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

Good afternoon, everybody. Thanks for joining us. I am Tazeen Ahmad. I'm one of the senior biotech analyst here at Bank of America. Welcome to our virtual Napa conference. As part of this afternoon's session, it's my pleasure to introduce our presenting company, Alnylam. Presenting for Alnylam for the next 50 minutes or so will be CEO, John Maraganore. John, good afternoon. Thank you for joining us.

Thanks, Tazeen. Good afternoon to you and to everybody, and thanks for inviting us.

So most people already know the story of Alnylam. And normally, we ask people to give a couple of minute intro. But I think given the audience that we have filed in, I think it makes more sense probably just to dive in to some questions. And so I thought maybe we could talk to you initially about COVID. On your 1Q call, you outlined what you called a recovery phase for 3Q and 4Q would approach the new normal. Now that we have pretty much closed on 2Q, getting ready for 3Q, what's your view on what the landscape looks like and what the recovery and new normal is for Alnylam?

Yes. Good question. Well, Tazeen, we talked in our Q1 call -- well, first of all, in our Q1 call, we announced very strong Q1 revenues for both ONPATTRO and GIVLAARI, our 2 marketed products, but we did do 2 things. We reduced our ONPATTRO guidance for the year by 5%, lowering our -- slightly lowering our range from $285 million to $315 million down to $270 million to $300 million for the full year. And we also guided that we expect that Q2 is going to be the toughest quarter that we could see as much as 10% decrease in ONPATTRO relative to Q1 in Q2. And that we expect Q3 to be a recovery phase and recovery quarter, and Q4 to be our new normal phase, if you will. And I think, in general, that framework is the right way to think about the story for our commercial execution for the year. I do think things have opened up a little bit earlier in Q2 than we had originally expected when we had our Q1 call. Whether that's good or not, time will tell, but we definitely are seeing more engagement with HCPs. We're seeing our Alnylam Act program coming back in numbers. We're seeing more PYP scans happening. We're also seeing, in other countries around the world, a greater opening up relative to the U.S. even. That's certainly true in Europe. It certainly continues to be true in Asia and Japan. So I think that the framework that we laid out in Q1, I think, is still the right framework, but there might be some things happening earlier than we would have expected in our call.

Okay. So we will talk about ONPATTRO in a couple of minutes, but I did want to spend a little bit of time talking about the update you provided this week for AGT. Wanted to just get your thoughts on what you think it is about the current drug landscape that just doesn't get patients to where they need to be in terms of lowering their blood pressure to their targets. Does it -- is it flow of mechanism of action? Is it low compliance? Is it something else?

So it's a little of both. So maybe taking a step back, ALN-AGT is our RNAi therapeutic targeting angiotensinogen for the treatment of hypertension, which we think can really be a way to reimagine the management of hypertension, a disease area of, frankly, significant unmet need that remains the #1 modifiable risk factor for coronary artery disease and CV mortality and morbidity in the world. And the issue really around existing drugs -- anti-hypertensive drugs, which, for the most part are generic drugs, is, as small molecules, they have -- saw 2 pharmacology that ebbs and wanes over the course of the day that also is associated with significant interpatient or intrapatient variability on a day-to-day basis. And so these drugs, because of the nature of their pharmacology, really, are not providing adequate consistent control of blood pressure. And then when you then say, "Okay, well, let's go to twice a day for patients," then the compliance challenges come into play. I mean there's compliance challenges already with a once-a-day pill, but there are even further compliance challenges that occur when patients are asked to take their anti-hypertensive drugs more frequently like twice a day. So that is really the nature of what we think is an exciting opportunity for ALN-AGT to provide tonic of control of blood pressure in patients. So essentially reducing the variability, reducing the compliance and adherence issue that you have with small molecule pills. And also, very importantly, providing a significant control of diurnal variation that occurs with blood pressure, that as it turns out, is a major associating factor for cardiovascular mortality due to hypertension. So all of these features together combine to make ALN-AGT a really interesting medicine that we think could be given once -- probably once every 6 months as a low-dose subcutaneous injection, very reminiscent of inclisiran with -- which is now being advanced by Novartis.

