Hi, good morning, everyone. I'm Ellie Merle, one of the biotech analysts here at UBS. Very happy to have Alnylam here with us for a fireside chat. Joining us from Alnylam is Jeff Poulton, Chief Financial Officer; and Sandeep Menon, Chief Development Officer. Thank you both for joining us this morning. Maybe just to start off, you've mentioned that we're approaching a large inflection point for the company. Maybe to start off, can you provide a summary of some of the highlights from this past year, but then also going forward, what we should be focused on?
Absolutely. I'll kick this off. So we reported our Q3 results at the end of October. We had a very strong quarter from a product sales perspective. Overall growth in the portfolio was 34%. And that was the third quarter of this year that we've had year-over-year growth of north of 30%. And both franchises, both the TTR business as well as the ultra-rare or rare business, are growing north of 30% year to date. That performance actually allowed us at the Q2 results to upgrade our guidance for the year on product sales by about 11%. So it's been a good year commercially. And I'm sure we'll talk more about some of the dynamics in the TTR marketplace, where we've got new competition for the first time this year. And then moving to the big event for the year, obviously, was the HELIOS-B readout.
We had top-line readout at the end of June, and then we presented the full results at ESC and had a simultaneous presentation in the New England Journal of Medicine. Data was terrific, obviously, from our perspective. We hit on all 10 endpoints, stat sig in the study, and we got very good feedback, I would say, from the marketplace and the KOL community on that data. We're now moving through the regulatory process. We announced, I think it was at our TTR Investor Day, that we had filed in the U.S. in early October. We've also completed submissions in Europe, and we announced this week in Japan as well. On the U.S. side, we'll use a priority review voucher. That means six months from the date of filing is when we would expect an FDA action date.
That would put the approval and launch early next year if you go from six months from early October. Let's see. I think we also held a TTR Investor Day in New York in October. We really talked about the opportunity that we see ahead in the cardiomyopathy part of the market, some of the dynamics in the market that are allowing it to grow at a pretty rapid pace, a lot of unmet need. We talked about why we think we're well-positioned for leadership there longer term. As it relates to the pipeline, a couple of things going on in the pipeline. One is, of course, our hypertension program. We have initiated a phase II study called KARDIA-3 that's looking at zilebesiran in combination with multiple standard of care medicines. We expect that study to read out next year.
That will really be informative for a CVOT that will follow. We've also made a lot of progress in the pipeline in CNS, our ALN-APP program. We provided some initial data in the multi-dose portion of that study where knockdown and safety still look good. We've also initiated a phase II study in CAA with mivelsiran. We've also recently announced that we've initiated a phase I study in Huntington's, which I'm sure Sandeep will have some comments on later. I think the things to look for towards the end of the year and early next year that people are interested in in the pipeline, ALN-APP, we have the potential to initiate a study, a phase II study in Alzheimer's at or around the end of the year.
And then I think the big thing that people are focused on in the pipeline is TTRsc04 and what the phase III design will look like. And we've commented that we expect to provide data on that in the first quarter of next year. So those are whistle-stop tour of the highlights, I would say, for the year so far.
Great. It's an exciting time.
I just want to add as well that for zilebesiran, we are waiting for the KARDIA-3 data that will come in the patients in high-risk, CV risk patients, and all going well, we want to start a CVOT study end of next year.
Makes sense. Maybe before we dive into some of the pipeline programs, starting with TTR. So the cardiomyopathy launch next year is going to be watched very, very closely. And helpful investor day on the TTR commercial landscape. But maybe just want to dive into a little bit sort of your views of the frontline market and how you view uptake in, say, naive patients versus switches. I think you made some interesting commentary around seeing sort of a lot of uptake in naive patients. Maybe just as we think of the cadence of the launch next year, where do you see sort of this initial uptake between the naive and switches?
Yeah, good question. And this was something that we spent a fair amount of time on, I think, at the TTR Investor Day to sort of frame out the different segments that we see in the marketplace. And that first line segment, first of all, in terms of the sizing of that, we think that right now there's about 18,000 globally new naive patients that are diagnosed and come on to treatment on an annual basis. And of course, that's something over time that could grow as you get more entrants into the market and you get more companies investing in disease awareness activity to drive up diagnosis rates. But there's a variety of reasons why we think that we have the opportunity to succeed in that first line setting. And I'd start with the clinical considerations from HELIOS-B.
