Amylyx Pharmaceuticals Q1 2025 Earnings Call Transcript

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May 8, 2025
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Operator

One. Good morning. My name is Min, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amelix Pharmaceuticals First Quarter Earnings Conference Call. All participants will be in listen only mode.

Operator

After today's presentation, there will be an opportunity to ask questions. To ask a question, please press star one on your telephone keypad. To withdraw your question, please press star two. Please limit your questions to one with one follow-up. If you have additional questions, you may rejoin the queue.

Operator

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, Vice President, Investor Relations and Communications. Please proceed. Good morning, and thank you all for joining us today to discuss our first quarter twenty twenty five financial results and business update. With me on the call today are Josh Cohen and Justin Klee, our co CEOs Doctor.

Operator

Camille Redrozian, our Chief Medical 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 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 vexatide, AMX thirty five, and AMX one hundred fourteen, statements regarding regulatory and clinical developments, the impact thereof and the expected timing thereof, and statements regarding our cash runway. Actual events and results could differ materially from those expressed or implied by any forward looking statements. You are cautioned not to place any undue reliance on these forward looking statements and Amalex disclaims any obligation to update such statements unless required by law.

Operator

Now I will turn the call over to Justin.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Good morning, and thank you all for joining us. 2025 is an important year of execution at Amelix as we advance three potential therapies across four clinical trials, each targeting diseases with high unmet need. Already this year, we've achieved several meaningful milestones. Last month, we dosed the first participant in our pivotal Phase III lucidity clinical trial of vevecetide in post bariatric hypoglycemia or PBH. We also dosed the first participant in our Phase I LUMINA clinical trial of AMX-one hundred fourteen in ALS.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

In addition, we strengthened our financial position by raising approximately $65,500,000 at the start of the first quarter, which extends our anticipated cash runway through the end of twenty twenty six. Now, I'd like to briefly walk through each of our programs. Starting with our lead asset, Avexatide, an investigational GLP-one receptor antagonist with FDA breakthrough therapy designation for post bariatric hypoglycemia. PBH is a chronic and often progressive condition that affects approximately one hundred and sixty thousand people in The United States. However, there are no approved treatment options.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

We believe vexatide has the potential to fill that gap. We are encouraged by the level of engagement from the clinical trial sites participating in our pivotal Phase III lucidity trial. We continue to expect enrollment completion in 2025 and top line data in the first half of twenty twenty six. In addition, we are preparing diligently to be launch ready, and if approved, we anticipate a commercial launch in 2027. Later during the call, Camille will share more details about Avexatide and the Lucidity trial.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Turning to AMX-thirty five, which is an oral small molecule therapy designed to target endoplasmic reticulum, or ER, stress and mitochondrial dysfunction. AMX-thirty five is currently being evaluated in Wolfram syndrome and progressive supranuclear palsy, or PSP. Wolfram syndrome is a monogenic progressive neurodegenerative disorder with premature mortality and no approved treatment options. This disorder is caused by mutations in the WFS1 gene. The WFS1 gene encodes a protein called Wolframin that spans the membrane of the endoplasmic reticulum, and mutations in Wolframin directly cause ER stress and mitochondrial dysfunction.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

We believe AMX-thirty five has the potential to address the urgent unmet need for the approximately three thousand people living with Wolfram syndrome in The United States. Last year, we reported positive top line data from the 12 person Phase II open label HELIOS trial in adults with Wolfram syndrome. Participants showed improvement or stabilization across all measured outcomes at week twenty four. In addition, longer term data for the subset participants who had reached treatment through week forty eight showed sustained improvement over time. We continue to follow participants in the HELIOS trial and plan to present full week forty eight data at the upcoming Joint Congress of the European Society for Pediatric Endocrinology and the European Society of Endocrinology, which is this coming weekend.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

