Shanghai Zhimeng Biopharma, Inc. ("Zhimeng Biopharma"), a clinical-stage biopharmaceutical company dedicated to innovative drug development for liver and central nervous system (CNS) diseases, today announced that its self-discovered next-generation KCNQ2/3 potassium channel opener, CB03-154, has received an approval from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) to initiate a Phase 2/3 clinical study in China for amyotrophic lateral sclerosis (ALS, also known as "Lou Gehrig's disease"). Previously, CB03-154 tablets had been granted Orphan Drug Designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of ALS patients. 

ALS is a severe neurodegenerative disorder that disrupts, impairs, or even causes apoptosis of neuronal cells in the brain and spinal cord, ultimately leading to the loss of muscle control. Initial symptoms of ALS often include muscle twitching and weakness in the arms or legs, difficulty swallowing, or slurred speech. The average survival period is typically 2-5 years after the disease onset. Without timely and effective treatment, the patient's condition progressively worsens, eventually resulting in the loss of mobility, speech, swallowing, and respiratory function, followed by death. Currently available ALS treatments can only slightly improve patient function or modestly extend their survival, with no therapies capable of halting or reversing the disease progression. There remains a significant unmet clinical need for ALS treatment. 

Although the pathogenesis of ALS has not yet been fully elucidated, research suggests a close association with ion channel dysfunction, altered synaptic transmission and connectivity, and an imbalance between neuronal excitation and inhibition. Among these, potassium (K+) channels are the most widely distributed and diverse class of ion channels, primarily involved in regulating neuronal excitability as well as the frequency and amplitude of action potentials. Currently, there are no approved KCNQ2/3 potassium channel openers available for patients. The only FDA- and EMA-approved KCNQ2/3 potassium channel opener, retigabine (Potiga, Ezogabine/Retigabine), was withdrawn from the market in 2017 due to risks such as vision impairment caused by pigmentation. 

CB03-154 is a next-generation KCNQ2/3 potassium channel opener with excellent ion channel selectivity, chemical and metabolic stability, anti-neuronal hyperexcitability activity, and favorable pharmacokinetic and safety profiles. It holds potential not only for ALS but also for other CNS disorders such as epilepsy and major depressive disorder. Preclinical studies have demonstrated that CB03-154 significantly reduces the hyperexcitability of ALS motor neurons, markedly slows the deterioration of muscle strength-related functional parameters, delays the disease onset, extends the life expectancies, and normalizes the morphology of muscle and neuronal cells. 

CB03-154, a potential therapy for ALS and other conditions of the central nervous system is being evaluated in Phase 1 clinical trials taking place in the U.S. and Australia for healthy adults, and also completed the bridging pharmacokinetic and safety study in Chinese healthy subjects. In 2024, the Phase 1 clinical trial results and the pre-clinical efficacy data of ALS and epilepsy of CB03-154 were presented at the American Neurological Association (ANA) Annual Meeting and the American Epilepsy Society (AES) Annual Meeting and generated significant attention from experts. Due to its innovation and excellent efficacy data, the abstract on ALS-related pre-clinical findings received the honor of best poster of ANA 2024 annual meeting, and Zhimeng received invitation to give an oral presentation at the Movement Disorder Special Interest Group symposium.

Dr. Huanming Chen, Founder of Zhimeng Biopharma, stated: "The approval by CDE is another important milestone in Zhimeng's global clinical development for ALS and other central nervous system diseases. We believe CB03-154 has the potential to become a first-in-class therapy for ALS. We hope our dedicated efforts will allow us to bring a safer and more effective medicine to ALS patients worldwide."