Good morning, ladies and gentlemen, and welcome to the Alnylam Q2 2025 Earnings Conference Call. [Operator Instructions] This call is being recorded on Thursday, July 31, 2025. I would now like to turn the conference over to the company. Please go ahead.

Good morning. I'm Christine Akinc, Chief Corporate Communications Officer at Alnylam. With me today are Yvonne Greenstreet, Chief Executive Officer; Tolga Tanguler, Chief Commercial Officer; Pushkal Garg, Chief Research and Development Officer; and Jeff Poulton, Chief Financial Officer. For those of you participating via conference call, the accompanying slides can be accessed by going to the Events section of the Investors page of our website, investors.alnylam.com/events. During today's call, as outlined on Slide 2, Yvonne will offer introductory remarks and provide some general context. Tolga will provide an update on our global commercial progress. Pushkal will review pipeline updates and clinical progress, and Jeff will review our financials and guidance followed by a summary of our upcoming milestones before we open the call to your questions. I would like to remind you that this call will contain remarks concerning Alnylam's future expectations, plans and prospects, which constitute forward-looking statements for the purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors including those discussed in our most recent periodic report on file with the SEC. In addition, any forward-looking statements represent our views only as of the date of this recording and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update such statements. With that, I'd like to turn the call over to Yvonne. Yvonne?

Thanks, Christine, and thank you, everyone, for joining the call today. As shown in our Q2 results announced today, Alnylam is firing on all cylinders, and we're swiftly establishing ourselves as a top-tier biotech company. We're doing so by focusing on 3 core elements of the business that we believe will drive sustainable growth and value creation for years to come. The first is TTR leadership. As highlighted in today's press release, the launch is off to a very strong start. And whilst it's still early days, we're encouraged by the pace, and we're deeply focused on laying the groundwork for long-term leadership in TTR. The next is growth through innovation, focused on the potential multibillion-dollar opportunities within our pipeline and an R&D engine set up to deliver sustainable innovation and value creation. To that end, I'd like to acknowledge the recent promotion of Pushkal Garg to Chief Research and Development Officer. Pushkal has been instrumental in progressing our pipeline. And in this role, Pushkal will oversee an integrated R&D organization to drive this exciting pipeline and platform into the future. Congratulations, Pushkal. The third element is strong financial performance with robust commercial execution and disciplined capital allocation approach, providing us with the opportunity to sustain profitability going forward. As Tolga and Jeff will highlight later, the strong therapeutic profile of AMVUTTRA and ATTR-CM, combined with a large and underserved market, positioned this as a flagship commercial franchise with robust and durable long-term growth potential. And of course, all of this is underpinned by a best-in-class team and our award-winning culture. Our results this quarter fit within each of these strategic pillars and represent one of the most impactful quarters to date for Alnylam. Our commercial performance was driven by TTR franchise revenues of $544 million, 77% year-over-year growth with…

Thanks, Yvonne, and good morning, everyone. I'm excited to share with you the results of our Q2 commercial performance. As Yvonne indicated, we are firing on all cylinders, and our Q2 performance was exceptional for the full portfolio. On a global basis, our commercial portfolio delivered $672 million in net product revenues, representing 64% year-over-year and 43% quarter-over-quarter growth. As you will see in a moment, the U.S. TTR performance was the major driver of growth given the ATTR-CM launch for AMVUTTRA. It is also encouraging that we saw very robust double-digit growth compared with Q1 across both our TTR and Rare franchises across the globe. All parts of our business are operating with focus and excellence. Let's quickly start with our Rare franchise. Our GIVLAARI and OXLUMO teams stayed focused and delivered $128 million in combined Q2 sales, up 24% versus last year. Growth was largely demand driven with a tailwind from favorable GIVLAARI gross-to- net adjustments in the U.S. Now turning our attention to TTR franchise, where we delivered $544 million in global net product revenues during the quarter, representing a 77% increase compared with the second quarter of '24 and a robust 51% increase compared with the first quarter of 2025. In the U.S., combined Q2 sales of ONPATTRO and AMVUTTRA rose 80%, up roughly $170 million from Q1, driven primarily by AMVUTTRA's ATTR-CM launch. We closed the quarter with approximately 1,400 cardiomyopathy patients on therapy, contributing an estimated $150 million in revenue. This performance was fueled by strong execution and faster-than-anticipated access across payers and providers. Regarding the year-over-year dynamics, the U.S. TTR franchise grew 125% compared with the second quarter of 2024, primarily driven by the significant increase in demand from the ATTR-CM launch that I just highlighted. Turning to our international markets. We delivered…

