Summary of Amylyx Pharmaceuticals (AMLX) Update / Briefing July 13, 2025 Company Overview - **Company**: Amylyx Pharmaceuticals (AMLX) - **Focus**: Development of Avexatide, a potential GLP-1 receptor antagonist for treating post-bariatric hypoglycemia (PBH) with Breakthrough Therapy Designation from the FDA Industry Context - **Condition**: Post-bariatric hypoglycemia (PBH) is a serious metabolic condition that occurs in patients after bariatric surgery, characterized by severe hypoglycemic episodes - **Prevalence**: Approximately 400,000 individuals in the U.S. experience clinically important hypoglycemia after bariatric surgery, with around 166,000 requiring medical management [42][43] Key Points and Arguments 1. **Patient Experience**: A patient shared her struggles with PBH, highlighting the debilitating nature of the condition, which severely limits daily activities and quality of life [8][9][15][16] 2. **Medical Need**: There is a significant unmet medical need for effective treatments for PBH, as current dietary modifications and off-label medications often fail to provide relief [39][40] 3. **Mechanism of PBH**: PBH is caused by an exaggerated GLP-1 response post-surgery, leading to hyperinsulinism and subsequent hypoglycemia. This condition can develop 2-3 years after surgery, but may occur anytime from 2 to 20 years post-operation [19][41] 4. **Current Treatments**: Existing treatments are limited and often ineffective, with no FDA-approved medications specifically for PBH. Dietary modifications and off-label medications have high failure rates and significant side effects [22][39] 5. **Avexatide's Mechanism**: Avexatide targets the GLP-1 receptor to normalize insulin secretion and stabilize glucose levels, addressing the underlying pathophysiology of PBH [49][50] 6. **Clinical Trials**: The Phase II and Phase IIb studies showed that Avexatide significantly reduced the frequency of Level II and Level III hypoglycemic events by over 50% [57][72] 7. **FDA Breakthrough Therapy Designation**: Avexatide is the only drug in development for PBH to receive this designation, indicating its potential to address a serious condition with high unmet medical need [57] 8. **LUCIDITY Phase III Trial**: The ongoing Phase III trial will evaluate the efficacy of Avexatide at a dose of 90 mg once daily, focusing on reducing hypoglycemic events [78][81] Additional Important Content - **Patient Education**: There is a critical need for increased awareness and education about PBH among healthcare providers and patients, as many patients are misdiagnosed or experience delays in receiving appropriate care [38][41] - **Quality of Life Impact**: The unpredictable nature of hypoglycemic events leads to social isolation and significant emotional distress for patients, emphasizing the need for effective treatment options [66][68] - **Future Outlook**: The company is actively recruiting for the LUCIDITY trial, with data expected in the first half of 2026, aiming to bring a much-needed therapy to market for PBH patients [85][86]

Summary of Amylyx Pharmaceuticals (AMLX) Conference Call Company Overview - **Company**: Amylyx Pharmaceuticals (AMLX) - **Focus**: Developing therapies for rare diseases, particularly post bariatric hypoglycemia (PBH) and other neurodegenerative conditions [5][6] Key Points on Lead Asset: Avexatide - **Indication**: Avexatide is a competitive inhibitor of GLP-1, targeting PBH, a rare condition following bariatric surgery characterized by severe hypoglycemic events [5][6] - **Clinical Trials**: - Five past trials demonstrated significant benefits, including a 53% reduction in level two hypoglycemic events and a 66% reduction in level three events [6][21] - Phase III study recruitment expected to complete by the end of 2025, with data anticipated in the first half of 2026 [7][49] - **Market Opportunity**: - PBH affects an estimated 160,000 people in the U.S., with the number expected to rise due to increasing bariatric surgeries (approximately 270,000 annually) [12][13] - Current treatment options are limited, primarily involving medical nutrition therapy [14][15] Regulatory Designation and Pricing - **Breakthrough Therapy Designation**: Received based on prior trial data, facilitating closer collaboration with the FDA [7][20] - **Pricing Strategy**: Pricing has not been finalized; however, the company is considering the orphan drug designation and recent market entries in rare endocrine disorders as benchmarks [17][18] Other Assets and Trials - **AMX35**: - Studied in Wolfram syndrome and progressive supranuclear palsy (PSP) [7][58] - Recent data from Wolfram syndrome trials showed stabilization and improvement in various outcomes over 48 weeks [60][61] - **AMX-114**: An antisense oligonucleotide targeting calpain two, currently in a clinical trial for ALS, with data expected by the end of the year [9] Competitive Landscape - **Current Competition**: No known drugs have shown efficacy in treating PBH, positioning Avexatide uniquely in the market [54] - **GLP-1 Agonists**: While there are concerns about competition from GLP-1 agonists, the company believes that the target population for bariatric surgery is distinct and will continue to grow [55][56] Future Milestones - **Phase III Trial**: Expected to provide pivotal data for FDA approval, with a focus on maintaining consistency with Phase II trial parameters [36][62] - **Market Access**: Preparations for market access strategies are underway, emphasizing the importance of ensuring patient access post-approval [52] Conclusion - Amylyx Pharmaceuticals is advancing its lead asset Avexatide through critical clinical trials aimed at addressing significant unmet needs in rare diseases, particularly PBH. The company is optimistic about its market potential and regulatory pathway, with ongoing efforts to ensure successful trial outcomes and market access strategies.