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

Good morning. Thanks for joining us for our 41st Annual Goldman Sachs Conference here. Before we start, I'm going to make some disclosures. We are required to make certain disclosures in public appearances about Goldman Sachs relationships with companies that we discuss. The disclosures relate to investment banking relationships, compensation received or 1% or more ownership. We are prepared to read aloud disclosures for any issuer upon request. However, these disclosures are available in our most recent reports available to you as clients of the firm on our firm portals. Disclosures and updates to these disclosures are also available by ticker on the firm's public website. In addition, disclosures available to research with respect to companies, if any mentioned herein, are available through your investment representative. Further information on the subject companies may be obtained from Goldman Sachs. Goldman Sachs may beneficially own 1% or more of the securities. Also the view stated by non-Goldman Sachs personnel do not necessarily reflect that of Goldman Sachs. With that, I'm Salveen Richter, Biotechnology Analyst at Goldman Sachs, and we're pleased today to have Alnylam with us. And we have John Maraganore, CEO.

So to start, John, with the potential launches of lumasiran and inclisiran by year-end '20, you'll have surpassed your Alnylam 2020 goal that you set in 2015 of launching 3 new products by this time frame. So what is the outlook for Alnylam over the next 15 -- or next 5 years?

Okay. 15?

15.

So thanks, Salveen. And thanks for having me, and Alnylam at the conference, the virtual conference. It's great to be here. Great to see you. Look, the company has been, I think, very successful. And over the last few years, we've seen the approval of the first RNAi therapeutic and the approval then of the second RNAi therapeutic, which happened to be the first that uses our GalNAc-conjugate platform. And now as you state, we have 2 products in registration, lumasiran and inclisiran, and we expect approval of both of those products by the end of the year. So we're going to exit 2020 with 4 products on the market, which is obviously very exciting. 3 that we're directly commercializing ourselves. If you fast-forward over the next 5-year period, we very much are aiming at becoming a top 5 biotech. And what's going to drive that is the flow of additional products that come to market. We've got in the near term, vutrisiran, which is our TTR subcu molecule, fitusiran with Sanofi, which is our hemophilia product. And then, of course, the clinical pipeline of 11 products behind it, including some important label expansion opportunities in the pipeline with products like ONPATTRO and vutrisiran as well. So we see a very strong potential to build Alnylam into that top 5 category in biopharma based on our product engine, our clinical pipeline and our commercial execution.

And then can you speak to your BD strategy, maybe start with the strategic decision to enter into a collaboration with Dicerna where you had competing indications? And do you see these as representative and then also touch on the Blackstone deal for monetization of inclisiran royalties here?

Yes. I mean, obviously, BD has always been part of how we've built Alnylam in the past. The Dicerna deal that we did relatively recently is a relatively small transaction to really focus, first of all, on a cross license for IP that was present in the primary hyperoxaluria space so that we can avoid lawsuits and go on and advance these products to patients without that type of overhang. The deal that we did as part of it with alpha-1 antitrypsin efficiency, really reflects our belief that, that product should be led by 1 company, not 2. Dicerna is going to do that. We retain commercial rights outside the U.S. for free as an Opt-in Right after Phase III is completed. And we're focusing more on large market opportunity products like our AGT product. The Blackstone deal that we did is really a financing, and frankly, our last ever financing. We've monetized our royalty for inclisiran for half of it for $1 billion and also brought in some corporate debt and are now in a position as a company where we expect to never have to raise equity ever again in the future as we get to profitability as a business.

That's great. And then are there therapeutic modalities you would look to bring in? Or are you just a pure RNAi company as you look to the future?

Yes. We're probably going to be a pure RNAi company for a long time. And we have so much in front of us in terms of programs and delivery approaches that we've expanded beyond the liver. We're now in the CNS and the eye and also in the lung. So we don't feel the need to find other technology platforms. We've got a platform that's delivering and don't see any need to augment that at this time. It could be different in 10 years from now, which is fine. But for right now, we're pretty focused on executing on what we've got in front of us.

