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]

Group 1: Core Insights - Goldman Sachs' latest report focuses on "2Q25 EPS updates," analyzing biotech companies such as Amylyx (AMLX.US), CG Oncology (CGON.US), GPCR (GPCR.US), and Ideaya Biosciences (IDYA.US), concluding that operational data largely meets expectations with minor adjustments to target prices due to cash flow or clinical milestones [1] Group 2: Amylyx (AMLX.US) - In Q2, Amylyx reported operating expenses of approximately $43 million, slightly above market consensus of $41 million and Goldman Sachs' estimate of $40 million, primarily due to higher R&D costs of $27 million compared to the expected range of $22 million to $25 million [2] - The management reiterated the timeline for the Phase III clinical trial for post-bariatric hypoglycemia (PBH), aiming for enrollment completion in 2025, data readout in the first half of 2026, and potential market entry in 2027, with an estimated patient population of around 160,000 [2] - Goldman Sachs maintains a "Buy" rating with a target price of $10 [2] Group 3: CG Oncology (CGON.US) - CG Oncology's BOND-003 Phase III trial data showed a complete response rate of 75.5% for its bladder cancer gene therapy, with 12-month and 24-month sustained response rates of 50.7% and 42.3%, respectively [3] - The company has $661 million in cash, sufficient to support operations until mid-2028, and Goldman Sachs maintains a "Buy" rating with minor model adjustments [3] Group 4: GPCR (GPCR.US) - GPCR's Q2 R&D expenses were approximately $54 million, significantly higher than market expectations of $36 million and Goldman Sachs' estimate of $44 million, attributed to workforce expansion and increased trial costs [4] - The company has $787 million in cash, expected to last until 2027, and plans to read out Phase 2b ACCESS data in 2025 [4] Group 5: Ideaya Biosciences (IDYA.US) - Ideaya reported Q2 R&D expenses of about $74 million, slightly above market expectations of $71 million and Goldman Sachs' estimate of $68 million, with cash reserves of $992 million projected to last until 2029 [5] - The core pipeline includes darovasertib in combination with crizotinib for HLA-A2 negative metastatic uveal melanoma, with Phase 2/3 results expected by year-end [5] Group 6: Terns Pharmaceuticals (TERN.US) and RNA (RNA.US) - Terns Pharmaceuticals plans to release preliminary data for its leukemia drug TERN-701 and obesity drug TERN-601 in Q4 2025, with cash reserves of $315 million sufficient until 2028 [6] - RNA has signed a manufacturing agreement with Lonza to ensure product supply stability from 2026 to 2028, with BLA submissions expected for its treatments by the end of 2025 and mid-2026 [6] Group 7: AI in Biotech - Goldman Sachs emphasizes the core role of biotechnology R&D, highlighting collaborations with institutions like OpenAI to drive innovation, while also focusing on the pricing potential of rare disease drugs and opportunities for indication expansion [7] Group 8: Overall Industry Outlook - The biotech sector is expected to see over 15 key clinical data readouts from late 2025 to early 2026, with a focus on companies like AMLX, CGON, and RNA for their potential breakthroughs [8] - Despite some companies facing increased short-term losses due to R&D spending, pipeline progress remains in line with expectations, and cash flow is generally secure [8]

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]

Investigational Therapies - The company is developing three investigational therapies: avexitide for PBH, AMX0035 for Wolfram syndrome and PSP, and AMX0114 for ALS[77][84][93]. - Avexitide has received Breakthrough Therapy Designation from the FDA for both PBH and congenital hyperinsulinism, with approximately 160,000 people affected by PBH in the U.S.