Q4 2022 Blueprint Medicines Corp Earnings Call
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Good morning, and welcome to the Green practice Medicine Conference call at this time, all participants are in listen only mode.
Missile, while about who I just call up for your questions. Please be advised that this call is being recorded.
At this time I'd like to turn of events.
Colin.
As a nation absolute percentages. Please proceed.
Thank you operator, good morning, everyone welcome to blueprint medicines fourth quarter and full year 2022 financial and operating results Conference call. This morning, we issued a press release, which outlines the topics. We plan to discuss today you can access the press release as well as the slides that we'll be reviewing today by going to the investor.
[noise] section of our website at Www Dot blueprint medicines dotcom.
Today on our call Kate Haviland, our Chief Executive Officer will provide a perspective on blueprint 2022 accomplishments and how that positions us to continue to grow and drive value in 2023.
Lina Li our Chief Commercial Officer will review Ava kits performance and our upcoming opportunity to expand the label and treat many more patients with F. N. Christy Rossi Chief operating officer will provide a preview of how we will further our S. M leadership at Quad AI as well as touch on portfolio milestones for the year and Mike lands at all our Chief Financial Officer.
<unk> will review, our fourth quarter 2022 financial results and 2023 guidance.
So I'd know Mooney President of research and development and Becker Hughes Chief Medical Officer are also joining our call and will be available for Q&A.
Before we get started I would like to remind everyone that the state once he wake on this conference call will include forward looking statements actual events or results could differ materially from those expressed or implied by any forward looking statements. As a result of various risks uncertainties and other factors, including those set forth in the risk factors section of our SEC filings in.
In addition, any forward looking statement made on this call represents our views only as of today and should not be relied upon as representing our views as of any subsequent date, we specifically disclaim any obligation to update or revise any forward looking statements I'll now hand, the call over to Kate.
Thank you Jennifer good morning, everyone and thank you for joining our call today.
In 2022, we significantly advanced our business, making important progress across our ever kit launch an advanced systemic mastocytosis and research and development execution on our portfolio of precision therapies.
As we kick off 2023 blueprint offers a compelling value proposition and a unique profile.
I would like to highlight three of the most important components of that position.
That suits us or position us well for substantial growth this year and beyond.
The first is our leadership in systemic mastocytosis.
In 2022, our first full year of Eva kit launch in advance that we.
We doubled our net product revenue year over year.
The U S accounted for the majority of these product sales and in 2020 three we will see our international launches and advanced key countries.
Yeah.
Importantly through the launch of Eva kidney advance such that we have built a strong team and a foundation of commercial capabilities and infrastructure.
We are.
We're ready now to scale the impact of Eva cat with a potential label expansion and ISR.
Selina will go into more detail on advocates performance in 2022.
In preview, how we plan to build what will become a blockbuster therapeutic category through our anticipated launch and I S hasn't bid yet.
The second.
Component is our clinical stage pipeline focused on best in class investigational.
Yes.
Our development efforts are focused in mast cell disorders lung cancer and breast cancer.
Within these areas each of our programs has a strong mechanistic rationale.
And a development strategy to achieve a first or best in class position.
In 2022, we work to build the foundation for these programs through dose escalation and dose optimization.
And we are poised this year.
The greatest opportunity to impact significant medical needs.
We also continue to broaden our discovery efforts expanding the range of high value targets. We can pursue as we aim to increase our already impressive research productivity.
Most recently demonstrated by the announcement of our New research program targeting wild type kit for common muscle diseases adjacent to systemic mastocytosis, including chronic or to carry out.
The third and last component is that we are operating from a position of financial strength.
Our strong cash position and disciplined approach to capital allocation ensures that we are well positioned to execute on a range of opportunities we have in front of us.
While driving towards a sustainable financial profile.
Today, we have greater than $1 billion in cash on our balance sheet and we are growing product revenue, which will continue to become a more significant portion of overall revenue this year.
Mike will go into our financial performance in more depth later on the call later on in the call.
Okay.
I blueprint, we have an incredible growth story right in front of us in 2023 and beyond.
We called this precision at scale.
This story starts with our existing commercial portfolio.
Which provides a certainty of value and a near term opportunity to drive revenue acceleration.
Beyond S M. Our discovery and clinical stage portfolios provide multiple opportunities for us to tackle increasingly large up opportunities in oncology and beyond.
This diversity of fundamental value drivers creates multiple avenues for growth and upside across all aspects of our business.
As a fully integrated company, we have critical mass.
Including the expertise the infrastructure and most importantly, the right people to deliver on these opportunities creating.
Creating extraordinary value for patients the medical community and for our shareholders.
Now, let me turn it over to Polina to review advocates performance and provide a perspective on the upcoming I used that much.
Thanks, Kate good morning, everyone, let's.
Let's start with advocate performance in 2022 we doubled Ava can't not product revenue achieving $111 million.
Fourth quarter revenues were $31 million was $26 $3 million in the U S.
We have established Ava kit as the standard of care and advanced S. N in the U S, where we continue to grow the number of patients treated with either year over year.
In 2022, we exited the year with nearly 500 patients on advocate.
The percentage of patients on free drug remained stable.
