Good afternoon. My name is Gary, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amylyx Pharmaceuticals Fourth Quarter and Full Year 2022 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 call over to Lindsey Allen, Head of Investor Relations and Communications. Please proceed.

Good afternoon and thank you for joining us today to discuss our fourth quarter and full year 2022 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 and cash runway. 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.

Thank you, Lindsey, and good afternoon everyone. Our mission is to one day end the suffering caused by ALS and other neurodegenerative diseases. We just celebrated Amylyx's 10th birthday and as we look back we are very proud of the progress we've made towards our mission over those 10 years. 2022 was in many ways the most important year for us with the FDA approval of RELYVRIO for the treatment of adults with ALS in the U.S. following its approval with conditions as ALBRIOZA in Canada. ALS is a relentlessly progressive and universally fatal disease and RELYVRIO is the first approved treatment for ALS to demonstrate both a statistically significant benefit in function in the clinical trials as well as in observed benefit on survival in the longer term post hoc analyses. We believe our therapy represents a meaningful advancement in treatment options for people living with ALS. Since the approval, we have seen strong interest in RELYVRIO and we are encouraged by the early success of our commercial launch. We are very proud of our teams for the way they have partnered with the ALS community and for the great progress they have made towards our goal of delivering RELYVRIO to every eligible person in the U.S. and Canada. But this is also just the start and all of us at Amylyx remain steadfast and committed to the work ahead in our commercial launches and as we work to transform what it means to be diagnosed with ALS. I will now pass to Jim to review our fourth quarter financial results and then to Margaret to share insights on our launch.

Thanks Justin. We're pleased to share that at this point in our launch we're meaningfully ahead of our expectations and encouraged by the interest and demand we've seen from the ALS community. Margaret will share some of the important early metrics that we're tracking, which should help you model our near-term opportunity and the total addressable market for the longer term, but first I'll summarize Q4. Net product revenues were $21.9 million for the quarter and $22.2 million for the year with the vast majority of that revenue from the United States. As you'll hear from Margaret in a few minutes, we're seeing robust demand from the ALS community. Gross-to-net adjustments were approximately 18% in the quarter and in-line with our expectations. We expect gross-to-net to remain in the 15% to 20% range for the year starting at the higher end of that range in Q1 due to the annual reset of co-pays and deductibles in Medicare Part D reenrollment as of January 1st. Inventory levels at December 31, were where we would have expected with roughly $7 million of inventory in the channel at specialty pharmacies. This represented approximately two weeks of sales at our year end run rate which we see is typical for a product launch at this point. Cost to sales were $2.8 million for the quarter. This is slightly higher than we expect for 2023 as a whole as a percentage of revenues given the royalty accruals we made during the quarter. We expect our ALS royalty obligations to be fully expensed in the second quarter of this year and we have no future royalties for sales in ALS going forward. Research and development expenses were $22.8 million for the quarter, compared to $13.4 million for the same period in 2021 and $24.9 million in…

Great, thanks Jim. Today, we are focused on three key priorities for our U.S. launch. The first is our effort to drive awareness and education about RELYVRIO for people living with ALS and clinicians. This includes educating that RELYVRIO is the first approved drug for ALS to demonstrate a statistically significant benefit and function in a clinical trial as well as an observed benefit on survival in a longer-term post hoc analysis, as well as sharing publications on supporting clinical data such as a peer-reviewed publication in the New England Journal of Medicine. Our second priority is engaging with payers to work towards our goal of ensuring that every eligible person who can benefit from RELYVRIO treatment has access as quickly and efficiently as possible. The third is ensuring that 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 for people enrolled in the Amylyx Care Team Support program helping navigate the insurance process, being able to field questions, and optimizing peoples experience as best we can. Now let's run through a few specific details to help illustrate the progress we are making on each of these focus areas. Starting with our first priority of ensuring broad awareness of RELYVRIO, we are seeing our efforts yield strong results and have observed rapid uptakes on the FDA's approval on September 29. There were just over 1300 people living with ALS on RELYVRIO in the United States at the end of 2022, and uptake has continued since then. We remain optimistic about our ability to continue growing from here as we believe people with ALS and their clinicians are eager to learn about and try new treatment options. By the end of this…

