Great. Good morning, everyone. My name is Jessica Fye. I'm a Senior Biotech Analyst at JP Morgan, and we're delighted to be continuing the 42nd Annual Healthcare Conference today with Alnylam. I'm joined by the company's CEO, Yvonne Greenstreet. She's going to give a presentation, and then afterwards, we're going to move into Q&A. If you want to ask a question in the room, someone will bring you a mic. If you want to submit a question over the portal, you can do that as well. But very happy to hear Alnylam today. So I'll turn it over to you.
Thank you, Jessica. It's a real pleasure to be here presenting on behalf of Alnylam in what we expect to be a milestone year for our company. I'm Yvonne Greenstreet, and I'm CEO of Alnylam, and I'm very pleased to be joined up here on stage by Pushkal Garg, our Chief Medical Officer, Jeff Poulton, our Chief Financial Officer, and Tolga Tanguler, our Chief Commercial Officer. So we've got a great panel with us here today. So during my presentation today, I will be making forward-looking statements. But I want to start off by just reiterating that Alnylam is the leader in RNAi therapeutics, and this holds true across many dimensions, and we have tangible results that demonstrate this, including outstanding R&D productivity, where we validated an entirely new class of medicines. We've delivered a commercial portfolio of five medicines approved in less than four years.
I think you all agree, a remarkable achievement. We've also got leading commercial capabilities. We're generating over $1 billion in annual product sales, and we have a commercial presence in over 60 countries, with direct sales in all the major markets. We're very proud of our robust and high-yielding pipeline. It currently consists of 15 programs in clinical development, and we expect this to double in the coming years with an additional 15 programs expected in the clinic by the end of 2025, as well as a strong financial position, something to be valued in this particular environment, where we are firmly on the path towards financial self-sustainability. Now, I'd like to quickly reflect on some of our really notable achievements in 2023, where we delivered strong progress across the entirety of the business. We really are firing on all cylinders.
So this included robust product growth, with our four wholly owned commercial medicines now driving $1.24 billion in global net product revenues, and with over 5,000 patients who are now benefiting on Alnylam commercial medicines. We've also continued to extend our leadership in RNAi, including the first-ever demonstration of RNAi-mediated target gene silencing of the human brain and preclinical data showing for the first time delivery of RNAi therapeutics to adipose and muscle, progressing zilebesiran for hypertension with very encouraging phase II results from the KARDIA-1 study. And really strengthening our business for the future through business development, including a landmark partnership with Roche, exemplary financial performance with $2.5 billion of cash on the balance sheet, and maintaining our award-winning culture, and this really has been a critical enabler of our success. So 2023 was a great year for Alnylam.
As we look ahead, we believe that there are three core elements of our business that are going to drive sustainable growth and value creation for years to come. These include strong commercial growth, a robust and high-yielding pipeline, and a sustainable innovation engine. Let me begin with our strong commercial growth. Our four wholly owned commercial products comprise a portfolio of transformational medicines, which are now delivering over $1 billion in annual product revenue. Yesterday, we pre-announced our fourth quarter and full year 2023 global net product revenues, and in total, achieved $1.241 billion. Now this represents a 39% year-over-year growth and with over 5,000 patients now on an Alnylam commercial medicine worldwide. This is since nine...
Since 2019, which is our first full year of being a commercial company, where we've seen impressive revenue growth with a 65% CAGR over this time period. So we'll be providing 2024 product revenue guidance and much more color on our commercial performance on our earnings call in February. But we believe that our strong commercial performance, the solid capabilities behind it, position Alnylam well for exceptional future growth. Now, the second key value driver is our robust and high-yielding R&D pipeline. I think one of the richest pipelines in the biotech sector today. Now, this high-level view of our pipeline shows 15 clinical stage programs across a broad range of disease areas and indications at all stages of development. We've also included here preclinical programs in IND-enabling development, and these comprise the next wave of innovative RNAi therapeutics.
Further, this slide shows programs targeting genes expressed not just in the liver, but also multiple programs targeting genes expressed in the CNS. As I said, this is arguably one of the most fulsome pipelines in the biotech industry today, and I'm going to highlight later in the presentation that we expect to see this undergo significant near-term growth. So let me first highlight the progress that we've made with our TTR franchise. As most of you know, ATTR amyloidosis is a debilitating, progressive, and often fatal disease in which misfolding of the TTR protein accumulates and damages a wide range of tissues, including the nerves, the heart, and the gut, and it causes irreversible damage and premature death in patients.
