Saniona AB (publ) announced that it has initiated the candidate selection phase with a proprietary subtype selective frontrunner molecule from the Kv7 lead optimization program for epilepsy. The compound has a unique selectivity profile and represents a potential new generation of effective and well tolerated epilepsy medicines. Epilepsy, a brain disorder characterized by recurrent seizures, affects millions of people worldwide.

There is considerable unmet need since about 30% of the patients are unresponsive to current medicines. Kv7 channels mediate potassium ion transport across the cell membrane of neurons, which decreases the likelihood of generating uncontrolled nerve impulses. Activators of Kv7 channels are therefore very effective in dampening overactive neurons and thus prevent the generation of epileptic seizures.

Mutations in Kv7 channels containing the Kv7.2 and Kv7.3 subunits are the second most common cause of inherited severe childhood epilepsies, which demonstrate their importance in controlling nerve cell activity. The non-selective Kv7 activator retigabine has provided both clinical and commercial proof-of-concept for treatment of patients with resistant focal onset seizures. Retigabine has also shown anti-epileptic effect and developmental improvement in smaller investigator-driven studies with children with loss-of-function mutations in Kv7.2. However, retigabine has been withdrawn from the market due to compound specific and non-target related side-effects.

The Kv7 channel family comprise five subtypes, of which channels consisting of Kv7.2 and Kv7.3 subunits are selectively expressed in the brain. The Saniona program focuses on development of subtype selective Kv7.2/Kv7.3 activators, thus avoiding retigabine´s troublesome side effects on the CNS and urinary system, which caused a high drop-out rate in the clinical studies and eventually resulted in quite low adherence to the drug despite good efficacy.