DNL919

DNL919 is a monoclonal antibody engineered to activate TREM2 (Triggering Receptor Expressed on Myeloid Cells 2), a receptor expressed by microglia, the resident immune cells of the brain. The drug uses Denali Therapeutics' Antibody Transport Vehicle (ATV) technology, which incorporates a transferrin-receptor binding sequence into its Fc domain to facilitate active transport across the blood-brain barrier. By activating TREM2, DNL919 aims to enhance microglial function and promote phagocytosis of amyloid plaques, potentially benefiting patients with Alzheimer's disease. Preclinical studies demonstrated increased brain uptake and improved pharmacodynamic response compared to non-ATV antibodies. Development was led by Denali Therapeutics in collaboration with Takeda; however, clinical development was discontinued after Phase 1 due to safety concerns related to moderate reversible anemia associated with TfR-mediated shuttling[1][4][6][8].

Other names

anti-TREM2 ATVanti-TREM-2 ATVanti-TREM 2 ATVATV-enabled anti-TREM2 antibodyATV-TREM2ATV-TREM-2ATV-TREM 2