All right, and we're off, I guess. Welcome, everyone. I'm Tiago Fauth. I'm a biotech analyst at Wells Fargo, joined today by Jeff and John from Alnylam Pharmaceuticals. Thank you so much for joining us for our fireside chat. And again, I think a lot of the debate is gonna be around cardiomyopathy. I wanna talk about profitability, some of the financials towards the end, but how has been the reception so far to the ESC detailed data? I know it's been out only a couple of days.
Yeah.
Let's kind of piece through what are some of the main takeaways.
Yeah, I mean, look, we put out an awful lot of data on Friday at ESC, and I would say generally, the data's been very well received. Importantly, I would say that the interactions that we had at the cardiology conference in London on Friday and then through the weekend with the physician community that was there was very positive in terms of their view of the data. So I think our excitement and enthusiasm for the opportunity that lies ahead is very positive at this point.
Got it. I, I think that's fair. And again, the, the key debate here is exactly how this is gonna play out over a long run, given there are no head-to-head trials. We're always cross-trial comparing, which we shouldn't, but we all do, and physicians do as well. So I guess if you were to kind of piece it apart, what are some of the market opportunities for Vutrisiran in cardiomyopathy? What is the pitch for, let's say, a newly diagnosed patient? Why would they potentially go into Vutrisiran instead of a stabilizer, for example? What, what kind of piece of data overall part of the package that you think would be most appealing to new patient starts in it? I wanna have the same discussion on switches and combo, but let's-
Yeah
Start with new patients.
I'll start. I'm sure John will have an ability to add some detail here around the data. I mean, we do think that the data that we've generated through the study supports first-line positioning for the drug. And I would say that where I would start in terms of our confidence in first-line positioning is the efficacy that we showed on the primary endpoint that looked at all-cause mortality and recurrent CV events. We showed a pretty dramatic impact on mortality, in particular. In the overall population, at the 33- to 36-month endpoint, we showed a 31% reduction, and then out to 42 months, we had a secondary all-cause mortality endpoint. That increased to 36%.
And I think particularly given the context of the study and the contemporary patient population, the significant use of, of concomitant meds, you know, 40% of the patients in that study were on Tafamidis at baseline. And then in the monotherapy arm, another 20% dropped in over the course of the study. The SGLT2 use in the study, diuretic intensification in the study, there was a very high bar from an efficacy standpoint for this study. And if you look at the placebo event rates across the study relative to the prior two studies that have been run in this space, lowest event rates, right? And so very high bar. So to deliver that kind of a mortality benefit, we think is, is quite striking, and I think, again, positions us well for first-line utilization.
Just a couple of other things to touch on in the study that further sort of bolster the argument. I think if you look at the secondary endpoints that looked at you know, function, health status, quality of life, those types of things. If you look at the observed data that we presented on six-minute walk in KCCQ, I think you see the drug arm. There's real consistency of effect, real stability in those patients, and how patients feel and function really matters. And so we think that's gonna position the drug very well from a first-line perspective. And then if you look across the subgroups in the study, there's a couple of things that I think, again, that are quite striking. First of all, there was a consistency of effect across all subgroups in the study, including patients that were on baseline Tafamidis.
But one of the things I think that stood out for us from an efficacy perspective was the patients that were either younger or a bit milder, if you look at BNP. And if you look at the patients that were at less than 2,000 BNP at the start of the study, the impact on mortality was 65% relative risk reduction in that patient population. And then if you further look at the patients that were on background Tafamidis, which was 40% of the patients in the study, not stat sig, the study wasn't designed to show a stat sig result in that subgroup, but the trends were very positive. On the primary composite, we reduced you know the composite of death and recurrent CV events by over 20% in the Tafamidis subgroup.
