Amylyx Pharmaceuticals, Inc.

Good morning, my name is Jenny, and I will be your conference operator today. At this time, I would like to welcome everyone to the Amalek's Pharmaceuticals 4th Quarter and Full Year 2024 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 2. 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 Lindsay Allen, Head, Investor Relations and Communications. Please proceed.

Good morning, and thank you all for joining us today to discuss our fourth quarter and full year 2024 financial results. With me on the call today are Josh Cohen and Justin Klee, our co-CEOs, Dr. Camille Bedrosian, our chief medical officer, and Jim Friedes, 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's provision of the Private Securities Litigation Reform Act of 1995. These statements include but are not limited to our expectation with respect to Avexatide, AMX35, and AMX114, 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 MLS 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 for joining us. As we look to 2025 and 2026, we're entering a pivotal stage for AMLEX with key milestones across three assets in four ongoing clinical trials, all targeting orphan diseases with few or no treatment options. We are excited to have started the pivotal study of Avexatide for the treatment of post-bariatric hypoglycemia and anticipate top-line results in the first half of next year. We also recently completed a financing, raising approximately $65.5 million to begin commercial preparations for Avexatide and to extend our cash runway through the end of 2026. Over the next 12 to 15 months, we are focused on execution as we look forward to three key data readouts. Our lead asset, Avexatide, is an investigational GLP-1 receptor antagonist with FDA breakthrough therapy designation in post-bariatric hypoglycemia, or PBH, as well as orphan drug designation. PBH is a debilitating condition that leads to persistent and often progressive hypoglycemia. There are no treatments approved for the approximately 160,000 people living with PBH in the U.S. today. Avexetide has already been studied in five clinical trials of PVH that showed consistent, dose-dependent, statistically significant reductions in hypoglycemia. We started recruiting Lucidity, our pivotal 16-week phase three clinical trial, in mid-February and expect that the first study participant will be dosed in March or April. We expect a complete recruitment of the approximately 75 participants by the end of this year, and anticipate top line data in the first half of 2026. Next in our pipeline is AMX35, a combination small molecule that is designed to target endoplasmic reticulum or ER stress and mitochondrial dysfunction. AMX35 is currently being evaluated in Wolfram syndrome and progressive supernuclear palsy or PSP, two diseases characterized by ER stress and mitochondrial dysfunction. Wolfram syndrome is a rare, fatal, monogenic, progressive diabetic, and neurodegenerative disease affecting an estimated 3,000 people in the U.S. There are no approved treatments. Like many childhood-onset monogenic diseases, the pathophysiology of Wolfram syndrome is well characterized. Our program is focused on people who carry mutations in the WFS1 gene, which encodes a protein called Wolframin that spans the membrane of the endoplasmic reticulum. These mutations in Wolframin directly cause ER stress and mitochondrial dysfunction. Last year, we reported our first clinical data in people with Wolfram syndrome. In our 12-person phase two open-label helios study, participants showed improvement or stabilization across all measured outcomes. We are continuing to follow participants in the ongoing helios trial and expect to share the week 48 data in the coming months. These data, along with regulatory interactions, will inform the design of a Phase III trial. We are also anticipating an interim readout of our Phase IIb3 Orion trial, evaluating AMX35 and PSP in the third quarter 2025. PSP is a rare, progressive, fatal neurodegenerative disease that affects an estimated 23,000 people in the U.S. at any one time and has no currently approved treatments. PSP is the most well-characterized pure tauopathy because all people with PSP have tau protein buildup in the brain. Genetics and model systems show that this abnormal tau buildup causes a characteristic brain degeneration and clinical presentation observed in the disease. AMX35 previously demonstrated that it reduced tau measured in the cerebrospinal fluid of people with Alzheimer's disease. We believe AMX35 is the first brain and cell penetrant agent that has previously shown significant tau protein reduction in CSF to be tested in PSP. The Phase 2b portion of our Phase 2b3 Orion trial evaluating AMX35 in PSP was fully enrolled in January with a total of 139 participants randomized. We expect safety and efficacy data from an unblinded interim analysis in the third quarter of this year. These data will inform our decision whether or not to move into the phase three portion of the trial. Powering analyses published in the PSP literature estimate approximately 80% power to detect a 30% slowing the rate of decline of PSPRS with a sample size. Our fourth clinical program is evaluating AMX114 for the treatment of ALS. AMX114 is an antisense oligonucleotide that knocks down Calpain 2. One of the key proteases driving axonal degeneration. Last month, the phase one multiple ascending dose Lumina trial of AMS and recruiting in Canada. We are working diligently to open additional sites in Canada and the US. We started recruiting Lumina and expect the first participant dose in March or April. We look forward to early cohort data from our phase one Lumina trial expected later this year. We are also actively working to build our pipeline in PBH and other rare diseases that may benefit from GLP-1 antagonism. Of particular note, at the end of last year, we announced a collaboration to develop a novel long-acting GLP-1 receptor antagonist with Gubra. Gubra is an industry leader in peptide-based drug discovery. We will continue to focus on clinical execution as we look forward to milestones in each of our programs over the next 12 to 15 months. I will now pass it to Camille to speak further on our Phase III lucidity clinical trial of Avexatide and PBH.