topic in depth. The way we are thinking about it is, as we said, chronic urticaria is our leading indication. On the other hand, given the profile of the molecule we believe is really a very good profile and we are filing the IND and taking into the clinic this year. It should if you look at a number of other indications because the enrollment of mast cell biology of numerous diseases is clearly and well established now.

We'll be doing a lot of preclinical work in other indications, but also we'll be doing proof of concept clinically for a number of indications. And we see where we really think that the full scope is and how to line of the additional indication beyond chronic urticaria. So we we believe this molecule if the clinical profile is consistent with the preclinical data that we are seeing and have the opportunity to really talk of a number of diseases and therefore would have to look at the POC for many of them.

Thanks, Mike. I am able to add that, we also believe that the profile, the compound and the fact we have an oral therapy here is going to enable us to be able to the therapy to address on different patient populations across all these different disease states. We think we're really well positioned in terms of the target product profile. The compound to evaluate this and bring forward was truly a pipeline in a pill opportunity.

Got it. Thank you.

Reni Benjamin, Citizens JMT.

Hey, good morning, guys. Thanks for taking the questions and congrats on the amazing quarter and really good guidance. That's the question for me. Of the top 400 or so on certain solutions, how many are prescribing and what's the between allergists and hematologists? And as we think about reasons that eligible patients might not be being prescribed the AYVAKIT, can you or are there any reason that a potential group of patients that is incorporated into that headroom calculation of other area could grow? And how do you plan on addressing that? Thank you.

Yeah. Thanks, Reni. And maybe to address both how we see demand coming from the deficit is what the most patients as well as out of positions from the tail and and how you see that dynamic in terms of demand and penetration as well as talking a little bit about cadence of new patient starts, right? And how that is informing our growth into the future.

Yeah, thanks for the question, Reni. I would start with the initial breadth and depth of prescribing that we've established in these first three full quarters of launch in ISM that's a really strong foundation for us, both in terms of the breadth of the penetration. What you want to see in rare disease is not that it's concentrated in just a handful of centers like what really fosters in plan for scene for sustainable growth and continued growth is that breadth of prescribing.

And the fact that we're seeing adoption across both hematology oncology as well as allergy immunology and split across academic and community settings is extremely important and is a great lead indicator for continued growth. And when we look at the top 400, that's really something that we laser into to illustrate what we see is more the kinetics of prescribing. It doesn't speak to the full penetration because that's really just a snapshot of the highest volume providers, both --

So what's really important, I think, to see from that is that first prescribing is really leading to positive experiences that lead to subsequent repeat prescribing for two, three or even more patients, even within that mix, we see it really right mix of allergists and immunologists, hematologists and that, I think headroom just across all segments and deciles of providers to continue to grow there. In terms of your question around eligible patients and prescribing there, the most important thing we're focused on is identifying when a patient is not well controlled.

And that is really that like a across, a across both our provider engagements as well as patient engagement. From a patient perspective, patients can also become aplimated to living with a new normal. They may be avoiding trigger some. And so it's really important to make them aware of a new treatment option and that reclaiming some of the freedoms of their prior life is actually possible. And so really our direct-to-consumer efforts are really focused on driving that. And again, there are a lot of headroom to grow.

Derek Archila, Wells Fargo.

Hey, good morning and congrats on the quarter. Was hoping maybe you could discuss on the assumptions behind the updated guidance. Seems to suggest a slowdown in net patient adds relative to the prior quarters. I guess trying to reconcile that with the very bullish commentary of the prepared remarks. Thanks.

Thanks, Derek. And I think, just to start that way, we think about a [Blueprint] philosophy on guidance. And we are in the early days of building a brand new market. And so as we think that the low end high end of our day range is driven by, ranges around a multitude of different inputs across numerous variables. I know point if you want to talk a little bit about how you think about those variables, but we certainly expect continued growth and the overall opportunity.

Yeah, Derek, I think that the first answer to your question is no, we do not expect a slowdown in net patient adds. We see strong and steady growth in the net patient adds, and we expect that to continue. The past quarter we saw that really driven by strong cadence of new patient starts, very low discontinuation rates on which really penned Well, I think, for chronic durations of therapy. And that's also, there are a number of additional on key revenue drivers that contribute to our guidance in addition to that can strong and steady growth of net patient adds that we expect.

So it's things like our compliance on the proportion of free goods, which exceeded for this quarter and is something we'll be looking to see see how that AYVAKIT over the course of the year and as well as things like our ongoing European launch. And so it's the inherent variability in these key revenue drivers moving forward, that factor into our guidance range. All of that said, if we look at the midpoint of that range, that represents nearly a doubling of the revenue that we achieved last year, and we believe it firmly does put us on that trajectory towards the peak.

Got it. Thank you.

Peter Lawson, Barclays.

