Blueprint Medicines at Needham Conference: Strategic Growth in Mastocytosis

On Monday, 07 April 2025, Blueprint Medicines (NASDAQ: BPMC) presented at the 24th Annual Needham Virtual Healthcare Conference, outlining its strategic advancements in treating mast cell disorders. The company emphasized both its financial robustness and innovative therapies, despite challenges in market competition and diagnosis rates.

Key Takeaways

• Blueprint Medicines projects AYVAKIT revenue to reach $680 million to $710 million in 2024, with a target of $2 billion by 2030.
• The company is exploring the potential of Alemastinib and Elenestinib to expand its market opportunities.
• Blueprint's strong financial position is supported by declining operating cash burn and strategic investments.
• The European market is expected to contribute 10-15% of overall revenue.
• Efforts are underway to enhance diagnosis through ultra-sensitive blood-based tests.

Financial Results

• AYVAKIT revenue guidance for 2024 is set between $680 million and $710 million.
• Blueprint aims for a $2 billion revenue from AYVAKIT by 2030.
• The combined peak opportunity for AYVAKIT and Alemastinib is projected at $4 billion.
• European markets are anticipated to contribute 10-15% of total sales.

Operational Updates

• AYVAKIT's launch for indolent systemic mastocytosis (ISM) is progressing strongly.
• Elenestinib has entered a registration-enabling HARBOR study focusing on bone health and chronic inflammation.
• BLU-808, a wild-type KIT inhibitor, is in Phase 1 proof-of-concept studies for allergic and inflammatory disorders.
• The company's operating cash burn is decreasing due to revenue growth and focused investment.
• Diagnosed ISM patients are growing at double-digit rates, with an estimated 60,000 to 65,000 patients in the US.

Future Outlook

• Blueprint aims to increase ISM market penetration through broader prescribing and improved diagnostics.
• The development of ultra-sensitive blood-based tests is a priority to enhance detection rates.
• The company is exploring wild-type KIT inhibitors for MCAS and other allergic disorders.
• Additional markets are expected to come online this year, impacting pricing and reimbursement strategies.

Q&A Highlights

• Tariffs are not anticipated to significantly affect financials due to low cost of goods sold and US-based intellectual property.
• Blueprint is closely monitoring regulatory changes to adapt strategies accordingly.
• The company expects symptom treatment to remain the primary competition for AYVAKIT.
• The HARBOR study of Elenestinib will assess key endpoints like bone health to potentially differentiate its label.
• Data from open-label studies for BLU-808 is expected by the end of the year, with further studies concluding next year.

In conclusion, for a deeper insight into Blueprint Medicines' strategic plans and detailed conference discussions, refer to the full transcript below.

Full transcript - 24th Annual Needham Virtual Healthcare Conference:

Ami Fadia, Senior Biotech Analyst, Needham: Good afternoon, everyone. Welcome to the next session with Blueprint. I'm Ami Fadia, senior biotech analyst here at Needham, and it's my pleasure to be hosting the team there. We've got with us Christy Rossi, who's the chief operating officer, and Fod Namoei, who is the president of r and d. Maybe if I could just ask you all to kick off with some opening remarks, and, we can dive straight into q and a.

Christy Rossi, Chief Operating Officer, Blueprint Medicines: Great. Thanks, Ami. Thanks to the Needham team for having us. It's great to be here. So, for those of you who may not be, familiar with Blueprint Medicines, we are focused on bringing innovation to patients, suffering from mast cell disorders, as well as a variety of other other diseases.

We have a, innovative portfolio of therapies anchored by AYVAKIT, which is, launching for indolent systemic mastocytosis, which is a very significant commercial opportunity. We have guided to, 680 to $710,000,000 in revenue for AYVAKIT this year. The launch has been off to a really strong start, and we are projecting continued growth towards, $2,000,000,000 by 2030. And then we believe that the SM opportunity could be, even more significant than that. And between avacit and alemastinib, which is our next generation KIT inhibitor, we believe, there could be a $4,000,000,000 opportunity for our portfolio.

