Alnylam Pharmaceuticals, Inc. ($ALNY)

Great. Good morning. Thank you, everyone, for joining us. It's a pleasure to have with us the Alnylam team. With us is Jeff Poulton, CFO; and Pushkal Garg, Head of Development. Maybe to start here, could you lay out your 5-year goals where you've talked about 25% revenue CAGR as well as 30% non-GAAP operating margin? Could you frame the contribution of AMVUTTRA relative to nucresiran in the context of that in the pipeline as it relates to the 2030 outlook?

Yes. Let me -- I'll sort of walk through the main categories of the goals that we rolled out earlier this year, we called Alnylam 2030. This is the fourth iteration 5-year goals that the company has put out, and this has really, we think, been part of the story in terms of driving performance for Alnylam, both externally in terms of being really clear with the market about the areas that we're focusing on our business, but also internally to make sure that the employees all are rowing in the same direction on the things that are important to us. So the areas that we focus the goals on this year for 2030 were around leadership in TTR, which clearly is a big focus of the market. and we've defined leadership across the period in 2 ways, being the sort of peak revenue franchise in 2030 and also cumulatively across the fire period. That's how we're defining leadership. So that's all for TTR. On the pipeline, this is really about driving diversification beyond TTR. And so we're very focused on advancing the pipeline to do just that by 2030. We've got a number of metrics, I'm sure Pushkal can go into these in more detail. But we're looking to have 2 plus new products that are either in the market or a line of sight getting to market that could be blockbuster pipe type opportunities beyond TTR, again, that's really important to us to start driving longer-term diversification of the pipeline. And then some other things that are important to us are expanding into new tissues because we think that, in particular, unlocks a lot of very attractive opportunities. So we're looking at 10 tissues by 2030. And then just the breadth of the pipeline, we're looking to have clinical programs by 2030. And then lastly, are the things that you touched on, which are really about how we're anticipating scaling the business financially. So we guided to top line CAGR, that's product sales, collaboration and royalty revenue. And I'll get to your question about nucre versus AMVUTTRA just a second. And then we also guided to non-GAAP operating margin of 30% across the period. And let me just touch on that for a second because I think that was an area where the market had to adjust a bit. The market was at a much higher rate by 2030. I think consensus at the time we guided to 30% across the period was more like 50% operating margins in 2030. And with our gross margin profile through 2030 given the AMVUTTRA royalty burden. I mean, the market consensus is around 75% gross margins, very difficult for us to be at a 50% operating margin in 2030. And we're also investing heavily in R&D across the period to drive the R&D goals that I talked about to drive long-term diversification. So back to the question about AMVUTTRA versus nucre, for 2030, that's primarily going to AMVUTTRA Invutra just because of the timing of the Phase III studies that we're running for nucre right now. Again, Pushkal can get more into the details. But we have 2 Phase III studies for nucre, the PN study will be quicker. We're looking at 2028 in terms of time in the market. And then we look at CM is likely at 2030. So the primary revenue driver is going to be in but across the period post 2030, assuming that we have a profile that we think we could have in terms of a best-in-class profile for nucre that will drive long-term top line growth, but also importantly, unlock more margins. We talked about 30% through 2030. But with a heavy royalty burden AMVUTTRA, we think that unlocks margin into the post the launch in cardiomyopathy.

And how does external business development fit into your strategy here? Maybe walk through SOC therapeutic area and potentially even expanding outside in terms of a different modality versus siRNA.

Just touch on what we said about R&D investment, and I'll let Pushkal talk a little bit more about the type that we might be interested in. The guidance on R&D reinvestment in the business as a percentage of revenue is 30% across the period. And that does include headroom to do business development, but I'll let maybe Pushkal to take the question about areas of interest.

Look, we're really excited about what we have in terms of just a product engine and the probability of success that's associated with that, right? And so if you think about it over the past years, we've had over 50% probably the success of things we put into the clinic coming out on the other side. So our primary focus is going to be in our internal pipeline. We have about 25 drugs in development, and we'll have 3 or 4 new INDs each year as we go into new areas. So that's the primary focus. But we also recognize there's a lot of innovation happening outside, and we now will have so really the financial where with all to be thinking about some of that, as Jeff outlined, is AMVUTTRA continues to grow. And so we are thinking about where we could deploy that capital A lot of that is going to be used where we do think about BD is where, a, we're going to have a very high bar, right? Again, it's going to have to compete internal programs, and so we'll make sure there's a strong scientific and economic basis for what we're doing. And we primarily see this not sort of to be confined to more or less early-stage assets that are actually going to either really help us advance whether it's on our delivery objectives, et cetera, or early-stage assets that synergize in some way with where we have a commercial business, right? And so I think those are probably the main areas where you'll see us focusing on for the next few years. But we're in no hurry to do it. We'll kind of be very thoughtful about what we do.

