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

Good morning. My name is Rocco, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amylyx Pharmaceuticals RELYVRIO FDA approval Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. I would now like to turn the call over to Lindsey Allen, Head of Investor Relations and Communications. Please proceed.

Good morning, and thank you for joining us today to discuss the FDA approval of RELYVRIO, previously known as AMX0035 in the U.S. With me on the call are co-CEOs, Josh Cohen and Justin Klee; and Margaret Olinger, Chief Commercial Officer. Chief Financial Officer, Jim Frates, will be joining us for Q&A. Before we begin, I would like to remind everyone that some of the statements that we make on this call and information presented in the slide deck include forward-looking statements that are based on our current plans and expectations, including with respect to RELYVRIO. Actual events and results could differ materially from those expressed or implied by any forward-looking statements as a result of various risks, uncertainties and other factors including those set forth in our most recent filings with the SEC and any other future filings that we may make with the SEC. You are cautioned not to place any undue reliance on these forward-looking statements, and Amylyx disclaims any obligation to update such statements. Now I am pleased to turn the call over to Justin.

Thank you, Lindsey, and thank you, everyone, for joining the call. Our mission is to end the suffering caused by neurodegenerative diseases. And while much work remains, yesterday's news is a major step towards the achievement of this goal. Before we begin, I want to recognize the ALS community, who inspires and motivates us in everything we do. Starting next week and continuing throughout the month of October, we will be rolling out communications to health care professionals and to people living with ALS and their families. Those calls will focus primarily on access as we understand how precious time is for people with ALS. Our product websites, relyvrio-hct.com and relyvrio.com, will be updated as we move forward. This call was organized for investors who provided us with the support to do the research that was needed to get us to this point today. Turning to Slide 5. The FDA has approved RELYVRIO for the treatment of amyotrophic lateral sclerosis, or ALS, in adults. We believe that RELYVRIO has the potential to make a significant impact on treatment of ALS within the community. Our commercial and medical affairs teams are in place and ready to help people living with ALS gain access to this important new therapeutic option, which will be available within the next 4 to 6 weeks. This is an exciting milestone for Amylyx, as this represents our first regulatory approval in the U.S. and our second regulatory approval worldwide. As announced in June, Health Canada also approved AMX0035 with conditions where it is marketed under the brand name ALBRIOZA. I would now like to take a moment to give a heartfelt thank you to the people living with ALS and their families, to the health care professionals and to so many others for their unwavering support. I would also like to recognize and thank our amazing team at Amylyx. I will now turn the call over to Josh Cohen, my fellow co-CEO. Josh?

