Financial Data and Key Metrics Changes - The company ended Q2 2025 with a cash position of $180.8 million, down from $204.1 million at the end of Q1 2025, indicating a decrease in cash reserves [21] - Total operating expenses for the quarter were $42.9 million, down 43% from the same period in 2024 [22] - Research and development expenses increased to $27.2 million from $23.3 million in Q2 2024, primarily due to increased spending on Avexatide and AMX-35 [22] - Selling, general and administrative expenses decreased to $15.6 million from $21.6 million in Q2 2024 [22] - Non-cash stock-based compensation expense was $7.4 million compared to $9.6 million in Q2 2024 [23] Business Line Data and Key Metrics Changes - Avexatide, the lead asset, is in a pivotal Phase 3 trial for post-bariatric hypoglycemia (PBH) with recruitment expected to complete by year-end 2025 [5][6] - AMX-35 is being studied in progressive supranuclear palsy (PSP) and Wolfram syndrome, with top-line data from the Phase 2b ORION trial expected this quarter [10][11] - AMX-114, targeting amyotrophic lateral sclerosis (ALS), is in a Phase 1 trial with early cohort data expected by the end of the year [11] Market Data and Key Metrics Changes - The estimated prevalence of medically important PBH is around 160,000 patients, with about 30,000 classified as critical PBH [33] - The company is focusing on the Roux-en-Y gastric bypass population for the Phase 3 trial, as it provides the most robust data [69] - There is a growing recognition of PBH as a serious condition, with increasing awareness among endocrinologists and at conferences [100] Company Strategy and Development Direction - The company is preparing for a potential commercial launch of Avexatide in 2027, focusing on building a commercial organization and market access strategies [6][7] - There is a strategic emphasis on GLP-1 receptor antagonism, with potential applications in other rare diseases beyond PBH [20] - The company is actively working on obtaining an ICD-10 code for PBH to improve diagnosis and treatment pathways [57] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the strength of their clinical pipeline and the momentum being built across all programs [12] - The company is encouraged by the engagement from clinical trial sites and the potential impact of Avexatide on patients' quality of life [6][25] - Management highlighted the urgency of addressing the unmet needs of patients living with PBH and the potential for Avexatide to make a meaningful impact [25] Other Important Information - The FDA granted Fast Track designation to AMX-114, allowing for more frequent interactions and potentially expedited review [11] - The company is collaborating with Gubra to develop a novel long-acting GLP-1 receptor antagonist, showing promising initial results [7] Q&A Session Summary Question: Market opportunity for Avexatide - Management discussed the breakdown of the patient population for Avexatide, estimating about 160,000 patients may benefit, with 30,000 classified as critical PBH [33] - Enrollment for the Phase 3 trial is expected to complete by the end of the year, with data anticipated in 2026 [35] Question: Phase III trial design and patient compliance - The company has implemented strict dietary training and monitoring to prevent patients from self-liberalizing their diet during the trial [39][40] - The decision to move forward with the PSP program will be based on clinical endpoints, biomarker data, and imaging results [43] Question: Feedback from the physician community - Positive feedback was received from the physician community at the ENDO conference, with increased interest in participating in studies and referring patients [97][100] Question: Diagnosis rates and guidelines for PBH - The company noted that new guidelines have improved awareness and understanding of PBH among endocrinologists, leading to better diagnosis rates [105]

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.