The poster will be made available on the presentations page of our website next Monday. And those findings, along with our ongoing discussions with the FDA, will inform the design of a Phase III trial. Now, I'd like to turn to AMX-thirty five as a potential treatment for progressive supranuclear palsy. TSP is a rare, progressive, and fatal neurodegenerative disease that affects an estimated twenty three thousand people in The U. S.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

And has no currently approved treatments. TSP is a tauopathy, which is defined by the buildup of tau protein in the brain. Based on its prior effect in reducing tau in cerebrospinal fluid in people with Alzheimer's disease, we believe AMX-thirty five is the first brain and self penetrant agent that has demonstrated a significant tau reduction in CSF to be tested in TSP. We completed enrollment in the Phase 2b portion of the ORION trial in January of this year, with a total of 139 participants randomized. We expect to report data in the third quarter of this year.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Those results will guide our decision about whether to advance into the Phase three portion of the trial. Next in our pipeline is AMX-one 14, our investigational antisense oligonucleotide targeting knockdown of CALPN-two for the potential treatment of ALS. This is a novel program built on decades of academic research linking the protease calpane-two to axonal degeneration, an early and destructive driver of ALS progression. In preclinical studies, AMX-one hundred fourteen showed potent and durable reductions in calpane-two levels, improved neuron survival, and reduced neurofilament light chain levels, a well established biomarker of axonal degeneration. We're excited to have dosed the first participant in our Phase one LUMINA trial last month.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

LUMINA is a multinational, randomized, double blind, placebo controlled, multiple ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX-one hundred fourteen in people living with ALS. We look forward to early cohort data from LUMINA later this year. With strong scientific rationale, clinical momentum, and a clear path ahead, we believe we're well positioned to execute across our clinical programs. With that, I'll now turn the call over to Camille to share more about the LUCIDITY trial and our work with Avexatide.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Thanks, Justin. We are very excited about the potential of Avexatide, our investigational GLP-one receptor antagonist. The GLP-one receptor, a mediator of important, well characterized biology, is an effective target to modulate this biology. The GLP-one receptor is one of the key regulators of insulin and glucose. Unlike GLP-one agonists, which increase insulin secretion, a GLP-one receptor antagonist decreases insulin secretion and therefore stabilizes blood glucose levels.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Avexatide has shown promise to treat post bariatric hypoglycemia, and as a result has FDA breakthrough therapy designation. Last month, we dosed the first participant in the sixteen week randomized double blind placebo controlled phase three lucidity clinical trial evaluating Avexatide in approximately seventy five individuals with PBH following Roux en Y gastric bypass surgery. Lucidity is designed to have similar inclusion and exclusion criteria to the previous successful phase two PREVENT and phase 2B trials of Avexatide in PBH. In addition, Lucidity is evaluating the FDA agreed upon primary outcome of reduction in the composite of level two and level three hypoglycemic events through week sixteen. PBH is a debilitating condition believed to result from an excessive GLP-one response following bariatric surgery.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

