Shanghai Zhimeng Biopharma announced dosing of the first participant in the US Phase I study in healthy subjects of its innovative small-molecule KCNQ2/3 selective opener (CB03), developed for the treatment of refractory epilepsy.

CB03 is a candidate drug for the treatment of refractory epilepsy, independently developed by Zhimeng. The phase 1 study is to evaluate the safety, tolerability, and pharmacokinetics of CB03 in healthy subjects.

"The successful completion of the first human administration of CB03 in the United States is a small but critical step in the clinical development of CB03 and an important milestone in its global clinical development." Said Dr. Huanming Chen, President and Chief Executive Officer of Zhimeng, "CB03 is the first drug candidate of Zhimeng to enter clinic trials in the area of central nervous system diseases. We hope that through our unremitting efforts, we can provide safer and more effective medicines to patients worldwide and improve their quality of live."

About CB03

Studies on the pathogenesis of epilepsy have shown that the imbalance between neuronal excitation and inhibition is the major underlying mechanism associated with alterations in ion channels, synaptic transmission and connections. As the structural basis of neuronal excitability and activity, ion channels dysfunctions are bound up with the development of epilepsy. As the most widely distributed and the most diverse group of ion channels, potassium (K+) channels are mainly involved in the modulation of neuronal excitability and the frequency and amplitude of action potential discharges. K+ channels alterations have been known to be associated with benign familial neonatal convulsions (BFNC) and severe epileptic encephalopathies. KCNQ2/3 potassium ion opener is not only used in the treatment of refractory epilepsy, but also for major depression (MDD), amyotrophic lateral sclerosis (ALS), neuropathic pain and other diseases

Retigabine (Potiga, Ezogabine/Retigabine) was the first KCNQ2/3 potassium channel opener approved by the FDA and EMA in 2011 for the treatment of refractory epilepsy, to which other drugs were ineffective. Unfortunately, retigabine was withdrawn from the market in 2017 because of the risk of vision impairment induced by hyperpigmentation.

CB03 is a new generation of KCNQ2/3 potassium channel opener. Compared with retigabine, it shows better chemical and metabolic stability, antiepileptic activity, pharmacokinetic properties, and safety. Moreover, CB03 has a more specific ion channel selectivity and is unlikely to present the same safety concerns as retigabine.