Okay. So I think one of the reasons that people are excited about this particular program is that hypertension would be a move to a very large primary care opportunity for Alnylam. And up until now, you've done a great job on focusing on more rare diseases. You talked about your plans to own this compound and try to think of forward yourself. How much synergy do you think there would be with your current infrastructure that you felt out for your rare disease programs? And how much would you need to build out further to support ultimately a launch of this size?

Well, I mean, let's take a step back. We believe that the current set of programs that are in late-stage development, of which there are 6 total programs, including 2 that are on the market, enable Alnylam over the next 5 years to build a top 5 biotech. And I would say that one way to think about the ALN-AGT opportunity, and frankly, other large prevalent disease opportunities in our pipeline is the creation of an opportunity for building a top pharma company with Alnylam because these are -- these very large prevalent markets are, obviously, areas of significant unmet need, where the revenue potential and the growth potential for the company as a result, we believe can be very substantial. Now keep in mind that we are going to be in the cardiology space in relationship to our wild-type ATTR opportunity that we have with both ONPATTRO and vutrisiran. So the expansion of our commercial footprint, as we imagine, bringing our ALN-AGT opportunity to the market in the '24, '25 time period is, frankly, just an expansion of a footprint that will already be in place as we build and develop our company. But it's also the expansion of our company beyond, again, a top 5 biotech toward a company that we believe could be a top pharma. And so I think when you contextualize it with where we will be at that time, we believe we can be ready to address this type of market and sales opportunity as a business.

Okay. So maybe we can now switch back to ATTR. As it relates to ONPATTRO, in 2Q, I know you can't guide quarterly, but to the extent that you can provide some qualitative information, can you talk to us about what you've seen on the impact of the launch this quarter? And what, if any, of those impacts do you expect to potentially persist longer term?

Yes. Well, obviously, we're intra-quarter, almost done with the quarter, so I can't get into too much -- as much color as you probably would like me to get into. But I can give you some general gist of things. I mean, first of all, overall, I think it's fair to say that Q2, which we thought would be shut down for the entirety of the quarter, we did see things open up really in the late May, early June time period. So I think that's a good overall dynamic. We are seeing more direct interactions with HCPs, whereas, everything in April and May was virtual. So I think those are encouraging features of Q2. The other metrics, if we go by region, the metrics that are quite interesting to consider, let's start with the U.S. for starters. We continue to see combination use taking place in the U.S. This is the use of ONPATTRO to treat polyneuropathy in patients with a mixed phenotype on top of the use of a TTR stabilizer to treat cardiomyopathy in these patients. And we did some market research in Q1, showing about 15% to 30% of our patients are getting combination therapy. We have reason to estimate that this may double during the course of the year. And we do see that trend continuing in Q2 that patients that are receiving ONPATTRO for the treatment of polyneuropathy might also be receiving a TTR stabilizer for the treatment of other manifestations of the disease. So that's a U.S.-specific phenomenon, but we do expect that to continue, and we do expect that to be beneficial to our growth in the U.S., given that a significant number of -- a significant amount of effort is going on from both Alnylam and Pfizer around disease awareness and improving patient diagnosis. So that's in the U.S. In Europe and Japan, we continue to see a significant amount of tafamidis switching. These are patients in those markets that have been traditionally treated and managed with tafamidis, which, as you know, has been on the market in those countries for quite a bit longer, who unfortunately progress while on that drug and that's been well documented in the clinical literature. And these patients are coming on to ONPATTRO as the next treatment option for them. So we're seeing a lot of switches taking place in other parts of the world, outside of the U.S. The other dynamic that's relevant in Q2 is, we've also continued to enjoy geographic expansion. For example, in Q2, we've launched in Italy. We've launched in Spain as 2 major markets in Europe that weren't open in Q1 that we've launched into in Q2. So I think that's the right type of color to provide at this time, Tazeen. And obviously, in a few weeks' time, in about a months' time, we'll give you the update on our results.

