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

Thank you guys for joining us. It's a pleasure to have Amylyx management join us. There's a lot to discuss. And I'm looking forward to the discussion, but let me first turn it over to you guys, if you want to kick it off.

Yes. Very happy to -- well, first of all, thanks so much for having us and really excited to get to share with you all. So Justin, Josh, Jim, so the management team here at Amylyx. Amylyx is focused in ending the suffering caused by neurodegenerative diseases. And I think particularly, things are focused right now around RELYVRIO in the U.S., ALBRIOZA in Canada, which is our newly approved treatment for ALS. So this is an exciting time for us. The FDA approval is just September 29. And our team is hard at work, focused on making sure that we deliver for a community that really needs us. The main things right now are everything you would expect at launch, although it's just the early weeks now. So there's only so much we can comment on, but we're encouraged and excited by what we've been hearing from the community. And then we also have our focuses outside the U.S., too, including we expect a decision from EMA in the first half of the year. So definitely exciting times here and excited to dig in with you guys.

Okay. Excellent. Well, let me just cut to the chase and start off with the question that matters. Last week, IMS shows 126 prescriptions on RELYVRIO, and I think I sent you that. And the week prior was 59, meaning if you look at the last 2 to 3 weeks alone, it suggests to me that there's over 200 patients actively getting prescriptions. And this is in the context of an IMS, which has been blocked by you. I think it's very important for all of us to have a good sense for to what extent we can or cannot read into that. And I realize, based on everything I'm seeing online that the launch is going very well. But I also want to make sure we sort of don't misinterpret or read too much into what we should or should not. So maybe let me ask -- let you answer that.

Sure. So I mean, I think, first, as you said, we have a closed pharmacy network where the data is kept internal. So there's no data flow. There's not supposed to be any data flow outside of the pharmacy network. And so we, quite frankly, really don't know where a group like IMS is kind of getting numbers from or otherwise. And so I think we'd advised a lot of caution. These could be surveys they do these could be some other source that they try to pull. But we just -- we really can't -- we'd advice people to be really cautious because it's certainly not or really shouldn't be any data that's coming from our pharmacies.

Got it. So it's an estimate of sorts from IMS. But I think it still leads the question because I know there were a few hundred million patients that were sort of on -- there were a few hundred million patients that were on various programs that you guys were funding coming into the launch, which makes it sound like if IMS is suggesting that there are a couple of hundred patients on therapy right now, that doesn't sound like a stretch. If you really had $400 million, $500 million on compassionate use expanded access and then some of them have rolled over into commercial insurance.

Yes. So I think it's just too early to comment on exact numbers. We haven't even gotten to our first launch quarter yet. I'd say that our focus right now, I think ALS is a tremendously unmet need. And given that the trial that led to the approval was run at many key centers in the U.S. The data was widely published. We had unprecedented 2 FDA advisory committee meetings. I think the data is pretty well known. And I think it's our belief that this may be a really important treatment for people with ALS. So I think really, the focus for us right now is on delivering. It's on all of the operations of getting the treatment to people getting covered, treatment to people, et cetera. Certainly, that means people who are in our expanded access program or other clinical studies, but I think the general community as well.

Okay. I guess maybe what I didn't hear you say, Justin, is whatever number of prescriptions are being picked up, whatever the actual number is, IMS may or may not be right, whatever the number is, is it reasonable to assume that those are all getting reimbursement now? Because I feel like there was also a bridge program in place. So not every prescription was necessarily a paid prescription, which is also an important -- something to keep in mind. Even if IMS is accurate, even if you really have, I don't know, 200 prescriptions being picked up every week, are those -- like can you speak to what percentage are actually paid prescriptions in real world?

Yes. I mean, our program is set up so that free drug is a tool we use when all fails. We really try to get every prescription towards commercial reimbursement and everything like that and go through the appeals process and otherwise rather than -- so I'd say BioMar, we expect free drug to be a very small percent of any prescriptions and everything like that. And it is a tool we use when we need to and when it's compassionately the right thing to do for patients. But we don't expect it to be much of the overall pool.

So if a prescription is being picked up, most likely it's a reimbursed prescription, is that right?

Well, I'd have some caution with that. I mean because first of all, right, Umer, it takes 30 to 45 days for the...

Right. Exactly what I was getting at.

For the prescription to work through the -- and to work through the insurance process, right? First, our team verifies it, then it goes to the SP, when the SP has to verify the prescription, then it gets shipped to the patient. And of course, we get paid when the SP buys inventory from us, but they are keeping a very close track on the number of shipments they have out the door that they're going to get paid for and the inventory that they need to fulfill that. So it is a process. And again, we're only a month into having drug roughly a month and a few days into having drug on the market yet. So that's not even 45 days. And I would also say that the 30 to 45 days we're talking about is an average, right? And so when someone is working through that process, that Josh mentioned, some people with the insurance will cover it and they'll sell through. Others, it will take a little bit of time, and it will take time for an appeal and it may take time for a doctor to doctor call that they sometimes do. And we do want to get through those. And some will be at the point where we do have to give free drug out. So still early days, I think. And it's just hard for us to make conclusions at this point what the ultimate percentages are going to be and how the insurance coverage is actually going to play out. And I know it's hard, but it's the early days here, and we've got interest, which is great and -- but making sure that we can connect what the interest in the top of the funnel means to pay prescriptions coming out the bottom of the funnel, which relates to net sales, which is ultimately important to Wall Street, it's just too early to know exactly what percentages we're going to have.

