# Clinical Development Enablement – Long Term Rodent Testing of the Carcinogenic Potential of the Alzheimer’s Disease Drug Candidate T3D-959

> **NIH NIH R44** · T3D THERAPEUTICS, INC. · 2024 · $1,009,699

## Abstract

T3D-959 is a new chemical entity, orally delivered, small molecule, dual nuclear receptor agonist aimed at
improving dysfunctional brain glucose energy and lipid metabolism in Alzheimer’s disease (AD), it is non-
amyloid/non-tau-directed. Metabolic homeostasis, inherently altered in AD, leads to protein misfolding resulting
in plaque formation, tangle formation and inflammation. Exploratory human clinical test results (Phase 2a study)
of T3D-959 in mild to moderate severity AD patients have shown multiple efficacy signals indicating a potential
to slow, stop or reverse the course of disease. A larger and longer Phase 2 clinical trial statistically powered to
measure significant differences versus placebo in outcome measures of cognition, function, and biomarkers of
disease is in progress and will complete in early 2023. This Phase 2 randomized, double-blind, placebo-
controlled ‘PIONEER’ Study is assessing multiple T3D-959 dose strengths vs. placebo (15mg, 30mg & 45mg
QD and placebo in a 1:1:1:1 ratio) to identify the most safe and effective dose or doses to use in subsequent
Phase 3 testing. The multi-center trial involves 256 mild to moderate AD patients (MMSE=14-26) dosed orally
once-a-day for 24-weeks. Co-primary outcome measures include the ADAS-cog11 cognition and ADCS-CGIC
global function measures. Secondary outcome measures include executive function as measured by DSCT and
change from baseline in plasma Aβ 42/40 ratio. With the trial 75% completed preliminary results of blinded data,
grouped as a single average of the 3 drug strength arms and placebo arm, show potential improvement in all 3
measures of cognition, function, and executive function, even before one subtracts out placebo data at trial
conclusion and un-blinding. With an anticipated successful Phase 2 clinical trial on the horizon, it becomes
prudent to conduct FDA-required, non-clinical trial studies necessary for initiation of Phase 3 clinical trials and
New Drug Application submission (NDA for market approval) in alignment with the application’s broad, long-term
objective to advance the development of T3D-959 to market in the most expeditious manner possible. The
application’s goal is to examine the long-term carcinogenic potential of T3D-959 in rats per FDA guidelines as
indicated in ICH guidance S1A for investigational new drugs, which requires 2 years of dosing in a least one
rodent species (preferably rats) prior to market approval. The objectives of carcinogenicity studies are to identify
a tumorigenic potential in animals and to assess the relevant risk in humans. The practice of requiring
carcinogenicity studies in rodents was instituted for pharmaceuticals that are expected to be administered
regularly, continuously over a period of at least 6 months (i.e., a substantial part of a patient's lifetime).

## Key facts

- **NIH application ID:** 10902097
- **Project number:** 5R44AG082580-02
- **Recipient organization:** T3D THERAPEUTICS, INC.
- **Principal Investigator:** John Didsbury
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,009,699
- **Award type:** 5
- **Project period:** 2023-08-15 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10902097

## Citation

> US National Institutes of Health, RePORTER application 10902097, Clinical Development Enablement – Long Term Rodent Testing of the Carcinogenic Potential of the Alzheimer’s Disease Drug Candidate T3D-959 (5R44AG082580-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10902097. Licensed CC0.

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