Amylyx Pharmaceuticals Inc

NASDAQ:AMLX

Earnings Call Transcript 2023-Q1

[Lindsey Allen, Head of Investor Relations and Communications]

Good afternoon and thank you for joining today to discuss our First 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 based on our current beliefs, plans and expectations, and are made pertinent 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 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 statement 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 unless required by law.

Now, I will turn the call over to Justin.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Thank you, Lindsey, and good afternoon. As everyone on this call knows, there's an enormous unmet need in ALS and other relentlessly progressive and fatal neurodegenerative diseases. It is our mission at Amylyx to one day and the suffering caused by these diseases. Our treatment delivery enabled us to make meaningful advances toward and continued investment in our mission. During the first quarter, we generated 71.4 million in net product revenues. Reflecting the significant progress we continue to make toward our goal of ensuring every eligible person living with ALS has access to RELYVRIO. RELYVRIO is the first and only approved treatment for ALS set in a randomized placebo controlled trial. Both met its pre-specified primary outcome demonstrating a statistically significant benefit and function and showed a benefit on survival and a longer term post hoc analysis. These data suggests that ALS can in fact be treated.

The full approval of RELYVRIO is an important step toward ALS one day being a manageable disease. The ALS community has been waiting for meaningful treatment options since the disease was first characterized over 150 years ago. And we believe that delivery will eventually be a foundational therapy for ALS. In the first quarter, we saw a continued high level of interest from the ALS community and RELYVRIO broadened insurance coverage, and high levels of engagement with our Amylyx care team, also known as act, just two quarters into launch over 10% of the approximately 29,000 people living with ALS in the US are now on RELYVRIO. Even with that success in our first six months, we have more to do. There remain many more 1000s of people living with ALS in the US and at least 200,000 people living with ALS globally. We are still in the early stages of our journey, and our team remains hard at work.

Shifting to our plans internationally, we are diligently preparing to help bring our medicine to all eligible people living with ALS around the world. The regulatory review process in Europe remains ongoing, and we continue to expect an opinion from CHMP mid year and a decision at the earliest in Q3. Overall, we believe we have a strong scientific position that is supported broadly by the ALS medical and advocacy community and a capable team who is leading our process. We continue to prepare to execute a successful launch in the EU if approved. We are proud of our team's progress on advancing our mission.

And now I'll turn the call over to Margaret to share a commercial update.

[Margaret Olinger, Global Head of Commercial and CCO]

Thank you, Justin. As we enter the seventh month since our US launch, we remain focused on three key priorities. The first is our effort to drive awareness and education about RELYVRIO among people living with ALS and clinicians. This includes educating that RELYVRIO is a first approved drug for adults with ALS to demonstrate a statistically significant benefit in function and a clinical trial, as well as a benefit on survival and a longer term post hoc analysis. Our efforts to drive awareness are yielding strong results. We are seeing continued interest and demand for RELYVRIO. As of March 31, there were roughly 3000 people on RELYVRIO in the US more than double the number of people on RELYVRIO at the start of the quarter. We are pleased that this many people have gained access to our important treatment.

I think it's worth spending a minute to provide some additional context on the strength of our launch. While we knew there was pent up demand, the fourth quarter and first quarter, were still well ahead of our expectations. The rate of net patient's [indiscernible] has begun to moderate as expected. However, we still see significant demand for people living with ALS, and physicians alike. Importantly, we still have plenty of room for growth, both at the top ALS centers, and the broader neurology community. [indiscernible].

Now, let me run through a few metrics that show our progress, but also the growth opportunities ahead of us. By the end of the first quarter, approximately 65% of the top 500 US prescribers and approximately 95% of the key ALS centers had prescribed RELYVRIO out to at least one person since launch. Prescribing remains fairly concentrated, with roughly 80 prescribers mostly at major ALS centers, representing approximately half of all RELYVRIO prescriptions during the quarter. While we are encouraged with these data points, we see an opportunity for broader and deeper uptake of key ALS centers, and the opportunity to continue to penetrate the group of top prescribers.

Additionally, we believe we have a large untapped opportunity for additional growth outside of this group of top prescribers as we expand our outreach and education efforts more broadly. Our second priority is engaging with payers to work towards our goal of ensuring that every eligible person who can benefit from RELYVRIO has access as quickly and efficiently as possible.

