On July 12, 2022 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 data from BT7480, a Bicycle tumor-targeted immune cell agonist (Bicycle TICA) targeting Nectin-4 and agonizing CD137 (4-1BB), was published in the Journal of Medicinal Chemistry (Press release, Bicycle Therapeutics, JUL 12, 2022, View Source [SID1234616605]). The article, titled "Discovery and Optimization of a Synthetic Class of Nectin-4-Targeted CD137 Agonists for Immuno-oncology" is available at the publications section of the Bicycle website at this link.

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"CD137 is a co-stimulatory receptor on immune cells that can drive anti-tumor immunity and Nectin-4 is a cell adhesion molecule that is overexpressed in a wide range of solid tumors. We discovered BT7480 by using a series of novel Bicycles targeting CD137, which were conjugated to novel Bicycles targeting Nectin-4," said Nicholas Keen, Ph.D., Chief Scientific Officer of Bicycle Therapeutics. "The work that was published today demonstrated our goal to discover a Nectin-4-targeted CD137 agonist clinical candidate with unique properties – small size, dependency on binding to Nectin-4 bearing tumor cells for activity and very potent CD137 agonism. Furthermore, we engineered the molecule so that it could be dosed once a week in the clinic. We deployed a multipronged approach to optimize the molecule’s affinity to both targets, linker length, binder stoichiometry, solubility, and pharmacokinetic properties. By exploring the valency of the Bicycles in rodent studies, it was demonstrated that the 1:2 format Nectin-4/CD137 may lead to promising immune response in solid tumors. BT7480 is currently in Phase I development with dose escalation ongoing."