Great. And as you think about the RNAi field, how do you keep evolving as a company to stay at the forefront here as you've been a leader? And do you see threats to the technology itself, given emerging therapeutic modalities? Or is it the case where we're matching biology to the platform here, and you have -- you know what your set group of diseases or targets are and that's how you kind of position yourself?

Yes. Salveen, I think it's the latter. Any -- for any target or any indication that we enter into, there's always a competitive landscape out there, potentially of other modalities, other products, either existing products or products in development. And so we look at all of those together and decide if it's an opportunity for RNAI, where we can create a differentiated successful medicine or not. And we'll enter given indications with strength if we have conviction behind what our modality can do and what Alnylam can do in that space or otherwise, if we think that there's another technology out there that might have an edge, we won't enter that space. So we take it case by case, indication by indication, target by target to make that type of assessment.

And with regard just to optimizing your own work here and on the IP front, how much work is done to create second and third and fourth generation and up?

Yes. Yes, we've had a long-standing and continue to have a very robust effort on our platform, advancing our platform. For many years, we were focused on optimizing our liver platform. We went from our LNP technology to GalNAc technology, then there was an ESC version of that and then an ESC+ version of that. I think at this point, we feel that our liver technology is pretty much optimal. I mean it's hard to make much improvement on it, if you will. So the focus has really gone to extra hepatic delivery of RNAi therapeutics. We've conquered the CNS. We'll have our first CNS program in the clinic next year. We've successfully achieved ocular delivery, lung delivery, and we're just opening up new frontiers almost annually, we're opening up a new tissue link. What's important is once you open up that new frontier or that new tissue or delivery of an RNAi therapeutic, you build an entire new pipeline in that space-based on the diseases and the targets and the opportunities that are there.

So when you look at these other tissues outside the liver, what do you think are the most derisked at this point? And then and I guess, how are you thinking to maybe other modes of delivery as well?

Yes. Yes. Well, I mean, without a doubt, the CNS work that our scientists have pioneered over the last couple of years, is extremely promising. It led to a major alliance that we formed last year with Regeneron in 2019, and we're building a very competitive CNS effort together with Regeneron with dozens of programs that are now in preclinical development. And again, we'll have our first clinical program in mid-2021. But of interest, the lung delivery work that we had been doing in stealth last year is going to come to the forefront, unfortunately because of COVID. And so our first extrahepatic delivery approach in this current era is going to be lung delivery of our ALN-COV molecule, which targets SARS-CoV-2. So based on the urgency, the public health need and so forth, that's going to step ahead of our CNS effort. But CNS is still going on in a very strong way, and we'll be in the clinic next year with that program.

Great. So moving into the portfolio here. So you talked about SARS-CoV-2 and the pandemic is still ongoing here. Can you start by walking us through the impact that you're seeing to your commercial portfolio with ONPATTRO and GIVLAARI and what steps you're taking here?

Yes. Well, look, I mean we talked a lot about this on our Q1 call, just recently. We had a very strong Q1 commercially with ONPATTRO and GIVLAARI. We beat our internal and external estimates. So we're really proud of the execution that our teams delivered on. Obviously, as we discussed in our Q1 call, we view Q2 as being the true depth of the pandemic from the standpoint of our commercial business. Much of our sales team is working remotely. Globally, we're obviously being impacted on new patient finding as well because of the impact on COVID in terms of being able to do certain diagnostic tests for patients. And we have guided that we do expect Q2 to be as much as 10% down compared to Q1. And for ONPATTRO specifically. But look, the framework that we laid out in our Q1 call of a pandemic phase, followed by a recovery phase in Q3, where we expect things to return. And then Q4 approaching the near normal, in our mind, remains the appropriate way to think about it from a planning perspective. And let's see how Q2 delivers. We're -- I think in some ways, Q2 is opening up faster than we expected. We have deal teams that are actually engaging directly now with HCPs, probably ahead of where we would have expected it to be when we talked about this in Q1. So perhaps there are some opportunities there as we complete the quarter and get into Q3, maybe with a better running start than we would have expected before.