In Q4, <unk> growth was driven by several important measures. We added nearly 50, new accounts, increasing the breadth of prescribing to approximately 400 accounts with Eva could experience.
<unk> penetration increased across all subtypes of advanced us out.
Approximately 75% of patients who start Ava kit are treatment naive, which is a promising lead indicator as we focus on growing the treated advanced SM market.
We are confident in our guidance of 130 million to $140 million in the Ava kit net product revenue this year across gist and advanced SM.
I want to emphasize this guidance is specific to our current indication.
The midpoint of this range represents a more than 20% increase in Ava kit revenues year over year and.
And we also expect to achieve additional revenue for Ava cat this year above and beyond our base guidance due to our anticipated launch in ISS.
Now, let's turn to iPhone.
Upon approval Ava kit will be the first FDA approved therapy for patients with I S. M P.
Patients and providers have been waiting for this a long time.
With our <unk> date in hand, our team is laser focused on building the market to deliver on this incredible opportunity to transform patients' lives.
Eva kit represents a blockbuster opportunity in S. M with an estimated one 5 billion dollar global annual peak.
Chances to make this kind of patient impact are rare in our industry and this has enabled us to rapidly recruit talent as we've incrementally expanded our highly experienced field team.
Our U S launch strategy focuses on 7500 patients with moderate to severe I S. M D.
These patients are actively seeking treatment, which is limited to symptom directed polypharmacy today.
We expect early adoption of Eva kit in patients with severe symptom burden followed by patients with moderate symptom burden overtime.
To prepare for ISR launch we're focused on three key areas first we're engaging a broader provider base, who are managing I S M patients.
Our field team is on the ground engaging the he marks an allergist immunologist, who are seeing the most I S M patients to understand their practices and to educate on S. M.
Our greatest focus is on the top 350 providers, who are managing approximately 1500 moderate to severe Ais a patients today.
Yeah.
From our field intelligence and primary market research providers say about half of their patients are not well controlled on current therapies, which ties well to the 7500 patients we can see in claims.
Our second area of focus is activating patients to country to consider a new treatment option.
Our patient and caregiver campaign, it's something has now enrolled thousands of highly motivated prospective patients who suspect that they may have S. M.
And we know that an educated and motivated patient is a catalyst for treatment.
Third we're focused on maintaining strong and rapid patient access to therapy.
Favorable access environment for Ava can't provides a strong foundation.
All doses are currently on the market today with virtually no access challenges and industry, leading time to fill.
Yeah.
Now, let's talk more about expectations for our initial launch ramp and I S M, which we expect to reflect a rare disease launch trajectory.
We think the H E E market is a good example for how I S. M can develop into a blockbuster market.
We see several similarities.
First H, a he's a rare disease treated by allergists multiple disease modifying therapies are approved and reimbursed today with price points above Ava Kids current list price.
Over the past 15 years, the introduction of these therapies catalyze the development of the AG market.
Hey, billing linear sales growth over this timeframe.
In 2021 global sales of prophylactic H, a therapies were approximately $1 $5 billion and still growing.
There are 7500 diagnosed and treated H a patients in the U S. Today.
Which is remarkably similar to the number of diagnosed and treated patients with moderate to severe I assembled.
So collectively the H a experience gives us confidence in the commercial launch trajectory for Ava kit in I S. M.
As you see with H E E. We expect a rare disease rent.
Well, we don't expect an initial launch bolus. There are several factors that should accelerate the development of the S M market, including our efforts over the past several years to increase disease awareness and diagnosis rates as.
As well as our advanced patient identification capabilities.
And this will further help to catalyze treatment and market growth.
As we drive towards the <unk> date for ice M. Eva has all the harbinger of a strong March hi.
High medical need first to market with a strong product profile and a highly motivated group of patients and providers, who are waiting for an FDA approved therapy.
With our experience and our leadership in S M.
We're confident in our ability to capture the significant opportunity ahead.
With that I'll turn it over to Christi, who will speak to blueprints leadership at Quad AI.
Thanks, Elena good morning, everyone.
Next week at quite AI, we are proud to share data across multiple presentations that further solidify our long standing scientific leadership and commitment to S. M.
The pioneer study definitively demonstrating that Eva kit potent and selective inhibition of kit. The 816 V reduces mass cell burden improve symptoms and therefore transforms the quality of life of SM patients.
Since presenting the top line data last August we've met with a variety of health care providers, who treat S. M patients to understand what data is most meaningful to them.
While the specific outcome measures that are most impactful will vary by physician and at times by specialty as allergists have a different reference frame for clinical trials and are much more used to PR OS for example than Hematologists are.
Some themes have emerged consistently.
The first is that safety is key.
A clean safety profile lowers the hurdle for prescribers and patients to consider a disease modifying therapy like aver cat.
Shifting the conversation from why try a new therapy like advocate to why not.
The second is that the totality of impact across symptoms and quality of life is paramount.
Our primary endpoint of mean change in TSS captures the symptom benefit broadly.
In addition S. M. Treaters are interested in the impact on patients most bothersome symptom, which can motivate a patient to want to initiate therapy.
As well as the impact of treatment across the specific symptoms captured in the TSS.
Finally, prescribers are looking for symptom and prove that to translate into impact on a patients quality of life, which is the ultimate goal of therapy.