PBH manifests as persistent, recurrent, and debilitating hypoglycemic events that can impose a life altering and enduring burden on a person's health, independence, and ability to engage in everyday life. On average, the symptoms appear approximately one to three years following bariatric surgery. Once people have PBH, the condition is chronic and often progressive. We estimate, based on our projections from data and published literature and claims based work, that there are about one hundred and sixty thousand people in The US who are living with PVH today. Additionally, bariatric surgery remains the standard of care for addressing obesity, particularly for people who require substantial and sustained weight loss.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Therefore, we believe the unmet need in PBH will continue to grow. A few weeks ago, the American Society for Metabolic and Bariatric Surgery, or ASMBS, published new 2023 surgery data. The results estimate that approximately two hundred and seventy thousand new bariatric surgery procedures occurred in 2023 in The US, including two hundred and twenty thousand of the two most common surgical types, Roux en Y gastric bypass surgery and sleeve gastrectomy. There was a slight uptick in roll on y gastric bypass and a slight downtick in sleeve. Overall, there was little or no significant change in the procedure trends from the prior year.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Importantly, we believe that the biology of PBH is the same regardless of the type of bariatric surgery patients receive. And despite dietary modifications, rescue measures such as glucagon, and off label drugs, many people with PBH continue to experience persistent symptoms and hypoglycemic events with no sustainable management options. Furthermore, there are no approved treatments for PBH, and the current options used off label generally are inadequate for this condition. The LUCIDITY trial is intended to build on the robust body of data generated to date for Avexatide, which includes five clinical trials demonstrating consistent dose dependent effects, including statistically significant and clinically meaningful reductions in hypoglycemic events. In the phase 2b trial, a once daily ninety milligram dose of Avexatide led to a 53% reduction in level two hypoglycemic events with a p value of 0.004, and a 66% reduction in level three hypoglycemic events with a p value of three.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Avexatide was generally well tolerated with a favorable safety profile replicated across the clinical trial. Ninety milligrams once daily of Avexatide, the dose we are evaluating in lucidity, also demonstrated a favorable pharmacokinetic profile, maintaining exposure in the therapeutic range through twenty four hours, supporting daily dosing. This characteristic translated to similar meaningful improvements in nadir glucose levels as measured by continuous glucose monitoring both during the day and overnight. We are excited to present additional analyses of the avexatide phase two and phase 2b studies at ENDO twenty twenty five in July. These presentations will include new population PK and PD data supporting sustained effects at the ninety milligram once daily dose regimen, as well as the composite rate of level two and level three hypoglycemic events.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

We are encouraged by the engagement from the clinical trial sites and continue to expect to complete recruitment by the end of twenty twenty five. We are grateful to our trial participants, investigators, and collaborators who inspire and guide our work each day. Now I'll turn over the call to Jim to discuss the financial highlights from the quarter. Jim?

James Frates
James Frates
Chief Financial Officer at Amylyx Pharmaceuticals

Thanks, Camille. We believe we're well positioned to achieve our goals. We ended the first quarter with a cash position of $204,100,000 which includes approximately $65,500,000 in net proceeds from our public offering, closed in January of this year. We believe we have the necessary cash to deliver our planned clinical milestones through the end of twenty twenty six. These milestones are top line data from the Phase III lucidity trial of Avexatide in PBH, week 48 data from the ongoing HELIOS trial in Wolfram syndrome, top line data from the Phase IIb portion of the Orion trial in PSP, and Phase I data from our LUMINA trial of AMX114 in ALS.

James Frates
James Frates
Chief Financial Officer at Amylyx Pharmaceuticals

In addition, our cash supports the advancement of our commercial preparations for the potential first to market launch of lebexatide in PVH. So let's turn to our results. Total operating expenses for the quarter were $37,800,000 down 82% from the same period in 2024. Research and development expenses were $22,100,000 compared to $36,600,000 in Q1 twenty twenty four, primarily due to a decrease in spending on AMX-thirty five for the treatment of ALS, a decrease in payroll and personnel related costs, and in preclinical development activities. Selling, general and administrative expenses were $15,700,000 compared to $57,800,000 in Q1 twenty twenty four, primarily due to a decrease in payroll and personnel related costs, and a decrease in consulting, professional and other services.

James Frates
James Frates
Chief Financial Officer at Amylyx Pharmaceuticals

We recognized $6,800,000 of non cash stock based compensation expense for the quarter, compared to $9,900,000 of non cash stock based compensation expense in Q1 twenty twenty four. We also used roughly $6,000,000 in cash related to product rebates and the settlement of purchase commitments for Amex 35 that were established prior to the voluntary discontinuation of sales of Relivrio and Albreoza in April of twenty twenty four. We recorded $1,400,000 of expense in the first quarter of twenty twenty five related to these payments, with the remaining expense recorded in prior periods. Going forward, the residual cash obligations related to the discontinuation of Relivrio and Albreosa are $3,100,000 which we expect will be paid through the remainder of 2025. We're pleased with our cash position as we progress through the year, and we're reiterating our expected cash runway through the end of twenty twenty six.