Thank you, Tolga, and good morning, everyone. I'm delighted to see the early success of AMVUTTRA in these first few months of the launch. It is a true testament to the outstanding execution of our commercial and medical teams and to AMVUTTRA's unique and compelling profile established in HELIOS-B. To that end, we continue to generate evidence from the HELIOS-B study that further supports the long-term efficacy and safety of AMVUTTRA with the aim of cementing it as the first-line treatment of choice for patients with ATTR cardiomyopathy. This slide highlights some of the unique and profound benefits of AMVUTTRA's rapid knockdown mechanism of action that are emerging from HELIOS-B. In the left column, you can see the benefits on NT-proBNP and troponin I, important clinical biomarkers of cardiac stress and injury, respectively. Not only do you see a larger effect -- a large effect in patients receiving drug versus those on placebo, but it's interesting to see a reduction compared to baseline in troponin I, suggesting a potential disease-modifying effect on this biomarker. Further to that point, echocardiographic data in the middle column shows improvements in critical aspects of cardiac function, both diastolic and systolic. And ultimately, we saw this translate into substantial improvements in all-cause mortality as well as cardiovascular mortality of 33% to 36%. In addition to data coming from the HELIOS-B study, we are continuing to generate evidence to further support the safe and effective use of AMVUTTRA via numerous registry and real-world evidence-based studies and investigator-initiated studies. We look forward to sharing data from these sources over time. Further to our leadership and commitment to innovation in ATTR amyloidosis, we announced in June the initiation of the TRITON- CM Phase III study for nucresiran, which may offer greater knockdown, greater efficacy and greater convenience for…

Thanks, Pushkal, and good morning, everyone. I'm pleased to be presenting a summary of Alnylam's Q2 2025 financial results and discussing our full year upgraded guidance. Let's begin with a summary of our P&L results for the second quarter compared with prior year. Total product revenues for the quarter were $672 million or 64% growth versus 2024, driven by 77% growth in our TTR franchise with particularly strong performance in the U.S. market, primarily related to an increase in demand associated with the launch of AMVUTTRA and ATTR cardiomyopathy. Collaboration revenue for the quarter was $61 million, representing a $166 million decrease when compared with last year. The decrease was primarily driven by the modification of our cemdisiran collaboration agreement with Regeneron, which resulted in approximately $185 million of revenue in Q2 2024. As a reminder, this amendment granted Regeneron an exclusive license to cemdisiran monotherapy. Royalty revenue for the quarter was $40 million, representing an $18 million increase compared with last year, driven by higher Leqvio sales. Gross margin on product sales was 79% for the quarter compared with 84% in the second quarter of 2024. The decrease in margin was primarily driven by increased royalties on AMVUTTRA as higher revenues in 2025 resulted in an increase in the royalty compared with last year. For the balance of the year, our gross margin on product sales is expected to decrease as the applicable AMVUTTRA royalty rates increase driven by higher sales of AMVUTTRA. Our non-GAAP R&D expenses of $274 million increased 11%, primarily due to increases in start-up clinical trial expenses associated with our cardiovascular outcomes trial for zilebesiran and the TRITON-CM Phase III study for nucresiran. Our non-GAAP SG&A expenses of $261 million increased 26% compared to last year, primarily driven by increased headcount and other investments in…

Thank you, Jeff. Operator, we will now open the call for questions. To those dialed in, we would like to ask you to limit yourself to one question each and then get back in the queue if you have additional questions.

