# Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial of T3D-959 in Mild to Moderate Alzheimer's Disease Subjects

> **NIH NIH R01** · T3D THERAPEUTICS, INC. · 2022 · $1,520,269

## Abstract

Exploratory human clinical test results (Phase 2a study) of the investigational new drug T3D-959 in mild
to moderate severity Alzheimer's disease patients have shown multiple efficacy signals indicating a potential to
slow, stop or reverse the course of Alzheimer's disease (AD). The next stage in the development of this drug to
eventual market is establishing clinical proof of concept (PoC) to validate these observed efficacy signals by
testing in T3D-959 in a larger and longer second Phase 2 human clinical trial. The objective of the proposed
project is to execute and complete this PoC study of T3D-959 in AD patients. The clinical trial will be a
randomized, double-blind, placebo-controlled, multi-center Phase 2 trial (RCT) involving 120 mild to moderate
AD patients dosed orally once-a-day for 24-weeks in 2 parallel arms (T3D-959 30mg active arm and a placebo
arm in a 1:1 ratio). Co-primary outcome measures will include the ADAS-cog11 cognition measure and global
function CDR-SB measure. Secondary and exploratory outcome measures will include the ADCS-ADL
measure of activities of daily living and FDG-PET neuroimaging. Based on ADAS-cog11 data in the completed
exploratory study, this RCT is 80% powered for significance; α=0.05, assuming an effect of a 4-point difference
vs. placebo at 24-weeks, and a standard deviation of 7.8 pts.
 T3D-959 is being developed as a potential disease-modifying agent for the treatment of cognitive and
functional decline in AD patients. In addition to the exploratory/feasibility Phase 2a clinical study in mild to
moderate AD subjects, T3D-959 has successfully completed Phase I studies in normal individuals with an
excellent safety and tolerability profile. In the non-placebo-controlled, dose range finding Phase 2a trial in 34
mild to moderate AD patients dosed orally once-a-day for 2-weeks with varying doses of T3D-959, there was
observed; (a) rapid, high magnitude, durable improvement in ADAS-cog11 with a significant ApoE genotype
association to response, (b) improvement in DSST (Digit Symbol Substitution Test), a second measure of
executive function and (c) FDG-PET neuroimaging showing; (i) T3D-959 penetrated the brain to effect changes
in glucose metabolism, (ii) T3D-959 increased glucose metabolism in the brain, (iii) a dose dependency to
FDG-PET outcomes, (iv) T3D-959 may increase relative glucose metabolism in all AD-vulnerable regions of
the brain prototypically glucose hypometabolic, (v) ApoE genotype influence on the effect of T3D-959 on
relative glucose metabolism. There were no observed safety or tolerability issues.
 T3D-959 is a small molecule new chemical entity, orally delivered, dual nuclear receptor agonist and
the first PPAR delta-activating compound to be developed for the treatment of AD. Uniquely, this drug also
activates PPAR gamma (at 15-fold lower potency) which may provide potential additive or synergistic effects in
regulating dysfunctional brain glucose energy and lipid metabolism in AD. PPA...

## Key facts

- **NIH application ID:** 10357575
- **Project number:** 5R01AG061122-04
- **Recipient organization:** T3D THERAPEUTICS, INC.
- **Principal Investigator:** John Didsbury
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,520,269
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357575

## Citation

> US National Institutes of Health, RePORTER application 10357575, Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial of T3D-959 in Mild to Moderate Alzheimer's Disease Subjects (5R01AG061122-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10357575. Licensed CC0.

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