T3D Therapeutics Receives $9 Million NIH Grant to Advance Alzheimer's Clinical Trial

T3D Therapeutics, based in Research Triangle Park, NC, received a $9 million grant over four years from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH). The funds will be used to partially support a Phase II clinical trial of T3D-959, the company’s novel treatment for Alzheimer’s disease.

T3D Therapeutics is taking a different approach to treating Alzheimer’s disease than most companies, which have largely focused—unsuccessfully—in removing or preventing the accumulation of beta-amyloid. T3D believes that Alzheimer’s is a metabolic disease of the brain related to poor energy metabolism and dysfunctional lipid metabolism.

There has been research that suggests Alzheimer’s is a sort of diabetes of the brain, with indications of faulty glucose metabolism found in the disease. For example, a 2017 NIH study found a connection between high levels of brain glucose and the severity of amyloid plaques and tau tangles. The research found specific problems in glycolysis, how the brain breaks down glucose, in the patients with the most severe forms of Alzheimer’s.

T3D-959 activates two nuclear receptors that are central regulators of normal glucose and lipid metabolism in the brain. It can be taken orally once per day. It is a PPAR delta-activating compound that may have additive or synergistic effects in regulating malfunctioning brain glucose energy and lipid metabolism in Alzheimer’s disease.

“We see this grant award as recognition that improving inherent metabolic defects in Alzheimer’s disease is a vital and largely unexplored therapeutic avenue in need of pursuit is a testament to the potential for T3D-959 to treat AD, a disease that we view as a chronic anorexia of the brain,” stated John Didsbury, T3D’s chief executive officer. “We are truly honored by the support of the NIA and the confidence that our peers have shown in the science underpinning T3D-959.”

The Phase II PIONEER trial (Prospective therapy to Inhibit and Overcome Alzheimer’s Disease Neurodegeneration via Brain EnErgetics and Metabolism Restoration) plans to begin patient dosing in early 2020. The trial is a double-blind, placebo-controlled, parallel-group Phase II safety and efficacy trial that expects to enroll up to 252 adults with mild-to-moderate Alzheimer’s disease. The patients will receive one of three different doses of T3D-959 or a placebo for about 6 months.

In July 2018, the company announced final Phase IIa data of the drug in mild to moderate Alzheimer’s disease patients at the 2018 Alzheimer’s Association International Conference (AAIC). That study found that the drug was safe and well tolerated. It found a metabolomics profile consistent with improving insulin resistance and found some efficacy data that suggested the potential to improve memory and cognition.

T3D-959 is the company’s lead program in Alzheimer’s but is also being investigated in the clinic for Huntington’s disease and NASH/NAFLD. The company also other has preclinical programs in Alzheimer’s, vascular dementia, and NASH/NAFLD.

“During my lengthy tenure treating AD patients I have seen firsthand the frustrations of caregivers and patients at the lack of an effective therapy with the plethora of recent drug development failures causing them to lose hope,” stated Warren Strittmatter, T3D’s chief medical officer and Emeritus Professor of Neurology at Duke University Medical Center and Alzheimer’s Association Zenith Award winner. “This award provides great support for our promising new therapy to give them renewed optimism. AD is being increasingly recognized as resulting from abnormal brain metabolism. T3D-959 is targeted toward those metabolic pathways which appear to ultimately produce amyloid plaques, tau tangles, inflammation and, most importantly, dementia.”