Okay. Okay. Makes sense. And then in terms of key bottlenecks or key insurance holdbacks, can you point to any of that? Are you seeing like higher rejection rates from certain quarters?

Yes.

I think it's still too early. What I would say is that new drug, everything is going through a medical exception process. But that's very tried and true. I mean all new drugs go through this, whether those are Medicare Part D plans or commercial plans. So I'd say at launch, really, it's a lot of just getting the systems working. I mean some of these insurance providers, they're gigantic organizations and it can sometimes be as simple as they say, "Hey, we've never heard of that drug. Well, refresh your computer, Oh, now we've heard of it. So it's just things like that, that happened at launch, but I'd say too early to see any trends or anything like that. But I'd say the exception process that this is going through is very [indiscernible].

Mike, do you have anything else on the launch?

Yes, I do. Just -- and I have 4 quick ones. When could investors expect that the IMS reporting restriction to be released? Any time frame on that?

Yes. I mean, I think having a close pharmacy network, we do just generally intend to keep the data within that network. So I don't think we have any intention of changing that at this time. But -- and this is not particularly uncommon when you have kind of very -- a closed distribution or a managed kind of distribution network like that. But I don't know, Jim, if you want to add there?

No, just in these cases, at least it's my understanding that some firms will go out and do broader surveys, and we'll see how those surveys, I think, do take a little while for us to understand how they're going to correlate. So again, I think in the early quarters, the first quarter or 2, I would have to say, let's wait and see how these things actually correlate to net sales. And one of the reasons why we're being cautious about metrics, which I know everybody wants is we don't want to give out metrics that don't correlate. And so...

I think what Mike and I are really getting at is when IMS puts up 126 prescriptions, and knowing that there's an IMS block, what everybody wants to at least be aware of, and we don't need to know what the precision. What we want to be aware of is if IMS capture rate is 20% or something, you guys might already be well north of 500 prescriptions a week. And if there's something like that, I think it's sort of generally helpful for investors to know before some massive surprise happens.

Right. And we understand that, and we'll do our best to provide that information. But...

I'd say, for example, even going to our third...

That does sound extreme, right? $500 a week like that sounds like 2,000 prescriptions on a monthly basis sorely into the launch. And people want to avoid that type of capture rate challenge coming out of IMS going from 2 prescriptions to 126 in a blocked IMS.

Well, again, Umer, we're not going to take any -- we could be above that number, we could be below it. We could be spot on that number. So we're just not going to comment on a number that we don't know how IMS got to. So...

Yes. And in terms of informing people like you're saying on our third quarter earnings call, the product was only approved for 1 day in the U.S. in the third quarter. But of course, we know it's on people's minds. And so that's why we wanted to at least give people a sense of how things were going, but it's, again, just being so early to comment on specifics.

Okay. Excellent. So maybe let's move on to a different topic then. Timing of additional trial initiations because I think there's 2 big valuation leverage for you guys, a, how this launch goes. We think it's going very well. I actually think it's a multiple of what IMS that, but I could be wrong. But separately, where -- like I think people are also very curious the odds of market withdrawal or not, and that's partially contingent on not just the ongoing study, but also any additional studies you will initiate. So can you speak to any clinical development program just to study different populations?

Yes. Go ahead, Justin.

No, I was going to say so. One, we do already have ongoing the Canadian neuromuscular disease registry. So this is a registry that we attempt to collect data on people who are on the drug in Canada. And we also had that registry ongoing when we were doing our what's called special access program, it's similar to EAP in the U.S. and Canada. So we are already generating kind of real-world evidence there. I'd say we're still working through our real-world evidence plan for the U.S., but it is an area of active focus.

No randomized trial, it sounds like...

We haven't shared any plans in that regard quite yet. I mean we're continuing to look into if there are important research questions we might want to answer. And if there are, we could do something like that. But I think that we have a lot of confidence in PHOENIX. So I think if we're going to run more studies, it's primarily going to be because there are important research questions to answer, which there might be. But I think that's kind of our lens we're looking through it.

Okay. So maybe let's segue into PHOENIX then. And I'll ask a question which I've never asked you before, which is...

