Alnylam Pharmaceuticals, Inc. (ALNY) Earnings Call Transcript & Summary

All right. We'll get started. Welcome, everyone, to the 40th Annual JPMorgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JPMorgan. I'm joined by Priyanka Grover, Malcolm Kuno and Caleb Smith from the team. Our next presenting company is Alnylam and presenting on behalf of the company, we have CEO, Yvonne Greenstreet. I want to remind all the attendees that there's an ask a question feature in the portal. And if you put a question in there, I'm happy to ask on your behalf during the session. With that, Yvonne, if you want to take the way.

Thanks, Anupam. Look, it really is an honor to be speaking to all of you today in my first public presentation as Alnylam CEO, and I couldn't be more excited about Alnylam prospects. Let's move to Slide 2. During my remarks this morning, I will be making some forward-looking statements. Next slide, please. Alnylam was founded in 2002 on the promise of harnessing the revolution in biology to create a new class of medicines to benefit human health. And this year, as we celebrate Alnylam's 20th anniversary, it is an opportunity to reflect on the journey of the past 20 years and the strong foundation we have in place for future growth. Next slide. As most of you know, Alnylam is the leader in RNAi therapeutics, having pioneered the translation of this Nobel prize-winning technology into a whole new class of innovative medicines. In addition to bringing the first 4 RNAi therapeutic to market in less than 3 years, we've built a robust and high-yielding clinical pipeline across rare and prevalent diseases and established a global company with strong commercial capabilities. And we've done all of this while maintaining a strong financial profile and are now firmly on the path towards achieving financial self-sustainability. Importantly, our derisk platform and proven track record put us in a unique position to create significant future value, underpinned by the items noted here. Next slide. Before I talk about what's in-store for Alnylam in 2022 and beyond, I'd like to reflect on the successes of this past year, some of which are highlighted on Slide 5. We saw tremendous progress with our commercial performance with 83% year-over-year growth in our wholly owned brands. We also made great strides in clinical development, completing enrollment in our 2 key Phase III studies in ATTR cardiomyopathy. And on the regulatory side, we filed 2 NDAs, or sNDAs, and advanced 2 programs towards the clinic, including our first CNS program. And we ended the year with a strong balance sheet and showed significant improvement in our year-over-year non-GAAP operating loss, signaling our path towards profitability. Let's now turn to Slide 6 for a closer look at our commercial performance in 2021. We just preannounced strong fourth quarter and full year 2021 global net product revenues. And in total, we achieved $662 million, representing year-over-year growth of 83%, with Q4 quarter-over-quarter growth of 19%, a particularly impressive result. And these results reflect the strong patient demand for our products, continuous progress in patient diagnosis and innovation in market access. We'll provide 2022 product revenue guidance on our earnings call in February, but we look forward to continuing this trend of commercial excellence across our marketed portfolio. On the next slide, in addition to our commercial assets, Alnylam has a robust and high-yielding clinical pipeline with over a dozen programs spanning Phase I to Phase IV, covering rare and prevalent diseases and now including programs targeting genes expressed in the liver and central nervous system. This is arguably one of the most fulsome clinical pipelines in the biotech industry today. You can also appreciate on this slide the substantial product ownership that Alnylam has retained for its pipeline, where we have global or 50-50 rights for the vast majority of our programs. Next slide, please. One of the reasons we're so excited about this clinical pipeline is that we have delivered outsized success rates relative to industry norms. Indeed, our track record is now nearly 65% from IND to positive Phase III compared with industry metrics of less than 10%, a remarkable and we believe a sustainable difference. This is not sheer luck, it's driven by the power of a reproducible and modular platform, combined with a continued focus on genetically validated targets. Next slide. Our clinical and regulatory efforts have provided a rich set of catalysts that position 2022 as another exciting year for Alnylam. For starters, it will be an important year for our TTR franchise as we present full 18-month results from the HELIOS-A Phase III study of vutrisiran, which I'm pleased to announce will be at the French Peripheral Nerve Society Conference on January 21. Also, we look forward to the potential approval of vutrisiran in April and subsequent launch. Mid-2022, we expect APOLLO-B results for patisiran, which, if positive, could pave the way for potential label expansion for ONPATTRO. We also look forward to multiple data readouts over the course of this year from our early and mid-stage clinical programs. So lots of significant catalysts to look forward to throughout the year. Next slide, please. But of course, the potential for Alnylam goes well beyond the developments expected in 2022. Last year at this conference, we announced our next 5-year vision, our Alnylam P5x25, which is all about establishing Alnylam as a top-tier biotech company with transformative medicines in both rare and common diseases for patients around the world and a robust and high-yielding pipeline of first and/or best-in-class product candidates from our organic product engine while delivering exceptional financial performance. More specifically on the next slide, as we think about our journey towards P5x25 and beyond, we would like to highlight some key potential growth drivers for Alnylam. Let me spend a few minutes touching on each of these. First, on the next slide is the potential near-term expansion of our ATTR amyloidosis franchise where we aim to become the global leader in delivering