Amylyx Pharmaceuticals (NasdaqGS:AMLX) FY 2025 Conference December 03, 2025 04:00 PM ET Company ParticipantsJustin Klee - Co-CEo and Co-FounderConference Call ParticipantsGeoff Meacham - Senior AnalystGeoff MeachamAll right. Okay, welcome to the Citi Global Healthcare Conference. I'm Jeff Meacham.Global Head of Healthcare.Global Head of Healthcare, thank you. And Senior Analyst, big cap and mid-cap biotech and pharma. Obviously, Jarvis Fang is up here with me from my team. We're thrilled to have Amylyx. So ...

Amylyx Pharmaceuticals (NasdaqGS:AMLX) FY 2025 Conference December 03, 2025 04:00 PM ET Speaker2All right. Okay, welcome to the Citi Global Healthcare Conference. I'm Jeff Meacham.Global Head of Healthcare.Global Head of Healthcare, thank you. And Senior Analyst, big cap and mid-cap biotech and pharma. Obviously, Jarvis Fang is up here with me from my team. We're thrilled to have Amylyx. So Justin Klee is with us, co-CEO. We won't trash the other co-CEO, you know. You got the look to Miami.Yeah, yeah, yeah, ...

One investor is making a bold bet on Amylyx just as its 2026 catalyst calendar starts to take shape.On November 14, New York City-based Commodore Capital disclosed a new position in Amylyx Pharmaceuticals (AMLX +2.76%), acquiring nearly 4.1 million shares valued at approximately $55 million, according to a recent SEC filing.What HappenedAccording to a filing with the U.S. Securities and Exchange Commission dated November 14, Commodore Capital LP disclosed a new stake in Amylyx Pharmaceuticals (AMLX +2.76%). ...

Summary of Amylyx Pharmaceuticals FY Conference Call Company Overview - **Company**: Amylyx Pharmaceuticals (NasdaqGS:AMLX) - **Focus**: Development of innovative therapies, particularly in the area of post-bariatric hypoglycemia (PBH) and other rare diseases Key Points on Avexetide and PBH - **Avexetide**: A competitive inhibitor of the GLP-1 receptor currently in a phase three pivotal study for PBH, following five successful prior studies that supported FDA Breakthrough Therapy designation [1][2] - **Market Size**: Approximately 160,000 people in the U.S. are estimated to have PBH, a number expected to grow due to the increasing prevalence of bariatric surgeries [3][4] - **Bariatric Surgery**: About 270,000 bariatric surgeries are performed annually in the U.S., with a significant portion of patients potentially developing PBH [7][10] - **Awareness and Diagnosis**: PBH has historically been under-recognized, but awareness is increasing, with presentations at medical conferences and discussions about creating an ICD-10 code for PBH [5][16] Clinical Development and Pipeline - **AMX0035**: In clinical development for Wolfram syndrome, with positive phase two results and phase three design pending FDA alignment [2][25] - **Calpain-2 Antisense Oligonucleotide**: Currently in phase one study for ALS, with safety and tolerability data expected later this year [2][25] Market Dynamics and Adoption Drivers - **Patient Journey**: Diagnosis of PBH can take one to three years post-bariatric surgery, with a significant number of patients actively managed at specialized centers [12][13] - **Educational Efforts**: There is a need for increased education among general endocrinologists and surgeons to recognize PBH symptoms and refer patients appropriately [13][15] - **Launch Expectations**: Anticipation of a bolus effect of initial patients seeking treatment upon approval, followed by a typical S-shaped launch curve [14][15] Phase Three Study Design - **Study Duration**: The phase three study has a treatment period of 16 weeks, increased from 4 weeks in phase two, with no evidence of tachyphylaxis expected [18][19] - **Outcome Measurement**: Primary outcomes will measure hypoglycemic events using the same methods as in phase two, ensuring consistency [19][20] Future Opportunities - **Potential for Other Indications**: The mechanism of Avexetide may have applications in other conditions related to persistent hypoglycemia, such as congenital hyperinsulinism and complications from upper GI surgeries [23][24] - **Market Size for Wolfram Syndrome**: Estimated at about 3,000 people in the U.S., with a larger population outside the U.S. [25] Conclusion - **Financial Position**: Recent financing provides a cash runway into 2028, supporting ongoing clinical programs and market entry strategies [2] - **Outlook**: The company is optimistic about its pipeline and the potential for Avexetide to address an unmet medical need in the PBH market [2][26]

