Q4 2023 Blueprint Medicines Corp Earnings Call

Participants

Jenna Cohen; Senior Director & Head of IR; Blueprint Medicines Corporation

Kathryn Haviland; President, CEO & Director; Blueprint Medicines Corporation

Philina Lee; Chief Commercial Officer; Blueprint Medicines Corporation

Christina Rossi; COO; Blueprint Medicines Corporation

Michael Landsittel; CFO; Blueprint Medicines Corporation

Becker Hewes; Chief Medical Officer; Blueprint Medicines Corporation

Brad Canino; Analyst; Stifel, Nicolaus & Company

Salveen Richter; Analyst; Goldman Sachs Group, Inc.

Marc Frahm; Analyst; TD Cowen

Reni Benjamin; Analyst; JMP Securities LLC

Mich Schmidt; Analyst; Guggenheim Securities, LLC

Derek Archila; Analyst; Wells Fargo Securities

Laura Prendergast; Analyst; Raymond James

Matth Biegler; Analyst; Oppenheimer & Co. Inc.

Ami Fadia; Analyst; Needham & Company, LLC

Peter Lawson; Analyst; Barclays Bank PLC

Presentation

Operator

I may Sure. Our of this. Okay. Okay. In. Good morning. My name is Jean. I'll be your conference operator today. At this time, I would like to welcome everyone to the Blueprint Medicines Fourth Quarter and Full Year 2023 financial results conference call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question and answer session. You would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star followed by the number two. Please plan to limit your questions to one. Thank you. Janet Cohen, you may begin your conference. Pedro, and

Jenna Cohen

Good morning, everyone. Welcome to Blueprint Medicines Fourth Quarter and Full Year 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 slides that will be reviewing today by going to the Investors section of our website at w. w. w. dot Blueprint Medicines.com. Joining me today are Kate have Lind Chief Executive Officer for Lina Li, Chief Commercial Officer, who are generally President, Research and Development, and Mike Lambert, our Chief Financial Officer, Christy Rossi, Chief Operating Officer, and Baker Hughes, 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 may cause our actual results to differ materially, including those described in our reports filed with the SEC through are cautioned not to place any undue reliance on these forward-looking statements and blueprint disclaims any obligation to update such statements. With that, I'll now hand the call over to Kate.

Kathryn Haviland

Thank you, Jennifer, and good morning, everyone. 2023 with a pivotal year for Blueprint Medicines as we successfully brought forward advocate to become the first and only approved medicine for patients with indolent systemic mastocytosis, or I have them as we enter 2024 AYVAKIT, it will continue to be the foundation of our thriving business with our early launch momentum, putting advocate firmly on the path to becoming a multibillion-dollar product. Our growing revenue also enabled us to invest in additional compelling opportunities in our pipeline to drive longer-term growth and deliver even more transformational medicines in the future. To achieve our goals this year, we're focusing on three key aspects of the business. Let's start with either kit blockbuster potential and its ability to drive durable revenue growth for Blueprint well into the next decade.
We know that the first three quarters of launch are critical in designing the sales trajectory for product. And we have driven a very strong first six months results and revised them launch, establishing the foundation for future growth. We've clearly demonstrated our ability to reach patients and drive revenue, achieving $204 million in global AYVAKIT revenue in 2023 and 84% increase over 2022.
This compelling growth was primarily driven by the uptake into bone in patients with IFM who comprise about 95% of all patients with us a sizable rare disease patient population that we estimate of 70,000 prevalent patients in the US and Europe alone.
Today, we are pleased to provide 2020 for AYVAKITrevenue guidance of $360 million to $390 million, putting us on pace to nearly double our sales this year. This revenue trajectory is very similar to other notable rare disease product launches such as Solaris and Jacobi perfect medicine approved to address significant unmet medical need and building a new multibillion-dollar market. The similar attributes. And importantly, similar sales trajectory is why we believe the launch of the AYVAKIT in FM is one of the most exciting rare disease launches happening across the industry today.
And we are just now scratching the surface in 2024 our primary focus is on reaching more patients with us and the U.S. and also now in Europe with our EMA approval in, I assume this past December, Kip compelling efficacy and safety profile, coupled with the chronic nature of IS. then mean that both new patient starts and the cumulative effect of patients staying on therapy for longer durations are important drivers of revenue this year and beyond. So we can do it over to Selina next on the call, it should go into more detail on EBIT performance in Q4 and why we expect our strong and steady growth to continue as we drive towards peak sales of greater than $2 billion.
And yes, we are now placing you all to a peak opportunity for advocate that is greater than $2 billion for the past 12 to 18 months since before FDA approval and ISM., we have been citing a piece opportunity for a decadedecade of greater than $1.5 billion. Now based on the strong underlying fundamentals that are driving our early sales trajectory and the rapid growth in diagnosis that has led to an expanding SME market, our conviction have grown. The EBIT will be able to achieve peak global sales of greater than $2 billion.
Now let's turn to our second area of focus, advancing our portfolio targeting allergic inflammatory diseases where mast cells play a central role. Last month, I shared how we're focusing our investments in our most exciting research and development programs with opportunity to address high unmet medical needs in large patient populations. And importantly, in therapeutic areas that play to our strengths by leveraging our expertise in our infrastructure. A primary area of focus for us here is to advance our portfolio of approved and investigational programs targeting that cell mediated diseases. Blueprint is uniquely positioned to drive novel science in this space. Competitive, our scientific leadership and targeting kit and our proprietary insights into muscle biology, an important area of science that has been historically under appreciated.
With a decade and L&S nib, we are fully covered and Nestle disease is driven by mutated kit. And this year, we are expanding into a much larger opportunities driven by wild type kit. We believe eight oh eight. We are particularly excited about the potential for blew it away to impact fundamental biology and a number of large diseases with significant metal medical need starting the chronic urticaria.
We believe this program will move quickly with a higher than typical probability of success at this stage. Given our track record of translating our discovery expertise and targeting kit into clinical impact in our commercial success. Next week, we will have a huge presence at the American Academy of Allergy, Asthma and Immunology meetings, often quite a high, which is the largest allergy and immunology conference in the U.S. and taking place in Washington DC. This year later on the call for will go into more depth on what we will be showcasing a Quad AI as well as provide an update on our development stage portfolio. The third area of focus for us is maintaining a strong and durable financial position. Cash management will continue to be a priority priority area for us to focus on into 2024.
And as we sit here today, we see a clear path to profitability through the combination of strong revenue ramp and disciplined operating expenses, which will result in significant decrease in operating cash burn in 2024 and beyond. Mike will talk more about our financial results and our approach to balancing disciplined capital allocation and investing at the same time in our compelling near and long-term growth opportunities. Business development will also continue to be core to how we build and optimize our business in a sustainable way to that. And I'm very pleased to say that we have made significant progress on a deal that will enable Gabilondo to continue to be commercially available to patients in the U.S. while minimizing the financial impact of Blueprint.
We look forward to updating you in the near future. Once that deal is finalized. Now I'll hand it over to Selina could go into more detail on our commercial performance with.

