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.