ALPN-202

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.

Preclinical data supporting ALPN-202’s therapeutic potential

Preclinical data supporting the unique mechanism of action and therapeutic potential of ALPN-202 have been presented over the last several years. This research includes data demonstrating ALPN-202:

• Improves tumor control in a human PD-L1 transduced mouse model of colon cancer compared to the FDA approved anti PD-L1 therapeutic durvalumab
• Creates a more robust intra-tumor inflammatory signature in the mouse colon cancer model than durvalumab, potentially indicating superior immune system upregulation to fight cancer
• Has the potential to be used as a monotherapy or in combination with standard of care chemotherapy or checkpoint only inhibition

Details of our published research can be found here.