On January 26, 2021 Bicycle Therapeutics plc (NASDAQ:BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that an article highlighting preclinical studies of Bicycle’s novel, fully synthetic Bicycle systemic immune cell agonists and tumor-targeted immune cell agonists (TICAs) was published in the Journal for ImmunoTherapy of Cancer (JITC) (Press release, Bicycle Therapeutics, JAN 26, 2021, View Source [SID1234574285]). The article, titled "Anticancer immunity induced by a synthetic tumor-targeted CD137 agonist" is available online via this link.
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"The data published in JITC describe the application of Bicycle’s unique technology to produce a new class of potential immuno-oncology therapies: tumor-targeted immune cell agonists, or TICAs," said Nicholas Keen, Ph.D., Chief Scientific Officer of Bicycle Therapeutics. "In contrast to immune checkpoint inhibitors, the use of antibodies as agonists of immune costimulatory receptors as cancer therapeutics has largely failed. Here we demonstrate the discovery of small, chemically synthetic Bicycles that bind to key co-stimulatory receptors and that can be coupled in a modular manner to tumor antigen binding Bicycles to produce tumor localized receptor agonism. We look forward to initiating a clinical trial for our lead TICA program, BT7480, this year."
The article outlines the work Bicycle is undertaking to unlock a new method of cancer immunotherapy via small molecule agonism of TNF superfamily receptors. In the studies, TICAs were evaluated in a suite of in vitro and in vivo assays to characterize the pharmacology and mechanism of action. Results showed that by linking a costimulatory receptor (e.g., CD137) targeting Bicycle to a tumor antigen (e.g., EphA2), targeting Bicycle potent agonists were created, which activated the costimulatory receptor selectively in the presence of tumor cells expressing that antigen. An EphA2/CD137 TICA efficiently co-stimulated human peripheral blood mononuclear cells in vitro in the presence of EphA2-expressing tumor cell lines, as measured by an increased secretion of interferon γ and interleukin-2. Treatment of C57/Bl6 mice (transgenic for the human CD137 extracellular domain, huCD137) bearing EphA2-expressing MC38 tumors resulted in increased infiltration of CD8+ T cells, the elimination of tumors, and generation of immunological memory. Tumor target-dependent CD137 agonism using TICAs afforded elimination of tumors in preclinical models using only intermittent dosing, suggesting the potential for a wide therapeutic index in humans.