And how successful have you been transitioning patients who receive care in infusion centers to home infusions? And do you think this is a trend that continues post the pandemic? And then maybe just what other learnings do you think you're seeing that will be incorporated going forward?

Yes. I mean, look, I think the report card there has been really quite good. In the U.S., we went from 9% infusion -- home infusion at the end of Q4 last year to currently around 20%. And in Europe, we went from around 17% Q4 -- end of year Q4 home infusion to now 40% in Europe. So -- and that's continuing. So I think the -- there is some silver lining, if you will, with regard to the pandemic in the case of home infusion care for many of our patients. Part of this, as you know, so being 65% of our U.S. business is Medicare, and Medicare has introduced a new rule that allows reimbursement of home infusion services. And that obviously is very favorable. I don't -- we don't know for sure, but I don't think that goes away. I think that there's going to be a continued push for home infusion, telemedicine and other ways of treating patients outside of the health care setting for the foreseeable future. And I think much of that will remain. It's good news for us. We actually -- obviously, because of home infusion is outside of infusion centers outside of 340B hospital systems, it's better for us, it's better for patients as well. But we still have a significant number of patients that will continue to want to go to their hospital setting or their infusion center to get care at those sites because they prefer to do it in those sites.

Yes. And are you seeing -- I mean, I guess you talked about the impact on new patient starts previously, but are you seeing a change in that trajectory now over time? Or do you think this is the second half dynamic?

No. We are -- we're beginning to see, for example, things like our Alnylam Act program, which has slowed down a little bit at the beginning of Q2. We now see more and more tests that are being ordered. We also track the performance of PYP scans. Many of our patients in the U.S. come through the cardiology setting, where their diagnosis had cardiomyopathy, cardiac amyloid, then they're found to have polyneuropathy, then they're administered ONPATTRO at that point in time. So we do benefit by patients going through cardiac imaging to detect cardiac amyloid and then obviously get a genetic test to confirm it's hereditary. That is a flow of patients in the U.S. market, which is important to us. But we're seeing more cardiac imaging coming back at this point in time from where it was before, when in April and May was virtually shut down in major hospitals.

Great. And so when we look at your trajectory here for ONPATTRO and how the launch has progressed, what are the key learnings to date that you maybe could highlight with feedback from -- on the profile physician willingness to prescribe it and how we should look at the trajectory from here when you incorporate that kind of into the launch.

Well, it's important that I answer that question on a region-by-region basis, if I can, Salveen because it is different by the region. Look, in the U.S., it's really a launch that has gone very, very well. ONPATTRO is clearly the product of choice for the treatment of polyneuropathy in patients with hereditary ATTR. The drug, I think, has performed incredibly well in the market and is widely viewed by physicians as being a very effective therapy. We think that it will continue to grow in the U.S. driven by new patient finding efforts. And in this regard, we think it's very beneficial to have significant share of voice out there with our efforts and Pfizer's efforts around disease awareness and hereditary and ATTR amyloidosis more generally. So that helps us enormously. And I think we're in a very strong position to continue to see U.S. growth when the diagnostic efforts continue in Q3 and Q4 and beyond. In the rest of world, much of our business is really driven by tafamidis switches. These are patients that have polyneuropathy, they're progressing at tafamidis. They come in to get ONPATTRO or in some cases, of course, we still get naive patients. But we're seeing that dynamic a lot in Europe and Japan. We're turning to the U.S. for just a minute. The other dynamic, which I think is very important is combination use. So we're seeing a lot of combination use going on for so-called mixed phenotype patients. They're receiving a stabilizer for their cardiomyopathy and then they're getting ONPATTRO for the treatment of their polyneuropathy. And the good news there is that we are getting reimbursed for our product. And also, at the same time, the cardiomyopathy product is getting reimbursed as well. So we -- that's a good dynamic because, obviously, to the extent that at this current time, we don't yet have a cardiac label until we develop that with our Phase III program. For patients that have polyneuropathy but also have cardiomyopathy, we are seeing patients being able to get both drugs and get reimbursement for both drugs.

