ADDF Grants $1.5M to Fund U.S. Arm of Phase 2a Trial for Vafidemstat in Alzheimer’s Patients

The Alzheimer’s Drug Discovery Foundation (ADDF) has awarded $1.5 million to Oryzon Genomics to support expanding an ongoing Phase 2a trial assessing the potential of vafidemstat (ORY-2001) in patients with mild to moderate Alzheimer’s disease to the United States.

The double-blind, placebo-controlled trial (2017-004893-32), called ETHERAL, is currently recruiting patients at 17 sites across the U.K., France, and Spain.

More than 90 patients have already been enrolled in the European arm of the trial, which is expected to include no more than 125 participants.

The U.S. Food and Drug Administration recently approved an investigational new drug application for vafidemstat, clearing Oryzon to extend the trial to patients in the U.S.

The new grant approved by ADDF’s board of directors will support the enrollment of patients into the ETHERAL-US trial (NCT03867253). Oryzon is planning to recruit up to 30 patients from multiple sites across the U.S. for an expected total of at least 150 participants, including the European arm. Sites in Florida and New Jersey are now enrolling; information on contacts and locations is available here.

During the trial, researchers will evaluate the impact of 24-week treatment with vafidemstat compared with placebo on patients’ memory and behavior, as well as alterations in the levels of several disease biomarkers in the cerebrospinal fluid, the liquid that circulates in the brain and spinal cord.

“Our continued investment in Oryzon reflects ADDF’s long-standing support of studies that focus on drugs targeted toward multiple aging pathways,” Howard Fillit, MD, founding executive director and chief science officer of ADDF, said in a press release. “We are pleased to help advance the development of epigenetic therapies and vafidemstat as a novel therapeutic option for Alzheimer’s disease.”

Vafidemstat is an investigational small molecule therapy that is able to cross the blood-brain barrier, a highly selective, semipermeable membrane that isolates the brain from the blood that circulates in the body. It works by inhibiting the activity of two enzymes in the brain, called lysine specific demethylase 1 (LSD1) and monoamine oxidase B (MAOB).

Preclinical studies have demonstrated that vafidemstat can reduce cognitive impairment, memory loss, and brain inflammation in animal models of Alzheimer’s disease.

“Support from the ADDF has been key over the years to advance the development of vafidemstat as a novel therapeutic option for Alzheimer’s disease, and we are deeply grateful. The ADDF’s decision to convert the grant into equity reflects its confidence in our project and the shared hope that this experimental drug may contribute to the cure of this terrible disease,” said Carlos Buesa, CEO and founder of Oryzon.

“With ETHERAL-US, the company is starting clinical operations in the U.S. and we expect to expand the clinical trials with vafidemstat in the U.S. to additional [central nervous system] indications soon,” he added.

Besides Alzheimer’s, vafidemstat is also being tested as a potential therapy for other neurological and psychiatric disorders, including multiple sclerosis, borderline-personality disorder, and attention deficit and hyperactivity disorder.