China-based Ascletis Pharma Inc. (HKG: 1672) announced the submission of an Investigational New Drug (IND) filing with the US FDA for its ASC10, an oral antiviral drug candidate targeting the viral polymerase of the monkeypox virus. This marks a significant step in the development of new treatments for monkeypox, a viral disease that has garnered increased attention globally.
ASC10 Profile and Mechanism
ASC10 is an orally bioavailable and broad-spectrum antiviral double prodrug with 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. By employing 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.
Preclinical and Clinical Data
Data from in vitro antiviral cellular assays with infectious monkeypox virus demonstrated that ASC10-A has potent antiviral activity against the monkeypox virus. Additionally, studies have shown 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). A Phase Ib clinical trial for the drug in COVID-19 patients is already underway in the US.
Future Outlook
With the IND submission to the FDA, Ascletis is poised to advance ASC10 into clinical trials for monkeypox, aiming to address the significant unmet need for effective antiviral treatments against this viral disease.-Fineline Info & Tech