James Frates
James Frates
Chief Financial Officer at Amylyx Pharmaceuticals

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

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

Thank you, Jim. As we look ahead, we remain grounded in our mission to develop novel therapies for diseases with high unmet needs. We are focused right now on strong execution across our four clinical trials, each targeting serious neurodegenerative or endocrine disorders. In the coming days, we are excited to share week 48 data from our HELIOS trial in Wolfran syndrome. And in the third quarter, we look forward to sharing unblinded Phase 2b data from the ORION trial in PSP.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

By the end of the year, we also expect early cohort data from the Phase one LUMINA trial of AMX114 in people living with ALS. And in the first half of next year, we expect top line data from the Phase three LUCIDI trial of Avexatide in PBH. We continue to believe we have the necessary cash to advance our pipeline and to support commercial preparations for the potential first to market launch of vexatide and PBH. Thank you for your continued interest and we look forward to keeping you updated on our progress. Now I would like to open the call up for questions.

Operator

We will now begin the Q and A session. To ask a question, please press star 1 on your telephone keypad. To withdraw your question, please press star 2. Please limit your questions to one with one follow-up. If you have additional questions, you may rejoin the queue.

Operator

At this time, we will pause momentarily to assemble our roster. Your first question comes from Michael DeFeore of Evercore ISI. Please go ahead.

Michael Difiore
Managing Director at Evercore

Thanks for taking my question and congrats on all the progress. Just two for me. One on adexatide. Your recent commentary on adexatide for PBH suggests that a large patient education campaign will be required. The question is, is this because the eight percent of symptomatic patients don't necessarily know they have PBH or will these educational efforts attempt to shore up and penetrate into less symptomatic patients?

Michael Difiore
Managing Director at Evercore

I have a follow-up.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Yeah, thanks Mike. Good and important question. So, I would say PBH, certainly among adult endocrinologists and sadly among people who are suffering with PBH is pretty well known including the signs and symptoms. You know, I think sometimes it can be a bit of a connecting the dots because oftentimes PBH takes years, on average one to three years following a bariatric surgery to manifest. But adult endocrinologists, when they can pretty clearly recognize the signs and symptoms of hypoglycemia.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

And then, of course, once they actually do testing in the clinic on blood glucose, then it becomes very clear, as well as at home measures as like finger stick blood glucose and CGM. So, I think it's certainly well recognized. And unfortunately, you know, it's quite a severe condition as well. People can have such severe events as sudden loss of consciousness or even seizures. And these are happening on a reasonably frequent basis.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

I think when we talk about the education, it's because this is kind of classic rare disease. There have not been treatments before for PBH. And I think as we find with many rare diseases, there are many unmet needs throughout the community. So, we see it as really our job to make sure that we're educating the medical educating advocacy and people living with TBH. And then hopefully if abexatide is approved, them on the potential benefits of abexatide as well.

Michael Difiore
Managing Director at Evercore

Very helpful. My second question is on PSP. I just wanted as we head into the interim data, I just want to confirm the efficacy bogey on the PSP rating scale that we should be looking for in the interim. Just given that the placebo group in many prior PSP trials declined by 10 or 11 points over fifty two weeks, should we expect roughly half of that in placebo? Furthermore, sources say that the minimally clinically meaningful difference on the PSP rating scale over six months is around six points.