Thanks, Margaret. I would also like to provide an update on where we see ourselves headed in the coming years in the United States and then provide updates on Europe, PHOENIX, and our new program in Wolfram syndrome. Starting with our current view of the addressable market, there are approximately 29,000 people living with ALS in the United States. Given the relentless and fatal nature of ALS disease progression and recognizing that not everyone will be interested in treatment, our hope is that eventually at least 10,000 people will be RELYVRIO at any point in time. Shifting to Europe, as expected we completed the SAG meeting last month. Certain major objections remain, and the CHMP has adopted another round of questions for us to respond to. We have those in hand, and due to this additional round of questions, we now 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 community and a capable team leading our process. While the review process is ongoing, we continue to prepare to execute a successful launch in Europe if approved. Now I would like to share some updates on PHOENIX. Last month, we announced that the study was fully enrolled with 664 participants, which compares to 137 in CENTAUR. As you may recall, our goal was to include 600 participants in Phoenix, and we ended up enrolling more due to high demand. PHOENIX is studying a similar group to CENTAUR with slightly broader inclusion and exclusion criteria. We have stratified PHOENIX based on whether people would meet the CENTAUR inclusion criteria or not, and plan to analyze the subset of participants who strictly meet the CENTAUR criteria, as well as the broader…

These studies have very promising results, some of which were recently published in the Journal of Clinical Investigation Insight. At this time, we are close to kicking off a Phase 2 study at WashU. This study is a 12-participant open-label study, which we believe will provide key insights to guide future studies directed at registration. At this point, our IND is open and Dr. Urano's site is activated and will hopefully enroll the first participant in the near-term. I'll now turn the call over to Justin for a few closing remarks.

Thank you, Josh. In parallel to all of the progress that we outlined on our call today, we are continuing to strengthen the breadth of our team's collective experience and perspectives. We are pleased to share that we recently appointed Karen Firestone to our Board of Directors effective March 16. Prior to co-founding Aureus Asset Management, Karen spent 22 years at Fidelity where among other responsibilities, she managed the Biotechnology Sector Fund. She has a demonstrated track record of applying her strategic acumen and commercial mindset to drive progress in this space, and we look forward to her counsel as we continue working toward our mission. In closing, we take our responsibility to make a difference in the lives of people with ALS very seriously. We are proud of the progress we have made to date and the fact that we are helping more than 1000 people and their families in their battles with ALS. There remains much work to do and we are focused on ensuring quick and efficient access to RELYVRIO for every eligible person who can benefit from it. Thank you all for your support and for your time today. Now, we'd be happy to take your questions. Operator, please open the call to Q&A.

[Operator Instructions] The first question is from Geoff Meacham with Bank of America. Please go ahead.

Good afternoon, guys. Thanks so much for the question. I just had one on commercial and then a quick one on Europe. In the U.S. you mentioned the centers that are responsible for the book of scripts, just want to get a sense as to the inquiries or the queue of patients across the broader ALS population. I'm just trying to get a sense of the breadth of awareness on whatever metric you guys can provide. And then on the European market, I know you probably can't get into specifics, but can you, can the questions that you've gotten be addressed with current data you think or longer follow up, or is it fair to say that you may have to wait till the PHOENIX study? I'm just trying to get a sense whether there's a, maybe a middle scenario with a more narrow label that you can still provide some limited EU access in the next say, 12 months or so. Thank you very much.

Thanks, Geoff. I could take your question on the U.S. market first and then I could turn it over to Josh and Justin on the EU. So as I mentioned, there's about 2700 physicians that prescribe for ALS, which is our broad target audience. During the first quarter, we are heavily focused on the top ALS centers and the top 500 prescribers of which 55% of them have written a prescription for RELYVRIO in the fourth quarter. So that continues to be our focus. There's a lot of opportunity that remains in those top prescribers, but also a lot of patients are being seen by the general neurologists out in the communities, and that's clearly our next runway that we have to continue to penetrate this market much more broadly than we have to date.

Yes, and I'll add on Europe. So first I'd say as you've seen in the U.S. and Canada, I think we have a really good case here. This drug has been approved twice and we have a team that's very used to making strong scientific arguments here. So what I'd say is, I think we have the right scientific arguments to make to support the approval of this product, but ultimately the decision is up to regulators. So I guess we'll have to wait and see, but I think we have all the right pieces in place to continue forward.

Okay, great. Thanks so much.

The next question is from Umer Raffat with Evercore ISI. Please go ahead.

Hi guys. Thanks for taking my question and congrats on the launch. By my math, I feel like you will either be at or fairly close to breakeven in 1Q. Could you please comment on that? And could you give me a sense for whether the patient numbers at the end of December, not as of now, but at the end of December was approaching about 1500 to 2000, if you could clarify that? And then finally how much inventory was in the 4Q number that we just saw? Thank you very much.