Financial Data and Key Metrics Changes - The company ended Q3 2025 with a strong cash position of $344 million, compared to $181 million at the end of Q2 2025, reflecting a public offering that provided approximately $191 million in net proceeds [12] - Total operating expenses for the quarter were $36 million, down 53% from the same period in 2024, primarily due to one-time expenses related to the acquisition of Avexitide incurred in Q3 2024 [12][13] - Research and development expenses decreased to $19.9 million from $21.2 million in Q3 2024, mainly due to reduced spending on AMX0035 for PSP and ALS [13] - Selling, general, and administrative expenses were $16.2 million, down from $17.8 million in Q3 2024, attributed to decreased consulting and professional services expenses [13] Business Line Data and Key Metrics Changes - The lead program, Avexitide, is focused on post-bariatric hypoglycemia (PBH) and has shown statistically significant reductions in hypoglycemic events across five clinical trials [4][8] - The pivotal phase 3 Lucidity Trial is designed to replicate previous trial results, with a focus on enrolling a similar patient population and collecting data consistently [4][9] - The company anticipates completing recruitment for the Lucidity Trial in Q1 2026, with top-line data expected in Q3 2026 [5][12] Market Data and Key Metrics Changes - The company estimates approximately 160,000 individuals in the U.S. suffer from PBH, highlighting a significant unmet need for treatment options [6][17] - The ongoing market research and claims analysis support the understanding of the burden of PBH and the urgent need for an FDA-approved treatment [6][17] Company Strategy and Development Direction - The company is preparing for a potential launch of Avexitide in 2027, pending FDA approval, and is building its medical affairs and commercial organizations [5][6] - The company is also advancing the clinical development of AMX0035 for Wolfram syndrome, with plans to initiate a pivotal phase 3 trial in the second half of 2026 [6][55] - The research collaboration with Gubra is progressing well, with new molecules demonstrating strong potency and extended half-lives [16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the execution of the Lucidity Trial and the potential of Avexitide to be the first approved therapy for PBH [10][18] - The company remains focused on addressing the significant unmet need in the PBH market, with ongoing engagement from clinical trial sites and high participant interest [9][51] - Management acknowledged the steady enrollment rate in the Lucidity Trial and emphasized the importance of quality in participant selection and data collection [22][51] Other Important Information - The company is preparing for early NDA submission efforts for Avexitide, with a focus on market research and disease education [5][6] - The anticipated cash runway extends into 2028, supporting the company's strategic initiatives and potential product launch [12] Q&A Session Summary Question: Enrollment update and operational dynamics affecting the study - Management acknowledged the importance of site startup and participant commitment to dietary restrictions, noting a steady enrollment rate and the focus on quality [20][22] Question: Phase 3 study patient history and screen failure rates - Management indicated that most patients would have been on dietary therapy for several years prior to entering the study, but did not disclose specific screen failure rates [27][28] Question: Addressable market for PBH and patient eligibility - Management reiterated the estimate of 160,000 PBH patients, emphasizing that this figure includes those not controlled on diet and experiencing significant hypoglycemic events [31][36] Question: Differences in site enrollment rates and engagement - Management confirmed that differences in enrollment rates across sites are common, but overall engagement from sites remains high [51] Question: Manufacturing and CMC processes for Avexitide - Management stated that registration batches have been manufactured and are undergoing stability testing, with a focus on quality and inspection readiness [49] Question: Measuring diet adherence in the Lucidity trial - Management confirmed that diet adherence is monitored through blinded continuous glucose monitoring (CGM) data, with interventions possible if significant deviations are observed [44] Question: Future regulatory path for Avexitide in other GI surgeries - Management indicated that while the current phase 3 study focuses on Roux-en-Y gastric bypass, there is interest in exploring other surgical types in the future [46]

