Bevonescein—A Peptide Dye Conjugate for Visualization of Peripheral Nerves in Patients During Surgery

Background/Objectives: The identification of peripheral nerves is critical for their preservation during surgery, as accidental transection or injury can lead to significant patient morbidity. Current methods for identifying nerves typically rely on qualitative white-light visualization of anatomy, texture, and color. To improve nerve identification during surgical procedures, we developed a novel nerve imaging agent, “bevonescein,” a derivative of the peptide–dye conjugate FAM-HNP401. Methods: Variants of FAM-HNP401 were designed to be synthesized completely on solid phase to enable the efficient generation of GMP (Good Manufacturing Practice)-qualified bevonescein. We determined the nerve binding affinity for each variant, CPC-17, CPC-18, CPC-19 (bevonescein), and CPC-20, using mean fluorescent intensity measurements after binding the agents to human sural nerve sections. Results: Bevonescein (CPC-19) demonstrated significantly superior nerve binding compared to other variants and controls. Bevonescein-labeled nerves exhibited a mean fluorescent intensity of 562 ± 34.7, compared to 252 ± 41.7 for CPC-17, 344 ± 34.7 for CPC-18, and 270 ± 41.7 for CPC-20. The dye-alone control, 5-carboxyfluorescein, showed a fluorescent intensity of 168 ± 41.4. Conclusions: Bevonescein represents a first-in-class molecule that can improve the visualization of peripheral nerves during surgery, potentially reducing nerve injury and associated morbidity. It has been successfully tested in a Phase 1/2 clinical trial demonstrating safety and efficacy at a 500 mg dose and is currently in Phase 3 clinical testing.