Sure. So based on what you just talked about with your experience thus far with ONPATTRO, has that given you any more clarity about the size of the ATTR population, both in terms of addressable patients in polyneuropathy as well as cardiomyopathy?

I think we've continued to get great insights on the disease and the patient population. I mean clearly, the hereditary ATTR polyneuropathy patient population, which includes a mixed patient population is a rare disease, but a recently sizable rare disease. I mean again, we continue to believe that the worldwide prevalence of that segment of somewhere around 25,000 to 30,000 patients worldwide is the right number to consider. But of course, the number of patients that are diagnosed is still a fraction of that. So there's a lot of work to do to still unlock the potential for earlier diagnosis, earlier treatment with ONPATTRO for those patients that have polyneuropathy. And we think that's an opportunity that will continue to increase over time on a global basis. So that's important there. Obviously, with cardiomyopathy including wild-type ATTR disease, we plan on opening up those opportunities with APOLLO-B, and ultimately, with HELIOS-B study. And we're -- we continue to believe that the wild-type opportunity is very substantial, at least 300,000 patients in the U.S. alone, and it could be a larger number in point of fact. I mean the significant amount of patients with preserved ejection fraction heart failure have ATTR amyloidosis wild-type disease. And obviously, with the Phase III work that we're doing, we're hoping to unlock the opportunities for both ONPATTRO and vutrisiran to address that very sizable market for the future of the company.

Okay. So now you talked about the HELIOS studies. For HELIOS-A, which is, of course, vutrisiran in polyneuropathy, there's going to be pivotal data for that early next year. And if that does prove successful and you're able to launch it, how do you envision this product being complementary to ONPATTRO?

Yes. Well, look, vutrisiran -- and the HELIOS-A study is a study that's aimed at bringing vutrisiran to the market as quickly as possible. It's fully enrolled. We expect to have top line data in early '21, and if positive, that will support a submission and potentially an approval by the end of '21. And it's a very exciting product. It's a once quarterly subcu injection. And so it really offers a very attractive alternative to patients. Because currently, ONPATTRO is given every 3 weeks by intravenous infusion, and vutrisiran would, of course, be a very welcome alternative that patients will consider. Now we do expect ONPATTRO -- we will have ONPATTRO remain in the market, of course. And we do expect ONPATTRO will continue to be used in many patients, especially patients that are already being treated by the drug, who are very comfortable with continued -- with their therapy, feel good and don't really want to switch. But we do expect new patients coming on board will likely transition to vutrisiran as a product of choice, given its quarterly subcu-dosing alternative, which we would expect to be very attractive to patients. And so it is going to be a product that we bring to market, while we also have ONPATTRO on the market. And we think it will be an important alternative for patients, but both products will be on the market for the foreseeable future.

Okay. And then for cardiomyopathy, both ONPATTRO and vutrisiran are in studies, but the endpoints for each of the drugs are different. Can you remind us what the differences are? And why you chose to design the studies in that fashion?

Yes. I mean the simplest way to look at it is the APOLLO-B study for patisiran, the nonbranded name for ONPATTRO, is used as a 6-minute walk distance, 12-month endpoint. It's aimed at getting a label expansion for ONPATTRO very quickly and opening up a wild-type ATTR market for that product very quickly. In contrast, the HELIOS-B study for vutrisiran is aimed at achieving the optimal label for a TTR silencer. So it will have a CV hospitalization and mortality endpoint. It's a 30-month primary endpoint. Although we will be doing an interim analysis with HELIOS-B, that could obviously get it to market even quicker. So that's the simplest way to think about the 2 different study designs. Your audience will be -- will smile with the internal name we give for both of these studies, we call them the Cardi Bs, collectively, and as a nod to the performer. And -- but there are obviously very important studies for the overall ATTR franchise that we're building. Obviously, we've had some impact on enrollment in both of those studies due to COVID, but we're expecting a 3 to 6-month delay for both of those studies, but we're also aiming to make up any lost time as we get to the other side of the pandemic. The good news is with this recovery that we've been saying, we are now seeing randomizations occur in both of these studies, which is encouraging to see.