If you look at mortality, it was a 41% reduction on that, on that secondary endpoint. So all of that, we think, positions the drug very effectively as a first-line therapy. This is a steadily progressive fatal disease. Typically, patients that are diagnosed with this disease are, you know, the mortality is 2.5-5 years from time of diagnosis. Our belief is that the patients and physicians are gonna wanna treat with the most potent, most efficacious drug as quickly as we can. Just what I described in terms of the package of data that we delivered, we think that we're gonna compete effectively in, in that first line. The other, the other thing to note around the market opportunity is obviously this is a substantial opportunity.
We think that there's probably conservatively two to three hundred thousand patients with the cardiomyopathy form of the disease. Pfizer's done a good job building the market over the last five years. The Tafamidis is doing very well, annualizing at $5 billion and growing the first two quarters of the year, you know, 70% on a year-over-year basis. We're at about a 20% treatment rate in the market today, right? So there's a massive opportunity here to continue to grow this space. So anyway, I gave you a very long answer there, but we think we've got great data to support first-line positioning, and there's a really big market opportunity here.
... Got it. No, and that, that's perfect. I appreciate that extra color there. And one of the pushbacks we always got in our more conservative stance was, again, even if you were to assume that silencers would be second line, either as monotherapy, sequentially, or combo, that would still be a massive market opportunity. So kind of even in a worst-case scenario, our estimates were a little too low. So, what data is there to suggest in terms of, of that dynamic, how quickly would patients progress on a stabilizer? How do you think you can capture that? And one topic that I wanna talk a little more is combo. I know we have emphasized more-
Yeah
- Mono as kind of the key driver here, but is the problem gonna be data, or is the problem gonna be pricing for a combo to become a real thing over a few years?
Yeah. So there's maybe another thing-
Another question
- to talk to. Maybe we just start with the switch opportunity and how are patients doing that are on Tafamidis and what might we see in terms of an opportunity there. Maybe I'll ask John to just sort of talk to that just a little bit based on, you know, sort of what we know-
Yeah
- and what we hear from physicians.
Yeah. You know, look, I think this question around progression is a really important one, and, you know, part of what you're asking is, how quickly is that gonna happen? And, you know, I mean, the short answer is, I don't, I don't know that anybody has a definitive answer to that. But I think what's more important here is that, you know, this is a, this is a deadly disease, and I don't think people are gonna wait around, you know, for people to get really bad before they decide to switch. We've shown here, as Jeff alluded to, this data in, you know, that, that suggests that the earlier you treat and the harder you hit it, that you're gonna have these outsized benefits.
I mean, that's a 65% reduction in all-cause mortality in those, in those patients in that milder segment, that's a really big deal. And so I, I think people are gonna be incented to, to try to make these decisions, to treat it as aggressively as they can, as early as they can.
I mean, what we know about Tafamidis today is sort of estimate is, again, about 20% of the market's treated. So let's say there's 40,000 patients globally that are on therapy. So there's a big, you know, group of patients that are being treated today. Not all of those patients are fully adequately responding, so there, there's going to be a switch opportunity. Probably early on, my expectation is that that may be the biggest driver of the early, you know, launch revenue trajectory. I mean, one sort of piece of anecdotal data that speaks to the potential need there is, again, there has not been a second product in the market to date. And when we read out the APOLLO-B results a couple of years back now, we had a successful study.
We opened up an early access program in the US, which allowed patients to get on and get access to the drug for cardiomyopathy, and that filled up very quickly, I would say, in the US. And if you think about that in terms of APOLLO-B and patisiran, it's an every three-week IV infused drug, and the primary endpoint in that study, probably as most people remember, was six-minute walk.
Yeah.
We didn't have data that supported an outcome, you know, benefit at that point, and so there was a significant amount of desire to get into that early access program. So it's an anecdotal piece of evidence, but my suspicion is when we are hopefully able to get through the regulatory process and get the drug to market and having a drug on the market with an orthogonal mechanism of action to the stabilizers, that I think that there's going to be a fair amount of demand from patients that are not adequately responding to tafamidis to get access to Amvuttra.
Got it, and again, just thinking about what could potentially drive this into a combo.
