Bicycle Therapeutics Announces First Patient Dosed in Phase I/II Trial of Bicycle Toxin Conjugate BT8009 in Patients with Advanced Solid Tumors

Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, today announced the first patient has been dosed in the Phase I dose escalation portion of a company-sponsored Phase I/II trial of BT8009, a Bicycle Toxin Conjugate (BTC) targeting Nectin-4. BT8009 is a second-generation BTC, which uses a valine-citrulline cleavable linker and a cytotoxin MMAE payload. It targets Nectin-4, which is a well-validated tumor antigen. Overexpression of Nectin-4 has been observed in several common tumor types and is associated with poor disease prognosis. The Phase I/II trial of BT8009 will be conducted in patients with advanced solid tumors associated with Nectin-4 expression.

“BT8009 is one of a new class of tumor-targeting agents that we believe represent the next generation of treatments for solid tumors. With a molecular weight 50-100 times smaller than that of a typical antibody drug conjugate, or ADC, and the anticipated ability to fully penetrate tumors with precision, we believe Bicycles may have significant advantages over antibody-based approaches to tumor antigen targeting, a hypothesis supported by results from our preclinical studies,” said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. “In preclinical head-to-head comparisons with an ADC targeting Nectin-4, BT8009 demonstrated superior anti-tumor activity, including complete regressions of very large and small tumors across multiple xenograft models. Given BT8009’s potential utility, we plan to pursue a clinical development path that could enable us to bring this novel therapy to patients efficiently.”

The Phase I/II multi-center, open-label trial will evaluate BT8009 administered once weekly. Enrollment is ongoing in the Phase I dose escalation of BT8009 given as a monotherapy, and the Company plans to evaluate BT8009 dosed in combination with an immune checkpoint inhibitor in future Phase I dose escalation cohorts. The Phase I portion of the trial is primarily designed to assess the safety and tolerability of BT8009, and to determine a recommended Phase II dose (RP2D). Following selection of an RP2D, Bicycle expects to initiate a Phase II dose expansion portion with the primary objective of evaluating the clinical activity of BT8009 in patients with Nectin-4-positive tumors.