Amylyx Pharmaceuticals - Q2 2023

Transcript

Operator (participant)

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 Q2 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. To ask a question, please press star then one on your telephone keypad, and to withdraw yourself from the question queue, please press star then two. 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.

Lindsey Allen (Head of Investor Relations and Communications)

Good afternoon, thank you for joining us today to discuss our Q2 2023 earnings. With me on the call are Joshua Cohen and Justin Klee, our co-CEOs, Margaret Olinger, our Chief Commercial Officer, and James 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 ALBRIOZA, statements regarding our clinical trials and regulatory developments and the expected timing thereof, our business strategy and outlook, and our expected financial performance.

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 obligations to update such statements unless required by law. Now, I will turn the call over to Justin.

Justin Klee (Co-CEO)

Thank you Lindsey, and good afternoon. In the Q2, we made significant progress in bringing RELYVRIO and ALBRIOZA to people with ALS in the US and Canada, respectively, and advancing our mission of one day ending the suffering caused by ALS and other neurodegenerative diseases. We are incredibly proud of our entire team, who has continued to deliver on the goals that we outlined following the full FDA approval of RELYVRIO last September. These goals included raising awareness and educating people living with ALS with it and physicians about RELYVRIO, working with insurers to provide access to our approved treatment, helping people who have been prescribed RELYVRIO through our Amylyx Care Team patient support program, and deepening our understanding of the ALS market. Let me walk you through our progress.

Our commercial organization is off to a strong start educating and raising awareness about RELYVRIO, as evidenced by the strong and steady demand we saw in the second quarter. As of June 30, 2023, there were roughly 3,800 people on RELYVRIO in the US, up from roughly 3,000 people on RELYVRIO as of March 31, 2023, and just over 1,300 at the end of 2022. As for insurance coverage, adoption has been rapid, and a vast majority of policies have been broad and supportive. Insurers covering nearly all people living with ALS have published formal policies and are covering RELYVRIO, and people living with ALS that have been prescribed RELYVRIO are now able to start therapy more quickly.

The average time between a prescription being written and RELYVRIO being shipped was about 25 days in the second quarter, down from around 30 days in the first quarter of this year and a little over 45 days when we shared this metric on our fourth quarter earnings call. Turning to Canada, we reached our 1-year anniversary of the Health Canada approval with conditions in June. As we reflect on our progress, we are pleased with what we have achieved on behalf of the Canadian ALS community. In the fourth quarter of last year, we announced that all major private insurers in Canada covered ALBRIOZA. We are pleased to share today that by the end of August, we expect ALBRIOZA - ALBRIOZA coverage to be in place for the vast majority of publicly insured lives in Canada.

The early success of our commercial launches has enabled us to both invest in bringing RELYVRIO to more people living with ALS globally and advance our pipeline opportunities that support our mission. We continue to expect a final opinion on our MAA from CHMP in the fall and prepare to execute a successful launch in the EU if approved. We are excited to initiate our new Phase III ORION clinical trial of AMX0035 in progressive supranuclear palsy later this year. Of course, we continue to work diligently to complete the PHOENIX trial, with top-line results anticipated in mid-2024. In summary, we are proud of our progress so far in 2023 and excited about what we can achieve as an organization. We have a clear mission, and we are executing on our goals.

I will now turn the call over to Margaret to provide an update on our commercial performance.

Margaret Olinger (Chief Commercial Officer)

Thank you Justin. In the Q2, 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 in function in a clinical trial, as well as a 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-R scale than the placebo group.

Even a 1 point change in the ALSFRS-R 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 6 months earlier and were on it for longer than participants starting on placebo, saw a greater survival benefit. During the Q2, 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 thirtieth, 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 had prescribed RELYVRIO to at least one person 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 3 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 the 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 ALBRIOZA remains high. We have made significant progress on our public insurance coverage efforts. We are thrilled that five Canadian provinces, Ontario, Quebec, British Columbia, New Brunswick, and most recently, Alberta, announced public reimbursement of ALBRIOZA.

