Amylyx Pharmaceuticals, Inc. (AMLX) Earnings Call Transcript & Summary

Great. Thanks very much, everybody. It's my pleasure to be hosting the Amylyx team. We've got Josh; Justin; and Jim here. They're going to give kind of a brief update on Amylyx for about 15 minutes, and then we'll have 10 minutes at the end for Q&A. So like with prior analysts, feel free to type a question into the link or shoot me an e-mail, and I certainly have a whole list of my own. So guys take it away, and thank you again for joining.

Well, thank you so much, Paul. Thanks, everyone, for joining. So as Paul said, we'll give a brief overview of Amylyx, who we are, and the latest and greatest, and then, yes, I'm very happy to take questions. So first, just to start, I think we're a really mission-focused company. We're focused in neurodegenerative disease but particularly ALS. So as you'll see through our presentation, we take that really seriously. Shown here is Mick, who is close to all of us and we miss early, but we continue to fight on Mick's behalf and so many other people. So just a brief disclaimer before we get started. So statements... [Technical Difficulty]

So it looks like Justin froze. But I think people understood we'll make forward-looking statements under the Private Securities Litigation Reform Act. It's pretty hard to talk about a biotech company and not make forward-looking statements, but we do suggest that you read our SEC filings for more information. Back to you, Justin, sorry.

Thank you, Jim. No, I appreciate it.

I'm good at doing those disclosures.

So very -- just the highlights of Amylyx. So we the company today has been primarily focused on a candidate, sodium phenylbutyrate/taurursodiol, that was approved last year under the brand name RELYVRIO in the U.S. and ALBRIOZA in Canada. So we're very excited that we're now into launches in both Canada and the U.S., and we'll share a little bit more on that later. We are waiting on an EMA opinion as well mid this year. And then I think really importantly, everything we've done from the start of the company is focused on our ability to execute, get this to patients, and that includes being able to protect it both through composition of matter patents, as well as our exclusivities from a regulatory point of view. So I think people are probably pretty familiar with ALS, but we like to remind people this is why we get up every day is to try to help people with ALS. Someone again we miss dearly, our friend, Sandy. She used to have some just really poignant sayings, and something Sandy used to remind us all the time is that we need to work on the ALS clock. She lost the privilege of working on the human clock. January 6, 2018, her clock's a lot faster. So it's, again, people like Sandy remind us why we have to keep pushing and why we really have to do better on behalf of people with ALS and their families. Again, I think this is probably pretty familiar to people, but ALS is just a really tough disease. It's relentlessly progressive, it's universally fatal. Most people don't have a family history. So the diagnosis just sort of strikes out of nowhere. On average, people are diagnosed at age 55 in the U.S., but there are people in their 20s and there are people in their 80s and 90s that get diagnosed with ALS. And I think what's particularly frightening is just how fast it is. On average, about half of people will pass away from ALS in just 2 years. So people will go from fully functional to locked in and ultimately passing away from respiratory arrest in just less than 2 years. And so again, that's why a huge unmet need here and why we need to keep pushing to do better for people. So we were tremendously excited. We have worked for many years and finally got the top line results from our first major clinical trial in ALS, which is the CENTAUR trial. And in that study, we showed a statistically significant slowing of disease progression based on the Gold Standard ALS Functional Rating Scale. So that was about a 2.5 point difference. This data was published in the New England Journal of Medicine. And I would highlight that this scale, I think if you talk to any clinician, they would say even a single point is meaningful on this scale. And again, I think it just highlights the degree of unmet need in ALS. So we were really excited about these results. But I think what made us and probably the ALS field even more excited were the long-term survival data. So as we tracked people further in an ITT overall survival analysis, we saw that, that functional benefit we saw early on turned into an overall survival benefit. So people lived longer. And I think what was really exciting about that is in a progressive fatal disease, this is the first time in a randomized controlled trial that we have seen both a slowing of disease progression and that people lived longer. And so it was on this basis that then we submitted for global approvals, and we are now commercializing. So just a brief picture so you get a sense of what the drug looks like and what the label says. So RELYVRIO is indicated for the treatment of amyotrophic lateral sclerosis or ALS in adults. It can be taken orally or via feeding tube. That's very important in ALS. People start, they can swallow fine, then they go through a period where they have challenges swallowing and then they need a feeding tube. And so all throughout that treatment journey, people can stay on RELYVRIO. And the adverse events we saw in the trial, primarily GI, mostly mild, occasionally moderate, and those seem to be more at the start of the study and less towards the end. So I think, generally, a pretty good benefit-risk profile especially when you look at such a severe disease like ALS. And of course, in Canada, it's the same thing, just ALBRIOZA instead of the brand name RELYVRIO. So that's a very brief overview of things on our side. I'll pass to Josh, but I think the main thing I want to highlight here is really the unmet need globally. There are 29,000 people living with ALS in the United States. There are another 3,000 people in Canada, there are another at least 30,000 in Europe and tremendously more worldwide. And so maybe just before we get into Q&A, we wanted to highlight probably what people are most focused on right now, which is how are the launches going. So we'll give a little sense of that. And then also a little more on our research and development strategy. So I'll pass to Josh, and then excited to get into the Q&A.