[78][79]. - The pivotal Phase 3 LUCIDITY trial for avexitide began in April 2025, with 75 participants expected to complete the study by 2025 and topline data anticipated in the first half of 2026[80]. - In the Phase 2b trial, avexitide 90 mg once daily resulted in a statistically significant 53% reduction in Level 2 hypoglycemic events and a 66% reduction in Level 3 events[82]. - AMX0035 has shown sustained improvement in pancreatic beta cell function in the HELIOS trial, with positive long-term data through Week 48[88][90]. - The Phase 2b/3 ORION trial for AMX0035 in PSP completed enrollment in January 2025 with 139 participants, and interim efficacy data is expected in Q3 2025[92]. - AMX0114 has received Fast Track designation from the FDA for ALS, with the first participant dosed in the Phase 1 LUMINA trial in April 2025[93][95]. - The company is collaborating with Gubra A/S to develop a novel long-acting GLP-1 receptor antagonist, with plans to identify a lead candidate for IND-enabling studies[83]. - The company aims to address high unmet medical needs in neurodegenerative diseases and endocrine conditions through its investigational therapies[77]. - The total number of people affected by PSP in the U.S. is estimated at 23,000, with no approved therapies currently available[91]. Financial Performance - Research and development expenses increased to $27.2 million for the three months ended June 30, 2025, compared to $23.3 million for the same period in 2024, marking a 17% increase[110]. - The increase in research and development expenses was primarily driven by a $7.1 million rise in costs related to the Phase 3 LUCIDITY clinical trial for avexitide and a $3.6 million increase for AMX0035 for the treatment of PSP[110]. - Selling, general and administrative expenses decreased to $15.6 million for the three months ended June 30, 2025, down 28% from $21.6 million in the same period in 2024[111]. - The company did not generate any product revenue for the three months ended June 30, 2025, due to the discontinuation of RELYVRIO®/ALBRIOZA™[107]. - Total operating expenses for the three months ended June 30, 2025, were $42.9 million, a 43% decrease from $75.3 million in the same period in 2024[106]. - The net loss for the three months ended June 30, 2025, was $41.4 million, a 43% improvement compared to a net loss of $72.7 million for the same period in 2024[106]. - For the six months ended June 30, 2025, product revenue was $0, a 100% decrease from $87.6 million in the same period in 2024[113]. - Research and development expenses for the six months ended June 30, 2025, totaled $49.3 million, an 18% decrease from $60.0 million in the same period in 2024[113]. - Selling, general and administrative expenses were $31.3 million for the six months ended June 30, 2025, compared to $79.4 million for the same period in 2024, reflecting a significant reduction in payroll and consulting costs[118]. - The company did not recognize restructuring expenses for the six months ended June 30, 2025, after incurring approximately $22.9 million in restructuring costs in the prior year[119]. - As of June 30, 2025, the company had cash, cash equivalents, and marketable securities totaling $180.8 million, with an accumulated deficit of $684.0 million[121]. - The January 2025 Offering resulted in proceeds of approximately $65.5 million, net of underwriting discounts and offering expenses[120]. - Net cash used in operating activities was $65.1 million for the six months ended June 30, 2025, compared to $67.1 million in the same period of 2024, indicating a slight improvement[127]. - Net cash provided by financing activities increased significantly to $65.6 million for the six months ended June 30, 2025, compared to only $0.2 million in the prior year[133]. - The company expects to incur significant expenses related to ongoing research and development activities, particularly for avexitide and AMX0035, as well as potential acquisitions or in-licensing of new product candidates[124]. - The company anticipates financing its near-term operations through existing cash and potential equity or debt financing, with no assurances that additional funding will be available on favorable terms[123]. Restructuring and Cost Management - The restructuring plan implemented in April 2024 resulted in a workforce reduction of approximately 70% and a significant decrease in external financial commitments[103]. - The company recorded approximately $117.9 million in charges related to inventory write-downs and losses on firm purchase commitments for the six months ended June 30, 2024[116]. - Research and development expenses decreased to $49.3 million for the six months ended June 30, 2025, down from $60.0 million in the same period of 2024, primarily due to a $22.6 million reduction in spending on AMX0035 for ALS[117].

