2020 EASL: Early results of the treatment of hepatitis B virus infection by Asheng Pharmaceutical IAP inhibitors were released.

On August 27th, Asasin Pharma announced that at the European Society for The Study of Hepatology (EASL) 2020 International Conference on Liver Disease (Digital ILC 2020), Professor Zhang Xiaoyong, Department of Infection Medicine, Southern Hospital, Southern Medical University, announced a clinical study on the treatment of hepatitis B virus (HBV) infection in the form of oral reports.
EASL is the world's authoritative Society for the Study of Hepatology, affected by the new crown outbreak, the annual meeting was held online from August 27-29 (Central European Summer Time).
APG-1387 is a new generation of apoptosis protein inhibitor (IAP) highly specific inhibitor developed by Asaan Pharmaceuticals with global intellectual property rights, which induces and accelerates the process of apoptosis mainly by simulating endogenous SMAC molecular degradation of IAPS.
as the first IAP inhibitor to enter the clinical phase in China, APG-1387 is currently conducting a number of clinical studies on chronic hepatitis B (CHB) and solid tumors.
The preclinical results of this oral report, completed by Professor Zhang Xiaoyong's team, showed that the dna of HBsAg, HBeAg and HBV in the serum was completely removed at 4-20 weeks using APG-1387 in three different models of chronic hepatitis B mice compared to the control group, and the replication intermediates of HBcAg and HBV in infected liver tissue were completely removed after discontinuation of treatment.
Although active caspase-3 expression can be detected in HBcAg-positive liver cells after injection, serum transaminase levels increase instantaneously, and their peak levels are associated with baseline HBsAg levels, pancaspase protease inhibitor Emricasan or Z-VAD-FMK cannot block APG-1387 antiviral action.
in-depth study found that HBV removal may be related to the increase in frequency and function of HBV-specific CD4 plus and CD8 plus T cells in the liver, and that TNF alpha knock-out, CD4-plus, or CD8-plus T cell defects can completely block the removal effect of APG-1387 on HBV.
In addition, gene avocation analysis of RNA-seq in liver tissue showed that APG-1387 injection induced an increase in intra-hepatic immunologic-related gene expression, and that these genes were similar to the differential gene expression spectrum in the liver of acute HBV-infected chimpanzee models.
These results show that APG-1387 can remove viruses from a variety of chronic HBV-carrying mouse models through unique apoptosis induction and immunomodulation mechanisms, and the use of IAP inhibitors is expected to be a new immunotherapy strategy for functional cures of hepatitis B.
, Professor Zhang Xiaoyong, said: "It is interesting to see that in addition to inducing apoptosis, IAP inhibitors also have the effect of regulating the body's immune system.
Our results show that APG-1387 can break the immune-resistant micro-environment in the liver of the HBV mouse model, significantly enhance the HBV-specific T-cell response, induce the 'chronic' infection to be converted into an immune state of 'acute' infection, and play an effect of promoting and accelerating the removal of HBV.
this new mechanism of action has brought light to the study of the cure of hepatitis B, and further exploration of its mechanism of action will also help to find new treatments.
" Currently, ASA Pharmaceuticals is developing APG-1387 worldwide, has completed clinical phase 1 dose climbing trials for solid tumors in China and Australia, and is conducting phase 1b/2 clinical trials in the United States in a joint treatment with Pabliju monoantigen.
approved in China in February this year to launch a phase 1b/2 clinical trial with yew alcohol and gisithambin to treat advanced pancreatic cancer.
is also conducting clinical studies in China on the treatment of chronic hepatitis B, APG-1387 combined with Entekave to treat chronic hepatitis B phase 2 clinical study in June this year completed the first patient drug treatment.
: Aachen Pharmaceuticals IAP inhibitor APG-1387 received an oral report at the 2020 Annual Meeting of the European Society of Hepatology (EASL 2020). Retrieved Aug 27, 2020, from.