impactful and highly differentiated medicines to patients with all forms of ATTR amyloidosis. Next slide. As most of you know, ATTR amyloidosis is a debilitating, progressive and fatal disease caused by misfolding of the TTR protein, which accumulates then and damages a wide range of tissues, including the nerves, the guts and the heart. Next slide. It's important to note that we are just at the beginning of the growth opportunity for our TTR franchise. Building on the foundation of ONPATTRO in 2022, we anticipate the approval of vutrisiran for hATTR with polyneuropathy, and the data readout from the APOLLO-B study of ONPATTRO in patients with ATTR cardiomyopathy. Thereafter, we see a further expansion of the TTR franchise, namely, we look forward to the outcomes data from HELIOS-B and the potential approval of patisiran for ATTR with cardiomyopathy. And we also anticipate vutrisiran's application to an important rare disease called Stargardt and ultimately, ALN-TTRsc04, which provides the potential for a once annual dosing regimen. The bottom line here is that with our leadership, innovation and commitment to help patients, we have a compelling road map to enable impact for patients, substantial growth and significant value creation for years to come. Next slide, please. An important step in the expansion of our TTR franchise relates to our cardiomyopathy studies, APOLLO-B and HELIOS-B. If successful, these studies will extend our commercialization efforts into a much larger patient population, including at least 300,000 wild-type ATTR amyloidosis patients worldwide. Those studies are fully enrolled and we expect top line results from the APOLLO-B study of patisiran in mid-2022 and top line results on the 30-month endpoint from HELIOS-B in early 2024. Next slide. With the APOLLO-B readout expected later this year, we have many reasons to feel confident that the study design and enrollment criteria have optimized our chances for a successful trial. The study incorporates rigorous diagnostic criteria for ATTR cardiomyopathy requiring positive biopsy or a positive technetium scan of Perugini Grade 2 or 3, and we have excluded patients with AL amyloidosis or other causes of cardiomyopathy. The study was conservatively powered and overenrolled at 360 patients. Importantly, there was a rigorous approach to administering the 6-minute walk test including limited baseline assessments to minimize any potential training effect. The study enrolled a broad population of ATTR-CM patients. The protocol targeted approximately 20% hereditary and 80% wild-type patients with NYHA Class I, II or III heart failure, and elevated NT-proBNP levels. Up to 30% of patients were allowed to enter on baseline tafamidis but only if they had experienced disease progression. And the study excluded patients who anticipated starting tafamidis in the first 12 months. And perhaps most importantly, we believe that patisiran offers a promising approach to treating this disease, in that it substantially reduces circulating levels of variant and wild-type TTR and has shown consistent exploratory data suggesting benefits in ATTR patients with cardiomyopathy. Some of these data are shown on the next slide. We have what we believe is a broad body of supportive exploratory evidence with both patisiran and vutrisiran in patients with cardiac manifestations of disease. This includes a post-hoc analysis of the APOLLO study, where we were able to demonstrate an approximately 50% reduction in all-cause hospitalization and mortality, along with favorable changes in biomarkers, echocardiographic parameters and walking speed. These findings are further supported by published results from investigator-sponsored patisiran studies, which have provided evidence of cardiac amyloid regression and also shown improvements in 6-minute walk distance, the primary endpoint in APOLLO-B. And as we will share with you later this month, vutrisiran in the HELIOS-A study continues to show evidence of favorable impacts on the cardiac aspects of this disease, including reduced technetium uptake in the heart. Next slide, please. We are also excited about a promising new near-term opportunity that we recently announced for patisiran and Stargardt disease, providing the potential to expand the use of vutrisiran to treat an inherited and progressive ocular disease. This stems from our realization that the vutrisiran mechanism of action by reducing vitamin A, can in turn reduce the buildup of toxic metabolites in the eye that lead to vision loss. We believe this represents an important expansion opportunity for vutrisiran in an area of high unmet medical need where no therapies exist today, and we intend to start a Phase III study in late 2022. Let's go on to the next slide. The second key growth driver is our expansion beyond rare diseases into prevalent diseases. Next slide, emboldened by the results from the Phase III studies of inclisiran, we believe that now is the time to address the many unmet needs in common disease settings such as hypertension, NASH and diabetes. Importantly, the pharmacological features of RNAi therapeutics are uniquely suited for the treatment of chronic prevalent diseases where durable effects enable infrequent dosing to maximize adherence and where clamped pharmacology creates the potential for improved efficacy and outcomes. Furthermore, as illustrated on the next slide, the commercial and medical affairs capabilities we've put in place around the world to support our rare disease launches can be scaled to support strong commercial execution, [ make some ] specialty with a potential launch of ATTR cardiomyopathy and thereafter in prevalent disease settings. Our global teams are empowered with great digital and data capabilities to effectively engage a broad range of customers. In addition, our scalable capabilities also include innovative access solutions like value-based agreements in the U.S. that have resulted in coverage of 95% of eligible lives. And in Europe, where we have achieved reimbursement an average of 3 months faster than industry norms. Next slide, please. Highlighted here, our programs and our growing portfolio of differentiated