Okay. As it relates to HELIOS-B, there is the option for doing an interim. What data are you going to need to see to decide whether or not that's going to happen? And when would we know about that?

Yes. So we have agreement with regulators that we will do an interim analysis, but the specifics of the IA have yet to be defined and don't need to be defined at this point in time. And part of our strategy here, Tazeen, is to actually use insights from APOLLO-B to ultimately lock down the design of that interim analysis. So we're going to have the benefit of a study, specifically APOLLO-B, reading out in the early '22, mid-'22 time period that will greatly inform what the interim analysis should be for the HELIOS-B study. And we'll have, obviously, a 6-minute walk distance data. We'll have mortality and CV hospitalization data out of APOLLO-B. These will be data sets from a very comparable population to what's being enrolled into HELIOS-B. So it will give us a lot of insights as to how we should think about the interim analysis to optimize that analysis for success.

Okay. Great. So maybe we can move on from ATTR now to lumasiran. You do have a December 3 PDUFA. You said that you view this as an opportunity, potentially in excess of $500 million, but you will have to go find the patients and the rate of diagnosis will need improvement. And so what do you see as the main challenges in finding patients currently with PH1? And what's your plan to address those?

Yes. I mean look, this has been an ongoing effort to improve disease awareness in this indication with our medical affairs colleagues and help improve patient diagnosis, but we have a good handle on this market right now. We are sharpening our pencil on the prevalence of active and diagnosed patients. We're going to update people at our lumasiran roundtable on how we think about that prevalence prior to the launch of the product. Right now, if you look at the estimates, it's in the range of 3,000 to 5,000 patients in the U.S. and Europe. But we know that a good number of those patients are not yet diagnosed. It's based on the genetic prevalence of the disease. So thinking about the market at a high level, there's the pediatric segment, and then there's the adult segment. The disease awareness and diagnosis rates in the pediatric segment are quite a bit higher than what you see in the adult segment. And the reason for that is if you have a toddler that's generating kidney stones, it's hard for that ultimately not to get diagnosed. What's a little bit more cryptic might be an adolescent patient who has nephrocalcinosis and has only had a few kidney stones who is on their way to develop end-stage renal disease. That's where it's important to try to enhance diagnosis rates and improve medical education, so that these patients will get recognized. And that's also true in the adult population. There are probably many adult patients that are out there who are -- have nephrocalcinosis, have a progression toward end-stage renal disease, but don't yet know it and have had stones, but not at a frequency that would warrant, necessarily warrant, seeing genetic counseling to get a test. So this is part of the effort that will obviously be very engaged with as we launch lumasiran to improve overall disease awareness and patient diagnosis rights. We do think this can be a very important product for us, probably similar in size to GIVLAARI over time. But there's also a potential with lumasiran that we could expand the opportunity into other settings as well.

Right. So I guess, as it relates to that, for ILLUMINATE-C, you're looking at patients -- PH1 patients who have impaired renal function. And I guess, I'm wondering what -- the top line data is expected next year, what success would look like from the results of that study?