Michael Difiore
Managing Director at Evercore

So taken together, should we expect maybe a flat to a one point improvement in the drug treated arm? Thank you.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

Sure. Maybe first on the efficacy, Bobbi. So this study has about 80% power to detect a 30% effect on the PSP rating scale. And I'd say the PSP rating scale is a primary endpoint, certainly going to be one of the main things we look at. But we do have other secondary endpoints and markers as well.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

So ultimately, our decision on the next steps for the program will be driven by all the data, not just the PSPRS. I'd say PSP has only had so much work in terms of clinical meaningfulness. We have assembled some doctors and spoken to them as well. And we've heard everything from a single point difference could be clinically meaningful. We've heard differences such as 20% or 30% change.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

And I think it maybe bears in mind to discuss what is actually happening in this disease. This is a disease that often has survival of six years, sometimes even less. And during that time, these patients almost in a way reminiscent of ALS become eventually locked in. They'll have progressive motor impairment, progressive walking impairment, speech and swallowing difficulties. So the ability to make that go a meaningful percentage slower, I think our view and certainly many of the KOLs view we've spoken to would be highly meaningful.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

So I won't put a specific line on it. We're going to look at all the data as it comes. But maybe just remind we're 80% powered to see a 30% effect.

Michael Difiore
Managing Director at Evercore

Very helpful. Thank you.

Operator

Your next question comes from Mark Goodman of Leerink. Please go ahead.

Basma Radwan
Vice President at Leerink Partners

Hi. Good morning. Thank you for taking our question. This is Basma on for Mark. We had a question on PBH regarding the prevalent population of 160,000 patients.

Basma Radwan
Vice President at Leerink Partners

Remind me again how many are seeking treatment. So this is basically a follow-up question to the previous one. So are all of these patients again are symptomatic? And also if you can provide any color on new incidents. We know that like two hundred thousand to three hundred thousand surgeries per year.

Basma Radwan
Vice President at Leerink Partners

Should we still assume that eight percent of the patient who undergo these surgery will eventually develop PBH in like three to four years timeframe, or should we assume something else? Thank you very much.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Yeah, thank you for the great questions on the TBH population. So, starting with your first question on the one hundred and sixty thousand, are those people seeking treatment? I'd actually say there's a larger group seeking treatment. And I can walk you through that. If you look at the number of people who have hypoglycemia following bariatric surgery, you know, in any form and any frequency, it's as high as thirty percent, forty percent, fifty percent of the population depending on the methodology you use.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Now, with hypoglycemia following bariatric surgery are counseled to use medical nutrition therapy, sometimes off label prescriptions like a carbosertide. So that, if you look at just even over the past decade of people, you're looking at a population of half a million to a million people in that group. When we're talking about PBH, we're talking about the people who had tried those things and yet still have persistent hypoglycemia. That's how we get to about eight percent or about one hundred and sixty thousand people. So, this is pretty rare.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

We're talking single digit percentage of people who get bariatric surgery and again years to manifest. But it's a single digit percentage of a population of millions of people who have had bariatric surgery. So, in terms of seeking treatment, as you might imagine, people who have such a debilitating condition where they're having sudden and from what they can tell unexplained drops in blood glucose that leads to neuroglycopenia, means their brains aren't functioning as they're supposed to, are certainly seeking medical attention. Back to the first answer, you know, I think with rare disease what often happens, if you don't have a treatment then and hopefully we can deliver one vexatide, then I think suddenly you have options that weren't there before. And I think as we were able to do with ALS, access is certainly important and education is very important as well.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Your second question on should we continue to model eight percent in the population? We certainly think so. I think as Camille mentioned, the new the twenty twenty three numbers from the ASMBS on bariatric procedures came out still well in two hundred and seventy thousand procedures in the year. And we know that with these upper GI surgeries that there is a portion of people, again single digit percentage, but a portion of people who will develop persistent hypoglycemia. So, we think that one of the major drivers of that is that the body seems to have a potential accelerated GLP-one response.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

We think that's why a GLP-one receptor antagonist makes a lot of sense in this condition. And we see that continuing. But again, I'd remind this is a single digit percentage. So, it's not everyone, but it's a very large population of people who are getting bariatric surgery.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

And I just add one small other detail. What we've observed in the literature and talking to KOLs is usually PBH appears one to three years following surgery. So it's possibly a little sooner than the three to four years you mentioned.