therapeutics against genetically validated targets in prevalent diseases. These programs offer the potential to reimagine the treatment of these common diseases affecting tens or hundreds of millions of patients around the world, and we look forward to growing this list over time. Let's go on to the next slide. The third growth driver for the company comes from our sustainable innovation engine. Next slide. We continue to maintain our leadership in RNAi and push the boundaries of this technology, bringing forward new platform enhancements, for example, with our GEMINI and IKARIA platforms. Another key growth driver is extrahepatic delivery. While we've had great success in targeting genes expressed in the liver, that's just one organ system. And there's a myriad of opportunities to target genes expressed in other tissues like the central nervous system, eye, lung, muscle, adipose tissue, even tumors. Growth can also come from innovation in finding new genetically validated targets, thereby driving further pipeline expansion to 2025 and beyond. We've continued to invest in major databases associated with rich genome and phenotypic data, including the U.K. Biobank and Our Future Health, the U.K.'s largest ever health research program that aims for genotype samples from up to 5 million participants. Next slide, please. One clear example of homegrown innovation is our GEMINI platform, which multiplexes siRNAs to create a single subcutaneous injection that can silence multiple targets with a broad range of potential applications in diseases such as cardiovascular, metabolic, CNS and oncology. A specific example from our GEMINI platform is GEMINI-CVR where we are developing a single construct to silence 2 highly validated targets in cardiovascular disease; ANGPTL3 which lowers the atherogenic lipids LDL and triglycerides; and angiotensinogen, which lowers blood pressure. It's really exciting to think about the resulting target product profile, a drug that patients with CV risk factors such as abnormal lipids and high blood pressure can take as a single injection, potentially annually, to prevent major adverse cardiac outcomes. That could enable a vaccine-like approach to managing cardiovascular disease at a population level. A drug like GEMINI-CVR would mean that patients wouldn't have to remember to take their pills, they can just get an annual shot. And that shot will address multiple risk factors, putting them at risk of diseases like stroke and heart attack. We hope to have a development candidate for this program by 2023. We're also pleased with our progress expanding delivery to address targets outside the liver. For CNS delivery, we've honed in on the C16 conjugate to provide robust knockdown, wide biodistribution with CNS and a long duration of action, and we are exploring peptides and antibody-based approaches for targeted siRNA delivery to additional tissues. Recently, we celebrated a huge milestone for Alnylam and for the fields of RNAi therapeutics with a CTA filing of our first CNS-targeted medicine ALN-APP, which targets amyloid precursor protein for the potential treatment of Alzheimer's disease and cerebral amyloid angiopathy. ALN-APP has the potential to offer a highly differentiated approach in Alzheimer's disease. By targeting APP upstream of where the antibody is currently target, ALN-APP has the potential to act both intracellularly and extracellularly to reduce the disease-causing peptides. We plan to initiate our Phase I study in early onset Alzheimer's disease in early 2022 with initial clinical data expected at or around the end of the year. And recognizing the tremendous burden and unmet need of these neurodegenerative diseases, we're determined to bring our innovation with RNAi therapeutics to other CNS disorders. Next slide, please. This schematic illustrates how we leverage genetically validated targets, combined with the power of our platform and our reproducible and modular approach to sustainably deliver innovation in an ongoing fashion. This combination of carefully selected targets and a powerful platform increases the probability of success at each stage, including ultimately the approval of transformative medicines. Let's now turn to the next slide for a brief discussion of our 2022 goals. Here's the full list of goals. But if you advance to the next slide, key milestones include: 5 commercial products on the market generating revenue, including vutrisiran, which we plan to launch this year, assuming successful review and approval by the April PDUFA date. We also anticipate our APOLLO-B Phase III study readout. And assuming that study is positive, an sNDA filing for patisiran in ATTR cardiomyopathy. We also have 5 Phase III programs, as well as 5 ongoing Phase II programs. And we plan to deliver on our commitment to sustainable innovation with 2 to 4 new IND filings stemming from our organic R&D engine. Next slide. Finally, I'd like to highlight a special ingredient that I believe has enabled our success to this point and which is critical to realizing our vision of building a top-tier biotech company, and that's our people. We're so proud of everything Alnylam has achieved, thanks to the amazing employees who are fully committed to our mission. We continue to be recognized across biotech and other industries for multiple elements of our culture, including our leadership in scientific innovation, diversity, equity and inclusion, social responsibility and, first and foremost, a steadfast commitment to the patients we serve. Next slide, please. I'd like to close by emphasizing that I could not be more excited to be taking over as CEO at this point in Alnylam's evolution. Alnylam is firing on all cylinders, and I'm fully committed to executing on our P5x25 strategy and delivering on our long-term vision. I also hope that all of you share this optimism that we will make this vision a reality. As I hope you can appreciate from what I have outlined in this presentation, Alnylam's future is looking brighter than ever, and we're just getting started. Thank you for your attention, and I will now welcome to the screen, some of my colleagues to join me for the Q&A session.

