Fragile X treatment KER-0193 found safe in healthy adults in trial
Developer now planning launch of proof-of-concept Phase 2 trial in patients
KER-0193, Kaerus Bioscience’s oral treatment candidate for fragile X syndrome, was safe and well tolerated, and showed predictable pharmacological properties, in healthy volunteers, according to new data from a Phase 1 clinical trial.
The therapy was also associated with changes in brain activity in regions known to be affected in fragile X patients, the developer noted.
Based on these positive results from the Phase 1 study (EUCT 2024-511468-94-00) — the first to test the experimental treatment in humans — Kaerus is now preparing the launch of a proof-of-concept Phase 2 trial in people with fragile X, the company said in a press release.
“These results are a significant milestone for Kaerus,” said Robert Ring, PhD, CEO of Kaerus. “We feel extremely excited and confident heading into Phase 2 in the target population.”
KER-0193 fragile X treatment linked to changes in brain activity
A genetic disease, fragile X syndrome is caused by mutations in FMR1. This gene provides instructions for producing a protein called FMRP that helps in the proper development of synapses, the sites of near contact between nerve cells where they relay electrical signals to communicate with each other.
In people with fragile X, nerve cells in the brain are thought to fire electrical signals more readily than usual. Known as hyperexcitability, this leads to sensory overload and hyperactive behavior, among other disease symptoms.
It occurs because mutated FMR1 fails to interact with nerve proteins, called calcium-activated potassium (BK) channels, to keep them open. BK channels control excitability by letting potassium ions exit nerve cells. The longer they remain open, the more potassium ions exit nerve cells, reducing excitability.
KER-0193 is designed to increase the time these BK channels remain open, which is expected to lessen excitability and ease symptoms of fragile X syndrome.
The now-completed Phase 1 study, launched in Belgium in mid-2024, evaluated the safety and tolerability of single and multiple ascending doses of KER-0193 in 56 healthy adults, ages 18 to 64. It also tested KER-0193’s pharmacokinetics, or its movement into, through, and out of the body, and its pharmacodynamics, which refers to a therapy’s effects on the body.
The results showed that KER-0193 was generally safe and well tolerated, and showed an “excellent, dose-proportional pharmacokinetic profile,” the release stated.
The researchers used an electroencephalogram, or EEG, to assess potential pharmacodynamic effects in participants’ brain electrical activity. Th team found that KER-0193 resulted in significant changes in the EEG signature, confirming that the therapy reached the brain and spinal cord.
The data clearly demonstrate our first-in-class BK channel modulator is active in the [brain and spinal cord], and is both safe and well-tolerated.
EEG data also showed that KER-0193 reduced excitability in regions of the brain that are commonly reported as abnormal in fragile X patients, providing preliminary evidence that KER-0193 may work as expected.
These findings were consistent with data from studies in animal models. Those earlier studies showed that a single dose of a BK channel opener eased behavioral challenges in a mouse model of fragile X.
“The data clearly demonstrate our first-in-class BK channel modulator is active in the [brain and spinal cord], and is both safe and well-tolerated,” Ring said, noting that these findings add to “the positive ‘proof of mechanism’ [seen] with EEG.”
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