[Operator Instructions] Your first question comes from Richter Salveen with Goldman Sachs.

Congratulations here on the quarter. Could you give some details here on the patient profiles for AMVUTTRA with regard to the frontline patients and whether you're seeing mostly mixed phenotype patients or more of a broader population mix? And help us understand from here what the field force is most focused on.

Thanks, Salveen. I mean I'll start by saying, look, it's early days yet, but we're incredibly pleased with where the launch is going, particularly with broad and robust uptake because I think it also really shows is the data that we generated from HELIOS-B is really resonating with physicians. The rapid knockdown of TTR, all-cause mortality improvements, infrequent subcutaneous administration, which provides both convenience and security. So we're seeing broad uptake across first-line patients as well as patients that progress on stabilizers. We're seeing use across the community physicians as well as academic physicians as well as new prescribers as well as repeat prescribers. So the trends are really very supportive in suggesting continued growth. Now I think it's fair to say that the initial pickup has been faster in the stabilizer progressing patients because when you bring in a new therapy and the patients who've been progressing on stabilizers, it's not surprising that physicians are looking for an orthogonal treatment for these patients. But we're now achieving a really healthy share of first-line patients. So we have a good mix of first- line stabilizer progressors. And what we're going to be doing is really consolidating and building on the foundation of this very early picture. Tolga, you probably want to add a couple of comments.

Actually, you pretty much covered everything. What I would say is, again, we're just 1 quarter in and what we're already seeing, what you described is validates our clinical thesis and commercial strategy.

The next question comes from Tazeen Ahmad with Bank of America.

I just wanted to get a sense on how you're thinking about net price for AMVUTTRA and gross-to-net moving forward?

Yes. No, thanks for that question. Jeff, perhaps you'd like to start off answering that. And if there are any additional perspective, Tolga and I can follow on from you.

Yes. Just a reminder of what we said back on the approval call in March. We said that we expected that we would reduce net price modestly and gradually over time. And that does hold for our expectation for 2025. 2025 relative to 2024, I would expect mid-single- digit reduction in net price for AMVUTTRA for the year.

Tolga?

Yes. I mean, look, I think one thing is also to importantly highlight is the fact that payer dynamics are moving very much as what we exactly expected. A lot of the payer policies are already out, both on Medicare Advantage as well as in commercial. And what we're seeing is a first-line access to those patients and patients actually paying minimal, in most cases, 0 out-of-pocket costs. So we will obviously manage that with early engagement with payers and the impact of the gross-to-net is going to be, as Jeff highlighted, will evolve over time.

Thanks, Jeff and Tolga.

The next question comes from Maury Raycroft with the Jefferies.

Congrats on the great quarter. Wondering if you can comment on whether there was any bolus effect in cardiomyopathy scripts in second quarter? And could you also please clarify to what extent did stocking contribute to the growth of U.S. AMVUTTRA revenue in the second quarter?

That's a great question. Look, I think Tolga has touched on this. We've really demonstrated very solid commercial execution. And that means that we've seen a little bit of faster progress than we expected, particularly around health system setup. So I touched on this already, but it's meant that we had initial faster pickup with stabilizer progresses. But as we went through the Q, we now have this very healthy share of first line. And we're just in the first quarter of launch. So I think the key message number one for me is that the results that we're sharing with you today are not just a flash in the pan. We expect continued sustainable growth, and that's the reason why we raised guidance today. And I think the second key message is really just the durability of the franchise. We expect to see AMVUTTRA deliver continued sustainable growth, but we'll be bringing nucresiran forward as well, as Pushkal highlighted, which gives us the potential to deliver franchise growth out into the 2040s.