[Q2 2025 Business and Financial Overview](index=1&type=section&id=Amylyx%20Pharmaceuticals%20Reports%20Second%20Quarter%202025%20Financial%20Results) Amylyx Pharmaceuticals highlights clinical pipeline advancements and stable financial performance in Q2 2025 [Management Commentary](index=1&type=section&id=Management%20Commentary) Management expressed encouragement regarding pipeline strength and progress toward key clinical milestones - The company is focused on disciplined execution across its clinical programs, with several key data readouts and updates expected through **H1 2026**[3](index=3&type=chunk) - Key upcoming milestones include: - **Avexitide (LUCIDITY Trial):** Complete recruitment in **2025**, with topline data in **H1 2026** - **AMX0035 (ORION Trial):** Unblinded Phase 2b analysis in **Q3 2025** to inform Phase 3 progression - **AMX0035 (Wolfram Syndrome):** Program update expected later in **2025** - **AMX0114 (LUMINA Trial):** Received FDA Fast Track designation; early cohort data expected later in **2025**[3](index=3&type=chunk) [Second Quarter and Recent Updates](index=1&type=section&id=Second%20Quarter%20and%20Recent%20Updates) Amylyx highlighted significant progress in its clinical trials and maintained a strong cash position through 2026 - Cash, cash equivalents, and marketable securities stood at **$180.8 million** as of June 30, 2025, with a projected cash runway through the end of **2026**[5](index=5&type=chunk) - Presented new data for avexitide (for PBH) showing the **90 mg once-daily dose** led to a **64% reduction (p=0.0031)** in hypoglycemic events versus baseline in a Phase 2b trial[6](index=6&type=chunk) - Presented long-term Week 48 data from the Phase 2 HELIOS trial of AMX0035 in Wolfram syndrome, demonstrating continued and sustained improvement in pancreatic beta cell function and stabilization in other disease progression outcomes[6](index=6&type=chunk) - Received FDA Fast Track designation for AMX0114, an investigational treatment for amyotrophic lateral sclerosis (ALS), in June 2025[7](index=7&type=chunk) [Upcoming Expected Milestones](index=2&type=section&id=Upcoming%20Expected%20Milestones) The company outlined several key catalysts expected in the near term across its clinical pipeline - **Avexitide (LUCIDITY Trial):** Expect to complete recruitment in **2025**, with data readout in **H1 2026** and a potential commercial launch in **2027** if approved[10](index=10&type=chunk) - **AMX0035 (ORION Trial for PSP):** An unblinded analysis of the Phase 2b portion is expected in **Q3 2025**, which will determine the progression to Phase 3[10](index=10&type=chunk) - **AMX0035 (Wolfram Syndrome):** An update on the program, including the design of a Phase 3 trial informed by positive Phase 2 data and FDA discussions, is expected in **2025**[10](index=10&type=chunk) - **AMX0114 (LUMINA Trial for ALS):** Early cohort data from the Phase 1 trial, evaluating safety and biological activity, is expected in **2025**[10](index=10&type=chunk) [Q2 2025 Financial Performance](index=2&type=section&id=Financial%20Results%20for%20the%20Second%20Quarter%20Ended%20June%2030%2C%202025) The company significantly reduced its net loss in Q2 2025, driven by lower operating expenses and a strong cash position [Financial Results Summary](index=2&type=section&id=Financial%20Results%20Summary) In Q2 2025, Amylyx reported a significantly reduced net loss driven by lower operating expenses, while maintaining a solid cash position | Financial Metric | Q2 2025 | Q2 2024 | | :--- | :--- | :--- | | R&D Expenses | $27.2 million | $23.3 million | | SG&A Expenses | $15.6 million | $21.6 million | | Net Loss | $41.4 million | $72.7 million | | Net Loss Per Share | $0.46 | $1.07 | - The company's cash, cash equivalents, and marketable securities were **$180.8 million** at the end of Q2 2025, with a projected cash runway through the end of **2026**[12](index=12&type=chunk) [Research and Development (R&D) Expenses](index=2&type=section&id=R%26D%20Expenses) R&D expenses increased in Q2 2025 due to advancing clinical programs for avexitide and AMX0035 for PSP | Expense Category | Q2 2025 | Q2 2024 | | :--- | :--- | :--- | | R&D Expenses | $27.2 million | $23.3 million | | Stock-based Compensation (in R&D) | $2.0 million | $2.4 million | - The increase in R&D spending was mainly due to advancing the avexitide and PSP programs[9](index=9&type=chunk) [Selling, General, and Administrative (SG&A) Expenses](index=3&type=section&id=SG%26A%20Expenses) SG&A expenses decreased in Q2 2025, primarily due to lower payroll and professional services costs | Expense Category | Q2 2025 | Q2 2024 | | :--- | :--- | :--- | | SG&A Expenses | $15.6 million | $21.6 million | | Stock-based Compensation (in SG&A) | $5.4 million | $7.1 million | - The decrease in SG&A was driven by reduced personnel costs and lower use of consulting and professional services[11](index=11&type=chunk) [Net Loss](index=3&type=section&id=Net%20Loss) The company reported a significantly reduced net loss in Q2 2025 compared to the prior year, reflecting improved cost management | Metric | Q2 2025 | Q2 2024 | | :--- | :--- | :--- | | Net Loss | $(41.4) million | $(72.7) million | | Net Loss Per Share | $(0.46) | $(1.07) | [Cash Position and Runway](index=3&type=section&id=Cash%20Position) Amylyx maintained a strong cash position of $180.8 million as of June 30, 2025, projected to fund operations through 2026 | Date | Cash, Cash Equivalents, and Marketable Securities | | :--- | :--- | | June 30, 2025 | $180.8 million | | March 31, 2025 | $204.1 million | - Based on current operating plans, the company's cash runway is expected to last through the end of **2026**[12](index=12&type=chunk) [Clinical Pipeline and Programs](index=3&type=section&id=Clinical%20Pipeline%20and%20Programs) Amylyx is advancing multiple clinical programs, including avexitide for PBH, AMX0035 for Wolfram syndrome and PSP, and AMX0114 for ALS [Avexitide Program (for PBH)](index=3&type=section&id=Avexitide%20Program%20(for%20PBH)) Avexitide is an investigational GLP-1 receptor antagonist for post-bariatric hypoglycemia (PBH), currently in a pivotal Phase 3 trial [About Avexitide](index=3&type=section&id=About%20Avexitide) Avexitide is a first-in-class GLP-1 receptor antagonist with FDA Breakthrough Therapy Designation for PBH and HI - Avexitide is an investigational GLP-1 receptor antagonist designed to inhibit the effect of GLP-1, thereby decreasing insulin secretion and stabilizing blood glucose[15](index=15&type=chunk) - The FDA has granted avexitide Breakthrough Therapy Designation for both post-bariatric hypoglycemia (PBH) and congenital hyperinsulinism (HI)[15](index=15&type=chunk) [About Post-Bariatric Hypoglycemia (PBH)](index=3&type=section&id=About%20Post-Bariatric%20Hypoglycemia%20(PBH)) PBH is a debilitating condition affecting approximately 160,000 people in the U.S. with no approved therapies - PBH is estimated to affect approximately **8%** of people in the U.S. who have undergone sleeve gastrectomy or Roux-en-Y gastric bypass surgery (approx. **160,000 people**)[16](index=16&type=chunk) - The condition can cause debilitating neuroglycopenic symptoms like impaired cognition, loss of consciousness, and seizures. There are no approved therapies for PBH[16](index=16&type=chunk) [About the LUCIDITY Trial](index=4&type=section&id=About%20the%20LUCIDITY%20Trial) The LUCIDITY trial is a pivotal Phase 3 study evaluating avexitide's efficacy and safety in PBH, with reduction in hypoglycemic events as the primary endpoint - LUCIDITY is a Phase 3, randomized, double-blind, placebo-controlled trial enrolling approximately **75 participants** at **20 sites** in the U.S[17](index=17&type=chunk)[18](index=18&type=chunk) - The trial is evaluating a **90 mg once-daily dose** of avexitide, with the primary outcome being the reduction in Level 2 and Level 3 hypoglycemic events through Week 16[18](index=18&type=chunk) [Other Key Programs](index=1&type=section&id=Other%20Key%20Programs) Amylyx is advancing AMX0035 for Wolfram syndrome and PSP, and AMX0114 for ALS, with several upcoming data readouts [AMX0035 (for Wolfram Syndrome & PSP)](index=1&type=section&id=AMX0035%20(for%20Wolfram%20Syndrome%20%26%20PSP)) AMX0035 is being evaluated for Wolfram syndrome and progressive supranuclear palsy (PSP), with key data readouts expected soon - **Wolfram Syndrome:** Long-term Week 48 data from the Phase 2 HELIOS trial demonstrated continued sustained improvement or stabilization across key measures, including pancreatic function and vision[6](index=6&type=chunk)[10](index=10&type=chunk) - **PSP:** The Phase 2b portion of the ORION trial is fully enrolled, and an unblinded analysis of Week 24 data in **Q3 2025** will inform a go/no-go decision for the Phase 3 portion[10](index=10&type=chunk) [AMX0114 (for ALS)](index=2&type=section&id=AMX0114%20(for%20ALS)) AMX0114, an investigational antisense oligonucleotide