Ascletis announced the completion of the first patient dosing of ASC22 (Envolimab) for the functional cure of chronic hepatitis B in the Phase IIb Extended Cohort Study

Ascletis Pharmaceuticals Limited (HKEx: 1672, "Ascletis") announced on September 28 that the Phase IIb Extended Cohort Study (the "Extended Cohort") of the subcutaneous PD-L1 antibody ASC22 (Envolimab) for the functional cure of chronic hepatitis B (chronic hepatitis B) has been completed
.

After a phase III clinical trial pre-clinical trial meeting with the Center for Drug Evaluation (MDA) of China in June 2022, ASC22 (Envolimab) has been approved
for the functional cure of chronic hepatitis B, including patient population, dose, course of treatment, etc.

This extended cohort study enrolled 50 patients with chronic hepatitis B with a baseline hepatitis B surface antigen (HBsAg) ≤ 100 IU/mL, treated with 1.
0 mg/kg ASC22 or placebo (4:1) plus nucleoside (acid) analogues (NAs) for 24 weeks and followed for 24 weeks, with the aim of confirming whether the functional cure rate of ASC22 is similar to the European Association for the Study of the Liver (EASL) 2022 International Liver Congress (ILC) in June 2022 2022) presented similar data in an oral report that showed that 42.
9% (3/7) of patients with baseline HBsAg ≤100 IU/mL achieved a functional cure
.
The enrollment of 50 patients with chronic hepatitis B in this expanded cohort is expected to be completed
in early 2023.

Prior to this extended cohort study, Ascletis had completed a randomized, single-blind, placebo-controlled, multicenter Phase IIb clinical trial in China using 1 mg/kg or 2.
5 mg/kg ASC22 or placebo-controlled treatment with NAs for 24 weeks and follow-up for 24 weeks, designed to evaluate the safety and efficacy of this regimen in 149 patients with chronic hepatitis B (ClinicalTrials.
gov: NCT04465890）
。

Chronic hepatitis B still has a large unmet medical need
worldwide.
About 86 million people in China are infected with hepatitis B virus (HBV) and about 1.
59 million people in the United States are infected with HBV ^[1].

NAs can only inhibit hepatitis B virus RNA reverse transcription into hepatitis B virus DNA, but cannot inhibit hepatitis B virus cccDNA transcription into hepatitis B virus RNA, so there is no inhibitory effect
on HBsAg.

ASC22 (Envolimab) is the world's fastest-advancing immunotherapy
for the functional cure of hepatitis B (i.
e.
, HBsAg clearance) by blocking the PD-1/PD-L1 pathway 。 In June 2022, Ascletis orally presented the latest results of the Phase IIb clinical trial of ASC22 in patients with chronic hepatitis B at the European Association for the Study of the Liver (EASL) International Liver Congress 2022 (ILC 2022), which showed that 42.
9% (3/7) of patients with baseline HBsAg ≤100 IU/mL achieved continuous clearance of HBsAg and did not rebound since the last dose of ASC22 (envolimab).
This suggests that a functional cure
of chronic hepatitis B may be achieved.
For oncology indications, Envolimab was approved by the China National Food and Drug Administration in November 2021 for the treatment
of adult patients with advanced solid tumors with unresectable or metastatic microsatellite highly unstable (MSI-H) or mismatch repair genologically deficient type (dMMR).

"We are encouraged by
the exciting progress made in ASC22 (Envolimab) clinical research in the functional cure of chronic hepatitis B over the past few months.
The results of ASC22 (Envoli (Envoli Mobumab), which we presented orally at EASL ILC 2022 in June this year, initially demonstrated the potential for
a functional cure of chronic hepatitis B.
As a large country with hepatitis B, China has a large number of patients with chronic hepatitis B with a baseline HBsAg≤100 IU/mL ^[2].

While exploring ASC22 (Envolimab) monotherapy regimen for patients with chronic hepatitis B at baseline HBsAg≤100 IU/mL, we are also negotiating with global partners for combination therapies targeting a baseline HBsAg >100 IU/mL patient population for the benefit of the broader patient population
of chronic hepatitis B.
Dr.
Jinzi Wu, founder, chairman of the board and CEO of Ascletis, said
.

[1] Lim J K, Nguyen M H, Kim W R, et al.
Prevalence of Chronic Hepatitis B Virus Infection in the United States [J].
The American journal of gastroenterology 2020, 115(9): 1429-38.

Jiang Haiyang, Gu Shengwang, Liu Huan, et al.
Consideration on greatly improving clinical cure based on the results of long-term follow-up of 1783 patients with chronic hepatitis B[J].
Journal of Hepatology, 2020, 25(2):4.

About ASC22(KN035)

KN035 is the world's first PD-L1 antibody drug developed by Suzhou Kangning Jereh Biotechnology Co.
, Ltd.
("Suzhou Kangning Jereh") that can be administered subcutaneously, which has the characteristics of good stability and small injection volume, thereby improving the safety, convenience and compliance of
patients.

The tumor indication of KN035 was developed by Jiangsu Kangning Jereh Biopharmaceutical Co.
, Ltd.
and was approved for marketing
by the National Medical Products Administration in 2021.

The viral disease indication of KN035 was developed by Ascletis Pharmaceuticals, and the phase IIa clinical study of hepatitis B indications showed a dose-dependent downward trend
of hepatitis B surface antigen.
The Phase IIb clinical trial has completed patient enrollment, and preliminary data show that KN035 at a dose of 1 mg/kg combined with nucleoside (acid) analogues is well tolerated for 24 weeks, and can induce HBsAg decline and even negative rotation
in patients with chronic hepatitis B.

The sepsis and sepsis shock indications of KN035 were developed by Suzhou Corning Jereh, and the phase I clinical study preliminarily confirmed that KN035 has good safety and tolerability in patients with sepsis and/or sepsis shock, which can significantly improve clinical safety indicators and accelerate the recovery
of patients.

Ascletis Pharmaceuticals (1672.
HK) has exclusive global rights to
ASC22 (KN035) for the development and commercialization of viral diseases.
At present, ASC22 (KN035) has made a number of positive developments in the field of viral diseases:

1) Functional cure of chronic hepatitis B: Phase IIb clinical data in China showed that ASC22 (KN035) had a good safety profile at a dose of 1 mg/kg combined with nucleoside (acid) analogues for 24 weeks, and 42.
9% of patients with baseline HBsAg ≤ 100 IU/mL achieved continuous clearance of HBsAg, showing the potential for functional cure of
chronic hepatitis B.
The findings were selected for an oral presentation
at the 2022 European Association of Liver Disease Annual Meeting.

2) Immune reconstitution/functional cure of HIV-1 infection: the first subject has been dosed in a phase II clinical trial in China; The Shanghai Public Health Clinical Center also initiated a clinical study initiated by researchers of ASC22 (KN035) in combination with cedamide; The US Phase I/II clinical trial application has also been approved
by the FDA.