Yes, hey Umer, it's Jim. I'll start with that maybe in reverse order. So we did mention there's about $7 million in inventory at the end of Q4 and that represented about two weeks at the run rate that we were at. So and we think that's appropriate for where we were in the launch. The first question I know was about when we're going to hit breakeven. I think that right now it's still just really too early to tell, right? We're only four months into launch. I think a lot will depend obviously on what we spend and versus the revenue that we pull in. But more specifically, I think as we're seeing the demand increase, right? And again, Margaret mentioned there were 1300 patients on drug at the end of 12/31 and at the end of Q4, and we're looking at roughly doubling that as we get to the end of March, so 2,600 patients plus or minus. I think that one does have to be careful though, right? Because all those patients don't come on at once, right? As they come on through the quarter we might get one month of revenue, we might get three months of revenue depending on when the patient started. And just as a reminder as well, we start for the first three weeks with a single dose of single sachet of product and we move two sachets a day for the remainder, the remaining 11 months of the year. So just be careful as you extrapolate revenue there. And I think I guess I would just say, we're off to a really good launch. I think we're probably going to be able to more than double our revenues in Q1. I'd say we'd be closer to tripling our revenues than we are to doubling our revenues, but wouldn't want to give more guidance than that.

Thank you.

You're welcome.

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

Hey guys, congrats on the quarter and thanks for taking my question. Just kind of following up a little bit on the last question, just thinking about the pace of starts, and it seems like there was a little bit of a warehousing effect as you expected in fourth quarter, but just trying to get a sense for how we think about the pace of starts after Q1. Do you expect this kind of 1300 patients per quarter to be kind of a sustainable rate or should we expect the pace of new starts to kind of start to decline thereafter? And then just on the PHOENIX commentary, should we, I mean, how should we think about, kind of next steps post the PHOENIX top line? I mean, it sounds like you're kind of guiding us to expect a decision on kind of the long-term kind of commercial status of RELYVRIO based more off of overall survival data, but just wanted to clarify if I heard that correctly. Thanks.

So yes, Neena, thank you so much for the question and I'll start, this is Margaret. So we just want to reiterate, we are very pleased with the growth we're seeing in the second, in Q4 of 2022 and so far this year. And we are -- and things are going really well. We're seeing an initial bolus in demand. And to be honest with you, we just don't know how big this bolus will be or how long it will last. But we expect continued growth and interest in demand as the initial prescribing has been relatively concentrated as I mentioned. We have a large untapped opportunity to build on in our ongoing outreach and education and efforts. We really see that we have a lot of runway ahead of us.

Yes, thanks Margaret. And just adding, so I think survival is definitely a key endpoint in ALS. I think it's just a biological reality, but it takes a while for survival events to accrue, so I want to be really upfront about that. But I wanted to come back to we're really confident in the trial design and execution. We're really looking forward to this data. I'll say personally, I can't wait to unveil the PHOENIX data when we have that next year.

Yes, and just one more point, as Margaret emphasized the demand, I think that's on the plus side, right? We're seeing early demand. It's very concentrated so far so we have a lot of breadth and depth to continue to look forward to, I think as we expand this product. On the other hand though, insurance coverage is still something that is not complete yet, and I don't believe it's going to be appropriate to make an estimate about what our future demand is going to look like until we get fully closer to 100% of the insurance decisions being made. And again, as Margaret mentioned, at this point, we're about a third of the way through that. So I think it's too early for us to really know what that demand curve is going to look like Neena, again, how big and how long that bolus might last until we really understand what the full breadth of coverage is. It's going well so far, but we're only a third of the way through.

Got it. That's super helpful. Thank you.

You're welcome.

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

Yes, good afternoon and congratulations on the quarter, guys. Maybe to start, just in terms of the EMA questions, I know you shared a bit already, but can you just provide a little more clarity? Are these questions that you could answer with data that you currently have on hand or is there any risk that you might have to generate additional data to sufficiently answer those?

Yes, I think, the question as always with any regulator is what we have sufficient or is more data needed. I'd say, this drug has already been approved by two regulators. I think we have clear and strong scientific arguments to support the approval of this drug, but of course the regular has to decide that too. So we're still going through the process. We’re still going through the back and forth, so it’s too early to know what the decision will be. But I think we have the right team and the right arguments to continue moving forward through the process.