Elanestinib just entered registrational, a registration enabling harbor part two study, so we're looking forward to bringing that forward to to patients as well. And then behind, avacit and elenasnib and our portfolio in systemic mastocytosis, we also are developing BLU-eight zero eight, which is a wild type KIT inhibitor. It's a very potent selective oral therapy that we just announced phase one data for earlier this year, and we're bringing that forward in a variety of proof of concept studies this year to better characterize the safety and efficacy of BLU-eight zero eight as well as the impact of wild type KIT inhibition, in a variety of allergic and inflammatory disorders and really see this as a pipeline and a pill potential that could have very broad impact. So across those three therapies, those are really our our, you know, most important priorities as a company where we're focusing the majority of our time, our effort, and our resources. The company is in a very, strong financial position.

Operating cash burn has been, continuing to rapidly decline, on the back of a growing top line revenue line as well as really disciplined focused investment, against our our top priorities.

Ami Fadia, Senior Biotech Analyst, Needham: Okay. Well, thank you for that. Maybe if I could just kick us off with a question that we've been getting, given tariffs is front and center for everyone this week. You know, as you sort of, think about your business, particularly with Advocate, maybe if you can share with us where, the API and manufacturing is based off of and maybe where IP is based. That's a common question we've been getting.

Yep. And, you know, as you think about kind of the changing world, how is Blueprint thinking about managing through it?

Christy Rossi, Chief Operating Officer, Blueprint Medicines: Yes. So maybe I'll I'll start big picture, and I can address the specific questions you just asked. So, you know, at Blueprint, I we are in a a fortunate position, in that we do have a very stable, healthy financial profile with a growing revenue line. And we are in a place where if I I think about the priorities we just outlined, what are most important things we're trying to accomplish this year, We believe those things are are largely within our our ability to influence and control. So for example, we don't have complex regulatory filings, where we're waiting for FDA feedback, etcetera, and we certainly feel like we have financial resources that enable us to prosecute, again, the the priorities that are gonna really move the business forward.

Our IP for AYVAKIT is is domiciled in The US. We have a supply chain that, you know, like many companies, has pieces in in different geographies, largely, The US, Europe, and and Canada. But, again, in a fortunate position in that AYVAKIT is a small molecule. Our COGS are very low. And so, you know, based on what we currently understand in terms of the landscape with tariffs, etcetera, while while that will have an impact, it's not significant for us, from a a financial perspective.

Obviously, something we're continuing to to keep eyes on, as we go forward.

Ami Fadia, Senior Biotech Analyst, Needham: Okay. Great. And, just with regards to, the FDA side of things, you know, you guys don't have anything in front of the FDA at the moment. But, you know, would you like to comment on kind of how is the industry thinking about this changing landscape and, you know, do we know enough to really sort of prepare ourselves to, adjust, you know, how we think about the regulatory process?

Christy Rossi, Chief Operating Officer, Blueprint Medicines: What I would say is, having a, you know, stable, functional regulatory environment is, I think, really essential for bringing innovation to to patients, in The US as well as outside The US. And so, you know, while we don't, again, have complex regulatory filings sitting in front of the agency right now, of course, you know, having that regulatory framework with which to operate in is is important certainly to our business over the long term as as it is, I think, for the rest of biopharma. So, certainly, you know, keeping a close eye on how things evolve and and look forward to to seeing how that, continues to evolve. And, hopefully, we will be in a place where we have, you know, that stable, environment that we can operate within, which I think is really important to to all of us.

Ami Fadia, Senior Biotech Analyst, Needham: Yes. Indeed. Okay. Let's talk about, Avocat. Maybe if you can sort of, you know, you mentioned the guidance for the year.

Maybe if you can kind of remind us of what drove the growth in 2024? How is that going to evolve or change in 2025? And as we think about your guidance, what are some of the puts and takes within the guidance range?

Christy Rossi, Chief Operating Officer, Blueprint Medicines: Yes. Great question. So, you know, maybe maybe just to start, with why is systemic mastocytosis such a large and, you know, frankly, attractive commercial opportunity. You know, the the market itself is is growing. It's a significant patient population with a high medical need, and it's a growing, growing population of patients both in terms of diagnosed patients as well as now our understanding of the true prevalence.