Well, obviously, these are patients that have very advanced disease. They've got renal impairment with GFRs less than 30. In some cases, they're on dialysis. In many cases, they're on waitlist for getting a dual liver-kidney transplant. So these are -- this is the most severe of the populations that we're studying. And I think without a question, showing significant reductions of plasma oxalate in these patients. And in this case, you measure plasma oxalate because urinary oxalate might be artificially reduced due to renal impairment. So plasma oxalate is the important thing to measure here. That would be obviously a very important endpoint, and that is the primary endpoint of the study. But any evidence that we can demonstrate around the improvement of systemic -- clinical systemic oxalosis, whether it's some of the skin manifestations or bone manifestations, cardiac, retinal, these are all part of the end-organ disease manifestations that are seen in these patients and having the ability with lumasiran to not only complement plasma oxalate reduction, not only see plasma oxalate reduction, but complement those data with clinical outcomes would obviously be a real home run. We're encouraged by that, in part because of the promising results that we showed with nephrocalcinosis in the ILLUMINATE-A study. And we'll obviously be very interested to see how that looks in ILLUMINATE-B as well. But that suggests that there can be end-organ treatment effects that occur even with just 6 months' worth of dosing. And so let's see how that looks over time in ILLUMINATE-A with the open-label study, ILLUMINATE-B. And then obviously whether we can see these type of effects in ILLUMINATE-C, that would be very meaningful for the product.

And by how much would it increase the addressable patient population that have this part of the label?

Well, it adds about 1/3. If you think about the buckets here, it would be about another 1/3 of patients that are in the systemic oxalosis category. These are patients, of course, that currently are on their way to double liver -- dual liver-kidney transplant. So it's about 1/3 addition beyond what we're achieving with ILLUMINATE-A and ILLUMINATE-B.

Okay. So maybe moving on to GIVLAARI. It's been close to 7 months or so since it got approved. Can you talk about how the feedback from the physician community and patients have been so far? And was there anything that was different from what you expected for the product so far?

I think the reception that we've seen so far has really been above our expectations. I mean, we had a very strong Q1. We came off to a good start. We got the approval in the U.S. ahead of schedule. And even in the few weeks that we had of Q4 of last year, we had some good encouraging signs, and then that continued into Q1. And obviously, we'll talk about Q2 in about a month or so. So I think the reception to the product has been good. We've seen a lot of patients that weren't even on our radar screen and prescribers that weren't on our radar screen be part of the early group of patients that -- early group of riders and patients that we documented in Q1. So that's been good. I mean GIVLAARI really is a very impressive medicine when you look at the treatment effect that's achieved. I mean the data were just published in the New England Journal and in the ENVISION Phase III trial, we achieved an over 75% or roughly 75% reduction in the annualized attack rate with some improvements and other measures of quality of life, overall. On a safety profile that one has to look at in the context of the benefit-risk with this product. I mean, we did note the findings on some renal findings and some liver enzyme elevations. But in the context of the overall treatment effect, that has to be considered, and we obviously are encouraged by the benefit-risk of the product. But the reception has been really good. We're going to be presenting some additional open-label data next week from the ENVISION study. I think, obviously, it will be of interest for people to look at the continued efficacy results and the continued safety results for the product. So we look forward to presenting those data in the coming week. But we're really pleased with the reception that we've gotten from the community, not only here in the U.S. but also in Europe.

Okay. So we look forward to that update. Just in general, John, can you talk about what we should expect in terms of the cadence of this launch?

Yes. I mean look, we're approved in the U.S. We've just launched in Europe. The European launch will -- was not in the Q1 numbers. You'll see that in Q2, beginning of that in Q2. We're engaged now on a country-by-country basis to get reimbursement in European countries. We expect to have Brazilian approval sometime in the middle of this year. And then that will start the pricing negotiations in Brazil, which probably won't yet generate revenues out of Brazil until early Q1. We're going to file in Japan later this year, and obviously, that will allow us to launch in Japan in early '21. So you're going to see growth -- new patient growth in our existing markets like the U.S. Geographic expansion happening in other markets, like Europe because of PNR and staging the PNR and new markets that we open up like Brazil and Japan. And all of that is going to happen in a way that I think will really drive continued and steady growth in revenues for the product. And we have a product in a space where there's not a lot of competition at this point. We do have the only product approved for the treatment of acute hepatic porphyria. And so that is an important distinction of this medicine. And obviously, it positions us well to be able to continue to deliver this important medicine for patients around the world.

Okay. Maybe moving on now to fitusiran. This was certainly front and center at the R&D Day that Sanofi hosted this week. We saw a new long-term data. Were there any surprises for you in that disclosure? And how do you think we should be thinking about that data?

