Davoceticept (ALPN-202)

Conditional (PD-L1-dependent) CD28 Costimulator and Dual Checkpoint (PD-L1/CTLA-4) Inhibitor for Oncology

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.

Results from the dose-escalation portion of NEON-1 (NCT04186637), a first-in-human, dose-escalation and expansion study of davoceticept monotherapy in participants with advanced malignancies, were presented at the 2022 AACR Annual Meeting. These data demonstrated that davoceticept was well tolerated, with no reported events of cytokine release syndrome. Despite a highly heterogeneous, heavily pretreated, advanced solid tumor population – the majority classically considered to be unresponsive to immunotherapy – 11 (23%) of 48 evaluable participants demonstrated tumor volume reduction; 26 (54%) achieved clinical benefit as defined as a best response of stable disease or better; Three (6%) remained on treatment beyond 6 months. Two partial responses were observed in colorectal and renal cell carcinoma. Initial data from NEON-1 were presented at 2021 ASCO Virtual Meeting.

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 filingscorporate presentation, and scientific publications.

Davoceticept: A Variant CD80 Domain (vIgD™) Fused to an “Effectorless” IgG Fc
CD28 is Critical for T Cell Activity During Checkpoint Inhibition
Davoceticept Drives T-cell Activation Through Conditional CD28 Costimulation and Dual Checkpoint Inhibition

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