WARMINSTER, PA — Arbutus Biopharma Corporation (Nasdaq: ABUS) this week announced that preclinical data for AB-343, its novel oral SARS-CoV-2 Mpro inhibitor, has been presented in poster format at the 36th International Conference on Antiviral Research (ICAR), in Lyon, France.
“We are excited that our preclinical data for AB-343 has been selected for poster presentation at ICAR. We developed AB-343, our newly nominated nsp5 main protease inhibitor, because there is an urgent need for oral antiviral therapies that are potent and active against circulating SARS-CoV-2 variants and do not require ritonavir boosting,” said Dr. Michael J. Sofia, Arbutus’ Chief Scientific Officer. “AB-343 has demonstrated these characteristics in preclinical studies. We look forward to completing IND-enabling studies and initiating a Phase 1 clinical trial with AB-343 in the second half of 2023.”
The poster, titled “In Vitro Antiviral Profile of AB-343, a Novel, Oral Potent SARS-CoV-2 Mpro Inhibitor with Pan-coronavirus Activity”, provided an overview of several in vitro preclinical studies conducted with AB-343 to determine its antiviral activity, pan-coronavirus activity and in-vitro selectivity profile. Many of the studies compared AB-343 to nirmatrelvir, the active ingredient in Pfizer’s Paxlovid™ and ensitrelvir, the active ingredient in Shionogi’s Xocova®.
The results showed that AB-343 targets SARS-CoV-2 Mpro and inhibits viral replication in vitro (EC50 ~ 20nM). Binding of AB-343 to SARS-CoV-2 Mpro resulted in longer residence times (>99 minutes versus 21.5 minutes for nirmatrelvir and 1.1 minutes for ensitrelvir) indicative of excellent target engagement. AB-343 also demonstrated pan-coronavirus inhibition (Ki 5-45 nM) against Mpro enzymes from multiple human coronaviruses. In enzyme assays against previously reported SARS-CoV-2 Mpro variants isolated in cell culture, AB-343 showed a differentiated in vitro resistance profile versus both nirmatrelvir and ensitrelvir, including a lower fold-increase in Ki for certain rare Mpro enzyme variants known to reduce in vitro susceptibility. AB-343 maintained potency against naturally prevalent SARS-CoV-2 variants including the Omicron variant. AB-343 also showed high selectivity for SARS-CoV-2 Mpro as it demonstrated little to no inhibition of an enzyme panel comprised of human and other viral proteases.
Based on the antiviral potency, selectivity and favorable PK of AB-343, Arbutus is moving this compound forward into IND-enabling studies and anticipates initiating a Phase 1 clinical trial in the second half of this year.
Some of these studies were conducted in part with Proteros biostructures GmbH under the discovery research and license agreement entered into in April 2021.
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