Philina Lee

Thanks, Kate. Fabricate achieved $204.2 million in net product revenues in 2023, representing 84% revenue growth over last year. Fourth-quarter revenues grew 30% quarter on quarter to quarter on quarter to $71 million was $63.6 million in the US growth was driven by several key factors. New patient starts, a decline in our share of free goods, low discontinuation rates and high compliance I assume is the clear growth driver with the majority of new starts and for 25 mid-dose starting with patients on therapy, we hit a major milestone in January with approximately 1,000 patients on EVA kit in the US.
We were looking to see if this would come in December or January, and we're encouraged by the strong demand we see coming into Q1. We're thrilled to hit the thousand patient milestone this early in the launch, and we're focused on driving continued growth today. We're setting revenue guidance that reflects the strong and steady, the continued growth we expect in 2024 as we get closer to realizing the kids blockbuster potential. Our guidance range of $360 million to $390 million assumes another year of more than 80% year-over-year revenue growth at the midpoint, we have good insight into the fundamentals driving our revenue, namely new patient starts, compliance, duration, free goods and our international performance. This range reflects the inherent variability in those fundamentals.
With guidance now in place, we're going to move away from providing a quarterly patients on therapy number. We will continue to share commentary on how the launch is progressing. Looking next persistent, we expected strong persistency, NISM. based on advocates, clinical profile and the chronic nature of the disease. And even though it's early days, all signs point to extended durations of therapy with low discontinuation rates and high compliance launch to date, we've been a surprise upside is how quickly these moves the needle on our free goods share dropping to approximately 25% as we grow the number of ISM. patients on therapy, we have just reported our second strong quarter of revenue from our ISM. launch.
Let me tell you why we expect to sustain this growth in 2024 and beyond. Our commercial strategy is grounded in strong, continued execution across multiple paths that will drive sustained growth in this market. First, ramping up our direct-to-patient marketing to further drive awareness and activate patients to seek treatment. The SIM market is growing and we've only captured a small fraction of it so far today, there are more than 20,000 diagnosed patients from the U.S. alone and about half are not well controlled on symptom directed therapies. We know this is a chronic market where patient preference is sticky. Once patients start advocate that positive clinical experience. Second, we're expanding EVA kits, prescriber base across all specialties and settings, and we're nowhere near saturation. We are seeing strong receptivity to advocates profile among both Humax and allergists in the academic and community settings.
Breadth of prescribing is happening exactly where we want as we're motivating more allergists to prescribe advocate, and we're adding more prescribers at the top of the concentration curve. You can see this in the chart on the left, which shows early, the kid adoption among the top 407 providers who see about 43 hundred unique SM patients. We continue to grow the breadth of prescribing here in light green. And we're also beginning to see depth of prescribing with providers who have already said two, three or more patients on therapy and darker green.
As we expected t he first positive experience is leading providers to recommend a ticket to the next patients who are coming in for their scheduled appointments. Breadth of prescribing is an important lead indicator for long-term growth. We are highly encouraged to see prescriber breadth and early signs of prescriber depth at this point in the launch over time, we expect to see the cumulative impact of growing this motivated prescriber base. Together with activating more patient, it's to seek what's possible with a bucket. That's why I'm so confident about our ability to both grow and capture this market. We understand the SM. market better than anyone else, what activate patients to move away from the symptom directed poly pharmacy there, habituated to and tried therapy designed to address the underlying driver of disease, what drives providers, urgency to treat what influences their prescribing behavior and how to ensure that access is seamless for patients and providers. We are making great headway to disrupt entrenched attitudes and behaviors about disease control and treatment and to drive patients and providers to take action with two quarters of strong performance and our guidance today, we are in the early innings of a pioneering rare disease launch. We are exactly where we thought we would be and we're delivering what we said we would deliver.
As we've seen from the launch trajectory of other rare disease blockbusters, we are right on track to capture a reach its peak opportunity of over $2 billion. With that, I'll hand it to flood to share what you can expect from Blueprint Medicines acquired.