Okay. Sure. Thanks, Justin. So I think it's first important to say that ALS is kind of a big rare disease. There are roughly 29,000 people living with ALS in the United States, 3,000 in Canada and over 30,000 in Europe. And the lifetime risk of developing ALS is about 1 in 400, which is similar to the lifetime risk of developing multiple sclerosis. But the reason that we see such a different prevalence is that people with ALS live much shorter than people who are diagnosed with multiple sclerosis. So this disease is actually a lot more common than people think, and there are today quite a number of people who are facing this major unmet need and who are in need of new treatments and new therapies. So I'll talk a little bit about how we're commercializing, and from our perspective, we look at this as the most important thing is that we can get access to everybody who has the potential to benefit from RELYVRIO. So we have an experienced commercial team. The 3 priorities they've really been focused on are driving awareness and education about RELYVRIO, engaging payers to get the best possible access and ensuring that people who get on our product have the best possible experience that they can. And so maybe just talking a little bit about each of these. So we shared recently that at the end of the fourth quarter, we had roughly 1,300 people on therapy that we expect to roughly double that by the end of this quarter. And I think that's a testament to getting out there and educating and bringing awareness. But our prescribing is still pretty concentrated. We focused initially at launch on those top most high-impact centers. And I think we've seen really good uptake in those. But there's still, with roughly 29,000 people in the U.S., there's still a tremendous room to run in terms of additional people that we want to get access to the drug. In terms of payers, we've seen policies that we're quite happy with, from about 1/3 of payers. And by and large, I think we've been seeing a lot of success. We already have good policies from groups like Optum, Aetna, United, Humana, and so we're continuing to work through with the payers but I think we're encouraged by what we're seeing thus far. And then in terms of ensuring people with ALS have good interactions, we've built in-house a group we call the Amylyx Care team or ACT. This is a group that helps people navigate the insurance process, provides kind of an advocate and a person who is supporting people living with ALS and the physicians, and also helps with financial assistance, if necessary and appropriate. So we've really been trying to make this as positive an experience as it possibly can be. So maybe just to give a sense, most ALS treatment is fairly concentrated. About 50% of patients are seen by kind of the top group of doctors. So there's quite a concentrated prescribing base. In our case, we found that about 70 prescribers are currently accounting for about 55% of our prescriptions, or at least were as of the end of Q4. So again, what we're seeing is that we've penetrated very well on some of the top, top centers, but there's a tremendous room to grow across the nation and across prescribers. And then the Amylyx Care Team, I touched on this a little, but again, this is something we built in-house and these are our own Amylyx employees. Many of them have been touched by rare disease or by ALS specifically. So these are people who are helping to go to that for every person living with ALS, for every physician who is enrolled in the program to try to support them through the insurance process and make sure that this is as positive an experience as it possibly can be, as well as providing financial assistance, if appropriate. So then we've launched in the U.S. We're well underway in the U.S. But actually, our first launch occurred in Canada. So we were approved in Canada June of last year. We launched in approximately the late summer last year. And have been working through what I think we can say is we've seen great uptake. We're excited by the uptake we've seen so far in Canada, and it's been broad across prescribers and across the country. However, in Canada, there is a complex reimbursement system. While we have about 80% of lives under the private insurance covered, we're still going through the public insurance process. And it's not uncommon that, that can take approximately 12 months to complete. So what we've shared is that while we're well underway starting at launch to not expect the revenues to become meaningful until at least 12 months into the launch. And then finally, we're under review in Europe. Europe is -- has a greater population than the United States. The number of people living with ALS scales with population, so there are more people living with ALS in the EU and the U.K. combined than there are in the United States. And also in Europe, there's only 1 approved therapy, Riluzole, which was approved in the '90s. So there really hasn't been a new therapy in the past 20 years. When we look at the prescribing habits in Europe, too, we see that Riluzole has much higher utilization as compared to the United States. In Europe, we see approximately 90% of people living with ALS in several major European countries being on Riluzole at any point in time compared to a number in the U.S., which might be more like 1/3. Exactly why this is I think we're still investigating, but it does seem that there's a lot more Riluzole use in Europe as compared to the U.S. So maybe just kind of jumping through the last couple of things, so people have also -- we've also shared that we're nearly complete with our PHOENIX Phase III clinical trial. We completed enrollment in February of this year. We expect top line data mid-2024. That will be the primary outcome, but we expect that survival may take at least a year more to accrue and to have enough data. We're really excited coming into this result. I think if we end up with 2 positive randomized placebo-controlled studies, I think that puts us in a pretty strong position to really address the unmet need of ALS and get the treatment to many, many people. And then finally, I'm realizing I'm running out of time, but finally I'll say that we have a lot of research we plan to do as well. This drug targets neuronal death. I think we've seen success with that approach in ALS. But we also believe by doing that, we can address other disease as well. So we shared recently that we have a clinical study about to start in Wolfram Syndrome, which is a disease we became interested in based on about 4 years of preclinical work together with Dr. Fumi Urano at Washington University. But overall, we're continuing to progress on additional pipeline programs, additional clinical indications, and expect to continue to have more to share in terms of AMX0035 in additional diseases and further growth of the pipeline. So maybe I'll stop there realizing we're running short on time, and pass it over to Paul for questions.