Thank you, Justin. As outlined on Slide 6, despite the availability of 2 FDA-approved therapies, ALS remains a relentlessly progressive and universally fatal neurodegenerative disease caused by motor neuron death in the brain and spinal cord. Motor neuron loss in ALS leads to deteriorating muscle function, the inability to move and speak, respiratory paralysis and eventually death. Sadly, the current median survival of people with ALS is less than 3 years from symptom onset and less than 2 years from diagnosis with many people receiving this diagnosis in the prime of their life. RELYVRIO is the first approved drug for ALS to demonstrate a statistically significant benefit in function in a clinical trial as well as an observed benefit on survival in a longer-term post hoc analysis. I will describe these benefits observed in the CENTAUR study in the next 2 slides. The approval of RELYVRIO is based on our data from CENTAUR, a randomized placebo-controlled trial in 137 participants living with ALS. The trial was conducted at 25 of the top ALS centers of excellence in the United States and designed in collaboration with researchers at Harvard Medical School and the Massachusetts General Hospital, including many individuals who have spent decades designing and optimizing ALS clinical research. CENTAUR enrolled participants 18 to 80 years old with definite ALS with an 18 months of symptom onset and with greater than 60% of normal breathing capacity by measure of slow vital capacity, or SVC. The trial did not restrict participants from receiving edaravone or Riluzole. As outlined on Slide 7, the results from CENTAUR demonstrated that participants receiving RELYVRIO score on an average 2.32 points higher versus placebo over a period of 24 weeks on the revised amyotrophic lateral sclerosis functional rating scale or ALSFRS-R, the gold standard in ALS clinical trials. The ALSFRS-R is a questionnaire-based scale that measures 12 aspects of physical function, and an improvement could mean a substantial change in a person's ability to perform activities such as walking, swallowing or breathing on one zone for longer. On Slide 8, in a post hoc exploratory long-term analysis of CENTAUR, participants randomized to RELYVRIO were observed to survive longer than those randomized to placebo. In the ITT analysis, as of the last participant last visit, up to 3.5 years of follow-up, the difference in median survival duration between the group randomized to receive RELYVRIO and the group randomized to receive placebo was 4.8 months. Detailed data from CENTAUR were published in The New England Journal of Medicine in 2 publications in muscle and nerve and in the Journal of Neurology, neurosurgery and psychiatry. These data should be interpreted with caution, given the limitations of this type of long-term survival study. In addition to being effective, RELYVRIO is generally well tolerated. The most common adverse events occurring with RELYVRIO were diarrhea, abdominal pain, nausea and upper respiratory infection. Gastrointestinal-related adverse reactions occurred throughout the study but were most frequent during the first 3 weeks of treatment. Let me now turn to the RELYVRIO label, shown on Slide 10. RELYVRIO has been approved by the FDA for the treatment of ALS in adults and is administered orally or via a feeding tube. The recommended dosage for the first 3 weeks of treatment is one packet daily, increasing to 2 packets daily starting at the beginning of week 4. RELYVRIO can be taken as a monotherapy or with existing approved treatments. I will now turn the call over to Margaret Olinger, our Chief Commercial Officer, to discuss our plans for the commercial launch in the U.S. with a focus on how our teams will help provide people with ALS access to RELYVRIO. Margaret?

