T3D’s Phase 2 Alzheimer’s trial yields promising results

Company reports topline data showing clinical improvement in cognition in Alzheimer’s patients with a high pTau-217 ratio.’

Neurodegenerative disease-targeting pharma company T3D Therapeutics has revealed promising findings from its Phase 2 PIONEER trial. The company reports that its flagship product candidate, T3D-959, has demonstrated potential as a disease-modifying therapy for mild-to-moderate Alzheimer’s.

T3D’s approach targets brain ‘starvation’ driven by poor energy metabolism and dysfunctional lipid metabolism in the brain, which it says leads to neurodegeneration and brain ‘strangulation.’ The company claims that T3D-959 targets both the brain starvation and neurodegenerative aspects of Alzheimer’s disease by treating multiple manifestations of the disease.

Designed to be delivered orally, once daily, T3D-959 is a small molecule that acts as a brain-penetrating PPAR delta/gamma dual nuclear receptor agonist, specifically designed to address metabolic dysfunctions associated with Alzheimer’s and other neurodegenerative disorders.

The PIONEER study was a double-blind, placebo-controlled investigation involving 250 adults with mild-to-moderate Alzheimer’s disease that aimed to assess the safety, tolerability, and effectiveness of T3D-959 in the treatment of Alzheimer’s disease at doses of 15mg, 30mg, or 45mg.

Key findings from the study, presented at the 16th International Conference on Clinical Trials in Alzheimer’s Disease, include the modification of multiple disease pathologies inherent in Alzheimer’s, as evidenced by biomarker data. Clinical improvement in cognition was observed in a subgroup of patients identified using a new blood biomarker for Alzheimer’s pathology known as the “pTau-217 ratio.” A high pTau-217 ratio in the blood appears to define a population that is responsive to T3D-959 therapy.

“The outcomes of this trial are encouraging and lay a foundation for advancing the further development of this new molecule to treat Alzheimer’s disease,” said Dr Pierre N Tariot, Director of Banner Alzheimer’s Institute.

The study also showed significant improvements in various biomarkers related to amyloid plaque burden, metabolic profile, neurodegeneration, inflammation, insulin resistance, mitochondrial dysfunction, and oxidative stress. The analysis of the overall patient population (including all randomized patients) indicated noteworthy progress with T3D-959 treatment compared to the placebo.

“The exciting results of this study show potential to modify the course of Alzheimer’s disease in a unique way,” said Dr Michael Weiner, Professor Emeritus at the University of California, San Francisco, and principal investigator of the Alzheimer’s Disease Neuroimaging Initiative. “I look forward to seeing these results confirmed and expanded in a larger and longer Phase 2b/3 clinical trial.”

The PIONEER study also noted an “excellent” safety profile for T3D-959, with no drug-related adverse events related to stroke and no clinical signs of ARIA (Amyloid-Related Imaging Abnormalities).

The results of the trial have raised hopes for the potential of T3D-959 in modifying the course of the disease in patients with mild-to-moderate Alzheimer’s. A 30mg daily dose of T3D-959 has been identified as providing optimal safety and efficacy for further investigation in a Phase 2b/3 clinical trial for mild-to-moderate Alzheimer’s patients.

“PIONEER positive outcomes achieved the goal to inform the design of a larger and longer Phase 2b/3 trial, with dose selection, a ‘responder’ population of AD patients and biomarkers to assess,” said Dr John Didsbury, CEO of T3D.

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