AMLX - NASDAQ

Good afternoon. My name is Tom, and I will be your conference operator today. At this time I would like to welcome everyone to the Amylyx Pharmaceuticals Second Quarter 2023 Earnings Conference Call. All participants will be in a listen-only mode. After today’s presentation, there will be an opportunity to ask questions. [Operator instructions] Please be advised that this call is being recorded at the company's request. I would now like to turn the conference over to Lindsey Allen Head of Investor Relations and Communications. Please go ahead.

Good afternoon and thank you for joining us today to discuss our second quarter 2023 earnings. With me on the call are Josh Cohen and Justin Klee, our Co-CEOs; Margaret Olinger, our Chief Commercial Officer; and Jim Frates, our Chief Financial Officer. Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are made based on our current beliefs, plans and expectations and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements include but are not limited to our expectations with respect to RELYVRIO and ALBRIO

Thank you, Lindsey, and good afternoon. In the second quarter, we made significant progress in bringing RELYVRIO and ALBRIO

Thank you, Justin. In the second quarter, we continued to make significant progress on our three key priorities. The first is our effort to drive awareness and educate about the benefits of RELYVRIO among people living with ALS and clinicians. This includes educating that RELYVRIO is the first and only approved drug for adults with ALS to demonstrate a statistically significant benefit and function in a clinical trial as well as the survival benefit and a longer term post hoc analysis. As a reminder, clinical trial data published in the New England Journal of Medicine demonstrated that after 24 weeks, participants treated with RELYVRIO scored on average 2.32 points higher on the ALSFRS scale than the placebo group. Even a one-point change in the ALSFRS score can indicate a significant difference in a person's ability to function independently with activities of daily living including eating, bathing, dressing, or walking. Participants treated with RELYVRIO at the start of the clinical trial, which means that they both started RELYVRIO six months earlier and were on it for longer than participants starting on placebo, saw a greater survival benefit. During the second quarter, interest in and demand for RELYVRIO continued to build at a steady pace from both those that are newly diagnosed and people who have been living with ALS for years. As a result of our educational efforts, as of June 30th, there were roughly 3,800 people on RELYVRIO in the United States. We are very pleased that so many people have gained access to this important new treatment so quickly. Now, let me run through a few key metrics that demonstrate our progress and growth opportunities ahead of us. Prescribing remains fairly concentrated with just over 80 prescribers mostly at major ALS centers representing approximately half of all RELYVRIO prescriptions at the end of the quarter. We are encouraged by the level of interest among this group and believe that we have an opportunity for growth as we bring our message to more prescribers and deepen our relationships within these key ALS centers. By the end of the second quarter, approximately 75% of the top 500 US prescribers and nearly all of the key ALS centers have prescribed RELYVRIO to at least 1% since launch. We are focused on driving awareness and education and on deepening our penetration within the top prescribers and key ALS centers. In addition, we have a large untapped opportunity for growth outside of this group of top prescribers as we expand our outreach and educational efforts more broadly. Our second priority is engaging with payers to work to help ensure that every eligible person who could benefit from RELYVRIO treatment has access as quickly and efficiently as possible. Consistent with the targets we previously outlined, by the end of the second quarter, our estimates suggest that US insurers representing nearly all ALS-covered lives had published formal coverage policies. The vast majority of these insurers provide broad access to RELYVRIO. This is a significant accomplishment just three quarters into our commercial launch. Our third priority is ensuring eligible people living with ALS have positive interactions through their treatment journey with RELYVRIO and ALS clinics have positive interactions with Amylyx. This includes facilitating an organized clear process to get people who have been prescribed RELYVRIO access to therapy as quickly as possible and optimizing people's experience obtaining RELYVRIO as best we can. Our team has done a tremendous job of facilitating the process, increasing the speed between a prescription being written and RELYVRIO being shipped. In the second quarter, on average this timeline was shortened to about 25 days, aided by the increase in insurance coverage. Our team continues to work expeditiously to get people living with ALS who have been prescribed RELYVRIO on therapy as quickly as possible. Turning to our launch in Canada, interest in ALBRIO