I'll comment on the second part of the question, which was about inventory. I think the headline for the quarter is, again, in the U.S., Tolga in his prepared remarks, highlighted the $170 million in growth in the TTR franchise in the U.S. Q2 versus Q1. Far and away, the biggest driver of that was the cardiomyopathy demand. 1,400 patients on therapy, $150 million in cardiomyopathy revenue for the quarter is what we're estimating. On the inventory side, we did see about a $25 million benefit in Q2 compared to Q1. That's not actually because days on hand increased between Q1 and Q2 as it actually stayed constant at around 20 days, which is at about the midpoint of the agreements that we've got in place with our distributors. What drove the increase in inventory in the quarter was the calculation of what a day of demand is -- or a day of inventory is worth, which is based on a 12-week moving average of demand. And so it was demand that really drove the increase in inventory in the channel in the quarter, which is, again, a high-quality increase in channel stocking in the quarter. Now on the gross-to-net side, we had an opposite movement. So a headwind that roughly offset the benefit that we had in inventory, which is why we're highlighting demand was the key driver of growth in the quarter. On the gross-to-net side, a couple of things. One is that we had an increase associated with the Part D rebate that we're paying like -- anybody that's got a Part D drug at this point is paying rebates on the IRA Medicare redesign. We do have a small portion of our TTR sales that go through the Part D channel, and that's the home care part of the business. Historically, that's been about 20% in polyneuropathy. So there is an increased rebate that we're paying there, which was in line with our expectations. We also saw modestly higher 340B utilization in the quarter. So on price -- net price, Q2 to Q1 was down slightly, which is consistent with what I said on the earlier question that we do expect net price '25 versus '24 for AMVUTTRA to be down mid-single digits.

Thanks, Jeff. I think a very important question, and I think you've clarified that for our investors. So thank you.

The next question comes from Jessica Fye with JPMorgan.

Can you speak a little more -- in a little more detail to the assumptions underpinning the updated TTR franchise guidance as it relates to like the pace of new starts? And I guess just in general, can you just maybe provide a little assurance or reaffirm that the new guidance is not somehow aggressive?

Okay. So 2 parts to that question. Maybe Tolga, if you start with the first part and then, Jeff, you can follow on from that.

Yes, absolutely. Hi, Jessica, I mean, look, at the end of the day, what we have already laid out is we're expecting a steady growth in both first line as well as the second-line patient flow. As Yvonne indicated, let me also provide a little additional color. As expected, we initially saw uptick concentrated in patients who had progressed on stabilizers. And these are often sicker patients. Physicians naturally look for an alternative therapy with a mechanism of action that's unique, that's accessible, easy to administer and so forth. But what's been really particularly encouraging, and this is why the guidance we're providing is over $0.5 billion uptick from where we were is, about a month into the quarter, we began seeing a very healthy and accelerating trend in first-line use, just as we had positioned from the outset. And frankly, that makes a lot of sense. This is a progressive and fatal disease. Physicians want to hit the disease early and hit it hard and not hold back their best therapy for later as they might in less serious conditions. So today, and this is where the guidance is really anchored in, we see both first-line and second-line segments are growing. They're growing rapidly. Uptake is broad across first and second-line and academic and community. And more importantly, we are seeing a good expansion of our prescriber base. We've just expanded by threefold, and that continues to move in the right direction. So as we move forward, our focus is clear: to continue reinforcing AMVUTTRA as the first-line treatment of choice, supported not only by our approved label, but also by growing evidence, as Pushkal highlighted, with new imaging data, emerging cardiac biomarker trends that suggests AMVUTTRA may even help reverse disease progress. So nonetheless, we're just 1 quarter in and already seeing that behavior that validates our clinical profile as well as our commercial ambitions. And I think the current guidance really reflect that.

