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

Okay. Good morning, everyone. Thank you so much for joining us here at our Virtual Bank of America Health Care Conference. It is my pleasure. I'm Tazeen Ahmad, one of the SMID biotech analysts here at BofA. It's my pleasure to introduce our next presenting company, Alnylam. Presenting for Alnylam this morning is Yvonne Greenstreet, Chief Operating Officer. Dr. Greenstreet has 25 years of global experience in the pharma industry, and she's had several senior roles in research and development as well as strategy and portfolio management. She successfully led product development and commercialization teams in a wide range of therapeutic areas. Dr. Greenstreet was previously Senior VP and Head of Medicine Development at Pfizer and a member of their executive team for the specialty business. She has a wide range of experiences in large companies and it is my pleasure to be speaking with you formally for the first time this morning, Dr. Greenstreet. Thanks for joining us.

Yes. Good morning, Tazeen, and good morning, and hello to everybody that's on the call. Thank you so much for joining us today.

So for all of the companies that we present, we like to assume that most everyone is familiar with what Alnylam is doing, but for those who may not be, I'm hoping you can give just a quick overview of the company, its platform, its main technology, and we can go from there.

Yes. No, it's great. And I think it helps to sort of set the scene with what Alnylam's focused on and kind of where we are. We've been pioneering RNAi therapeutics as a whole new class of medicine since 2002. And it's based on Nobel Prize-winning technology where we can essentially silence any gene in the genome, and therefore, significantly reduce disease-causing proteins or toxic metabolites that contribute clinical manifestations of a wide range of diseases. And over the past 16 or 17 years, we've been harnessing this mechanism, and we've been able to build an organic product engine, which can now deliver sustainable innovation and be able to bring medicines to patients and important diseases around the world. So we're really excited about our journey. We think we have a really unique opportunity with the product engine that we've built. And right now, we're multi-product, global commercial company with a presence in many markets around the world. We have 2 products on the market right now, 2 products that are at registration and a very rich pipeline behind that. And given our organic and what we think is a very robust product engine for innovation, we have set ourselves on the course of delivering 2 to 4 new INDs per year as a business. I think the other important point to note is that we've conducted a number of studies in different indications and some very large studies with our RNAi therapeutics. And we are at a point where we think that the -- we believe that the platform that we've developed has really been derisked from a safety perspective. So we're in a position where we can continue to deliver exciting medicines for the foreseeable future, ONPATTRO and GIVLAARI, the 2 products that we brought to market so far. And we are looking forward to continuing harness this technology to bring important medicines that make a big difference in patient's lives. Now I know that's a very high overview that really just summarizes kind of the type of company we are and where we are in our growth. There's probably just one other thing to add that I think is really quite important in where we are as a company right now and that's the landmark strategic financing deal. We entered into with Blackstone earlier this year, representing up to $2 billion and is anchored by the partial monetization of our future increase for our royalty stream. So the really important thing about this deal is that it allows us to secure a bridge to achieving a self-sustainable financial profile without the need for future equity raises. So we really think we're in a very good position to continue building the business and delivering to patients.

Okay. Thank you for that overview and maybe we can drill a little bit into some of the topics that you've just mentioned. So as it relates to your commercial portfolio, with both now GIVLAARI ONPATTRO comfortably launching and now it's part -- they're part of this COVID environment. What have you learned about what's working and what doesn't work for marketing purposes? And are there changes that you've made that might even become permanent in a non-pandemic environment?

