On April 4, 2022 Alpine Immune Sciences, Inc. (Nasdaq: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for cancer and autoimmune and inflammatory diseases, reported a publication in Nature Communications on the preclinical development of davoceticept, Alpine’s lead immuno-oncology therapeutic candidate uniquely designed to combine PD-L1-dependent CD28 costimulation with dual PD-L1 and CTLA-4 checkpoint inhibition (Press release, Alpine Immune Sciences, APR 4, 2022, View Source [SID1234611404]). CD28 is a critical T cell receptor recognized as a principal target of immune checkpoints like PD-1 and CTLA-4.

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"Lack of sufficient CD28 costimulation in the tumor microenvironment may underlie checkpoint inhibitor resistance and, therefore, CD28-directed treatments hold much promise. Davoceticept is an exciting first-in-class CD28-targeting drug that is distinct among others in this space for its triplicate mechanism and structural elegance," said Rafi Ahmed, PhD, Professor of Microbiology and Immunology and Vaccine Center Director at Emory University, and member of Alpine’s scientific advisory board.

"This achievement is the culmination of years of our scientists’ efforts to target CD28 in a highly differentiated fashion," remarked Stanford Peng, MD PhD, President and Head of R&D at Alpine. "It distinctively illustrates the unique yet powerful approach of our discovery platform, and further encourages us to continue to pursue clinical development of davoceticept with vigor."

Davoceticept is being studied in two clinical trials, NEON-1 as monotherapy, and NEON-2 in combination with pembrolizumab, in adults with advanced malignancies. Data from NEON-1 will be presented at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in New Orleans on April 12.

About Davoceticept (ALPN-202)

Davoceticept (ALPN-202) is a first-in-class, conditional CD28 costimulator and dual checkpoint inhibitor intended for the treatment of cancer. Preclinical studies of davoceticept have successfully demonstrated superior efficacy in tumor models compared to checkpoint inhibition alone. Completion of dose escalation and initiation of expansion cohorts of NEON-1 (NCT04186637), a Phase 1 monotherapy dose escalation and expansion trial in patients with advanced malignancies, is anticipated in the first half of 2022. NEON-2 (NCT04920383), a combination study of davoceticept (ALPN-202) and pembrolizumab was initiated in June 2021 and is currently on partial clinical hold.