Lenire to Develop Oral Therapy for Fragile X Under New License Agreement

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by Lindsey Shapiro, PhD |

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The University College of London (UCL) has licensed VSN16R, an investigational oral treatment for fragile X syndrome, to U.S.-based Lenire Biosciences.

Although originally developed by UCL researchers for treating muscle spasticity in multiple sclerosis, recent preclinical data showed that VSN16R could lessen behavioral symptoms in a mouse model of fragile X.

Lenire will now work to develop the therapy for fragile X patients under the license agreement.

“The effect of our drug in the disease models is transformative; we are very excited to see this drug go forward to the clinic in people with fragile X,” David Selwood, PhD, a professor at UCL and the original developer of VSN16R, said in a press release.

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Large conductance calcium-activated potassium channels — known as BK channels — are prevalent in the brain, where they are involved in regulating the behavior of nerve cells. Studies have shown that BK channels are less active in animal models of fragile X, which could in part underlie the neurological symptoms of the disease.

“Extensive research into the role of altered BK channel expression, activity and regulation in [fragile X] models provides a strong rationale for pharmacologically augmenting its activity as a disease-modifying treatment for [fragile X] that may improve many of its core symptoms,” said Peter Vanderklish, PhD, co-founder of Lenire.

VSN16R is an oral small molecule that activates BK channels. It was designed to mimic some of the activities of anandamide, a chemical produced in the body as part of the endocannabinoid system.

While the endocannabinoid system has received much recent attention as a therapeutic target for brain disorders, its broad activation can cause neurological side effects, like sedation. According to researchers, while VSN16R emulates anandamide’s ability to activate BK channels, it avoids binding to cannabinoid 1 receptors. This mediates many of the known side effects associated with the endocannabinoid system.

VSN16R in mouse and human trials

A preclinical study recently showed that VSN16R treatment rescued behavioral deficits — including repetitive behaviors, hyperactivity, memory impairments, and aggression — in a mouse model of fragile X.

Those findings provide support for the therapy’s use in humans with the neurodevelopmental disorder, scientists say.

A double-blind, placebo-controlled Phase 1 study (EudraCT 2013‐002765‐18) evaluated the safety of single or multiple ascending doses of VSN16R against a placebo in healthy male volunteers.

In the single ascending dose portion, results showed that no significant adverse drug-related events occurred at doses ranging from 25–800 mg. Reported adverse events (side effects) included dizziness, headache, indigestion, and nausea; all were mild.

In the multiple ascending dose part, participants were given twice daily doses of 25, 100, or 400 mg of VSN16R, or a placebo, for one week.

Again, the treatment was well-tolerated, with no serious events reported. Reported side effects included throat pain, rhinitis (congestion, sneezing, runny nose), bloating, abdominal pain, and nausea.

Consistently, safety data from a Phase 2 proof-of-concept trial (NCT02542787) showed that VSN16R was safe and well-tolerated at doses up to 800 mg in people with multiple sclerosis.

Notably, VSN16R has not caused side effects of sedation in human trial participants, a common challenge with therapies that target or mimic the endocannabinoid system.

“We are excited to collaborate with Lenire to test VSN16R in patients with [fragile X],” said Craig Erickson, MD, a professor at Cincinnati Children’s Hospital Medical Center and director of the Cincinnati Fragile X Research and Treatment Center.

There currently are no approved disease-modifying treatments for fragile X.