Yvonne, if you want to just take a quick second and introduce the broader team on the line, we'll get started with the Q&A.

Yes, I'd love to. So we have Jeff Poulton, who is our Chief Financial Officer, we have Pushkal Garg, our Chief Medical Officer; we have Tolga Tanguler, our Chief Commercial Officer; and of course, our President, Akshay Vaishnaw.

[Operator Instructions] Look, I think there's an obvious question that's on everyone's mind. You guys kind of started addressing this on Slide 16 of your presentation about why to have confidence in APOLLO-B. But in light of the BridgeBio readout late December, how are you thinking about placebo performance? How are you controlling for placebo? Is ATTRCM more heterogeneous than we all thought?

Yes. Thanks, Anupam. That obviously is an important question is on people's mind. Look, I'd just like to start off by saying that we've got over a 10-year track record, in delivering successful studies, successful TTR studies. And we're very confident in the design and conduct of our ongoing cardiomyopathy studies, APOLLO-B and HELIOS-B. But I'll turn it over to Pushkal, who will provide a little bit more perspective on our thinking.

Sure. Thanks, Yvonne, and thanks, Anupam for the question. I certainly know it's on people's minds. So let me -- maybe just start by -- I think we should acknowledge how disappointing this news is for patients. It's a rapidly progressive disease, and it's -- patients were looking for another treatment option. So this is certainly a setback there. In terms of what happened with the BridgeBio results, we're relying really right now on what we've heard from the company. And they've talked about issues such as context bias, learning bias, something around the diagnosis of the patients. And that's what we have to go on. I think we're all looking forward to seeing them present and share them and the investigators more data at a forthcoming meeting so we can really understand what happened with regard to the study. From my perspective, as I kind of sit back and look at the results, I think some of the data seem to suggest that maybe there was some issue with the way that the 6-minute walk test was implemented or administered. Why do I say that? It looks like the KCCQ and the BNP, there was placebo progression in those endpoints, and there was some evidence of a treatment effect. And with regard to the 6-minute walk test, we know that patients like this with NYHA Class 1 or 2 heart failure progress with regard to their 6-minute walk test. And the best evidence for that comes from the Pfizer ATTRACT study, where we saw placebo patients, who had substantial declines in their 6-minute walk test over the course of that study as early as 6 months and progressively over the 36 months of that study. And in fact, the treatment effects of tafamidis were seem to appear to be larger on 6-minute walk test in those NYHA Class I and II patients. So all of that suggests possibly that this was something related to how the 6-minute walk test was conducted. But again, we look forward to seeing more data. As it relates to our study, I think as Yvonne said and highlighted in our plenary presentation, we remain very confident about both the design and the execution of our study. It starts with the rigorous criteria that were implemented to diagnose patients with this disease, whether it's biopsy or technetium uptake with Perugini Grade 2 or 3 and excluding other causes of cardiomyopathy, enrolling a broad patient population and targeting up to 20% of patients with hATTR amyloidosis, and 80% wild type, a broad spread of NYHA class from 1 to 3 with evidence, clinical evidence of heart failure and elevated BNPs, allowing 30% of patients to be on baseline tafamidis, but only if they'd experienced disease progression. And then based on our 10-year experience in this disease and studying a number of other diseases, really rigorous administration and ascertainment of study endpoints, right? Including careful protocols and efforts to minimize what's been talked about with regard to a potential training effect with 6-minute walk test by minimizing the number of screening and baseline assessments. And finally, I come back to -- there's really a confluence of evidence that seems to suggest that by turning off the production of the disease-causing protein through an RNAi mechanism that there can be favorable effects on the cardiac aspects of this disease. We've seen favorable impacts on NT-proBNP. We've seen impact, favorable impacts on echocardiographic parameters, on outcomes and in technetium uptake. And importantly, on functional measures, such as 10-meter walk test and 6-minute walk test across the range of studies. So what we're waiting for now is the pivotal trial data, which we'll expect in the middle of the year. But we remain very confident about both the design and the execution of that study.

