Our Focus

Ascletis focus on breakthrough therapies for HBV functional cure with subcutaneously injected PD-L1 antibody - ASC22 and Pegasys® as cornerstone drugs. 



HBV Functional Cure: ASC22 mechanism

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Prolonged activation of T cells leads to high expression of PD-1. By blocking the connection between PD-1 and PDL-1 through PD-1 antibodies or PD-L1 antibodies, T-cells can remain activated and exert immune functions, ultimately leading to clinical cure.

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In the area of chronic hepatitis C, Ascletis has twoall-oral regimen, among which ASCLEVIR®/GANOVO®regimen has been approved for marketing for marketing in China by National Medical Products Administration (NMPA).


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The human immunodeficiency virus (HIV) is an infectious virus that is primarily transmitted through certain body fluids and attacks the immune system. Patients with HIV have a weakened immune system that is more susceptible to other infections and diseases.

 

In 2017, 1.1 million people are living with HIV in China, with approximately 100,000 new infections in the same year. Without any cure for HIV and due to the inaccessibility to HIV medication, sharing unsterilized needles and social stigma surrounding HIV, HIV patient population in China is expected to grow to 1.73 million in 2025.


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ASC09F

ASC09F is a fixed dose combination (FDC) of ASC09 and Ritonavir. ASC09 is a potential best-in-class protease inhibitor to treat HIV type-1 infections. ASC09 has an unprecedented genetic barrier to resistance and has completed phase I and phase IIa clinical trials, which have shown that ASC09 has potent anti-viral activity, and is safe and well-tolerated. After two weeks of treatment of mono-therapy, ASC09 demonstrated up to a 1.79 log viral load decrease (62-fold reduction of viral load in blood samples of patients). ASC09 has unprecedented genetic barrier to resistance. Studies have shown that ASC09 requires more than seven mutations before HIV develops resistance to ASC09, indicating that ASC09 has a high genetic barrier to resistance compared to other approved protease inhibitors. The high genetic barrier to resistance makes ASC09 a promising candidate for HIV-therapy for both treatment-naïve and treatment-experienced patients. 


Current Therapies and Limitations


Currently, there is no cure for HIV/AIDS. Current HIV treatments need to be taken for a lifetime. The currently available primary HIV therapy in China is a  combination  therapy  of  nucleos(t)ide reverse transcriptase inhibitors (“NRTIs”) and non-nucleos(t)ide reverse transcriptase inhibitors (“NNRTIs”). Although such combination therapy is available in China, patients taking such therapy, such as Lopinavir, may develop drug resistance. As a result, HIV patients generally will turn to a combination therapy of protease inhibitors and NRTIs.


We believe only one HIV protease inhibitor, Lopinavir, was approved and marketed in China. Limitations of this drug primarily include:


• Resistance. During life-long treatments, many HIV  patients have or may develop viral resistance mutations that lower the effectiveness of the treatment. Resistance to protease inhibitor drugs remains a critical factor in the failure of antiretroviral therapy. Patients in China failing approved protease inhibitors due to the emergence of resistant viruses face limited therapeutic options.


• Tolerability. Because current HIV treatments are life-long treatments, prolonged use of protease inhibitors has side effects, including dyslipidemia, insulin-resistance, lipodystrophy and cardiovascular and cerebrovascular diseases. Thus, there is a strong need for safer HIV treatments.


Advantages of ASC09F


We believe that, based on clinical trials and pre-clinical studies, ASC09F has the potential to be a best-in-class HIV protease inhibitor and address the limitations of current HIV therapy in  the following aspects:


• Anti-viral activity. A phase IIa clinical trial has shown that ASC09 displayed similar high anti-viral potency for patients with three or more protease inhibitor resistance-associated mutations as well as for patients with less than three protease inhibitor resistance-associated mutations at baseline. After two weeks of mono-therapy, ASC09 demonstrated up to a 1.79 log viral load decrease (62-fold reduction of viral load in blood samples of patients).

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• Safety and tolerability. The phase IIa clinical trial has indicated that short-term treatment with ASC09 boosted by ritonavir was generally safe and well tolerated. We believe ASC09F has strong potential to be a more tolerable alternative to current therapies for HIV.


• Unprecedented genetic barrier to resistance. During the lifetime treatment, almost all patients will develop resistance to protease inhibitors. Therefore, HIV protease inhibitors with high genetic barrier to resistance have a significant therapeutic advantage over those protease inhibitors with low genetic barrier to resistance. Studies have shown that ASC09 requires more than seven mutations before HIV develop resistance to ASC09, indicating ASC09  has  high  genetic  barrier  to  resistance  compared  to  other  approved  protease inhibitors. The high genetic barrier to resistance makes ASC09 a promising candidate for HIV-therapy for both treatment-naïve and treatment-experienced patients. ASC09 is more active than any of the approved protease inhibitors against multi-protease inhibitors resistant clinical isolates.


