Conditional CD28 Costimulator and Dual PD-L1/CTLA-4 Inhibitor for Oncology

ALPN-202 is a first-in-class, clinical-stage therapeutic engineered to provide direct T cell costimulation and dual checkpoint inhibition to enable the immune system to mount a robust anti-tumor response.

Despite significant progress in immunotherapy for oncology, the majority of patients treated with approved checkpoint inhibitors fail to respond or develop resistance. Because immune checkpoints like PD-1 and CTLA-4 appear to suppress anti-tumor immune responses in part by inhibiting activating signals via CD28, simultaneous costimulation of CD28 on T cells and checkpoint inhibition may be required to substantially improve anti-tumor responses.

ALPN-202 binds PD-L1 expressed on the tumor, blocking PD-L1/PD-1 interactions. Localized to the tumor, ALPN-202 drives T cell activation by binding CD28 (PD-L1-dependent CD28 costimulation). Additionally, ALPN-202 binds CTLA-4 expressed on T cells and blocks CTLA4-CD80/CD86 interactions, further potentiating T cell activity.

Enrollment is now open in NEON-1, an open-label Phase 1 trial of ALPN-202 in patients with advanced malignancies.

ALPN-202: A First-in-Class Conditional CD28 Costimulator and Dual Checkpoint Inhibitor