Now, RNAi therapeutics are uniquely suited to address the root cause of ATTR amyloidosis by providing rapid knockdown of the disease-causing TTR protein, as highlighted with both the vutrisiran and patisiran in this figure from our HELIOS-A study. And in fact, a majority of healthcare professionals surveyed said that the speed of reaching 80% mean reduction of serum TTR is an important factor impacting treatment consideration. And we've seen the transformative impacts the rapid knockdown has had on the treatment of polyneuropathy in hereditary ATTR amyloidosis patients, where both Onpattro and Amvuttra have demonstrated definitive evidence of substantial benefit in neuropathy, impairment, and quality of life. This really is a compelling clinical profile, and it's resulted in strong commercial uptake that we've heard about in patients with hATTR amyloidosis, with polyneuropathy, with nearly $1 billion in annual revenues and a dominant market share.
With an estimated 25-30,000 patients living with this form of the disease, there remains a substantial opportunity for significant growth within this patient segment alone. You know, at the same time, we're witnessing a dynamically evolving market for ATTR amyloidosis with cardiomyopathy. Since the introduction of the first approved therapy for ATTR amyloidosis with cardiomyopathy in 2019, and the availability of non-invasive diagnostic tools like scintigraphy, there's been a steady increase in diagnosis rates. And furthermore, just like other underdiagnosed and undertreated disease areas, we believe that the diagnosis rates will continue to increase, driven by the introduction of new products over the next several years.
Now, assuming successful data and approvals, we believe we're well positioned to deliver the potential of RNAi therapeutics to what we believe remains a significant unmet patient need, and we remain confident in our ability to be a potential leading option in this fast-growing disease category. So to that end, we intend to expand the label for Amvuttra to include the treatment of cardiomyopathy in both hereditary and wild-type ATTR amyloidosis patients. And many of you may be familiar with this slide. We're pursuing this via the HELIOS-B phase III study of vutrisiran, and we're on track to report top-line results in early 2024. So we believe that there are a wide range of factors that make HELIOS-B well positioned to successfully demonstrate an outcomes benefit with vutrisiran in ATTR cardiomyopathy patients.
So the treatment effect on cardiomyopathy was most recently demonstrated in the APOLLO-B study, where patisiran showed a favorable impact on functional capacity, disease markers, and mortality. Now, while these data did not result in a successful approval for patisiran, we believe that these data are nonetheless exceedingly important, and they support the potential for patisiran to demonstrate an outcomes benefit in HELIOS-B. Furthermore, the HELIOS-B study was designed and powered to deliver outcomes, and it's twice as large and three times as long as APOLLO-B. The study is also enriched for patients who are most likely to show strong benefit, and HELIOS-B provides the longest follow-up of any study conducted in ATTR cardiomyopathy, with a follow-up for 36 months in most patients. The study was conservatively powered, and there were additional tailwinds.
The study over-enrolled by 10%, bolstering our confidence in the sample size, and we came in below our 50% target for patients on baseline tafamidis, with a low rate of tafamidis drop-ins that remains well within the expectations that we used to power the study. So I hope you'll all agree that we have many reasons to believe that HELIOS-B is well positioned for success. Now, assuming positive data and regulatory approval, we also believe that patisiran would be very well positioned to serve patients in ATTR cardiomyopathy, addressing unmet needs with a highly competitive, market-leading profile, including a unique mechanism of action that works upstream of protein production and enables rapid knockdown of TTR.
An impactful clinical profile with the potential to reduce mortality and cardiovascular hospitalizations and halt the inexorable decline in functional capacity and quality of life, as well as an attractive quarterly dosing schedule that aligns very well with doctor visits and supports strong adherence. So assuming positive data, we believe that Amvuttra's compelling clinical profile could support first-line positioning that could drive significant growth in our TTR franchise over the long term. So between now and the loss of exclusivity of tafamidis, which is anticipated in late 2028, we expect the market to be primarily monotherapy driven, given the cost of combination therapy. And assuming positive data and a regulatory approval, we anticipate that Amvuttra has the potential to become first-line treatment for newly diagnosed cardiomyopathy patients, as well as those patients that continue to progress with stabilizers.