Yes. Look, I think I just want to emphasize that it's early days yet. We're only -- we've only just achieved our first full quarter here. And when we came up with the guidance -- we've given guidance that we expect to achieve. We're going to be focusing our team on continued execution. And as we progress, we will continue to update and share our perspective.

Yes. Maybe just a little bit more context on the guidance. Again, if you look at the -- what I've highlighted in terms of the midpoint of the guidance and what it implies in terms of year-over-year growth for TTR, about $1 billion, right, is what I highlighted. Last year, the PN franchise grew $300 million versus '23 and was growing at about 30%, right? So if you just sort of assume that, that's the growth that we're going to get from PN this year, that would imply $600 million plus from cardiomyopathy. We just did $150 million in the second quarter, and we feel really good about growth sustaining through the second half of the year. So I do think we have a high level of confidence in the guidance that we provided, Jess.

The next question comes from Paul Matteis with Stifel.

One for Tolga and the team. As it relates to stabilizer progressors, can you talk a little bit more about the criteria physicians are using? And I guess now that you've been in the market, do you have a sense of what percent of patients who are on a stabilizer currently would be dictated to be a progressor and a good candidate for AMVUTTRA based on the clinical criteria that are being implemented?

Yes. So we'll start with Tolga and then I'd like Pushkal to provide a clinical perspective.

Yes. So Paul, I mean, look, based on our research and obviously published data, clinical evidence suggests that anywhere between 1/3 to half the patients on stabilizer at one point progresses. And we see that number is continuing to grow. And then obviously, the only real option in terms of mechanistically and the clinical evidence suggests that it would be AMVUTTRA at this point. But let me turn it over to Pushkal, who can also provide some more clinical perspective about what we're seeing and how those guidelines are actually progressing.

Yes. Thanks, Tolga. Thanks, Paul. Look, I think it's really important. This is -- we talk about ATTR cardiomyopathy. And the thing here is that it has a clear cause, which is the accumulation of TTR protein in the -- misfolded protein in the myocardium. But as it clinically presents, it's a form of heart failure. And doctors have been treating heart failure for decades, and they know how to modify drug therapy for patients. They might add diuretics or SGLT2s or other agents as patients are progressing. And so I think they're well accustomed to actually looking at a variety of factors. And frankly, you have to rely on a variety of factors. There's not any one specific indicator. An easy way to think about that is when you look at the European guidelines that were put out a couple of years ago, and they had a variety of considerations, including biomarkers, echocardiographic factors, exercise tolerance, patients' ability to lie flat at night, different things, pedal edema. And so I think what we're seeing now in these early days is that doctors are applying that general clinical rubric of looking at a patient, how they present their symptoms, their signs, and other factors in terms of determining how patients will progress. We do think that over time, more and more guidelines in this category will develop over time. But our expectation is that there will not be some one single factor that clinicians or payers will be able to rely upon to say specifically that the patient is progressing, but we rather have to look at the constellation of factors that affect the patient's symptomatology.

The next question comes from Luca Issi with RBC Capital.

Congrats on the strong quarter. Maybe if I can circle back on the TTR guide, maybe, Jeff, like if I assume $200 million in revenue for the year from ONPATTRO, that essentially means $550 million to $650 million in revenues for the next 2 quarters for AMVUTTRA, which is actually not dissimilar from the $492 million that you already printed today. I guess what I'm trying to say, it feels to me that this guide has still a good degree of conservatism in it, especially given that you're going to start selling this drug in international markets like Brazil, Europe, U.K., Japan, et cetera. But I would love if you have a different view here. So any thoughts there, much appreciated.

Yes. Luca, I appreciate the question. I'll again reiterate what I said to the earlier question here. We're guiding to $1 billion of TTR growth year-over-year. Last year, PN grew $300 million and is growing at about 30%. So that gets you to $600 million plus for cardiomyopathy. We just did $150 million in Q2. I think we feel very confident about that. If you look at historically, the guidance that we've given and the consistency with which we either met that or exceeded that, that's how we feel about the guidance that we're providing. I don't know if it's conservative at this point, honestly, we're 1 quarter into this. And certainly, we look forward to coming back at Q3 and reassessing things.