I think the thing that we've gotten the most feedback on, positive feedback about the results, is the fact that these results were delivered in a contemporary patient population. So what does that mean? That means patients that are milder in the course of the disease than prior studies that have been conducted in this patient population. And patients that were on significant concomitant medicines. In HELIOS-B, we know at baseline that 40% of the patients were on tafamidis. And so having that patient population and showing these results, I think, gives the physician community a lot of confidence about the clinical effectiveness of the drug. And then if you go through the clinical results in the study, starting with, of course, outcomes, the all-cause mortality data in the study was particularly impressive.
I think in the primary endpoint at 33 to 36 months in the overall population, we saw a 31% reduction. And then the secondary endpoint that went out to 42 months, we saw a 36% reduction in the overall population and 35% in the monotherapy population. A lot of confidence, I think, in the drug because of that. Looking beyond the outcome measures in the study on functional status, health status, functional endpoints, quality of life, we also showed data that looked particularly impressive from a stabilization perspective. If you look at the six-minute walk curves and the KCCQ curves in the observed patients, you really see very stable outcomes there. And then lastly, I think it was the consistency of effect across the subpopulations in the study that also generates confidence and allows us to potentially compete very effectively first line. Two things to point out there.
In the TAF subgroup in the HELIOS-B study, we showed pretty remarkable efficacy on top of tafamidis. If you look at the all-cause mortality benefit in that 42-month secondary endpoint, we showed a 41% benefit on top of tafamidis. And then also, if you look at the study in the younger patients and the less on NT-proBNP, the patients at less than 2,000 at baseline, the outcome data there was particularly striking, which seems to argue for early treatment. So it's all of that together, I think, that gives us a lot of confidence that we're going to compete well in a first-line setting. And a reminder that this is a steadily progressive fatal disease. Patients typically, when they're diagnosed, have a two-and-a-half to five-and-a-half-year life expectancy. So there's the desire to go on the most efficacious product and the one that's going to have the biggest impact. We think that package allows us to potentially compete very effectively first line.
Absolutely. It's very compelling data. And another topic of conversation, and this is something that we've certainly heard from physicians. I find that sometimes I get a different answer from physicians on if I say, well, what medicine would you want to be on versus what are you going to prescribe, where reimbursement is a huge factor. I know there's a lot of conversation around B, D, and understanding that. But yeah, what drives your confidence?
Yeah. I mean, and this is another area we tried to provide some information to educate the investment community on what we expect. And so we really highlighted a lot of what the experience has been in the PN part of the market. And we actually think the CM market's going to look the same for us in terms of payer mix. So what we highlighted is that this is a population that's heavily Medicare. So about 75% of the population that we expect to be reimbursed via Medicare. And for us, we think that'll be split between traditional Medicare or original Medicare. It'll be about half of that amount. And the other half would be Medicare Advantage. 20% would be commercial, and then 5% would be Medicaid and other.
And today, with that payer mix on the hereditary polyneuropathy part of the market, we've got about 99% access across the U.S., so almost complete availability of the product. And from an out-of-pocket cost perspective for patients across that payer mix today in PN, we have about 70% of the patients that have a $0 out-of-pocket cost. And so we expect that to be similar in the CM part of the market. And I think that that could be sort of a real benefit for us as we launch in cardiomyopathy.
Absolutely. It makes sense, and just from a coverage perspective, so logistically, how does this take place? You already have the coverage in polyneuropathy. Do you then automatically get coverage in cardiomyopathy?
Not automatically. We're actually already starting those conversations with payers, obviously, to educate them on the HELIOS-B data that we've got. But those conversations will continue as we work through the regulatory process, ultimately get a label and get an approval. But that's what we're anticipating is where we're going to end up. I think we anticipate very broad access. And from an out-of-pocket burden perspective to the patients, we think it'll be quite modest.
Any color you can share from recent conversations with the payers?
Not a lot of specifics. I mean, I think the field team is out and have started those conversations. I think the conversations are going well. But those won't complete and wrap up with coverage decisions until we get an approval and a label.
Understood. And another topic of conversation is how to think about the market long term, particularly when tafamidis goes generic. I mean, theoretically, this could be a very good thing or a very bad thing, depending on how the payers treat it. What's your perspective?