Summary of Amylyx Pharmaceuticals FY Conference Call Company Overview - **Company**: Amylyx Pharmaceuticals (NasdaqGS:AMLX) - **Focus**: Clinical-stage biotech developing therapies for neurodegenerative and endocrine diseases [1][2] Key Programs and Developments - **Avexitide**: - Late-stage asset focused on post-bariatric hypoglycemia (PBH) - Phase 3 LUCIDITY study ongoing, with expected enrollment completion by the end of 2025 and data release in the first half of 2026 [3][20] - First-in-class GLP-1 receptor antagonist with FDA Breakthrough Therapy Designation for PBH [5][6] - Mechanism: Blocks GLP-1 to reduce insulin production, addressing hypoglycemia caused by hyperinsulinemia [6][8] - Phase 2 studies showed a 64% reduction in level 3 hypoglycemic events and a 53% reduction in level 2 events [13][14] - Safety profile: Generally well tolerated with mild to moderate side effects [15] - **Wolfram Syndrome**: - Rare, progressive disease with no current treatment - Using AMX0035, showing positive outcomes in C-peptide and HbA1c levels [21][24] - Estimated 3,000 to 3,500 patients in the U.S. [25] - **ALS Program**: - Targeting axonal degeneration with AMX0114, an antisense oligonucleotide aimed at Calpain 2 - First patient data expected by the end of 2025 [26] Financial Position - Recently completed financing of $175 million, extending runway into 2027 - Cash balance of $180 million as of June 30, 2025 [27] Market Opportunity - Over 160,000 individuals in the U.S. suffer from persistent hypoglycemia post-bariatric surgery, a significant unmet medical need [18][20] - Over 2 million bariatric surgeries performed in the U.S. over the last decade, with 8% developing PBH [18] Regulatory and Patent Status - Patent rights for avexitide extend through 2037, with orphan designation granted for PBH [20][21] Conclusion - Amylyx Pharmaceuticals is actively advancing multiple programs in rare diseases with significant unmet needs, backed by a strong financial position and promising clinical data [27]

Summary of Amylyx Pharmaceuticals (AMLX) Conference Call - September 02, 2025 Company Overview - **Company**: Amylyx Pharmaceuticals (AMLX) - **Focus**: Development of therapies for post-bariatric hypoglycemia (PBH) and Wolfram syndrome Key Points on PBH and Avexitide - **Avexitide**: A GLP-1 receptor antagonist currently in Phase 3 trials, aimed at reducing hypoglycemic events in PBH patients [1][2] - **Market Opportunity**: Approximately 160,000 individuals in the U.S. suffer from PBH, a rare complication following bariatric surgery, with an estimated 8% of bariatric surgery patients developing PBH [5][6] - **Unmet Need**: Current treatments for PBH are limited, primarily involving medical nutrition therapy, which is often ineffective and burdensome [9][10] - **Patient Impact**: PBH significantly affects daily life, causing anxiety and limiting activities due to the risk of severe hypoglycemic events [3][8] - **Clinical Trials**: Recruitment for the Phase 3 LUCIDITY study is on track to complete by year-end 2025, with data expected in the first half of 2026 [11][12] Competitive Landscape - **Current Treatments**: Limited options exist, with off-label therapies showing minimal efficacy and significant side effects [10] - **Differentiation**: Avexitide is positioned as a unique treatment with a strong competitive profile, addressing a significant unmet need in the PBH market [10][21] Insights on Patient Population - **Demographics**: Predominantly affects women in their 40s, often misdiagnosed due to overlapping symptoms with menopause [24][26] - **Awareness and Diagnosis**: Increased awareness among endocrinologists and advocacy groups is leading to better identification of PBH cases [36][37] Wolfram Syndrome Insights - **AMX0035**: A combination therapy for Wolfram syndrome, showing promise in initial studies with stabilization or improvement in diabetic outcomes [27][30] - **Patient Community**: Strong advocacy from families, particularly mothers, is driving awareness and support for research in Wolfram syndrome [35] Future Directions - **Long-Acting Formulations**: Collaboration with Gubra aims to develop a long-acting GLP-1 receptor inhibitor, enhancing treatment options for PBH and potentially other conditions [39][41] - **Regulatory Engagement**: Ongoing discussions with regulatory bodies to streamline the path for pivotal studies in rare diseases like Wolfram syndrome [31][32] Conclusion - **Overall Outlook**: Amylyx Pharmaceuticals is positioned to address significant unmet needs in both PBH and Wolfram syndrome, with promising clinical data and a strong focus on patient impact and education [23][27]

