Development of M102 to Investigational New Drug (IND) Stage for Initiation of Phase 1 Clinical Trials for Treating Amyotrophic Lateral Sclerosis (ALS)
Abstract
This project is focused on the preclinical development of M102, a proprietary small-molecule new chemical entity (NCE), in a collaborative effort involving Aclipse One, Inc., and the Sheffield Institute for Translational Neuroscience (SITraN, University of Sheffield, United Kingdom). The ultimate applicability of this research is to lead to the regulatory approval of M102 for its clinical use to treat amyotrophic lateral sclerosis (ALS) patients. M102 is a disease-modifying drug candidate for ALS that activates NRF2 (nuclear factor erythroid 2-related factor 2) and HSF1 (heat shock factor 1) signaling pathways, recently understood disease pathways in ALS. Aclipse is one of the first companies taking a multiple-pathway, multiple-disease mechanism approach to ALS. With this approach, the development of M102 is aimed at the treatment of all familial and sporadic ALS patients. As a pro-electrophilic drug, M102 has advantageous properties and is unique, since it only activates the NRF2 and HSF1 pathways in cells under oxidative stress, thus reducing potential off-target effects. When combining our strong preclinical data for M102, existing research experience with ALS, and extensive drug development experience of the Principal Investigator (PI)/co-PIs, we believe we have a sound and de-risked foundation for completing regulatory-viable preclinical development studies and therefore realizing a successful investigational new drug (IND) application to initiate first-in-human clinical trials. M102 has received the U.S. Food and Drug Administration (FDA) orphan drug designation and the European Medicines Agency (EMA) orphan designation. M102 is protected by four patent families covering composition-of-matter, method of use, pharmacokinetics, formulations, and process. Our plan is to proceed to clinical studies in healthy volunteers and ALS patients at the end of this project, and, if successful, we would expect a potential new drug application (NDA) approval by the FDA. M102 is expected to be mechanistically superior to the currently available drugs and may lead to significant slowing of disease progression in ALS. Even if clinical impact is not an immediate outcome, the development of therapeutically relevant biomarkers will contribute to the continuous effort to develop effective disease modifying therapies for ALS and more robust and nimble clinical trials to evaluate potential new neuroprotective agents. Thus, the proposed research has strong potential to deliver a sustained impact on the trajectory of this devastating condition.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210175
Entities
People
- Ning Shan
Organizations
- United States Army