BT8009, now carrying the nonproprietary name zelenectide pevedotin, is Bicycle Therapeutics' lead Bicycle toxin conjugate. The drug pairs a small, constrained bicyclic peptide that binds Nectin-4 with the cytotoxic monomethyl auristatin E (MMAE) payload via a cleavable linker. Nectin-4 is the same antigen targeted by Padcev (enfortumab vedotin), but BT8009 hits it as a roughly 1,500-dalton bicyclic peptide rather than an antibody-drug conjugate, producing a different tissue-distribution and toxicity profile.
In the dose-optimization stage of Duravelo-2 (Phase 2), the optimal dose of zelenectide pevedotin plus pembrolizumab produced response rates comparable to published standard-of-care data in previously untreated locally advanced or metastatic urothelial carcinoma, with roughly four-fold lower skin reactions and about half the peripheral neuropathy. Yohann Loriot presented the data in a June 1, 2026 rapid oral session at ASCO (Abstract 4516); the Duravelo-1 Phase 1 expansion in cisplatin-ineligible patients had previously delivered a 45% ORR and 11.1-month median DOR. The drug headlines a broader Bicycle pipeline that includes BT5528 (EphA2 conjugate, nuzefatide pevedotin).
Stories here cover BT8009 trial readouts and the bicyclic peptide-drug conjugate field. See #bicycle-therapeutics, #zelenectide-pevedotin, #duravelo-2, and #nectin-4 for adjacent threads.
In the June 1 rapid oral session (Abstract 4516, Yohann Loriot), the dose-optimization stage of the randomized Phase 2 Duravelo-2 trial showed the optimal dose of the bicyclic peptide-drug conjugate zelenectide pevedotin (BT8009) plus pembrolizumab produced response rates comparable to published standard-of-care data in previously untreated locally advanced or metastatic urothelial carcinoma, with roughly four-fold lower skin reactions and about half the peripheral neuropathy. The separate Duravelo-1 Phase 1 trial showed median progression-free survival comparable to standard of care in cisplatin-ineligible patients.
Bicycle Therapeutics released Duravelo-2 Phase 2/3 interim analysis data at ASCO 2026 — zelenectide pevedotin (BT8009, a Nectin-4-targeting bicyclic peptide-MMAE conjugate) plus pembrolizumab in previously untreated locally advanced or metastatic urothelial cancer. The full data presentation is scheduled for Monday June 1, 8:30-8:36 AM CT in the GU Cancers oral session (Abstract 4516). The Duravelo-1 monotherapy comparator anchor — 65% ORR (13/20) in cisplatin-ineligible 1L mUC at 5 mg/m² + pembrolizumab combination, with median DOR 11.1 months in the monotherapy expansion — sets the bar for what the Duravelo-2 combination interim must clear. Bicycle's five-abstract ASCO package includes the oral Duravelo-2 piece plus four posters covering Duravelo-1 monotherapy update, BT5528 EphA2 monotherapy and combination cohorts, and BT8009 second-line urothelial data.
Bicycle Therapeutics confirmed the Duravelo-2 oral abstract presentation slot at the ASCO 2026 Annual Meeting on Monday, June 1, 8:30–8:36 a.m. CT. The abstract reports interim analysis results from Duravelo-2, a Phase 2/3 trial of zelenectide pevedotin (BT8009) plus pembrolizumab as first-line treatment for previously untreated locally advanced or metastatic urothelial carcinoma. Zelenectide pevedotin is Bicycle's Nectin-4-targeting bicyclic peptide-drug conjugate, a separate program from the EphA2-targeting nuzefatide pevedotin (BT5528) covered earlier on this site. The Q1 2026 print (April 30) reaffirmed $559.5M cash and runway to 2030 supporting the Phase 3 expansion of the platform.