for ALS, received FDA Fast Track designation, with early Phase 1 data expected in 2025 - AMX0114 received FDA Fast Track designation in June 2025, allowing for more frequent communication with the agency[7](index=7&type=chunk) - The Phase 1 LUMINA trial is a multiple ascending dose study in approximately **48 participants**, with early cohort data expected in **2025**[10](index=10&type=chunk) [Financial Statements](index=5&type=section&id=Financial%20Statements) Detailed financial statements for Q2 2025 show balance sheet and income statement performance [Condensed Consolidated Balance Sheets](index=5&type=section&id=CONDENSED%20CONSOLIDATED%20BALANCE%20SHEETS) As of June 30, 2025, Amylyx reported total assets of $194.6 million and a strong cash position of $180.8 million | (in thousands) | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Assets** | | | | Cash, cash equivalents and marketable securities | $180,826 | $176,501 | | Total assets | $194,598 | $193,634 | | **Liabilities and Stockholders' Equity** | | | | Total liabilities | $26,721 | $28,869 | | Stockholders' equity | $167,877 | $164,765 | | Total liabilities and stockholders' equity | $194,598 | $193,634 | [Condensed Consolidated Statements of Operations](index=5&type=section&id=CONDENSED%20CONSOLIDATED%20STATEMENTS%20OF%20OPERATIONS) For Q2 2025, Amylyx reported no product revenue and a net loss of $41.4 million, a significant improvement from Q2 2024 | (in thousands, except per share data) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | | :--- | :--- | :--- | | Product revenue, net | $— | $(1,023) | | Total operating expenses | $42,857 | $75,263 | | Loss from operations | $(42,857) | $(76,286) | | Net loss | $(41,443) | $(72,700) | | Net loss per share — basic and diluted | $(0.46) | $(1.07) |

Core Insights - Amylyx Pharmaceuticals presented new exploratory analyses of avexitide at the Endocrine Society's annual meeting, focusing on its potential to treat post-bariatric hypoglycemia (PBH) [1] Group 1: Clinical Trials and Efficacy - The Phase 2b trial of avexitide showed a 64% reduction in moderate to severe hypoglycemic events with a 90 mg once-daily dose, and over half of participants experienced no such events during treatment [2] - The ongoing Phase 3 LUCIDITY trial is evaluating avexitide's safety and efficacy in approximately 75 patients with PBH following Roux-en-Y gastric bypass surgery, with a primary endpoint of reducing Level 2 and 3 hypoglycemic events [3] - Previous trials demonstrated consistent, dose-dependent reductions in hypoglycemic events, with the 90 mg dose showing sustained 24-hour GLP-1 receptor inhibition [4] Group 2: Safety Profile and Future Prospects - Across five clinical trials, avexitide has shown statistically and clinically meaningful efficacy with a favorable safety profile [5] - LUCIDITY is expected to complete enrollment in 2025, with top-line results anticipated in the first half of 2026 and a potential commercial launch in 2027 [5] Group 3: Market Impact - Following the presentation of these findings, AMLX stock increased by 7.55%, reaching $8.26 [5]

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]

Core Viewpoint - Bragar Eagel & Squire, P.C. is investigating potential claims against Amylyx Pharmaceuticals, Inc. due to a class action complaint alleging breaches of fiduciary duties by the company's board of directors during the specified class period [1][2]. Summary by Relevant Sections Allegations of Misconduct - The complaint asserts that the Individual Defendants made false and misleading statements regarding the Relyvrio commercial launch, claiming significant demand that was not sustainable [2]. - It is alleged that the initial surge in demand for Relyvrio was temporary and had already subsided within months of its launch, undermining growth potential among newly diagnosed ALS patients [2]. - The complaint highlights that there were high, undisclosed discontinuation rates for Relyvrio, which negatively impacted the drug's commercial viability and inflated the perceived potential for acquiring new patients [2]. Legal Representation - Bragar Eagel & Squire, P.C. is representing long-term stockholders of Amylyx and is open to inquiries regarding the claims and rights of investors [3]. Firm Background - Bragar Eagel & Squire, P.C. is a recognized law firm specializing in representing individual and institutional investors in various complex litigations across state and federal courts [4].