Third data on measures of mast cell burden helps to explain the biological rationale for the benefit that health care providers are seeing in their patients.
Seeing meaningful inconsistent impacts in these measures increases prescriber confidence and a therapies potential to alter the course of disease.
Finally in a chronic lifelong disease like S. M. Prescribers are very interested in understanding the impact of treatment over time.
We designed part three of pioneer specifically to assess and capture the benefit of treatment over the longer term.
With that feedback in mind, we are looking forward to sharing more from pioneer and three presentations at quite AI.
An oral presentation on Sunday February 26, we'll detail the statistically significant and clinically meaningful results that Eva kit achieved across the primary and all key secondary endpoints in pioneer.
We plan to show additional data on our primary and secondary endpoints, including information on individuals' symptom benefit.
As well as data from the 48 week crossover portion of the study.
We will also have two additional presentations that will focus on Eva kept the fact on skin signs and symptoms and quality of life.
We are excited to share these important results in detail for the first time, demonstrating the disease modifying benefits of Dave a cat and showing how advocate empowers physicians to address the most important concerns there I S M pesos.
Other presentations at the meeting well characterized the burden of disease and showcase new approaches to accelerate diagnostic rates and continue to grow the ISR market.
We look forward to this important conference and to sharing more detail during our corporate call on Monday February 27th.
I'll now turn briefly to our portfolio updates for this year.
In January we guided to a variety of milestones across our portfolio as we work to expand our impact on patients globally.
We just got two important <unk> milestones already this morning, the upcoming presentation of the pioneer data at Quad AI as well as our anticipated approval and launch in I S M by midyear.
Today. We are also pleased to confirm that we have received E. M. A validation of our type two variation for advocate in I S that.
Bringing us a step closer to this important indication expansion and launch in Europe .
We're on track for our other corporate milestones for the year, including I N D submission for Blu 525 and presentation of initial dose escalation data from blip, both blue for a five one and Blu two to two and the first half of the year.
Last week, we announced that the FDA had issued a partial clinical hold on the valor trial due to visual adverse events observed in a limited number of patients.
Patients who are currently enrolled in the study are continuing to receive study drug and we are working expeditiously with the FDA to resolve the partial hold and resume steady enrollment.
More broadly we look forward to sharing additional data across our portfolio as we reach these milestones and made progress towards our 2027 blueprint.
With that I'll turn the call over to Mike to review our financial updates.
Thanks Christy.
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 $204 million, including $111 million in net product revenues from sales of eight or 10 and $93 million in collaborations and license revenues exceeding the high end of our.
2022, total revenue guidance of $200 million.
Of these full year revenues $31 billion of net product revenues and $8 $7 million in collaboration revenues were recorded in the fourth quarter.
That's probably in a noted for advocate we saw continued growth in advanced SM patients starts and product revenue.
Our total operating expenses were $723 $7 billion for the full year and $183 $7 billion for the fourth quarter.
Our Q4 operating expenses showed a quarter over quarter decline from Q3, as we continue to leverage operating efficiencies across our businesses.
In 2023, we anticipate that we will achieve a 130 million to $140 million in Eva kit net product revenues for advanced SM and just.
We also anticipate full year collaboration revenues of $40 million to $50 million from existing collaborations.
This guidance highlights our expectations for both the continued diversity of revenue and a continued but more moderate growth David Kid product revenue in advanced SM and just.
I want to reemphasize that this guidance is specific to our existing advocate indications and it does not include growth from our anticipated label expansion into I S. M.
We expect our operating expenses to grow moderately in the first quarter of 2023, and this will be driven by our preparations for the launch of <unk>, including the impact of our incremental field force expansion.
As well as planned manufacturing investments to support the continued progress of our clinical programs.
We then anticipate operating expense growth will flatten in the second half of the year as we recognize economies of scale across our portfolio.
As we enter 2023, we are in an exceptionally strong financial position with nearly $1 $1 billion in cash that will fuel our 'twenty 'twenty seven blueprint to achieve precision at scale and create transformative value for patients and shareholders.
With that I'll now turn the call over to the operator for questions operator.
Thank you we will now start today's Q&A session.
Your question please.
Follow up on one thing you have now.
Your line. Please press star followed by two things.
Supposed to be reminded that we don't have time for one question.
Our first question today comes from Dave Raymond James Your line is open.
Hi, Thank you for taking the questions and congratulations on all the progress I think for.
The guidance that you've outlined this morning.
We have a number of questions coming in and they're pretty similar from investors.
There are kind of focused around when you look at the current prescriber base of <unk>.
What the overlap is at those centers with patients you identified as being ISR patients.
Who could be eligible for treatment once you get the approval and I think the Genesis of that is sort of trying to help people of once you get the approval.
Where the launch could be initially focused in and kind of what.
Percentage of the target population would be representative of your current prescriber base.
Yes.
Okay. Thanks for that question and I'm going to do you can you weigh in on them. Yeah. Thanks very much for that question. So as you know our teams are in the market and on the ground today engaging with top volume prescribers of Eva kit as well as.
The top volume providers, who are treating ISR patients and in fact, we do see some overlap and so within those top 350 high volume prescribers, they're treating nearly 400 moderate to severe <unk> patients today, who are potential candidates to start Ava kit rapidly upon approval.
