BT7480 with nivolumab

April 30, 2026: Bicycle Therapeutics plc (NASDAQ: BCYC) reported Q1 2026 results and provided clinical/regulatory updates across its EphA2 and Nectin-4 programs, highlighting upcoming oncology data presentations.

Nuzefatide pevedotin (formerly BT5528; EphA2-targeting Bicycle Drug Conjugate): At AACR 2026, the company presented Phase 1/2 combination data with nivolumab in metastatic urothelial cancer (mUC). As of the Feb. 9, 2026 cutoff, 14 patients treated at nuzefatide 6.5 mg/m² Q2W + nivolumab 480 mg Q4W included EphA2+ subgroup outcomes of 40% confirmed ORR (4/10) and 100% confirmed ORR (3/3) in EphA2+ MMAE-naïve tumors. Treatment was generally well tolerated with no Grade ≥3 TRAEs of clinical interest; one DLT of Grade 3 fatigue was reported. Preclinical PDAC and HNSCC xenograft data were also presented. Bicycle began enrolling a Phase 2 trial in recurrent pancreatic ductal adenocarcinoma (PDAC) in March 2026; first patient dosed April 2026; preferred dose 8 mg/m² Q2W.

EphA2 imaging: AACR 2026 human PET/CT data from a gallium-68–labeled EphA2 Bicycle Imaging Agent in PDAC showed rapid tumor uptake (6/7 patients) and detection of metastatic lesions; results were stated as representative of 15/18 PDAC patients imaged to date.

Zelenectide pevedotin (formerly BT8009; Nectin-4; Duravelo-2 in mUC): Initial dose-selection data showed physician-assessed ORR 65% and BICR-confirmed ORR 58% at a 27-week cutoff (62% with an additional post-cutoff confirmed response), with 6 mg/m² (two weeks on/one week off) and one discontinuation due to TRAE at the cutoff. The company is evaluating preliminary regulatory feedback from EMA/FDA/MHRA, converting Duravelo-2 to a randomized Phase 2, and deprioritizing internal development. Initial dose-selection data will be presented at ASCO 2026 (May 29–June 2, Chicago). Duravelo-3 (NECTIN4-amplified breast cancer) and Duravelo-4 (NECTIN4-amplified NSCLC) are being discontinued (enrollment closed).

Financial/corporate: Cash and cash equivalents were $559.5M as of March 31, 2026; strategic reprioritization includes ~30% workforce reduction and expected cash runway into 2030.