Thanks for taking the questions. Just as we think the other item patients you mentioned there was a low discontinuation rate. Anything else you can comment around those patients, whether there's any shifting components of the essentially fandoms use and sense of drug holidays, for instance? Thank you.

Yeah. Thanks, Peter for the question. I think what are the things I think the team has done a tremendous job in Q1 is, and we know that Q1 can often be very challenging across as Philina mentioned our prepared marks across the pharmaceutical industry and biotech. R&D just did a tremendous job on executing in the room certification process and making sure that compliance and state to state very high. But it will finance that you thought about [CNA] the US say that's the metric from patient discontinuation perspective.

Yeah. Thanks, Peter. So what we've seen in terms of discontinuation rates so far has been very much in line with what we've expected when we see AYVAKIT really favorable benefit risk profile from Pioneer. So discontinuation rates have been low. The very early trends towards duration of therapy have been very, very positive. And we've even seen a lengthening on the advanced SM side. To your question around compliance and holidays, like in fact, that has also trended extremely positively in terms of patients staying on therapy.

When we think about this patient population, they're very sticky, right? Like they have a regimen that they are adapting to, and they're really not taking does holidays. And so this is a really important point because as we progress in the launch and we increased the total number of patients on therapy, it's not just new patient starts anymore, but also the cumulative the effect of these patients remaining on therapy that will contribute to overall revenue growth.

There are thinks that's what's really important in the sense that as as that pool of patients on therapy get some much larger point changes and compliance and or free goods make a big difference from a revenue perspective. So I think that we're certainly seeing that.

Matt Biegler, Oppenheimer.

Hey, guys. Congrats from us along the quarter. I'm curious if you're seeing any signs of growth in advanced SM maybe because of the increased prescriber awareness from England launch? Or I guess should we still think of advanced is pretty flat going forward? Thanks.

Yeah. Maybe I'll just start quickly, does that mean we are so pleased to see that duration of therapy and advance SM being at 25 months and then either patients with very, very aggressive disease. And I think that bodes well for both the advanced SM opportunity as well as the rebid. We I have some opportunity. You on top of the growth in number of new patient investors put it.

Yeah, Matt, I would say we do continue to see growth on the advanced SM portion of our business. And that's obviously a relatively moderated compared to ISM which is our primary growth driver and now represents the majority of patients on therapy with AYVAKIT. But we do see, I think, a potential halo effect that with the -- now the awareness of AYVAKIT for ISM as our breadth of prescribing increases, it's happening. You not just analogy, but also with a number of new hematology oncology prescribers as well, who are activated and interested to get involved through ISM.

That's great. Thanks.

Ami Fadia, Needham.

Thanks. Congrats on the quarter. My question is on BLU-808, what data you need to generate to understand your goal forward with clinical development plan for indication beyond chronic urticaria? And how soon can you start to initiate clinical trials of those indications? And secondly, if you could provide any additional color on how you're planning to develop an elenestinib, any update from previous? Thank you.

Ami thank you for those questions. Becker do you want to talk about the data you want to see BLU-808 and how we're thinking about the end of broad proof of concepts as well as the plant for Harbor starting with our elenestinib which, as we've said before, IMS, unless it is really positioned to maximize the long-term performance of our Assam franchise. And so we certainly are going to be spending more time. I'm talking about that a second half this year.

Yeah, Ami. So BLU-808 being are exquisitely targeted. Well-timed KIT inhibitor is one that we're taking in healthy volunteers first, and that's obviously to get the initial PK and tolerability. But it also gives us an opportunity to see the ability of the drug to reduce tryptase even in normal healthy volunteers. And we believe that will give us a good steer of what the therapeutic range maybe inpatients.

And as Kate mentioned earlier, this is a very tolerable drug where we expect to be able to use it across a wide range of therapeutic doses. And that may be in as a single agent as we illustrated in our mast cell webcast last week where the mast cell really the driver like chronic urticaria. And then we've shown in our BLU-222 program and our EGFR program that we make highly combinable molecules when that's going to be to use the essence of that.

Our next wave of investigations where we're looking in more complex diseases where the standard of care as well established, such as asthma, where the combination is going to be necessary to really for the field in those indications. And so as we enter into patients next year, that will give us a sense of what our dose ranges work for patients who have vessels that are causing disease. And then we'll be able to look at as flood set in a number of different more complex indications and understand where that therapeutic ranges and get quick proof of concept in those indications.

And then with respect to our elenestinib as we said, we are getting more and more data as we study the patients on Pioneer. And we learn more from commercial patients about the really complex nature of systemic mastocytosis and the broad breadth of patients that can benefit many different ways. And so we look forward to sharing more about the before the end of the year about our design of Harbor and really our holistic approach to the development of L&S elenestinib in Assam.

Colleen Kusy, Baird.