Summary of Conference Call for Apogee Therapeutics Inc (APGE) and Amelix Apogee Therapeutics Inc (APGE) Industry and Company Overview - Focus on developing treatments for atopic dermatitis, asthma, and eosinophilic esophagitis (EOE) with a pipeline that includes phase two trials for multiple indications [1][2][4] Core Points and Arguments - **Atopic Dermatitis Trials**: Aiming for a six-month endpoint with reduced dosing frequency, targeting a market similar to psoriasis [1][4] - **Head-to-Head Trials**: Plans to launch a trial against Dupixent, with results expected next year [2][6] - **Market Dynamics**: The atopic dermatitis market is described as "white space," with Dupixent being the primary competitor [4][14] - **Dosing Innovations**: Emphasis on improving dosing frequency to every three months or better, which is expected to enhance efficacy [5][6][12] - **Efficacy Measures**: Data indicates deep and sustained inhibition of type two inflammation, suggesting potential for longer dosing intervals [7][8] - **Market Potential**: The atopic dermatitis market could reach $50 billion, with significant patient preference for less frequent dosing [14][15] Additional Important Content - **Patient Feedback**: Over 80% of surveyed patients preferred a drug with less frequent dosing compared to Dupixent [14] - **Financial Position**: The company has a strong balance sheet with over $680 million, providing a runway into Q1 2028 [17] Amelix Industry and Company Overview - Focus on developing treatments for rare diseases, including post-bariatric hypoglycemia (PBH) and Wolfram syndrome, with a pipeline that includes Avexatide [19][20] Core Points and Arguments - **Lead Asset - Avexatide**: A GLP-1 receptor antagonist with breakthrough therapy designation for PBH, currently in phase three trials [20][36] - **Clinical Data**: Phase two trials showed significant reductions in hypoglycemic events, with a 53% reduction in level two and a 66% reduction in level three events [38][40] - **Unmet Need**: Approximately 160,000 people in the U.S. suffer from PBH, with no approved treatments available [37][42] Additional Important Content - **Wolfram Syndrome**: Positive phase two data showing stabilization or improvement in C peptide levels, indicating better beta cell function [28][31] - **FDA Discussions**: Ongoing discussions with the FDA regarding trial design and endpoints for potential approval [30][40] - **Patient Experience**: High patient satisfaction reported, with most rating the treatment highly due to improvements in energy and reduction of hypoglycemic events [44] This summary encapsulates the key points from the conference call, highlighting the strategic focus, clinical developments, and market potential for both Apogee Therapeutics and Amelix.

Financial Data and Key Metrics Changes - The company ended the first quarter with a cash position of $204.1 million, which includes approximately $65.5 million in net proceeds from a public offering closed in January 2025 [23] - Total operating expenses for the quarter were $37.8 million, down 82% from the same period in 2024 [25] - Research and development expenses were $22.1 million compared to $36.6 million in Q1 2024, primarily due to decreased spending on AMX-thirty five and reduced payroll costs [25] - Selling, general and administrative expenses were $15.7 million compared to $57.8 million in Q1 2024, mainly due to decreased payroll and consulting costs [25] Business Line Data and Key Metrics Changes - The company is advancing three potential therapies across four clinical trials, including Avexatide for post bariatric hypoglycemia (PBH), AMX-thirty five for Wolfram syndrome and progressive supranuclear palsy (PSP), and AMX-one hundred fourteen for ALS [7][8] - Avexatide has shown promise in treating PBH, with a pivotal Phase III trial (Lucidity) initiated, and the first participant dosed [10][18] - AMX-thirty five is being evaluated in two indications, with positive Phase II data reported for Wolfram syndrome and ongoing trials for PSP [12][14] Market Data and Key Metrics Changes - There are approximately 160,000 people in the U.S. living with PBH, a condition with no approved treatment options [9][19] - The American Society for Metabolic and Bariatric Surgery reported around 270,000 new bariatric surgeries in 2023, indicating a stable market for potential PBH patients [20] - The company estimates that 8% of patients who undergo bariatric surgery will develop PBH within one to three years [48][50] Company Strategy and Development Direction - The company aims to develop novel therapies for diseases with high unmet needs, focusing on execution across its clinical trials [28] - The company is preparing for a potential commercial launch of Avexatide in 2027 if approved [10] - The company is actively engaging with clinical trial sites and expects to complete recruitment for the Lucidity trial by the end of 2025 [22] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving clinical milestones through the end of 2026, supported by a strong cash position [23][24] - The company is focused on educating the medical community and patients about PBH, given the lack of awareness and treatment options [34][46] - Management highlighted the importance of access to treatments for patients suffering from debilitating conditions like PBH [65] Other Important Information - The company plans to present week 48 data from the HELIOS trial in Wolfram syndrome at an upcoming conference [12][28] - The company is preparing for potential FDA discussions regarding trial designs for its various programs [56] Q&A Session Summary Question: Will a large patient education campaign be required for Avexatide? - Management acknowledged the need for education due to the rarity of PBH and the lack of prior treatments, emphasizing the importance