Pushkal, that's a very comprehensive answer. I just wondered if even Akshay had anything to add to that?

No. I think Pushkal covered all the main points. And I have to reiterate that the -- to date, the flawless execution we have had we're proud of, and I think we're very confident in the design. And TTR silencing to us has always looked like the way to treat this disease. And so we look forward to the data in mid-year.

We've got a question in the e-mail portal here, which is, you talked about your TTR franchise. How does the company view the successes of other companies, such as Intellia, who are addressing outside of the RNAi approach? How do you maintain your leadership position in the space?

Well, I mean, I'll just start by saying that we believe that we're building the leading TTR franchise with approved products ONPATTRO and hopefully soon to be approved product with vutrisiran. And both these medicines are somewhat derisked. I think when you look at some of the earlier approaches to addressing TTR, they've still got a long ways to go. They look a little bit like how -- where Alnylam was probably 7 or 8 years ago. But maybe what I'll do is I'll hand this question over to Akshay to provide even his perspective.

Yes. I mean, look, clearly, congratulations to Intellia with those data last year showing TTR knockdown. But as Yvonne said, it's start of a long road. And I think we need to obviously understand much more about consistency of effect, durability of the effect, most importantly safety in the long run with this approach, in this kind of population, much of which is old. And then they have to get through the rough and tumble of clinical trials. I mean, we've been able to do placebo-controlled studies. They will almost certainly have to do head-to-head studies, and active comparator studies with the treatment landscape elaborated with our drugs and others. And then there's the whole market access and payer piece and how you reimburse the therapy like that, which as we've seen with gene therapy and other similar modality is not trivial and especially for a population of septuagenarians and octagenarians. So I think it's a big step forward for gene editing as a proof of concept. But as to drug development and ultimately getting a drug to patients is a long way to go. And I think a once annual reversible approach with the kind of drugs that we have, whether it's 6-months with vutrisiran or the ultimate[ TTR-SUR4 ] which is annual which we'll put into the clinic later this year. To us seems like a very smart way to go, and we're confident that we can lead the field with those drugs.

Another e-mail portal question here. In regards to APOLLO-B, are you looking for improvement in 6-minute walk distance stabilization or a change from natural history, so a slowing of the progression. Like what's the win scenario here?

Pushkal, maybe that's one for you to take.

Sure. Look, I think maybe a couple of points on the 6-minute walk test endpoint. First of all, it's important to remember, this is a validated endpoint in this disease. It's recognized by the regulators. A win is going to be a statistically significant result, and a result that's comparable or better to tafamidis. We know that tafamidis does appear to help. But patients continue to progress despite that therapy. We saw that in the ATTRACT data very clearly where there was a regular and a continuous decline in terms of their function ability with regard to 6-minute walk test as well as quality of life. And so I think that win is offering another treatment option that is comparable or better to tafamidis for these patients. Certainly, we look forward to the data and what we've seen in the neuropathy setting is the potential for this type of upstream mechanism to actually halt or reverse aspects of the disease. But there's a lot of opportunity to provide better treatment options for these patients. And the last point I would bring up is just it's important to remember that 6-minute walk test is measuring an important functional ability for patients, right? These patients want to live, but they want to live actually and be able to engage in their activities of daily living and go about their lives. And 6-minute walk test really measures sort of that cardiopulmonary reserve and their ability to engage. And so it's really clinically important and meaningful assessment for patients as well.