Why do you think outside the U.S., the dynamic is more switch versus a combination if you're seeing that combinatorial approach here in the U.S.?

It's really the payer challenge and outside the U.S. that's going to be a dynamic that is going to be a little bit more difficult in rest of world countries. There's some combination use that we're aware of in -- outside the U.S., but for the most part, that's a U.S. phenomena.

And then with the entry of maybe 1 more and more in the future, how capable do you think this market is of hosting various players in the space?

We've thought for quite some time that this is like an MS. market, especially when you include the wild-type ATTR component to the whole thing. And look at the MS market, I mean it's got dozen -- over a dozen products that are out there and obviously, many of these are blockbuster products. So we think that's the type of setting that we're going to see emerge in the overall ATTR amyloidosis setting. So I believe for the future, there will be stabilizers out there. There'll be silencer drugs. We're obviously the leaders in silencer drugs by far, and there'll probably be multiple drugs in each category that are out there. There might also be other modalities that emerge over time as well. But it's a significant unmet need. It's a large market, especially when you include that wild-type ATTR setting. And Alnylam is positioned to be a leader in that space.

And John, patient identification through diagnostics is a key driver of growth here. So how do we think about the state of diagnostics and trajectory here? You can sort of see an exponential ramp when those really get pulled in. And I think you've seen Pfizer really talk about their uptick in diagnostic rates. So just curious how this is impacting ONPATTRO.

Yes. I sort of mentioned it before. I mean the technetium scans that are being done, so-called pyrophosphate scans, bone scans that can pick up cardiac amyloid in -- are really dramatically changing the landscape for diagnosis of hereditary and wild type ATTR. Obviously, we're focused now on hereditary. And that's just a really important diagnostic tool because in the past, the only way to really detect cardiac amyloid was with biopsy, which, of course, is much more invasive. And the symptoms of polyneuropathy can often be missed in many patients. So for now, we're benefiting quite a bit by these so-called PYP scans that are being done in cardiac nuclear imaging centers around the country -- around the world.

And how does the Alnylam Act and then 23andMe kind of come in and aid in this process?

Yes. So once a patient is suspected as having TTR amyloidosis, the question is, is it hereditary or not. And obviously, that's where the genetic test comes into play. So our Alnylam Act program, which is a free genetic test program that we support is done by Invitae. It has been running at about 3,000 tests a quarter. It won't be that high in Q2 because of the pandemic. But even in Q1, we had about 3,000 tests, and we're seeing about a 6% to 8% hit rate quarter-on-quarter. And that rate has not gone down. Even with increasing -- increases in the number of tests. So that's a really important part of the overall diagnostic guideline for hereditary ATTR amyloidosis. We obviously support that with our program. And then on top of it, with the 23andMe program, we're using that to help patients that have the mutation to basically be able to get more tests so they can provide that to their family members. And then ultimately, if they develop symptoms, they are aware of their mutation. They're also aware of drugs that are out there like ONPATTRO that can be used to treat those mutations.

Great. And then can you talk as you look to expand outside the U.S. what the cadence of the launch is in these various regions? So what are the most important drivers of growth geographically? And you've mentioned that Japan would be the second largest market behind the U.S. Can you just remind us of the dynamics and how the launch is tracking there?

