Novel antiviral outperforms remdesivir in COVID-19 cell assays

Bold Therapeutics has released data on the novel antiviral BOLD-100.

In a series of experiments conducted by Dr Stephen Barr, Associate Professor in the Department of Microbiology and Immunology at Western University, BOLD-100 and remdesivir were tested head-to-head in a cytopathic effect assay against a live Wuhan strain of SARS-CoV-2 (COVID-19) in Vero E6 cells.

Consistent with prior experiments, BOLD-100 showed low nanomolar IC50 values, a magnitude lower (1/10th) than the IC50 values of Gilead’s remdesivir, the only currently approved therapeutic for COVID-19. This data clearly demonstrates that BOLD-100 is a highly potent antiviral agent.

BOLD-100 is a first-in-class ruthenium-based small molecule drug which selectively inhibits stress-induced upregulation of the chaperone protein GRP78. In cancer, GRP78 plays a critical role in resistance, survival and proliferation, whereas in viral infections, GRP78 plays a critical role in host recognition, viral entry and viral replication. There are now more than two hundred independent academic articles highlighting the critical role that GRP78 plays in viral infections (e.g. Ha DP, Van Krieken R, Carlos AJ, Lee AS. The stress-inducible molecular chaperone GRP78 as potential therapeutic target for coronavirus infection. J Infect. 2020 Sep;81(3):452–82.).

This empirical data on BOLD-100 as an antiviral is supported by additional work carried out by Bold Therapeutics’ other COVID-19 Consortium members including François Jean, PhD, Associate Professor in the Department of Microbiology and Immunology and founder of the UBC Facility for Infectious Disease and Epidemic Research (FINDER); Ted Steiner, Professor and Division Head, Division of Infectious Diseases at the University of British Columbia; Marc-André Langlois, Faculty Professor of Medicine at the University of Ottawa and Canada Research Chair in Molecular Virology and Intrinsic Immunity; and Len Seymour, PhD, Director of Clinical Pharmacology at the University of Oxford. Bold Therapeutics is also collaborating with international researchers at McMaster University, the University of Southern California, the University of Pennsylvania, Georgetown University, Queens University Belfast, the University of Vienna, and the Medical University of Vienna, among others who are collectively advancing our understanding of both the GRP78 pathway and BOLD-100’s selective inhibition of stress-induced GRP78.

“Bold Therapeutics’ ongoing collaboration with some of the top virologists in Canada continues to produce independent data supporting BOLD-100 as a novel antiviral,” stated Mark Bazett, Bold Therapeutics’ Director of Preclinical Development.

Dr. Bazett continued, “Today’s data is particularly impressive, showing that BOLD-100 is substantially more potent as an antiviral than remdesivir, the only recently Health Canada approved treatment for COVID-19. The collective evidence on BOLD-100 supports further, rapid development of this novel treatment option to support patients with COVID-19.”

While much attention has been given to vaccine development, it is a challenging and high-risk endeavour. And even if an effective vaccine is successfully developed and subsequently manufactured, effective antivirals for infected patients unable or unwilling to take vaccines will still be needed. BOLD-100 has the potential to substantially reduce severity of infection, shortening hospital stays and reducing morbidity and mortality – but this can only be definitively determined through clinical testing. Perhaps most importantly, BOLD-100 could be effective against not just the current pandemic, but also future viral pandemics – whereas COVID-19 vaccines would necessarily be ineffective.

Bold Therapeutics has already manufactured more than sufficient drug product to support immediate clinical studies in COVID-19 due to an ongoing Phase 1/2 trial of BOLD-100 in combination with FOLFOX in the treatment of advanced GI cancers, with an open IND with the U.S. FDA and a February 2020 NOL from Health Canada. In an earlier Phase 1 dose-escalation study of 46 patients with advanced cancer, BOLD-100 was safe and well-tolerated, potentially allowing BOLD-100 to move immediately into Phase 2 trials in COVID-19. These factors allow BOLD-100 to be developed and potentially approved as an anti-COVID-19 therapeutic in a relevant timeframe, rather than years from now.

Image credit: Tai’s Captures

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