Shanghai, China, Apr 14th, 2021 - Shanghai Henlius Biotech, Inc. (2696.HK) announced that the first healthy volunteer was dosed in a Phase 1 clinical trial of HLX71, a recombinant human angiotensin converting enzyme 2 (hACE2)-Fc fusion protein independently discovered and developed by the Company, for the treatment of COVID-19. The successful development of HLX71 will not only address the unmet treatment needs of patients with moderate/severe COVID-19, but also can be used in the prevention of COVID-19.
HLX71 is a recombinant hACE2 fusion protein with IgG1 Fc at the C-terminal, which is independently discovered and developed by Henlius. Binding of the RBD domain on the S1 subunit of the viral spike protein with hACE2 will lead to cell endocytosis of the virus, which is a critical step for viral entry[1-2]. Because of its nature of an ACE2 fusion protein, HLX71 has dual mechanism of action in prevention and treatment of COVID-19. On one hand，the ACE2 part of HLX71 can act as a bait to bind with the viral RBD domain with a high affinity, preventing the binding of virus and host cell ACE2. Via this mechanism, the ACE2-Fc fusion protein can inhibit SARS-CoV-2 virus infection and can be potentially used in the treatment of COVID-19. Besides, with ACE2 enzymatic activity, HLX71 can also inhibit inflammatory reaction by regulating the renin-angiotensin signal pathway thus enhancing its effect in treatment of COVID-19.
Non-clinical pharmacology, pharmacokinetics and toxicology studies were performed by Henlius to evaluate the efficacy and safety of HLX71 according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. Results from these studies showed that HLX71 can significantly inhibit SARS-CoV-2 virus infection with a good safety profile via intravenous injection and was sensitive to neutralize all pseudovirus mutant SARS-CoV-2 strains which has been tested. It’s worth noting that, HLX71 has demonstrated stronger neutralizing activity in the binding of some pseudovirus mutant SARS-CoV-2 virus.
Currently, COVID-19 vaccine is gradually penetrated and effectively blocked the spread of the epidemic in China. However, effective treatment of COVID-19 is indispensable to bring the epidemic to an end. Looking Forward, Henlius will accelerate the clinical research of HLX71 and plan to market the product via Emergency Use Authorization (EUA) to fulfill the unmet treatment needs of COVID-19 patients, contributing more in the fight against COVID-19.
Reference Notes
[1] Wang Q, Zhang Y, Wu L, et al. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2[J]. Cell, 2020, 181(4).[2] Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2[J]. Science, 2020, 367(6485): 1444-1448.