Vancouver, Canada’s Bold Therapeutics, formed in 2018 by group of seasoned biopharma veterans, sought to develop and commercialize BOLD-100, what they consider a first-in-class anti-resistance therapeutic. Just in May 2020, the company executed an option agreement with South Korea’s Hana Pharm Co. Ltd. for the exclusive rights to a small molecule drug, which selectively inhibits stress-induced upregulation of GRP78—an important resistance, survival and proliferation pathway common across cancers. Under the terms of the agreement, the Vancouver-based company would collaborate with Hana Pharm on upcoming Phase 1b/2a adaptive clinical trials testing the drug in gastric, pancreatic, colorectal and bile duct (cholangiocarcinoma) cancers while also exploring this new drug against triple-negative breast cancer. Now called BOLD-100, Bold Therapeutics’ executives’ world changed with the onset of SARS-CoV-2 and the COVID-19 pandemic. Forming a COVID-19 coalition, the startup too was on the hunt for treatments against the pathogen out of Wuhan, China. Recently, scientists researching out of Western University, led by Dr. Stephen Barr, made a striking discovery: that in a lab cell culture involving a live Wuhan strain of SARS-CoV-2 in Vero E6 cells, BOLD-100 performs substantially better than remdesivir in attacking the pathogen evidencing powerful antiviral qualities.
Bold Therapeutics has been calling attention to BOLD-100’s since March. They have pointed out that as the drug’s main mechanism of action inhibits stress-induced upregulation of GRP78 (a protein encoded by the HSPA5 gene), a common receptor for viral recognition of host cells while a recently publication suggested GRP78 as a potential binding site for COVID-19. Other early-stage research hypothesized that inhibiting or blocking GPR78 could reduce viral loads or viral replication in Ebola, Japanese Encephalitis Virus and Dengue Virus.
The Western University Experiment
Dr. Stephen D. Barr, a molecular biologist, runs his namesake lab out of Western University in Ontario, Canada. A professor in the Department of Microbiology and Immunology, the researcher and team tested BOLD-100 and remdesivir head-to-head in a cytopathic effect assay against a live Wuhan strain of SARS-CoV-2 in Vero E6 cells. Barr and team validated other experiments showing BOLD-100 produced 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. Bold Therapeutics declared that these data points clearly evidences the potential of BOLD-100 as a highly potent antiviral agent, not only potentially targeting COVID-19 but also viruses.
Recently, other researchers part of the Bold Therapeutics’ COVID-19 Consortium have come up with similar conclusions. The members include the Department of Microbiology and Immunology and founder of the UBC Facility for Infectious Disease and Epidemic Research (FINDER); Ted Steiner, MD, 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 the understanding of both the GRP78 pathway and BOLD-100’s selective inhibition of stress-induced GRP78.
The Case for Antivirals
The case for vaccines is obvious but the successful development involves complexity and risk. It isn’t clear yet if the first generation of COVID-19 vaccine candidates will be safe and effective, although there are promising signals with candidates now in Phase 3 testing. However, there is still much about the novel coronavirus to learn, such as how it morphs or evolves, and researchers don’t know yet how these first generation of vaccines will truly perform in the clinic. Moreover, although some of the vaccines may turn out to be safe and effective, it may not be fully effective, meaning it doesn’t work for all people all the time. Additionally, there are many people unwilling or unable to take vaccines.
TrialSite has followed a number of potential therapies that could possibly reduce the severity of SARS-CoV-2 infection, while shortening hospital stays and reducing morbidity and mortality. The premise: that the world will benefit from powerful antiviral medications that can materially impact the severity of COVID-19 will be incredibly valuable for humanity. Currently, remdesivir must be administered intravenously in a hospital, is expensive, and only shortens hospitalization from 15 days down to 11 days according to pivotal Phase 3 studies. Although there are observational data points, there is no direct evidence from clinical trials that Gilead’s antiviral can reduce the death rate from COVID-19.
A Call for Phase 2 Clinical Trial
The company’s latest press release is a call for help. The company’s executives and supporting academic partners, such as Dr. Barr from Western University, declare the findings in the lab cannot be ignored. The company has produced sufficient quantities of the investigational drug product to support immediate clinical trials targeting COVID-19 patients 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, BODL-100 was deemed safe and well-tolerated, potentially allowing BOLD-100 to move immediately into Phase 2 trials in COVID-19. Due to these factors, it is feasible that BOLD-100 could be possibly accelerated as an anti-COVID-19 therapeutic.
Partners & Investors
According to Pitchbook, Bold Therapeutics accomplished one round of investment and, according to the company via its website, it expects to initiate a B round at some point in 2020. The company has established that it is interested in either partnering with another biopharmaceutical sponsor and/or raising more capital to properly fund a comprehensive COVID-19 clinical program.
Dr. Barr would be a good contact to verify the tests thus far.