At the end of the first quarter, U.S. insurers, representing approximately 50% of covered lives, have published formal coverage policies, including many of the key national and regional plans. The vast majority of these insurers provide broad access to RELYVRIO. For people living with ALS who go through the medical exception process we are pleased that approximately 80% of prior authorization requests have been approved on the first admission. We continue to see a wide range of people living with ALS in terms of time sense initial diagnosis, interested in and gaining access to RELYVRIO. Our team remains engaged with insurers across the country. And we continue to anticipate most plans will formalize their policies during the first half of this year.

Our third priority is ensuring eligible people living with ALS, have positive interactions with their treatment journey with RELYVRIO and ALS clinics have positive interactions with Amylyx. This includes facilitating an organized, clear process to get people prescribe RELYVRIO access to the therapy as quickly as possible and optimizing people's experience accessing RELYVRIO as best we can.

Our team is working expeditiously to get people living with ALS, who have been prescribed RELYVRIO on therapy in the first quarter. On average, it took about 30 days between receiving an enrollment form, and RELYVRIO being shipped down from a little more than 45 days in the fourth quarter. And we expect to make additional progress on this metric in the second quarter with the benefit of more insurers having formal coverage decisions. In the limited cases where access hasn't been granted through an insurer, our interim access program and our patient assistance program are available for eligible patients. In the first quarter, roughly 10% of people taking RELYVRIO were part of these programs.

We are pleased with the progress we've made so far on our goal to ensure that every eligible person living with ALS, has access to RELYVRIO which we see as a potential foundational therapy and neurodegenerative disease. Our launch is off to a strong start. And it is our hope that eventually RELYVRIO will become the most commonly used ALS medication. While we are clearly focused on the launch of RELYVRIO in the U.S. that we also have a large opportunity internationally.

ALS is a global disease, affecting more than 200,000 people worldwide interest in ALBRIOZA remains high in Canada, and we continue to negotiate public insurance coverage consistent with the expected public timelines for coverage. In addition, a few weeks ago, we appointed Masako Nakamura to lead our efforts in Asia Pacific and Latin America, as we pursue additional opportunities to bring AMX0035 to as many people with ALS globally as possible. He brings 30 years of commercial general management and operational leadership experience in the biopharmaceutical industry, with a strong track record of introducing rare disease therapies worldwide across multiple therapeutic areas. We are very pleased that she decided to join our team to further explore opportunities for AMX0035 access around the world.

I will now turn the call over to Josh to provide an important update on our R&D pipeline.

[Josh Cohen, Co-Chief Executive Officer and Co-Founder]

Thanks, Margaret. We're very pleased with how quickly we are bringing our important new treatment to people with ALS. Our top focus day-to-day remains the success of our commercial launches. These efforts enable the continued investment needed to bring RELYVRIO to more people living with ALS worldwide. They also enable the research and development needed to advance our pipeline in support of our mission. There's tremendous scientific interest among the neurodegenerative community to further investigate AMX0035 in other diseases, we have positive randomized clinical trial data and ALS, encouraging biomarker data from the randomized phase two Pegasus study in Alzheimer's disease and a wealth of preclinical models demonstrating the effects of AMX0035 in reducing neuronal death. To prioritize which diseases to focus on, we look at the following criteria.

Clear unmet need, strong scientific rationale, existing and robust understanding of the natural history of disease, biomarkers to track treatment effects, adjacencies and synergies with ALS, potential to move directly into a phase three pivotal study and interest and support from KOLs. We are excited to announce today our plans to initiate a global pivotal phase three study of AMX0035 in Progressive Supranuclear Palsy, or PSP, a disease which meets all of these criteria. For those of you who may not be familiar with PSP, it is a rare progressive and fatal neurodegenerative disorder that affects body movements, walking and balance, speech and swallowing and eye movement. It's typically fatal within just five to eight years. The estimated prevalence is five to seven and 100,000 people worldwide, translating to between roughly 15 to 20,000 people in the United States.