So the market is is larger. You know, we believe that the prevalence in The US is something on the order of sixty to sixty five thousand patients based on our updated view of the epidemiology of the disease. And we've continued to see diagnosed patients growing, at double digit rates, which, again, is something you would hope to see, with a rare disease where we finally have effective treatment, available for patients. And our understanding of the disease, our ability to diagnose, the technology has obviously evolved quite rapidly over the last several years. So what when I think about what will catalyze our growth over the longer term to, you know, the 2,000,000,000 by 2030 towards potentially a 4,000,000,000, peak opportunity for the for the franchise, you know, the the pieces that really drive that long term growth are continuing to penetrate this opportunity and have more and more patients being treated for their their SM.

So, what drives that is continuing to drive breadth and depth of, prescribing. So having, physicians, you know, treat their first patient, have that positive first experience, and then continue to find more patients to treat, having physicians have a widening lens on who they want to treat, right, who who is an appropriate AYVAKIT patient, and then keeping those patients on therapy. And, you know, it's really kind of that basic. That is what really drives the opportunity over the long term. And we've seen, you know, really consistent positive trends on those on those dimensions where, you know, we're seeing more and more physicians gaining experience.

We're seeing growing breadth and depth, enabling more patients to be treated. We see very strong trends in terms of duration of treatment, very high patient compliance. So when patients start on AYVAKIT, they are doing really well, and they're staying on therapy. And so those are those are the things that kind of drive that long term long term view, and we're obviously a big driver of our performance last year and continue to underlie, our guidance assumptions when we think about this year where, you know, the assumption is that we'll have, any, you know, growing new patient starts to the year, continued strong trends on duration, etcetera. Then there's other dynamics that are also really important to revenue, and can, you know, impact, certainly on a quarter to quarter basis.

One dynamic last year that was really important for us was the evolution of our free to commercial mix. So we saw, you know, favorable trends there through the year, which is a really positive thing for the business, largely because we were able to have more of our Medicare patients treated on reimbursed therapy, through the year due to some of the changes, with the IRA in terms of the Medicare Part D, benefit design, which enabled more patients to access paid therapy, which was which was really positive. We don't that that dynamic in terms of evolution, we don't expect to see, you know, a lot of continued evolution there this year. I think we're in a, you know, the right kind of general ballpark. We may see fluctuations in free commercial, which again can have impact, you know, on a quarter to quarter revenue basis.

But overall, the business is in a really positive place, in terms of that free commercial commercial mix. And then we look at other dynamics as we think about quarterly revenue, like, you know, compliance, international growth as markets are coming online, etcetera. So it's a lot of those same dynamics that informs how we think about guidance this year. We we certainly incorporated some of the longer term factors that are driving growth of the brand as well as some of these other factors that may impact quarter to quarter, and making sure that we were accounting for those dynamics as we set the

Ami Fadia, Senior Biotech Analyst, Needham: guide. Okay. Maybe a follow-up question on some of your comments around, you know, how do you the the parts to achieving the 2,000,000,000 Yeah. In in revenue. Obviously, the overall market is growing.

The diagnosed patients are growing. Right. And and, of course, you know, you're focused on continuing to kind of penetrate more and more physicians and kind of patients within that. I guess there is sort of, maybe just trying to understand kind of this the range of severity of patients and, you know, the different types of practices around there. Like, by how much do you need to really increase your penetration within the market to be able to get there?

Or do you think just the, you know, overall growth of the market is gonna drive the majority of that? How do you kind of think about those two drivers?

Christy Rossi, Chief Operating Officer, Blueprint Medicines: Yeah. It's a great it's a great question. You know, we have we have said, you know, as a kind of way of contextualizing, the 2,000,000,000 by 2030 that, you know, being at about 6,000 patients on therapy in The US, assuming some ex US contribution would get you to a $2,000,000,000 run rate roughly, and that that is, you know, a fraction of the patients who are diagnosed today. And to your point, we would expect diagnosis rates to continue to to grow. So, you know, we expect both things to happen.