Thank you.
Right.
Our next question today comes from Bob Kraut from Cowen. Your line is now open.
Yeah.
Hi, guys, Jeremy Rodriguez for Mark.
For taking my call that in the quarter.
You mentioned that the most bothersome symptom endpoint that will be presented with the pioneer theater. Later this month, so it's important to be focused in flooring.
It seems that with most of your Brooklyn, Let me give you a patients.
Do you think that.
You show symptom benefit.
The overall goal per se.
And how do you think the threshold clinical meaningful meaningful net differed from the ECB.
PSA score.
So any I'm sorry, I think you were breaking up a little bit. We appreciate the question I believe what you're asking is how are we thinking about the breadth of impact across various symptoms and in the pioneer data versus kind of the interaction with the most bothersome symptom I believe that was your question.
What we can is that is that correct. Okay. So I think what what Christina.
Great. So I think what Christy was laying out is is really that we have in pioneer we have demonstrated statistically important and clinically meaningful benefits to patients across a range of ways of looking at treatment impact and that includes the impact of pathological mast cells from a quantitative measures. It includes.
The impact on both the overall symptom burden of patient experiences as measured by the T. S S as well as impacts across all the individuals' symptoms and in domains and so we really look forward at quad AI to be able to put that data out to show that the impact that the broad and kind of impact that that Eva has and I think importantly it.
Is that the early impacts we see as well as the deepening overtime.
There's going to be important to prescribers as we've talked about.
Alright, that's helpful. Thank you.
Our next question today comes from Brad <unk> from Stifel. Your line is the whole thing.
Thanks, and good morning, maybe on the CDK to I'd like to ask you if over the past week have any more patients completed eye exams, particularly the patients that have the grade three of them.
Those results then consistent with what you previously thought and then if you can just quickly walk through the current thinking why those vision events are unlikely to impede the full development of this asset and the logistical steps to reactivate the trial. Thank you.
Thanks for the question Becker, where you pick up yeah. So with respect to the question on the eye exams for the patient with a grade three and it really applies to all of the patients that we have for eye exams on this really absolutely nothing abnormal showing up on these.
Ophthalmology programs and Theyre very extensive extensive ophthalmologists exams and I think this is really consistent also with the symptomatology, which are which are very brief episodes.
<unk>.
Either changing of the intensity of light or a bit of blurriness patient with a grade three also had an MRI is showing that there was nothing in the central nervous system that could explain the symptoms, but it's.
It's really the really brief nature of the symptoms and the fact that they've resolved so quickly.
Upon either.
Briefly stopping the drug and then restarting at a lower dose.
So and then with respect to the timeline or the steps needed to get the the program back on study on track we have been working very closely with the FDA has been extremely cooperative. The main reason as we've said for the partial clinical hold is simply to modify the protocol to put ophthalmology specific dosage.
<unk> criteria in there and grading criteria and then to change the informed consent. So that everyone's aware that these are potential things that could occur.
And then in terms of.
Well, how I'm thinking about this and the overall development as we've said before we're nearing the end of dose escalation I think we have a range of potential doses available.
So we see the end of the single agent dose escalation in sight.
These events again are very brief they are usually grade one and they.
Having some ophthalmology or visual changes in many cancer drugs is it's really not uncommon and this is so mild and transient that I really don't see this as potentially dose limiting and again with a with a drug that has such a.
Clean kind of them and it's so targeted to CDK too I think we have a good range, where we can see potential in the future for clinical benefit for patients.
Great. Thanks for the color.
Okay.
Yeah.
Yeah.
Our next question comes from <unk> Yang from Jefferies. Your line is now live.
Thank you so oh, we awaiting details so on the pioneer data.
Quad AI, but I wanted to just ask you.
Paul This piece.
Key secondary endpoint of responder rate.
What's the minimum delta between the two arms need to achieve statistical significance.
No.
Yeah. Thanks, Thanks for the question, you and and I'm going to hand over to Kristy to talk more about that yeah. So thank you and as you know what I mean, we hit a we were.
Highlights significant across all of our primary and key secondary endpoints and so you know I think part of it.
And it just sort of how how we interpret the variety of data on these endpoints and how do clinicians interpret them in terms of being meaningful and you know as we've engaged on that side, but I would say two things. One you know as we've said before the totality of the data across all of these end points is really what is most impactful.
Different health care providers interpret different pieces of data you know in different ways. What's interesting about response rate is that it's actually not an endpoint that is used in allergy frequently and so as these gate engaged and allergists with allergists. They found or are to kind of be the least interpretable of of all the airplanes, but we're very eager to share it and certainly some hematologists find it.
Incredibly compelling.
And so you know we will be looking at both responder analyses as we've indicated across the secondary endpoints it'll be also a really interesting to see how those rates evolve overtime again kind of demonstrating the long term impact of Eva cat and it's that totality of the data along with the other secondaries in the primary that you.
You know we've we've found prescribers have found very compelling and we're looking forward to sharing all of that data and then a couple of weeks.
And I think where you will encounter unusual position you're in that that the study has demonstrated significant impact across multiple ways of looking at it right. If everything from kind of the most fundamental biological impacts on kind of the pathologic measures of muscle cells as well as you know the the.