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• High anti-viral activity against DRV-resistant viral strains. Darunavir (DRV) is considered to be a best-in-class protease inhibitor among approved protease inhibitors globally. Virological studies suggest that ASC09 is a promising candidate for 72% clinical isolates resistant to DRV, indicating ASC09 has the potential to be the best-in-class protease inhibitor.




Publications


Title

Venue

Type

Date

HBsAg Loss in Chronic Hepatitis B Patients with   Subcutaneous PD-L1 Antibody ASC22 ( Envafolimab ) plus Nucleos (t)ide Analogs   Treatment : Interim Results from a Phase IIb Clinical TrialThe Liver Meeting® 2021 of the American   Association for the Study of Liver Diseases (AASLD)Oral11/2021
A Phase IIa trial of Subcutaneously Administered PD-L1 Antibody ASC22   (Envafolimab) in Patients with Chronic Hepatitis BThe Liver Meeting® 2022 of the American   Association for the Study of Liver Diseases (AASLD)Oral11/2021
Efficacy   and safety of ravidasvir plus sofosbuvir in patients with chronic hepatitis C   infection without cirrhosis or with compensated cirrhosis (STORM-C-1):   interim analysis of a two-stage, open-label, multicentre, single arm, phase   2/3 trialThe Lancet Gastroenterology &   Hepatology, Volume 6, Issue 6.Paper04/2021
Significant in vitro and in vivo inhibition of   HBsAg and HBV pgRNA with ASC42, a novel non-steroidal FXR agonistThe   International Liver Congress™ 2021 of the European Association for the Study   of the Liver (EASL)Poster
04/2021
First clinical study using HCV protease   inhibitor danoprevir to treat COVID-19 patients Medicine (2020) 99:48 Paper11/2020
利托那韦强化的达诺瑞韦联合达拉他韦治疗1b型慢性丙型肝炎的临床疗效分析中华临床感染病杂志,   2019(05):350-351-352-353-350-353,371.Paper10/2019
Efficacy and Safety of All-oral, 12-week   Ravidasvir Plus Ritonavir-boosted Danoprevir and Ribavirin in Treatment-naïve   Noncirrhotic HCV Genotype 1 Patients: Results from a Phase 2/3 Clinical Trial   in ChinaJournal of Clinical and Translational   Hepatology 2019;7(3):213-220Paper09/2019
Efficacy and  safety of 12-week   interferon-based danoprevir regimen in patients with  genotype 1 chronic   hepatitis CJournal of Clinical and Translational   Hepatology 2019;7(3):221-225Paper07/2019
All-oral, 12-week  ravidasvir plus   ritonavir-boosted danoprevir and ribavirin delivers 100% svr12 in   treatment-naive noncirrhotic hcv genotype 1 patients with    resistance-associated substitutions of a phase 2/3 clinical trial in   ChinaJournal of Hepatology 2019 vol. 70 | e141–e382Poster04/2019
12 week Ravidasvir plus ritonavir-boosted   Danoprevir and ribavirin achieves 99% SVR12 in treatment-naı ¨ve non- cirrhotic HCV GT1 patients: Subanalysis of phase 2/3   clinical trial in China Hepatol   Int (2019) 13 (Suppl 1):S86Paper02/2019
达诺瑞韦及其联合PR方案治疗慢性丙型肝炎研究进展中华临床感染病杂志,2018,11(02):84-89.Paper04/2018
Twelve-week  Ravidasvir plus   ritonavir-boosted Danoprevir and ribavirin for non- cirrhotic  HCV   genotype 1 patients: A phase 2 studyJournal of Gastroenterology & Hepatology, 2018, 33(8).Paper01/2018
The Effcacy and  Safety of All-Oral,   12-Week Ravidasvir Plus Ritonavir-Boosted Danoprevir and  Ribavirin in   Treatment-Naïve Non-Cirrhotic HCV Genotype 1 Patients : Results  from a   Phase 2/3 Clinical Trial in ChinaThe Liver Meeting® 2018 of the American Association for the Study of Liver Diseases (AASLD)Poster11/2018
MAKALU:  Twelve-week of treatment with   Ritonavir-boosted Danoprevir Pluzs Peginterferon  and Ribavirin produces   96% SVR12 in HCV Genotype 1-Infected Non-Cirrhotic  Chinese PatientsHepatol Int (2017) 11 (Suppl 1):S190Poster02/2017
Ritonavir-boosted  danoprevir plus   peginterferon alfa-2a and ribavirin in Asian chronic  hepatitis C   patients with or without cirrhosisJournal of Gastroenterology and Hepatology 31   (2016) 1757–1765 Paper10/2016
DAUPHINE: a randomized phase II study of   danoprevir/ritonavir plus peginterferon alpha-2a/ribavirin in HCV genotypes 1   or 4Liver International,2015,35(1):108-119. Paper01/2015