RESEARCH TRIANGLE PARK — In a landscape littered with disappointment in the battle against the global scourge of Alzheimer’s disease, an RTP-based company is offering a new chance for hope.

T3D Therapeutics, a 7-year-old company started with loan help from the North Carolina Biotechnology Center, said today it is launching a Phase 2 clinical trial with its unique product candidate, T3D-959, to treat mild to moderate forms of Alzheimer’s disease (AD).

T3D-959 is a chemically synthesized once-daily oral drug described as a brain-penetrating dual nuclear receptor agonist. It targets glucose and lipid metabolism dysfunctions associated with AD and other neurodegenerative disorders.

“AD is being increasingly recognized as resulting from abnormal brain metabolism,” said Warren Strittmatter, M.D., chief medical officer of T3D and emeritus professor of neurology at Duke University Medical Center.

“T3D-959 is targeted toward those metabolic pathways which appear to ultimately produce amyloid plaques, tau tangles, inflammation and, most importantly, the dementia.”

Targets multiple pathologies

Unlike most Alzheimer’s therapies in development that have targeted one disease pathway, such as beta amyloid plaques or tau bundles, T3D says T3D-959 acts on multiple pathologies, including a potential trigger for the disease — insulin resistance in the brain.

As a dual nuclear receptor agonist, T3D-959 may regulate many genes involved in Alzheimer’s and could be a powerful insulin sensitizer, anti-inflammatory and neuroprotectant, offering a greater potential to slow, stop or even reverse disease progression, the company has reported.

“We are excited to expand our testing of T3D-959 in Alzheimer’s patients in this new Phase 2 study,” said Strittmatter, whose credentials include winning the prestigious Alzheimer’s Association Zenith Award. “It uniquely targets inherent dysfunctional brain metabolism which we believe underlies the formation of plaques, tangles and inflammation in this disease.”

A four-year federal grant expected to total $9 million from the National Institute on Aging (NIA), part of the National Institutes of Health, is helping to fund this test of a unique daily oral treatment for Alzheimer’s.

NCBiotech awarded T3D a $50,000 Company Inception Loan in 2013 and a $250,000 Small Business Research Loan in 2014. Then in 2015 the company won a $1.8 million Phase 2 Small Business Innovation Research grant, also from the NIA, to further develop T3D-959.

The test starting today is called PIONEER (a loose acronym for Prospective therapy to Inhibit and Overcome Alzheimer’s Disease Neurodegeneration via Brain EnErgetics and Metabolism Restoration).

PIONEER is a double-blind, placebo-controlled, parallel-group safety and efficacy study expected to enroll up to 256 adults with mild to moderate Alzheimer’s disease. PIONEER will enroll people who will receive one of three different doses of T3D-959, or a placebo, for 24 weeks.

Based on solid preliminary evidence

“We are encouraged by the recent data from our exploratory, feasibility Phase 2a trial of T3D-959, in which T3D-959 was well-tolerated and evidenced multiple signals of potential efficacy, setting a foundation for the PIONEER study” said John Didsbury, Ph.D., chief executive officer of T3D.

Didsbury is a former GlaxoSmithKline executive who took his pharmaceutical company experience into the Triangle’s booming entrepreneurship realm by founding T3D in 2013.

This Phase 2 PIONEER trial will assess the safety, tolerability, clinical efficacy and pharmacodynamics of T3D-959, as well as its effects on biomarkers of neurodegeneration.

According to NIA, Alzheimer’s disease is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills, and, eventually, the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear in their mid-60s. Estimates vary, but experts suggest that more than 5.5 million Americans, most of them age 65 or older, may have dementia caused by Alzheimer’s.

Alzheimer’s disease is currently ranked as the sixth leading cause of death in the United States, but recent estimates indicate that the disorder may rank third, just behind heart disease and cancer, as a cause of death for older people.

Alzheimer’s is the most common cause of dementia among older adults. Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—and behavioral abilities to such an extent that it interferes with a person’s daily life and activities. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a person’s functioning, to the most severe stage, when the person must depend completely on others for basic activities of daily living.

George Vradenburg, chairman and co-founder of UsAgainstAlzheimer’s, had this to say of the NIA grant to T3D: “Given the enormous and growing impact of Alzheimer’s on patients and families, there is an urgent need to develop and rigorously evaluate a larger and more diversified portfolio of promising late clinical-stage treatments.”

“NIA’s support of Phase 2 studies — including this study from T3D Therapeutics — is to be commended and scaled if we are going to achieve our national goal of effectively treating Alzheimer’s in the near future.”

To learn more about this study, visit www.clinical and reference study number NCT04251182.

(c) North Carolina Biotechnology Center

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