Core Viewpoint - Guggenheim Partners has initiated coverage on Amylyx Pharmaceuticals, highlighting the potential of post-bariatric hypoglycemia (PBH) as a significant market opportunity for the company [1][2]. Company Overview - Amylyx Pharmaceuticals is positioned as a first-to-market player in the PBH space, which is estimated to be a $2 billion+ market opportunity [2]. - The company's lead drug, avexitide, is advancing towards pivotal Phase 3 results in the LUCIDITY study, expected to read out in the first half of 2026 [3]. Market Potential - Guggenheim estimates that there are 50,000 to 100,000 individuals in the U.S. suffering from moderate to severe uncontrolled symptoms of PBH [4]. - The global market for GLP-1 antagonists to treat PBH could exceed $2 billion by 2035, with projections of $1.8 billion in the U.S. and $410 million internationally, assuming a 60% peak market share among patients with severe PBH [4]. Competitive Landscape - The main competitor in the PBH market is MBX Biosciences, which is developing a once-weekly GLP-1 antagonist called MBX 1416 [5]. - Analyst estimates suggest that a once-weekly competitor could launch by 2031, while Amylyx's life cycle management strategy may enhance its market position [5]. Stock Performance - As of the last check, Amylyx Pharmaceuticals' stock (AMLX) has increased by 24.5%, reaching $6.25 [5].

Study Overview - The HELIOS trial evaluated the safety, tolerability, and efficacy of PB&TURSO in Wolfram Syndrome patients [1, 15] - The study was an open-label Phase 2 trial [1, 16] - The trial included 12 enrolled participants, with 11 in the Per Protocol (PP) population who had genetically confirmed Wolfram Syndrome [16, 26] Efficacy Results - At Week 24, the Per Protocol group (N=11) showed improvement in C-peptide response to Mixed Meal Tolerance Test (MMTT) compared to screening [30, 31] - At Week 24, C-Peptide AUC increased by 16.8 min*ng/mL in ITT population and 20.2 min*ng/mL in Per Protocol population [34] - 10 out of 11 participants in the Per Protocol group maintained or decreased time to peak C-peptide at Week 24 compared to screening [37, 38] - HbA1c levels showed a mean change from baseline of -0.09% in the ITT group and -0.16% in the Per Protocol group at Week 24 [40, 45] - 9 of 11 Per Protocol participants demonstrated reduced or unchanged HbA1c from Screening to the latest available time point [42] - 8 of 11 participants in the Per Protocol group demonstrated improved or stable visual acuity in their best eye from Screening to the latest available timepoint [51] Safety and Tolerability - PB&TURSO was generally well-tolerated [53] - 91.7% of participants (11 out of 12) experienced at least one Treatment Emergent Adverse Event (TEAE) [53] - Diarrhea was the most common TEAE, affecting 50% of participants, but all cases were of mild severity [55]