Spanish regulators have signed off on Oryzon Genomics’ plan to conduct a Phase 2 clinical trial of its Alzheimer’s therapy ORY-2001.
The ETHERAL trial, which will cover patients with mild to moderate forms of the disease, will be the first to assess the effectiveness of an epigenetic therapy for Alzheimer’s. This approach involves regulating genes’ function without altering their makeup. The trial will also assess the treatment’s safety.
Ninety patients are expected to take part in the study, whose objectives will include seeing if ORY-2001 can improve patients’ memory and behavior. Researchers also want to know if it can improve cerebrospinal fluid biomarkers of the disease.
Oryzon is expected to begin enrolling participants in the second quarter of 2018.
Regulators approved the Phase 2 trial after a Phase 1 study showed that ORY-2001 could penetrate the central nervous system and cross the blood-brain barrier to reach the brain. The oral therapy also proved safe, and the 106 healthy volunteers tolerated it well, researchers said.
ORY-2001 inhibits two enzymes in the brain — Lysine Specific Demethylase 1 (LSD1) and Monoamine oxidaseB (MAOB).
In preclinical-trial studies, it restored the memory and reduced the aggressiveness of mice with Alzheimer’s. It also led to rat models that had been isolated becoming more sociable than untreated rats.
Oryzon is already conducting a Phase 2 clinical trial of ORY-2001 as a potential treatment for multiple sclerosis. Some of the patients in the study have the relapsing-remitting form of MS and some the secondary progressive form.
“The approval of ETHERAL, the first Phase IIa clinical trial for an epigenetic agent in AD [Alzheimer’s disease], represents an important milestone for the company and the scientific community,” Roger Bullock, Oryzon’s chief medical officer, said in a press release. Preclinical-trial studies “validate the potential of ORY-2001 to treat cognitive defects and neuroinflammation by increasing the plasticity [ability to form new connections] and functionality of neurons [nerve cells],” he said.
“This is the first step in exploring this novel approach,” Bullock said. “We have chosen to study this in mild to moderate AD patients, where we believe there is still physiological room to make a significant therapeutic intervention.” This patient population “is underserved with the conventional approaches,” he added.
“ORY-2001 is a molecule with disease modifying potential that acts on different domains that are presented in AD patients,” said Carlos Buesa, Oryzon’s president and chief executive officer. “We have identified CSF [cerebrospinal fluid] biomarkers altered in AD that can be modulated by ORY-2001.”
The research has opened “an important range of possibilities, not only for a better understanding of the biology of the disease but also in terms of regulatory development for the drug,” Buesa said. “We expect to be able soon to start further exploratory studies,” he said, adding that Oryzon is committed to exploring epigenetic treatments for other neurodegenerative disorders.
Among the future trials that Oryzon is planning will be one in the U.S., the company said.