Yeah
- or early-stage combo, it seems like it's been... It's harder and harder to get outstanding data in this patient population, right? Patients are managed a little bit better.
Yeah.
There's gonna be more background therapy. So do you think it's gonna require more data from a combo perspective to clearly establish the clinical benefit, or is there enough, and it might be just related to cost or just clinical experience over a few years?
Yeah, I mean, I think our view of how we see the market evolving has been fairly consistent, and what our view is, is that, until Tafamidis goes generic, it's primarily gonna be a monotherapy market. Certainly, ex-U.S., I see it very, very challenging to get combination therapy reimbursed, and even within the U.S., I think for drugs that will then have overlapping labels that are high, you know, high-cost drugs in a part of the market, and the disease that's growing rapidly and becoming a bigger sort of cost item for insurance companies, I do think that it's gonna be pretty restrictive in terms of the ability to get combination therapy reimbursed. Not impossible, but I don't think that's gonna be the driver for the market, until TAF goes generic.
I think when TAF goes generic, and I think our view of in the U.S., of when we anticipate that happening, I think our view is consistent with what Pfizer has said, right? So Pfizer has said that they think the end of 2028 is when we'll see generic competition in the U.S. So we do agree with that. I think at that point, the combination opportunity becomes more significant. I think our... You know, given the data that we delivered in the study in that Tafamidis subgroup, not stat sig, it wasn't designed for that, but certainly the trends were very positive and suggested of additional efficacy there. I think that will position us to compete effectively in that part of the market, and frankly, creates a what I view as a very durable franchise, even post TAF generic.
Got it, and again, just to check the box. In any meaningful gaining stats right now into filing a potential approval, because if this sets you up for a Q2 2025 launch, is that reasonable?
John, you wanna talk about sort of maybe the-
Yeah
- expected timelines and what we're focused on right now?
Yeah. I think probably the best we can do is to just highlight what we have typically done, which is it's taken us between three to four months to file from the time of top-line release.
... and we've, as we've discussed, we plan to use our Priority Review Voucher, and we would, and you'd anticipate a six-month cycle with the FDA in the context of a Priority Review Voucher. So you can kind of do the math, and it should put you in the ballpark.
Got it. And then another point of debate, more on the near-term launch dynamics, is reimbursement and the fact that the Part B drug versus Part D for Tafamidis. What are some of the pros and cons? There are some considerations in terms of out-of-pocket, et cetera. Can you just kind of untangle that a little bit?
Yeah, this is a good question, and I think that based on conversations that we've been having with investors, this is probably an area that people are not quite as well educated on as they need to be, and I do think that we're gonna have a TTR Investor Day in New York on October ninth. This will be something that we'll probably talk more about. This is a heavy Medicare population, so we're probably looking at between 70% and 80% of the patients that will ultimately be treated will be Medicare patients, and this is important. We're a Part B drug, so that means, you know, physician or healthcare professional administered. Tafamidis is a Part D drug.
BridgeBio, assuming that they get approved, would be a Part D drug, and ultimately Ionis AZ, assuming they get an approval, they'll also be a Part D drug. So three drugs, at least, from what we see right now, Part D, one that would be Part B, will be us. So let's just talk about the differences. First, I think from a patient perspective, in terms of out-of-pocket burden to be on these therapies, Part D versus Part B. Good news for patients on the Part D side is with the IRA redesign, there's a cap that's being instituted that will cap the out-of-pocket expenses for patients at $2,000. That cap will be fully implemented next year. It's actually being sort of phased in. The cap this year, I believe, is $3,250.
Okay.
Yeah. And so actually one of the things that Pfizer's commented on in the first two quarters, if you look at the U.S. results, in particular for their Tafamidis franchise, been really exceptionally strong growth. And they've commented that part of that was impacted by this cap coming into effect this year and allowing and enabling more patients to afford to be on the drugs. So that's a good thing for all the patients. So ultimately, that'll get down to $2,000 next year. Compare that to what we see on the Part B side. If you look at our existing book of business for the hereditary PN population, about 70% of the patients today have zero out-of-pocket, right? The...
