June 5, 2025- Shanghai Zhimeng Biopharma, Inc., a clinical-stage biopharmaceutical company focused on innovative drug development for liver and central nervous system diseases, today announced that its self-developed next-generation HBV core inhibitor, ZM-H1505R（Canocapavir, ZM-H1505R）, for the treatment of chronic hepatitis B, has officially reached agreement with the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration to initiate a pivotal Phase 3 clinical trial for the treatment of chronic hepatitis B.
The upcoming Phase 3 trial is a multicenter, randomized, double-blind, and placebo-controlled study to evaluate the efficacy and safety of ZM-H1505R, comparing the combination with nucleos(t)ide analogues (NAs)vs. NAs monotherapy, in patients with chronic hepatitis B who have received NA treatment for at least 12 months. The aim of this trial is to provide the critical evidence to support the New Drug Application.
“ZM-H1505R is Zhimeng’s first self-developed new drug advanced to Phase 3 clinical development. We sincerely appreciate the CDE’s recognition of ZM-H1505R’s potential in treating chronic hepatitis B,” said Dr. Huanming Chen, founder and CEO of Zhimeng. “The initiation of this pivotal Phase 3 trial marks another major milestone in Zhimeng’s history and further demonstrates our continued innovation in CHB drug development. I would like to thank our R&D team, collaborators, and investors for their contributions in making this milestone possible. We will try our best to accelerate the clinical development progress and to reach the commercialization status of our pipeline to benefit more patients and fulfill the trust and expectations of both patients and healthcare professionals.
According to relevant data, China has approximately 86 million hepatitis B virus (HBV) carriers, including about 30 million chronic hepatitis B patients. However, the diagnosis rate is only 18.7%, and the treatment rate is less than 11%, significantly below the WHO’s 2030 targets (90% diagnosis rate, 80% treatment rate). In China, over 80% of hepatocellular carcinoma (HCC) cases are attributed to chronic HBV infection. While current NA antiviral therapies can effectively control HBV replication and slow the liver fibrosis progression in most patients, a substantial proportion of patients exhibit inadequate or no-responses. Current therapies are rarely able to achieve a functional cure for CHB. Patients typically require life-long treatment and face the risk of viral rebound after discontinuation. Therefore, there is an urgent need for novel therapeutic approaches targeting different stages of the HBV lifecycle.
ZM-H1505R is a potent small-molecule HBV core protein inhibitor that effectively suppresses the formation of HBV nucleocapsids. Phase 2 clinical trial results have demonstrated its potential to significantly improve antiviral response rates in NA-suppressed CHB patients, potentially reducing the risk of liver cirrhosis and hepatocellular carcinoma (HCC). Compared to existing Type I and Type II HBV core protein allosteric modulators, ZM-H1505R is a novel pyrazole molecule, which retains potent antiviral activity against viruses resistant to Type I/II HBV core inhibitors and NA therapies due to gene mutations.
As an innovative drug development platform focused on liver diseases, Zhimeng’s pipeline targets multiple stages of the HBV life cycle, including core protein inhibitors for suppressing viral replication, immune modulators, and RNA destabilizers that inhibit surface antigen expression. Zhimeng aims to achieve a functional cure for chronic hepatitis B (CHB) by multi-pronged approaches that inhibit viral replication and protein expression while inducing effective antiviral immune responses.
Dr. Zhihong Lu, Chief Medical Officer of Zhimeng, said: “ZM-H1505R has demonstrated favorable tolerability, safety, and promising efficacy in completed Phase 1 and Phase 2 clinical trials. The goal of this Phase 3 trial is to confirm the efficacy and safety of ZM-H1505R in combination with NAs in CHB patients who have been on NA treatment for at least one year without achieving complete virological suppression, thereby supporting a future New Drug Application (NDA). We will work diligently to advance the Phase 3 study with full dedication, speed, and high quality, striving to provide patients with a more optimal treatment option as early as possible.
Beyond its CHB functional cure program, Zhimeng is also actively developing small-molecule therapeutics for CNS disorders. Among them, CB03, Zhimeng’s proprietary CNS candidate, KCNQ2/3 potassium ion channel opener, received orphan drug designation (ODD) from US FDA for the treatment of ALS, which is an important milestone in its global clinical development for ALS. In addition, CB03 has its potential for becoming a safe and effective treatment for other CNS diseases. A Phase 2 clinical trial for focal epilepsy has been initiated in Australia.
About Zhimeng
Founded in 2018, Shanghai Zhimeng Biopharma, Inc. is a biopharmaceutical company dedicated to develop small-molecule drug discovery with focused on the functional cure of chronic hepatitis B (CHB), as well as novel therapies for intractable CNS disorders, including epilepsy, neuropathic pain (e.g., cancer-related pain), amyotrophic lateral sclerosis (ALS), major depressive disorder (MDD), and bipolar disorder. Zhimeng has successfully completed multiple rounds of financing.
About ZM-H1505R
ZM-H1505R is an investigational HBV capsid formation inhibitor that is being developed by Zhimeng Biopharma for the treatment of HBV infection. Different from the reported Type I and Type II HBV core protein allosteric modulators (CpAMs), ZM-H1505R is a novel pyrazole molecule and has a new mechanism of action. It hinders the packaging of pre-genomic RNA (pgRNA), and effectively blocks the formation of HBV cccDNA. In January 2025, ZM-H1505R received the breakthrough designation from CDE for the treatment of chronic hepatitis B.