Okay. I appreciate it. And like other panels, folks listening, just feel free to email me or type them in. Just as it relates to the early launch progress, I mean your last quarter looked great. As I think about investors trying to project forward, is there anything distinct or different we're just finding about the population of early adopters versus where you're going to need to attain more growth over time, either be it the types of centers are treated, good versus less optimal payer coverage, things like that?

Yes, great points, and that's exactly where we and our team are focused right now. So early, right, we've only gone through the first quarter and now just rounding on the second launch quarter. But I'd say we're really encouraged. I mean, first, I think oftentimes people talk about demand. Yes, there's certainly demand, but we also had over 1,300 people on treatment as of the end of the quarter. And we shared, too, that we expect to roughly double that in the second quarter of launch. I think the things that we're really focused on are, one, who's prescribing. Right now, it's been very concentrated. 70, 7-0, prescribers account for about 50% of our prescriptions. This is not surprising. We wanted our teams to focus on those centers of excellence. But I think as we look at the prescriber base, it means there's a lot of room to run. And so I think over time, we'll want our teams to focus more broadly. The other thing is on the payer access. So we had great success. I think our [ ax ] program is really successful. 80% of prior auths went through in the first submission. So again, that means the doctor's office gets all the paperwork together, sends it to the payer, and it goes through on the first time round. Now you can always appeal, but 80% on the first time is pretty good. We're now starting to see policies as well. We have about 1/3 of lives covered from some of the big plans, too. And the vast majority are providing broad access, so very close to label. So I think so far, we're really pleased. And maybe 1 last thing I'll say, too, is we're seeing people who are just recently diagnosed. We're seeing people on RELYVRIO who have had -- who were diagnosed a while ago. We're seeing people on monotherapy, we're seeing people on triple therapy. So I think we're seeing a really broad group so far. So we're really pleased. But to be clear, it's early days.

Makes sense. What has to go right for you to get to your 10,000 patients on therapy goal? I mean when you think about reimbursement, global approvals, things like that, and I don't know exactly what specifics you'll give, but realistically, how quickly you can get there.

Yes, so we haven't shared exactly how quickly we think we'll get there. But in terms of what has to go right, I think it's primarily penetration and adherence. We have to continue spreading out to have a broader prescriber base as possible and to have as many people who are eligible to the drug, getting access as they possibly can. And I think the other side is when people are on drug, probably the most important variable as you model this out is often how long people stay on drug. And so that's something we're really trying to educate on and support, both through our Amylyx Care Team and through education, to make sure that if people can benefit from drug that they are on the drug.