And what will we see from the pipeline within the next 12 months? And what do you see from that -- from the overall portfolio is kind of the key levers of next growth beyond TTR?

Yes. So I think if you -- I'll maybe start with the second part, if you think we have we've got nucresiran that's obviously in the clinic now, and Jeff touched on that, that's moving. We have nucresiran now, which offers continuous control of blood pressure, 2 injections reduce variability, improve adherence, restore nocturnal dipping. We think that result in a real cardiovascular outcomes benefit. So that ZENITH study is underway and enrolling well. That's not going to readout until around 2030 time frame. . In the nearer term, we have a number of things that we're going to be seeing data on. We have our first metabolic disease asset going into the adipose tissue, ACVR1C or ALK-7. So that's started. We think that's going to be a big driver of reducing visceral fat of preserving muscle mass. And we see the overall obesity overweight market evolving in some segmenting quite a bit, and so we see a real role for that. Perhaps as a monotherapy, certainly in combination with other therapies against a variety of metabolic health conditions. We have a dining program targeting Huntington's disease that's going to give us some data this year. We have a very unique approach that targets not only the mutant Huntington's protein, the full length -- but actually, this important isoform, the exon 1 fragment that I think really -- now there's a huge consensus in the academic community is critical to the sort of propiation of the Huntington aggregates. And so we can specifically knock down both the protein, the transcript, both of which are believed to contribute to disease. And that's in contrast to prior approaches to silence Huntington's or another existing approaches. So it's a very unique way. And so later this year, we'll have some exciting data, we hope, in terms of both knockdown being able to get high levels of knockdown, infrequent dosing good associate safety. And with those data, I think we'll be in a good position to actually move into more advanced pivotal trials. And so that's something we'll be updating on later this year. And then the third big asset that we have is an exciting program that targets plasminogen. And that is an agent that has the potential to be a universal hemostatic agent. It's about 3 million relief for brands disease. We don't have effective proactive therapies for most of these. And so what we're bringing forward is a drug that will be a few times a year and actually stabilize clots. And the beauty here is that the genetics and the preclinical data suggests it can stabilize clots without increasing the risk of thrombosis. The first indication we're pursuing is something called hereditary hemorrhagic telangiectasia, which causes bleeding through in the GI tract, nasal cavity, et cetera. And so we'll be able to look at bleed data from that program later in the year.

Great. Maybe just pivoting over to your TTR franchise here. So in the context of the 2026 revenue guidance, how do you view the AMVUTTRA trajectory for the remainder of the year, including any other idiosyncratic items such as shipping weeks or ex U.S. pricing adjustments, for instance?

