Bicycle Therapeutics doses first patient in Phase I dose escalation of its toxin conjugate with Nivolumab

– Monotherapy Phase I dose escalation remains ongoing; BT5528 appears well-tolerated as dosing approaches clinically relevant levels

– BT5528 is the Company’s first second-generation Bicycle® Toxin Conjugate and targets EphA2, a target for which antibody-based approaches have been unsuccessful

CAMBRIDGE, England & BOSTON–(BUSINESS WIRE)–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 that the first patient has been dosed in a Phase I dose escalation of BT5528 in combination with nivolumab. The Phase I trial includes both a monotherapy arm as well as a combination arm. Per protocol, the monotherapy arm began first, with the first patient dosed in the fourth quarter of 2019, and dosing in both arms is now underway. In the monotherapy arm, doses administered to date appear well-tolerated as the escalation continues toward clinically relevant doses. BT5528 is a Bicycle Toxin Conjugate (BTC) that targets EphA2, an antigen believed to be overexpressed in tumor types with high unmet need and a target for which antibody-based approaches have been unsuccessful to date.

“We have been able to move the Phase I/II trial forward quickly by leveraging learnings from the ongoing clinical development of our first generation, pathfinder BTC, BT1718, which is sponsored by Cancer Research UK. We are very pleased with the progress we’ve made thus far in the BT5528 trial, which is intended to demonstrate the potential of Bicycles as a new therapeutic modality capable of addressing therapeutic needs that can’t be reached by conventional treatment options,” said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. “Doses of BT5528 administered to date continue to be well-tolerated, suggesting that BT5528 may circumvent limitations that have caused prior antibody drug conjugate, or ADC, approaches that target EphA2 to fail. Because we believe BTCs may result in improved safety and efficacy over ADCs, in part through more selective delivery of toxin to tumor, we similarly believe that our approach may improve on anti-tumor activity and immunologic effects observed for ADCs in combination with checkpoint inhibitors.”

The Phase I/II multi-center, open-label trial of BT5528 is currently enrolling patients with advanced solid tumors in indications associated with EphA2 expression. The Phase I dose escalations of BT5528 as a monotherapy and in combination with nivolumab are primarily designed to assess safety and tolerability and to determine a recommended Phase II dose (RP2D). Following selection of an RP2D, we expect to initiate a Phase II dose expansion portion with the primary objective of evaluating the clinical activity of BT5528.