Christina Rossi

I think some consumer more than 10 years of experience in systemic mastocytosis. We have built an extensive repository of knowledge to uncover some insights into SMDs. You biology, our patient journeys, the prescriber management of the disease spectrum from ISM. two ASM. of Blueprint Medicines. We are redefining how SIM is true across a broad network of academic leaders and prescribers with whom we are not only expanding the frontier of innovation in SM, but also in many other mass of driven disease. We do all presentations and seven posters blueprint. We need SIM science and medicine into 2024 quarter IR conference, the long-term efficacy and safety data from Pioneer. We continue to establish the records of the standard of care and the only available option to treat the root cause of systemic mastocytosis. Additional data will include has outcomes measures and a reduction in poly pharmacy. Turning now to our pipeline. The extension data we generated from Pioneer and from real-world evidence in SM, coupled with the regulatory experience we gained with a record development, are enabling us to build a robust differentiated development path for administering our next-gen migration DTA, 16 via YouTube inhibitor.
We did recently presented data showing administered to derive a clinically meaningful symptom improvement. Of course, those levels with a well-tolerated safety profile. We see a lot of potential with administrative as the core part of expanding our SAM franchise. Mast cells are well established key drivers for many allergic and inflammatory diseases where there is still a high medical need. However, variable as therapeutic targets for inflammation has often been under appreciated in our industry at Blueprint Medicines, we are building on our expertise in muscle biology to identify targets and develop therapies for a variety of massive driven inflammatory deduce.
Last month, we presented for the first time more detail on the preclinical profile of grew eight oh eight, a profile that met or exceeded all our key criteria. It is potent from one pocket, highly selective, and it has drug properties compatible with once daily oral administration. Next week, we will also share comparing in vivo activity of Blue eight weight in models of masks, vision and asthma that support our development strategy into these diseases. Mb&o. We are on track to submit an IND in the second quarter of this year, and then we will initiate the SAD MAD study.
Finally, on the solid tumor part of our pipeline, we are advancing our CDK2 inhibitor grew to two to one of the most exciting programs that we have. A clinical development due to the two is an important value driver for Blueprint Medicines and one that we are looking to move forward in the context of a partnership. Cdk2 is a clinically validated. So targets with the potential to impact a large patient population would have hormone positive HER2 negative breast cancer blue to do to have a very encouraging profile with a broad therapeutic window best in class selectivity. Our goal is to pursue it in combination with a proven CDK four, six medicines for lung breast cancer patient survival. We have had significant engagement on this program with the range of potential partners, and those conversations continue very productively. With that, I will turn the call over to Mike to review our financial updates.

Michael Landsittel

Thanks, shrug. Earlier this morning, we reported detailed financial results in our press release. For today's call. I'll touch on a few highlights. For the full year. Total revenues were $249.4 million, including $204.2 million in net product revenues from sales of Advocate and $45.2 million in collaboration and license revenues. Of these full year revenues, $71 billion of aggregate net product revenues were recorded in the fourth quarter. In 2024, we anticipate that we will achieve $360 million to $390 million and advocate net product revenues. We expect that the USXUSA. for kit revenue split in 2024 will be approximately consistent with what we observed in 2023 as we launch first in Germany before expanding to other countries. As pricing and reimbursement is negotiated.
Today's guidance illustrates, we are on the path to capturing advocates peak opportunity of $2 billion. This revenue growth, coupled with expense discipline and focused investment is what is accelerating our path to profitability. We do not anticipate any material collaboration revenue from existing collaborations in 2024. We are nearing a path forward for GAAP revenue in the U.S. and plan to provide for our existing agreement with Roche. We continue to expect that the wind down of the Roche collaboration forget Roberto, will result in significantly lower year over year operating expenses related to capital and will have no material impact to our overall expense plans in 2024.
Total costs and operating expenses continued to decline and were $735.7 million for the full year and $177.1 million for the fourth quarter. We anticipate our R & D expenses will continue to decline in 2024 as we wind down our early-stage EGFR clinical programs, partially offset by increased investments in our programs for mast cell mediated diseases. Specifically blue eight oh eight.
We expect only a small increase in SG&A expense as we gain operating leverage from our commercial infrastructure and continue to drive significant increases in revenues. Last month, keep shared our vision for maintaining financial strength that blueprint. We have a focused spending plan that allows for continued reduction in operating expenses while also investing in opportunities for longer-term growth. We prioritize capital allocation towards a portfolio of built around mast cell mediated diseases, solid tumors implicated by cycling dependent kinase biology and ongoing early research efforts as we believe these areas provide the best opportunity to drive long-term value.
Entering 2024. We are in an exceptionally strong and durable financial position with $767.2 million in cash. We are commercializing advocate globally, a first and best-in-class medicine that is growing revenues on the weight of blockbuster status. We expect our operating cash burn to further decline in 2024, even as we advance our portfolio of high potential medicines. Like blue, a rate, our Pathway to Profitability is becoming clear, solidifying our financial profile and our ability to generate long-term value. With that, I'll now turn the call back over to the operator for any questions. Operator?