Thanks, Margaret. We're encouraged by the strong interest and demand we continue to see from the ALS community in the second quarter. From a financial point of view, our business remains strong. Net product revenues were $98.2 million for the quarter, compared to net product revenue of $71.4 million for the first quarter of 2023, with the vast majority of that revenue coming from the United States. Gross to net adjustments were approximately 10% in the quarter, which is a little lower than that we would normally anticipate due to the favorable true-up of reserve estimates in the second quarter based on our actual experience in the past nine months. Going forward, we anticipate gross to net discounts will be in the 12% to 15% range. Inventory levels at the quarter end were as expected, with approximately two weeks of inventory in the channel at specialty pharmacies, similar to what we've seen in previous quarters. Cost of sales were $5.6 million for the quarter roughly 6% for net product revenues and our expectation is that COGS will remain in the range of 6% to 10% of sales going forward. Note that we fully expensed all of our remaining royalty obligations this quarter and will not be incurring any additional royalty expenses related to sales in ALS going forward. For modeling purposes, keep in mind that roughly 10% of the people on RELYVRIO are receiving it for free, through either our interim access program or patient assistance program. Research and development expenses were $29 million for the quarter. You should expect R&D expenses to be in the $30 million to $40 million range per quarter for the remainder of the year. As we outlined in our Q1 call, our expectation is that R&D expenses will move toward the higher end of this range later this year as we start enrolling patients in our new Phase 3 trial in PSP. Selling, general and administrative expenses or SG&A were $43.4 million for the quarter, in line with the $45 million per quarter run rate that we mentioned on our first quarter call. We continue to expect SG&A expenses in this range for the remainder of the year. These results led to an excellent bottom line. We generated $22.1 million in net income, representing our second quarter in a row of profitability. Finally, we ended the quarter with cash and short-term investments of $357.3 million and zero debt. We're pleased with our strong financial results and with the disciplined execution throughout the organization. From a capital perspective, we have the resources we need to execute on our mission. We're well positioned to grow our top line, invest in our pipeline to provide more much needed treatments for neurodegenerative diseases and deliver on our bottom line. I'll now turn the call over to Josh to discuss our R&D programs.

Thanks, Jim. We have demonstrated the benefit of AMX0035 in ALS and believe it could help in other neurodegenerative diseases. When we originally developed AMX0035 our goal was to target endoplasmic reticulum stress or ER stress and mitochondrial dysfunction two connected central pathways that lead to neurodegeneration. As we announced on our last call, we intend to initiate a global pivotal Phase 3 study in PSP later this year called Orion. Orion is a well-powered study that will enroll approximately 600 participants and it was designed and planned in collaboration with key global academic leaders, people living with PSP and advocacy groups. PSP is a rare but recognizable progressive and fatal neurodegenerative disease with clear and well-known clinical hallmarks that include progressive disability with respect to eye movement, walking imbalance, speech and swallowing and cognitive function. There are currently no disease-modifying treatments for PSP and we are hopeful that AMX0035 might be able to help. PSP is characterized as a tauopathy, with genetic and pathological findings, supporting a primary role for tau in this disease. Given AMX0035's proposed mechanism of action that targets pathways upstream of tau aggregation and the Phase 2 placebo-controlled PEGASUS clinical trial data, which demonstrated that AMX0035 significantly lowered both plasma tau 181 and total tau in the cerebrospinal fluid of people with Alzheimer's disease, we are excited to pursue this indication in PSP. We recently hosted a webcast with Professor Dr. Gunter Hadinger, a leading expert in PSP and the primary investigator for our Phase 3 ORION trial. As part of the webcast, we shared insights into the scientific rationale for studying AMX0035 in PSP and an overview of the Phase 3 trial design. Additionally, Dr. Hoglinger provided his perspectives on the PSP treatment landscape, the role of tau in this disease and the potential to use AMX0035 in people living with PSP should it be approved. The replay is available in the Events section of our IR website and we encourage you to listen to it, if you didn't have a chance to join us for the live event. In addition to this exciting study in PSP, we are also pursuing a program in another rare disease Wolfram syndrome called HELIOS. Wolfram syndrome is a rare disease that leads to multisystem failure resulting in blindness, deafness, diabetes, ataxia, neurodegeneration and often death in early adulthood. Our R&D team conducted roughly four years of in vitro and in vivo studies of AMX0035 in Wolfram syndrome together with a leading researcher Dr. Fumihiko Urano at Washington University. These studies have promising results some of which were published in the Journal of Clinical Investigation Insight. Several papers characterize the disease as a prototypical disease of ER stress. And as we have discussed in the past, we believe this study which is currently enrolling participants will provide key data to guide future studies and we expect top line results next year. We also continue to broaden our ALS and neurodegenerative disease pipeline. We believe that in order to ultimately find a cure for ALS, it's going to take a combination approach, targeting multiple cellular pathways implicated in disease pathogenesis. We continue to progress AMX114, our antisense oligonucleotide targeting Calpain2, through IND-enabling studies. We have presented data on this candidate at the NEALS, MDA, and TIDES conferences. We're excited to present more data on AMX114 and other advancements in our pipeline in the future. In closing, we are proud of our team's progress and the work that we are doing on behalf of the ALS community. We are in a very strong financial position which allows us to continue to support our launches in ALS and invest in our pipeline to find new treatment options for people living with ALS and other relentlessly progressive neurodegenerative diseases. Now, we'd be happy to take your questions. Operator, please open the call up to Q&A.