By the end of August, we expect ALBRIOZA coverage to be in place for the vast majority of publicly insured lives in Canada. Our goal is to ultimately change the way people living with ALS are treated, and we believe RELYVRIO is becoming a foundational therapy for ALS. As we move into the third quarter, our team remains focused on driving awareness and education about RELYVRIO among people living with ALS and clinicians. I will now turn the call over to Jim to discuss our financial results for the second quarter.

James Frates (CFO)

Thanks, Margaret. We're encouraged by the strong interest and demand we continued 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 Q1 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 what we would normally anticipate, due to the favorable true up of reserve estimates in the Q2, 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 2 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% of 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 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 III 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 Q1 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 Q2 in a row of profitability.

We ended the quarter with cash and short-term investments of $357.3 million and 0 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.

Joshua Cohen (Co-CEO)

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, 2 connected central pathways that lead to neurodegeneration. As we announced on our last call, we intend to initiate a global pivotal phase III 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 and balance, 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 phospho-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. Günter Höglinger, 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.

Höglinger 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 multi-system failure, resulting in blindness, deafness, diabetes, ataxia, neurodegeneration, and often death in early adulthood. Our R&D team conducted roughly 4 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 had promising results, some of which were published in the JCI Insight. Several papers characterized 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 AMX0114, our antisense oligonucleotide, targeting calpain-2 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 AMX0114 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. We'd be happy to take your questions. Operator, please open the call up to Q&A.

Operator (participant)

We will now begin the question and answer session. To ask a question, please press star then one on your telephone keypad. To withdraw your question, please press star then two. We ask that you please limit yourself to one question and one follow-up, and if you have additional questions, you may rejoin the question queue. We will pause momentarily to assemble our roster. The first question comes from Corinne Jenkins with Goldman Sachs. Please go ahead.

Corinne Jenkins (Equity Research Analyst)

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

Margaret Olinger (Chief Commercial Officer)

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, 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 6-month trial, approximately 70% of participants remained on drug, and we're tracking close to that in terms of the commercial setting. I would say this is clearly an area where we're gonna continue to keep a very close eye on, you know, as we expect the patient mix to shift over time.

Joshua Cohen (Co-CEO)

Maybe I'll just add on the compliance...

Corinne Jenkins (Equity Research Analyst)

Reasons. Yeah.

Joshua Cohen (Co-CEO)

Yeah, sure.

Corinne Jenkins (Equity Research Analyst)

Sorry, go ahead.

Joshua Cohen (Co-CEO)

On the compliance side, on the reasons. On the compliance side, we've seen, you know, most, 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. In terms of reasons for discontinuation, they're varied. You know, people with ALS are going through many different, many different things. You know, of course, one of, one of the more common ones certainly is, is, is death and disease progression, which, which is expected, you know, in ALS as well.

Corinne Jenkins (Equity Research Analyst)

Thanks.

Operator (participant)

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

Geoff Meacham (Research Analyst)

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

Joshua Cohen (Co-CEO)

Sure. On the EU and CHMP, as we've showed previously, you know, the EU adopted initially a negative opinion. We strongly disagree with that opinion, I think the basis for that is we ran a randomized placebo-controlled study, met our pre-specified primary outcome, showing a slowing in the rate of progression on the ALSFRS-R. We've also observed a difference on overall survival. That data, of course, led to our approval by our full US FDA approval and our approval of conditions in Health Canada. We believe we have a data package that should, in our view, support approval. Of course, ultimately, this is up to CHMP. We submitted for reexamination.

That's roughly a 4-month process under which two new rapporteurs are assigned and review the application. We submitted that shortly after we got the negative opinion. You can expect that, you know, near the end of this year, we'll hear back regarding that opinion. In terms of capital deployment and potential BD, I'll pass to Jim.

James Frates (CFO)

Yeah. Thanks Jeff. you know, and, and, and clearly, the 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, and the, and the vast, you know, the dearth of options that people living with ALS have had so far. 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, we're really focused on what we have on our plate now, right? With, 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.

You know, we've, we've started off and, and are interacting with the Japanese and, 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, you know, I'd say the watch word around here right now is focus. Now, longer term, I think we have the opportunity with our launch and, and, and with the, you know, the business that we're in to potentially do some business development over the longer term. I think that, you know, hopefully we'll be able to grow the top line, grow our bottom line, and then also invest in a robust pipeline. We have a pretty high standard here for new programs, and, and as I said, I think right now the watch word is on focus.

