Shanghai Zhimeng Biopharma has received regulatory approval from China's National Medical Products Administration (NMPA) to advance its investigational ALS therapy CB03-154 into Phase 2/3 clinical trials. The Center for Drug Evaluation (CDE) approval marks a significant milestone for the next-generation KCNQ2/3 potassium channel opener, which previously received FDA Orphan Drug Designation for ALS treatment.
Addressing Critical Unmet Medical Need
ALS represents one of the most devastating neurodegenerative disorders, disrupting neuronal cells in the brain and spinal cord and ultimately leading to loss of muscle control. The disease typically manifests with muscle twitching and weakness in the arms or legs, difficulty swallowing, or slurred speech, with patients facing an average survival period of 2-5 years after disease onset.
Currently available ALS treatments can only slightly improve patient function or modestly extend survival, with no therapies capable of halting or reversing disease progression. Without timely and effective treatment, patients progressively lose mobility, speech, swallowing, and respiratory function, ultimately resulting in death.
Novel Mechanism of Action
Research suggests ALS pathogenesis involves ion channel dysfunction, altered synaptic transmission and connectivity, and an imbalance between neuronal excitation and inhibition. Potassium channels, the most widely distributed and diverse class of ion channels, play a crucial role in regulating neuronal excitability and the frequency and amplitude of action potentials.
Currently, no approved KCNQ2/3 potassium channel openers are 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 The only FDA- and EMA-approved KCNQ2/3 potassium channel opener, retigabine (Potiga, Ezogabine/Retigabine), was withdrawn from the market in 2017 due to risks including vision impairment caused by pigmentation.
Promising Preclinical Profile
CB03-154 demonstrates excellent ion channel selectivity, chemical and metabolic stability, anti-neuronal hyperexcitability activity, and favorable pharmacokinetic and safety profiles. The compound holds potential not only for ALS but also for other CNS disorders such as epilepsy and major depressive disorder.
Preclinical studies revealed that CB03-154 significantly reduces the hyperexcitability of ALS motor neurons, markedly slows the deterioration of muscle strength-related functional parameters, delays disease onset, extends life expectancies, and normalizes the morphology of muscle and neuronal cells.
Clinical Development Progress
CB03-154 is currently being evaluated in Phase 1 clinical trials in the United States and Australia for healthy adults, and has completed bridging pharmacokinetic and safety studies in Chinese healthy subjects. In 2024, Phase 1 clinical trial results and preclinical efficacy data for ALS and epilepsy were presented at the American Neurological Association (ANA) Annual Meeting and the American Epilepsy Society (AES) Annual Meeting, generating significant attention from experts.
The ALS-related preclinical findings received the honor of best poster at the ANA 2024 annual meeting, and Zhimeng received an invitation to give an oral presentation at the Movement Disorder Special Interest Group symposium.
Company Leadership Perspective
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."
Founded in 2018, Shanghai Zhimeng Biopharma focuses on small-molecule drug discovery for chronic hepatitis B functional cure and novel therapies for CNS disorders, including epilepsy, neuropathic pain, ALS, major depressive disorder, and bipolar disorder. The company has successfully completed multiple rounds of financing.