We we think there's a lot of headroom to grow penetration, certainly from where we are now, but the market is growing underneath. So, actually, you know, to the question, you need to continue to increase patients treated just to tread water from a penetration perspective on the on the back of a growing market. I would expect both of these things to to contribute. I think a key message here is that, you know, we don't need to see the majority patients on therapy in order to reach, these these numbers that we're talking about. You know, we expect symptom treatment to still be, you know, the dominant sort of competition for AYVAKID, for the foreseeable future where really what we're doing is catalyzing a change in treatment paradigm where we expect more and more patients to be treated with, a therapy that targets the driver of the disease versus just being on symptom directed therapy.

And and driving that change in, treatment paradigm is gonna be the work that we're focused on, you know, over the next several years. The last thing I'll say is that, you know, this this idea of severity, I think, is one that continues to evolve. So, certainly, we historically had talked about uncontrolled patients or moderate to severe patients, and that's still a paradigm that I think a lot of people think about in in ISM and can be very much based on symptom severity in a patient and how much their day to day life is being impacted by their by their symptoms. Obviously, a view on that continues to change as as, you know, there's a better understanding of the alternative that could be available to these patients with with treatment on AYVAKIT. And we also know that there's there's other health impacts from living with systemic mastocytosis that go beyond how a patient may feel day to day.

Certainly, the bone data that we presented, for AYVAKIT acquired AI was really meaningful because I think it demonstrates the impact that targeting the driver of the disease can have, not just on how patient feels in the day, but over some of those longer term health consequences that can really be quite scary and and very severe, in this patient population, particularly in younger patients.

Ami Fadia, Senior Biotech Analyst, Needham: Yeah. That makes sense. You know, you mentioned, obviously, sort of, you know, diagnosis seems to be a very big part of, the shifts that we're seeing in the in the in the market. Yeah. Maybe can you talk about kind of what's evolving with regards to how patients are being diagnosed?

And how are you guys at Blueprint thinking about addressing that or, you know, sort of channeling resources towards sort of helping that trend move forward? And, you know, from a resourcing perspective, do you think you you still are at kind of where you need? Because, you know, the market's expanded a lot more compared to where it was at when we were thinking about the launch of I I ISM, you know, just a couple years ago. So Yeah. Maybe kind of address that as well as part of that.

Christy Rossi, Chief Operating Officer, Blueprint Medicines: Yeah. You know, certainly, driving disease awareness and diagnosis has been a priority for the company for years. You know, we are not new to to SM. We've been working with the community for more than ten years. Well well well more than that and have been really working on catalyzing disease awareness and diagnosis as as part of that effort, because it's important.

Right? We think it's really important for patients. These patients suffer from, you know, often these odysseys of bouncing around for years without knowing what's behind their symptoms. And so we wanna continue to to support that. To your point, I mean, we have a very large, you know, pool of diagnosed patients that we can penetrate, commercially.

And so when I think about, you know, the day to day efforts of our commercial team, it is very much focused there, on helping to, address the treatment approach for patients who are diagnosed. But as a company, we wanna continue to to support diagnosis and make it easier, frankly. You know, the advent of molecular testing and and blood based testing has been really important, in terms of evolving how these patients are diagnosed. Certainly having blood based KIT d eight sixteen v tests available has been an incredibly important lever. You know, the community, I think, is starting to understand more about some of the other markers of disease and how to interpret them.

For example, that tryptase may not be the most reliable marker to identify an ISM patient where many of these patients have, tryptase that may be, you know, close to normal. So, you know, we're certainly continuing to focus on that. Blood based testing and high sensitivity test testing is not and we know that we miss patients today. Right? We know that many ISM patients may not be picked up even by a digital droplet, p s PCR test on blood.

And so, one of our priorities is continuing to work on an even, higher sensitive, ultrasensitive test, that we hope to have, you know, in the commercial domain, you know, going forward and think that could be an important tool, again, just to make this process easier and certainly easier for the physicians that are seeing the majority of these patients, which is not hematologists. Right? Most of these patients are not being treated in academic centers by hematologists. Most of these patients are sitting in the community. They're being treated by allergists.

