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First in Human Study of a Tau Self-Association Small Molecule Inhibitor in Healthy Volunteers

首次在健康志愿者中进行 Tau 自联小分子抑制剂的人体研究

基本信息

批准号：
10673633
负责人：
William A. Erhardt
金额：
$ 203.96万
依托单位：
OLIGOMERIX, INC
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10673633
关键词：
Adult Adverse event Alzheimer&apos s Disease Alzheimer&apos s disease patient American Benchmarking Biological Assay California Canis familiaris Caregivers Cause of Death Clinical Clinical Research Clinical Trials Development Disease Dose Drug Kinetics Elderly Evaluation Female Formulation Frontotemporal Dementia Future Goals Grant Human In Vitro Incidence Investigational Drugs Investigational New Drug Application Kilogram Lead Medical Monitor Mus Nerve Degeneration Neurodegenerative Disorders Outcome Pathologic Processes Patients Pharmaceutical Preparations Pharmacology Phase Population Prevalence Preventive Progressive Supranuclear Palsy Randomized Rattus Research Safety Schedule Single-Blind Study Special Event Study Subject Tauopathies Therapeutic Therapeutic Intervention Therapeutic Studies Toxicology United States Work Writing appropriate dose clinical development cohort cost cost effective design drug development efficacy study first-in-human healthy volunteer human study in vitro Assay in vivo in vivo evaluation inhibitor interest male manufacture monomer mouse model pharmacologic pre-Investigational New Drug meeting prevent programs response safety assessment safety study small molecule small molecule inhibitor success tau Proteins tau aggregation volunteer

项目摘要

PROJECT SUMMARY This program is focused on developing a disease-modifying drug for Alzheimer’s disease (AD) by advancing its small molecule drug OLX-07010 into clinical development. There are no disease-modifying drugs for AD, and the prevalence of AD is increasing worldwide. This program is progressing to fill this need with a disease modifying drug that, if successful, will have a tremendous impact on the more than 6.2 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 $355 billion (projected to be $1.1 trillion by 2050) to our nation (Alzheimer's Association 2021 Alzheimer's Disease Facts and Figures). Key requirements for treating early-stage AD include safe, efficacious, and cost- effective therapeutic interventions. This small molecule, CNS drug-like lead substantially fulfills these requirements based on our preliminary results. This highly differentiated approach targets tau self-association at the beginning of the tau aggregation cascade. Small molecules were screened and optimized using in vitro assays to select molecules that inhibit the formation of tau oligomers from tau monomers. In vitro pharmacology and pharmacokinetic (PK) studies in mice were used to select a lead compound for evaluation of in vivo efficacy. Preventive and therapeutic studies in two mouse models of tauopathy, representing tau aggregation in Alzheimer’s disease (AD) and four-repeat-tau tauopathies, demonstrated proof-of-concept and supported the selection of this compound for further development. 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. A pre-IND meeting written response with FDA is scheduled for July 23, 2021 (PIND Number 156701) to finalize dose selection for the 28-day GLP safety studies in dogs and rats. The Investigational New Drug (IND) application is planned for the first quarter in 2022 to enable the first in human (FIH) studies that are the subject of this application to commence early in the second quarter of 2022. This R01 Phase 1a single-blind, randomized, three-part study is designed to evaluate the safety, tolerability, and pharmacokinetics of the tau self-association inhibitor, in single ascending doses, multiple ascending doses, and a single dose in healthy elderly. The Aim of this application in Year 1 is to demonstrate safety and PK of OLX- 07010 in healthy volunteers after single dosing, and during Year 2 the Aims are to demonstrate safety and PK of OLX-07010 in healthy volunteers after multiple dosing, and to demonstrate safety and PK of OLX-07010 in healthy elderly volunteers after single dosing. These studies will enable the determination of dosing for subsequent proof-of-concept studies in AD and other neurodegenerative diseases.

项目总结