Patient impacts on symptomatology, all the way through to quality of life and.
It's it's very rare to have such statistically and clinically meaningful outcomes across such a broad array of measures.
In the study and so we're really looking forward to showing that data.
Thank you.
Yeah.
Okay.
Our next question comes from Derek <unk> from Wells Fargo. Please go ahead.
Hey, good morning, and thanks for taking the questions just two quick ones from US first one just on the 2023 guidance I just want to understand that this is more about driving new account activations or is this more about Jeff that current accounts and I guess, if it's the latter how much depth is really left in terms of new patients that these current.
<unk> you already asked.
And then I just want to make sure I heard you correctly I think it was <unk> question. So I think on the 350 providers I think that you are initially targeting so the overlap for ISR patients is about 400 out of the initial 500. So is it fair to assume the other thousand patients are being seen by allergists.
Yes.
Yeah Derik. Thanks, so much for the question I'll hand, it over to the leader to answer the specifics I think but to your first part of your question I think what we're so pleased to see in this launches that we are we have the dominant share of the current market of patients who were treated with advanced SM and we're seeing that consistent demand, where we're where we'd continue to.
Drive new patients broadening the prescriber base, adding new new accounts or new prescribers as we really work to expand the overall size of the S. M market as well and so I think we're going to continue to see both of those dynamics, you'll play out through launch and if you want to talk about the numbers in more depth, yeah sure Derik I think at the heart of your question. Your first question is really about.
<unk> has the advance S. M opportunity peaked for what is sort of the headroom on that.
So to be really clear, we see headroom significantly to continue to grow the advanced SM opportunity. We know that this is going to happen at a more measured rate than the growth trajectory that we saw early in the launch and.
And that growth is driven by several factors. So you know we're still early in penetrating into the overall advanced SM patient population. We are the standard of care in the treated patient population, but the biggest lever of growth. It's truly activating the fuller breath of advanced SM patients to be treated for their S. M.
And so penetration across all subtypes significant room to continue expanding on the breadth and depth.
Of the prescriber base as well as the durations of therapy, which are favorable and as we shift towards a more treatment naive patient population.
That is also a favorable harbinger of longer durations of therapy.
Over extended periods of time.
So to your second question about the 400 patients. So just to be really clear that is just the moderate to severe I S. M patients who are treated by the top 350 of our current prescriber base and importantly, we know that it's important to engage a broader prescriber.
Who are treating that 7500 moderate to severe I S M patients.
Who are diagnosed and actively seeking treatment today. So when we think about where early adoption of of Eva could happen post I assume approval, we see it not only among those 400 patients treated by the current top volume prescribers, but also among that broader group of patients who really have severe symptomology.
<unk>.
Yeah.
Thank you.
Okay.
Our next question comes from I'm.
Sorry from Goldman Sachs. Please go ahead.
Good morning. This is Don for solving and thank you for taking our question. So on the ISR launch, we're just trying to understand what patients would be the early adopters. So from the 400 patients that you mentioned, what proportion would not be well controlled on current treatments.
And then just quickly on the CDK to program.
With your proposed actions as the FDA aligned.
The changes to the protocol.
Thank you.
So, but thank you for that question and maybe it will start with the overall numbers last time I think we're getting a little bit confused on the 400. So I just want to make that really clear for people. So maybe christie can take that and then back up you could take the CDK to yes, we're happy to yourself.
Both of the last few questions I think are getting a little bit to sort of where the patients are in breadth and depth. So just to be clear on the 400, and we see 400 moderate to severe not well controlled ISR patients amongst physicians, who currently have aitken experience. So I think you know that gets to the earlier question on overlap as well. So you know I think the overall idea here that there.
Theres a lot of potential with ISR amongst prescribers, who have current Ava can experience. It's certainly early in the launch you know that is a place that we will focus them to drive growth.
7500 patients in total when we throw that number out and talk about that all of those patients are.
Patients that we view to be moderate to severe not well controlled and candidates for therapy, and maybe just to close out on kind of the breadth and depth of questions that are coming up you.
We see opportunity in both places right. So if I think about advanced Assam them. You know we are continuing to deepen our usage at existing prescribers and what the dynamic that you see is often that they will get comfortable treating a patient and then they will start to identify additional potential candidates and so we definitely seen ready to defend.
But breast continues to be really important in a rare disease market like this and so we're really pleased to see the number of new accounts that we added in and Q4 and expect to see that continues.
Yes, and this is becker and so with respect to the process with the FDA just a little bit of background about how this generally happens. So the initial call that we had with them started the process and the way it will and we'll be with written notification that the.
Partial hold has been and it had been lifted and we've been working very closely with the FDA. We're rapidly modifying the informed consent and the protocol in the IP and so far it's been going extremely smoothly. This is very collaborative.
Action spray interaction with the FDA.
We've had had alignment all along the way. So this is really about informing people and making sure that the rite grading system is in the protocol and any dose adjustments are very clear so there's been quite a bit of all of them.
And just out.
That collaborative nature of the conversations have been really have been very constructive we are working to submit the documents of course, we're not in control of the FDA timeline on the other side, but I think that collaboration and in kind.
Kind of joint sense I was getting that study back on track gives us a lot of confidence that will resolve this in a short time frame.
