Bicycle Therapeutics builds bicyclic peptides — short peptide sequences cyclized through a chemical scaffold to combine antibody-like specificity with small-molecule pharmacokinetics. The platform has produced multiple oncology candidates against targets that traditional ADCs struggle with.
Lead programs covered on this site: BT5528 / nuzefatide pevedotin (EphA2-targeting bicycle drug conjugate) in solid tumors — 40% confirmed ORR in EphA2+ urothelial patients on the nivolumab combination at AACR 2026; BT8009 / zelenectide pevedotin (Nectin-4) in urothelial cancer; and the EphA2 gallium-68 PET imaging program. In April 2026 Bicycle dosed the first patient in a Phase 2 nuzefatide pevedotin trial in recurrent pancreatic cancer, extending the program into a difficult tumor type where companion EphA2 imaging at AACR reinforced target validation. The Duravelo-2 dose-selection readout is set for ASCO 2026 (Rapid Oral Abstract Session, June 1).
Stories here cover trial readouts, AACR and ASCO data, and partnership announcements. See #bicyclic-peptide for the chemistry class, #nuzefatide-pevedotin for the lead program, and #peptide-drug-conjugate for adjacent platforms.
Bicycle Therapeutics delivers an oral presentation (Sunday, April 19, 4:05-4:20 PT) on preclinical activity of BT5528 (nuzefatide pevedotin), its EphA2-targeting bicycle drug conjugate, in cell-line-derived xenograft models of head and neck squamous cell carcinoma. Lukas Stanczuk, Ph.D. leads the presentation under abstract 1325. The HNSCC program complements ongoing Phase 1/2 clinical work combining BT5528 with nivolumab in advanced solid tumors.
ApexOnco analysis frames AACR 2026 as a breakout moment for private peptide-based biotechs. Circle Pharma (macrocyclic peptides), Bicycle Therapeutics (bicyclic peptide drug conjugates), and SignaBlok (TREM-1 peptide) all landed prominent slots. Antibody-drug and peptide-drug conjugates remain the dominant theme, with conjugate-related abstracts outpacing any other modality in the clinical late-breaker sessions.
Bicycle Therapeutics will present Phase 1/2 clinical results for BT5528 (nuzefatide pevedotin), an EphA2-targeting Bicycle Drug Conjugate, in combination with nivolumab in patients with advanced solid tumors at AACR 2026. Additional preclinical posters cover BT5528 activity in head and neck squamous cell carcinoma and pancreatic ductal adenocarcinoma xenograft models, plus a novel phage-display-derived bicyclic peptide for EphA2-specific PET imaging.