Manufacturing of ABCA1 agonist small molecule peptide CS6253 to support chronic toxicology studies in Wistar rats and Cynomolgus monkeys

PROJECT SUMMARY The primary aim of this proposal is to manufacture the ABCA1 agonist small molecule peptide CS6253 for upcoming chronic toxicology studies (outside of this grant scope) in Wistar rats and Cynomolgus monkeys. Following this, Artery Therapeutics, Inc. (ATI) plans to oversee the execution of these studies and then provide the FDA with the reports including in SEND format. The ultimate goal is to lay the groundwork for Phase 2-3 cognition trials lasting 6 months or longer, focusing on patients with Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). In addition to manufacturing the material for toxicology studies, this campaign will also include long-term stability testing. The data generated will be utilized to update the Drug Master File. CS6253 has demonstrated its safety, tolerance and favorable pharmacokinetics (PK) in the clinical Phase 1 SAD-MAD-Bioequivalence trial ATI-CS-001 (grant 1R44AG076299, National Clinical Trial # 05965414). Following these successful Phase 1 results it is imperative to proceed to cognition trials. Cognition trials typically span 6 to 9 months or longer and necessitate a comprehensive toxicology package affirming long-term safety prior to trial commencement. The chronic toxicology studies require approximately 2.3 kilograms of Good Manufacturing Practices (GMP) like Drug Substance material. To meet this demand, we will engage the services of AmbioPharm, Inc, our trusted manufacturer from previous CS6253 Drug Substance campaigns. AmbioPharm is a full-service Contract Development and Manufacturing Organization (CDMO), has successfully produced ATI's CS6253 non-GMP toxicology and GMP clinical Drug Substances that supported the Investigational New Drug (IND) application and the ATI-CS-001 clinical trial. AmbioPharm currently produces commercial peptides up to multi-kg quantities and has a quality assurance system in place for GMP peptides for clinical trials, as demonstrated by their work with CS6253 at its current stage and with other commercial peptide products. CS6253 Drug Substance has displayed 32+ months stability when stored in -20 degree C condition. Also, the ongoing ICH Drug Product stability testing shows that CS6253 in solution remains stable for more than 9 months in 5 degree C.