Yes. I mean, look, the overall global drivers of growth for ONPATTRO are new patient finding, geographic expansion and evidence generating activities, right? Those 3 and in CEMEA, in Europe, specifically, we are very much in a market expansion, geographic expansion mode, driven by new countries where we're getting PNR lined up. And so recently, we launched in Spain, we launched in Italy. We continue to see growth in other countries, but we're adding new markets to our ONPATTRO story in Europe. So that's the dynamic that's going on there. In Asia, obviously, Japan has been a remarkable story for us. It's going to continue to be this year. Interestingly, there's not been much of an impact of the pandemic on our Japanese effort overall. So that's continued extremely strong even in Q2. And without a doubt, it will be our second largest market. But in Asia, we're also opening up Taiwan. We expect to be in Taiwan later on this year and also in other markets in Asia as well. So the geographic expansion aspect of the launch is going to continue to be even into 2021, an important part of growth for the product.

And can you touch on APOLLO-B. So here you're looking to expand use in to...

APOLLO-B -- [indiscernible] my APOLLO-B shirt on, by the way.

Nice. Nice. So you're looking to expand into 2 populations here and/or into the hATTR and wild-type ATTR patients with cardiomyopathy. So could you talk about the trial design?

Yes. Yes.

And whether you have -- do you have to do a head-to-head versus tafamidis? Or what might be required there?

Yes. Yes. Thank you. So we're excited about APOLLO-B. So probably is the opportunity to bring ONPATTRO to patients with both hereditary and wild-type ATTR cardiomyopathy. And Salveen, it really builds on the very exciting data we generated in the original APOLLO study, looking at echocardiographic impact and biomarker as well as functional impact of ONPATTRO in patients with cardiomyopathy in their overall clinical characteristics. And it builds further on some more recent data that we presented around PYP scans in patients that are getting patisiran where we're seeing pretty striking evidence for cardiac amyloid regression in patients that get patisiran when you look at a PYP scan after 1 year of treatment. So those type of data really give us strong encouragement about the prospects for APOLLO-B. APOLLO-B is a double-blind, placebo-controlled randomized study, where patients that come into the study are either naive to a stabilizer or are progressing on a stabilizer, okay? We allow as much as 30% of the baseline patients to come in with background tafamidis in their -- as part of their characteristics. And then they're treated with either ONPATTRO or placebo for 1 year. And the primary endpoint is the 6-minute walk distance after 1 year of treatment compared to placebo. So we're hoping to see a halting of progression of decline in 6-minute walk, which is what you would expect for this population over that 1-year period of treatment. The study was started in around September of last year. It was enrolling very well. Obviously, it's had some impact related to the COVID situation. We now expect to complete enrollment in 2021 and should have data from that study in early to mid-2022.

And then you have a second drug, vutrisiran, where you're looking to -- a second-generation drug, I should say, and you're looking to -- I guess you're looking to have this enter. How would it compare to ONPATTRO and where are you in development? And then how do you think about the market dynamics here? Do you expect cannibalization then on ONPATTRO if this were to enter the market?

Yes. So vutrisiran is our GalNAc-conjugate targeting TTR, which enables subcu injection and is given once a quarter subcu. So it's a very durable. Obviously, a very potent molecule. And so it's in the HELIOS-A Phase III trial. That's actually completed enrollment. We expect to have data from that study in early '21. So just less than a year from now, we'll have that readout. And assuming that's positive, that is going to go for the approval of vutrisiran for the treatment of polyneuropathy. So it's really a bridging study between ONPATTRO and vutrisiran for the purposes initially of the polyneuropathy setting. And then as you know, Salveen, the second study we're doing with vutrisiran is called HELIOS-B, which is the study that's being done to enable its ultimate use in the cardiomyopathy setting, both wild-type and hereditary. And that's a longer-term study because we're using CD hospitalization and mortality as a primary endpoint for that study. So we're excited about vutrisiran. We think that it's going to be a very exciting molecule for patients. It's going to give patients a great option between ONPATTRO and a subcu alternative. Yes, over time, we expect more and more patients will select vutrisiran. But ONPATTRO will always be out there, and there will be many patients who've been receiving ONPATTRO for many years who, frankly, are doing very well and won't want to change because patients don't like to change their medicine if they're doing well, when they're getting it. So I suspect it will always be out there. But over time, we think there'll be more growth in the vutrisiran asset compared to ONPATTRO given its profile of a once quarterly subcu injection.