Basma Radwan
Vice President at Leerink Partners

Got it. Thank you so much. That's very helpful.

Operator

Your next question comes from Tim Anderson with Bank of America Securities. Please go ahead.

Susan Chor
Susan Chor
Equity Research Associate at Bank of America

Hi, good morning. This is Susan on for Tim Anderson. We're really looking forward to the upcoming HELIOS data next week. My question is on the ongoing discussions with the FDA on trial design. What are some of the remaining questions or debates that you guys are having with the FDA on trial design?

Susan Chor
Susan Chor
Equity Research Associate at Bank of America

And what are we expecting to learn from the forty eight week data that will help inform one way or the other some of the decisions that will need to be made on trial design. Thank you.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Yep, thank you for the question. This is Camille. We too are looking forward to presenting the week forty eight data next week at the end of scientific medical meetings. And I'm going to answer your second question first. What to expect?

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

I ask you to recall the Istad data that were presented for the week 24 data in the Wolfram study last year. And now we have twice as much time for those participants in the study. So we will be looking at similar endpoints and change in AUC and the C peptide response to a mixed meal tolerance, as well as other glycemic measures such as hemoglobin A1c,

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

as well

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

as visual acuity and overall global impressions of change. So I invite you to look at those data and see how things have evolved over an additional twenty four weeks. Recalling that these are adults with this genetic disorder, And it is a neurodegenerative and beta cell degenerative disorder where progression is expected in these folks. Your first question was regarding the phase three and the FDA. So we really do not go into the details of our interactions and discussions with the FDA.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Having said that, for sure the week forty eight data will inform and is informing our phase three program. And when we have additional information in alignment with the agency on the phase three protocol, we expect to be able to share that information. Just to remind also, this is the very first clinical trial of an agent to potentially impact Wolfram syndrome. So the design there's no template for the design of a trial in Wolfram syndrome. And so we're having those discussions with the FDA.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Well.

Susan Chor
Susan Chor
Equity Research Associate at Bank of America

Thank you. Think next question.

Operator

All right. Our next question comes from Greg Sibanyeva of Mizuho. Please go ahead.

Samuel Lee
Samuel Lee
Equity Research Associate at Mizuho Financial Group, Inc.

Hi, this is Sam on for Greg. Thanks for taking question. Maybe a couple on vexatide. First, will there be any kind of subgroup analysis within the study separating level of severity of PBH in terms of number of episodes and such? And then also assuming approval, do you anticipate any kind of step up or restrictions from a payer perspective that would limit access based on either severity of the disease or type of surgery or anything like that?

Samuel Lee
Samuel Lee
Equity Research Associate at Mizuho Financial Group, Inc.

Thank you.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

Good questions. So I'd say maybe first, our focus on the study is in the full study population. We are enrolling a population, all of which are required to be having during a run-in period. We have a three week run-in period and people have to be having at least one level two or level three event per week. So we are enrolling a population that is having frequent events.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

So all of the patients we have will have that characteristic as well. In terms of step therapy, there are no currently approved therapies for PBH. So I would say we do not anticipate step therapy in this indication. And certainly as we get closer to launch, we'll spend time interacting and educating payers. But we do believe we have a quite exciting and differentiated approach here.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

We have FDA breakthrough therapy designation, five prior trials showing differences in patients who are already trying their very best to reduce these symptoms. And we're still seeing those differences even in that context.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Yeah. And I would say that access is very important to us. If we believe if you have a treatment that can help people, you need to make sure that people can access it efficiently. So, our team is already working on that. And I'd just remind, per what I was saying earlier, that we're already talking about people who have been on medical nutrition therapy, which is really standard of care right now, and yet still have these persistent hypoglycemic events which are very, very debilitating.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

And I think that's important because we're talking about a population that really needs help, And from a physician and payer perspective, these are people who have to regularly seek medical attention for very dangerous events. So I think those will be very important messages as we do our market access education.

