Benzinga | Dec 17, 2020 08:01AM EST

Aligos Therapeutics Presents Update on Development of SARS-CoV-2 Therapeutic Candidate and Screening Method in Collaboration with KU Leuven at RespiDART & Emerging Viruses 2020

Aligos Therapeutics, Inc. (NASDAQ:ALGS), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, today announced that the company delivered an oral and poster presentation today at the RespiDART & Emerging Viruses 2020 meeting. The presentation highlighted the company's progress with developing a SARS-CoV-2 therapeutic candidate, as well as the development of a screening method to assess potential candidates. Aligos performed all research in collaboration with Belgian University KU Leuven, in particular its Centre for Drug Design and Discovery (CD3), and the Rega Institute for Medical Research.

The presentation, titled "Structure-based discovery of potent and selective SARS-CoV-2 3-chymotrypsin-like cysteine protease inhibitors using a multiplex screening platform," describes the authors' mass spectrometry-based assay developed to assess putative coronaviral 3-chymotrypsin-like cysteine protease (3CLpro) inhibitors in development for therapeutic use against SARS-CoV-2, including Aligos' own 3CLpro inhibitor candidate, ALG-097111. Coronaviral 3CLpro is a promising therapeutic target, as it is essential and conserved among coronaviruses but is not found in humans.

Aligos and collaborators launched a structure-based approach to identify novel coronaviral 3CLpro inhibitors that were evaluated in the in-house developed multiplex SARS-CoV-2 3CLpro/human rhinovirus 3C (HRV3C) protease assay to assess their specificity and selectivity.

Unlike all other SARS-CoV-2 3CLpro compounds tested with the screening platform to date, Aligos' lead compound ALG-097111 demonstrated potent SARS-CoV-2 3CLpro inhibition, without inhibiting human cathepsin L protease activity up to the highest concentration tested (IC50 > 10 ?M). Cathepsin L has been shown to be involved in a highly redundant entry pathway of SARS-CoV-2 into different cell types. As the competition between the viral 3CLpro and the host cathepsin L might eventually act as a decoy mechanism in vivo, the identification of potent inhibitors selective for the viral 3CLpro represents an important breakthrough.

"We are pleased that our work with CD3 and the Rega Institute has yielded a platform that we can use to optimize our SARS-CoV-2 3CLpro inhibitors," said Pierre J.M.B. Raboisson, Pharm.D. Ph.D., Vice President, Head of Small Molecule Medicinal Chemistry and European Site Head at Aligos. "A highly specific, selective small molecule anti-coronaviral therapeutic will likely be indispensable as part of an effective treatment regimen against SARS-CoV-2, whereas treatments repurposed from other viral indications may fall short. We are encouraged to see potent protease inhibition activity with ALG-097111 and we continue to refine the candidate's chemistry for optimal potency."