Question and Answer Session

Operator

(Operator Instructions) Pratt Canada from Stifel. Your line is now open. Please go ahead.

Brad Canino

Good morning and congrats on the quarter. It would be great to hear a description of how the team reviewed its overall approach coming into guidance here and then what you believe this guide now represents about the opportunity. And then I've got a follow-up. Thank you.

Jenna Cohen

Thank you very much. Appreciate that. Christian will take the question on guidance.

Christina Rossi

Swire that at so as Kate said, and we now have two full quarters of experience and our about with either cat and those two quarters have sat on an incredibly strong foundation for the trajectory that we see for this product. We also have a sense now based on those two quarters of what some of the key drivers are of revenue performance and falling. I walked through those things like new patient starts, duration of therapy, which increasingly and a chronic market like this is becoming a variant Horton driver of revenue growth as we have a strong and growing base of patients on therapy and then factors like compliance and et cetera, free drive rates and said, we've understood those variables and we understand what reasonable ranges are around those variables that informs our guide, which, as you know, like other external milestones, et cetera, that we communicate were really putting out so that we can help everyone understand what we think is a reasonable expectation, fire for revenue that share.
And one important factor is that we are not even 12 months into this launch and sell one of the things that were understanding as we go through some of the quarter-on-quarter dynamics and how those things will play out. Absolutely. I talked about, for example, seasonality in Q4, and we know that Q1 is often a quarter that we know and many and pharma generally where you see the impacts around compliance, fresh, that, et cetera. So we're understanding how those factors will also plan as we think about the quarter on quarter ran through the year.
I think the important thing is the pullback is that at this guide represents more than 80% year on year growth, again for advocates. And it is very, very clear. If you look at the revenue trajectory that we are on, that we are very much marching down that road towards a $2 billion at our peak. And the trajectory is very much aligned with what we've seen with other compelling rare disease launches. And so we feel like we're in an incredibly strong place and very much demonstrating with each quarter. The opportunity that we've been saying is there an FM great system?

Brad Canino

And I want to ask on Slide 7, which was very helpful. Visualization of the proportion of practices were only one or two patients have started a record. But what are the key execution steps that got that disclosed minority of activated accounts to three to 10 patients? And how are you going to be replicate that in the remaining my majority that are at one to two. Thank you.

Philina Lee

Thank, but they're going to talk more about that dynamic. Yes. Thanks for the question, Brad. And we're really encouraged by early in the lines to see both strong signs of growing prescriber breadth across all specialties and setting. So Sumant AI. and an even split cross academic and community that Varian represents how well that real world experience with Advocate strong profile is playing out and the receptivity and you know, to the point of what's leading providers with their first experience to put on two or more patients. And it's really as simple as they start a kit and can see that positive benefit. It brings it to life in these providers of what's possible with patients. And that is leading to further repeat prescribing and deepening in these accounts. And would it from an executional standpoint, I would highlight the efforts of our team that are that have the greatest amount of promotional focus on the providers who are seeing the greatest number of SM patients, political spending from that targeting, as well as the strong relationships that our team has forged with these top volume prescribers on the ground.

Brad Canino

Thanks and congrats again.

Operator

Our next question today comes from Salveen Richter from Goldman Sachs.

Salveen Richter

Good morning and thanks for taking my question here to on the pipeline and for Blue two six three following positive data from Part one portion of the Phase two three trial of NISM., the next key event in the Part two trial, how will you demonstrate that differentiation of this asset relative to advocate that portion? And then separately, on the CDK. two program, we are going to see some data in the first half. Just walk us through your expectations, what you present and the benchmark here for success and differentiation versus the other CDK2 inhibitor.
Thank you. Yes. Thank you for the question, Salveen, and I'll hand it over to slide. But we look at our message has been a really core part of how we're going to maximize the long-term performance of our overall as and franchise. And as we said before, you're able to set a very, very high bar. So I'll hand over to Phil to talk about how we're going to have a going to be able to bring out.

Becker Hewes

We presented at ASH few weeks ago, very robust data on the activity in terms of improving food and investing in patients with indolent systemic mastocytosis. We also showed very good safety and tolerability profile. So the Phase two POC is various solid. There and we are and we continue to gain scientific information from Pioneer will show some of this upcoming quarter, i.e., meeting we have information from real-world evidence. We also gained a very robust experience from a regulatory perspective, not only in the United States, but also in Europe. And so all these items are being put together to really put together a differentiated strategy to develop understanding for what we believe ISM. patients will be in a few years from now, what would be where back in 2016, 2017? I think you will see this reflected in our development strategy as we start the registrational trials.
For the CDK. two question, I think we're happy that the study is continuing to dose escalation in the Phase one, mostly focused on the combination of we mentioned in my prepared notes notes on the combination with CDK4/6 citizens. And we will be presenting the early safety data from the combination of ribociclib and Bluetooth to all would be uncharacteristic and the profile of this combination together. The goal there is really to show that as we go to home and Paul positive HER2 negative breast cancer or the goal is to show that we can combine safely and that's safe combination will drive the efficacy in the short and long-term.
So stay tuned for data coming from the VALOR study.