Thank you, Josh. The commercial organization has been eagerly awaiting and preparing for this approval for many months. As Josh stated, ALS is a relentlessly progressive and universally fatal neurodegenerative disease, with a median survival of less than 2 years from diagnosis. As outlined on Slide 12, ALS is classified as a rare disease, but public sources estimate that ALS affects at least 200,000 people worldwide with approximately 29,000 people living with ALS in the United States. Sadly, approximately 6,000 people in the U.S. pass away from ALS each year. And there are also approximately 6,000 people in the U.S. who are newly diagnosed each year. The current lifespan for a person with ALS is far too short, with an average time from diagnosis to death is less than 2 years. It is our goal to improve these statistics. We have already completed the hiring, onboarding and training of the entire commercial organization needed for the U.S. launch. This includes our field force, a highly seasoned key account manager team with approximately 20 years of experience on average. We also have national account managers focused on educating payers and pharmacy benefit managers, including commercial and government plans and regional access managers responsible for educating physician accounts on the access and coverage process. Importantly, our preparatory work included discussions with the largest insurers in the country. We are already deep in discussions with payers and PBMs, both in commercial and Medicare plans who recognize there is a very high unmet need for effective ALS treatment options. Our commercial team's top priorities with this launch are ensuring that people living with ALS have access to this new important medicine and that clinics in which they are treated have the right information to make educated treatment decisions. We view ourselves as partners to these clinics and to people living with ALS. And we have spent many years listening to and engaging with the ALS community. Based on those conversations, we have activated 4 core market development priorities as outlined on Slide 13. These priorities include raising awareness of RELYVRIO and Amylyx, educating on this disease state and RELYVRIO data, partnering with key accounts to educate on the access and coverage process and deepening our understanding of the market. We are thrilled to make RELYVRIO available in the U.S., and our team is fully ready to serve this community as we have done in Canada. Speaking specifically about Canada, following our June approval, [ our field teams ] continue to work closely with all stakeholder groups within the country. The interest in prescribing RELYVRIO has been wide and national in scope thus far. Speaking to access, we are in negotiations with the 4 largest private Canadian insurers, which represent approximately 80% of the private insured population. We have already closed 1 negotiation and expect the others to follow quite soon. On the public side, we achieved a positive recommendation from the Catex Health Technology Assessment body, thus further supporting the process to enable the start of negotiations with the provinces and territories. The ALS community expects equitable coverage to be made available as soon as possible, all while understanding the sequential nature of the public reimbursement system. Currently, most people with ALS are receiving therapy at no cost, limiting the revenue opportunity in Canada until contracts are negotiated with insurers. Like we did in Canada, we have also spent the past year doing extensive work to map out ALS treatment centers and health care professionals treating people living with ALS across the United States. As outlined on Slide 14, we intend to initially focus on leading centers while also dedicating time to smaller local centers and neurology practices, to help ensure every person living with ALS has access to an information on RELYVRIO. We expect to have RELYVRIO in the channel in the next 4 to 6 weeks. As a specialty medication, we are working expeditiously to make RELYVRIO available to people living with ALS through key national specialty pharmacies that have extensive experience in rare diseases, and with the capability to ship to people living with ALS in the United States. Health care professionals will be able to write prescriptions for RELYVRIO immediately and enroll people living with ALS into the Amylyx Care team support program. Our goal is that every eligible person who can benefit from RELYVRIO will have access as quickly and efficiently as possible. As we know, people with ALS and their families have no time to wait. After considering the input of many stakeholders throughout the ALS community, we made the decision to price RELYVRIO below the latest FDA-approved product available to people with ALS. Justin will further address our approach in his closing remarks. This important decision balances the advice and feedback we heard from the broader ALS community allows us to invest in our mission and was also considered with patient out-of-pocket expenses in mind. The wholesale acquisition cost, or WAC, for a 28-day prescription of RELYVRIO, will be $12,504.24 or approximately $158,000 per year for the first year. However, this does not reflect the price people living with ALS can expect to pay. For people with ALS who have commercial insurance, Amylyx is committed to providing financial assistance by bringing co-pays to $0. While pharmaceutical manufacturers cannot offset co-payments, for people covered by government insurance. We are working to ensure that people with government-funded insurance like Medicare or Medicaid will have access to RELYVRIO as quickly as possible. The Amylyx care team will be able to provide people with government-funded insurance information on potential options for financial assistance with co-pays. In addition, for U.S. residents with ALS that are uninsured or underinsured, meet certain financial eligibility criteria and who have exhausted all other options we intend to provide RELYVRIO at no cost. As mentioned, we have been actively engaging in payer discussions. We anticipate formal coverage policy decisions will be made in the next 3 to 6 months. Prior to formal payer coverage, people living with ALS should have access through the medical exception process, which is very similar to other newly approved rare disease products. And our Amylyx care team will be immediately available to support people living with ALS and their health care professionals throughout the process. We recognize the challenges people with ALS space, and we will take significant novel steps to provide support that goes beyond medication. To that end, we have built a team of dedicated employees called the Amylyx care team, or ACT who will support patients with access to the therapy, financial assistance and questions as they take the therapy. The Amylyx care team is unique, as many members of our team have personal connections to ALS. Through the Amylyx care team, a dedicated single point of contact is provided for people living with ALS who have been prescribed RELYVRIO to help streamline the treatment journey. It is worth noting that we are fully prepared for rapid uptake. We expect a gradual commercial ramp-up, given that it can take up to 30 to 45 days for a person to get on treatment through the payer's medical exception process until the insurance plans create formal policies. It will take us until the first quarter 2023 to get a sense of how quick that ramp can be. Also as we think about demand for RELYVRIO over the next few months, many physicians who want to see their patients before they prescribe a new medication, and the holidays always play a role in the fourth quarter. Our focus over the next few months will be on enrolling people in our ACT program and working closely with insurers through the medical exception process with a goal of having RELYVRIO in the channel around the same time that we start to receive approvals from insurers. In parallel, we will be partnering with major insurers to help ensure coverage decisions that allow for clinically appropriate access for people living with ALS. From our many conversations with the community, we know that a new medicine in the ALS space will cause added work for clinics, including many questions from people living with ALS. Our team is prepared to answer questions and assist in the process. Our field teams and the Amylyx care team support program are also ready to ensure health care professionals and the community have the tools and answers they need. I will now turn the call over to Josh and Justin for closing remarks.