They're being seen by derms. And so, making this process easier for those specialties is what I think will ultimately really unlock, that broader commercial opportunity. Are you on mute, Amy, maybe? Sorry.

Ami Fadia, Senior Biotech Analyst, Needham: Thanks, Cassie, for letting me know.

Christy Rossi, Chief Operating Officer, Blueprint Medicines: I'm sorry. We can't actually see you with our setup. Ami, so I'm talking I'm talking

Ami Fadia, Senior Biotech Analyst, Needham: to a blue screen. Oh, Alright. That's good to know. Yeah.

Christy Rossi, Chief Operating Officer, Blueprint Medicines: So I don't if you were talking, we didn't hear we didn't hear in the last bit.

Ami Fadia, Senior Biotech Analyst, Needham: Okay. Alright. We I'll repeat the question. So a common question that we get is the overlap between the MCAS patient population and the SM patient population. Yes.

And, you know, sort of, some of the SM patients may be getting misdiagnosed currently as MCAS. So if you can sort of help quantify that and help talk about kind of what's happening with regards to, you know, kind of how these patients are getting diagnosed.

Christy Rossi, Chief Operating Officer, Blueprint Medicines: Sure. I'll start it. I don't know if you wanna chime in on this, Bhuwad. So, you know, MCAS is a really interesting, population for us at the. We think it fits with our portfolio in a pretty unique way.

You know? And there's two pieces to this. Right? So one is that within the broader population of patients complaining of of mast cell, symptoms, we believe, and there's a lot of evidence, that there are ISM patients there. Right?

So that is, you know, part of our interest in characterizing MCAS is to better, find those patients who may be suffering from from ISM. And I think, you know, we're we're increasingly having tools available to us that will enable us to do that. And then the second piece of it is that nonmutated patients, are still suffering from a number of, pretty debilitating symptoms, and we think, that could be a place where a wild type KIT inhibitor may play a role.

Fod Namoei, President of R&D, Blueprint Medicines: As in in terms of symptoms, Amy, it's some there's a big overlap including symptoms between in terms of symptoms between, ISM and MCAS. Skin symptoms look more like hives than the SM, skin, symptoms, GI symptoms, like diarrhea, neurocognitive symptoms like brain fog. So there's a lot of overlap. And actually importantly, these patients with MGAS, they have many anaphylactic reactions that are unprovoked without most of the time specific trigger for the anaphylactic reaction. So it's a really very bothersome disease.

We believe that probably given exploratory work done by the the the the researchers in Spain, namely doctor Alberto Orfao, that the percent of within the MCAS within patients with MCAS symptoms probably somewhere around twenty percent of them could be actually bonafide SM patients with the D816V mutation, but it was not detected just given the lack of sensitivity of the testing that we use. And this is going to work. I think it's I'm impressed now. So it it is a disease that we are interested in outside of those who should be treated with available therapies when they have a d a sixteen mutation, but the other really should would would definitely benefit from a wild type kit approach, I know we're we'll talk later about wild type kits.

Ami Fadia, Senior Biotech Analyst, Needham: Got it. Yes. That's helpful. I just wanna talk about the European launch of AYVAKIT as well. You know, you've sort of indicated that it's a certain percentage of kind of The US sales currently, and that's kind of how you see it Mhmm.

Even at peak. You know, for for as as we sort of think about the ramp in Europe, should know, is there some kind of detail you can provide around how we should think about the adoption curve as you launch in additional European countries, and maybe any comments around pricing as well?

Christy Rossi, Chief Operating Officer, Blueprint Medicines: Sure. So we have talked about, you know, a percent of revenue just because there's as you well know, right, there's there's a lot of complexity underneath the international business, a lot of it, you know, individual markets, each with their own their own dynamics. And so, you know, thinking about it as on a contribution level, I think, can be helpful just in terms of how to how to model. And, you know, our expectation is we hope to see it growing over time as even as a percent of our business, but always with The US as kind of the dominant driver. And so, you know, that is still the expectation.