Now, once tafamidis goes generic, it may open up the additional opportunity for combination therapy. So all of this gives us confidence that Amvuttra has the potential to be a major growth driver for our business in both the near and the long term. And given the importance of the opportunity that we have in Alnylam in TTR, we'll continue to invest in additional evidence generation activities, which will support Amvuttra's compelling profile. And of course, you know, what patients really want is to be able to forget about their disease, and a once-a-year therapeutic offering that reversibly suppresses TTR could represent a significant improvement in the treatment paradigm. So we're expanding our TTR franchise with ALN-TTRsc04. This is our latest generation TTR targeting RNAi therapeutic that utilizes our IKARIA platform.
Initial phase one results, shown here, support a best-in-class profile with a rapid knockdown of serum TTR that was robust and highly durable, greater than 90% at six months, and this supports the potential for an annual subcutaneous dosing regimen. The data also demonstrated an encouraging safety profile. The phase I study is ongoing, and we plan to advance ALN-TTRsc04 to a phase III study in ATTR amyloidosis with cardiomyopathy that is expected to start at or around the end of 2024. Let's shift gears a little, and let me now tell you about another exciting late-stage program in our pipeline, zilebesiran, which offers an exciting opportunity to reimagine, reimagine the treatment of hypertension. Hypertension is a highly prevalent disease. There are over 200 million people with primary hypertension in just the seven major markets.
Almost 80% of them, 80 million of them, have elevated cardiovascular risk, and despite the widespread availability of treatments to manage the disease, about 80% of these high cardiovascular risk patients are not at their target blood pressure control. You can see here on the slide that actually fairly modest reductions in blood pressure lead to substantial clinical benefits with respect to major CV events, stroke, et cetera. Increased cardiovascular risk is further exacerbated by variability in blood pressure control, inadequate nighttime control, and poor adherence to medications. All of these factors contribute to a substantial risk of cardiovascular morbidity and mortality and highlight the critical need for new differentiator therapies that can provide tonic control of blood pressure and improve adherence. Zilebesiran is our investigational RNA therapeutic for hypertension, which, as I said, we believe could transform the treatment of this disease.
Data we recently presented from the KARDIA-1 phase II study highlight this potential, where we demonstrated clear evidence for over 15 millimeters of mercury reduction in systolic blood pressure at six months after a single injection, and 24-hour tonic blood pressure control, which was also maintained out to six months. Zilebesiran was also generally well tolerated in this study. We intend to progress. Given the opportunity that we have in our hands, we intend to progress a robust development plan for zilebesiran, generating cardiovascular outcomes data prior to launch and thereby optimizing the commercial opportunity globally. In partnership with our colleagues at Roche, we've designed a comprehensive clinical development plan focused on exploring the benefits of tonic blood pressure control to potentially reduce cardiovascular risk in patients with uncontrolled hypertension.
Next up is the KARDIA-2 study, where we're evaluating zilebesiran in combination with single antihypertensive agents, and we look forward to reporting top-line results from KARDIA-2 in early 2024, as well as initiating the KARDIA-3 study, exploring the combination of zilebesiran with two or more antihypertensive medications in patients at high risk, high cardiovascular risk with uncontrolled hypertension. So to realize the full potential of an innovative therapy like zilebesiran, we believe that it is critical to launch the product with a robust and comprehensive data set that will ensure rapid and smooth adoption of zilebesiran into the treatment paradigm. So to that end, we plan to conduct a cardiovascular outcomes study as a pivotal trial, and assuming a successful study and regulatory approval, we expect that the data from this study could significantly differentiate zilebesiran and provide the most compelling value proposition at launch.
Another key program that I'd like to highlight, where we're also very excited about the potential, is ALN-APP, our first investigational RNAi therapeutic, targeting a gene expressed in the CNS and in development for the treatment of Alzheimer's disease and cerebral amyloid angiopathy. ALN-APP could offer a highly differentiated approach in the treatment of these two diseases. By targeting APP upstream of where antibodies currently target, ALN-APP has the potential to reduce pathogenic peptides, both intracellularly and extracellularly. And we're excited. Actually, we were thrilled by the positive results that we saw from the phase one study in patients with early-onset Alzheimer's disease, where ALN-APP treatment resulted in rapid, dose-dependent, and sustained reductions in CSF levels of both soluble APP alpha and beta, both biomarkers of target engagement.
