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AAIC 2022 | Phase IIa exploratory trial of T3D-959 in mild-moderate Alzheimer’s disease

John Didsbury, PhD, T3D Therapeutics, Inc., Research Triangle Park, NC, introduces T3D-959: a novel therapeutic aimed at improving dysfunctional brain glucose energy and lipid metabolism in Alzheimer’s disease (AD). The rationale for its use is based on the metabolic hypothesis of AD, which states that dysfunctional glucose and lipid metabolism leads to brain starvation, pathological protein accumulation, inflammation, and neurodegeneration. T3D-959 targets PPAR delta/gamma: central regulators of normal glucose and lipid metabolism in the brain via gene transcription. Through dual nuclear receptor agonism, T3D-959 is hypothesized to provide disease modification in AD. In mouse models of AD, T3D-959 administration resulted in improved motor function and reversal of streptozotocin-associated cerebellar degeneration. In an exploratory/feasibility Phase IIa study of T3D-959, patients with mild to moderate AD showed improvements in cognitive function (ADAS-Cog11 and DSST) as well as glucose metabolism by FDG-PET (significant CMRgl changes). A Phase II multi-center, double-blind, placebo-controlled study to evaluate the safety, tolerability, and efficacy of T3D-959 in patients with mild to moderate Alzheimer’s disease is currently enrolling (PIONEER; NCT04251182). This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.