Marc Goodman (Equity Research Analyst)

Okay, thanks, guys.

James Frates (CFO)

You bet.

Operator (participant)

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

Michael DiFiore (Research Analyst)

Hi, guys. congrats on the quarter, and thanks so much for taking my question. 2 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? My, my follow-up is this: I want to push 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 would have been on drug for at least 6 months now. Would you be able to provide any color as to what % of them are still on therapy at this point? Again, just among the patients who started in 4Q.

Margaret Olinger (Chief Commercial Officer)

Yeah, maybe I'll just start with your question regarding the bolus. You know, 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, people who have been diagnosed and living with ALS for many years. You know, 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. 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 of obviously our mission and what we've been focus, focused on for some time.

As far as the growth opportunities, which is equally important to us, we see several different opportunities ahead of us. First, the prescribing remains fairly concentrated with the 80 prescribers, mostly at the major ALS centers, where our focus was at the beginning of launch, representing about half of all RELYVRIO prescriptions this quarter. We're also encouraged at the level of interest among this group and believe that we have a large opportunity for growth ahead of us as we bring our messaging to more prescribers and deepen our relationships within those key centers. I think importantly, too, we're seeing those prescribers be much more prolific in their prescribing, which I think is an important part. 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, you know, everybody's aware that RELYVRIO is the first and only product to have both function and survival demonstrated in a clinical trial, and we believe we can change the paradigm for treatment, moving forward. Maybe just to answer your second question on discontinuation. You know, again, we're only going to be reporting on net patient numbers per quarter. Indeed, I think it's important to reflect that the first cohort of patients who started on therapy at launch, many of those who had been really fairly progressed early on. 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, you know, trends there.

James Frates (CFO)

Yeah, one thing I'll remind that, I think Margaret shared earlier as well, you know, we in the CENTAUR study, approximately 70% of people completed that study on study drug. What we're seeing in the real world, is not, is not so different from that. Again.

Michael DiFiore (Research Analyst)

Thanks so much.

James Frates (CFO)

Of course.

Operator (participant)

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

Marc Goodman (Equity Research Analyst)

Yes, hi. First question is, are you going to make any comment about what kind of trends you're seeing, you, you saw in July? 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.

James Frates (CFO)

Yeah. Hey Marc, it's Jim. Yeah the, the 10% of the patients that are receiving free drug is, is included. Those 10% are included in the net patients. Those are all the patients on therapy at the end of June. You know, yeah, free drug would be included in gross-to-net. Excuse me, free drug is actually in COGS, right? You're giving the drug, and you're not getting any rep, any sales for it. The free drug goes in COGS. Any patient assistance that we pay, you know, in terms of co-pay assistance or things like that, that's what goes in the gross-to-net. Just to be clear on that.

Then finally, in terms of, you know, July, I think we'll comment on the July trends when we report our, our quarterly results for Q3. You know, I, I, I think our business is, is, you know, with now 3 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.

Marc Goodman (Equity Research Analyst)

Sure. Thanks.

James Frates (CFO)

You bet.

Operator (participant)

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

Gregory Suvannavejh (Research Analyst)

... Okay, thanks so much. Congrats on the quarter. Just 2 questions. 1, 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, kind of, metrics you can provide there and how that's evolved? Then, my follow-up is, I'm, I'm curious about the expansion efforts to go beyond the ALS centers, and if you could perhaps put into context, you know, the, the portion of ALS prescribers that you're targeting, or that you hope to get that are, outside of the ALS center setting. Thanks.

Justin Klee (Co-CEO)

Yeah. Maybe I'll, I'll start and then and then have Margaret join in too. Again, you know, we're, we're three quarters into launch. We have roughly 3,800 net people on treatment as of the end of Q2, which, you know, we're very pleased about. I mean, that's 3,800 people with ALS we're helping. That means that there's many, many more people that we'd like to help as well. You know, I think we all here are constantly reminded of the the the mission at hand. You know, I, I think the ALS market in, in many ways is unique. It's because it's a large, rare disease.