[Operator Instructions] And the first question comes from Corinne Jenkins with Goldman Sachs. Please go ahead.

Good afternoon everyone. Maybe just first, what are you seeing with respect to compliance and discontinuation rates? And I'll just go ahead with my follow-up here. Are you seeing any emerging trends with respect to the primary reason for discontinuation; it would be helpful whatever you share there.

Thanks very much for the question. Maybe just to start, as a reminder, we report on net patients on therapy. So this is inclusive of any discontinuation. We are really pleased with our ability to serve the roughly 3,800 net patients on RELYVRIO at the end of Q2. I would say it's really too early to see any long-term trends at this point in our launch. But maybe a reference point in the CENTAUR trial, which again, as a reminder, was a six-month trial. Approximately 70% of participants remained on drug, and we're tracking close to that in terms of the commercial setting. But I would say this is clearly an area where we're going to continue to keep a very close eye on as we expect the patient mix to shift over time.

On the compliance side of the reasons. So on the compliance side, we've seen most rare disease drugs, you'll find in the 75% to 80% range in terms of drug compliance. We're in that range as well. And in terms of reasons for discontinuation, they're varied. People with ALS are going through many different things. Of course, one of the more common ones certainly is death and disease progression, which is expected in ALS as well.

Thanks.

The next question comes from Geoff Meacham with Bank of America. Please go ahead.

Hey guys. Thanks for the question. Congrats on the quarter. I had a couple. The first is the EU, the CHMP process. I wanted to ask how you guys view that process now. And maybe just help us with how you view the next steps here. I wasn't sure for reexamination what the protocol or the success rate could be there? And the second question is just related to capital deployment. I know you guys have done some deals, some BD. I want to ask maybe how that's evolved over time as you look to be sustainably profitable? Thank you very much.

Sure. So on the EU and CHMP, so as we've shared previously, the EU adopted initially a negative opinion. We strongly disagree with that opinion. And I think the basis for that is -- randomized placebo-controlled study on meta pre-specified primary outcome, showing a slowing in the rate of progression on the ALS FRS, we've also observed a difference on overall survival. And that data, of course, led to our approval -- by the US FDA approval and our approval of conditions in Health Canada. So we believe we have a data package that should in our view, support approval. But of course, ultimately, this is up to CHMP. So we submitted for reexamination. That's roughly a four-month process under, which two new apertures are assigned and review the application. We submitted that shortly after we got the negative opinion. So you can expect that near the end of this year, we'll hear back regarding that opinion. In terms of capital deployment and potential BD, I'll talk to -- I'll pass to Jim.

Yes. Thanks Geoff. And clearly profitability this early on in our launch is very gratifying. I mean, I think that ultimately is a direct result of the need in this patient -- in this area and the vast -- the dearth of options that people living with ALS have had so far. So we're very proud to be filling some of that need. You know, I think the other thing I would say too is we're really focused on what we have on our plate now, right with obviously still in the middle of the launch in the United States and Canada, working through what's going to happen in Europe and potentially hopefully looking forward to a launch next year. We've started off and are interacting with the Japanese and other places around the world too to see where we can continue to take this drug. With our PSP program and our Wolfram program ongoing first that we're doing. I'd say the watch it around here right now is focus. Now longer term, I think, we have the opportunity with our launch and with the business that we're in to potentially do some business development over the longer term. But I think that hopefully we'll be able to grow the top-line, grow our bottom-line and then also invest in a robust pipeline. But we have a pretty high standard here for new programs. And as I said I think right now the watch word is on focus.