There's a, you know, vast majority of patients that are on the Part B side in terms of the Medicare coverage that they've got. They've got Medigap or supplemental coverage that, you know, covers all of the out-of-pocket expenses that they might be liable for. So the vast majority of patients on the Part B side are still gonna be advantaged relative to Part D in terms of the $2,000 cap. I think the other thing to look at in terms of Part B versus Part D is the payer management and likely where is that, you know, gonna potentially be more intense? And I think this is probably the area of the Part D, you know, the IRA impact on Part D that's less understood.
Pre-IRA world, the liability for the cost for, you know, covering the cost of these drugs for drugs that are in the catastrophic coverage, you know, portion of the liability, which is everything today, it's about above $8,000, enters the catastrophic coverage portion of the liability. Pre-IRA, the plans that administer the drug benefit were responsible for 15% of that. So again, everything above $8,000 for a drug like Tafamidis that has a list price of $250,000, plans were responsible for 15% of that cost. That is increasing to 60% in the post-IRA world. So next year, the plans that administer the drug benefit for that catastrophic drug sort of expense, 60% of the cost will be the plans.
And so their focus in managing drugs in that category will be much more, I think, intense and focused than what it's been historically. And so, on the Part B side, we'll be immune to a lot of that, right? And I think from a payer management perspective, there's some benefits there for us.
Got it. And then just to wrap up the access, the at-home HCP, again, that seems to be a important driver in polyneuropathy. How would that play out in cardiomyopathy, just in terms of more patients? Like-
Yeah.
Is there a bottleneck in the system potentially for this?
It's a good question, and so because we're a Part B drug, you know, the drug has to be administered by a healthcare professional. And the approach that we've taken is to give patients and physicians options on how they want to have the drug administered. And today, about 25% of the patients actually get it in the home. So some, you know, somebody comes to the home, administers it.
Yeah.
It's a very simple injection. I mean, I think, John, what is this, 15 seconds to inject the drug? Yeah.
If that.
So it's a very simple process. So about 25% of the patients have elected to get it in the home. Twenty-five percent of the patients today, roughly, are getting it at freestanding infusion clinics, generally speaking, conveniently located to where they live. And then the remaining 50% are getting it in a hospital outpatient setting. And so one of the things to look at, I think, to understand the sort of the convenience of how the, the drug is administered, is to look at the compliance rates that we've had historically. Actually, both on Onpattro, which is an every three-week IV infused drug, and then obviously Amvuttra, which is a quarterly subQ. We've seen compliance rates and adherence to therapy well north of 90%.
And so I do think the fact that we've made getting the treatment as convenient as possible has been one of the reasons that you've seen those compliance rates as high as they've been. And so, I think that will continue to support you know, the growth and the launch of the therapy as we move into the cardiomyopathy part of the market.
The question that everyone asks, Riley, polyneuropathy supports a different pricing. There's a different model.
Yes.
You have Tafamidis as a comp on the cardiomyopathy side. Do you think Vutrisiran has established a differentiated enough profile where you could have a premium over standard of care from a pricing perspective?
I mean, it's a little early for us to talk specifics on price, and also it's a competitive marketplace, so we're not ready to go there yet, but let me just sort of talk about the dynamics and ultimately the things that we're thinking about that will ultimately lead to, you know, sort of a final decision on how we're going to price. First thing I should be clear about is, you know, we won't have the ability to have one price for the polyneuropathy part of the market and a different price for the cardiomyopathy part of the market.
No branding.
No, it's not. There won't be split indication pricing. It's the same product. It's administered, you know, same way with the same frequency. So we'll have one price for our franchise overall. So whatever we choose to do with price on the cardiomyopathy, as we expand the label and launch there, it will have an impact on the existing business that we've got. And the existing business is doing, you know, very well, right? We're annualizing at more than $1 billion in revenue and polyneuropathy today, and that's a part of our business that continues to grow at a very healthy pace. And so we'll have to factor that in to our thinking. But the two things that we really think most about in terms of how we price this is the value that we bring to the healthcare system.