There's a huge unmet medical need. Historically, there, there have been few treatment options. I think the way that we've thought about our business, as Margaret was sharing, is to focus on the ALS specialists, continuing to look to broaden out. I think as we look at our prescription numbers, where our people have focused, is where we're seeing the prescriptions as well. Margaret, I'll invite you to share, share any more details on that.

Margaret Olinger (Chief Commercial Officer)

Yeah. As we've indicated, we 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 those ALS centers for multiple reasons. Either they, they can't transport, they, they can't get there at a reasonable time, you know, and it's, you know, they typically need to go there every quarter to see the multidisciplinary care. There are a number of general community neurologists that are equally important to be educated, and that's where we're expanding our focus, and we are continuing to increase our, our penetration and reach out to those, you know, what we call our Tier A, Tier B targets.

We're just going to continue to work on that expansion moving forward because it's really important for us that, you know, 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 (participant)

Again, if you'd like to ask a question, please press Star, then one to join the queue. The next question comes from Aman Ghosh with H.C. Wainwright. Please go ahead.

Aman Ghosh (Research Analyst)

Hi, guys. Thanks for giving me time. Also congrats on the quarter. So I have 2 questions on the ALS program and 1 for the PSP. The first question is basically some of the question which keeps coming from the investor community, and that would be, you know, if PHOENIX is a required confirmatory study for accelerated approval of RELYVRIO, and what... If it fails, then can FDA initiate a process to pull it off from the market? So any clarification on that would be great. Then I have a follow-up question on the ALS program and then PSP.

Justin Klee (Co-CEO)

Sure, thank you for the question Aman. There's a full FDA approval. There's no condition of the PHOENIX study. In Canada, it's an NOC/c, which means a notice in compliance with conditions. 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. We continue to run the PHOENIX study. We'll have those results mid-next year. That's a very highly powered study, and the ALS community are looking forward to those results. From an FDA perspective, it's a full FDA approval.

Aman Ghosh (Research Analyst)

Great. Thank you. The next question is, you know, the last quarter, you had a remark that the patient ad might, you know, show signs of s- stability. Is it, is it still... If that, if that statement still remains valid for as we think ahead in terms of the growth with the RELYVRIO?

Justin Klee (Co-CEO)

Well, you know, I, I think the, the question you're bringing up on, on patient responses is, is a, is a critical one in, in neurodegenerative disease, and it's a, it's a new, it's a new area for, for all of us, and I think it's really, really exciting. I'd say, you know, it's still too early to, to really tell. Now, in, in the, in the CENTAUR study, we certainly, we saw some people who seemed to progress very little and others who progressed faster. 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 I'd say, you know, at this time, it's, it's just too early to know. 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.

Aman Ghosh (Research Analyst)

Got it. Thanks. My last question is on PS, PSP. You know, based on some natural history data, we kind of saw that the PSP studies in general has a couple of disadvantages. One is a very high rate of dropouts, and you know, some of the scales to assess cognition and depression mostly fails, at least in the, you know, historical PSP trials. What has been your thought on it, and how, you know, how have you kind of incorporated these, these into, into your Phase III trial design?

Joshua Cohen (Co-CEO)

We showed, and probably even more importantly, Professor Dr. Günter Höglinger shared on a recent call that we did that's published on our website, you know, a much more in-depth view of PSP and our upcoming clinical trial. In our PSP trial, we are designing the study based on the PSPRS, 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, over approximately 1 year, with a pretty small error bar and a pretty, pretty tight kind of variance when, when you're, when you run these studies. Dropout is not, in our view, and has not been in previous studies, beyond what, what you might have in, in other neurodegenerative diseases. Again, as has been shown from the previous studies, this is, this is a, a space actually where the power is quite good compared to most neurodegenerative diseases. I'd say overall, and, and again, I encourage people to listen to the, to the webinar, where we go into this in a lot more detail.

I'd say overall, we feel very strongly that, you know, that we have a great trial design, we have a great scientific rationale, and this is a great indication to take AMX0035 into.

Aman Ghosh (Research Analyst)

Great. Thanks very much.

Operator (participant)

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

Justin Klee (Co-CEO)

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

Operator (participant)

The conference is now concluded. Thank you for attending today.