Great. And then switching to GIVLAARI, so that's a recent launch here. And when you look at these patient starts that you're receiving, what proportion are coming from newly diagnosed versus previously identified patients at centers? And then maybe how you're leveraging the ONPATTRO launch to apply here to the U.S. and European launch.

Yes. Well, I mean, obviously, we're excited about GIVLAARI. It was approved last year in November for the treatment of acute hepatic porphyria. It's really a transformative medicine. It achieved over a 70% decrease of annualized attack rate. The data just got published in the New England Journal of Medicine from the Phase III study, just today, just last night and then today. So we're excited about that as well. The launch has gone really well. We -- in Q1, we announced $5.3 million of initial sales. That was our first full quarter, over 50 patients that are on commercial product at this point in time. And we've now started our launch in Germany and our ATU in France. So in Q2, you'll also see the benefit of some European sales for the product as well. We think this can be north of a $500 million peak sales opportunity product in our pipeline. It's an ultra-rare orphan disease, huge unmet need. And there's potential for growth. This is a very underdiagnosed disease. We believe that as we're out there, improving disease awareness that we have a potential to really grow the brand even beyond where we are, obviously, today into the future.

And how do you see the EAP having an impact here with regard to those patients entering?

Well, in the U.S., the EAP didn't have much of an impact because we got approved well before the PDUFA date and well before the EAP was up and running. But in Europe, the EAP has a significant double-digit type number of patients in it that will, when countries open up from a pricing and reimbursement standpoint, those patients get transitioned right away onto commercial product. So patients that were in Germany on the EAP as of last quarter have now transitioned into commercial product right away. So that gives you an initial source of patients on commercial drug. And as we open up new countries across Europe, we'll also be transitioning those patients from the EAP into commercial product.

And John, maybe moving over to fitusiran here. So post the restructuring of the deal with Sanofi, where do you stand here in supporting Sanofi through this development process? And how should we be thinking of that program?

Yes. So 2018, we did a swap with Sanofi, as you alluded to, where Alnylam took on global rights to ONPATTRO and fitusiran, and Sanofi took on global leadership of our fitusiran program. And we have royalties that go both ways so that we're compensated and rewarded for success in the program. So right now, the ATLAS Phase III trials, which are being run by -- we initiated them and they're now being run by Sanofi, 3 of the 4 studies have completed enrollment, which is terrific. And we should expect to see data from the fitusiran Phase III studies sometime early next year. And so that's exciting, and we're looking forward to seeing how effective the drug is, and how safe the drug is. The key thing here is, can we get a robust ABR, a low ABR, annualized bleed rate, with a very clean safety profile as it relates to thrombotic risk. And we're optimistic so far from the Phase II open-label data that they've continued to show. We're optimistic that we can achieve that type of profile with fitusiran and have a product that is going to be competitive with hemlibra in heme A and completely distinct in heme B as a subcu drug alternative for patients with hemophilia B, which is an unmet need at this point in time. So we're excited about the potential, and Sanofi will lead that, and we get rewarded with royalties that range between 15% and 30%, so pretty significant royalties.

And then one of the programs you partnered with Blackstone on is the ALN-AGT program for treatment-resistant hypertension. And you've shown a 10-millimeter mercury reduction here in the monotherapy early Phase I. Can you put into context for us what the clinical significance is of that type of reduction in the context of patient population you're targeting?