Operator

Thank you. Our next question comes from Marc Frahm from TD. Cohen.

Marc Frahm

Yes, thanks for taking my questions and congrats on all the growth in the quarter. And maybe go into that slide of the patients per prescriber. Can maybe give a sense of what's the opportunity from the breast side rate of just deepening at those existing 400 treaters versus the depth of that, the data that. But then what sort of opportunity more expanding out to mine more prescribers and kind of relate to that guidance implies get the midpoint maybe like 125 hundred 150 patients per quarter kind of being added to the franchise versus the recent trends been more like 200. So I guess maybe you could square those.

Jenna Cohen

Thanks. Mark. I will hand over to Selina. I also just want to reiterate some of the question about the guidance that we are. We are six months into launch. We have not had an opportunity. You see a full year of higher than revenue and where you're continuing to get a sense of some of the seasonal dynamics. I mean, we're incredibly excited that the guidance puts us on that trendline for kind of comparable rare disease products that have just created a really compelling markets. But we do with us on the specifics yet.

Philina Lee

Hey, Mark. So to your question about sort of the opportunity that this represents. And when you look at the top 400 treaters by SM. patient volume, collectively, they're seeing about 4300 already diagnosed SM. patients today. And there is substantial headroom to grow both in breadth as well as debt just within the top 400. So when we look at the penetration, only about 20% of these top 400 have yet prescribed EVA kit, and we see this growing steadily and that sort of light like clean and improve on the top.
And you also see that substantial opportunity for for deepening. I mean, we sort of talked about how the first positive experience leads to repeat prescribing. And that's both recognition of the clinical benefit, which is leading providers to think of advocate for a broader range of their patients. They typically start with a more severe symptoms, symptomatic type of patients and their broadening that lens over time. And I know it's also exciting to see the growth in allergy penetration within and beyond this segment as they become familiar with a they get accustomed to the access process. And then again, ours is Keno fishing and identifying those next patients as they're coming in for treatment.
And so I think the take-home there is, you know, we see significant potential for growth as this continues to accumulate over time, both breadth and depth. To the second part of your question, pardon me, this is not a sort of 125 to 150 per quarter. Story alone. I think that the limitations of patients on therapy at the end of every quarter, you just it doesn't tell you on when those new patient starts are happening, what the duration of therapy is for these patients, and we've highlighted how much more important duration will be a contributor going forward. And in this launch, and it's a rare disease were early on. There's there's variability month-over-month, as Keith alluded to, we're learning those quarterly dynamics. And so I think a better lens to take is probably that moving average as well as a breadth of factors that are contributing to that revenue guidance that Christie just and just highlighted, I think taken together were really pleased with the first two quarters. And when we look at the other two are faster opportunity comparators that Keith mentioned, we're well within the pack of the trajectory that they've been on towards realizing that blockbuster opportunity for advocate.

Operator

Thank you. Our next question comes from Ren Benjamin from Citizens, JMP. Your line is now listed. Hey, good morning.

Reni Benjamin

Thanks for taking the questions. Congratulations on a great quarter in a more impressive guide. Can you talk a little bit about the trajectory in Europe and maybe what contribution of the guidance is coming from Europe? I know you mentioned in the prepared remarks for launch will start in Germany. But can you maybe just talk us through the retaining some of the countries come online and who's doing the actual selling? And just as a follow up, you've talked now about the $2 billion peak revenues. How do you think about how long it might take to get to peak revenues vaccine?

Jenna Cohen

Yes. Well, thank you for those questions. Could you do want to talk about a bit about your ability to actually answer? So I think Jens as so we were pleased to see the European approval come through before the end of last year, as I think everyone knows and add even more pleased to see that we saw ISM. patients being treated in Germany than before by the holidays and which was which was great to see yourself out of the gates in Europe and ISM. And Germany is really going to be the primate in a market that's driving ISM. this year and due to the cadence of pricing and reimbursement sell, other other markets will start to come online. But I would expect that more towards kind of the end of this year into next year. I think the important thing is if we're thinking about from a revenue perspective, certainly outside does encompass International, and that's yet another variable actually, as we think about sort of the guidance range that launch gets underway at my general expectation is that if you look at the percent of revenue, that the international business contributed to indicates a in 2023, and it's probably going to be roughly the same range as the U.S. continues to grow very well. Batch percent mine assets is probably not a bad assumption to think about Europe. And in terms of the peak in, I think again, as Kate mentioned, where I ran a very clear trajectory that I think looks a lot like other rare disease launches the time to peak in those launches at various right that these are never markets that are sort of up to saturation within two or three years. And that and flattening, I expect a ticket revenue to drive growth for Blueprint and for several years to come at you. one thing that I think that's an interesting about time to peak is that there's often a positive relationship between time taking what the peak as So we just talked about EL., our view of the P kind of coming up to $2 billion. And if you look at, you know, markets like HA., if you look at even geography or Solaris and those drugs have continued to grow and the peak opportunity has also continued to grow because the market grows underneath that drug launch. And so we'll see what happens. It wouldn't surprise me if our view of the peak continues to be evolve as we see as we move through this launch.

Operator

Our next question comes from Michael Schmidt from Guggenheim.