Yes. So the guidance is set for the year is $4.4 billion to $4.7 billion. Q1 was held by both U.S. and ex U.S. by some phasing factors that will not impact the balance of the year. In our international markets, we had a price reduction in Germany at the end of 2026 for the launch in cardiomyopathy, which has an impact on the existing PN business obviously unlock a much larger opportunity. But in the quarter, when you take the price reduction, it does have a headwind effect on the business. So our international markets were down $7 million between Q4 and Q1. We absolutely expect growth for the balance of the year in our international markets. we're now launched in the majority of, I would say, the major markets ex U.S., so Japan, Germany, the U.K. and Italy. We're continuing to work on opening up France and Spain, but we do, again, do expect growth for the balance of the year in our international markets. In the U.S., in the first quarter, we grew up $60 million versus Q4 and the things that we had flagged that were headwinds for Q1 from a phasing perspective were the typical insurance reauthorization process, which we did see impact the business, particularly in January. And then with the way our product gets ordered and shipped in revenue booked, the number of Wednesdays in a quarter actually has an impact and what the way the calendar fell. There were more Wednesdays in Q4 than Q1. None of these things that I've just described will impact the rest of the year. In the U.S., the focus is really around 2 things to drive the business. First, I would say, the foundation in terms of what we've accomplished to date. One is on the sort of preference side, what we see where physicians are using AMVUTTRA, right? And they've got 3 choices to make 3 options to have to treat these patients today. But where doctors are experienced with AMVUTTRA for cardiomyopathy, we have a leading share amongst those physicians. That's a good starting place for us. Secondly, I think on the access side, we've done a very good job in establishing the opportunity for physicians to write the product and feel confident that the patients can get the drug. So from a payer perspective, we're at more than 90% of patients have first-line access to AMVUTTRA. It's terrific. The only part of the market where there are some steps in place is the commercial part of the market, but that's a fairly small part of this market. patients, the majority of the patients here out of pocket, right? So it's not a financial burden for the majority of the patients and then from a provider perspective, we've really done a nice job on buying bill side, both with the health networks, the hospital networks where we've got the drug on formulary. And then for physicians that may be outside of those hospital networks where they don't want to buy and build their infusion clinics. There's about 2,000 clinics in a network that we've created that make that -- where they can refer the patients to the clinic to do the buy and bill. So that's all in place. What we're really focused on for the balance of the year is first, expanding the prescriber base. Again, I talked about we have leading share when physicians are using it. We want to drive more utilization into the part of the market where they're not using it today. So some of that's based on sales force targeting and really focusing more energy on docs that are not using the product yet. And then additionally, we are still starting to put a little more effort behind driving earlier diagnosis. We announced a partnership with a company called Viz.ai that has an AI algorithm that can get connected to electronic health records and review echo tests, right, both prospectively and retrospectively, and we'll run a pilot with them and 5 health networks to see if we can have success in driving more diagnosis. So those are the things I would say are highlights for the U.S. that will help drive more growth for the balance of the year.

And how are you thinking about the cadence of the ex U.S. launch and just the trajectory with regard to gross to net dynamics for the TTR drive?

Yes. I mean, that's really on a market-by-market basis. Obviously, we're negotiating. I mentioned right now in France, in Spain and look, the impact that, that will have on the business depends on ultimately where we land in terms of an agreed price. We have had some success in certain markets where we're priced at a premium to the existing standard of care in markets outside the U.S. and in other markets, it's more priced at parity. So that really is determined on a market-by-market basis based on negotiations with the local authorities. .

And the U.S. net price decline?

Yes, we -- so I would say the story here has been consistent since the time of launch. We talked about a gradual reduction in net price over time. as the business scales. Last year, that meant about a 5% net price decline versus 2024, and we've guided to something similar this year compared to 2025, and I think we're on track to -- that's the right guidance for the market. .

Got it. Have you seen patients covered for tafamidis and [ Invitae ] combination use and in which segment? And maybe talk to evidence of cross management and Medicare Advantage.

We have seen some combination use. I think combination use is generally restricted in the commercial part of the market as well as the Medicare Advantage part of the market. That leaves the fee-for-service part of the market where there's no active payer management that are putting policies in place to restrict combination use. And in the cardiomyopathy part of the market for us, that's probably about half of our business. And so we have seen in particular in that segment of the market that there has been some combination use. Of course, we have data in our label, right? That's one of the subgroups that was studied in HELIOS-B study, and we saw a consistent effect in patients that were on tafamidis as well. And so I think that's been supportive of some of that combination use that we see ongoing. We think the more significant unlock for the combination opportunity in terms timing happens when TAF goes generic. And with Pfizer announcing recently the settlements that they've had with the generic filers that's middle of 2031, which from a timing perspective for us, given the design of the nucreus study, which is largely going to be a combination study, and we think we bring that to market in 2030. That's probably a good timing for us.

You've framed that when it was Phase III data in ATTR-CM in second half could support combination use here. How are you thinking of positioning the payer and price dynamics as monotherapy in combination, especially in Medicare Advantage, we're cross-managing...

Yes. I mean again, I think what I talked about is the -- on the Medicare Advantage and the commercial parts of the market, they typically have policies in place today that do restrict combination use. So we're not seeing a lot of combination use in that part of the market. It's really more in the fee-for-service part of the market today. And I don't think that will change significantly until, as I mentioned, before we get to the unlock on tafamidis, tafamidis, goes generic and then you've got a much cheaper option to do the combination with. That's what will really open up more opportunity for combination in our view. .

And how are you thinking about just your pricing relative to the other drugs and their...