Yes. How do you actually educate someone like that, right? I mean it's hard to see over benefit, right, because patients don't get better. And from a tolerability perspective, it's sort of is what it is. Like what's in your control from your perspective?

Yes, it's a really important point. And I think in short, the reason we were saying 10,000, in the U.S. if you look at Riluzole, which is standard of care, there's maybe 9,000 or so people on Riluzole at any 1 time. So we think if we want to be standard of care, then 10,000 is a good metric to look at. But I think a lot of this is can we transform the ALS diagnosis? I mean it's sad to say, but historically, I think it's viewed as a death sentence. And I think we can say this is not a cure, but it's a treatment that will slow progress in people, keep people alive longer. The second thing I'd say we learned from, I think our rare disease colleagues at really successful groups, Genzyme, our Chief Commercial Officer, Margaret comes from Alexion, is the importance of patient support services. They can help tremendously on the front end, getting people on treatment. But it's those relationships that as people progress as people have challenges with adverse events, they can help them. They can make sure they have the right education. By and large, though, I'd also say it helps that I think the safety profile is very good here.

Yes. I might just say, too, Paul, that a few people say part of the issues with the ALS market as you know, sort of apathy. Physicians aren't really engaging with their patients to use more drugs to try and change the course of the disease. I think we prefer to look at that kind of as resignation, right, because it's a pretty tough disease to be treating so many patients. And after a few years, you have more patients that are no longer with us than patients that you're taking care of today. I do think that RELYVRIO gives us the opportunity to kind of change that mix, and yet it's also teaching the offices and the groups to -- it's the first time they're kind of going through Medicare Part D, it's a new system. And so getting people comfortable with that and the process that's required in the United States with our many hundreds, if not thousands of different insurers, so that's super important. And then in Europe, we find that engagement with treatment is actually much, much higher, right? You'll see numbers of 70% or 80% of people's patients being on the 1 generic drug Riluzole that's available in Europe. And our target for 10,000 patients is the United States, actually. And that's roughly 1/3 of the patient population. So that's certainly what we're aiming for, but we won't stop there if we can do better.

Okay. So maybe the last question, so I don't formally cover Amylyx, but we're just talking to different investors. I think 1 of the fears or impediments some folks have or on the bare pieces in the stock is just related to the confirmatory study. It's neurology, right? So even if your drug works, [indiscernible] and fail, the P value in the last year was .03, right? You just don't know if you were to experiment what might have happened. And then maybe less so as it relates to FDA consequences. But I think on the payer side, right, if the study wasn't as robust or didn't work, what could that do to access patient retention? I guess, what do you guys think? What's your kind of, one, level of conviction in the study will likely be positive, and two, if it's not how should we think about any consequences?

Well, I really appreciate your first point just because we get this question a lot, which is it's a full FDA approval. And so I think that's really important. I think people have thought about it as maybe an accelerated approval or something like that. It's a full approval. So the PHOENIX study is not a formal commitment. But of course, we are running it. In terms of our conviction, I mean, I think we go back to the data we had. We ran a 137-patient study. We saw for the first time in ALS a benefit on functional progression and on survival. We're now running a 664-patient study. So we think the powering is significantly greater. And we're really proud of our team. I think we're running a really high-quality study. In terms of access, I think it's a sad thing to say, but we have to look at it in the context of ALS. ALS has 2 approved therapies. Riluzole, which is standard of care, was approved on 2 studies neither of which met their primary endpoints. So that's the backdrop, that's what we have here. I think what we'll do is what we've always tried to do, which is to work closely with the medical community, closely with the patient community and try to make sure that we do what's right. But I think if we look at it today, I have to say, I think the best sort of market data we're having is there's obviously a lot of excitement about this treatment. ALS is a really tough disease, and I think that's based on the data we have in hand.

Excellent. I know we're out of time, these are all very quick. Any parting words before we let you go? And I look forward to seeing you tomorrow evening in Boston.

We're really looking forward to it. Thanks so much for hosting. I'd say, our big focus right now is the U.S. launch. We're really proud of where we are so far, but we got a lot more people to help, too. So stay tuned, and our teams will keep focused. So thanks so much for having us, Paul.

Okay. Congratulations on the progress, guys.

Thank you.