Yeah. I mean, I think our view is that until tafamidis goes generic, it's largely going to be a monotherapy market. And that's based, again, on the experience that we've had in the polyneuropathy part of the market. And if you look at Amvuttra today, which is labeled for hereditary polyneuropathy, about 90% of the commercial plans that cover Amvuttra today have exclusions for combination use. And about two-thirds of the Medicare Advantage plans that are covering Amvuttra for PN today also have exclusions for combination use. So that's reflective of what we'd expect, probably even more exclusions as we get into cardiomyopathy. And I think the things that lead us to believe that, in addition to what we've experienced in PN, is this is a larger market opportunity in CM. So it's more on payers' radar. And we see a lot of growth coming in the segment.
Payers, we think, will manage this pretty carefully in terms of excluding combination use, two very expensive medicines together. We think that'll evolve and change as tafamidis goes generic. We agree with Pfizer on the timing of that. We expect that to happen at the end of 2028. At that point, we think that given the affordability of tafamidis as a generic product, that combination opportunities will become more prevalent. Of course, that will be driven by data to support that. Fortunately for us, as I mentioned earlier, the data that we had from HELIOS-B in the TAF subgroup was really pretty compelling. Now, it wasn't stat-sig. It wasn't designed to be stat-sig, but certainly pretty strong trends across all the endpoints in favor of Amvuttra in combination with tafamidis. We think that positions us well for that combination opportunity post-2028.
And so it gives durability to the franchise. Of course, we have another opportunity in our pipeline with TTR sc04 to also think about that combination market and the importance of that as we're thinking about the phase III study design. If we think that's particularly important from a commercial perspective, we can consider that in delivering that kind of data in the pivotal study. But more to come on that. We expect to provide detail to the market, as I mentioned in my introductory comments on sc04 in the first quarter.
Interesting. Could you tell us a little bit more about that? Maybe just the different potential strategies that you could take with sc04?
Let me just talk about how we're thinking about it, I think, from a long-term commercial perspective, and then I'll let Sandeep offer any additional comments that he may have from a clinical perspective, but as we're thinking about the design of the study here, this is meant to be a successor to Amvuttra, and it has IP out to 2042, and so we're thinking about the long game with this asset, and so we're thinking about how the market may evolve over that time, and so we want to design a study that's going to give us data that's going to allow us to be successful commercially for the long haul. That's probably the best way to put it. We've gotten a lot of questions about, could you take a quick-to-market strategy and look at a biomarker endpoint? Potentially, you could.
But you'd also have to think about whether or not that positions you well long-term commercially in a market that will have multiple generics over time, including Amvuttra at a certain point. So all of those things are considerations in our thinking about how to design the study. But anything else you want to say clinically?
I think from our perspective, Jeff, you've covered it extremely well. From a clinical perspective, we are designing a trial to ensure that it's relevant for the next 15, 20 years or so, basically based on what the market is going to evolve. So for us, it's important to have that thinking process. And what we are planning to do is in the next few months or so, in the first half of next year, we will be sharing our plans. And then we are excited to even start the study by next year. So I'll keep it at that at this point because there's a lot of work that is going on in the clinical development plan.
And the good news is with the HELIOS-B data, we have a lot of confidence that that's a therapy that's going to work in the clinic. And we have so much rich data from HELIOS-B that we can use in the design of that study. And so that's really what we're taking our time to do right now.
Is a head-to-head study versus, say, tafamidis something that's in the realm of consideration?
I don't know if I want to comment any further.
Yeah. I think it's a little bit early, actually, because we are processing all the data that we have received from, and obviously, we are in the midst of the regulatory review as well. There's a lot going on for us, so in the next few months or so, we will unveil our plan.
Understood. Okay, and another question that you perhaps might decline to answer, but we're all trying to think about how to model the cadence of uptake in cardiomyopathy next year. How are you thinking about that?
I'm not ready to give guidance yet, if that's the question. Look, I think that the way I would guide investors to think about this is to think about the different segments of the market that we already talked about the first-line segment. And globally, we think that's about 18,000 patients. So you need to think about that and what sort of share and uptake will we get there. Obviously, we're not launching globally. That's a global number, about half of that in the U.S. And so that's going to be the nearest-term opportunity. We haven't talked about the second-line opportunity yet much. We did highlight that segment also at the TTR Investor Day. And we think it's about 50% of the patients that are on tafamidis are progressing. And there's lots of different opinions on that. There's lots of different information in the marketplace.