Yes, absolutely. So Salveen, ALN-AGT is our RNAi therapeutic, targeting angiotensinogen for the treatment of hypertension, and it is a very exciting program as we look at it because hypertension is an area that has missed innovation for decades now. There's really been nothing new that's come out. And the problem with patients that have uncontrolled hypertension is that their current antihypertensive drugs don't provide a tonic and consistent control of blood pressure. And one of the beautiful things of the RNAi technology is that clamped knockdown of disease targets. We saw that with inclisiran and PCSK9. We're now seeing those type of data with angiotensinogen in our Phase I study. And in addition to the lowering the knockdown of the target gene that we've achieved, we're also seeing this pronounced over 10-millimeter mercury reduction of systolic blood pressure in a very stable, consistent manner after just a single injection. So we think that this type of an agent, this type of an innovative approach, if you will, for hypertension, can really begin to transform the landscape there for new medicines and a drug given once every 6 months for the treatment of hypertension, would really be a game changer and something that would be very welcome in the management of a very common prevalent disorder, and obviously a very large market opportunity for Alnylam.

Can you just touch base on the safety profile just given historically what's been seen with Dual Ras Blockades?

Yes. Well, that's a key question as it relates to the ongoing development program that we'll obviously get some initial data out of the combination arm that we're doing in Phase I, but then we'll get more robust data out of the Phase II. But there is reasons to be optimistic there because we're only targeting liver, angiotensinogen, and there is data to suggest that the production of the early activity, the Ras system in the kidney, and Dual Ras in activation of the system in the kidney is what's problematic and what leads to hyperkalemia in a number of patients. So the ability to target liver-specific angiotensinogen without impacting the kidney is really the opportunity we have of avoiding any of the renal injury that's been noted with Dual Ras Blockade.

And John, I guess, what would you need to see from this program as it continues to then progress it into larger trials? And how are those going to be designed?

Yes. So we're really interested in 2 distinct populations, and we're going to look obviously at both, but prioritize one over the other. And the 2 distinct populations include patients with resistant refractory hypertension. These are patients that are unable to get to their target blood pressure even with 2 or 3 antihypertensive drugs on board. So that's one area of unmet need. There are about 11 million Americans that have resistant refractory hypertension. The other population of interest are people that have -- that are high-risk of cardiovascular disease, these are patients with ASCVD, if you will, the same population that was studied with inclisiran. And there the goal would be to have a consistent and significant blood pressure control relative to placebo. And so we're looking at design opportunities and trial opportunities in that setting as well. There's clearly an unmet need for better blood pressure control in those high-risk CAD patients. And so the ability of achieving that with ALN-AGT would be the objective of that study. And that's an area where, depending on how you cut it, there is anywhere from 5 million to 15 million Americans with ASCVD that require better blood pressure control based on our market research. So these are large unmet need opportunities where we believe this drug can be very effective, and again, we've already shown blood pressure lowering. We need that to continue in the Phase II and Phase III program, which we expect it will, and then we just really need to have a strong safety database to support its use in a large population.

And then a final question here. So you touched on this earlier, your approach to COVID-19. Maybe you could touch base on that and the rationale there and time lines associated with the program?

Yes, sure. I mean we're obviously doing what we can with RNAi in this current situation. We've started the program together with Vir, collaboratively with Vir, targeting SARS-CoV-2 the genome directly. It's an RNAi virus. We have a technology that degrades or targets RNAi for degradation. And obviously, it's well suited for targeting the viral genome directly. We're also doing some work to target host factors, both Phase II and TMPRSS2, which are known host factors for viral entry are of interest to us to consider in addition to directly targeting the SARS genome. But right now, the most advanced effort is really the work on SARS-CoV-2 directly. We selected a development candidate, and we're working toward getting that in the clinic at around year-end of this year. So we're doing the work, the pre-IND work, if you will, to get to that stage at this point.

Great. Well, with that, thank you so much, John, really appreciate your time this morning.

Great. Salveen. Thanks, everybody. Bye-bye now.

Bye.