Yeah.
Thank you.
Our next question comes from Michael Schmidt from Guggenheim Securities. Your line is now open.
Hi.
Hey, Good morning. This is Paul on for Michael Thanks for taking my question.
Just one from us on the CDK to maybe could help so that's an expectation for that initial clinical readouts. This year.
Specifically on the Pharmacodynamic markers of activity that anything that you should highlight that we should expect such as a reduction in Boston, a or b or its like when your protein that'd be really helpful. Thank you.
If I can we can pick up yet so.
As we've said earlier our guidance has been for dose escalation data mid year and then an early look at the combination.
We are able to start the combination before we reach a recommended phase two dose and so we look forward to presenting that including safety and biomarker data midyear. This year with respect to Biomarkers, we have a number of them. They are circulating biomarkers their tumor biomarkers and so what we'll be presenting is an emerging holistic look at the activity.
And selectivity of <unk> in these multiply relapsed phase one patients.
Okay. Thank you.
Okay.
Our next question comes from Michael <unk> from Morgan Stanley . Please go ahead.
Yes.
Yep. Thanks.
Good morning.
Maybe I can just ask another question on the ISR opportunity and how you're thinking about the early trajectory here I know in your prepared remarks, you commented, you're you're not anticipating a bolus here.
But I'm just curious what impact could presentation of the data quality and next we have on those views.
Could it drive additional interest and could it potentially change your view on the early trajectory. Thanks.
Yeah. So so thank you for the question, let me take the first part of the bullish I think the and they pointed can weigh in on the impact of quite a I I think from both perspective. The reason why we're not saying that we don't expect it because we designed the pioneer study to evaluate long term follow up of patients and so you know in a product launch when you see.
A bowl, it's often because your swap youre switching patients off of clinical trials into commercial drug and we believe the long term experience of <unk> treatment. In these patients is critically important to the overall that value as we continue to look at that impact over time. So we're retaining patients within the pioneer study for up to five years. So that is that is why we don't expect it.
All that's coming out of clinical trials into commercial therapy.
Glenn you want to talk about the how you see the impact of Kodiak.
Yeah sure. So I mean, I think first and foremost the I want also talk about the efforts that the team is doing to prepare for the launch and and sort of see towards the ultimate ramp upon approval as well so as.
As I mentioned, we're hyper focused on three critical areas the broader provider engagement, both within the existing prescriber base for Ava kit as well as that broader prescriber base future prescriber base, including Allergist Immunologist I'm, we're focused on activating patients and maintaining our strong patient access.
Yes.
And so among that when when we think about.
The importance of quite a I clearly it will increase the awareness of Eva kit.
Especially among that allergists and Immunologists community.
Awareness of Eva kit as well as the data.
As far as our teams focus as well a couple of factors that we think will help with the ramp is that for many years, we have been engaging to increase disease awareness as well as diagnosis rates.
And our team has been really honing in perfecting our skills with the advanced SM launch. So we know how to leverage advanced analytics and our field acumen to find patients we know how to identify their providers and we know how to engage these providers leveraging our deep disease state expertise.
So we are confident as we think about that overall $1 5 billion dollar peak opportunity.
That we will ultimately be able to capture this opportunity.
Very helpful. Thank you.
Our next question comes from Benjamin from JMP Securities. Your line is not a license.
Hey, guys. Thanks for taking the questions and congratulations on the quarter and outlook for 2023 can you talk a little bit about how we should be thinking about the sales force and their switch to focused on an allergist.
Something that likely we're going to have to increase as we get into the year and after approval.
Approval do you have a sense as to how many docs are currently aware of okay.
This versus <unk>.
<unk> versus <unk> as well.
Yeah, Hey, thanks. Thank you Ron for the question and I'll I'll turn it over to Selina to answer the question about cell phone sales force I think one of the great attributes of this launch for US is that it is really an extension of what we've been doing in S. M and it is still a very its a specialty market. So it's a it's a market that that.
We can certainly access with incremental growth in our field infrastructure, but if we could talk a little bit about how you're thinking about that.
So as Keith mentioned with the advanced US and provides a strong foundation right. So the primary specialty a focus historically for us has been in hematology and oncology.
But as we prepare for the ISR launch, we know that we'll need to engage a broader provider in specialty base, including allergists and so we've incrementally expanded our field force and strengthened our capabilities in allergy immunology as well as rare disease.
And to your question on awareness you know at this point, we're in a very strong position with awareness of Eva kit among target prescribers of over 40%.
The unaided awareness. So I think that's that's unusual at this point and you know this early in a prelaunch phase that to have that level of awareness.
And so you know I think I also think it's important as I had mentioned before our data analytic capabilities is critical here. This is not a reach and frequency model.
This is about getting to a health care providers at a time when it is most relevant to them, meaning they've seen a patient recently and so that is something again that we have really worked hard on and and the team has done an incredible job through the advanced SM launched getting that model up and running.
Yeah.
Great. Thank you.
Yeah.
Yeah.
Our next question comes from Joel Beatty from volatile.
Yes.
Great. Thank you.
Current payer coverage for ISR.
To help frame what approval rate you've been seeing burgers for ISR.
Yeah. Thanks, Thanks for that question I think.