There are currently no disease modifying treatments for PSP. In addition to PSP, meeting our criteria for a significant unmet need with a well characterized natural history there is also a strong scientific rationale for the potential use of AMX0035 in treating PSP. PSP is both a disease of rapid and significant nerve degeneration. And its pathology is characterized by significant tau protein deposition in affected regions of the brain and the Pegasus Alzheimer's study of AMX0035. AMX0035 treatment demonstrated a statistically significant lowering of both phospho tau 181 and total tau in the CSF of people living with Alzheimer's disease. AMX0035 is an oral well tolerated FDA approved medication for ALS that has been shown preclinically to protect neurons against degeneration and clinically to lower tau, the Hallmark protein of PSP. This has led to significant and strong support from key opinion leaders in PSP, and we are excited to work with them to test AMX0035 in a phase three study, which I will now outline.

In designing and planning the study. We have collaborated with key global academic leaders, people living with PSP and advocacy groups working in this field. With an open IND in hand, we plan to enroll approximately 600 people in a randomized placebo controlled study making this likely the largest PSP trial to-date. We expect to have the study up and running by the end of this year. We are hopeful that we can provide a new treatment options, especially since there are currently no disease modifying treatments available for this devastating disease.

While we prepare to launch our pivotal phase three study, we also remain hard at work in Wolfram syndrome. Earlier this year, we announced Helios, a phase two trial studying AMX0035 in Wolfram syndrome. This study is now enrolling participants. Wolfram syndrome is a disease that leads to multi system failure, resulting in blindness, deafness, diabetes, ataxia, nerve degeneration, and often death in early adulthood. Several papers characterize the disease as a prototypical disease, endoplasmic reticulum stress, and as we have discussed in the past, we believe AMX0035 plays a role in reducing the stress. Data on AMX0035, and models of Wolfram syndrome were published in the Journal of Clinical Investigation insight.

We believe this study will provide key data to guide future studies and expect top line results from the study next year. Importantly, we are also investing in new ALS research to continue to transform how the disease is treated. We believe that it is going to take a combination approach targeting multiple cellular pathways implicated in disease pathogenesis to make ALS more and more manageable, and ultimately to find a cure. For this reason, we are investigating other therapies with different or potentially complimentary pathways to treat ALS and other neurodegenerative diseases. This includes an antisense oligonucleotide, called AMX114 that our internal R&D team has developed, IND enabling studies of AMX00114 are underway and progressing well. We continue to expect to build our pipeline, both through internal and external sources.

Before turning the call over to Jim, I wanted to share that Phoenix, our phase three study of AMX0035, and people with ALS, continues to progress as planned. In February, we announced that the study was fully enrolled with 664 participants, a reminder that there will be no interim data readout, and we expect data on the primary outcome and several secondary outcomes in mid 2024. Overall survival data will take another year or more to mature and therefore won't be available until at least mid 2025.

I will now turn the call over to Jim to review our financial results for the first quarter.

[James Frates, Chief Financial Officer]

Thanks, Josh. We're encouraged by the strong interest in demand we continue to see from the ALS community. From a financial point of view, our businesses strong. Net product revenue were $71.4 million for the quarter, compared to net product revenue of $21.9 million for the fourth quarter of 2022 with the vast majority of that revenue from the United States. [indiscernible] net adjustments for approximately 16% and a quarter consistent with our expectations in the 15% to 20% range. Inventory levels at the quarter and we're as expected, with approximately two weeks of inventory in the channel at specialty pharmacies. [indiscernible] were $5.3 million for the quarter and in the range of our expectation as sales volume grows. And for modeling purposes, keep in mind that roughly 10% of the people on RELYVRIO receiving it for free through either our interim access program or patient assistance program. Research and development expenses were $24.2 million for the quarter compared to $21.5 million in the same period in 2022. These costs were primarily driven by our phase three Phoenix study and added personnel as we support our programs.

Starting in the second quarter, we expect R&D expenses will increase as we incur meaningful expenses to initiate our phase three pivotal study in PSP. You should expect R&D expenses increased this year, in a range of $30 million to $40 million per quarter as we move through the remainder of the year. Selling, general administrative expenses or SG&A were $44 million for the quarter compared to $26.3 million for the same period in 2022. We're investing in SG&A to support our strong commercial launch, and expect our spin to settle in around $45 million a quarter for the remainder of the year. Overall, we're very pleased with our results this quarter, including achieving $1.6 million of net income, just two quarters into our [indiscernible].