Thank you, Margaret. In this last part of today's presentation, we would like to further elaborate on 2 critical topics, our U.S. pricing decision and our business priorities. Josh and I have had the privilege of working closely with the ALS community for nearly a decade. So many have invested their precious time to make this milestone a reality today. Many are no longer with us. We owe it to all of them to do this right. At Amylyx, we have always done everything in partnership with stakeholders in the community. This is core to us and part of the reason we are announcing this exciting news today. We are proud of our commitment and leadership in neurodegenerative disease, which includes advocating for and using patient-centric clinical trial designs, allowing continued access to AMX0035 to all trial participants even after the trial is over, running large expanded access and early access programs in ALS in Canada and the U.S. and building a robust patient support program to ensure access. The ALS community's input was also central to our plans for pricing and access. We met with many stakeholders throughout the ALS community, including leading doctors, people living with ALS and leaders in advocacy to discuss potential pricing of RELYVRIO and access to it. We also talked with every major insurance company in the U.S. and did extensive modeling to understand impact to people's potential out-of-pocket expenses. We also want to ensure that we can continue our mission doing everything we can to help people with ALS today and continuing to invest in new treatments so that ALS first becomes a manageable chronic condition and ultimately is cured. All of these considerations were taken into account when we made the decision to price RELYVRIO below the most recently FDA-approved ALS treatment. We believe the price selected balances the needs of and input from the ALS community and will be supported by insurers. The price also allows Amylyx to sustain programs to help people who can benefit from RELYVRIO access it. Importantly, it supports Amylyx' mission of as our dear friend, Sandy Morris, used to say to us before she recently passed away, research, like our lives, depend on it because it does for people with ALS.

As with everything at Amylyx, our decision-making is driven from our values and principles, which I would like to take a moment to address. We are a mission-focused company. Our mission is to 1 day and the suffering caused by neurodegenerative diseases. Too many of us have been affected by these diseases and yet, there are too few treatment options. Our first focus is ALS. We now have approvals in the United States and Canada that we believe can redefine the treatment paradigm in ALS. We, therefore, now have a responsibility to deliver it to the ALS community as effectively as possible. We await the decision by the European Medicines Agency, our marketing authorization application for the EU, which we expect in the first half of 2023. Launching in the U.S., launching in Canada and preparing for potential EU approval are our primary focuses as a company. But ALS does not stop at geographic boundaries. In the coming months, we will further outline our plans to reach the global ALS community. There is also significant science to pursue. RELYVRIO is already actively being investigated in our Phase III study, PHOENIX as well as in our real-world registry study in Canada through the Canadian neuromuscular disease registry. In the coming months, we will further outline additional ALS studies with RELYVRIO, which will include real-world evidence studies. There is also tremendous scientific interest in the potential role of RELYVRIO in other neurodegenerative diseases, and we are working to prioritize which indications to tackle next. There is considerable and exciting science to pursue, and this is just the start for us. But first, our focus is on people living with ALS today. We are committed to ensuring that every eligible person, who can benefit from RELYVRIO, will have access as quickly and efficiently as possible. We know people with ALS and their families have no time to wait. Thank you for joining us and for your support of us on our mission. We welcome questions. Operator, please open up the call to Q&A.

Today's first question comes from Corinne Jenkins with Goldman Sachs.

Maybe a couple from us. First, and you referenced this earlier, what have you learned from the ongoing launch in Canada that you've been kind of might have read across to what we could expect from the early launch in the U.S.?

Corinne, this is Justin. Thank you for the question, and I'll help moderate, but I'll turn that question over to our Chief Commercial Officer, Margaret.

Yes. So we've had great -- as I mentioned earlier in the script, our Canadian launch is doing well. We have a broad access across the nation. I would say there's really not any new information that I can add other than what we had in our approved -- comments, and that is that -- we are in negotiations with the top 4 private insurance that represent about 80% of the private insurance business in Canada. And as you know, the reimbursement and process in Canada is very different than in the U.S. On the public side, it could take anywhere from 6 to 12 months. We have made the decision for patients who really needed an immediate access to ALBRIOZA treatment in Canada, they are on free drug. But we do expect to transition those 2 commercial products as soon as we finalize negotiations and work through the process with them. But the process in Canada does take slightly longer, especially on the public side, where it could take anywhere from 6 to 12 months. But overall, we're very excited about the progress we've made in Canada. And I'll just put a plug in, we have a phenomenal team there.

