Amylyx Pharmaceuticals' Q2 2025: Key Contradictions in PBH Patient Estimates, Trial Analysis, and Market Opportunities

PBH patient number estimations, detailed PSP trial analysis, Avexitide's safety profile as a GLP-1 antagonist, PBH market opportunity and patient awareness, dietary management in LUCIDITY trial are the key contradictions discussed in Amylyx Pharmaceuticals' latest 2025Q2 earnings call.



Pipeline Progress Across Clinical Programs:
- Amylyx Pharmaceuticals made significant progress across its clinical programs in the first half of 2025. Notably, they dosed the first participant in the pivotal Phase III LUCIDITY trial for Avexitide, an investigational GLP-1 receptor antagonist for treating postbariatric hypoglycemia (PBH), following Roux-en-Y gastric bypass surgery.
- The company remains on track to complete recruitment by year-end, reflecting the team's focus and executional rigor.

Financial Performance and Cost Management:
- Amylyx ended the second quarter with a cash position of $180.8 million, a decrease from $204.1 million at the end of Q1.
- Research and development expenses were $27.2 million, with a decrease in spending on AMX0035 for treating ALS, while increasing spending on Avexitide and AMX0035 for PSP to support ongoing trials.
- Selling, general, and administrative expenses decreased by 43% to $15.6 million, partly due to reduced payroll and consulting costs.

PBH Prevalence and Market Opportunity:
- According to a prevalence model by Dr. Colleen Craig, approximately 400,000 people in the U.S. who previously underwent bariatric surgery experienced clinically important hypoglycemia, with 167,000 having recurrent events significant enough to require medical attention.
- The breakdown shows approximately 119,000 people with Roux-en-Y gastric bypass and 48,000 with sleeve gastrectomy, aligning with Amylyx's focus on Roux-en-Y surgeries.

PSP Program and Regulatory Efforts:
- Amylyx expects top-line data from the Phase IIb portion of the ORION trial in PSP in the current quarter, which will inform a go/no-go decision on moving into a Phase III program.
- The company aims to achieve a 20% slowing of disease progression on the PSPRS, setting a high bar for clinical activity and potential improvement in patient quality of life.