Our plan to fully know, but I have to say that market access has been an incredible strength of our launches to date and we are very well positioned moving into the iPhone launch you want to talk more about that point of view.
Yeah, and so to be clear I S M.
Just a small fraction of our current business today and coverage and access are strong across the full spectrum of SM patients Theres, one broad S. M code okay.
Here's aren't necessarily able to distinguish the difference between advanced SM and ISI am today.
And as we've talked about previously we are exceptionally strong payer coverage with with virtually no no access challenges.
Thank you.
Okay.
Yeah.
Our next question comes from Peter Lawson from Barclays. Please go ahead.
Thanks, so much.
Maybe a question for <unk>.
Becker just on getting to recommended phase two dose with you.
<unk> two inhibitor.
Good point, because you've cause.
The ability to start the combination regimen.
So any sense, whether we should see that recommended phase two dose.
First half or if we should be kind of wait until you have a partial clinical hold.
Yes, I mean, so far.
First of all S. K mentioned, you know the FDA timeline as the FDA timeline, we don't have control over that but we are encouraged by how quickly we are working with them.
Both the recommended phase two dose and the combination dose are important because this is a potentially very broad program that involves a number of tumor types determination is relevant for breast cancer, but CDK to is really central to the biology is quite a few different tumor types and different biology. So.
With respect to we've gone really quickly through dose escalation and so in terms of its really not just a phased recommended phase II dose. It's a range of activity, where we have a good safety profile and I already think we have that insight. So I think that the data that we are able to present mid year will provide.
A clear view of where we're going both with single agent and then very early data on the combination will need more time to escalate more deeply into that Riboside combination. It's also important to realize that.
I can start the chemotherapy combination as well in the near future. After we come out of the partial clinical hold so.
I think it's important to focus not just on that one dose, but also in the holistic program.
Okay.
<unk> captured the project up to us as well.
We have the the project Optimus philosophy in mind as we look at the doses, we intend to have a very close relationship with the FDA with respect to making sure that we've covered the basis that they're looking at to understand the right single agent in combination.
Asian dose so that as we go into bigger trials, we're not having to do a lot of dose finding beyond this initial trial. So project Optimus is.
Really the lens that we look at all of our programs here at this point.
Great. Thanks, so much.
Yes.
Our next question comes from David Lebowitz from Citi. Your line is not a license.
Thank you very much for taking my question I've got one on ASM and one on my awesome.
An ASM I guess to start.
There was we talked last quarter about specifically the adoption and the.
Associated Hematological Neoplasm group and I know you had data.
Cash a lot of focus on that specific group.
I guess my thoughts are or what.
How are things looking now and how do you think that data could help.
And then David You said you had a second question on I guess I'm just.
If you want the Ias them upfront.
On the <unk> I guess specifically.
You were talking about how different doctors are going to prescribe the therapy in different ways.
And my question is when reporting your data quality I later this month, how deeply will you go into the benefit.
On each specific symptom within the TSS score.
And is there any thoughts as to which symptoms. Most doctors are emphasizing most in your view.
Alright, Thanks, David for both those questions I think.
Starting with advanced that salmon SMH and me as as we've talked about we are the standard of care in the patients who are treated for their advanced S M, which tend to be the patients who have mcl and aggressive S. M. And then it's the it it's the same age and patients where they are just a very complex clinical presentation and that's the group of patients.
That we have worked through that very compelling data as you mentioned that we saw at ash.
Look at monotherapy impact of Eva Cat, both on response rate symptoms and and overall survival. It is certainly it.
Fueled conversations with prescribers and in that group of patients were changing practice right and they're very complex clinical patients and so that's where we'll continue to see that work as we expand the overall size of the S. M market, which is why the growth has moderated a bit there.
As you think about the I S M presentation at pioneer.
We're going to show kind of the totality of data, including the impact on patients across all symptoms within the TFS in terms of as Christian was mentioning different specialties have different context for clinical trial data.
PRN hours are commonly used and any allergy immunology space not as much in hematology.
Measures are more common to hematology and so what is great about this dataset is it we see compelling and consistent impact across all of these measures.
And so that is something.
They can appeal to all of our potential prescribers and so I think we're really looking forward to getting that out in terms of the symptomatology that debt. You know physicians are most focused on it's really what impacts the patient the most.
It's not it's not that they want to see one or the other they want their patients' quality of life to improve and so that is again why we designed the CRO to look at a rate a array of symptoms because one giving patient may have predominantly neuro cogs, sometimes in very you know not much on other domains. Another given patient may have predominant skin.
Sometimes and not another domains and so it's a very heterogeneous disease presentation and that's exactly why we designed apparel as we did and we will look we will be showing all of that data.
Our next question comes from Nishu from Bernstein. Your line is not like them.
Good morning, Thanks for taking my questions.
I wanted to ask a question related to market access.
Do you anticipate a separate code for ISN when when when the product.
It's going to launch and then related to that what's your expectation for gross to net.
Thanks very much.
Okay. Yeah. Thank you for that question and I'll hand over the question on the coach to to Selina and then Mike can take the rest of that.
Yeah, I mean, I think at the heart of your question is what kind of.
Access we anticipate as <unk> comes to market and you know just to answer that head on we expect and are highly focused on maintaining strong patient access to I S. M.
