Discovery and Process Development of a Novel Auristatin Drug-Linker: PF-08081016

Auristatins are a class of clinically validated payloads utilized extensively in antibody-drug conjugate technology. Auristatin payloads have several desirable properties, including strong anticancer cytotoxicity, bystander activity, and induction of immunologic cell death. While auristatin-based ADCs have been remarkably successful, there remains opportunities to understand and improve payload properties. Bystander activity is one such property that can greatly impact the balance between efficacy and tolerability. Herein, we present discovery chemistry for a new auristatin payload (PF-08077285) and drug linker (PF-08081016) and the process development that enabled an efficient and scalable synthesis for clinical studies.