SHANGHAI, CHINA, October 19, 2023. Shanghai Zhimeng Biopharma, Inc. (“Zhimeng”), announced that one of its innovative small-molecule KCNQ2/3 selective opener compounds (CB03), developed for the treatment of amyotrophic lateral sclerosis (ALS), received orphan drug designation (ODD) from US FDA. CB03 is also being developed for other central nervous diseases, such as refractory epilepsy, major depressive disorders (MDD), etc.
CB03 is a candidate drug for the treatment of ALS and other central nerve system (CNS) diseases independently developed by Zhimeng. A phase 1 study for the evaluation of the safety, tolerability, and pharmacokinetics of CB03 in healthy subjects is currently ongoing in Australia and US. The phase 1 study is expected to complete the dosing phase (both single dose and multiple dose) before the end of 2023.
“The orphan drug designation by US FDA for CB03 is an important milestone in its global clinical development for ALS and other central nervous system diseases.” Said Dr. Huanming Chen, President and CEO of Zhimeng, “Since ALS is a very serious disease without adequate treatment options, we hope our dedicated efforts will allow us to bring a safer and more effective medicine to ALS patients worldwide as the first indication for CB03.”
Studies on neurons indicate that the hyperexcitability of neurons is the one of the important underlying causes associated with neurodegenerative and neuropsychic CNS diseases, including ALS, epilepsy, MDD, neuropathic pain, among others. 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. CB03 as a KCNQ2/3 potassium ion channel opener thus has its potential for become a safe and effective treatment option for ALS and other CNS diseases.
There was only one KCNQ2/3 potassium channel opener, Retigabine (Potiga®, Ezogabine/Retigabine), approved by the FDA and EMA in 2011 for the treatment of refractory epilepsy. Unfortunately, Retigabine has to be withdrawn from the market in 2017 because of vision impairment induced by hyperpigmentation and other potential risks.
As a new generation of selective KCNQ2/3 potassium channel opener, CB03 showed better chemical and metabolic stability, higher biological/pharmacological activities in in vitro and ALS animal disease models, more druggable pharmacokinetic properties, and safety than Retigabine. Thus, CB03 is unlikely to present the same safety concerns as Retigabine and warrant further clinical development to demonstrate potential benefits in the ALS patient population.
About Amyotrophic lateral sclerosis (ALS)
ALS is a neurodegenerative disease that affects nerve cells in the brain and spinal cord. ALS causes loss of muscle control and the disease gets worse over time. The exact causes of ALS are still not known, but neuron hyperexcitability causing neuron damage may play an important role in disease initiation and progression. A small number (about 10%) of ALS cases are inherited.
ALS often begins with muscle twitching and weakness in an arm or leg, trouble swallowing or slurred speech. Eventually ALS affects control of the muscles needed to move, speak, eat, and breathe. A large percentage of ALS patients may only survive for 3-5 years after diagnosis of the disease. There are a few drugs approved for treating the symptoms of ALS or slowing down the disease progression, but currently no cure for this fatal disease.
This press release contains forward-looking statements. While Zhimeng considers the projections to be based on reasonable assumptions, these forward-looking statements may be called into question by a number of hazards and uncertainties, so that actual results may differ materially from those anticipated in such forward-looking statements.