Ascletis Pharma announced that the Investigational New Drug (IND) application of ASC10, an oral antiviral drug candidate targeting viral polymerase of monkeypox virus, has been filed with the FDA.
ASC10 is an orally bioavailable and broad antiviral spectrum double prodrug which has a new and differentiated chemical structure from the single prodrug molnupiravir. After oral administration, both ASC10 and molnupiravir are rapidly and completely converted in vivo into the same active metabolite ASC10-A, also known as β-D-N4-hydroxycytidine (NHC) or EIDD-1931. Ascletis has filed multiple patent applications globally for ASC10 and its use in viral diseases including monkeypox virus infection.
The data from the in vitro antiviral cellular assay with infectious monkeypox virus demonstrated that ASC10-A has potent antiviral activity against monkeypox virus, suggesting that ASC10 has the potential to be an effective treatment of monkeypox virus infection. This study was conducted at IIT Research Institute, headquartered at Illinois Institute of Technology in Chicago, U.S. and sponsored by Ascletis.
In August 2022, a research paper was published by Dr. Watashi et al. at the National Institute of Infectious Diseases, Tokyo, Japan. In this research, Dr. Watashi et al. tested 132 drugs and showed that molnupiravir (active metabolite ASC10-A) and other two drugs have potent cellular antiviral activity in the infectious monkeypox virus assay. The rest of 129 drugs such as remdesivir, favipiravir, sofosbuvir and ribavirin, etc. do not have antiviral activities against monkeypox virus.
Monkeypox virus is an orthopoxvirus that causes a disease with symptoms similar to smallpox. As of October 26, 2022, there had been over 75,000 confirmed cases globally and monkeypox virus had been spread in over 100 countries according to data from World Health Organization (WHO). In particular, a total of 28,061 confirmed monkeypox/orthopoxvirus cases have been reported in the U.S. In China, the first confirmed case was reported on September 19, 2022. WHO assesses the risk of monkeypox virus in the European Region and the Region of the Americas as high.
By applying a double prodrug strategy, ASC10's permeability in Caco-2 cells (human colorectal adenocarcinoma cells) and active metabolite exposure in monkeys reached 3.2-fold and 2.1-fold of molnupiravir's, respectively. Studies have demonstrated that ASC10-A has potent cellular antiviral activity against various Omicron variants (BA.1 EC50=0.3 µM; BA.2 EC50=0.25 µM; BA.5 EC50=0.23 µM; BA.2.75 EC50=0.90 µM). The Phase Ib clinical trial in COVID-19 patients is underway in the U.S.
"As China's leading biotech company in antiviral area, Ascletis is dedicated to applying our sciences to address the challenges of viral diseases. Currently there is no treatment approved for monkeypox virus infections globally. This IND filing of ASC10 for monkeypox in the U.S. will further broaden Ascletis' pipeline portfolio in viral diseases, and may provide a solution to monkeypox virus infections." said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.
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