Yes. So maybe taking a step back for people on the call. Fitusiran is really an innovative approach for the treatment of hemophilia A or hemophilia -- and hemophilia B in patients with and without inhibitors. That it's an RNAi therapeutic that targets antithrombin with the goal of increasing thrombin generation, which really is a central defect of hemophilia. It's a disease characterized by a loss of thrombin generation due to a deficiency in Factor VIII or Factor IX. And fitusiran corrects the fundamental defect of hemophilia by increasing thrombin generation in patients. The open-label data that Sanofi presented at the World Federation Meeting just last week was very exciting. They continue to see consistent knockdown of antithrombin, consistent increases of thrombin generation at the lower end of the normal range, which is terrific. And bleed ABRs that are less than 1 with a once-monthly subcutaneous injection, and this is in patients with both hemophilia A and hemophilia B with and without inhibitors. So very attractive set of data. And they have now completed Phase III enrollment in 3 of 4 ATLAS Phase III programs that are aimed at obtaining approval for fitusiran. They've guided that they will have top line results from these Phase III studies in early '21. And assuming it's positive, they should be in a position to file their NDA for the product in the second half of '21. So we think fitusiran could be an exciting alternative to Hemlibra in the hemophilia A market, and it could be the only subcutaneously administered treatment for hemophilia B in that market -- in that segment of the market, and really could be an exciting product. And obviously, it's part of the broader franchise that Sanofi has built in hemophilia based on their Bioverativ acquisition. So it's very well positioned in a committed organization in the management of hemophilia.

Okay. On safety, the company mentioned that they see no thrombotic events in patients that have followed this lead mitigation protocol. You know exactly what that is, and how that can be applied in the commercial environment?

Yes. We know exactly what it is because we designed it. So we know exactly what it is. And I don't have specific facts in front of me right now, but we have presented those guidelines previously, and we could certainly make them available. But what we basically did, we had an unfortunate thrombotic event that was misdiagnosed and led to a patient death in 2017, that, obviously, we put the program on hold to understand that event better and then to understand how we can manage the risk around that for the future. And we instituted lead management protocols such that, if a patient has a breakthrough bleed while receiving fitusiran, instead of using normal strength replacement factor or bypass agent, we have guided for a reduced strength of the replacement factor or the bypass agent as a way of managing that breakthrough bleed, and we know that that's very effective. We know that patients are able to achieve very nice control of any breakthrough bleed if they happen to have one with markedly reduced doses of Factor VIII, Factor IX or bypass agent, whether it's FEIBA or NovoSeven. And so that came out of work that we did at Alnylam and as we transferred the program over to Sanofi, when we did the swap between TTR and fitusiran. We basically put that set of guidelines in their hands to institute. It is very well thought through, and it's been very successful so far, which is great to see. And in terms of the commercial translation of it, it's something which can be readily communicated commercially as patients take -- come on to fitusiran therapy. And of course, these are patients that already are aware of guidelines for how they should treat breakthrough bleeds and other breakthrough bleeds in particular because there are guidelines that exist for Hemlibra out there, right now, based on adverse events that they've seen linked to the use of bypass agents with Hemlibra. So there is a presence for this. We feel confident that we'll be able to provide this type of sets of guidelines for patients in the commercial setting, just like we've done in the clinical setting as well.

Okay. Great. And can you just remind us what the addressable patient populations are for heme A and heme B?

Well, I mean, the combined population is roughly 250,000 in the major markets and much larger beyond that. It is a global disease. Some of the features of fitusiran that make it attractive globally is that it's a room-temperature-stored product that is given once a month. It does have a prefilled syringe for administration. So this will be a very liberating type of product. Assuming the trials are positive and the product gets approved, it will be a very welcome treatment option for patients with hemophilia around the world.

Okay. So maybe leaving that topic, moving on to inclisiran, have you had interactions with Novartis? And can -- if you have, can you talk about what the strategy might be to capitalize fully on inclisiran's market potential?