I want to pause a moment on our overall financial results with the strong demand for RELYVRIO driving near term profitability ahead of our expectations. We want to reiterate our long term financial goals driving top line revenues as RELYVRIO become standard of care, growing profitability for our investors, and investing in a pipeline that has the potential to provide much needed treatments for neurodegenerative diseases. We're well-positioned to build a profitable financially strong organization for the long term. We ended the quarter with cash and short term investments of $345.7 million and 0 debt. We're currently in a position to fund the programs, we discussed it without the need to raise additional capital.

Finally, just a word on guidance. Last quarter, we gave some specific guidance on how the first quarter was going as we reported in Midmark. Since we're still early in the quarter, it's premature to provide a specific range of revenue guidance for the second quarter, or for the full year at this time. The road ahead over the next few quarters is fairly simple execute on the launch, and execute on our call and pipeline development programs. I'm excited about the progress that we've made, and most importantly, our ability to have a positive impact on the lives of so many people living with ALS.

With that, I'll turn the call over to Justin for some closing remarks.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Thanks, Jim. And thank you to everyone for joining us today. We covered a lot of exciting news. Our commercial ramp in the U.S. and Canada is proceeding very well and we will know more on Europe later this year. We're expanding our clinical pipeline into PSP, a market that is likely as large as ALS with a product that has already been shown to have a favorable safety profile and another disease and that has a demonstrated effect on relevant biomarkers. And we achieved our first quarter of profitability in just the second quarter of our commercial launch in the U.S. We remain committed to our goal to help additional people with ALS and other relentlessly progressive neurodegenerative diseases gain access to new therapies.

Now, we'd be happy to take your questions. Operator, please open the call up to Q&A.

[Operator]

We will now begin the question and answer session. [Operator Instructions] The first question comes from [indiscernible] with Bank of America. Please go ahead.

[Unidentified Analyst]

Great. Thanks for taking the question. This is [indiscernible] for Geoff Meacham. So I have two questions, please. The first one is, you mentioned that the rate of pace has moderate somewhat expectations going to perhaps the second quarter. Can you just provide [indiscernible] And my second question just to provide a little more details, we got the parents discussions that you have any kind of what's your expectation for the remainder of the year? Thank you.

[Margaret Olinger, Global Head of Commercial and CCO]

Sure. So this is Margaret, thank you very much for your question. And we continue to be incredibly pleased with our launch today. And more importantly, our ability to bring a new treatment option and hope to the ALS community, especially given that this is the first product to demonstrate in a clinical trial, a statistically significant benefit in both function and survival. So maybe if I could just reiterate a few key points, we ended the quarter with roughly 3000 patients, again, double what we started with at the beginning of the quarter.

And that's about 10% of the 29,000 patients living with ALS. So not surprisingly, our net patient ads can't double forever. So in Q2 we are expecting the number will be lower than what we delivered in Q4 and Q1. I think more importantly, we continue to see significant interest in demand for RELYVRIO both from patients and HCP. And we have a tremendous opportunity for us to grow both in depth and breadth at all the key ALS centers as well as the broader neurology community. And then the second question was on payers and again, we're very pleased with the progress we're making with payers with 50% of the covered lives to date having a published policy, and we expect that to only get better over the first half of the year.

[Unidentified Analyst]

Thank you.

[Operator]

The next question is from Michael [indiscernible] with Evercore. Please go ahead.

[Unidentified Analyst]

Hi, guys, congrats on the quarter. And thanks so much for taking my question. A few for me. The first question, I have a follow up to the previous one, like now that more commercial payers have come on board. And given the fact that you said the rate of net patient ads is beginning to moderate? Could you perhaps provide any updated views on how big this initial bolus of patients could be? And how long it could last before you achieve a steady state trajectory of new starts? That's my first question. And the second one is regarding the phase three finished trial, you mentioned that the OS data is going to take at least a year or more to read out, and that it's a critical endpoint. So if you if we assume conditional approval in the EU based on [indiscernible] and a [indiscernible] on ALS FRS in Phoenix, are you expecting the EMEA to still maintain their conditional approval until the OS data finally comes in? And could there be a scenario when full EU approval could be granted based on just positive ALS, FRS data alone? Thank you.

