PRI-002, Oral Therapy Candidate for Alzheimer’s, Deemed Safe in Phase 1 Trial

Alzheimer’s oral therapy candidate PRI-002, being developed by Priavoid, has proven safe for human use in healthy volunteers during a Phase 1 clinical trial.

These positive trial results provide important evidence that supports progressing PRI-002 into studies of patients who have Alzheimer’s disease.

“Our next goal is the proof of efficacy in patients,” Dieter Willbold, PhD, director of Jülich’s Structural Biochemistry Institute (ICS-6), and one of the inventors of PRI-002, said in a press release. “We hope to successfully take this path with the company Priavoid.”

The trial (NCT03944460) investigated the safety, tolerability, and availability and metabolism in the body of five different doses — 4, 12, 36, 108, and 320 mg capsules — of PRI-002 administered just one time. A total of 40 healthy male volunteers were enrolled in the study, 10 of whom received an equivalent dose of placebo.

In a previous analysis, the investigational therapy proved safe at its highest dose, and reached the expected therapeutic level in the blood of healthy individuals. “Now we were also able to demonstrate the safety of the compound after four weeks of daily administration,” said Willbold, who also is head of the Institute of Physical Biology at Heinrich Heine University Düsseldorf, which is equally involved in the compound’s development.

PRI-002, also known as contraloid acetate, was discovered based on a different approach than that used for other prior therapy candidates for Alzheimer’s disease. Instead of avoiding the production of — or destroying — amyloid beta, a protein crucially involved in the progression of Alzheimer’s disease.

PRI-002 was specifically designed to directly destroy the amyloid beta toxic aggregates (oligomers), disassembling them into single units of the protein, which are harmless. Its activity is believed to hold potential to cure or at least  reduce cognition, memory, and behavior deficits associated with Alzheimer’s disease. Still, treatment with PRI-002 aims to actively reduce brain amyloid plaques or total amyloid in the cerebrospinal fluid (the protective fluid in the brain and spinal cord).

“We considered a different approach for our drug candidate, because the principle that it is not a question of the formation of amyloid beta itself but of its aggregation into oligomers, has been known for several years,” said Antje Willuweit, PhD, researcher at the Institute of Neuroscience and Medicine (INM-4) and managing director for Priavoid.

PRI-002 belongs to a class of molecules called D-peptides, which are structural “mirrors” of our natural amino acids. This means it is not degraded by the body, or it is at a very slow rate, being stable enough to be delivered orally, as a tablet or capsule. These particular characteristics make PRI-002 a very attractive and non-invasive strategy to treat patients, particularly elderly people.

Preclinical studies have provided positive evidence of PRI-002’s effectiveness in mice with Alzheimer’s-like disease. “The memory and cognition of the treated mice were significantly improved compared to the placebo group and could even no longer be distinguished from the memory performance of healthy mice,” said Janine Kutzsche, PhD, a scientist at Willbold’s group.

In a more recent study, researchers showed that PRI-002 could recover the memory and reverse the cognitive impairments in elderly mice that already had full-blown disease. These findings suggest this new treatment strategy is “relevant not only for disease development and progression, but also (…) for the causal treatment of Alzheimer’s disease,” researchers wrote.

Priavoid, which is advancing the clinical development of PRI-002, is a spin-off from research centers Forschungszentrum Jülich and Heinrich Heine University Düsseldorf, in Germany. The therapy’s development has been funded by the Helmholtz Validation Fund and this first safety trial also was supported by the U.S.-based Alzheimer’s Association.