January 22, 2021

Progress

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 progress updates across its wholly-owned and partnered programs in oncology and non-oncology indications.

“We and our partners have recently achieved important progress in the advancement of our pipeline that we believe could catalyze the next stage of growth for Bicycle,” said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. “Cancer Research UK has identified a recommended dose, which is within the therapeutic range predicted by preclinical models, for the Phase IIa study of BT1718, which we expect to commence this year. Our next-generation Bicycle Toxin Conjugates (BTCs), BT5528 and BT8009, are quickly progressing through respective stages of development. In addition, we believe our recently announced early discovery collaboration with Genentech will allow us to make considerable investments in expanding our portfolio of immuno-oncology assets, including our wholly-owned programs nearing late preclinical development. Beyond oncology, we continue to make progress on our partnered programs and to execute on our strategy of leveraging our collaborators’ expertise in specific therapeutic areas to advance the development of Bicycle-based medicines across a broad range of serious diseases.”

Dr. Lee continued: “While we expect that the evolving COVID-19 pandemic may impact the pace of clinical development, at this time, we believe the strong progress we’ve achieved across our pipeline to date will enable us to reach our anticipated 2020 milestones as planned.”

BT1718, a potential first-in-class BTC targeting key tumor antigen MT1-MMP

  • Cancer Research UK Completed Phase I Dose Escalation of BT1718 in Patients with Solid Tumors, Established Recommended Phase II Dose (RP2D) at 20 mg/m2. The key objectives were met in a Phase I dose escalation sponsored by Cancer Research UK and evaluating safety and tolerability of BT1718 in an unselected group of patients with advanced solid tumors. Based on study results, Cancer Research UK established an RP2D for the expansion cohorts at 20 mg/m2 administered once weekly. This recommended dose is within the efficacious dose range predicted by preclinical models, in which an equivalent dose level was associated with complete responses. With once-weekly dosing, BT1718 appeared tolerable, with manageable adverse events.

    Though not a key objective of the Phase I portion of the Phase I/IIa study, preliminary signs of anti-tumor activity were observed during the dose escalation. As reported at the European Society of Medical Oncology (ESMO) 2019 Annual Congress, 13 of 24 evaluable patients (54%) had stable disease at the eight-week timepoint, including a patient who experienced a 45% reduction in a target lesion, with findings generally remaining consistent as the trial progressed. Today, Bicycle announced that, in addition, one patient with small cell lung cancer experienced a partial response, with a 68% reduction in a target lesion.

    The Company anticipates that Cancer Research UK will initiate the Phase IIa portion of the Phase I/IIa study of BT1718 in 2020, although timing may be

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