Davoceticept is 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 either fail to respond to therapy or develop resistance. Recent work has demonstrated that immune checkpoints work primarily by inhibiting CD28, a critical costimulatory receptor in T cells. Anti-PD-1 and anti-CTLA-4 treatments inhibit the brakes on CD28, but do not provide activating “gas” signals to CD28 required to induce an anti-tumor response.
Davoceticept is based on a variant CD80 extracellular domain, engineered by directed evolution to bind PD-L1 as well as CD28 and CTLA-4. Localized to the tumor by high-affinity binding to PD-L1, davoceticept activates T cells by clustering and agonism of CD28 only in the presence of PD-L1. Additionally, davoceticept 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 davoceticept monotherapy in patients with advanced malignancies, were presented at the 2021 ASCO Virtual Meeting. These interim data demonstrated that davoceticept was well tolerated, with dose-dependent pharmacokinetics and pharmacodynamics. In addition, although most enrolled participants had tumors considered classically nonresponsive to immunotherapies, 61% (14 of 23 evaluable) appeared to derive clinical benefit as defined as a best outcome of stable disease or better.
In addition to NEON-1, we are currently enrolling patients in NEON-2, a Phase 1 study of davoceticept in combination with KEYTRUDA® (pembrolizumab) in patients with advanced malignancies. A collaboration and supply agreement with Merck to evaluate the safety and efficacy of davoceticept 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.