There was a paper that was presented at HFSA by Dr. Fontana, actually, that looked at 800 cardiomyopathy patients in the U.S. for a year and looked at electronic health records and claims data, and what they found is 50% of the patients progressed over that one-year period, so that's a good estimate, I think, so we think roughly there's 40,000 commercial patients on tafamidis around the world today, so that would mean 20,000 maybe are progressing and would be an opportunity. We certainly think with our orthogonal mechanism of action that we're very well positioned to be the leader in that second-line segment. I think the questions that we have there about second-line, again, there's switch versus add-on. We've talked about the fact that add-on may be challenged for a period of time until we get to a TAF generic.
But there's not a switch behavior in the marketplace today because there's only been one therapy. So physicians haven't had to think about, what do I look at to determine whether or not a patient's progressing? And so it may take a little bit of time for that sort of protocol to develop and switching start to develop. We're obviously going to be working hard on that. But I'd think about that segment in terms of thinking about sort of an initial uptake and projection. And obviously, then the longer-term driver of growth is really the increased diagnosis rates in cardiomyopathy. We think that about 20% of the market is diagnosed today. So there's lots of room for long-term growth. And we'll obviously focus our efforts there too to continue to drive awareness and education.
But it's the first-line and the switch opportunity that people just need to think about the size of those segments. We've given you that detail. And then how quickly we're able to penetrate there. That's how people should be modeling this, in my opinion.
Great. Well, we'll definitely come back to some of the modeling and thinking about break-even. But first, I just want to touch a little bit more on the pipeline. So Sandeep, you mentioned a handful of programs. Maybe just, excuse me, in some of the earlier-stage pipeline, Huntington's, Alzheimer's, what are you most excited about? And talk us through some of the milestones we can expect to.
Sure, so actually, just to build on what Jeff was talking about, in the next 12 to 18 months, it is a very exciting time, and a very busy time for us, actually. We'll have the FDA approval in the first half and then a rapid launch. After that, sc04, we are going to unveil the development plan and then start the study. Zilebesiran, as we talked about before, the K3 study is going to read out, and then we plan to start our CVOT study, then we have the two CNS programs that are exciting. The first one is the ALN-APP, which is the mivelsiran, where we are targeting the amyloid precursor protein for the treatment of Alzheimer's disease and cerebral amyloid angiopathy, CAA.
These two programs are obviously the Alzheimer's program is ahead because it's the EOAD, which is the early-onset Alzheimer's disease, where we are collecting a lot of data, and you've seen some data that we have already shared in the Q3 earnings, which is our multi-dose, which was very, very exciting. The CAA study has started recruiting, and then we have the HTT, which is our Huntington program, which is a very unique mechanism of how we are trying to target the Huntington protein. I'm happy to go deep dive if you want in that one, but that is also recruiting now, so we are very, very excited about all of these programs.
And then in addition to that, you've seen that we are targeting different tissues now, where we are looking at muscle in addition to the CNS and the liver, which is already in the clinic. Plus, we are going into adipose. So it's an exciting time of innovation at Alnylam because there's not only a lot of things happening in the forefront in the commercial, but late-stage, we have a few studies that are going to be starting. But then we are going to double our pipeline next year by this time. So hopefully, we can talk more at that time or.
It's very exciting. In terms of the Huntington's program, you recently started a phase I study. Can you tell us a bit more about what you're looking to see from this study? What would be good data? And when can we maybe see this data?
Yeah, sure. So the Huntington program for us, this is exciting because this is our third CNS program, which is a milestone in itself for this platform. And then based on this mechanism, we are planning to develop an asset which can take care of or target the mutant Huntington protein. Now, for us, the way we are thinking about this is in the preclinical studies, we have both in the rodent and the non-human primates, human primates, we have seen no safety or tolerability issues. So our mechanism is a little bit or the targeting approach is a little bit unique.
So there has been growing evidence in the literature that not only targeting the full-length mutant protein, but beyond that, if you're targeting the mutant small exon 1 fragment, it will help in halting the progression of the disease, basically, because this disease otherwise is a rapidly deteriorating disease. So our approach is unique from that perspective because we are targeting the highly conserved region of exon 1, which helps us not only to take care of the mutant Huntington protein, but also the small exon 1 fragment transcript and the protein, which helps us to take care of most of the mutant species of the Huntington protein, which is very, very exciting in terms of the science perspective and how we are differentiated from the others who are already in the clinic or who have already failed.