Yes. Look, I think there's -- we're the only drug in the Part B part of the market today. We're competing today against 2 stabilizers that are in the Part D part of the market that are at a lower price point than where we are. We're obviously waiting on the data from the AstraZeneca ones product. We -- our belief is that largely will also be a Part D product, although it sounds like they have some optionality between D and B. And so I'm not sure that that's going to change anything when they come to market if it's predominantly a Part D product in terms of pricing dynamics for us. So we feel relatively confident about where we are right now from an access perspective. .

Pushkal, do you want to speak to maybe your thoughts on how that trial will play out, both from the overall standpoint, but also in the TAS combo arm and whether that could actually be stat sig?

Yes. Look, I think they've got -- clearly, we know that molecule is effective, right? It showed good results in the PN population. And so here, they're doing an outcome study. It's about twice the size, a little bit more of HELIOS-B. So I think they're well set up to have a clinically important effects seen. I think if I had to benchmark, I would sort of say that it's probably going to be more or less in the same size of treatment effects that we've seen already with AMVUTTRA and HELIOS-B. It's a little bit shorter. So maybe they could have a little bit of a lower effect size as a result of that. But I think the fact that their population is so large, still sort of sets them up, I think, for statistical significance. Now I think they've also announced recently some changes to the hierarchy of their endpoints, how that's going to play into how far down on the hierarchy they can get. It's hard for me to kind of prognosticate on that. But I think our going-in assumption is they're going to have an effective drug. It's going to be -- it's going to be effective across the 2 segments of the population, the effect size will be in the range of what we've seen with HELIOS-B and so I think, again, we feel well positioned for AMVUTTRA, and the fact that we already have a label that allows combination use. And again, as Jeff was saying, that -- we're following that up with nucresiran, which now is a much larger study, which is predominantly a combination on both of those data sets at the time that tafamidis goes generic in 2031.

And for your next-generation TTR asset nucresiran, for the Phase III CM study, do you believe the majority of patients will be on background stabilizer therapy and what gives you confidence in the timing of events and the separation of the curves in that context?

Yes. So -- it is largely a combination therapy study. We expect there'll be some monotherapies, but a lot of it will be on background stabilizer. And we kind of again designed this in anticipation of where we see the market evolving over time. We designed this with a lot of insights from HELIOS B. So we have several hundred patients worth of combination therapy in that study. So we have really good individual level data to be able to understand what is the rate of sort of events that we can expect, what kinds of events, how they accrue, et cetera. And so that gives us a lot of insight in terms of as we designed the TRITON CM study with nucresiran. And it was using those insights that we kind of set the study up. We also recognize that it's likely, as we've seen successive clinical trials in this space that patients are getting diagnosed earlier they're going to be somewhat milder. Enrollment has gone actually far ahead of schedule, and we've been really excited about that and shows the real strong interest in this molecule. But we also, as somewhat predicted, saw that patients are a little bit on the milder side relative to what we saw in HELIOS-B, we had a predefined provision in the study to increase the sample size by 500 and given the speed of enrollment, we pulled the trigger on that. And that's going to help us really accrue more events and compensates for the fact that maybe there'll be a somewhat lower event rate given the milder population. It's also an event-driven study. So obviously, we'll follow until we get enough of those events.

Maybe a last question on the TTR side, but can you frame the size of the overall TTR market and your confidence in Alnylam share here? And where you expect these additional drugs, why no antibody depleters and gene editing to ultimately fit in?

Maybe I'll start off. I'm going to repeat some things that we said on a TTR webinar that we did earlier this year around sort of our revised view of the size of the opportunity. We've talked about in the U.S., 200,000 or more patients and then globally, 500,000 or more I think what's important is we're still very early in diagnosing and treating that patient population, right, that prevalent patient population. So we're probably around 20% of those patients are treated today. So there's a significant opportunity here to continue to drive diagnosis and treatment rates over time. But Pushkal, I don't know if you want to add more.