We've also seen marked reductions in A beta 42 and A beta 40, the soluble forms of the amyloidogenic peptide that aggregate into amyloid deposits in Alzheimer's disease and cerebral amyloid angiopathy. So just as we've done in ATTR amyloidosis, here, too, we're showing reductions in biomarkers directly tied to disease pathogenesis. The safety of single doses of ALN-APP has also been encouraging. Dose escalation of the single dose portion of the study continues, and we are initiating the multi-dose part B in approved regions, while that part of the study remains on partial clinical hold in the U.S. We also look forward to initiating a phase II study in cerebral amyloid angiopathy in early 2024.
Overall, we are just so pleased about these impressive human data, showing the potential for RNAi to silence disease-causing transcripts in the CNS, where we're now building a rich pipeline of programs to address a wide range of neurological diseases where there is high unmet need. We look forward to leveraging the reproducible and modular approach that has served us so well in the liver and applying it now to progress in the CNS. We also look forward to the growth opportunities and value creation from programs discovered by Alnylam and led by our partners. Of particular near-term interest is fitusiran, which is in development for the treatment of hemophilia and is being progressed by our partners at Sanofi, who guide it towards an NDA submission later this year.
So let me now talk about how we're not just going to deliver growth that we have done and over the next few years, but our plan to sustain growth well into the next decade with a third growth driver for the company, and that's our sustainable innovation engine. The clinical results that I've shared with you thus far that have led to the approval of our commercial medicines are all products of a highly differentiated and de-risked platform. So harnessing the power of RNAi has created a profile for our medicines that is characterized by a few very important points: rapid knockdown to silence the production of disease-causing proteins, a clamped pharmacology that creates the potential for improved efficacy and outcomes, extended durability that enables infrequent dosing to maximize adherence, and favorable safety.
So going forward, we plan to continue to apply the same modular and reproducible approach towards developing one of the most exciting pipeline of innovative medicines in the biopharmaceutical industry. All of this has resulted in a historical probability of clinical success that is multiples higher than industry standards, driven by human genetics. So how do we take this special sauce and use it, as I've said, to create substantial growth for the future? You can see the answer here. So we aim to deliver RNAi therapeutics to all major tissues by leveraging our advances in extrahepatic delivery. We'll continue to invest in platform advances. We're a platform company to enhance the fundamental designs of siRNAs to make them yet more efficacious, safe, and convenient.
We plan to harness the power of human genetics via access to large databases to continue to identify novel, genetically validated targets. Combining these core elements of our innovation engine, by the end of 2025, we aim to file our Alnylam-led INDs for nine programs, including five against targets expressed in the liver, two in the CNS, and two new tissues, namely adipose and muscle. If we include partner-led programs, the total number of new INDs anticipated by Alnylam is 15 by the end of 2025, and this represents a doubling of our clinical pipeline over the next 12-24 months. As you can see, we truly are spring-loaded for tremendous growth in the years ahead. Wrapping up, here's a list of our company goals for 2024, which capture the key elements of the exciting year ahead.
I'm not gonna walk through all of these, but at a high level, we look forward to ongoing commercial execution for our commercial products. We look forward, many in the industry are also looking forward to results from the HELIOS-B Phase III study of patisiran. Assuming a positive study, we'll be submitting an sNDA to expand the label for patisiran to include ATTR amyloidosis with cardiomyopathy. We'll be getting results from the KARDIA-2 Phase II study of zilebesiran. We'll have six clinical study starts across all stages of development, and we'll be filing three new INDs from our organic R&D engine to advance new programs into the clinic and position Alnylam for future growth. So we believe that all of this progress will move us further along our path to achieving our five-year vision, Alnylam P5x25 by 25.
This vision is aimed at establishing Alnylam as a top-tier biotech company with transformative medicines in both rare and common diseases for patients around the world. A robust and high-yielding pipeline of first and or best-in-class product candidates from our organic product engine, all while delivering exceptional financial performance. So in closing, we're very excited about the future at Alnylam. We know our vision is bold, but the roadmap to get there is clear and is actionable, and I hope that all of you share our enthusiasm. So with that, I shall turn it over to Jessica for our Q&A. Over to you.
Great, thanks for that presentation. And as a reminder, if you wanna ask a question in the room, feel free to use the portal, or you can raise your hand, and someone will bring you a mic. This is, like, all you guys get questions on, but-
We're happy to, Jessica.
So with the HELIOS-B readout right around the corner, I guess just to start, can you just help us understand what we should be expecting in terms of level of detail with the top-line release and whether you will be co-commenting on key subgroups, for example, those on and not on background tafamidis?
