Amylyx Pharmaceuticals, Inc.

Good morning. My name is Lynn, 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. After today's presentation, there will be an opportunity to ask questions. To ask a question, please press star 1 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. 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 2025 financial results and business updates. With me on the call today are Josh Cohen and Justin Klee, our co-CEOs, Dr. Camille Bedrosian, our Chief Medical Officer, and Jim Freites, 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 Avexatide, AMX35, and AMX114, statements regarding regulatory and clinical development, 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 statement. You are cautioned not to place any undue reliance on these forward-looking statements, and AMLEX disclaims any obligation to update such statements unless required by law. Now, I will turn the call over to Justin.

Good morning, and thank you all for joining us. 2025 is an important year of execution at AMLEX 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 three lucidity clinical trial of the vexatide in post bariatric hypoglycemia or PBH. We also dosed the first participant in our phase one lumina clinical trial of AMX 114 and ALS. In addition, we've strengthened our financial position by raising approximately 65 and a half million dollars at the start of the first quarter which extends our anticipated cash runway through the end of 2026. Now, I'd like to briefly walk through each of our programs. Starting with our lead asset, Avexatide, an investigational GLP-1 receptor antagonist with FDA breakthrough therapy designation for post-bariatric hypoglycemia. PBH is a chronic and often progressive condition that affects approximately 160,000 people in the United States. However, there are no approved treatment options. We believe Avexatide 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 three lucidity trial. We continue to expect enrollment completion in 2025 and top line data in the first half of 2026. 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. Turning to AMX35, which is an oral small molecule therapy designed to target endoplasmic reticulum or ER stress and mitochondrial dysfunction. AMX35 is currently being evaluated in Wolfram syndrome and progressive supranuclear palsy or PST. 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. We believe AMX 35 has the potential to address the urgent unmet need for the approximately 3,000 people living with Wolfram Syndrome in the United States. Last year, we reported positive top-line data from the 12-person phase 2 open-label Helios trial in adults with Wolfram Syndrome. Participants showed improvement or stabilization across all measured outcomes at week 24. In addition, longer-term data for the subset of participants who had reached treatment through week 48 showed sustained improvement over time. We continue to follow participants in the Helios trial and plan to present full week 48 data at the upcoming joint congress of the European Society for Pediatric Endocrinology and the European Society of Endocrinology, which is this coming weekend. 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 AMX35 as a potential treatment for progressive supernuclear palsy. PSP is a rare, progressive, and fatal neurodegenerative disease that affects an estimated 23,000 people in the U.S. and has no currently approved treatments. PSP 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 AMX35 is the first brain and cell penetrant agent that has demonstrated a significant tau reduction in CSF to be tested in PSP. We completed enrollment in the Phase IIb 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. Those results will guide our decision about whether to advance into the phase three portion of the trial. Next in our pipeline is AMX-114, our investigational antisense oligonucleotide targeting knockdown of Calpain-2 for the potential treatment of ALS. This is a novel program built on decades of academic research linking the protease Calpain-2 to axonal degeneration an early and destructive driver of ALS progression. In preclinical studies, AMX-114 showed potent and durable reductions in Calpain-2 levels, improved neuron survival, and reduced neurofilament light chain levels, a well-established biomarker of axonal degeneration. We were excited to have dosed the first participant in our Phase I Luminous Trial last month. Lumina is a multinational, randomized, double-blind, placebo-controlled, multiple ascending dose trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX114 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 Avexotide.