And I think given the clinical data and the efficacy that we've talked about and highlighted in this study, we think the value that we bring is substantial, right? So we'll think about that. And then from a patient perspective, we want to make sure that we position the drug in a way that we can get this drug to as many patients as possible. And obviously, we talked about minimizing the patient, you know, cost burden as we do that. Those are the things that we'll think about. We've obviously got a rich data set from HELIOS-B that we're now using to do a lot of market research with payers to really make this decision. So I think we'll have more to share on the specifics of that around the time of launch.
Got it. And perhaps just one final question on the competitive landscape related to AstraZeneca. I guess one of the questions we usually get is, again, they're running a larger trial. Can they actually generate differentiated claims? And again, it's kind of tough to make that call right now, given how much placebo has changed across different trials and different periods of time. This is around the same time, but again, just very difficult to compare across trials. So let's leave that aside for now. But how should we think about the long-term competitiveness from vutrisiran versus other silencers?
Yeah
and how would that play out longer term, in your view?
Yeah. Obviously, as you said, we'll have to see when the data comes out. Our assumption is that they're going to have a successful study. I'm sure that their sort of internal expectations for that probably have gone up as they've seen the HELIOS-B results. Certainly, from a planning perspective, that's what we're assuming they're going to have a successful study. But, you know, we've already sort of detailed the strength of the data from that we announced on Friday last week, and we do think that it positions us very well from a first-line perspective, very well from a switch perspective, and ultimately, very well from a combination therapy perspective. I think we also have the ability over time to potentially generate more data, right?
We've got a heck of a lot of data from the study itself, but we have the ability to continue to generate more data to support use of our product, and I think we intend to do that. You know, competitively, I think one of the other important things here is assuming that Astra and Ionis let their study go to sort of the full conclusion of the study, which I think is around a 32-month endpoint. You know, we'll have a lead in terms of time to market, probably 18-24 months, which I think is a-
Okay
... is a fairly substantial advantage, and we certainly want to take full advantage of that to establish ourselves firmly as the leading silencer in the space. And again, I think that'll be to our benefit. And then lastly, I would say, you know, it doesn't end with Amvuttra, right? We've got another program that's moving towards a phase 3 clinical study that will allow us to potentially generate data to support approval and label claims that we hope will allow us to be very competitive long term as well. And actually, maybe have John just talk about ALN-TTRsc04-
Four.
What that program is, why we're excited about it, and sort of where it is from a timeline of clinical development standpoint.
Yeah. Yeah, I know we are super excited about ALN-TTRsc04, and it's our next generation compound, where we will see deeper and more durable knockdown. We believe that we can have very deep knockdown with annual or biannual dosing. We shared a little bit of that data last December at our R&D day. What we're seeing in the phase 1 is knockdown over 90% within fifteen days, by day 30, over 97%. That's durable out to... we're still over 90%, six months out.
So really durable, really deep knockdown, which now that we have proven this therapeutic hypothesis, in HELIOS-B, that reduction in this pathogenic protein results in the type of outcomes that we've seen, we think there's potential that we could see even-
... even greater benefit that with this, with this deeper knockdown. So very, very excited about that. On with regard to timeline, we are the phase 1 study is ongoing. We're continuing to look at even higher doses, and be planning to share thoughts around phase 3 design at around the end of the year, and really, really excited about that. I don't know if you wanna talk about the Roche- the-
Yeah, I mean, one of the things that's attractive, in addition to the potential, you know, convenience, advantages, and potentially, you know, better efficacy, given the deeper knockdown, is that from a financial perspective, there's no royalty burden to Sanofi on that particular product, and on Amvuttra, the royalty burden is between 15% and 30%, and that sort of ratchets up as the sales on Amvuttra would increase over time, so even if you just think about switching the existing business-
Longer term, the margin profile looks-
Yeah, I mean, just even if you switch the existing business and not actually expand the opportunity, there's a pretty substantial economic benefit to that. And, and from an IP perspective, that this, you know, has IP out into the 2040s. And so, look, I think this is what leaders do in a particular space, is to sort of continue to innovate and, and invest, to, to sort of drive long-term value, and I, I think that this is a, an exciting program for us.