Yes. I mean look, we're -- we couldn't be more excited with inclisiran and Novartis, as a partner, to commercialize the product. They're very, very committed to the product, and they're going to be an amazing global partner. We've obviously been in close touch with them related to their filings that they've done in the U.S., Europe. And obviously, they are going to -- they have activated the global Novartis regulatory filing machine to bring inclisiran to patients around the world. So we've obviously stayed in close touch with them about that. And we expect that this product should get to the market, should get to an approval in 2020. And obviously, that will initiate their commercial activities in late '20, early '21. So it's under review by global regulatory authorities. I can't really comment any further than that, given that it is obviously confidential. But we believe that inclisiran could be a very promising treatment option for patients for the management of hypercholesterolemia, which remains an area of significant unmet need.

Great. And people have long spoken about the differences in the potential ramp for inclisiran versus the anti-PCSK9 antibodies. Is there any new color that you can provide either from conversations with Novartis or your own thoughts about why the trajectory of inclisiran launch should be much different than what you thought for the antibody?

Well, I can only give you our perspectives that we've talked about publicly before and can't comment on any perspectives from Novartis, but what I can say is that there definitely are learnings from the anti-PCSK9 antibodies. I think everybody agrees that they were probably overpriced when they were launched. I don't think you hear a different answer from Sanofi or from Regeneron, or from Amgen to that point, and you've seen all of those manufacturers reduce their price over time. But frankly, that's a hard thing to recover from. They really had a tough start with a lot of payer concern around their pricing. And that is a lesson that I'm sure Novartis will learn from. I think the ability to achieve robust LDL lowering of over 50% with a once every 6 monthly dosing regimen is going to be a major positive for inclisiran relative to the anti-PCSK9 antibodies that are at best given once a month, but frankly, are typically given once every 2 weeks. And for a disease that is -- even a secondary prevention for a disease that is in a -- typically nonadherent population, that's a big burden on patients. And so inclisiran can really be transformative as it relates to adherence rates. So I'm optimistic that Novartis will learn from what took place with the anti-PCSK9 antibodies and do a great job in commercializing the product.

Okay. So that's another data point for us to track in the future. In a few minutes that we have left, I did want to touch upon a couple more topics, one of which is your partnership with Vir as it relates to COVID. There are several companies that have fortunately entered this race to help either find a vaccine or find sufficient treatment options for the pandemic. And I just wanted to get your thoughts, John, about, first, the status of this program. You had previously said that you expected to enter the clinic with the antiviral with Vir around year-end. And just wanted to see how this program could be differentiated from everything else that could be out there?

Yes. Well, look, I mean, we have a technology that targets RNA for destruction in a very specific manner, and SARS-CoV-2 is an RNA virus. So it's about as well suited to target that virus as it gets out there. And we've generated very promising results with our sRNAs and have identified a development candidate that shows potent antiviral effects with direct targeting of the SARS-CoV-2 genome. And we've also obviously made great progress with lung delivery of sRNAs. And so the -- when inhaled antiviral with an sRNA targeting SARS-CoV-2 could be a promising approach for the treatment of this pandemic. Now look, we would be delighted if the antibodies are fully effective or vaccine happens a lot quicker than expected, and we would be delighted if that happens, we all would be. But we also know that we can't count on any one approach necessarily being fully effective. And it's industry's obligation, I would argue, to deploy its best and greatest technologies with the goal of fighting this pandemic, and that's what we're doing as a company. I think it's a moral responsibility that we have to do it, and I feel strongly about that. So we are aiming to file our IND at or around year-end 2020. And we are engaging -- have engaged and are engaging further with regulators to get aligned on our pre-IND activities. And we think this could be an important treatment option in the future. If it comes too late because other therapies are successful, hallelujah. So we would not be upset. We would not shed a tear. But this therapy might be useful in future pandemics. And one of the things that we've learned is that we're targeting highly conserved sites in the SARS-CoV-2 genome that are conserved all the way back to SARS from 2003. And so it's very likely that this strategy could work for future outbreaks that probably will occur. Let's be realistic now. These outbreaks will probably reoccur in the future. And it will be great to have this medicine available in the future if another pandemic emerges or another outbreak emerges linked to coronavirus. On top of it, we're going to get some important data on the effectiveness of lung delivery of sRNAs in a way that can be leveraged for more commercially focused programs that we might engage in the future in other lung diseases, like idiopathic pulmonary fibrosis or cystic fibrosis, asthma, COPD, the list goes on. So we're -- we think there's a lot of upside beyond doing what we must do as a company to address the pandemic beyond SARS-CoV-2 and COVID-19 itself.