Now, in the phase I program, which is in the clinic now, we are collecting data that is for the clinical biomarkers data, the NfLs, which is helping to understand the progression of the disease. There is neuroimaging data, and we have got, obviously, different doses to test. So it's exciting, and the major regulators have cleared us, U.K., U.S., and Canada. And we also shared for U.S., we do have a dose cap. But then technically, we don't think we need that kind of dose even to get to the efficacious or the clinical efficacy that we are looking for. Obviously, we'll still work with the FDA on understanding the dose cap. But at least from a program perspective, it's a green signal, and we are already recruiting as we speak. So very, very exciting in terms of what we bring to the table for the patients.
Great. Yeah, absolutely. And then when it comes to the Alzheimer's and CAA programs, I mean, we've seen target engagement as we've seen with all of your programs. You're successfully able to reach the protein. But maybe how should we think about the timing for when we could see clinical data and understand the effects on cognition?
Sure. So for the APP program, right, that is the amyloid precursor protein program, you've seen some exciting data that we shared lately in our Q3 earnings, so just to give a little bit of a background on the program, so this is an investigational RNAi therapeutic targeting the amyloid precursor protein for the treatment of both Alzheimer's and the CAA. Now, for what we have shown in the past is just one dose of APP has knocked down or helped the reduction of the soluble APP beta and the soluble APP alpha, which are the biomarkers of target engagement, pretty robustly, and it was also durable, so it was not just knocking down. It was a very durable effect with just one dose.
That also helped in subsequently reducing the Aβ 40 and Aβ42 , which are the peptides of the actual disease involved in the disease pathogenesis. So that's number one in terms of the early data that we shared. Then after that, in the Q3 earnings, we also shared that for the multi-dose section, when we dose one more time, which is at month six, within a month's time, we are seeing about 92% reduction in the target engagement biomarkers, which is the soluble APPβ. And this is, I want to knock on wood, that without any safety or tolerability issues. So it's very, very encouraging safety and tolerability. So now, as we are collecting more data, so our phase I is ongoing. We're collecting more data, especially for the multi-dose section. So we are collecting data on the biomarkers, cognition. We are collecting data on the imaging, which is a lot of data that is going to come in the next year or so. So.
This early Alzheimer's, you said it earlier, that's EOAD and.
EOAD, yeah. Yeah, so it's early-onset Alzheimer's disease, basically. So just to be clear, thanks for punctuating that, Jeff. So technically, we are getting to a place where we will have a lot of data from Part B in the near future, which we plan to share in different congresses. And obviously, for the CAA, it started. And we are enrolling patients. So it's a little bit too early to comment on that.
Got it. And it seems like you do have a growing pipeline. But from a BD perspective, can you tell us a little bit more about your philosophy from here? Are there areas that you think that, for instance, we've seen a lot of development in the RNA editing space? Are there any sort of technologies that you feel like would complement the Alnylam platform?
Yeah, I think from an innovation perspective, our focus has really been on internal innovation, so continuing to invest in RNAi. I mean, I think given the success rates that we've had historically, that argues pretty persuasively that's where we should be investing. And also based on the fact that, as Sandeep said, we're starting to expand into new tissues. So we don't see a shortage of high-quality targets to pursue with RNAi. So that continues to be the focus for innovation at the company is internally focused. Per your comment, I think that from a BD perspective, certainly, we do keep an eye on technologies that may be complementary to our platform, particularly in delivery. We've made some investments there.
I anticipate for the foreseeable future that that's really where our focus is going to be from a business development perspective, rather than looking more broadly at sort of whole new technologies. We're going to continue to stay focused on RNAi for now.
Absolutely. That makes sense, and maybe just when it comes to thinking about profitability, you're typically doubling your pipeline, major launch in cardiomyopathy. How do we think about that look from here?