Umer, if you don't mind, too, though, on your point on other indications. I just -- I want to make sure I talk about that briefly because I think it's such an important point. Between our ALS results, and we haven't talked about it that much, but our early phase Alzheimer's biomarker results, where we sell biomarker changes that we think have implications across neurodegenerative diseases. There's tremendous interest from the medical community in trying this treatment in many different neurodegenerative diseases. I think our goal is thinking about how do we prioritize those based on a variety of factors, certainly clinical rationale, but also time to market. So for example, diseases where we can run a single pivotal study and expand to an additional indication, I think, makes a lot of sense. So in 2023, that's going to be one of our high priorities. And I think, as I said, there's really tremendous interest. And if you look across really all of these diseases, they're tremendously on medical needs.

Got it. Makes sense. Phase III PHOENIX trial, first, if you could speak to the recruitment curve.

Yes. We'll probably say we're still very much on track. I think we've guided that we expect the results to be mid-2024. The most recent recruitment number we gave, we don't intend to give recruitment numbers regularly, but the most recent recruitment number we gave was at the AdCom, September 7, which was that we had recruited over 350 patients as of that point and obviously continuing to recruit from there. So again, we remain on track with our goals and data readout goals and everything like that.

Is there an interim possible in this trial?

We don't plan for one. I'd even go further to say almost definitely not in terms of an interim. The reason being that, you pretty quickly get to a point where it just makes a lot more sense to finish the trial rather than kind of split your alpha and all the risks, kind of the data integrity risks that come with an interim, it just makes a lot more sense to finish the trial.

Got it. How is the power rate broken down between ALSFRS and the survival on the primary endpoint?

Yes. So I think that this is -- I'm actually really glad you asked the question because I think this has caused maybe a bit of confusion. So our primary endpoint in the study really is, in effect, plan to be an ALSFSR (sic) [ ALSFRS ] related endpoint. I think what we've heard is that the various regulators want to include some sort of adjustment for mortality, includes some sort of worst case when a patient happens to die on study. So what we're looking into are statistical models that are essentially measuring the ALSFSR but including an adjustment when there's the mortality of that. All that being said, we expect during the main trial period, there would be pretty few mortality events. So we expect this to be a pretty gentle adjustment. So I think you can think about it in kind of all of our modeling of adjusting for mortality versus not adjusting for mortalities that it's a pretty gentle -- you're very unlikely to get a divergent result versus a pure ALSFRS and an adjusted ALSFRS like that.

Got it. Got it. Got it. Got it.

We continue to follow people to look at overall survival as well. So in the same way we did with the CENTAUR study, but we expect that to be at a considerably later time point, the same way we did with CENTAUR.

Okay. Mike, did you have a follow-up?

I have a question. Yes. So Phase III PHOENIX, it's obviously a riskier trial because you're enrolling patients who are further along in their disease. So have you got any subgroup analyses in CENTAUR that could give you some insight into how efficacy may play out in the trial? Like for example, did you analyze patients who were enrolled very shortly after diagnosis compared to patients who enrolled maybe at the 18-month mark or 18-month mark from symptom onset and maybe how these later onset patients who enrolled in CENTAUR, how that could possibly translate to PHOENIX in any way?

Yes. Maybe I'd say first that maybe just first kind of broad thing to say. I actually think CENTAUR was the riskier trial because we didn't have a previous randomized placebo-controlled study going into CENTAUR. But all that aside, talking about PHOENIX specifically, first of all, we look and our statistical modeling suggests that it's pretty incremental or modest difference in inclusion/exclusion criteria. It's not like a sea change or anything like that. So I'd kind of advise people that not to look at it as this is a dramatically different population or something like that. Second, I'd say that it's not necessarily the case that people are further in disease in terms of progression. -- or even necessarily in terms of symptom onset. Both trials are in roller range, right? CENTAUR was less than 18 months from symptom onset. PHOENIX is less than 24, but you're going to get patients across the whole spectrum from very recently diagnosed to less than 24 when you enroll that. We haven't done too much in the way of subgroup analysis for CENTAUR primarily because you get to pretty small numbers and those subgroups might be pretty hard to interpret. But I'd say, by and large, we did do a lot of sensitivity analysis. We've cut the data a lot of ways in CENTAUR and you get a pretty consistent story. So I think we come into PHOENIX with a lot of confidence that we've seen a placebo-controlled benefit, and we're studying a population that, by and large, is quite similar to what we studied in CENTAUR.

One final question for me in the interest of time. Just regarding the European process. So this one comment that raised a couple of eyebrows on the call -- in your earnings call was that the EMA had some remaining major objections to your, I guess, responses from the day 120 listed questions. Should this be concerning? Or any color to offer along those lines?

Our goal there is just to be transparent as I hope people always find us, but this is a very regular part of the process. EMA, their review process is that they identify a whole list of questions and which they think are major objections which are minor, which -- et cetera. And then the review process is you go through those. And if all of the major objections are done, then the drug gets approved. So it's -- again, this is a very regular part of the process. We think we have good answers to address them, and we're on track for the decision in the first half of the year.

Excellent. Umer, anything else?

No. I was just running sensitivities for the quarter. Thank you, guys.

Thanks so much, guys. Appreciate your time.

Thanks so much, guys.

Thanks for having us today. We had a good day.

Excellent. Thank you guys.