On July 16, 2019 Cyclica, a Toronto-based biotechnology company leveraging AI and computational biophysics for drug discovery, and Professor Igor Stagljar from the Donnelly Centre for Cellular and Biomolecular Research, Department of Biochemistry & Department of Molecular Genetics at the University of Toronto, reported a collaboration to optimize lead compounds and de novo design of novel compounds in an effort to advance precision medicine with the next-generation EGFR-inhibitors in non-small cell lung cancer (NSCLC) (Press release, Cyclica, JUL 16, 2019, View Source [SID1234537555]). The Stagljar Lab is located in the Donnelly Centre, a cutting-edge, interdisciplinary research institute in the heart of Toronto’s research district.
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NSCLC makes up approximately 85% of lung cancers. Evolved drug resistance has been a key challenge for treating NSCLC due to EGFR mutations, which are present in roughly 17% of people with lung cancer in the United States. The prevalence of these mutations increase to 50% in people of Eastern Asian descent, and are more common in women than men. Additional research in treating NSCLC is critical to developing effective precision medicines that can target the evolving nature of this disease.
MatchMaker, Cyclica’s proprietary deep learning protein-ligand binding technology, will be used to batch deconvolute a shortlist of shared targets among a group of promising lead compounds identified at the Stagljar Lab using their proprietary MaMTH-Drug Screening (MaMTH-DS) assay to drive new mechanistic insights of such a disease. Ligand Design, Cyclica’s multi-targeted and multi-objective drug design platform, will then create structural variants of the existing lead compounds, and computationally design novel compounds that have the preferred polypharmacological, pharmacokinetic, and physicochemical properties. Recently, Nature Medicine online published an article featuring Cyclica’s drug discovery platforms, and highlighted the value of designing multi-targeted drugs for oncology. The Stagljar Lab will synthesize selected the novel compounds, and conduct downstream validation through its proprietary set of assays for further research and commercialization opportunities. All IP generated from this project related to the compounds will be shared equally by Cyclica and the University of Toronto.
"We are thrilled to be working with the world class Stagljar Lab to leverage our drug discovery platform to progress our shared interests in creating novel advanced lead compounds for non-small cell lung cancer," says Naheed Kurji, President & CEO, Cyclica. "This project is an example of the growing integration between science and industry focused on commercialization, and a testament to the hyper innovative work being done in our own backyard at the University of Toronto."
"We are extremely pleased to be working with Cyclica since our collaboration represents a unique approach that unites two completely novel and complementary approaches, Cyclica’s artificial intelligence MatchMaker and our MaMTH-DS live-cell drug discovery assay, for the rapid identification and validation of novel EGFR inhibitors in NSCLC. I’m positive that our joint efforts will accelerate our ability to build novel EGFR inhibitors with these cutting-edge technologies and will thus speed up their implementation in the clinics," says Dr. Igor Stagljar, University of Toronto.
Cyclica is a Toronto-based, globally recognized biotechnology company that leverages AI and computational biophysics to reshape drug discovery. Cyclica provides the pharmaceutical industry with Ligand Express and Ligand Design, an integrated, holistic, and end-to-end enabling platform focused on polypharmacology. Ligand Design and Ligand Express augment how scientists design advanced lead like molecules that minimize off-target effects, and gain insights into structural pharmacogenomics. By doing more with artificial intelligence, Cyclica aims to revolutionize a system troubled with attrition and costly failures, accelerate the drug discovery process, and develop medicines with greater precision.
The Stagljar Lab at the University of Toronto is focused on protein-protein interactions (PPIs), with a particular interest in disease progression due to altered signalling pathways. They examine how proteins involved in these signalling pathways interact with each other, and try to understand how impaired PPIs lead to numerous human diseases such as lung cancer, pancreatic cancer, breast cancer, brain cancer and aging. In close collaboration with medicinal chemists and clinical investigators, the Stagljar lab investigates the molecular mechanisms behind challenging, unexplained observations on drugs and on pathological events.
The Donnelly Centre for Cellular and Biomolecular Research is an interdisciplinary research institute at the University of Toronto in which scientists make fundamental discoveries in biology to improve health. Founded in 2005, the Centre is globally recognized as a leading biomedical research hub thanks to our researchers’ landmark discoveries in genetics, stem cell biology and the molecular basis of disease, as well as state-of-the-art tools in large-scale data analysis. As well as making discoveries, our researchers also strive to translate their findings into tangible advances in medicine to help patients.