Yeah, I mean, we made this commitment back in January of 2021 when we rolled out our P5 strategy, which had a couple of financial goals associated with it. One was around top-line growth across the period where we anticipated top-line growth of 40%+ . We're on track to achieve that. And I'm optimistic about next year that we'll be able to cross the finish line and achieve that goal, given the launch in cardiomyopathy that we talked about in the U.S. early next year. And then we also committed to achieving non-GAAP profitability by the end of the period. And I think on our Q2 results call, when I upgraded the guidance on product sales, I commented at this point in time, I think I'm as confident as I've ever been in our ability to achieve that.
There's a couple of things that I think underpin that confidence. One is the base business, which continues to perform very well. And maybe I should comment on the TTRPN business in the U.S. AstraZeneca launched Wainua at the end of last year in the U.S. And so there were some questions about what impact might we see on our base PN business in the U.S. And the good news is we haven't really seen any impact from that. In the quarter before they launched, the U.S. grew 38%. And the three quarters that Wainua has been on the market, it's grown 35%, 40%, and 37%. So we've seen very consistent growth in the face of a competitive launch. And the competitor is doing OK as well. So what we're seeing is what we thought we would see. It's expanding the market. And we're the leader.
We're taking the majority share. That's particularly good. That confidence in that base business continuing to grow allowed us to upgrade the guidance. That should carry over into 2025. Given the HELIOS-B results and the strength of that, I think that we have an opportunity to have a favorable launch next year, which will obviously contribute top-line growth and ultimately support getting to profitability. We can do all of that and do all of these things that Sandeep's talked about. That's always been the focus for the company to get the profitability. It's not been squeezing R&D or limiting what we're investing in R&D. The success on the commercial side is enabling us to get the profitability, but also continue to significantly invest in the pipeline for the long term. That's what we intend to do.
Great. And as we think about the cardiomyopathy sort of sales force and the buildup there, just with the U.S. as well as ex-U.S., sort of where are you in this buildup already?
Yeah, I mean, in the U.S., we've completed it. We were ready to go when we had the HELIOS-B results. And once those results came back positive, very quickly, the commercial team started to do the recruitment to expand the size of the field team. And I would describe it as a step up, but not a significant leap in terms of what we're doing to build that field force to be ready for the launch in cardiomyopathy. Remember, we're building off of the foundation that we had in polyneuropathy. And we actually gave a couple of statistics, I think, at R&D Day that reflected the benefit that we've got from being in the market for the last five years.
If you look at the physicians that are writing prescriptions and treating patients on tafamidis, there's about 3,700 physicians that are covering about 95% of the patients that are under treatment. Before expanding into cardiomyopathy, we were already calling on 65% of those physicians, so we're going to get a lot of benefit from the five years of experience that we've had in the marketplace. Oftentimes, in the large treatment centers, the academic centers, they're treating the whole sort of spectrum of patients, hereditary, wild type, et cetera, so this is a community that already knows Alnylam quite well, knows our technology well, and we're going to benefit from that, so again, I would say it's a step up from where we've been, and in the U.S., we're ready to go. We got the field team fully hired and staffed and getting trained and ready to go.
Great. And then ex-U.S., how are you thinking maybe about the commercial opportunity there in cardiomyopathy relative to the U.S., as well as the investment?
Yeah, I mean, I think it's a very outstanding opportunity. If you look at the business that we've had over the last five years in polyneuropathy, we're probably at about 55% U.S., 45% ex-U.S. So the international part of our business in TTR has been a significant contributor to what we've built. And I would anticipate over time that they're going to contribute in cardiomyopathy as well. It'll take time. I mean, typically, the working through the reimbursement and the pricing process takes longer outside the U.S. I do anticipate that we'll have a few additional launches outside the U.S. in the second half of next year that will contribute some growth. But over the long haul, we'll be invested to grow the business ex-U.S. as well.
Great. And one thing we didn't touch on as it relates to TTR are the mixed phenotype patients.
Yeah.
And I mean, we've heard a wide range of estimates of what proportion. And how does this play into some of the prescribing behavior?
Yeah, I mean, it's really difficult. We don't have the granularity to tell you of the 5,000 patients roughly that we have on commercial therapy for polyneuropathy today, how many would fit that mixed phenotype definition. We just don't have that level of detail. The reality is probably a lot of them, because this is a spectrum disease. And typically, most patients, depending on the mutation, do have some complications of both PN and CM. But we don't have that level of detail to precisely answer that question today.
Great. Well, I think we'll end it there. But Jeff, Sandeep, thank you so much for the time and the insights.
Thanks for having us.
Thank you.