Yes. No, that's a really good question. And I'm pleased to say that despite the pandemic, we've delivered very good revenues for both ONPATTRO and GIVLAARI. We're delighted where those 2 medicines are in their trajectory, but yes, we have had to deal, as with everybody else, with COVID. I think one of the opportunities that we had was that even prior to the pandemic, we've really started to think about digital approaches for engaging with customers. And I think this is one of the important learnings from the pandemic, is how you think about digitization and virtualization of the commercial infrastructure. If you take GIVLAARI, for instance, that's the RNAi therapeutic that was approved last November for the treatment of patients with acute hepatic porphyria. We were highly prepared with various digitization and virtualization approaches for that launch, given the very diverse prescriber base. And I think the results so far underscore how well those capabilities have served us. In-person interactions are always going to be great and preferred. I would much rather be with all of the folk on the call today, in person. But I think we have learned how to maximize the digital and virtualization approaches that we have. And I think we're doing pretty well getting to health care providers, educating them, reaching out to patient advocacy groups, et cetera. And I think even when we return to the new normal, whenever that is or whatever that looks like, I think there will be some of these approaches that will be maintained going forward because actually doing global KOL meetings is actually, probably a bit easier to do virtually than just to try and fly everybody in and get everybody able to attend at the very same time. So I think it'd be interesting to see which of these approaches actually we continue to focus on and drive going forward. I think the other thing, from an Alnylam perspective, is that for us, it's been a really nice validation of the global strategy that we built as a company, in terms of commercializing our products worldwide. It's kind of enabled us to kind of appreciate the different dynamics within different health care systems around the world and strategize accordingly. In some countries and regions, the pandemic has been better or worse at different times. And this has really allowed us to engage in different ways around the world. And I think the efficiency that we're building and the operational reach that we have, it will only continue to grow and evolve and I think will continue to be a really important element of our business.

Okay. That's super helpful. And then as we think about all the different potential areas that you could expand into -- and some of these questions would be specific to your current programs. For example, for ATTR, the company has recently given an update on all of the patient finding efforts and you're using multiple different fronts to do so. Can you give us a little bit of color if you can on your perspective, given all of your experience so far on how important is it to engage in these patient finding efforts now? And can you give us a rough sense of where you are in your goal of trying to tap as much of the population as possible for ATTR?

Yes, Tazeen, that's a really, really good question because I'm sure there's many folk listening on the call today know that patient finding efforts, particularly in rare diseases, are incredibly important to be able to help those patients get tested, get diagnosed and access treatment. And for many diseases, this could be a multiyear journey. And we've been very focused on trying to truncate this journey for patients and get patients appropriately treated. And I think there's been -- TTR, in particular, I think there's been a significant evolution of the market over the past few years. I think there is substantially greater disease awareness and probably driven by the educational efforts from companies like ourselves that have introduced new medicines. I think this whole diagnostic field is evolving as well with the emergence of PYP scan. It's a really good way to identify cardiac amyloid. And I think providing patients with greater access to genetic testing have really helped augment these patient finding efforts. I think one area that I'd just like to highlight is our Alnylam Act program, which is a genetic testing and counseling service that's provided through a third-party, continues to be used robustly. And so far for TTR, we've had about a 6% positivity rate, which is helping, hopefully, a lot of patients. But that being said, TTR amyloidosis does remain significantly under-diagnosed and we think the hereditary population is 200,000 to 300,000 patients worldwide. We've come to this number based on looking at patient registries, looked at our reviews and our internal research. But for the wild-type form of the disease, we think that there are many, many, many times more patients with this. I mean, prevalent estimates ranging between 200,000 to 300,000 patients worldwide, some estimates even larger. And clearly, as we evolve our TTR portfolio, there's going to be a lot to be done here to help these patients.

Okay. And then as we look at, for example, vutrisiran, specifically in ETT or polyneuropathy, there's going to be an important data set happening early in 2021, the HELIOS study. And as we prepare to see what those results will show, is there any way of framing what we should be looking for as investors, and what we should consider to be good data from that?