Samuel Lee
Samuel Lee
Equity Research Associate at Mizuho Financial Group, Inc.

That's helpful color. Thank you so much.

Operator

Your next question comes from Joel Beatty of Baird. Please go ahead.

Joel Beatty
Senior Research Analyst at Baird

Thanks. My question relates to Avexatide. GLP-one agonists seem to have many favorable short term and long term health effects. So with that in mind, in that context, what gives you confidence that GLP-one antagonists like Avexitide won't cause some type of safety issue? And then I have a follow-up.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

Sure, great question. So one, we do have a good amount of safety data both non clinically and clinically on Avexatide. And to date, Avexatide has generally been well tolerated. So I'd say first empirically what we've seen is a good safety profile thus far. I'd also maybe add that vexatide is a competitive antagonist.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

So it's not running the GLP-one receptor in reverse. It's attenuating the GLP-one that you have endogenously. And so I'd add with that, we don't really see or we haven't seen weight gain, hyperglycemia, any of the things you might think about in that context. So maybe I'd say that overall we've seen good safety profile to date and just kind of highlighting as well in the animal studies we even dosed many fold above from a human equivalent dose perspective, many fold above what we're dosing in the human clinical trials. And even there, we don't see particular adverse events of concern.

Joel Beatty
Senior Research Analyst at Baird

Great, that makes sense. And then as a follow-up, how are you currently thinking about potential business development activities?

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

So, I would say, one, we're very excited about our pipeline. We have major milestones across each of our four clinical trials over the next twelve to fifteen months, which is very exciting. And each is in disease where there's no treatment or substantially inadequate treatment. So, we're very excited at the potential in each one of these programs. We, you know, are always our mission is to help people who have unmet medical needs.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

And so with that, you know, we're always making sure that we stay on top of what's promising. But our focus right now, as I was mentioning in my remarks, is really on execution, because we have some very exciting milestones ahead.

Joel Beatty
Senior Research Analyst at Baird

Thank you.

Operator

Your last question comes from Ananda Ghosh of H. C. Wainwright and Company. Please go ahead.

Ananda Ghosh
VP - Equity Research Biotech at H.C. Wainwright & Co.

Hey, hi. Congrats on the quarter. Maybe one question with respect to the ALS trial. You know, given the importance of NfL in this trial, and especially with the preclinical data showing the effect of knocking down CALPIN-two on NfL, can you remind me if the inclusion criteria for the trial like, during the inclusion criteria of the trial, did you consider the NfL levels of the ALS patients, which might be higher compared to the natural history? Or how did you think about the trial given the focus on NfL?

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

Ananda, that's a great question. It's actually something we discussed a lot as we were planning and designing the study as well. We do not have an inclusion criteria that requires particularly high Nf L levels going into the trial. I think a couple of things went into that. One, just to put context on it as well, in the CSF and ALS, Nf L levels are often 10 times as high as normal.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

And it's quite a stark separation as well. So you can generally expect in ALS that particularly when you're measuring CSF, you're going to see pretty high levels. And then additionally, given that this is our first in human with the drug, we didn't want to over subset and potentially miss populations or signals that could be quite important. So, we definitely will be looking at that, looking at those patients who maybe come in with higher as compared to lower neurofilament, but we didn't want to exclude them from the trial in the initial trial.

Ananda Ghosh
VP - Equity Research Biotech at H.C. Wainwright & Co.

Got it. Makes sense. Thanks.

Operator

Thank you. We still have one question from Dan Akshutti of Pareto Securities. Please go ahead.