So this year, Europe will also be growing. As The US grows, we expect it to, you know, kind of stay in that same range from an overall top line perspective. Right? So somewhere in that 10 to 15%, contribution range. So growing in step, basically, as The US grows.

Obviously, underneath that, what you see in Europe is it's a larger patient population, so more more more patients kind of, suffering from SM there, but with with pricing dynamics that are that are obviously different than than The US. You know, what we have said is that we expect some additional markets to come on online this year from a pricing and reimbursement, perspective. We, are launched in Germany in ISM. You know, we had, we've we've sort of completed the pricing negotiation process there. Germany is the one market where your your negotiated price is public.

And so, you know, I think that was published in in February, and provides a nice benchmark as we embark on negotiations in other in other countries where, you know, pricing is confidential. You're always gonna see prices at a at a variety of of, you know, levels. Usually, Germany is is a high watermark for for Europe, but we'll continue to work work through that and, you know, certainly have a lot of the same, you know, positive dynamics that have helped us to date, which is, you know, we've got a very robust dataset in PIONEER, showing very robust impacts across, you know, not only symptoms and objective measures, but also quality of life. It's placebo controlled. You're still dealing with, you know, kind of a rare orphan orphan disease, and so all of those all of those factors, you know, continue to be positive.

The last thing I'll say is that, you know, we're continuing to look at other opportunities to expand our global footprint. You know, the SM opportunity is more concentrated in, kind of US, Europe, you know, LatAm, Canada, Australia, those markets. Diagnosis has been lagging in Asia, although we think the the opportunity could be there with market development. And so, you know, we continue to look at opportunities for geo expansion. But we're we're very mindful of, you know, where we have our own resources versus where we we've used partnerships through distributors to kind of access opportunities based on based on how, you know, significant they are and what the level of investment would be.

Ami Fadia, Senior Biotech Analyst, Needham: Mhmm. Okay. Let's talk about elenestinib, which is, you know, core to your life cycle management strategy for the franchise. And, you know, you've you've shared with us that in the HARBOR study, you're evaluating, several other endpoints which hadn't been prospectively studied, in in the PIONEER study, such as bone health and and FLACS frequency and chronic inflammation, etcetera. Based on the real world experience with AYVAKIT, can you share with us your level of confidence that, you know, we are seeing clinically meaningful impact on those types of outcomes?

And, you know, and we will see something similar with that.

Fod Namoei, President of R&D, Blueprint Medicines: Yes, Ami. We so we we reported actually recently at a retrospective analysis of a smaller group of patients from PIONEER part two where we demonstrated retrospectively that avapritinib improved the the bone health in the in this subgroup of pioneer part two. So avapritinib works actually on on on bone health by improving it. This is the feedback and the experience we are having from the real world evidence and practicing physicians. In fact, it is something that people are interested in because almost, you know, half of the population of ISM patients can present bone health issues, osteopenia, osteoporosis.

And it's not a rare thing in patients with ISM to have fractures, spontaneous fractures at a very young age. So it is really an important topic. And the way we are doing it, with elenestinib is very innovative. We are looking prospectively to it. We're looking at it at a key endpoint in in in the study and assuming success, we believe this will impact the labeling of, elenestinib, in the future.

Ami Fadia, Senior Biotech Analyst, Needham: I wanna go back to your longer term guidance for the franchise of 4,000,000,000. And, obviously, elenestinib is sort of a not only a life cycle management strategy, but also the trial design is positioned to sort of drive kind of some of the other clinical benefits, home. How important is it for elenestinib to be able to demonstrate differentiation on some of these additional endpoints or what one or more of these additional endpoints that you're studying to be able to tap in you know, to get to that 4,000,000,000 peak revenue potential?

Christy Rossi, Chief Operating Officer, Blueprint Medicines: I if I think about, you know, continuing to grow the SM opportunity from a life cycle perspective, you know, we're starting with a a frame that AYVAKIT is a really good drug that has a growing experience base behind it. Right? So, fast forwarding towards the end of this decade into the twenty thirties, you're going to be dealing with a therapy that has, you know, very significant amount of long term efficacy and safety data, you know, a growing amount of commercial experience. And if you, you know, are trying to kind of launch into that environment and grow, continue to grow, and if you think, you know, particularly in a world where you may have generic avapritinib on the market at some point down the road, differentiations can be really important. Right?

