AMX0114 / Amylyx - LARVOL DELTA

Amylyx Pharmaceuticals Announces First Participant Dosed in Phase 1, Multiple Ascending Dose LUMINA Trial of AMX0114 in People Living with Amyotrophic Lateral Sclerosis (Businesswire) - "Amylyx Pharmaceuticals...announced that the first participant has been dosed in LUMINA, the Company’s Phase 1, multinational, randomized, double-blind, placebo-controlled, multiple ascending dose clinical trial of AMX0114, an investigational, potent antisense oligonucleotide (ASO) targeting calpain-2, in people living with amyotrophic lateral sclerosis (ALS). The Company continues to expect early cohort data from LUMINA in 2025. The LUMINA trial (NCT06665165) will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AMX0114 in people living with ALS."

P1 data • Trial status • Amyotrophic Lateral Sclerosis

Amylyx Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "Completion of enrollment for the pivotal Phase 3 LUCIDITY clinical trial of avexitide in PBH expected in 2025, with a data readout anticipated in the first half of 2026 and, if approved, commercial launch anticipated in 2027; Early cohort data from the Phase 1 LUMINA clinical trial of AMX0114 in ALS expected in 2025."

Enrollment status • Launch • P1 data • Amyotrophic Lateral Sclerosis • Hypoglycemia

Amylyx Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results (Businesswire) - "Unblinded interim analysis of the Phase 2b portion of the Phase 2b/3 ORION trial evaluating AMX0035 for progressive supranuclear palsy (PSP) in the third quarter of 2025. ORION is an operationally seamless Phase 2b/3 clinical trial in people living with PSP. The Phase 2b portion was fully enrolled in January with a total of 139 participants randomized. Amylyx expects safety and efficacy data from an unblinded interim analysis in these participants through Week 24 and will use this data to inform a go/no-go decision on the Phase 3 portion of the trial. Early cohort data from the Phase 1 LUMINA clinical trial of AMX0114 in ALS expected in 2025. LUMINA clinical trial sites were activated in Canada in the beginning of 2025 and are recruiting participants. Amylyx is also working to open U.S. sites for screening, enrollment, and dosing."

P1 data • P2b data • Trial status • Amyotrophic Lateral Sclerosis • Progressive Supranuclear Palsy

LUMINA: AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Amylyx Pharmaceuticals Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders • CAPN2 • Plasma NfL

Amylyx Pharmaceuticals Announces FDA Has Lifted the Clinical Hold on AMX0114 Phase 1 Clinical Trial for the Treatment of Amyotrophic Lateral Sclerosis (Businesswire) - "Amylyx Pharmaceuticals, Inc...today announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold placed on the Phase 1 clinical trial of AMX0114, an investigational antisense oligonucleotide (ASO) targeting calpain-2 for people living with amyotrophic lateral sclerosis (ALS). With the clinical hold lifted, Amylyx is now working to open U.S. sites for screening, enrollment, and dosing...The announcement comes as Amylyx expects to initiate the Phase 1 LUMINA clinical trial in Canada in the beginning of 2025. LUMINA is a multicenter, randomized, placebo-controlled, multiple ascending dose trial evaluating the safety and biological activity of AMX0114....Amylyx continues to anticipate early cohort data from LUMINA in 2025."

FDA event • P1 data • Trial status • Amyotrophic Lateral Sclerosis

A Phase 1, multicenter, randomized, placebo-controlled multiple ascending dose study to evaluate the safety and tolerability of AMX0114 in Amyotrophic Lateral Sclerosis (LUMINA) (ALS-MND 2024) - "The primary endpoints of the study include the incidence of adverse events (AEs), serious AEs, and dose limiting toxicities. Secondary endpoints will be PK concentrations, including plasma and cerebrospinal fluid (CSF) levels of AMX0114. Tertiary endpoints include plasma and CSF bio-markers as well as functional measures of ALS progression."

Clinical • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • CAPN2 • NEFL

Amylyx Pharmaceuticals Reports Third Quarter 2024 Financial Results (Businesswire) - "Upcoming Expected Milestones: i) The Company plans to initiate the Phase 1 LUMINA clinical trial of AMX0114 in people living with ALS by the end of 2024 or in the beginning of 2025 in Canada...Amylyx expects early cohort data from LUMINA in 2025...ii) Data from an interim analysis of the Phase 2b/3 ORION clinical trial of AMX0035 in progressive supranuclear palsy (PSP) continue to be expected in mid-2025."