That's fair. And you already mentioned, for the October event, we're gonna get some more details on the reimbursement dynamic. What else should investors expect to see there? And probably a little too early, but do you have a sense of what metrics will investors-
Yeah
... be able to follow semi-real time to track the launch?
Yeah, I think that, you know, now that we've put out as much data as we've had, you know, on the trial results, I think that as investors absorb that data and understand it better, I think the sense that we have is people are gonna start to pivot towards thinking more about the commercial opportunity and where are we in terms of planning and preparation to launch, as John indicated, sometime, you know, first half of next year. And so that's really what the primary focus of that investor day will be. I can't sort of outline the agenda for you just yet, but it will be primarily focused on commercial topics around, again, preparation for the launch.
We certainly will talk about some of these access and reimbursement dynamics, which I don't think are fully understood by the market yet. So those would be the types of things I think that we would cover. As I think ahead to, you know, the types of information that we'll be able to share with the market, again, you're right, it's probably too early to for me to be able to fully commit. But one of the things actually that may make it just a little bit challenging is that, you know, as we report revenues for Amvuttra, we won't have the ability to say Amvuttra PN was this, and Amvuttra CM was this, right? It's gonna be Amvuttra, right, overall.
Obviously, as we launch into cardiomyopathy, I think the cardiomyopathy opportunity is gonna be the driver of that growth, but we won't be able to sort of split that out because we won't have that detail, but if I think about the things certainly that I know that we'll be tracking very closely internally, certainly in the U.S., we have, you know, the start of the process to get a patient on a drug like this requires what's called a start form. So we'll have the ability to track those, and typically, when we've launched new therapies, we've provided that kind of detail for at least a couple of quarters post-launch.
I think other things that we'll be looking at very carefully will be, you know, access and reimbursement metrics in terms of our ability to sort of open up, you know, different plans and things like that. That'll be tracked very carefully. We'll be looking at expansion of the prescriber base. I think we'll be looking at sources of business, right? How much is coming from switch versus how much are-
Right
... are naive to therapy. So we'll have a lot of that data. Again, I'm not ready to commit to exactly what we're gonna put out into the market, but it'll. We clearly understand that it's gonna be important for us to educate the market on the performance of the launch, and so we'll be thinking about that and refining our thinking on that as we move towards the launch.
And again, you've been fairly successful self-commercializing the rare disease space. Again, this is still relatively rare. It's a slightly different end market, but again, how should we think about that launch? I guess my key question here is just operating leverage into that launch. Like, how much incremental investment are you gonna have to do?
Yeah.
What would that look like for the next few years, potentially?
I mean, it's a good question. Let me talk about a couple things. I wanna talk about sort of the commitment that the company made to profitability and sort of where we are in thinking about that. And then I wanna come back to this point about operating leverage, 'cause I think it's a key one. But first on sort of financial performance, in January 2021, at JPMorgan, we put out a series of goals that we sort of coined P5x25.
Yeah.
And there were two financial goals that were part of that. One was around top-line revenue growth across that five-year period that would end in 2025, where we committed to a CAGR of at least 40%. And then the second financial goal was to get to non-GAAP operating profitability by the end of that period. I would say based on where I sit right now, with a year and a half to go, I think our confidence level in achieving both of those is at an all-time high, and it's really driven by two factors. One is the base PN business is really performing very well, even in the face of new competition in the US, that entered the market at the end of last year.
