Development and Commercialization of a Tau Oligomer Inhibitor for AD/RD

PROJECT SUMMARY: This R44 supplement application is focused on the development of a comprehensive publication strategy to meet the company’s long-standing goal of disseminating its findings to the scientific community. The proposed work is designed to create a long term publication plan for the company which will include the writing and publishing of (2) manuscripts during the project term. The prevalence of AD is increasing worldwide. There remains an urgent need for disease modifying drugs for AD that are cost-effective and easy to administer. This program is progressing to fill the need with an economical, disease-modifying drug that is stable, oral, and can be self-administered. If successful, it will have a tremendous impact on the more than 6.5 million Americans who currently have AD (projected to be 12.7 million by 2050) and their caregivers, and will help reduce the current cost of $321 billion (projected to be $1 trillion by 2050) to our nation (Alzheimer's Association 2022 Alzheimer's Disease Facts and Figures). We have now completed all preclinical work for our IND application to FDA for our first-in-human phase 1a study, and our IND application was successfully submitted to FDA on June 1, 2022 (IND # 156701). A summary of this work follows: TO-0582 demonstrated pharmacologic activity in two mouse models of tauopathy (the htau model that has human tau with all 6 isomers best representing tau aggregation in AD and in the JNPL3 mouse model that has a P301L mutation and represents four-repeat tauopathies), reasonable pharmacokinetic characteristics, minimal DDI potential, lack/minimal effects on cardiovascular, pulmonary and CNS systems, and a lack of genotoxicity. Relatively modest, non-adverse toxicity was observed in 28-day rat and dog GLP toxicity studies. The no adverse effect level for both the rat and dog 28 day studies were the highest dose tested. Thus, TO-0582 is an excellent candidate for clinical development for treatment of neurodegenerative diseases. Manufacture of kilogram quantities for non-clinical safety studies (NCSS) and drug pre-formulation work has been completed. A GMP batch was also prepared for the manufacture of our drug product OLX-07010. The goal of this supplemental aim is to create a comprehensive publication strategy that will fulfill the tasks of disseminating novel and highly relevant information to the scientific community, and writing, editorial review and submission of scientific manuscripts. This includes development of a gap analysis for AD and tau-based development programs based on published literature and a review of the body of Oligomerix’s pre-clinical data. This aim will include literature searches, editorial review and submission of manuscripts. As the National Institute on Aging is the primary Federal agency for AD research, the development of a DMT for AD, has the highest relevance for its mission.