Mich Schmidt

Hey, guys, good morning. Thanks for taking my question. I had one on Blue eight oh eight as we head towards Quad AI next week. How do you think about the overall development opportunity for this of was to KIT inhibitor? And talk a bit about how you see potential for differentiation from biologics that are in development for a wild-type kit? Thanks so much.

Kathryn Haviland

Thank you, Michael. We're really excited about Lloyd. I'm glad you could talk a bit more about that,

Christina Rossi

and that's at a calls if you think you might come through. What's your question first, I have to say I'm very happy to be to see a proof of concept having been achieved in inhibit by inhibiting wild type of case with the strategy using monoclonal antibodies so that you will see you there. No flu A. do it is a small molecule checkpoint inhibitor that is highly point on what that could very selective, which will have a promising safety profile as we have run the SAD MAD studies, I believe it is very flexible way to administer the drug and it will be very simple to give compared to all the strategies. The most important thing that's my opinion will be a key inflection point for us. You grew eight away is the safety and pharmacology data that we gather from the SAD MAD.
After that, I think the POC of wild-type could be superior strategy of inhibition in C issue has already been shown in some Phase two data beyond see issue or chronic spontaneous urticaria. There is called in UC Berkeley carrier, as we all know, the overall mass. So they mentioned in my earlier remarks, has been reading under appreciate the target in type two inflammation. And now that we started this in our industry, I believe the offer opportunity to leverage blew it away than wild-type inhibition overall in the number of inflammatory disorders, such as Type two asthma or M. cash. Others will be very important. I think patients will have the end of the day, like from oral agent that we can buy up and down depending on the need for the diseases. Yes. And thanks for this. I just want to add one thing.

Becker Hewes

This is Becker. I guess the question a lot about how a lot of KIT inhibitor, what might compare with what is currently being developed. And I think one thing to remember is we're talking about a very wide spectrum of disease with different manifestations in different tissues and different levels of severity. And using a blunt instrument like an antibody that either the might eliminate a number of mast cells isn't exact, isn't where you want to go with a lot of these diseases. And so we think that a tunable, um, solution that is we can we can titrate to what each patient that patient population needs is the right things in this property, they are in these diseases. The other thing to remember is that most of these approaches, whether it's PTK. or antibodies, don't directly address the true driver of the mast cell, which is kit BTK inhibitor activation integration, but really doesn't address the biology of the of the math. And even the antibodies that are active in asthma, really an orthogonal approach to the disease methodology. So really kit is the Achilles' heel of these diseases.

Operator

Thank you. Our next question today comes from Derek Archila from Wells Fargo. Your line is now open. Please go ahead.

Derek Archila

Hey, good morning and congrats on the results. Here are just two questions from us. You talked about kind of an increasing rate of diagnosis for ISM. So I guess I'm just curious, do you think, you know, current estimates and might be so slow for the number of patients out there? And I guess what inning do you think we are in terms of increasing diagnosis rate? And then just a follow-up on any additional kind of quantitative color on the chart discontinuation rate you're seeing banks.

Kathryn Haviland

Thank you. The first question is you maybe just starting with the epidemiology may be updated epidemiology at JPMorgan, and we've seen really nice growth in the diagnosis of Assam that is predominantly a U.S. only because of better than patients are our model smaller or less intense diagnostic odyssey, just given the manifestations of disease. And we're very early innings on understanding the size of this market. And we anticipate will continue to grow very substantially over the next set of years. It could you talk about what we've seen other rare disease launches? So you're talking about can you the durability with a and and how that because it's a big part of negative future value prospect of Advocate?

Philina Lee

Yes, sure, Derrick. We've been really pleased to see the clinical profile of a vacant really playing out positively in terms of real-world experience. Compliance has been really high. And while we're really early in the launch, but very low discontinuation rates, which bode well for chronic durations of therapy with Advocate. And at this point in the launches, we continue to add more patients that duration and the cumulative impact of adding more patients and more patients staying on therapy is going to be a substantial contributor to the revenue growth going forward.

Derek Archila

Understood. Thank you.

Operator

Our next question comes from Laura transit gas from Raymond James.

Laura Prendergast

Hey, guys, congrats on a Congrats on the video today. Very exciting to see just two questions from me offers. What is driving these new patient impact you think of myself and the patient awareness side or education and provider here during routine visits?
And then my second question is, as you think about that CDK., two partnerships to this focusing on just partnering to asset or are you amortizing unit partnering the whole CDK2 franchise reaction and integrator? Yes, but at the JPMorgan, we are taking the questions before I do want to talk a little bit about how we see the drivers, new patient starts.

Christina Rossi

Yes. Thanks for the question, Laura. So you know, we entered the launch already with strong awareness among our targeted hemoglobin AI.'s. Initially the drivers, obviously, some of the hallmarks coming in with experience with a they can at our various adoptions. That was honestly been really exciting to see is an expansion in the breadth of new prescribing in hematology oncology as well. You know, they're motivated there. They're so much more excited about ISM. and the opportunity in the need here as well as on an increasing proportion of Allergy and Immunology who are prescribing and So significant growth to date, there's significant headroom to grow. As we've said today, the majority of that growth has been driven by provider engagement. And we've talked about how out of the gate we have made available a lot of really patient facing initiatives and JPMorgan.
We shared that we almost doubled patient awareness of a bucket, which activates then to speak to their provider about it. But I would say with the with the patient activation and that's early days, and that's even more headroom to grow on that front. And we know patients are critical stakeholder in this type of chronic disease where there are a key part of that share decision making with their providers into this year. And we're really embarking on deeper direct to patient initiatives to promote increase the awareness of a bit and really encourage them to seek options that can give them better disease control. And we're excited to share more about that. And we're also doing that, I should say on in a very resource effective way based on our deep knowledge of where these pace patients are going to look for inflammation, burned about the disease and engage with providers.