[Margaret Olinger, Global Head of Commercial and CCO]

Great, thank you. This is Margaret. Again, thanks for your question. Regarding the bolus, it's really too early to tell when the bolus will finish. But what I can say is that we know in Q4 and in Q1, we did see that high level of demand due to the pent up demand that we had. And they were quite frankly, even ahead of our expectations. So we have begun to see the rate and new patient ads moderate. But again, I want to reiterate, we have a tremendous opportunity for growth, because even within the key accounts that we penetrated. And just remind you of some of the metrics, we said 95% of all the key ALS centers have prescribed for at least one patient every account, you see one account, you see one account. It's typical rare disease. So some accounts are highly penetrated. And some accounts have a great deal of room ahead of us to penetrate. And we really have just started to get out into the broader neurology community. So again, we see tremendous growth ahead of us to serve all the remaining patients that are depending on us.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Yes and hi Mike this is Justin. Thanks for the question. So first just sort of baseline for everyone. So we continue to expect an opinion from the CHMP midyear and decision at the earliest in the third quarter. And in the meantime our team is preparing for approval in launch. So, in terms of the Phoenix trial, and how that could affect the conditional approval. So the way that the EMEA So first we won't know if it's a conditional approval or full approval until we get the final decision, but in terms of what our expectations is on a conditional marketing authorization, so the way that that works is that you get approval, but with the condition that you do a follow on study, and in this case, our expectation would be that it would be the Phoenix trial, and then you have to renew that every single year until you meet the condition. So then, the question is will we meet the condition depending on the, the ALS FSR functional results, or the survival results. And that's really up to the regulators. While say high level though, is that if we have a functional benefit if we have a survival benefit, if we have both, it's the best data anyone's seen in ALS. So I think either is a very positive situation, but ultimately, it's up to the CHMP and EMEA.

[Unidentified Analyst]

Thank you.

[Operator]

The next question is from Corinne Jenkins with Goldman Sachs. Please go ahead.

[Corinne Jenkins, Goldman Sachs]

Good afternoon, everyone. Maybe a couple from us, I guess. One with more than 3000 patients now and drug up from the 1300 even understanding that there could be some moderation. How long are you thinking it will take you from here to get to the 10,000 patients, you had set stated as a target for being stable on therapy at steady state. Maybe the second one for me is just given the clinical priorities that will soon be initiated do you expect to maintain profitability through the balance of the year? And then the final one, just could you talk through the rationale of moving straight into a large phase three program in PSP without doing sort of like an earlier stage phase two or otherwise, and help us understand the relevant clinical endpoints for that indication.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Sure Corinne. I will take the first question and then I'll turn it over to Josh and Justin and probably Jim as well. So just we have not provided a timeline on how long it will take us to achieve the 10,000 patients. Our goal of getting to the 10,000 pathway patients really reflects our vision that delivery will become the most commonly used ALS medication so basically standard of care. And we feel that that's very achievable given it is the first product to demonstrate benefit on both function and survival. I will tell you that right now, we are heavily focused on the launch execution with the goal of getting there as quickly as possible, because patients are depending on us.

[Unidentified Company Representative]

And maybe, I will turn over to, yes go ahead Jim. Sorry.

[James Frates, Chief Financial Officer]

Sorry Josh. I will take the next one on profitability. We decided not to guide at this stage Corinne. So that will include also not guiding on profitability, because essentially, obviously, that's guidance. But I think you all can see the math in terms of the hydraulics in our P&L. And as long as we can go revenue faster than we grow expenses, we'll be able to maintain that profitability. I think importantly, for us longer term, it just really highlights the opportunity we have in this business and how unique the ALS market is. And ultimately, I think we have to recognize, it's the needs of the patients that's driving this launch, and the fact of the matter, the data that we have went for livery out. So we're gonna continue to focus on our long term goal is I tried to outline in the prepared remarks, making RELYVRIO the number one ALS therapy, that's first and foremost, driving long term profitability for our investors, right, because that's how we get to be a sustainable business long term. And I think that's also another thing that differentiates us from a lot of other companies out there. We don't need to continue to go back to the market to fund our business because of how well the launch is going, and the interest that we're seeing in the community. But then also we're going to invest in, in our pipeline, because there's a real need in neurodegenerative diseases. And I think we can do all three, which is what makes me so excited to be here at Amylyx at this time. Josh back to you.