Today, we have virtually unencumbered payer coverage and we expect based on.
The payer market research that we've done.
That that that's not expected to change or or limit the target patients that should should adopt them and you can see.
Your specific question about the code no at this point, we don't expect a new code for for S. M.
So just to be really clear Theres, just one code for <unk> and you can't distinguish between subtypes within it and so that's what we'd expect to continue Mike do you want to take that question that Theyre for Kristian is currently with advocate, we see a gross to net for instant about the mid 80% range as for gross margin.
Near term, we expect that to continue once we announced pricing for ISR and get further into that launch. We've said there will be some flexibility on how we think about contracting going forward. If we need to do that that could lead to some erosion, but the mid eighteens is a good starting point and I think on the ISR market. It's also important to remember theres puts and takes here right. So.
S M market, we have a larger percentage of our patients are covered by commercial insurance.
So there that will give us some tailwind and then we have that room as Mike mentioned that if we need to do any type of contracting to ensure that seamless market access, which we may or may not but we have some space there as well. So it's it is there's a slightly different payer mix in this group than we've seen in advanced SM.
Thank you very much.
Okay.
Yeah.
Our next question today comes from Amy <unk> from Needham Your line is now.
Okay.
Hi, good morning, Thanks for taking the question.
Just ahead of the quality I data presentation.
I wanted to just sort of understand how to interpret some of the data that will be presented there.
It's clear that there's a huge heterogeneity in the patient population base.
With each base and having a very different symptom domains bothersome. So how do we take the change in <unk> score across each of the domains that we will be presenting at the meeting and think about how clinically meaningful it may be important.
For an individual patient and how those position really interpret that data. Thank you.
Chris you want to take that sure. Thanks, Amit So you know as he said before.
What physicians are looking at is the consistency and totality of the data.
When we look at sort of change in individuals' symptoms again, the TSS as a new endpoint, it's not used in clinical practice. The lens that I think physicians are interpreting this data through is to say one whatever my symptoms whatever whatever symptoms. My patient is suffering from do you have confidence that Eva kept well.
Improve their quality of life and it puts us sometimes and so I'm you know I think what what we've heard is that what physicians are looking for is consistency of improvement across individuals' symptoms.
I think looking at that longitudinally over time is going to be interesting as well.
And then importantly, addressing a patient's most bothersome symptom because we know that these patients are heterogeneous as you say and and what specific symptom may be most impactful to our patient is going to be different from patient to patient.
What is compelling about eve of CAD is that we do see consistent and packs and we know that regardless of the specific presentation patient symptomatology.
We're confident that that patient will benefit and I think that's the lens that the prescribers will be looking at this data set through as well.
Thank you.
Our next question today comes from Greg <unk> from <unk>. Your line is daunting.
Oh, Hey, guys. Thanks for squeezing me in I wanted to ask about median duration on therapy and ASM.
He can comment on that is it getting longer or shorter and I guess that would be indicative of the severity of patients you're treating and whether youre, making inroads into that H N component.
Right.
Yeah. Thanks, so much for the question I pointed you want take that.
So our median duration of therapy is trending towards 18 months. We're highly encouraged that this is this is standing up well in clinical practice and certainly as we shift towards a mix of more treatment naive patients, we expect that over time to increase.
Yeah.
Thank you.
Yeah.
Our final question comes from Chris Raymond from Piper Sandler Your line is now isn't it.
Good morning. This is Nicole goodbye stay on for Chris Thanks for squeezing us on so.
So I guess, we were just wondering of those 400 moderate to severe asthma patients that you had referenced just given the experience of Eva with those providers are any of those patients currently receiving drug off label.
I'm, sorry, if I missed it but would you be in a position to provide updated 2023 either kept guidance that includes the I assume revenue potentially later this year post approval.
Yeah. Thank you. Thank you very much for that question.
So starting with I'll just answer knowing that we're coming up against time here, but the 400 patients are really not being treated today with Eva you know, we see a small number of patients with ISI am who are being treated but it's it's not substantial.
<unk> to our overall number of patients being treated and then as we talk about guidance I mean, I think our goal today is to line on where our current business stands with our prove indications of advanced SM and just and really set the foundation for all of US as we move towards this anticipated launch and you know in any given launch there are uncertainties, including what our label will look like as we go through.
The FDA negotiation process and how the first few months will play out. So we look forward to working with all of you as we as we move into this really exciting launch.
So thank you very much for that.
Yeah that's helpful. Thanks.
Okay.
That concludes the Q&A portion of today's call him or her confidence.
Continents for closing remarks.
Thank you operator, and really is as we kind of come out of the Q&A and taking a step back I mean today, we have highlighted the significant opportunities that we have as blueprint right in front of us to create value for patients and for our shareholders, including our continued commercial execution, our anticipated launch and <unk> as well as ambitious and achievable goals.
We have for our pipeline and we are confident in our ability to deliver on these opportunities this year and beyond we thank you all for taking the time and joining us today and your continued support of blueprint medicines and we look forward to talking to you again soon this time from San Antonio from it in the Quad AI conference. So I'm looking forward to it.
Okay.
That concludes today's blueprint medicines.
On this one.
You may now disconnect your lines.
Okay.