IBI363: A Comprehensive Clinical and Scientific Profile of a First-in-Class PD-1/IL-2α-Bias Bispecific Antibody

I. Executive Summary

IBI363 represents a significant advancement in the field of immuno-oncology, engineered as a first-in-class Programmed Death-1 (PD-1)/Interleukin-2 alpha-bias (IL-2α-bias) bispecific antibody fusion protein. Developed independently by Innovent Biologics, this novel agent is designed to overcome the limitations of current immunotherapies by simultaneously addressing two critical pathways of immune regulation.[1] Its core strategic objective is to reactivate the anti-tumor immune response in patients who have developed resistance to standard checkpoint inhibitors and to successfully treat immunologically "cold" tumors, which have historically been unresponsive to such therapies.

The molecular architecture of IBI363 combines a PD-1 blocking antibody with an engineered, α-biased IL-2 cytokine. This dual-action mechanism not only releases the inhibitory "brakes" on T cells via PD-1 blockade but also provides a potent, targeted stimulatory signal through the IL-2 pathway. The key innovation lies in the IL-2α-bias, which directs the cytokine's activity preferentially toward tumor-specific T cells co-expressing PD-1 and the high-affinity IL-2 receptor subunit, IL-2Rα (CD25). This precision targeting is designed to maximize anti-tumor efficacy while mitigating the severe systemic toxicities associated with traditional high-dose IL-2 therapy.