Philina Lee

And one thing I'd just add to that is out nothing is as impactful to patients, a series of other patients who've been on the therapy. And now the as we sit today, we're over 1,000 patients at 3,000 patients in the US. And we see and patients want to be sharing those experiences and chat rooms and online. And we're also have some more formal live programming around that, where we can connect patient to who are on a decade with patients who are considering it as a therapy, which I think it can be very impactful this. Yes. Could you do want to talk about the CDK2?

Christina Rossi

And so as you said, you know, we have a significant amount of strategic interest in that target, right? I think the target as clearly now on, that's going to be incredibly important to any company that wants to be a player in the box cancer, the market going forward. And you know, our focus on conversations on BD perspective has been to Q2, certainly. And we have a next generation asset that, you know, could be a part of those conversations are exploring an open to defense, different possibilities that add that. I think there's also a lot of interest in our degrader platform level. And and we will look at that, as you know, essentially a different modality and approach to addressing that target.
So we'll see how the conversations evolved and certainly open to different collaborations structures by our overall goal of maximizing the value of the franchise. And in totality. Thank you. And just when can we expect to see more and more information on this?

Laura Prendergast

Great. Our platform before I

Michael Landsittel

do want to talk a little bit more about that. We are very I'm very happy with the rapid progress that we made on our digital platform. As you may remember, we started this a little bit more than two years ago. And today we have a number of degree. There's development. We mentioned CDK2 degraders in the cycle independent kinase space, but this is only the tip of the iceberg of that. We ended up CADE shared at the JPMorgan conference, I think down the road and you will see, you know, some with the greater CDK2. Clearly, our targets are to targets in the treatment of cancer, and we will really give more time line again as we get closer and ready to share that type of information.

Kathryn Haviland

Maybe one other thing to mention too is and I know we've said in our press release, we were we're also doing quite a bit of work in the muscle and look at other mass all different targets as well. And so stay tuned on that as well as we move forward.

Operator

Our next question today comes from Mike Harrison from Morgan Stanley. Your line is now like to go ahead.

Hi, good morning. This is Ryan on for Mike. Thanks for taking our questions. Can you just talk about the breakdown of your 2020 14 guidance on how much do you attribute to a some versus I have some? And then can you talk about any trends you're seeing thus far for 2024? Thank you.

Kathryn Haviland

So if you do want to take the guide, I mean, one thing I'll say about 2024 that were a few weeks in here where this is our first experience with the Q. one dynamic that Chris, you mentioned you see often in pharma with IFM. So we're just taking teams working through that, what they see how that plays out. But really the underlying demand from both new and existing patients appears very strong this year and very early days because you do that. But the guidance so ourselves,

Christina Rossi

As you all have heard us say many times, you don't we don't break out revenue by indication, however, and ISM. is clearly driving our revenue growth rate. Are you seeing that clear inflection upon the first two quarters out of line? And I think if you look at the revenue trajectory we're on it, it's obviously that growth is coming from from ISM. and 14 a share that now more than 70% of our new starts are coming at the 25 milligram dose, which is an imperfect, you know, sort of way I'm looking at them, I think is a relevant data point that again, just highlights that. Yes, we're really seeing the growth coming from and from a SIM and would expect that to continue well into the future as we as we capitalize on that in our $2 billion opportunity for advocate. And as Keith said, we are early in Q1. As you know, the one thing I would highlight is we were really pleased to have 7,000 patient back in January, right? So I think that speaks to certainly and the continued that demand that we're seeing in terms of new patient starts, et cetera, that we're seeing that other dynamics in Q1 that, you know, I wouldn't be surprised if we face tough first quarter of launch and certainly in my previous experience, especially in these types of chronic immunology markets.
I mean, do you often see hits around compliance and gross-to-net as and co-pay dynamics have set ourselves. We're only partway through the quarter. Obviously, what we'll see how that all plays out that And Q1 is often more of a challenging one. And just if you look at quarter-on-quarter dynamics of the other.

Operator

Our next question comes from Matt Biegler from Oppenheimer. Your line is now open. Please go ahead. Hey,

Matth Biegler

Hi guys, congrats from us as well. On give us more granularity on the prescriber mix. I think last quarter we saw around 25% of new scripts from allergists. Have that figure continued to increase? And also what's the contribution of dermatologists and GI docs as well?

Kathryn Haviland

Yes. I think that I know that that fully I mean, we've been really pleased to see that contribution analysis, immunology, which are the key prescriber target for us to continue to grow. Furniture went up or above.