of informing both medical professionals and patients [32][34] Question: What is the expected efficacy for the PSP trial? - Management stated the study has 80% power to detect a 30% effect on the PSP rating scale, with multiple endpoints being considered for decision-making [37][39] Question: How many of the 160,000 PBH patients are seeking treatment? - Management indicated that a larger group, potentially up to 1 million, may experience hypoglycemia post-bariatric surgery, but only about 160,000 have persistent symptoms warranting treatment [46][47] Question: What are the remaining questions with the FDA regarding trial design? - Management noted that the week 48 data will inform the Phase III program, but specific details of FDA discussions were not disclosed [56] Question: Will there be subgroup analysis in the Avexatide study? - Management confirmed that the study will focus on a population experiencing frequent hypoglycemic events, with no anticipated step therapy restrictions [61][62] Question: What gives confidence that Avexatide won't cause safety issues? - Management highlighted the good safety profile observed in both non-clinical and clinical data, noting that Avexatide is a competitive antagonist rather than a GLP-1 agonist [70] Question: How does Avexatide compare to other drugs in the space? - Management emphasized Avexatide's strong profile and breakthrough therapy designation, noting that other programs are earlier in development and face hurdles [82][84]

Financial Data and Key Metrics Changes - The company ended Q1 2025 with a cash position of $204.1 million, which includes approximately $65.5 million in net proceeds from a public offering closed in January 2025 [21] - Total operating expenses for the quarter were $37.8 million, down 82% from the same period in 2024 [22] - Research and development expenses were $22.1 million compared to $36.6 million in Q1 2024, primarily due to decreased spending on AMX-35 for ALS treatment [22] - Selling, general and administrative expenses were $15.7 million compared to $57.8 million in Q1 2024, mainly due to reduced payroll and consulting costs [22] Business Line Data and Key Metrics Changes - The lead asset, Avexatide, is in a pivotal Phase III trial for post-bariatric hypoglycemia (PBH), with the first participant dosed in April 2025 [6][8] - AMX-35 is being evaluated for Wolfram syndrome and progressive supranuclear palsy (PSP), with positive Phase II data reported for Wolfram syndrome [10][12] - AMX-114, targeting ALS, has initiated a Phase I trial with the first participant dosed in April 2025 [13] Market Data and Key Metrics Changes - Approximately 160,000 people in the U.S. are estimated to be living with PBH, a condition with no approved treatment options [7][17] - The American Society for Metabolic and Bariatric Surgery reported around 270,000 new bariatric surgeries in 2023, indicating a stable market for potential PBH patients [18] Company Strategy and Development Direction - The company aims to advance three potential therapies across four clinical trials, focusing on diseases with high unmet needs [6] - The anticipated commercial launch of Avexatide, if approved, is expected in 2027 [8] - The company is preparing for a potential first-to-market launch of Avexatide in PBH, emphasizing the need for patient education and market access strategies [31][60] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in achieving clinical milestones through the end of 2026, supported by a strong cash position [21][22] - The company is focused on executing its clinical programs and is optimistic about the upcoming data releases from ongoing trials [25][26] Other Important Information - The company has received FDA breakthrough therapy designation for Avexatide, highlighting the high unmet need in PBH [8][82] - The Phase III Lucidity trial is designed to evaluate the reduction in hypoglycemic events, with a robust body of data supporting Avexatide's efficacy [19][20] Q&A Session Summary Question: On Avexatide and patient education needs - Management acknowledged the need for a patient education campaign due to the rarity of PBH and the lack of prior treatments [28][31] Question: Efficacy expectations for PSP - Management indicated the study is powered to detect a 30% effect on the PSP rating scale, with multiple endpoints being considered [34][36] Question: Treatment-seeking behavior in PBH population - Management clarified that while 160,000 are estimated to have PBH, a larger group experiences hypoglycemia post-bariatric surgery, with many seeking treatment [40][42] Question: FDA discussions on trial design - Management stated that the week 48 data will inform the Phase III program, but specific details of FDA discussions were not disclosed [50][54] Question: Subgroup analysis in Avexatide study - Management confirmed that the study focuses on a population with frequent hypoglycemic events, and they do not anticipate step therapy restrictions from payers [58][60] Question: Safety concerns regarding GLP-1 antagonists - Management reassured that Avexatide has shown a good safety profile in clinical trials, with no significant adverse events reported [66][68] Question: Business development activities - Management emphasized a focus on executing current clinical trials rather than pursuing new business development opportunities at this time [70] Question: Inclusion criteria regarding NfL levels in ALS trial - Management explained that while NfL levels are high in ALS patients, they did not set specific high NfL level criteria for trial inclusion to avoid missing important signals [73][75] Question: Comparison of Avexatide to other drugs - Management highlighted Avexatide's strong profile and breakthrough therapy designation, noting that it is well-positioned compared to earlier-stage competitors [80][82]