New findings accelerated by Cyclica’s drug discovery platform suggest lung cancer drug capmatinib demonstrates robust antiviral effects in experimental COVID-19 models.
Cyclica, the partner of choice for data driven drug discovery, in connection with leading Canadian research institutions, has predicted a repurposing drug, capmatinib, with evidence that it attenuates the impact of coronavirus. The discovery was made in collaboration with Ryerson University, The Vector Institute, along with other prominent Canadian research institutions; funded by the Canadian Institute for Advanced Research (CIFAR) and Natural Sciences and Engineering Research Council of Canada (NSERC) Alliance COVID-19 grants, with funding support from FedDev Ontario.
Capmatinib, an FDA-approved MET inhibitor, marketed by Novartis under the name Tabrecta, is used clinically to treat patients with (Non-Small Cell) Lung Cancer. The consortium of research institutions showed promising results when testing capmatinib in a collection of experiments evaluating viral infectivity, entry and mechanism.
The manuscript sharing the findings has been published in BioRxiv, and is currently being submitted for peer-review.
With Canadian infection rates recently breaking the 1 million mark and deaths topping 23,000 and counting, and the global infection rate reaching ~132 million, with nearly 3 million deaths to date, intervention is critical.
"By targeting human proteins necessary for the coronavirus lifecycle, we are developing therapeutic strategies applicable to future strains or variants," said Dr. Bo Wang of the Vector Institute. "Unlike high throughput screens, accurate AI predictions aimed at specific human-based, antiviral targets provided us with a risk-adjusted strategy to search for drug-repurposing opportunities using scientifically accurate experiments with high biological relevance."
The discovery of capmatinib’s antiviral activity is a shining example of the power of collaborative research programs. The Vector Institute team’s graph convolutional network (GCN) identified possible human targets relevant to COVID-19, which fed directly into Cyclica’s PolypharmDB - a database for finding repurposing opportunities, generated using Cyclica’s deep learning approach MatchMaker. Several candidate drugs were identified using these sophisticated artificial intelligence models, with capmatinib showcasing prominent activity. Dr. Costin Antonescu from the Department of Chemistry and Biology at Ryerson University confirmed that capmatinib’s activity was independent of its known target MET, with evidence pointing towards its inhibition of the IRAK1/IRAK4 pathways.
"COVID has highlighted how important repurposing discoveries are to the future of medicine," said Antonescu. "These drugs move to clinical trials and through regulatory approval quickly and can therefore reach patients faster. We’ve found a drug that has demonstrated robust antiviral activity in our model systems and we look forward to getting this data in the hands of pharma. There is still much to learn about the etiology of COVID-19, and unravelling the dichotomy of the IRAK pathway as both protective against infections but also critical for viral proliferation may be an important piece to combating this terrible disease."
This research is a part of the Cyclica COVID Stimulus Program launched in March 2020 in which the company engaged in a multi-institution collaboration to use a full-stack AI approach to identify a non-obvious repurposing candidate for COVID-19.
"We’ve committed to advancing the COVID research landscape in Canada and globally," said Naheed Kurji, CEO of Cyclica. "Our business model has always relied on tight collaboration with partner institutions, accelerated by our AI drug discovery platform. This research project is no exception. Our goal with the COVID Stimulus Plan was to make a measurable impact on patient lives today through proposing new therapeutic candidates, as well as advance our understanding of COVID-19 and other related diseases. This is important as in addition to COVID-19, two additional coronaviruses were responsible for deadly outbreaks in the past 20 years that had pandemic potential."
To learn more about the research, please click here. To learn more about Cyclica’s drug discovery platform, please visit https://www.cyclicarx.com/.
From Molecule to medicine, Cyclica embraces the complexity of disease. Our work spans dozens of collaborations with large pharma and biotech as well as several joint ventures. We are a passionate team of biotech and pharma professionals, biologists, chemists, and computer scientists who live and labor at the intersection of our collective expertise. To learn more about Cyclica and how we partner, please visit www.cyclicarx.com
About Ryerson University
Ryerson University is Canada's leader in innovative, career-oriented education. Urban, culturally diverse and inclusive, the University is home to more than 46,000 students, including 2,900 Master's and PhD students, 3,800 faculty and staff, and over 200,000 alumni worldwide. For more information, visit ryerson.ca.
About The Vector Institute
The Vector Institute drives excellence and leadership in Canada’s knowledge, creation, and use of AI to foster economic growth and improve the lives of Canadians. Vector’s Three-Year Strategy aims to advance AI research, increase adoption in industry and health through programs for talent, commercialization, and application, and lead Canada towards the responsible use of AI. Programs for industry, led by top AI practitioners, offer foundations for applications in products and processes, company-specific guidance, training for professionals, and connections to workforce-ready talent. Vector is funded by the Province of Ontario, the Government of Canada through the CIFAR Pan-Canadian AI Strategy, and industry sponsors.
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Jennifer Sacco | email@example.com
Director of Marketing and Communications, Cyclica