Xingyao Kunze's HT-101, China's First GalNAc-siRNA Therapy for Chronic Hepatitis B, Receives IND Approval

Recently, Suzhou Hepa Thera Biotech Co., Ltd. (hereinafter referred to as "Hepa Thera"), an innovative liver disease treatment platform company incubated by the new drug innovation fund of Fosun Pharma's subsidiary Fosun Healthcare Capital, announced that the Investigational New Drug (IND) application for Hepa Thera’s lead product, HT-101 injection, for the treatment of chronic hepatitis B virus infection (CHB), has been approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration.

HT-101, an innovative GalNAc-conjugated siRNA drug entity, will become the first GalNAc-conjugated siRNA hepatitis B product in China to enter the clinical stage, providing a "Made in China" treatment option for the large patient population with hepatitis B.

Nearly 100 million people in China are infected with HBV, and there are approximately 30 million patients with chronic hepatitis B (CHB).

Currently, the most important first-line clinical drugs for chronic hepatitis B are nucleoside analogs, such as Lamivudine, Entecavir, Adefovir, Telbivudine, and Tenofovir Alafenamide. The mechanism of action of this class of drugs is to integrate into the viral DNA via the hepatitis B virus (HBV) reverse transcriptase, causing termination of DNA chain replication, thereby reducing HBV DNA. Although nucleoside analogs can effectively control the condition, once the medication is stopped, the virus may rebound. They cannot eliminate the virus, require daily administration, and patient compliance is poor.

The ultimate treatment goal for hepatitis B is to achieve functional cure or even complete cure, but currently there are no clinical treatments that can reach this goal. There is still a significant unmet clinical need for achieving functional cure of hepatitis B. Therefore, the development of drugs capable of achieving functional cure for hepatitis B has the potential to address the urgent needs of a large patient population.

The emergence of RNAi (RNA interference) technology has provided a powerful tool for achieving functional cure of hepatitis B. siRNA (small interfering RNA) and ASO (antisense oligonucleotide), both based on RNAi, are currently the two most important forms of RNAi drugs.

HT-101 Demonstrates Efficacy in Preclinical Trials: A Single Dose Reduces the Expression of Multiple Key Components of the Hepatitis B Virus and Sustains Viral Suppression for Over 70 Days. In foreseeable clinical studies, this will significantly reduce the dosing frequency for patients, thereby improving treatment adherence while also lowering treatment costs.

In the field of hepatitis B, Hepa Thera has also developed a neutralizing antibody targeting the hepatitis B S antigen, HT-102. In animal efficacy studies, HT-102 alone demonstrated significant inhibition of S antigen activity, and its combination with HT-101 showed a marked synergistic effect. The neutralizing antibody HT-102 also submitted a pre-IND application in September 2022, with consideration given to adopting a combination or sequential treatment regimen of siRNA and neutralizing antibodies in future clinical trials. It is worth noting that the combination of siRNA and a neutralizing antibody is a first in China. The combination therapy will significantly expand the target patient population and could cover a broader range of hepatitis B patients with higher viral loads.

Editor: Liuli

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