Just to remind everybody that vutrisiran is our investigational RNAi therapeutic targeting TTR. And it uses our ESC GalNAc-conjugate chemistry. And we feel that we've delivered a very compelling profile. It's going to be a simple subcutaneous demonstration of a low volume product with a pre-filled syringe, 25 mg once every 3 months. I think that's a really compelling proposition for patients. Based on our Phase I data and doing some additional remodeling work, we're also exploring a additional 50 mg biannual dosing regime. So from a patient perspective, I think you can see how this could transform the treatment and actually kind of free them from the anxiety and complexity of having in a more frequent regimen. So we're looking at vutrisiran in the HELIOS clinical program across the full range of patients with ATTR amyloidosis. The HELIOS-A study that you referred to is in patients who had hATTR amyloidosis with polyneuropathy and we were delighted to have completed enrollment in the study earlier this year and we expect topline results in early 2021. And HELIOS-A, we were actually very pleased with the design of the study. It's an innovative bridging study between ONPATTRO and vutrisiran, and it's really aimed at bringing vutrisiran to the market as soon as possible. It's an open-label study. And what we're looking at is comparing the efficacy of the vutrisiran treatments, the placebo arm of the original APOLLO study with a change in [indiscernible] at 9 months as the primary end point. So in the near term, what we're looking to do is to get this therapeutic option on the market for hATTR amyloidosis patients with polyneuropathy as soon as possible, while we continue to expand the franchise of both treatments into the full ATTR amyloidosis population, including patients who have cardiomyopathy through our APOLLO-B study, which is with patisiran; and our HELIOS-B study, which is with vutrisiran. So lots happening, and we're looking forward to those top line results next year.

Okay. In line with the same topic of ATTR. Now on several calls -- several quarterly calls, we've been hearing from your team that there is significant use of both silencers as well as stabilizers and especially in patients who have these mixed phenotypes. And I wanted to get your thoughts on -- as it relates to potential business development, partnerships, would Alnylam be open to the potential of partnering with other companies that are doing ATTR, that could be complementary to the mechanisms that you're developing?

Well, I think it's important to say that the dynamics in different regions are different. So you're absolutely right. So the fourth quarter of 2019, in the U.S., we've been seeing growing evidence of use and reimbursement from ONPATTRO where it's used together with the TTR stabilizer. And I think that's positive for patients who are suffering with multiple manifestations of hATTR amyloidosis. And because of this, we think concomitant use will continue to increase over time for patients whose disease manifestations include polyneuropathy as well as cardiomyopathy. However, outside the U.S., I think it's been a slightly different dynamic. It's been much more of a switch dynamic. There's a greater recognition of disease progression on tafamidis, a much more extensive physician experience with stabilizing drugs. There's no doubt that ATTR amyloid is a severe life-threatening disease. And I think efficacy is going to be the primary consideration for patients and physicians. We believe that the TTR silencer mechanism of action is really the way to go in polyneuropathy. And we look forward to this being the case in ATTR cardiomyopathy as well, and we eagerly await data to confirm this. So really, we think that RNAi is capable of addressing the full spectrum of disease manifestations as a monotherapy. And as we progress in this direction, we intend to focus on this approach. But obviously, we're always kind of open-minded to all sorts of approaches. But right now, we think we have in our hands a portfolio of opportunities for patients with TTR amyloidosis. And that's really where we're going to be focusing to try to help patients with this very devastating disease.

Okay. Before we move into what seems to be a very, fruitful pipeline, I wanted to ask maybe one more question on your current commercial portfolio, and that's on GIVLAARI. Given your feedback from some doctors thus far, how do you think that GIVLAARI has performed in a real-world setting versus what was shown with the clinical data for these acute hepatic porphyria patients that had, had low to no attacks and low to no human use in the median over like the 6- to 12-month period that was studied?