And and so, you know, that has always been our view. And I think as we started to really understand the profile of AYVAKIT, we had the PIONEER data in hand, You know, we were very, very thoughtful and intentional around our strategy for elanesinib for that reason. The idea that you would just sort of redo PIONEER and, try to make arguments based on, you know, kind of point changes here or there. Just we we don't believe that's that's gonna cut it, frankly, over the long term. And so, you know, having this trial design where we're really looking at, you know, generating a dataset that is speaks to where the puck is going, you know, where, where where the disease understanding is going, the kinds of evidence that people wanna sort of understand around the longer impact longer term impact of of SM on on patients, we think is really important.

Now, you know, we just mentioned that we have some interesting bone data for avapritinib. So these are things that we could, you know, potentially explore, certainly with AYVAKIT as well. But we think elenestinib provides a really important vehicle with that view towards continuing to to drive long term growth of our franchise into the next decade and and beyond.

Ami Fadia, Senior Biotech Analyst, Needham: Yep. That makes sense. I'd like to shift gears to Blue eight zero eight, which is obviously, you know, another key focus area for investors. Maybe if you can just maybe start by talking about the indications that you've selected to take into the clinic this year and, why you chose to prioritize those particular indications?

Fod Namoei, President of R&D, Blueprint Medicines: Yeah. Great question, Amy. I think if you look at 8808, I would look at it with a bigger picture of what's happening across the class in terms of exploring why type kit as a target. I think very, very good work was done by the antibodies earlier than, eight eight eight zero eight start and really gave a very clear indication of the potential in terms of proof of concept, of targeting wild type kit in, chronic urticaria spontaneous and cold induced urticaria. So that that that's an important first milestone for the for targeting wild type gait.

We try to go to diseases where the biology are not derisked and not a lot of people are trying to derisk because we believe that the mast cell is mast cell is actually a major, if not the key player in these type two inflammation disorders. So for example, allergic asthma, increasing amount of evidence showing that, mast cell play major role more than eosinophils and more than basophils and what we call allergic asthma. So that's an important one we are exploring from a POC perspective. Similarly, allergic rhinitis, allergic conjunctivitis, I talked about chronic urticaria, and we earlier talked about MCAS or mast cell activation syndrome. I think we would like for these diseases outside of urticaria where we are doing the phase two, but we would like for the others really to derisk the biology, understand whether or not eight zero eight can show some good clinical data in these patients.

This will allow us in in the next couple of years to really prioritize what is our development or what are our development priorities and and and and strategy when we are ready to go to the regulatory part of for registrational part of the work.

Ami Fadia, Senior Biotech Analyst, Needham: Yeah. That makes sense. Now the studies that you're, you know, kind of launching or kind of already, initiated, Some of them are open label, whereas the others are, more of sort of competitive studies. Can you talk about how collectively, that's gonna help inform, which indications as well as what doses you're gonna use. I think that's kind of, a common question that we give investors to really sort of figure out, like, how is the data how are the data readouts that are gonna come at the back of those studies gonna inform us as an investment community?

Fod Namoei, President of R&D, Blueprint Medicines: Yeah. I think the, one of the major advantages of, Blueprint Medicine running these multiple POCs in different studies is really to not allow us to, on one hand, obviously, derisk the biology, as I mentioned earlier, but on the other hand is to be able to test different doses and schedules, with, eight eight zero eight and then collect the totality of the data. And by the time we get into the regulatory or the registrational work, then we will feel more confident about, you know, the the dose and the schedule that we are taking to registrational work. I, in the past, talked about, you know, we are looking at single continuous doses. We are looking at, titration to effect dosing, which is important.

