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

> **NIH NIH R01** · OLIGOMERIX, INC · 2024 · $336,857

## Abstract

PROJECT SUMMARY
This program is focused on developing a disease-modifying drug for Alzheimer’s disease (AD) by advancing our
lead compound into clinical development. There are no disease-modifying small molecule 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 6.7 million Americans who currently
have AD (projected to be 13.8 million by 2060) and their caregivers, and will help reduce the current cost of $345
billion (projected to be $1.1 trillion by 2050) to our nation (Alzheimer's Association 2023 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 significantly fulfills these requirements based
on our preliminary results. This highly differentiated tau self-association inhibitor 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
studies 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. Methods development and manufacture of 1.61 kg of the
lead compound was completed for non-clinical safety studies. GMP manufacture of a 2.8 kg batch of drug
substance for initial clinical studies was completed, and pre-formulation studies for development of drug product
were completed. The IND was submitted (June 1, 2022) for first in human (FIH) studies that initiated in early
2023. The awarded Phase 1a study is a double-blind, randomized, three-part study designed to evaluate the
safety, tolerability, and pharmacokinetics of the tau self-association inhibitor, in single ascending doses, multiple
ascending doses, and single doses in healthy elderly. This Supplement is to cover unanticipated incremental
costs related to project delays directly attributable to FDA requests for additional toxicology data on the
compound prior to progressing to higher doses in human volunteers. The Aims of this one-year supplement are
as follows: Aim 1. GMP Manufacture of additional batches of capsules, at two different strengths, using
established process and formulation to provide additional clinical supplies. It is urgent that these activities be
supported and started as soon as possible as currently available clinical supplies will reach their expiry date prior
to the anticipated date of completion of clinical activities. Any delay in providing this support will result ...

## Key facts

- **NIH application ID:** 10992968
- **Project number:** 3R01AG076565-02S1
- **Recipient organization:** OLIGOMERIX, INC
- **Principal Investigator:** William A. Erhardt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $336,857
- **Award type:** 3
- **Project period:** 2022-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10992968

## Citation

> US National Institutes of Health, RePORTER application 10992968, First in Human Study of a Tau Self-Association Small Molecule Inhibitor in Healthy Volunteers (3R01AG076565-02S1). Retrieved via AI Analytics 2026-06-13 from https://api.ai-analytics.org/grant/nih/10992968. Licensed CC0.

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