Thanks, guys.

You bet.

And the next question comes from Michael DiFiore with Evercore. Please go ahead.

Hi, guys. Congrats on the quarter and thanks so much for taking my question. Two for me. Now with the passage of more time do you have any better sense of the size of the patient bolus at this point? And my follow-up is this I want to press you a little bit on the discontinuation rates. I mean among the early patients to have received commercial drug in 4Q of last year presumably some of these patients are -- would have been on drug for at least six months now. Would you be able to provide any color as to what percent of them are still on therapy at this point again just among the patients who started in 4Q?

Yes. Maybe I'll just start with your question regarding the bolus. We continue to be pleased that the interest in and demand for RELYVRIO, continues to be as at a very strong pace and I think importantly includes a mix of both newly diagnosed patients and people who have been diagnosed and living with ALS for many years. Again at the end of Q2, we had roughly 3,800 net patients on therapy up from roughly 3,000 patients in Q1 and just over 1,300 in Q4. So we really believe that at this point in time RELYVRIO is really starting to become a foundational therapy in ALS and meeting a really high unmet need for this patient community which is obviously our mission and what we've been focused on for some time.

And second we have a really large untapped opportunity for growth outside of this group. As I mentioned, we were heavily focused on the key ALS centers at launch. We're continuing to expand our outreach and educational efforts more broadly because we believe it's critically important that everybody is aware that RELYVRIO is the first-and-only product to have both function and survival demonstrated in the clinical trial and we believe we can change the paradigm for treatment moving forward. And maybe just to answer your second question on discontinuation, again, we're only going to be reporting on net patient numbers for a quarter. But indeed, I think it's important to reflect that the first cohort of patients who started on therapy at launch many of those who have been really fairly progressed early on. So I think we're going to see the dynamic of the patients change over time. So it's a little too early to really give any trends there.

Yeah. And one thing, I'll remind that, I think Margaret shared earlier as well we -- in some of central study approximately 70% of people completed that study on study drug. And what we're seeing in the real world is not so different from that. But again --

Great. Thank you so much.

The next question comes from Marc Goodman with Leerink Partners. Please go ahead.

Yes. Hi. First question is are you willing to make any comment about what kind of trends you're seeing you saw in July? And then secondly, can you just confirm -- you mentioned 10% of the patients are getting free drug. Just to be clear that, 10% is in the numbers that you provide right in the 3,800 patients that you were talking about and it's all included in your gross-to-net calculation and everything? I just want to be clear on that. Thanks.

Yeah. Hey, Marc, it's Jim. Yeah, the 10% of the patients that are receiving free drug is included. So those 10% are included in the net patients. Those are all the patients on therapy at the end of June. And yeah, free drug would be included in gross-to-nets -- excuse me, free drug is actually in COGS, right? You've given the drug and you're not getting any sales for it. So the free drug goes in COGS. Any patient assistance that we pay in terms of co-pay assistance or things like that that's what goes in the gross-to-nets just to be clear on that. And then finally, in terms of July, I think we'll comment on the July trends when we report our quarterly results for Q3. But I think our business is -- with now three quarters under our belt, we're all starting to get a chance to see what our business is like moving forward. But we won't be giving specifics on July at this stage.

Great. Thanks.

You bet.

The next question comes from Graig Suvannavejh with Mizuho. Please go ahead.

Thanks so much. Congrats on the quarter. Just two questions. One maybe another way to ask a question that people seem to be trying to get at. Do you have any color on -- or can you provide any color on kind of new prescription trends versus refill trends? Any metrics you can provide there and how that's evolved? And then my follow-up is I'm curious about the expansion efforts to go beyond the ALS centers. And if you could perhaps put into context the portion of ALS prescribers that you're targeting or that you hope to get that are outside of the ALS center setting. Thanks.

So I'll start and then have Margaret join in too. So again, we're three quarters into launch. We have roughly 3,800 net people on treatment as of the end of Q2 which we're very pleased about. I mean, that's 3,800 people with ALS we're helping. But that means that there's many, many more people that we'd like to help as well. But I think we all here are constantly reminded of the mission at hand. And I think the ALS market in many ways is unique. And it's because it's a large rare disease, there's a huge unmet medical need. And historically there have been few treatment options. And so I think the way that we've thought about our business, as Margaret was sharing, is to focus on the ALS specialists, and then continuing to look to broaden out. And so I think as we look at our prescription numbers, where our people have focused is where we're seeing the prescriptions as well. And then Margaret, I'll invite you to share any more details on that.