Philina Lee

Yes, thanks for the question that we do continue to see the allergist contribution grow. It's now over 30%, probably in the mid 30s. I think we've talked about 20%, 25% previously. We're really excited to be motivating this prescriber base among allergists. That's also adoption among the academic as well as the community setting. And they're finding advocate easy. They're obviously very attuned to the symptom management and the quality of life impacts of IFM. on these patients and are motivated to treat a disease modifying option.
You know, among German GI. and A. in our experience, German GI.'s really much more of a referring specialty, whereas a Advantest are the primary prescribing specialties. And that really has been our focus to date from a promotional standpoint. For example, when you look at the top 400 treaters, that is completely dominated by by hem-onc NAI., and that continues to be our primary focus to drive the adoption where we're most likely to see repeat prescribing when it comes to derm, gee, I would say they do play an important role in diagnosis and multidisciplinary care until we do have other sort of arms of educating to to help these specialties identification.

Kathryn Haviland

Now just to add to that, our medical team has done a really great job here actually. And they've been focusing on some of these other specialties deploying this point. But making sure we're finding the right medical dermatologists who actually have an interest in SMCSM. patients tend to be a part of that those patients journeys. And so if you had the full group effort here and and the energy immunology and hematology oncology are going to be the drivers of this opportunity for the foreseeable future. Thanks again.

Operator

Our next question comes from Ami Fadia from Needham. Your line is now open. Please go.

Ami Fadia

Thank you. Let me add my congratulations on the strong quarter and guidance, but I had a follow-up on guidance and trying to square away and what are some of the variables as I think about on what the guidance implies on. It seems to be that in Q4 you had it had more than 200 patients and guidance implies roughly a little over 100 patients per quarter. So what are some of the other variables we should be thinking about what's your assumption with regards to discontinuation of patients from the and thousand patients that you have had in January? And then how should we think about duration of treatment? And is there any other sort of variables we should be thinking about? Thank you.

Kathryn Haviland

Yes, I mean, Chris, do you want to dive into guidance, but so on and so on.

Christina Rossi

The I would say the guidance does not imply that and I would I know Mark asked a similar question earlier. There's a range of assumptions on each of these variables that you can kind of think about to get into that guidance range?
We're obviously thinking about a number of inputs here, right? So new patients prescribed discontinuation rates, both of those things kind of impact net patient adds on a on a quarter on factors like compliance, what our percentage of free drug looks like, et cetera. And then we touch about the international launch. So you could probably get to more than 1,000 scenarios if you play with those variables, depending on the assumptions. And I think there's some people blueprint that have probably done that. But, you know, it was safe to say is that our first couple of quarters of launch and our experience there really set the foundation for sort of what are the key assumptions that we're taking forward. And certainly, one of those is that we're continuing. We're going to continue to have very steady and consistent new patient starts and, you know, discontinuation rates that are that are very much in line with what we've been seeing, which, you know, support extended durations of therapy that we've seen could be multiple years. And so that that is sort of forms the foundation of our assumptions based on the last two quarters of experience that was where we started and then you kind of think about reasonable ranges and assumptions around each of those things. And that really informs how we got potential.

Operator

Our next question comes from Peter Lawson from Barclays.

Peter Lawson

Your line is now open for some of the guidance and all the details on the anything that happened during 4Q or the P&L of 1Q, that kind of changes there view that TSNASM. revenues should essentially be flat?

Kathryn Haviland

Wonderful, I think, Pierre, for that for that question, I mean the answer is no, but I don't know if you have any more color. I mean, we've been very consistent. I mean, we have said for maybe 18 months now that just did contribute about $8 million a quarter that is steady.
Eddie, that is you've been very, very consistent quarter over quarter for a long period of time now has and continues to have growth and it's just not the same growth rate, as I said on top of that?

Philina Lee

Yes, the short answer, Peter is no, and the launch is not flattening. I think that our guidance guidance is the clearest signal of that with over 80% of growth at the midpoint and all leading indicators being very positive.

Operator

Our next question comes from Colleen twosy from Bard.

Great. Thanks. Good morning. Congrats on the progress and thanks for taking our question. I think you talked about 20% of the top 400 doctors that have prescribed e-ticket. So I know that 80% of docs that haven't Can you explain to them? What's the hurdle for them and what they can and the start .

Kathryn Haviland

Yes. So what you should dive in here, just to be clear that that's been since the ISM. approval, just to be clear or we're trying to track here position to see them generally. But we're looking at the we can't yet, as Kristian said, you were in Florida. We can't really distinguish between events as M&I or some other time different diagnosis code. We do look at the dosage 25 milligram as an imperfect proxy for that. And so this is really looking at your physicians, the physicians who have been prescribing since our Q3 and Q4.Right? So I don't know if we know if you want it.

Christina Rossi

Yes.Thanks for the question. As you know, this is a market where the cadence, the timing of patient visits is a really critical factor in when they're able to engage and have that conversation about indolent SM with their providers. And so I would I would say at this point, this early in the launch, we're actually really excited and to have had penetration into 20% of this group with room to grow the adoption, both within that group as well as broadening beyond to those who haven't and I would say awareness among this group is very strong that they are all having personally engaged a number of these providers and they're all motivated. They are excited about advocates, benefit risk profile, and they're waiting for those patients to come in and have that conversation.

That's helpful. Thank you.

Operator

We are coming from the hour and going to end the call. I will now turn back over to the speakers.

Kathryn Haviland

Thank you, operator. And I want to thank you all for taking the time to join us today and thank you for your questions. And we look forward to seeing you in the near term here.
Many of you at Quanta in Washington D.C. And so and have a great day, and we'll see you soon.

Operator

Concludes today's call. You may now disconnect your lines.