Great. Thanks. Good morning. Thanks for taking our questions and congrats on the quarter. Any commentary on how you're measuring the early success of your DTTC campaign and what your plans are to invest further in the second half of this year?

Yeah. So I think you had it Philina, I think our direct to consumer campaign really is evidence of our conviction that we have a tremendous opportunity to help just a vast array of patients with ISM. Philina have you want to think about those efforts and how we make sure that we understand their [bank roof].

Yeah, Colleen, one of the most direct things that we look at is the patients on awareness of AYVAKIT. And we've been really encouraged that the efforts to date have already increased the unaided awareness of AYVAKIT eightfold while continuing to have a lot of headroom to grow. So this is really an area that we will continue to lean into in a highly targeted way. We lower these patients are looking for information on the disease, and we're really targeting both our media campaigns. And another thing we've talked about is the and the monthly opportunities we have for patients to come together with other patients to share their experience on AYVAKIT.

That element of patient storytelling is so important in a rare disease where in many cases and SM patient hasn't yet add in another patient. So the opportunity to connect here about their experiences and what the journey to AYVAKIT has been like for them, we believe will be really compelling. And so we do expect to continue growing on these initiatives through the second half of the year in a highly targeted way.

That's helpful. Thank you. And as a follow-up, just in your early market research, what's resonating most patients to keep them on treatment? And what gives you confidence in maintaining this low discontinuation rate in future?

Yeah. Colleen I mean, I think that really is a testament to AYVAKIT clinical profile. I mean, patients, it's a highly tolerable drug, easy to take. I mean, we saw in the Pioneer study that the side effect profile of AYVAKIT was for us superior to standard of care and the cocktail of symptomatic treatments that patients are on.

And then it's a testament to the activity and the fact that we see clinical impact across a wide range of symptoms in patients. I think it wouldn't such a heterogeneous disease that is absolutely critical. And that a patient, regardless of what they're most bothersome symptom is seeing great impact in AYVAKIT. I think that is just a pro pound equation for people that we see is resonating in patients are staying on. Becker you (inaudible)

Yeah. I think this is a couple of questions have since my interest, the one about drug holidays and optimism about convincing patients to stay on the drug. As Kate said, when they feel better, they don't need to take holidays. They don't need to be consents to stay on the drug. And so that really speaks to also the way that allergists think about treating this disease and having a very tolerable therapy and treating patients see how they do. And on this just speaks to why that there's consistent our treatment duration. And I also wanted to comment on the advanced SM duration. We're into two years in a leukemia like disease. And that really bodes well for the ambulance situation as well.

[Christina] do want to add.

Yeah, maybe I would add on Colleen, these are patients who are really highly motivated to and to regain quality of life. And just to share, I think even just some sound bites from engaging customers across the country, you have shared some of their patients' experiences is what we hear is patients getting their energy back, being able to go back to work at the jobs that they had to pull back on previously due to the symptoms of SM and the ability of patients to go and participate in activities with their kids or friend or loved ones are going to count for the first time. And really, reclaiming and starting to remember what normal looks and feels like. So it's really a profound thing and I think we really are even just at the beginning of this journey.

Great. Thanks for taking my questions.

David Lebowitz, Citi.

Hi, this is Dibanjana on behalf of David. On this on the [C basis] of promotion, I wanted to ask that they deliver swing from 25% to 20%. How should we think about patient growth versus actual sales growth? And what proportion of patients will beyond freed up by the end of the year? And I have one more follow-up.

So unfortunately, at the limit to one question just has are coming on close a time here. But so I believe the question is around how are we thinking about just the overall dynamic relative to free goods, again, being very early in the launch of a new therapy and building a new market. How are you guys thinking about that as you gave this year of around 20% since launch? And and how do we think about that as a driver of top line versus some of the other variables, including compliance, new patient starts? Are European launch all the other things that are adding into top line.

Yes, it's your question. I think there's really a couple of things that factor into our free goods mix as we saw that decreased to 20% this quarter. So it's both the payer mix of patients with ISM which trends more and more towards commercial. And the second piece is that more patients were able to access paid therapy. In terms of what to expect through the rest of the year. Free goods mix is really something we will need to continue to watch because as you said, more patients will continue to add on and be treated with AYVAKIT. So we're in the early days of the IRA internally to watch how that plays out.

Our expectation continues to be continued strong and steady growth in the number of patients on therapy and favorable it low discontinuation rates, high compliance, and we'll watch the free goods Nexon and continue to watch our international launches.

Thank you. There are no further questions at this time. I will now turn the call back to Kate.

Thank you, operator. We feel great about the progress we've made in Q1. And we recognize that there's a lot of work head of us this year. And as we move forward into the middle of the year, we do so from position of strength, we are well positioned to build on the momentum we've achieved here coming out of Q1, and we look forward to updating our progress. So thank you all for taking the time to join us today and for your continued support of Blueprint Medicines.

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