Financial Data and Key Metrics Changes - The company ended 2024 with a solid cash position of $176.5 million, excluding approximately $65.5 million in net proceeds from a public offering that closed on January 13, 2025 [28] - Total operating expenses for Q4 were $39.9 million, down 62% from the same period in 2023 [29] - Research and development expenses were $22.9 million compared to $44.9 million in Q4 2023, primarily due to decreased spending on AMX0035 and other cost reductions [29] - Selling, general and administrative expenses were $17.1 million compared to $52.2 million in Q4 2023, reflecting a decrease in payroll and consulting costs [29] Business Line Data and Key Metrics Changes - The lead asset, avexitide, is in a pivotal Phase III clinical trial targeting post-bariatric hypoglycemia (PBH) with top line results expected in the first half of 2026 [6][7] - AMX0035 is being evaluated in Wolfram syndrome and progressive supranuclear palsy (PSP), with ongoing trials showing promising early data [9][12] - AMX0114 is in a Phase I trial for ALS, with recruitment expected to begin in March or April [16][17] Market Data and Key Metrics Changes - There are approximately 160,000 people in the U.S. living with PBH, a condition with no approved treatments [8][36] - The company estimates that about 8% of individuals who undergo Roux-en-Y gastric bypass will develop PBH, indicating a substantial market opportunity [46] Company Strategy and Development Direction - The company is focused on executing clinical trials and preparing for a potential commercial launch of avexitide in PBH, with a target launch anticipated in 2027 [34][39] - A collaboration with Gubra aims to develop a novel long-acting GLP-1 receptor antagonist, indicating a strategic expansion of the company's pipeline [18] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming data readouts and the potential impact of avexitide as the first approved treatment for PBH [19][39] - The company is preparing for significant milestones in 2025 and 2026, including data from multiple ongoing trials [32][40] Other Important Information - The company has approximately $7.8 million in obligations remaining from previously recognized items related to the discontinuation of RELYVRIO/ALBRIOZA, expected to be paid through 2025 [31][32] - The company appointed Dan Monahan as Chief Commercial Officer to lead commercialization efforts, highlighting a strengthened leadership team [35] Q&A Session Summary Question: Why limit the entry criteria to just Roux-en-Y gastric bypass procedures for the PBH Phase III trial? - Management noted that they have the most experience with avexitide in patients who have undergone Roux-en-Y gastric bypass, but they recognize the pathophysiology is consistent across bariatric surgeries [45] Question: How will efficacy be interpreted in the PSP ORION study across regions? - Management indicated that both the 10-item and 28-item PSP rating scales will be analyzed, and they expect similar results from both [48] Question: What is the target profile for the long-acting GLP-1? - Management clarified that avexitide is a GLP-1 antagonist, which has shown reductions in insulin and hypoglycemia, differentiating it from GLP-1 agonists [51] Question: How is the market for PBH forecasted to change over time? - Management believes the market will continue to grow due to the chronic nature of PBH and ongoing demand for bariatric surgeries [55][59] Question: What are the expectations for the week 48 data in the Wolfram syndrome trial? - Management is looking for sustained improvements in C-peptide response and visual acuity, which would support regulatory confidence in AMX0035 [64] Question: Is there potential for avexitide to be developed for other indications beyond PBH? - Management acknowledged the potential for avexitide in other diseases characterized by hyperinsulinemic hypoglycemia but emphasized that the current focus remains on PBH [65]