Bicycle Therapeutics reports AACR 2026 data showing encouraging safety and efficacy of nuzefatide pevedotin targeting EphA2, with Phase 2 trial underway in pancreatic cancer.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
Bicycle Therapeutics presented updated data from its EphA2-targeting pipeline at the American Association for Cancer Research Annual Meeting 2026, highlighting progress of nuzefatide pevedotin and its bicyclic peptide-based platform.
EphA2 has historically been considered difficult to target due to safety and efficacy challenges seen with earlier antibody-based approaches.
CEO Kevin Lee indicated that the company’s Bicycle® technology may offer a differentiated approach, with emerging data from more than 150 patients showing a generally favourable safety profile both as monotherapy and in combination with checkpoint inhibitors.
He noted that integrated analyses, including tumor expression, imaging, and preclinical studies, have identified opportunities across multiple cancers, with an initial focus on pancreatic ductal adenocarcinoma (PDAC), and confirmed that 8 mg/m² administered every two weeks has been selected as the preferred monotherapy dose.
Phase 1/2 data evaluating nuzefatide in combination with nivolumab in metastatic urothelial cancer demonstrated clinical activity in a heavily pretreated population, with a confirmed overall response rate of 40% among patients with EphA2-positive tumors and 100% in those naïve to MMAE-based therapies.
Responses appeared durable, as patients achieving partial response or sustained stable disease remained on treatment for at least 56 weeks, with many continuing therapy at the data cutoff. The combination was generally well tolerated, with no Grade 3 or higher treatment-related adverse events of clinical concern, no hemorrhagic toxicity, and a single case of Grade 3 fatigue that resolved without dose reduction, supporting a differentiated safety profile relative to prior EphA2-targeted approaches.
Additional human imaging data using a gallium-68–labeled Bicycle® imaging agent demonstrated rapid tumor uptake and primarily renal clearance in patients with PDAC, with PET/CT scans detecting metastatic lesions across multiple sites. Similar findings were observed in the majority of evaluated patients, supporting EphA2 as a viable target and highlighting potential applications in radiopharmaceutical imaging and therapy.
Preclinical studies further supported activity, with EphA2 expression identified across all evaluated PDAC patient-derived xenograft models and anti-tumor responses observed in most, including several with high sensitivity, while strong activity was also seen in EphA2-expressing head and neck cancer models.
Based on these findings, Bicycle Therapeutics has initiated a Phase 2 trial in recurrent PDAC to evaluate efficacy, safety, and pharmacokinetics, with patient enrollment beginning in March 2026 and the first patient dosed in April. The overall dataset supports continued development of nuzefatide in pancreatic cancer and other EphA2-expressing tumors.
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About the Writer
Samiksha Vikram Jadhav is a B.Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She has a keen interest in healthcare advancements, clinical research, medical writing, and emerging therapies. Her work focuses on presenting developments in the pharmaceutical and healthcare sectors through clear and