Yeah. I mean, so clearly, we're looking forward to the HELIOS-B results in early 2024. And just a reminder, for those who are not familiar with the Alnylam lexicon, early 2024 actually means the first half of 2024, so Q1 and Q2. And look, you know, we'll do what we've always done, the standard practice. We will report, you know, P values for the primary and secondary endpoints. We'll make a qualitative assessment of safety, and then, you know, we'll look for the most proximal medical conference in which we'll share more fulsome results.
It's just when you think about timing, how long should we expect it'll take for you to lock the database, perform that data analysis after the follow-up from the last patient is complete?
Yeah. It wouldn't surprise any of you in this room that we're uber focused on executing a successful study here for HELIOS-B. And obviously, you know, we will be, you know, analyzing and interpreting the data as expeditiously as possible, as soon as the study concludes. You know, in general, that process takes a matter of weeks. So it's not a matter of days, it's not a matter of months, but it's a matter of weeks to be able to turn all of that data around when the study concludes and be in a position to present that data externally.
Okay. And then sticking with that trial, can you remind us why the primary endpoint includes all-cause mortality and not just cardiovascular mortality, obviously, in addition to the recurrent events?
Yeah. Look, that's a great question. I think from a patient and physician perspective, mortality is mortality. A death is a death, and particularly for a multi-system disease like ATTR amyloidosis, we wanted to capture all-cause mortality. And, you know, we thought about it quite hard and we also recognized the precedent in previous studies, the ATTRACT study, which had used this endpoint, and we thought it was the prudent thing to do to base a study on existing information.
Okay. And it's just... This is something kind of everybody's thinking about these days.
Yeah.
But can you walk through the rationale for why Amvuttra could drive further benefits on outcomes beyond what could be achieved with a stabilizer like tafamidis?
Yeah. So I think it's important to recognize that patients on tafamidis continue to progress. We've seen that in the ATTRACT study. It's quite clear we get that same feedback from physicians and patients. And I think what physicians and patients are really looking for is another treatment, one that has an orthogonal mechanism of action. That's something that we'll be able to provide with vutrisiran. What's also quite interesting is, and the proof points, I think one of the proof points for this, is how rapidly we enrolled our expanded access program for patisiran. So, we opened up an EAP. We had a cap of close to 200 patients, and these were patients who were on tafamidis, many of them continuing to progress.
Within record time, that study was fully enrolled and with a limited number of sites. So we think there are a number of proof points that indicate how much physicians and patients are looking for better treatments in TTR amyloidosis with cardiomyopathy. And if we think about the, you know, profile that's emerging here, and if we're able to deliver the promise of HELIOS-B, where we hit on, you know, the primary endpoint of all-cause mortality and recurrence of the events, we're able to show stabilization, you know, of disease across, you know, multiple parameters. And we're able to show consistency of effect in key subgroups. In a key subgroup, patients on tafamidis and patients not on tafamidis. If we can, if you can demonstrate all of that...
We believe that we're gonna have a really compelling profile for vutrisiran in patients with cardiomyopathy. And a profile where, you know, physicians will, you know, switch patients who are progressing onto tafamidis. It'll also be used as first-line monotherapy, given that profile. And there may be some combination use, but as I pointed out in my presentation, prior to patent expiry of tafamidis, combination therapy, I think, is going to be somewhat prohibitive. And so we really see vutrisiran making an impact in monotherapy switch patients with some limited combination use.
So some questions from the portal here, also on HELIOS-B.
Oh, yay.
Given that there is still time to tweak your endpoint in the statistical analysis plan, are there any thoughts on updating it relative to what's currently on ClinicalTrials.gov?
So I don't think there's anything more to say on that matter than we have done already. We feel very confident in the design and execution of the HELIOS-B study. You know, as is common practice actually in the industry, there is an opportunity to make modest tweaks to the stats and the stats analytical plan prior to database lock. And you know, we will only look at doing that if we feel that there's a good reason to, in terms of you know, improving the profile of what we get out of that study. So for now, there's really not much more to add on that.
I guess, is that to say that you've already thought about it and sort of decided that you don't have to make changes?
No, it's exactly what I've said. It's just, it's just, you know... Again, I think most people in the industry understand that there is the opportunity to do this. We've just stated that. So I don't think there's anything to read into the comments that we've made.
And then the next one in here is: What can you share about blinded mortality or cardiovascular event data from HELIOS-B? Anything, any comments you can make on blinded data?
No, we're not going to be making any comments on blinded data. Clearly, we have a small team in the company that look at blinded data, you know, with the perspective of maintaining quality and study integrity, but there's nothing to add with respect to sharing blinded events rates at this point in time.