Understood. And then maybe you talked a lot about kind of the different access options that you plan to provide. But as we think about how this launch curve will play out and, obviously, getting patient the drug is the top priority. And how should we think about when that starts to translate into revenue, when you have reimbursement kind of up and running?

Corinne, thanks. It's Jim. I think, as Margaret outlined, too, given where we are in the fourth quarter and the time it will take us to get to market in Q4, I think we'll start to see that ramp in Q1 and Q2. And obviously, we'll give you as many updates as we can as we learn the slope of that curve. Right now, it's just too early to predict.

And our next question today comes from Umer Raffat with Evercore ISI.

This is Mike DiFiore on for Umer. Congrats on the approval. I guess the first one from me is that some investors were expecting the possibility for an accelerated approval, which was contingent upon, I guess, the success of the Phase III PHOENIX trial readout next year. Given that it is approved under the traditional pathway, what happens if PHOENIX fails? And then I have a follow-up.

Mike, this is Justin. So I'm happy to address that. And thank you, I think this is an important question. So first, yes, it is a traditional full approval, and the Phase III trial is not a formal commitment. However, it is a commitment in Canada. We expect it to be a commitment in Europe. And as we've said, we plan to continue to run that study. I think for those who know us, I hope it came as no surprise at the FDA Advisory Committee meeting that we answered the way we did when we were asked about PHOENIX. To be clear, we will always do what is right for patients and right for the community. I mean, I guess, in short, why would we keep a drug on the market that doesn't help people? But the data we have today is that RELYVRIO showed an impact on function and survival in a disease that's rapidly progressive and universally fatal. So we have a responsibility to the community to deliver. And what's also right for the community is to continue to study the drug. The PHOENIX trial has always been part of our plan. It's very highly statistically powered based on the results from CENTAUR. And we and, I think I can say, the global ALS community are excited about the results in 2024. And we will continue to study the drug both in ALS, such as we mentioned with our ongoing real-world evidence study with the Canadian Neuromuscular Disease Registry as well as in other neurodegenerative diseases. But again, our priority today is making sure that anyone who can benefit from RELYVRIO can access it.

Got it. That's very helpful. And just my follow-up is just from looking at the IMS data, roughly 6,000 patients are currently receiving Riluzole every month. And the common question we received from investors is how come only 6,000 of the roughly 29,000 patients in the U.S. are on drug? And how should we think about penetration into the 6,000 Riluzole patients? I assume this is a drug that can be taken on top of Riluzole. Any color you could add along those lines would be helpful.

Thank you for the question. And as you know, in our clinical trial, we were studied on top of Riluzole and edaravone as well as there were some patients that were taking monotherapy. So we've fully prescribed in all of our market research that we did with physicians. Physicians want to treat patients with every possible drug that they can. They believe in combination therapy that this is a multifactorial disease that will take multiple shots on goals for these patients to really optimize treatment. So we believe that RELYVRIO treatment will be added on top of standard of care as it was in the clinical trial. And then we also believe as we have 6,000 newly diagnosed patients each year, we feel very strong with our label with both function and survival that hopefully, we'll be able to penetrate those 6,000 newly diagnosed patients every year on top of the prevalent patient population that we'll expect at launch. Again, I would just caution that with the medical exception process, it will take 30 to 45 days to just work through that process, while at the same time, we're getting product supply in channel. So I hope that answers your question.

Yes. Just one point of clarification. How come only 6,000 of the roughly 29,000 ALS patients in the U.S., would you say are only receiving Riluzole at this point? You would think that number will be a lot higher.