Dan Akschuti
Equity Partner - Biotech Analyst at Pareto Securities

Hello, everyone, and thank you for taking my questions. Congrats on the progress and excited for the HELIOS readout next week. Just a more general question, how you compare it, avexatide, to other drugs that could enter the space that are more inhibiting insulin and GLP-one secretion like somatostatin analogues, and how you see the placebo response risk in post bariatric hypoglycemia for the Phase three trial? Thank you.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

Yeah, good questions. So maybe first I'd remind you, we're in Phase three with Avexatide. We have breakthrough therapy designation built on five prior successful trials. So we think the profile of Avexatide is quite strong, both in terms of what we've seen thus far in terms of safety and efficacy. I think any other programs in the space are quite a bit earlier and have a number of hurdles, I would say to overcome.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

And so, we're focused on Avexaside at this time and do believe that as the best profile we've seen thus far.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Yeah. And I'd just reiterate too, the reason that Avexaside was granted FDA breakthrough therapy designation is because PVH has a high unmet need and because of the promising data from Phase II's breakthrough therapy means benefit over existing treatments. And of course, right now there are no existing treatments or approved treatments for PVH. So, we're very excited about the potential and that's why we're focused on rigorous execution in this study.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

Yeah, and I realize you also asked about placebo rate. So, in the Phase II study, there was a placebo period as well. And we did not see a meaningful difference between the run-in and the placebo. So I'd say empirically, we haven't really seen much of a placebo effect in this indication. That being said, when we did the powering analysis for the study, we certainly thought about that.

Josh Cohen
Josh Cohen
Co-Founder & Co-CEO at Amylyx Pharmaceuticals

And we do believe our power is robust, that even if there is some degree of placebo effect, we should have enough power regardless in the study.

Camille Bedrosian
Camille Bedrosian
Chief Medical Officer at Amylyx Pharmaceuticals

Yeah, and this is Camille. I would just also comment that these individuals have tried and are trying everything to manage this very debilitating condition. And that really isn't going to change whether they're in a clinical trial or not. So their daily life will not be changing because of being in a clinical trial.

Operator

There is no question at this time. I'll turn the call back to Mr. Klee.

Justin Klee
Justin Klee
Co-Founder, Co-CEO & Director at Amylyx Pharmaceuticals

Thank you, operator, and thank you all for your time. If you have any follow-up questions, please reach out to Lindsey. We hope you have a great rest of your day.

Operator

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.

Executives
    • Justin Klee
      Justin Klee
      Co-Founder, Co-CEO & Director
    • Camille Bedrosian
      Camille Bedrosian
      Chief Medical Officer
    • James Frates
      James Frates
      Chief Financial Officer
    • Josh Cohen
      Josh Cohen
      Co-Founder & Co-CEO
Analysts
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Key Takeaways

  • First patient dosings: Amelix initiated dosing in its pivotal Phase III LUCIDITY trial of vexatide for post bariatric hypoglycemia and in the Phase I LUMINA trial of AMX-114 in ALS.
  • Avexatide progress: The investigational GLP-1 receptor antagonist holds FDA breakthrough therapy designation for PBH, with enrollment completion expected in 2025, top-line data in the first half of 2026, and a potential 2027 launch.
  • AMX-35 pipeline updates: Positive Phase II HELIOS data in Wolfram syndrome showed sustained improvements through week 48, while Phase IIb ORION results in progressive supranuclear palsy are anticipated in Q3 2025 to inform Phase III design.
  • AMX-114 ALS program: The antisense oligonucleotide targeting calpain-2 knockdown began a randomized, double-blind placebo-controlled multiple ascending dose trial, with early cohort safety and biomarker data expected later this year.
  • Strong financial position: A $65.5 million public offering boosted Q1 2025 cash to $204.1 million, extending runway through the end of 2026 to fund four ongoing clinical trials and commercial preparations.
AI Generated. May Contain Errors.
Earnings Conference Call
Amylyx Pharmaceuticals Q1 2025
00:00 / 00:00

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