I think as we think about treatments over time and look, just this is a growing market. I think there's going to be a lot of space for multiple therapies in this disease area. I think we certainly feel very good about where the silence are class is, I think, going to evolve into being a foundational therapy starting with AMVUTTRA, particularly when nucresiran comes along and to have sort of a twice a year drug that gets to 95% knockdown, I think it was going to be really great for patients. But look, there's going to be continued innovation. The depleters are very interesting, right? We have 2 depleter studies going on now, large Phase IIIs. I think we'll see what those data ultimately look like. I think the conventional wisdom is these are somewhat cumbersome right now. They're IV, they're given monthly. I think there's several hour infusions, and that they may be particularly used then for patients who are more advanced when they present sort of Class 4 types of patients, Class III patients and really is a shorter-term induction approach to kind of clear some of the amyloid hopefully and then keep them on a backbone ideally of a silence or perhaps a stabilizer depending on the physician and patient's preference. So we look forward to seeing those data and it will be interesting to see how that all plays out. But that's, I think, the conventional wisdom right now. I think in terms of the gene editing approach, Look, I think it's a very, very interesting approach. I think -- and I'm sure there will be a segment of the population that may benefit from that or choose to opt that way. I think the relative benefits compared to, for example, twice a year nucresiran, that gets you to 95% silencing. I think it starts to become a little bit more difficult to see how that market evolves and given that they'll also have some challenges to figure out in terms of pricing and how that all works with the one-and-done therapy. So again, we think there'll be plenty of space for a number of players here, but we feel very good about what we're doing with both AMVUTTRA and ultimately nucresiran.

As you noted earlier, you'll have data from 3 early-stage programs this year. Maybe starting with ALN-HTT. What's your confidence in that program in terms of the mechanism and the ability to achieve sufficient distribution here in Huntington's? And what's the bar for HTT knockdown?

So look, we're really excited about the program. We have, as we said, very strong genetic data and a lot of scientific data that's accumulating in terms of the specific way that we're targeting around this exon 1 fragment. In terms of delivery and safety, our C16 platform, and we put out now data on APP, which is the lead program in that platform. Now we have, I think, over 18 months, 24 months of data out there. I suggest we can get to very high levels of knockdown over 70% with biannual dosing, and it's well tolerated. That's -- just to remind you, if you think about prior programs like tominersen program against Huntington's disease, they got to about 25% or 30% lowering MAX, and that wasn't well tolerated. They actually kept trying to have to reduced dose and space out dosing, that early generation ASO. And so I think we feel good that our general approach both now from human data from APP, what we've seen preclinically, where we can actually get very good biodistribution there as well. in nonhuman primates and deep levels of lowering with infrequent administration and good tolerability. So I think overall, the platform we're very confident on in terms of the C16 platform. We have now multiple products that are in the clinic between us and our partners at Regeneron using that platform, and we've seen good safety, good knockdown and good biodistribution. I think we all have to have a little bit of humility going into an entirely new disease. So while we're very confident in the approach that we're taking scientifically at the end of the day, we're going to generate data in patients to show that there's a clinical benefit that comes from that. In terms of the target, I would say, in general, I think the genetics and the preclinical data and sort of expert consensus, which is if you get over about 50% knockdown, then we should be in a good range to sort of explore the therapeutic utility of that. So that's what I would be looking for.

And you have ACC and obesity that's reading out as well. Maybe walk us through the strategy here with this asset and whether you could -- you would need to combine it with a Glip versus use it as a monotherapy.

Yes. Look, I think, obviously, the glips have transformed the entire space here. I mean it's -- but there are -- I think there still remains a fair amount of unmet need. We see the market segmenting over time. patients with various types of comorbidities, some patients who can't tolerate the GLiPs are certainly at full doses. People need to preserve muscle mass, and you can't tolerate the risk of sarcopenia that comes from the glips - and so we're developing ACVR1C, where we think we have very strong, again, genetics and preclinical data, this can really specifically target visceral fat. And we know that visceral fat is the key factor in terms of cardiovascular morbidity and mortality, diabetes risk, et cetera. And so -- what we're doing this year is this is our first adipose targeting program. We'll have data at the end of the year, primarily on knockdown safety but also some visceral fat data. And then we'll kind of come back and talk to you a little bit more about what we might be doing with this in terms of segments of the population, potential in combination with glips, but potentially in combination with other agents as well, where we think that we can really discern and make a meaningful impact on aspects of cardiometabolic disease.

