First Alzheimer’s Patients Dosed with PTI-125 in New Phase 2b Clinical Trial

The first two patients with Alzheimer’s disease have been dosed with Cassava Sciences’ investigational small molecule PTI-125 in a new Phase 2b clinical study.

PTI-125 is a small molecule that has been designed to bind to an abnormal form of a protein called Filamin A (or FLNA), and restore its normal structure and activity. FLNA is found misfolded in the brains of many patients with Alzheimer’s disease, and is believed to be an important contributor to neuroinflammation and the buildup of toxic plaque inside nerve cells.

Supported by the National Institutes of Health (NIH), the trial (NCT04079803) will evaluate the safety, tolerability, and therapeutic activity of PTI-125, as well as its effect on known disease biomarkers, in approximately 60 people with mild-to-moderate Alzheimer’s disease.

Recruitment is ongoing in the United States, and participants will be randomly assigned to oral administration of 50 mg or 100 mg of PTI-125, or a dose-matching placebo, twice daily for 28 consecutive days.

For more information about study locations and contacts, click here.

“There is a profound and timely need to develop new therapies for this devastating disease,” Remi Barbier, president and CEO of Cassava Sciences, said in a news release. “We are pleased to advance PTI-125 into this randomized, placebo-controlled study … and are eager to report how results of this study will expand upon the clinical data set for PTI-125.”

Advancing PTI-125 into Phase 2b studies was supported by clinical data from a prior open-label Phase 2a trial (NCT03748706). The study enrolled 13 Alzheimer’s patients who received 100 mg of PTI-125 orally twice a day for 28 days.

The Phase 2a trial showed that the treatment reduced the amount of tau protein by 20% and the levels of neurofilament light chain (NfL) — a biomarker of neurodegeneration — by 22%. The levels of neurogranin, a biomarker of cognitive decline, were also reduced by 32% after treatment.

Additional analysis showed that PTI-125 could effectively reduce neuroinflammation, with decreased levels of important pro-inflammatory molecules such as IL-6, IL-1beta, and YKL-40.

The ratio of phosphorylated tau and beta-amyloid protein (P-tau/Aβ₄₂), a biochemical indicator of Alzheimer’s, also improved in all patients.

Cassava is currently developing a simple diagnostic test to help detect Alzheimer’s disease with only a blood sample. The investigational product, called PTI-125Dx, is also being financially and scientifically supported by the NIH.

Preliminary data collected from clinical studies revealed that PTI-125Dx could detect more than 10-fold differences between Alzheimer’s patients and age-matched healthy controls or young cognitively healthy subjects.

“If successful, we believe PTI-125Dx has potential to make obsolete many of the current approaches for diagnosing Alzheimer’s disease,” the company states on its website.