Pharma Focus America

T3D Therapeutics Announces Positive Top-Line Results from the Phase 2 PIONEER Trial of T3D-959 in Mild-To-Moderate Alzheimer's Disease

Saturday, November 04, 2023

T3D Therapeutics recently presented the top-line results of its Phase 2 PIONEER study at the 16th International Conference on Clinical Trials in Alzheimer's Disease (CTAD). In this double-blind study, 250 patients with mild to moderate Alzheimer's Disease (AD) were enrolled, and three different doses of T3D-959 were compared to a placebo. The treatment was administered orally once a day for a duration of 24 weeks. The outcomes of this study indicate the potential of T3D-959 to have a disease-modifying effect on Alzheimer's patients with mild-to-moderate severity. Biomarker data revealed changes in multiple disease-related pathologies associated with AD. Furthermore, clinical evidence indicated improvements in cognition among a subset of patients identified using a new blood biomarker for Alzheimer's disease pathology, specifically the pTau-217/Non-pTau-217 ratio.

The analysis of the study findings showed the following results:

  1. In the intention-to-treat (ITT) population, which includes all patients who were randomly assigned to treatment, there were significant improvements observed with T3D-959 compared to the placebo in various aspects:
  • Reduction in a biomarker reflecting amyloid plaque burden (plasma Ab42/40 ratio) was observed with a 30mg dose of T3D-959.
  • Positive changes in fasting plasma glucose, insulin, HDL, and other lipid markers, suggesting an improved metabolic profile.
  • A decrease in a plasma biomarker related to neurodegeneration, neurogranin.
  • Improvements in multiple plasma biomarkers associated with AD neurodegeneration, inflammation, insulin resistance, mitochondrial dysfunction, and oxidative stress.
  • Favorable changes in multiple plasma proteomic biomarkers linked to AD, including amyloid plaque formation, neurodegeneration, inflammation, mitochondrial dysfunction, and oxidative stress, as measured by LC-MS.

       2. The ITT population demonstrated an excellent safety profile, with no drug-related adverse events related to stroke and no clinical signs of ARIA.

       3. Within the high pTau-217 ratio group (comprising 55% of subjects with AD pathology, as indicated by a pTau-217/Non-pTau-217 ratio ≥0.015), those treated with 30mg of T3D-959 (N=30) exhibited:

  • A 2-point improvement in ADAS-cog11 compared to the placebo, with an effect size at 24 weeks that was equivalent to or better than what has been observed for anti-amyloid plaque antibodies at 76-78 weeks.
  • A more substantial improvement in the plasma Ab42/40 ratio compared to the entire ITT population.

      4. The study identified that a daily dose of 30mg of T3D-959 offered the optimal balance between safety and efficacy for further investigation in a Phase 2b/3 clinical trial involving patients with mild-to-moderate AD.

John Didsbury, Ph.D., CEO of T3D, expressed his satisfaction with the study's positive results and emphasized that they inform the design of a larger and more extended Phase 2b/3 trial, focusing on dose selection, a specific population of AD patients, and biomarker assessments.

Experts in the field, including Michael Weiner MD and Pierre N. Tariot MD, have expressed optimism regarding the study's encouraging outcomes and the potential for advancing the development of T3D-959 as a treatment for Alzheimer's disease.

T3D-959 is a small molecule administered orally once daily, designed as a brain-penetrating PPAR delta/gamma dual nuclear receptor agonist to address glucose and lipid metabolism dysfunctions associated with AD and other neurodegenerative disorders.

The Phase 2 PIONEER study enrolled 250 adults with mild-to-moderate Alzheimer's disease and received support from the National Institute on Aging and the Alzheimer's Association's Part the Cloud Gates Partnership Grant Program. For more information about the study, you can refer to the website and search for study number NCT04251182.



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