Okay. And thinking in a blue sky scenario, one question that always comes up for companies is, if you do end up with successful data, what kind of accelerated path could we think about for this program? And how are you thinking about manufacturing?

Yes. Well, obviously, we're going to be using it as treatment, right? So the manufacturing burden is not going to be as high as what you have to achieve with a vaccine, which ultimately has to address billions of people for a drug that is used as a treatment. You're depending on what segment of the population you're going to address. You're probably talking about hundreds of thousands of people that you would want to be able to treat, maybe close to 1 million, but not much more than that. And so that type of manufacturing capability is already in hand when you think about the top of opportunities we're addressing with inclisiran, and our HBV program that we're doing with Vir, and obviously, future programs like our AGT hypertension program. So that is very much achievable with current scale and capabilities. So I think that's the right way to look at it, Tazeen.

Okay. So if you do end up going per plan to start the study around year-end, could we realistically expect to see an update next year?

Yes, we could. I mean, I think that just like some of the other programs that are entering Phase I right now, the antibodies, where they're expecting to have data in the fall, we would expect to have initial data from our Phase I studies that we would start early next year, sometime in mid '21 at the latest late '21, yes.

Okay. Okay, so something else to look forward to. And then maybe to wrap up the conversation, we've -- you've talked now about several molecules that are close to being marketed, are marketed or in the pipeline. And as we think about the future of Alnylam, how can we expect -- like how do you suggest we think about the R&D portfolio and what areas you think the company will move into in coming years as you have moved from specifically esoteric at least, initially, rare disease to more commonly occurring indications, and now, obviously, moving into hypertension and beyond?

Yes. Well, it's a terrific question. I mean, we obviously remain very committed to the rare disease space and genetic medicines, but you're going to see increasingly Alnylam focusing on also large prevalent disease opportunities, where the type of pharmacology we achieve with RNAi therapeutics is extremely differentiating and addresses many of the shortcomings that exist with existing therapies that are out there, and that's certainly going to be true with hypertension. It's also going to be true with our NASH program that is about to go into the clinic. This is a 50-50 program with Regeneron targeting HSD17B13, which we think is the PCSK9 of NASH. And then we have a number of earlier pipeline programs that we're advancing that address similar opportunities in large prevalent diseases, where there's significant unmet need. So I think stay tuned on all that. The other part of our pipeline that we haven't talked about is what we're doing on the CNS side, where we, together with Regeneron, have formed an industry-leading alliance to advance new innovation for the treatment of major CNS diseases. And this is another place where RNAi therapeutics are incredibly well suited because of the ability of targeting overproduction of pathogenic proteins, many of which are causative in neurodegenerative diseases with a drug that can be given very frequently by intrathecal administration and achieve potent knockdown. So these are features in our CNS pipeline that you will begin to see clinical programs start next year from what we're doing with Regeneron. So lots to look forward to in the coming years out of our R&D engine.

Yes. Since these will occur in a while, we'll be looking forward to those updates. With that, our time together is up for today. So thanks so much for joining us. We certainly always learn a lot when we speak with you, John, and today was no different. We hope that you continue to stay safe, and we look forward to speaking with you, hopefully, on your next earnings call.

Yes, terrific. And stay safe, everybody. Talk soon.

Thank you, everyone. Bye-bye.

Bye-bye.