Yeah. As we've indicated heavily focused at launch which I think was the right strategic decision to focus on the key ALS centers where the majority of ALS patients are actually treated. However, there's also a number of ALS patients that are treated outside of ALS centers for multiple reasons, either they can't transport, they can't get there at a reasonable time and it's -- they typically need to go there every quarter to see the multidisciplinary care. There are a number of General and Community Neurologist, that are equally important to be educated and that's where we're expanding our focus. And we are continuing to increase our penetration and reach out to those, what we call our Tier A or B targets. And we're just going to continue to work on that expansion moving forward, because it's really important for us that every physician who treats an ALS patient is educated about the significant RELYVRIO benefits that we can bring to be able to serve this patient community optimally.

[Operator Instructions] And the next question comes from Ananda Ghosh with H.C. Wainwright. Please go ahead.

Hi guys. Thanks for giving me time and also, congrats on the quarter. So I have two questions on the ALS program and one for the PSP. The first question is basically some of the question which keeps coming from the industrial community and that would be. If PHOENIX is a required confirmatory study for accelerated approval of RELYVRIO and what -- if it says, then can FDA initiate a process to pull it off from the market? So any clarification on that would be great. And then, I have a follow-up question on the ALS program and then, PSP.

Sure. And thank you for the question, Ananda. And yeah, I mean, first, there is a full FDA approval. There's no condition of the PHOENIX study. In Canada, it's an NOC/c which means, a Notice of Compliance with Conditions. And again, our expectation in Europe, if there's an approval is that it would also be a conditional marketing authorization and the condition there would be PHOENIX. So we continue to run the PHOENIX study. We'll have those results mid-next year. That's a very highly powered study. And we and I think the ALS community, are looking forward to those results. But from an FDA perspective, it's a full FDA approval.

Great. Thank you. The next question is the last quarter you had remarked that the patient that might show signs of stability. So, is it still -- is that segment still remains valid for as we think ahead in terms of the growth with RELYVRIO?

Well, so, I think the question you're bringing up on patient responses is a critical one in neurodegenerative disease. And it's a new area for all of us and I think it's really, really exciting. But I'd say, it's still too early to really tell. Now, in the Centaur study, we certainly -- we saw some people who seem to progress very little and others who progress faster, but whether that was due to their specifics, whether it's genetics or environmental or whether that was just due to their course of disease, those are the questions that we're still asking and we haven't been able to ask, because we haven't had effective treatments. But at this time, it's just too early to know. But certainly, those sorts of real-world evidence-type approaches is something that we're very, very excited to do more of, because I think you can start to ask some really, really critical questions when you have an effective treatment.

Right. Thanks. And my last question is on PSP. Based on some natural history data, so we kind of saw that the PSP studies in general has couple of disadvantages. One is a very high rate of dropouts. And some of the scales to cognition and depression mostly fails at least in the historical PSP trials. So what has been your thought on it? And how have you kind of incorporated these into your Phase III trial design?

Yes. So, we shared and probably even more importantly Professor Dr. Gunter Hullinger shared on a recent call that we did, that's published on our website, a much more in-depth view of PSP and our upcoming clinical trial. So, in our PSP trial, we are designing the study based on the PSPRF, the PSP rating scale. This is a scale that tracks primarily -- I would say, primarily kind of motor and functional, rather than cognitive outcomes of PSP. The PSP rating scale studied in several past trials, what's been found quite consistently is an approximate 10-point progression over approximately a year with a pretty small error and a pretty tight kind of variance when you're in these studies. Dropout is not in our view and has not been in previous studies beyond what you might have in other neurodegenerative diseases. And again, as has been shown from the previous studies, this is a space actually where the power is quite good compared to most neurodegenerative diseases. So, I'd say overall -- and again, I encourage people to listen to the webinar where we go into this in a lot more detail. But I'd say overall, we feel very strongly that we have a great trial design, we have a great scientific rationale and that this is a great indication to take AMX0035 into.

Great. Thanks, very much.

This will conclude our question-and-answer session. I'll turn the conference back over to Justin Klee for any closing remarks.

Well, thank you operator and thank you all for joining us on the call today and for your support. So we hope, you all have a good evening. Thanks for joining us.