Amylyx Pharmaceuticals, Inc. Common Stock Study result

Please go ahead. Good morning, and thank you all for joining us today to discuss the top line results from the phase III LUCIDITY trial of avexitide in post-bariatric hypoglycemia, or PBH.

The slide deck accompanying our remarks this morning will be available on the investors section of our website for your reference following the conclusion of the call. With me on the call today are Josh Cohen and Justin Klee, our Co-CEOs, Dr. Camille Bedrosian, our Chief Medical Officer, Dr. Marilyn Tan, principal investigator of the LUCIDITY clinical trial and Clinical Professor of Medicine at Stanford University School of Medicine. Jim Frates, our Chief Financial Officer, and Dan Monahan, our Chief Commercial Officer, will join us for the Q&A portion of the call.

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, the therapeutic potential and safety of avexitide as a treatment for PBH, expectations regarding the timing for NDA submission with the FDA, the potential benefits of regulatory designations held with the FDA, the plan to present data at an upcoming medical meeting, and expectations regarding the timing and preparations for potential commercialization of avexitide if approved.

Actual events and results could differ materially from these expressed or implied by any forward-looking statements 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'll turn the call over to Camille.

Thank you, Lindsey, and thank you all for joining us this morning. It is with great enthusiasm that we share the positive top-line results from the phase III LUCIDITY trial of our lead asset, avexitide, an investigational first-in-class GLP-1 receptor antagonist in post-bariatric hypoglycemia, or PBH, following Roux-en-Y gastric bypass surgery. LUCIDITY met its FDA agreed-upon primary endpoint, demonstrating a 55% reduction in the composite rate of level 2 and level 3 hypoglycemic events compared to placebo, P value of 0.000003. The trial also met all secondary endpoints, demonstrating consistent reductions in both level 2 by self-monitoring blood glucose, or SMBG, and continuous glucose monitoring, or CGM, and level 3 hypoglycemic events versus placebo. Importantly, avexitide was generally well-tolerated through the double-blind study period with a favorable safety profile.

LUCIDITY is the sixth clinical trial of avexitide to generate statistically significant results in PBH and the largest and longest study conducted to date. Taken together, these findings support the potential for avexitide to become the first FDA-approved therapy for PBH, a condition with a profound unmet medical need. I would like to briefly recap the design of the phase III LUCIDITY trial. LUCIDITY is a multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of avexitide in adults with PBH following Roux-en-Y gastric bypass surgery. The pre-specified primary endpoint was the composite rate of level 2 and level 3 hypoglycemic events compared to placebo through week 16. In addition, we evaluated secondary endpoints of level 2 hypoglycemic events as measured by SMBG and by blinded CGM and level 3 hypoglycemic events.

Level 2 events are defined as glucose levels below 54 milligrams per deciliter, an established threshold for clinically significant hypoglycemia, and level 3 events are defined by significant cognitive or physical impairment requiring assistance from another person. These endpoints capture hypoglycemic events that matter to patients and can have meaningful consequences for safety and day-to-day functioning. In a few moments, Dr. Tan will speak about the day-to-day impact of PBH on those living with this condition. In the trial, 78 participants were randomized three to two to receive either avexitide 90 milligrams once daily or placebo. The treatment groups were generally well-balanced. More than 90% of the participants completed the 16-week double-blind treatment period, and all eligible participants entered the ongoing open label extension portion of the trial.

Avexitide met the primary endpoint, demonstrating a 55% reduction in the composite rate of level 2 and level 3 hypoglycemic events compared to placebo through week 16, with a P value of 0.000003. It is important to note that these results are on top of current standard of care, medical nutrition therapy. We are deeply inspired by these results and the potential to address a longstanding unmet need for people living with post-bariatric hypoglycemia. In addition, LUCIDITY met all secondary endpoints, demonstrating consistent, highly statistically significant, and clinically meaningful reductions in level 2 hypoglycemic events by SMBG, level 2 hypoglycemic events by CGM, and level 3 hypoglycemic events compared to placebo. Taken alone, each of the pre-specified primary and secondary endpoints yielded highly statistically significant and clinically meaningful results. Taken together, these efficacy findings demonstrate a compelling body of evidence for avexitide in PBH.

Avexitide was generally well-tolerated in the double-blind portion of LUCIDITY, with a safety profile consistent with that observed across all PBH clinical trials completed to date. The majority of adverse events were mild to moderate, and there were no serious adverse events deemed related to avexitide treatment. The most common adverse events were diarrhea, injection site redness or erythema, and injection site bruising. Furthermore, there were no changes in body weight observed in either the avexitide or placebo groups over the 16-week double-blind period. To close, the LUCIDITY results demonstrated highly statistically significant and clinically meaningful reductions in hypoglycemic events, together with a favorable safety profile. Based on these positive data, we believe that avexitide has the potential to be the first ever FDA-approved therapy for PBH.

I want to thank the PBH community for their collaboration and participation in the study, including the 21 LUCIDITY sites, investigators, study coordinators, and importantly, the participants. I also want to acknowledge our outstanding Amylyx team for their unwavering dedication to running such a robust and high-quality trial. Now, I would like to turn over to Dr. Tan, Principal Investigator of the LUCIDITY clinical trial, to give an overview of PBH and what these trial results mean to the PBH community.