[Josh Cohen, Co-Chief Executive Officer and Co-Founder]

Thanks, Jim. And so talking about PSP. So I think the first thing I should share is over the last several years, we've gone through a process internally to try to select those indications that are highest priority for the company. And I outlined some of the things that we look at for that, but most importantly, PSP met all of the criteria that we were looking at for an indication to prioritize as a company and we already have shown in a randomized placebo controlled study data against what is thought to be the primary pathology of progressive supranuclear palsy. And so I think that's part of what's driving our exciting meant, as long as the excitement we're hearing from the KOL and the community about this indication. And just as an add to, there's also some preclinical data that that's also supporting and making us excited here. But I think it's that constellation of factors that makes us really excited to go into this PSP study.

[Unidentified Analyst]

Great, thanks all.

[Operator]

The next question is from Neena Bitritto-Garg with Citi. Please go ahead.

[Neena Bitritto-Garg, Citi]

Yes, thanks for taking my question. And congrats on the update. So just in terms of trying to figure out this bolus, can you talk a little bit about what you're seeing in terms of start forms versus net ads? I'm just curious if you can talk about the trend you're seeing there? And then give us any color on duration of therapy so far, or any dropouts that you're seeing, that'd be great. Thanks.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Yes. So we're not providing any guidance on the number of patients for the quarter again, I'll just go back to, we think our net patient adds, they can't double forever. So we'll be lower in Q2 than we've been able to deliver in Q4, Q1 because we believe that was the initial pent up demand. Again, we don't know, when that bolus will be over. So it's hard for us to really give any guidance on that. In terms of duration of treatment, it's really too early in the launch to give that I mean, the first patients who started on therapy, we're basically at the end of October, beginning of November. So they really haven't been on therapy long enough for us to give, any, any clarification there. In terms of discontinuation rates, that's sort of similar as well. People just haven't been on therapy long enough, I can tell you that the general trends that we're seeing are kind of in law, in line with what we saw with Centaur nothing is, out of line there. And just as a reminder, with Centaur we seen roughly about a 25% discontinuation rate at six months. So, again, patients haven't really been on therapy for six months yet. So we're going to continue to monitor that very closely.

[Neena Bitritto-Garg, Citi]

Got it. That's helpful. Thank you.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

You are welcome.

[Operator]

The next question is [indiscernible] Marc Goodman you are on the podium right now.

[Marc Goodman, SVB Securities]

Hey, sorry, I couldn't hear. Can you talk about the mechanism for 114? And then second, just the data support the Wolfram study. And the reason the rationale for moving there. Thanks.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Sure. So first 114. So 114 is an antisense. oligonucleotide targeting calpain 2 So there's a pathway called valerian degeneration. That's been around since the 1850s, which is the pathway whereby a neuron will destroy its own axon in response to injury or stress. And, that pathway over the last 150 years, the pharmacology has become pretty clear on what proteins need to be activated and otherwise, for that axonal degeneration to occur. And what you'll find digging into the valerian degeneration pathway, is that calpain 2 is one of the key proteins involved in that. And then in addition, there's been preclinical studies with both kind of knock in models and knockout models that have shown that calpain 2 inhibition can be effective in several animal models of ALS.

And then finally, there's a lot of evidence out there linking calpain 2 different ALS biomarkers, including TDP 43. And then turning to Wolfram. So Wolfram, as we said, in the last conference call is a space we've done at least four years of preclinical work together with Washington, Washington University, and Dr. [indiscernible] there. And broadly, those experiments studied both cellular models of the disease, as well as an animal model of the disease. Much of that data is published in the Journal of clinical investigation insight. But broadly, what we saw was some degree of rescue of the phenotype, both in the cellular models as well as in the animal model. So I think that was the data that that got us really excited to go forward there.

[Marc Goodman, SVB Securities]

Thanks.

[Operator]

The next question is from [indiscernible] Securities. Please go ahead.

[Unidentified Analyst]

Hey, good afternoon. Thanks for taking my questions and congratulations on the quarterly results. I've got two questions if I could, first is more commercially related the second pipeline related so on commercial. Do you have any sense in these early days kind of how the drug is being used in patients? And by that, do you have a sense of distribution of its use whether what percent is in monotherapy versus some combination setting versus a potential triple combination? Any thoughts there would be great. And then on the pipeline. I just had a question on the new phase three PSP study. And maybe it's a twofold question. First, in light that, there have been attempts in PSP. In the past, one was with an anti tau antibody. Is it really just the movement on markers that gives you confidence that it'll be able to work in PSP? Is there some other elements? And then maybe the part B of that is, is the strategy more biomarker driven in terms of kind of the momentum we're seeing in the neurodegenerative space? And how FDA seems to be very open and receptive to biomarker driven strategies? Thanks.