The next question comes from Ellie Merle with UBS.

Congratulations on the quarter. Just to drill into this a little bit more, how should we think about the rate of new patient starts per quarter from here? 1,400 is obviously a phenomenal number. Should we think of this cadence of new starts continuing in 3Q and beyond? And second, in terms of the mix, you mentioned now seeing more balanced starts mix between the new patients -- newly diagnosed and the progressors, whereas initially, it was more of the progressors. How do you expect this mix to evolve over time from here?

Okay. So I think 2 questions. You can probably take both of them, Tolga.

Yes. So, thank you. Look, at the end of the day, we're very pleased, obviously, with 1,400 paid patients within a 3-month period. And as you had highlighted, while the patient starts initially was more predominantly stabilizer progressors very quickly, that switched into a balanced and broad patient uptake. We certainly expect to see both of those categories continue to grow. Now in terms of the specific numbers, we kind of went out our way to be able to provide that clarity. As you know, AMVUTTRA is a single SKU, so we can't really isolate CN patients with precision. So we're going to continue to provide additional color and those numbers, obviously, we expect to go up. But in terms of the specific precision about how it's going to go quarter after quarter is not going to be -- we're not going to be able to report that.

The next question comes from Kostas Biliouris with BMO Capital Markets.

Congrats on the impressive launch. One question on payers from us, although you already touched a little bit on that. We have seen some commercial payers requiring stabilizer use prior to AMVUTTRA treatment in cardiomyopathy. Can you comment on how common those requirements are across the different plans? And what percentage of patients do these plans cover?

Yes. No, that's a great question. I mean I'll just start off by saying that as we look at this, access is just not a barrier. We're seeing broad coverage across Medicare fee-for-service, Medicare Advantage, commercial payers and the vast majority of patients are getting first-line with no step and this is exactly what we predicted coming into the launch and what we've been working on for quite some time. I think it really speaks to the AMVUTTRA profile as well as the nature of the disease. But Tolga, you might want to, I don't know other perspective.

I mean, you got it, Yvonne. I think the broad headline is really as predicted, we're not facing a significant headwind in terms of payer coverage. What I'm really pleased to see was within a short 3-month period, majority of both Medicare Advantage as well as commercial payers have published policies. And in those policies, AMVUTTRA, in broad strokes are covered first line. Now we also had actually flagged that there could be some commercial payers that could actually provide a step edit in their policies. We're seeing that, but it is incredibly minimal. It's in the single digits. And frankly, we don't anticipate that to continue to grow as most other large commercial payers have already written policies that covers AMVUTTRA as first line. Now when it comes to step edits, we have the tools and the support systems that enables us actually, frankly, to help patients and providers to circumvent that or make sure that it's managed very, very carefully. This is -- it's -- we've actually built over the years a quiet engine, driving real impact in terms of our patient services -- and I'm really pleased to see how we've been able to pull through on all 3 segments. Patients are already getting on treatment, whether it's fee-for-service, whether it's Medicare Advantage, also on commercial payers, including those plans that have actually step it. So we don't see that for now. And obviously, we're going to closely monitor and continue to engage with payers to make sure that these patients that deal with the severe condition are getting a seamless access with our medicines.

Yes, that's great, Tolga. And one data point that really struck me was actually just the minimal use we're seeing of our Quick Start Program. We introduced a Quick Start Program with all of our launches to make sure that we can help patients with access. And we're just not seeing much use, which I think, again, is very encouraging.

The next question comes from Gena Wang with Barclays.