So to be honest with you, the range vary depending on what data sources you're looking at, we have purchased claims data through Komodo and that data just shows that there's anywhere from 8,000 to 9,000 patients, it's depending on how many claims you get to look at that data, it could be as high as 11,000 patients on Riluzole at any given point. But we do know that on average, when we look at chart review studies, patients stay on average on Riluzole therapy. On average for 15 months, there's obviously tails to both ends of those numbers. So I think most patients actually do get prescribed Riluzole therapy, but at any given one time, that's how many patients will be on therapy.

And Mike, I'll just -- this is Justin. I'll just add in. I think it's a really important point too. And what's very interesting it’s contrasting with Europe, for example. In Europe, in most major countries, we see as high as 90% plus people with ALS are on Riluzole. So again, different treatment practices but I think it just speaks to the importance, too, of the work that we need to do. I think ALS right now very sadly, no one wants to give the diagnosis. And oftentimes, unless you get to a specialist, it's a diagnosis of, well, I'm sorry, we don't have much for you go home, get your affairs in order. And so I think that's incredibly important to the work that we need to do to try to transform this disease.

And our next question today comes from Neena Bitritto-Garg with Citi.

Congrats on the approval. Can you remind us how many patients are in the EAP in the U.S. currently? And then how quickly you think you can transition those patients over to paid drug? And then my second question is just if you can remind us as well, the powering of the PHOENIX study, how comfortable you are kind of with that if you do start to see some patients drop out in the U.S. to go on commercial drug?

Neena, great questions, and thank you. So first, I would say, maybe starting with the kind of powering question. I would say that we designed the PHOENIX trial to have very, very strong statistical powering, even to be robust in the face of dropouts or otherwise. We have long -- as we submitted for the U.S., we certainly modeled and considered what might happen with the U.S. approval and how that might affect powering and the trial. And I'd say that we still have confidence that we'll have ample statistical power in that study based on the results from CENTAUR.

All right. And I'll just add to that, too, that this has been in the works for a long time now. So as we announced that the FDA Advisory Committee meeting, we halted recruitment early in the year so that we would make sure we did not have truncated data on people in the U.S. So that's been in the works for a long time. Sorry, for the second question. I'll pass back to Josh.

Yes. And on the second question about the EAP, we haven't fully disclosed how many patients are in the EAP or how many can transition. But we do have a robust transition plan and certainly expect that those will be some of the early patients transitioning over to commercial therapy.

Yes. And I can just add, we have a dedicated regional access manager team that will be working with all of the clinics where we have EAP patients, PHOENIX patients, any compassionate use patients. They will be working very closely with our Amylyx care support team to transition those patients to clinical, assuming their physicians and the patients want to continue on therapy as quickly as possible.

And our next question today comes from Marc Goodman with SVB.

Yes. Can you give us an update on the single component study that's going on in Europe? What have you heard about it? And what are your thoughts about whether the results go either way? What does that mean for your product? And secondly, what are you all doing with respect to the compounding of these 2 agents right now to make your product? Are you going to go after these compounded areas and try to eliminate them?

Yes, good question. So I think with regards to the single component study, the [indiscernible] trial that's ongoing in Europe. Again, I think it's important to first note that is primarily an academic run study. That study completed recruitment or announced that they completed recruitment earlier this year. They ended, I think, due to COVID issues recruiting less than they expected in that study, and it's an 18-month study. So we expect that the readout will not be until at least 2024, I think that we see our product as differentiated from that. And so we're certainly eager and excited about those results, but don't expect that there will be the, I don't know, just positive for our product or otherwise. And then in terms of compounding, we certainly monitor and track these types of things. We believe we have a strong intellectual property position and are exploring all options with the counsel and otherwise, to make sure that we do the smartest and most reasonable things around that.

Yes. And Mark, I'll just add to this is Justin that as we said in our presentation, and I think you'll hear us say probably again and again, there's nothing more important than access to us, and we have our Amylyx care team. We've made our commitment in terms of helping people with access. I think this is all part of the same thing. Time is so precious for people with ALS. And so we need to make sure that if we have a treatment that we think can benefit people, we need to make sure they can get it.

Thank you. And ladies and gentlemen, this concludes today's question-and-answer session and today's conference call. We thank you all for attending today's presentation. You may now disconnect your lines and have a wonderful day.