Yes and Corinne, I’ll just add to that. In the EMA, while we don’t know yet, our anticipation is that this may be a conditional marketing authorization and the conditioning marketing authorization the condition would likely be completion of the PHOENIX trial. So I think that’s an important part of your question, too.

Yes, that’s really helpful. And then you mentioned 10,000 patients on drug target kind of steady state. And in the past, we’ve talked about what the launch curve might look like with an initial bolus and then steadying out until we get to steady state. How are you thinking about it now that you’re in the market and seeing kind of the demand that you’ve had thus far?

Yes. So we’re very excited about the opportunity in the long-term to hopefully be able to treat 10,000 patients at any given time. As you know, there’s 29,000 ALS patients suffering with this disease. Some patients we know will not be able to, just unfortunately, due to the natural progression of the disease, be able to access treatment to the drug. But we do know that really is all today is roughly 9,000, but the range is anywhere from 8,000 to 11,000. So we do have a goal and aspiration to become standard of care with the first drug to really have function plus survival on the long-term post hoc analysis. So that’s sort of our goal and aspiration and we feel confident that we can meet that goal. How long it will take us to get to that point? I think it’s way too early in the launch to see that. And then just in terms of the slope of the ramp, to your point, it is very early months of the launch, but we are seeing very encouraged levels of interest from both people living with ALS and clinicians and we said that Q4, we ended with 13 [Later changed by the Company to "1300"] people on therapy. We expect to double that by the end of Q1. And again, I just want to reiterate to everybody that is on a net basis, which should give you a good sense of how the launch is progressing. And while we do have that initial bolus of demand, we don’t know how big and how long that will last, we do really are very confident in the long runway we have ahead of us. So our focus remains on the 1,300 patients that are on therapy today and keeping them on therapy. And then also, we’re very encouraged by the insurance favorability that we’re seeing, while it’s only a third at this point we have very broad access to date, and we’re encouraged at the future.

Okay, thanks.

The next question is from Marc Goodman with SVB Securities. Please go ahead.

Yes. Hi, there’s a lot of conversation about the PHOENIX study. I was just making sure I understand, just to be clear. When you make a decision on whether the PHOENIX study is successful or not, would you be waiting for the survival data to actually make that determination? Thanks.

Yes. I think what we’ve said and I think what’s the case is, we’re going to do what’s best for patients. I’m really, really excited about the data that we’re going to unveil. And as the data comes in, we’ll make the appropriate decisions in collaboration with the ALS community. But again, we have a lot of confidence in the trial design and the execution here and we’re really excited to unveil those results next year.

Yes. And Marc, just going further to your point, too, it’s Justin. So first, we measure function at 48 weeks, and then we will measure survival. These are really key endpoints for people living with ALS. They are really key end points for doctors and the care team who look after people with ALS. It’s also what we saw in the CENTAUR study. So the study design and the data that we’re collecting are based off of both what we saw in the first study as well as what’s important to the ALS community.

Right? And what you’re saying is survival is very important to the ALS community. So you’re going to need to see that data to really understand what you don’t have.

It’s certainly a critical endpoint.

Okay, thanks.

And our last question today comes from Ananda Ghosh with H.C. Wainwright. Please go ahead.

Hey, hi guys. Thanks and congrats for the quarter. On behalf of Andrew, I just had one question, like even post approval, there were questions on Phase 2 data and potential positive Phase 3 data. Now what has been the feedback as you have been negotiating with the peers, especially in terms of the data?

Yes. So I think the question relates to how payers have asked about ongoing studies and ongoing data. I’d say, thus far, we’ve seen broad and really good coverage from the payers. Of course, we’re only third of the way through. It’s only a third of payers have released their policies. But thus far, the engagement has been great, and we’ve been, the vast majority have had broad coverage policies that we’re very happy with.

And I would just add to that, that we have a really strong payer and medical affairs team that are having ongoing discussions with the clinical teams and I think these payers are really understanding just how devastating this disease is and more broadly, our payer interactions today have been highly encouraging.

Great, thanks.

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

Thank you, operator. We are proud of the progress we’ve made to date and encouraged by the early success of our commercial launch. We remain focused on the work ahead to pursue our goal of delivering RELYVRIO to every eligible person living with ALS. Thank you all for joining us and thank you for joining the call. Have a good evening.

The conference has now concluded. Thank you for attending today’s presentation. You may now disconnect.