EphA2 is a receptor tyrosine kinase overexpressed in many solid tumors, making it a credible target for peptide-drug conjugates. Bicycle Therapeutics' BT5528 — a bicyclic peptide-toxin conjugate against EphA2 — is the lead clinical candidate, with AACR 2026 readouts adding to the Phase 1/2 dataset.
Adjacent programs covered on this site include earlier-stage EphA2-targeting bicycle constructs from Bicycle's pipeline and academic collaborators, alongside the broader peptide-receptor tyrosine kinase ecosystem (Nectin-4 with BT8009, MT1-MMP with earlier conjugates).
Stories here cover BT5528 readouts, AACR and ASCO presentations, and EphA2-related discovery work. See #bicycle-therapeutics, #bt5528, and #peptide-drug-conjugate for context.
Bicycle Therapeutics reported Q1 2026 financial results April 30 — net loss of $60.8M ($0.87 per share) on R&D of approximately $44M, with $559.5M in cash and equivalents at March 31 supporting a cash runway into 2030. The pipeline update reaffirmed that nuzefatide pevedotin (BT5528) Duravelo-2 dose-selection data in EphA2-positive solid tumors will be presented at the ASCO 2026 Rapid Oral Abstract Session on June 1, the Phase 2 nuzefatide pevedotin trial in recurrent pancreatic cancer enrolled its first patient in April, and the EphA2 gallium-68 PET imaging program continues to accumulate first-in-human data. Bicycle remains the leading bicyclic-peptide-platform pure-play in oncology.
Bicycle Therapeutics confirmed in its AACR 2026 update that the company began enrolling patients in a Phase 2 study of nuzefatide pevedotin (BT5528) in adults with recurrent pancreatic ductal adenocarcinoma in March 2026, with the first patient successfully dosed in April. The bicyclic peptide-drug conjugate targets EphA2-expressing tumor cells. Earlier Phase 1/2 data — through a February 9, 2026 cutoff — showed 40% confirmed ORR in EphA2+ urothelial cancer patients on nuzefatide 6.5 mg/m² plus nivolumab, rising to 100% confirmed ORR in MMAE-naïve EphA2+ patients (n=14). The company has identified 8 mg/m² Q2W as the preferred monotherapy dose. The PDAC trial extends Bicycle's footprint into a difficult tumor type where EphA2 imaging readouts at AACR 2026 reinforced target validation.
Bicycle Therapeutics announced April 21 its program for the 2026 ASCO Annual Meeting (May 29-June 2 in Chicago), with an oral presentation and five poster abstracts on nuzefatide pevedotin — its EphA2-targeting bicyclic peptide drug conjugate. Key data from Phase 1/2 include the recently disclosed 40% ORR in checkpoint-refractory urothelial cancer, expanded head-and-neck squamous cell carcinoma preclinical data, and the selected 8mg/m² Q2W dose for the Phase 2 recurrent pancreatic cancer trial. The program solidifies Nuzefatide's positioning as a leading bicyclic peptide drug conjugate in oncology.
On the final day of AACR 2026, the German Cancer Consortium presented first-in-human imaging data for EphA2 BIA — a gallium-68-labeled bicyclic peptide targeting EphA2 — in pancreatic ductal adenocarcinoma patients. Seven patients underwent PET/CT imaging up to three hours post-injection, with rapid tumor uptake and primarily renal excretion in six of seven. The tracer successfully detected liver, bone, lymph node, and peritoneal metastases in 15 of 18 patients imaged to date, validating bicyclic peptides as a radioconjugate imaging modality.
Bicycle Therapeutics presented first clinical experiences of a phage-display-derived EphA2-specific bicyclic peptide PET imaging agent in the Diagnostic Biomarkers 2 session at AACR. The imaging agent complements Bicycle's EphA2-targeted therapeutic pipeline (including nuzefatide pevedotin) and could enable patient selection for EphA2-targeted bicyclic peptide drug conjugates across multiple tumor types.
Bicycle's EphA2-targeting bicyclic peptide-drug conjugate nuzefatide pevedotin (BT8009) at 6.5 mg/m² Q2W plus nivolumab achieved 40% confirmed ORR (4/10) in metastatic urothelial patients who had progressed on checkpoint inhibitors, and 100% (3/3) in MMAE-naive EphA2+ patients. No Grade ≥3 treatment-related adverse events of clinical interest. Presented at AACR 2026 on April 20.
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.
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.