We've got another question in the e-mail portal here. Actually, it relates to lumasiran and how you think about the biologic rationale for lumasiran in the broad current recurrent stone formation population. How do you think about competition with BridgeBio's GO1 inhibitor mechanistically and how compelling is GO inhibition versus LDH inhibition in this population?

Well, there's quite a lot of questions in that one. I'll start off and say that, as we move forward with lumasiran in recurrent renal stones, I think it's a fantastic example actually of the approach where we can achieve approval with a drug in a rare condition like primary hyperoxaluria 1, and then extend that indication to a much more prevalent setting of recurrent renal stones. Maybe we'll start with Akshay just commenting on the differences and mechanisms. And then we'll turn to Pushkal, maybe to talk about the clinical status. Akshay?

Yes. So I mean, in terms of mechanism versus LDH, the most ready example that comes to mind is, of course, the work of Dicerna who targeted LDH. But I think -- whilst there will be no head-to-head studies and we should be always very mindful of that. Our data are quite clear with GO silencing in patients of all phenotype. So whether we consider the very young in terms of babies with this disease, or the older patient, whether we consider patients with established renal dysfunction, indeed, even renal failure. And whether we look at patients with extra renal forms of the disease, we have clear data on all those different aspects. And I think with LDH the data, again, Dicerna should speak for the data, but I think others have not seen them as encouragingly. And versus any additional therapies that are in the development with BridgeBio or others, I mean, look these are [indiscernible] patients, and we always should welcome new potential treatments for patients. So I hope that therapy makes progress. It's a small molecule that targets GO. Small molecule journeys are always -- they're exciting in the beginning, but there's a lot to prove, and there are a lot of -- it is in growing events that can occur relative to a reproducible and relied try upon platform like ours. And remember, they'll have developing renal failure and a variety of special populations, including very young children. So that's pretty short term demand for an [ ultra-small ] molecule. But again, hopefully, they and others make progress, this is a bad disease. Pushkal, do you want to pick up on the recurring statements?

Absolutely. Yes. Look, I think building on what Akshay said, Anupam, I think this is a really exciting life cycle management opportunity. I think it's important to remember again that lumasiran has shown evidence of reducing urinary oxalate, and that is really what leads to the production of oxalate stones in the kidney. And we've shown that across a whole range of patients with disease severities with -- including severely impaired renal function in the PH1 population, as well as a really encouraging safety profile for that molecule. So it gives us a lot of opportunity to study this in the recurrent stones population. These patients, 80% of them, have recurrent calcium oxalate stones, right? So we've already shown the reductability of reduced oxalate levels by 50% or more. And so it's a natural extension to go into this population. So we kicked off our study at the very end of 2021, and we're hoping to complete enrollment and develop some proof-of-concept data later this year. And so we're very excited about the prospects there.

Last question really quickly from the e-mail portal again. On APOLLO-B, do you plan on checking in on mortality at 12 months? Or is this really going to be a 30-month assessment?

For APOLLO-B, so I mean, let me just kind of remind you that APOLLO-B is final to hit on its primary endpoint of 6-minute walk distance, and not necessarily the secondary endpoint of all-cause mortality and CV events. But Pushkal, is there anything that you'd like to add?

Sure. I mean I think building on what you said, I don't know Anupam if the question may have been more on HELIOS-B. But certainly for APOLLO-B, that's a 12-month study with a 6-minute walk test endpoint. We will be looking at -- there is a secondary endpoint to look at outcomes, including hospitalization and mortality. And -- but the study is not powered for that. So we'll be looking for that. And perhaps there will be some interesting trends. We're encouraged by what we saw coming out of the post hoc studies analyses of APOLLO where they did appear to be about a 50% reduction in death in hospitalization, as Yvonne pointed out in her presentation. But importantly, it looked like the separation of the curves occurred relatively early. Now there's no head-to-head data, but the published ATTRACT data suggests that with a silencer mechanism, it may take some time for that separation to occur. So we're encouraged, and we'll look at those data. And certainly, that will be informing how we think about HELIOS-B and the potential for an interim analysis in that longer study that's ultimately directed towards demonstrating outcomes benefits.

Perfect. Well, Yvonne and team, I want to thank you guys so much for a productive session. And I hope you guys have a great rest of the conference.

We're looking forward to it. And thank you so much for hosting us here today. Thank you.

Thank you. Thanks.