BOSTON — Bicycle Therapeutics plc presented new data on its cancer drug pipeline at the American Association for Cancer Research Annual Meeting, highlighting early clinical and preclinical results for its lead EphA2-targeting therapy, nuzefatide pevedotin.
The experimental drug is designed to target EphA2, a protein commonly found on tumor cells that has historically been difficult to treat due to safety and efficacy challenges with earlier approaches.
“EphA2 is a potentially high value target that is widely expressed in cancer and has been considered undruggable following the failure of multiple antibody-based approaches due to toxicity or insufficient efficacy. Encouraging results presented at AACR demonstrate the potential of our Bicycle platform to drug this target with a generally well tolerated and differentiated safety profile and enhances our understanding of how best to deploy EphA2-targeted therapeutics,” said Kevin Lee, Ph.D., CEO of Bicycle Therapeutics. “Nuzefatide pevedotin has demonstrated an emerging differentiated safety profile as a monotherapy and in combination with a checkpoint inhibitor, in over 150 patients to date. Consequently, using a combination of expression analysis, preclinical patient-derived xenograft efficacy studies, and human patient imaging, we have identified significant opportunities for this molecule in a number of cancers, including pancreatic cancer.”
In a Phase 1/2 clinical trial, nuzefatide pevedotin was tested in combination with nivolumab in patients with metastatic urothelial cancer who had previously been treated with checkpoint inhibitors. Among patients with EphA2-positive tumors, the therapy achieved a 40 percent confirmed overall response rate, with higher response rates observed in certain subgroups.
Patients who experienced partial responses or stable disease for at least 16 weeks remained on treatment for extended periods, with many continuing therapy at the time of analysis. The combination therapy was generally well tolerated, with no severe treatment-related adverse events of clinical concern reported.
The company has identified 8 mg/m² administered every two weeks as the preferred dose for monotherapy and has begun enrolling patients in a Phase 2 trial for pancreatic ductal adenocarcinoma. The first patient has already been dosed.
Additional imaging data presented at the meeting showed that a radiolabeled agent targeting EphA2 was able to detect metastatic cancer sites in patients with pancreatic cancer, including in the liver, bones, lymph nodes, and peritoneum.
Preclinical studies also demonstrated strong anti-tumor activity for nuzefatide pevedotin across pancreatic cancer models and in head and neck cancer models expressing EphA2.
The company said the findings support further development of its targeted therapies and radiopharmaceutical approaches for cancers that have limited treatment options.