You have your plasminogen knockdown program as well in bleeding disorders. Is there a benchmark that you see as meaningful with regard to reduction in bleeds in HHT and you did recently initiated a study in Von Willebrand disease and heavy menstrual bleeding. So maybe speak to the unmet need and rationale for the 3 [indiscernible]

As I was saying earlier, this target really addresses -- it [indiscernible] a protein called a liver protein called plasminogen, which basically leads to clot breakdown. It promotes tubinolysis. And so by silencing it, we can actually have an antifibrinolytic inflect and stabilize clots. And the beauty here is that you can actually hopefully stabilize clots, reduce bleeding without increasing the risk of thrombosis, which is what all the data would suggest. And this mechanism is such that it really should work across a variety of bleeding disorders. So if you think about HHT. It's really a disease of vascular malformations that happen. . If you think about Von Willebrand disease, which is really the most common bleeding disorder, HHD is the second most common bleeding disorder. It's really a platelet disorder, platelet aggregation. So we can attack bleeding disorders through a number of different mechanisms, all with this unifying approach that's downstream in the overall bleeding cascade. So we picked these 2 because they both have a tremendous amount of unmet need. They're fairly prevalent with regards to rare bleeding disorders. As I said, on Von Willebrands is the #1 and HT is #2. And they both -- HHC there's no approved therapies. Von Willebrands, there are treatments that are available. They're primarily used for acute treatment. They're not really suitable for prophylaxis. And what we're thinking about is a drug that would probably be given several times a year, subcu and really reduce bleeding risk. In terms of the magnitude of effect, look, I think it's going to vary a little bit. There's not just the number of bleeds, but there's the intensity of the bleed that we want to reduce. If you think about HHT for instance, there's patients who have bleeds, nose bleed that last several hours a day that can be 3 to 4 days out of a week. The impact is devastating in terms of their ability to interact in social circles to go to school, to go to work. And so we'll be looking at all of that to characterize the efficacy of the drug.

[indiscernible] that being studied here in Alzheimer's. Also [indiscernible]. Maybe help us understand the approach there and you can speak to the tau approach as well.

Yes. So a lot's happening in that space. So mivelsiran targets amyloid precursor protein, which is really the top of the cascade where all that amyloid is ultimately produced Amyloid can actually come in a couple of forms. The beta 40 and 42. And they -- some of that leads to Alzheimer's disease. Actually, AB40, is actually involved in a disease, a closely related disease called cerebral amyloid angiopathy where the amyloid deposits in the blood vessels of the brain cause them to become brittle and it's the second leading cause of hemorrhagic stroke, this disease CAA. So we have a Phase I that's been going on in early onset Alzheimer's disease. We've reported out on that. We've seen great levels of knockdown tolerability. We've started the CAA study. We have a goal that we've announced this year to complete enrollment in that study. It's a 200-person study by the second quarter of this year. And that will set us up to have data end of '27 early '28 time frame. And there we're looking at bleeds. We're hoping to see bleed reduction. On the Alzheimer's side, we actually just -- I think it just got posted today announced a small Phase II study in Down syndrome, Alzheimer's disease. We think that this approach is going to be most effective in somewhat of a preventative setting, getting an early in disease and start stopping amyloid deposition. And it's also important because it can reduce both intracellular and extracellular amyloid as well as all the various isoforms of amyloid that form without increasing the risk of ARIA. And so this down syndrome population is actually -- the mechanism lines up very nicely [indiscernible]. It's the belief that actually the overexpression of APP in that setting is what actually leads to the Alzheimer's disease, which is 100% penetrated in down patients. If they live to about 40 to 45 years old, which the majority now do, there's about 50,000 such patients about 90% to 95% of them will ends. And so we think our approach can be a benefit to that population. So we're doing a stay there. And the learnings from there will also then inform approaches into the sporadic AD population as well. As you touched on, there's also advances happening on the tau side. Biogen just put out some top line data suggesting that with their ASO, they may be seeing some benefits in terms of cognitive function. And we have an siRNA that we're bringing forward. It's in Phase I development against Tau as well. And so we look forward to seeing those data. And then that will open up for us a little bit thinking about how we bring that molecule forward. in Alzheimer's, potentially as a monotherapy. Potentially, we can think about combination approaches. So really, we think we're really well set up as we kind of think about the next stage of innovation in the Alzheimer's space to make some progress.

Perfect. Jeff, it looks like you're on track for investing 30% of revenue in R&D side.

I think we'll have the opportunity to do it, right? And again, importantly, what that's about is driving long-term top line growth also beyond TTR, which we think is critical and the time is now.

Yes. Perfect. Well, with that, thank you so much. Really.

Thank you, Salveen. Thank you.