P1 data • P2/3 data • Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders • Progressive Supranuclear Palsy

LUMINA: AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis (clinicaltrials.gov) - P1 | N=48 | Not yet recruiting | Sponsor: Amylyx Pharmaceuticals Inc.

New P1 trial • Amyotrophic Lateral Sclerosis • CNS Disorders • CAPN2 • Plasma NfL

Amylyx Pharmaceuticals Reports First Quarter 2024 Financial Results (Businesswire) - "Data from an interim analysis of the ORION study of AMX0035 in PSP are expected in mid-2025....The Company plans to file an investigational new drug (IND) application, then initiate a multiple ascending dose clinical trial of AMX0114 in people living with ALS in the second half of 2024."

IND • New trial • P3 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Progressive Supranuclear Palsy

Next Steps in Development for AMX0114: An Antisense Oligonucleotide Targeting Calpain-2, a Critical Effector of Axonal Degeneration (MDA 2024) - "Conclusions AMX0114 targets a key early contributor to ALS pathogenesis and will be evaluated in first-in-human studies in 2024. A more detailed study design will be shared during MDA 2024."

Amyotrophic Lateral Sclerosis • CNS Disorders • CAPN2 • NEFL

Amylyx Pharmaceuticals to Present Updates on its AMX0114 and RELYVRIO Programs in ALS at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference (Businesswire) - "Amylyx Pharmaceuticals, Inc...announced that two abstracts detailing next steps in the development of the Company’s investigational antisense oligonucleotide (ASO), AMX0114, for the potential treatment of amyotrophic lateral sclerosis (ALS)...will be presented at the Muscular Dystrophy Association (MDA) Clinical and Scientific Conference on March 3-6, 2024 in Orlando....The Company is advancing AMX0114, our internally developed ASO targeting calpain-2, a critical effector of axonal degeneration in ALS and other neurodegenerative diseases, through investigational new drug enabling studies, with the goal of entering the clinic in 2024. This poster shares details on pre-clinical efficacy studies as well as introduces the design approach for the first-in-human study, anticipated to begin later this year."

Clinical protocol • New trial • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders

RELYVRIO and AMX0114 Data to be Presented at 34th International Symposium on ALS/MND (Amylyx) - "Amylyx Pharmaceuticals, Inc...today announced that several abstracts detailing data on AMX0035 (sodium phenylbutyrate and taurursodiol [PB&TURSO]) and the Company’s investigational antisense oligonucleotide, AMX0114, for the potential treatment of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases will be presented at the 34th International Symposium on ALS/MND. New data using a model for assessing mortality-adjusted progression (MAP) for clinical trials of ALS and encore posters will be presented." "

Clinical data • Amyotrophic Lateral Sclerosis • CNS Disorders

Update on AMX0114: An Antisense Oligonucleotide Targeting Calpain-2 a Critical Effector of Axonal Degeneration (ALS-MND 2023) - "The most potent candidate ASO, AMX0114, selected from a screen of 80 ASOs, reduced CAPN2 mRNA expression in iPSC-derived human motor neurons by >90% without cytotoxicity at the highest concentrations tested. In kinetic profiling experiments, AMX0114 treatment resulted in a maximum CAPN2 mRNA knockdown of 94% on Day 0 (48 hours after gymnosis) with a slight decrease over time to 77% on Day 21. A stable knockdown of calpain-2 protein was also achieved compared to the negative control ASO."

Amyotrophic Lateral Sclerosis • CNS Disorders • CAPN2

RELYVRIO and AMX0114 Data to be Presented at 22nd Annual Northeast ALS Consortium (NEALS) Meeting (Businesswire) - "Amylyx Pharmaceuticals, Inc...today announced the acceptance of several abstracts for presentation at the hybrid 2023 Northeast ALS Consortium (NEALS) Annual Meeting. The data being shared are related to AMX0035 (sodium phenylbutyrate and taurursodiol [PB&TURSO]) and the Company’s investigational antisense oligonucleotide, AMX0114, for the potential treatment of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases....The in-person component of the NEALS Annual Meeting will take place in Clearwater, Florida October 4-6, 2023."

Clinical data • Preclinical • Amyotrophic Lateral Sclerosis • CNS Disorders