Nuzefatide Pevedotin (BT5528) (EphA2 BDC)

April 30, 2026 — Bicycle Therapeutics plc (NASDAQ: BCYC) reported Q1 2026 financial results and provided pipeline updates focused on its Bicycle® Drug Conjugates and radioligand programs. At AACR 2026, the company highlighted Phase 1/2 data for EphA2-targeting nuzefatide pevedotin (BT5528) plus nivolumab in metastatic urothelial cancer (mUC): among EphA2+ tumors, confirmed ORR was 40% (4/10), and 100% (3/3) in EphA2+ MMAE‑naïve patients; responders/long stable disease remained on treatment ≥56 weeks. Safety was described as generally well tolerated with no Grade ≥3 treatment-related adverse events of clinical interest; one dose-limiting Grade 3 fatigue resolved without dose reduction. Preclinical data showed EphA2 expression in all 16 PDAC PDX models, with 10/14 sensitive to nuzefatide. Bicycle initiated a Phase 2 trial in recurrent pancreatic ductal adenocarcinoma (first patient dosed April 2026; preferred dose 8 mg/m² Q2W). Human PET/CT imaging with a gallium‑68 EphA2 Bicycle Imaging Agent in PDAC showed rapid uptake (6/7 patients) and detection of metastases; overall 15/18 PDAC patients imaged to date showed representative findings, supporting EphA2 targeting and radiopharmaceutical potential.

For Nectin‑4-targeting zelenectide pevedotin (Duravelo‑2), initial dose selection data showed physician-assessed ORR 65% and BICR confirmed ORR 58% at 27 weeks (62% with a later additional response), with one discontinuation due to a treatment-related AE; these data will be presented at ASCO 2026. The company is converting Duravelo‑2 to a randomized Phase 2 and deprioritizing internal development, while discontinuing Duravelo‑3/4 (breast/NSCLC) enrollment, implementing a ~30% workforce reduction, and projecting ~50% annual opex reduction and runway into 2030.

Financials: cash/cash equivalents were $559.5M at March 31, 2026; Q1 net loss was $60.8M ($(0.87)/share). Collaboration revenue fell to $0.9M due to terminated Genentech/Novartis collaborations.