Ascletis Pharma is a Chinese biotech that currently has three products approved for use in China and a pipeline focused on viral diseases, nonalcoholic steatohepatitis (NASH)/primary biliary cirrhosis (PNC), and oral cancers/immune checkpoint inhibitors.
The biotech announced that the US Food and Drug Administration (FDA) had accepted its investigational new drug (IND) application for ASC10, an oral antiviral drug candidate, in an indication against monkeypox.
Ascletis received approval for its IND against COVID-19 in August 2022, and has a Phase Ib clinical trial in COVID-19 patients underway in the US.
According to the company, ASC10 is an orally bioavailable and broad antiviral spectrum double prodrug, which targets viral polymerase of the monkeypox virus.
Both ASC10 and molnupiravir, which is an oral treatment for COVID-19, are converted into the same active metabolite, ASC10-A, also known as β-D-N4-hydroxycytidine (NHC) or EIDD-1931. However, Ascletis’ drug candidate has a differentiated chemical structural from the single prodrug molnupiravir.
The IND application was based on data from preclinical studies, which showed that ASC10-A has antiviral activity against the monkeypox virus in research conducted at IIT Research Institute, in Illinois.
The company stated that due to the double prodrug strategy, in tests it was found that ASC10’s permeability in Caco-2 cells and active metabolite exposure in monkeys reached 3.2-fold and 2.1-fold of molnupiravir’s, respectively.
Ascletis’ work focusing on ASC10 was backed up by findings in a research paper published out of the National Institute of Infectious Diseases based in Tokyo, Japan.
In the paper, 132 drugs were tested and the efficacy of the mode of action of only molnupiravir, and two other drugs (atovaquone and mefloquine), proved to have cellular antiviral activity in the infectious monkeypox virus assay. Other treatments, including remdesivir, favipiravir, sofosbuvir, and ribavirin, were not found to have antiviral activity.
The threat of monkeypox
Monkeypox is a viral zoonosis with symptoms similar to those previously seen in smallpox patients, though less clinically severe. Monkeypox primarily occurs in central and west Africa, often in locations located close to tropical rainforests.
However, since May 2022, cases of monkeypox have been reported in countries where the disease is not endemic and continue to be reported globally. According to the WHO, this is the first time that many monkeypox cases and clusters have been reported concurrently in non-endemic and endemic countries in disparate geographical areas.
As of the end of October, over 75,000 cases have been reported globally, across over 100 countries. Of these cases, more than 28,000 were confirmed in the US.