Okay. And then the next one's sort of about the, kind of, I guess, baseline characteristics. Are you expecting the patients in HELIOS-B would be healthier than in APOLLO-B or in the BridgeBio ATTRibute study?
Well, maybe Pushkal, you might like to comment. I think we're looking at a very similar set of demographics, but you may have more to add.
Yeah, absolutely. Look, I think, I think what's important to recognize, as Yvonne highlighted, is coming out of APOLLO-B, the substantial effects that we saw across so many different endpoints when we did TTR lowering with patisiran. We saw benefits on functional status, quality of life, imaging parameters, cardiac biomarkers, and even disease progression indices. We saw stabilization of some of those parameters out to two years in the open-label extension. What we're seeing is actually a very remarkable and potentially very differentiated approach and profile from other therapies that have been brought forward in this space. In terms of the patient population, one of the things that Yvonne highlighted in her presentation is that we purposely looked at patients who were somewhat earlier in their disease course.
We know that those are the patients who have the greatest opportunity to benefit, and both APOLLO-B and HELIOS-B were designed with sort of similar inclusion criteria to really overindex on that group of patients. And so I think what you can expect is that we'll be looking at the patient demographics will be relatively similar between HELIOS-B and APOLLO-B.
So, I guess this one is-
Do you want a pipeline question?
This one is kind of like: Can you elaborate on how your endpoint is sort of similar to or different from the ATTRACT and ATTRibute endpoints? And I guess when people go to inevitably do their cross-trial comparisons, you know, what would you consider good data in the context of, you know, not having identical endpoints?
I think the important thing is you've got to be very cautious about making, you know, cross-study comparisons. And I think, I think people know what the different endpoints are in the study. I'm not sure there's an awful lot to kind of add to that, that question, actually.
I guess the last one here is: How do you think about the commercial opportunity if HELIOS-B shows its most kind of compelling data in patients who are not on background tafamidis? And are there data that you could present to show why you would be better than tafamidis in those patients? Or if not, is this a, you know, would that kind of position the product for a post-tafamidis opportunity?
So I think the question is how we're thinking about commercialization, you know, with vutrisiran. I mean, Tolga, maybe you want to tackle that question.
Yeah, I mean, obviously, we're excited about what we've already done with the polyneuropathy. There are certain elements of this product will remain the same. The rapid onset of action, which we believe is actually a significant differentiator. The fact that, you know, we've been able to demonstrate it again in PN, you know, reversal and halting the disease, which we believe, you know, with the cardiomyopathy, will demonstrate that. If we reach the outcomes, we believe, with an ideal subcutaneous administration and a very favorable access coverage, this product, and, and as Yvonne indicated, there's still a significant number of patients that are still being undiagnosed and undertreated. We believe, this is gonna be a really important option for the patients.
Thank you, Tolga.
So maybe switching to zilebesiran, given the impressive data that we've seen so far on blood pressure lowering, how are you thinking about what kind of lowering effect we should expect to see in either KARDIA-2 or KARDIA-3 when you're going on top of standard of care?
Yeah. No, that's a great question, actually. Thanks for that, Jessica. We're. As I indicated to you in my presentation, we really are excited about the results that we've generated thus far for zilebesiran. You know, the KARDIA-1 phase II data, I mean, honestly, a single subcutaneous injection delivering that magnitude of blood pressure control in a tonic fashion. I think this is going to be a real advance in the field. So what we're doing is that we're elucidating the benefits of zilebesiran in a very methodical, thoughtful fashion. So the KARDIA-1 phase II study was a monotherapy study. The KARDIA-2 studies, we're studying zilebesiran on top of one of three classes of antihypertensives. And in the KARDIA-3 study, we're studying zilebesiran in patients at higher risk of cardiovascular disease.
So patients who are on two or more antihypertensives and have a history of atherosclerotic cardiovascular disease or chronic kidney disease. I think it's really important to assess the benefits of zilebesiran in these patient populations, and we're expecting to see some additive benefits on top of existing hypertensives. But it's also important that we assess safety of a new agent like zilebesiran on top of antihypertensives. So we're really looking forward to these data. The KARDIA-2 data, we'll be sharing. Again, when I say early, you'll know what that means, in early 2024, and we will be kicking off the KARDIA-3 study in 2024 as well.
Great. We're out of time, so thank you.
Thank you.