[Unidentified Company Representative]

Yes. So I'll take your first question. I would say that regarding the use of whether or not it's mono therapy, or a combination therapy, it's really a broad mix from single use of RELYVRIO to combination therapy with all three available products. And we're really seeing the utilization and a very broad patient population. So we continue to see patients that have been diagnosed with this disease, for many years get prescribed this drug, as well as newly diagnosed patients. And we define newly diagnosed patients and patients who have been diagnosed in the last six months. I would say, from an ease of access perspective, some physicians may start first with really is all and then they'll switch to or add really use all relive re out to really easily, just because again, it could take it was taking up to 30 days last quarter or the in Q1 for a patient to get access to the drug from the time to enrollment on average. Again, again, we expect that to continue to improve as more policies come on board.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

And Greg, thanks for the question on PSP. It's Justin. Yes I mean, first, I would say, I think the PSP community and especially the key opinion leaders are really excited about this. I mean, in RELYVRIO we have an oral, safe drug that's FDA approved for another neurodegenerative disease. And then in terms of the rationale for PSP preclinically, we've shown that AMX0035 protects against neurodegeneration PSP, is a rapidly progressive neurodegenerative disease. And then clinically, we show the very significant reductions in tau in our Alzheimer's study. And while yes, there have been antibodies against how they were unsuccessful in PSP, PSP, it's still a cow apathy. That's the canonical protein associated with it. In terms of the study design, we're not going to get into that today. But I think it's really all of the above that makes us and probably more importantly, the key opinion leaders, so excited about the study and PSP, so we'll continue to share more on that. But we're really excited about starting that study.

[Unidentified Analyst]

Thank you.

[Operator]

The last question comes from Ananda Ghosh with H.C. Wainwright. Please go ahead.

[Ananda Ghosh, H.C. Wainwright]

Hi, guys, congrats on the quarter. I have two questions on PSP. The first one is how similar is PSP with concerning the downstream degeneration pathway. And the second is, we never got to hear about the mechanism with which AMX0035 impacts the tau in your phase two trial, which is sent or do Is there any insights?

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Yes. So maybe first on PSP and ALS and their degenerative pathways. So, I think for both of these diseases, there's still a lot of research into exactly, all of the etiology and pathology. I think our view and the literature, there's a lot of literature on this as well, is that both diseases see significant cell death related to endoplasmic reticulum and mitochondrial related pathways, which is what we developed AMX0035 to target. And then in terms of the pathways, whereby AMX0035, may affect tau. So I think there's a lot of literature on the link between tau and endoplasmic reticulum stress. And so that's something that we've focused on there. But this change in tau we've seen both in preclinical models including ones that are published as well as in our face to Alzheimer's randomized placebo controlled study. So, we feel that that's a pretty robust and, consistent finding.

[Ananda Ghosh, H.C. Wainwright]

Great. Thanks.

[Operator]

Thank you. There are no further questions at this time. I'll turn the call back to Mr. Klee for final comments.

[Justin Klee, Co-Chief Executive Officer and Co-Founder]

Thank you all very much for joining us this afternoon. We covered a lot of exciting news, our commercial ramp in the U.S. and Canada is proceeding really well. We're expanding into another clinical indication, which has a huge unmet need and has a market that is probably likely as large as ALS. And with a product, as we said, that's already been shown to be safe and well tolerated in a neurodegenerative disease, as well as show quite significant reductions in tau. And maybe one other thing we only talked on briefly, but we achieved our first quarter profitability and just the second quarter of commercial launch in the U.S. which we're really excited about. We're a mission driven company. We have many more people to help and many more people to help around the world, both with ALS, and we hope with other neurodegenerative diseases as well. Achieving profitability is what's going to allow us to have a sustainable business to keep moving forward and keep helping more and more people with neurodegenerative diseases. So thank you all very much for joining us and for your support, and we hope you have a great rest of your day.

[Operator]

The conference is now concluded. Thank you for attending today's presentation. You may now disconnect.