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.

Initial data from NEON-1, a Phase 1 study of ALPN-202 monotherapy in patients with advanced malignancies, were presented at the 2021 ASCO Virtual Meeting. These data demonstrated that ALPN-202 was well-tolerated as of the cutoff date with dose-dependent pharmacokinetics and pharmacodynamics. In addition, although most enrolled participants had tumors considered classically non-responsive to immunotherapies, 61% (14 of 23 evaluable) appeared to derive clinical benefit.

In addition to NEON-1, we are currently enrolling patients in NEON-2, a Phase 1 study of ALPN-202 in combination with KEYTRUDA® (pembrolizumab) in patients with advanced malignancies. A collaboration and supply agreement with Merck to evaluate the safety and efficacy of ALPN-202 in combination with KEYTRUDA® (pembrolizumab) was announced in June 2021. For more information on our ongoing clinical trials please refer to the Clinical Trials portion of our website.

For additional information please refer to our corporate filings, corporate presentation, and Scientific Publications.

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