I also wanted to congrats on the outstanding quarter. So maybe, Yvonne, I think you mentioned that the vast majority will be the first- line patient. Is it fair to say that out of the 1,400 patients treated so far, will be over 50% of patients is a first-line patient? And then out of this 1,400 patients, how many of them received free drug?

Tolga, you love breaking this down.

Yes. Look, Gena, good to hear from you. I think what we had said very thoughtfully, I would say, is our uptake has been broad and balanced. So that included, again, early on, some patients that were actually progressing on stabilizers. And then what we're seeing a very, very strong trend of first-line indication. We're in the early innings. And I think the job is to -- and we're getting, I would say, our fair share of first-line patients, but the job is not done yet. What we want to make sure is that we continue this trend and make sure that we continue to educate both patients as well as prescribers why AMVUTTRA has a compelling product profile to be a first-line patient. So I just wanted to reiterate that.

Yes. It's really important that we clarify exactly where we are...

I think she also had a question about the 1,400 patients and how many of them were in the Quick Start Program. It was de minimis, right? It was very, very little.

It was absolutely very minimal.

The next question comes from Mike Ulz with Morgan Stanley.

Congrats on the strong launch as well. Maybe just a follow-up on TTR cardiomyopathy. You highlighted you're getting some nice broad use in the frontline as well as the stabilizer progressor patients. Just curious if you started to see any combination use early in the launch. I know you're not expecting it, but we've picked up some combination use in some of our [indiscernible].

Yes. No, thank you for that question. Tolga, why don't you take that?

Yes. Look, we certainly do see a very small portion of those patients getting a combination use. We would certainly expect that as tafamidis goes generics over the years to become more prominent. But right now, it's really be -- difficult to be very specific about looking at the specific combination use. But I think where it's allowed and where access is permissible, we do some utilization of combo.

I think we've got time for one last question.

The next question comes from Ritu Baral with TD Cowen.

Congratulations on the quarter. A quick question on variants. You guys addressed the mixed phenotype. But in your first-line and first-line accent -- access, what trends are you seeing in the V122I variant population as [ KOL ] feedback, at least on my model, has suggested I'm underestimating that prevalence by about 6x, but it is a more severe phenotypic presentation. And just a very quick follow-up. This is probably semantics, but you guys, Tolga, you've mentioned step-through and step-edits. Are they the same thing as prior authorizations? Or do you have a different set of prior authorizations?

Yes. So let me take your last part first. The step edit policies that we've seen, again, it's incredibly small. It's in the single digit, and it's mostly predominantly in the commercial setting. There are no real -- specific limitations other than patients putting on a stabilizer first. And frankly, there's no even a time limit or duration, and it's really up to the physician if the patient is progressing. So we find these policies relatively easy to manage for the patients. And there are no specific hereditary or V122I indication. And frankly, we're not surprised about that. We have, I think, what we've demonstrated early on with the polyneuropathy, hereditary condition and then later with the broad cardiomyopathy label is that AMVUTTRA is well positioned to be a first-line patient for all diagnosed ATTR-CM patients. And we're really not seeing that trend. Now -- maybe I'll turn it over to Pushkal, if he has any specific commentary on the trial.

I think you said it well. Look, I think what we've seen in HELIOS-B is that AMVUTTRA works equally well in wild-type patients and in V122I patients. And as Tolga mentioned, this is the one class of drugs that's shown actually a benefit in hereditary patients, which constitutes the wide range of mutations, and we've seen benefits across that. So across, I think, all ranges of severity, whether it's NYHA Class I, II, III, whether it's hereditary or wild type, I think -- that's, I think, what really cements our belief that this is really -- and what we're hearing from prescribers in terms of the opportunity to treat patients with this drug as a first-line agent, Ritu.

Thank you, Ritu, I think this brings our call to a close. And I'd just like to thank everybody for joining us today on this call. Look, Alnylam is continuing to execute strongly across all areas of the business, and we're very much looking forward to providing you further updates as we progress throughout the year. Thanks a lot.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.