I mean, outside of developing drugs for cancer, this is really completely different universe from what what people have been doing and what people do in developing drugs for cancer. We're also thinking about starting at a high dose and very quickly continuing or maintaining with with much, much lower dose over time. And I must also add here, our experience with avapritinib, although different disease and different approach, but really we learned a lot from finding the right dose. And we actually can see today, you know, avapoprenib twenty five milligram. It's really impact on patients every day as it really it is a dose that people are very comfortable with and and and happy with it some its activity.

Ami Fadia, Senior Biotech Analyst, Needham: Mhmm. My next question is really and and I think we're almost running out of time. So, I I do wanna get to this, question, which is how do you define what is enough of a proof of concept before it can support a registrational trial. Does it have to be compared to, you know, the current standard of care? How much of duration of treatment you need?

Maybe kind of put some guardrails around that for us.

Fod Namoei, President of R&D, Blueprint Medicines: Yeah. I think, I mean, it's it's it's very early. Proof of concepts are not bona fide, regulatory oriented phase two b's. Like, there's not very big phase two b's that you repeat in a phase three in the the nononcology type of development. It is really a number of studies where we'll be look looking at clinical markers.

Some of them are the endpoints you will be using later in registrational studies, and others are surrogate endpoints you look at to translate into key endpoints for regulatory purposes. I think we would look at the effect that we see on patients or in patients within these studies. And sometimes we'll be really comparing to placebo and sometimes we'll be seeing also this in the totality of the evidence in a given disease, what other drugs are doing and where we think we are. So, I mean, I I know it's not really, know, black and white type of answer, but I I think the totality of the data will really allow us to understand whether or not we have biologically reached a level that makes us confident to go into the registrational work.

Ami Fadia, Senior Biotech Analyst, Needham: Mhmm. Maybe maybe a last question from me. You know, you've kind of identified a couple of indications for your studying, you know, chronic spontaneous urticaria, idiopathic urticaria, allergic rhinitis, and, allergic conjunctivitis. Maybe from a timing perspective, give us a sense of when we might get to proof of concept for one or more of these.

Fod Namoei, President of R&D, Blueprint Medicines: Great question. I mean, as you mentioned earlier, some some studies are open label and others are, blind studies. So I think for the open label studies, it could be as early as late this year. I mean, obviously, depending on when we don't have specific timeline because the study needs to start recruiting patients and move forward and so on. So that's why I'm I don't have specific timelines.

The majority of the other non open label studies will probably read to sometime next year. I think, Amy, the closer we get in the more information we get about the study conduct, the recruitment, how we're progressing, the better we'll be able to really give more guidance on the timing later, in the year.

Ami Fadia, Senior Biotech Analyst, Needham: Yeah. That makes a lot of sense. Okay. Maybe if I can just squeeze in one last question around kind of your protein degrader platform, actually. Maybe just in a snapshot, tell us what gets you excited about that platform.

Fod Namoei, President of R&D, Blueprint Medicines: Targeted protein degrade targeted protein degradation is is really a platform that has evolved over the years. When we talk about degraders, I mean, they existed, I mean, for a long period of time. It's a point five mechanism of action. That's your image out of degraders and, you know, the similar for the estrogen receptor. Where we've taken degraders with the technologies we have today is to create a heterobifunctional degrader or sometimes glues, being able to match complex things that they would not match otherwise randomly.

And the idea of degrading a target is always when we cannot inhibit the target or there is not a good way to do it. We are very excited about it. We started in the cyclin dependent kinase universe. Actually, have proven we have not published this data yet, but we have proven that, for example, CDK two degradation seems to be better approached than CDK two inhibition from our nonclinical work so far. Obviously, we said we have a CDK four degrader that will reach the development candidate level this year.

But importantly, this platform also is being directed toward this NI targets, and we will have the opportunity in future to talk about, you know, what do we think of the role that our degradation platform will play in the I n a space.

Ami Fadia, Senior Biotech Analyst, Needham: Well, lot of exciting stuff coming up on the horizon for sure, but, I think we have to close here. Thank you so much for your time, and I appreciate all the investors joining as well.

Fod Namoei, President of R&D, Blueprint Medicines: Thank you, Amy.

Ami Fadia, Senior Biotech Analyst, Needham: Thank you.

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