In our and on our Q2 earnings call, we upgraded guidance for this year fairly substantially, about 10% from the midpoint of the original guidance to the updated guidance. Second factor that speaks to the confidence of achieving the financial goals are the HELIOS-B results themselves, right? And the fact that we'll be launching, you know, early to mid-next year, we think certainly will be a big time tailwind in terms of revenue growth for next year. And so both of those things, I think, put me in a confident position that we're gonna achieve both of those goals. As it relates to operating leverage, this is one thing I just want to emphasize around the launch, is that, you know, we're not starting from scratch, right?
We've been in the hereditary PN part of the market for more than five years. And the way this disease is treated, and John can speak to this a lot better than I can, is typically you know there's a lot of academic centers of excellence, where you've got physicians that are cardiologists that are already using our product, frankly, to treat PN patients. And so they're familiar with the product, they're familiar with the mechanism, they're familiar with Alnylam and how to work and operate with us. And so we're gonna be building off of that as we launch into cardiomyopathy. And so there's some benefits just in terms of know-how and knowledge, but there's also some benefits of we've already got the infrastructure in place to facilitate a lot of this.
Now, there's no question that we're gonna have to scale that up some, given the substantially larger opportunity. But I think it's really important to note that we're leveraging the foundation that's already been successful in polyneuropathy as we move into the cardiomyopathy setting. So all of that, I think, will be supportive of the goal to get the company to profitability, and then sort of beyond profitability as we start to think about, you know, operating margins and things like that. That's an area that I think that we will get leverage over time.
Got it. And we are almost out of time, and I just, so I just wanna touch a little bit perhaps on the overall pipeline. Just where do you think it's most overlooked right now? I think it's difficult to answer the question in the light of CM being such a big driver, but where should investors start to pay attention on the earlier stage?
I mean, I think all of it's been overlooked - for the last couple of years just because of the focus on, on, you know, TTR and, and first APOLLO-B and then HELIOS-B. I mean, I think the investment community has spent about 90% of their time as they've been thinking about Alnylam, thinking about that. If I just base it off the amount of time that we spent with investors and answering questions, and so-
The buyer side.
Yeah. And so I, so I do think as we, as we move past Helios-B, there's still gonna be an intense focus on the commercial preparation and the launch. But I do think that people will start to, to think about and look at other things in our pipeline, and I think as, as they should. I think we've got, you know, a very successful platform. We're a true platform company. I mean, everything that we've got in the market is based on the, the, you know, the underlying RNAi platform. Everything that we've got in the pipeline is also based on that same platform. And so I, I do think people will start to focus more on, on the pipeline. John already touched on TTRsc04. Again, it's another TTR program, but that's a, a program that's gonna be moving into a pivotal study next year.
I think people will start to be, or will be very interested in the design of that study, in terms of thinking about how that might be positioned from a commercial standpoint. I think the next program up that people are starting and will spend more time on is our hypertension program, which is in phase 2. That's a program that we've partnered with Roche. We have a, you know, one ongoing phase 2 study called KARDIA-3, that's looking at, you know, zilebesiran in combination with two or more concomitant medications. And I think the readout from that will really help us develop and size and power the CVOT.
We've talked about this being that we're gonna run an outcome study there to get the drug to market, and so the data that comes out of that study will really inform the design of that CVOT. But I anticipate that we'll be moving into the CVOT there next year. The other thing that I would say, just more broadly in terms of what we're trying to do with the technology, is to expand into additional tissue types. We didn't touch on our first CNS program, ALN-APP, which,
That's around, yeah.
... is moving into phase 2, and we've got an ongoing collaboration with Regeneron to bring more CNS therapies forward. But at our R&D Day in December last year, we also are targeting to take our technology into two additional tissues by the end of next year. We've highlighted muscle and adipose as areas of particular interest. I think there's gonna be a lot to think about as the pipeline expands pretty significantly in the next eighteen months.
Got it. And I guess with that, we can probably wrap up. Jeff, John, really appreciate you spending the time. Thank you so much.
Thank you.
Thank you.
We appreciate you having us here.