Yes. Just to remind everybody about GIVLAARI and acute hepatic porphyria. So acute hepatic porphyria is a rare and debilitating disease, and of course, is acute and potentially fatal; neurovisceral attacks, also chronic symptoms with pain and fatigue. And it really poses a tremendous burden onto patients, some of whom essentially tried to just live their lives around their attacks and recurrent hospitalizations. So last November, we got the U.S. approval of GIVLAARI, and that was followed earlier this year in Europe and more recently, in Brazil. And in our last earnings call, we -- at the end of the second quarter, we reported that we had over 100 patients on commercial GIVLAARI therapy. And I think -- as you, I think, indicated, GIVLAARI's results in the Phase III study were very positive, where GIVLAARI demonstrated a 74% mean reduction in the annualized rate of composite attacks of patients treated over 6 months. And I think these are the sort of foundational data for GIVLAARI and have carried through to the real world to a significant degree. We receive a lot of positive anecdotal feedback from doctors who have come to value GIVLAARI's ability to keep patients with AHP out of the hospital. I think it's important to note that this has been a particularly important feature during the ongoing pandemic. I think physicians have told us that they see an improvement in their patients' lives. The attacks reduced in frequency. But I think the real transformational impact of GIVLAARI has been just allowing patients to gain control over the disease and get back to owning their lives. And we get many patient reports. And we get patient stories, and they tell us how they're able to do things that they've never been able to do before, and they finally feel that they're living again and to be honest, it's sort of -- those sorts of stories that really continue to drive us and really continue to bring RNAi therapeutics to patients. I wish I could share some of the patient stories with you, but it would probably take quite a lot of time, but they really are very motivational. Actually, one thing just to quickly add, if anybody is interested in learning a little bit more about GIVLAARI because you probably don't have time today, is that earlier this week, we had a roundtable, an RNAi roundtable webinar which focused on our GIVLAARI program and it talked about clinical and commercial progress. And there's a lot more detail on that webinar if anybody on the call is interested in following up on that.

Okay. Great. So let's talk about the pipeline. We'll start with something that's very near term, lumasiran. There's a December 3 PDUFA for that product in primary hyperoxaluria. How have your commercial prep been as you try to think about the upcoming launch, again, in the context of now launching into a full COVID environment?

Yes. I mean, launch preparations have actually been progressing well. I think we've benefited from having launched 2 previous drugs, ONPATTRO and GIVLAARI that we've just discussed. And that's really helped us build the capabilities and develop a playbook for how you best approach commercializing rare diseases. And we're applying all of these learnings as we prepare for the potential commercial launch of lumasiran. It's focused on some of the things that we've talked about already, enhancing disease education and awareness that you can get earlier diagnosis and improved diagnosis rates. And we've also been engaging with payers around disease awareness. I think many people on the call will be familiar with some of the innovative, value-based agreements that we've engaged in and we found that a very important way of being able to ensure that there are no kind of headwinds from the payer front around our launches. In it, we're utilizing websites and disease campaigns that we can help physicians think about the possibility of PH1 in both pediatric and adult patients who have stone events and really helping physicians start to consider PH1 as part of the differential diagnosis. And we've built very strong relationships with leading patient advocacy groups. So I think we've really benefited from our previous experience and we're really excited to look forward to the potential launch of what will be our third RNAi therapeutic, assuming, of course, a positive regulatory decision.

Okay. Now this is always a difficult question for anyone to answer ahead of time, but we as analysts try to get as much color as we can. How should we think about the potential steepness of this launch relative to the other indications you've launched so far?

The potential what? Sorry, I didn't hear you.

The steepness of the launch trajectory relative to your other ongoing launches?

Right. I mean, I think as you pointed out, it's hard to comment. I think PH1 is, again, another devastating condition. I think the difference here is that as well as an adult population, we're also targeting a pediatric population because patients are diagnosed with PH1 as early as infancy. It may be that when it comes to patient diagnosis, it could be easier to identify patients in early childhood rather than adults as many patients remain undiagnosed at adulthood due to variable disease manifestations. And I think the real driver behind the lumasiran long-term opportunity is going to be centered around increasing diagnosis of these patients. And just to add, that we have a full suite of studies with lumasiran. We've got the ILLUMINATE-A study, which is our first study. We've got ILLUMINATE-B, which is our second Phase III study that's been conducted in PH1 patients less than 6 years old. And then we're also progressing the ILLUMINATE-C study. So we are committed to developing the data set that will support patients with a full range of features of primary hyperoxaluria 1. So patients, at least 6 years old with... [Technical Difficulty]

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