TG-1801 is an investigational first-in-class, bispecific anti-CD47/CD19 monoclonal antibody. It is the first therapy to target both CD19, a B-cell specific marker widely expressed across all B-cell malignancies, and CD47, the “do not eat me” signal used by tumor cells to evade macrophage-mediated phagocytosis, or ‘tumor cell eating’. CD47 is also expressed ubiquitously on normal cells, including red blood cells and platelets, where it helps to regulate the renewal of these cells in the body. The CD19 component is designed to improve the targeting of TG-1801 to malignant cells that express CD19, which would preempt binding of the bispecific antibody to normal cells expressing CD47 In addition, the targeting of CD19 provides a secondary mechanism of direct anti-tumor activity through the engagement of effector cells and induction of antibody dependent cellular cytotoxicity (ADCC). By targeting both CD19 and CD47, TG-1801 offers the prospect of killing the tumor cell through each of these two distinct mechanisms.
In preclinical assays, TG-1801 has demonstrated a potent ability to induce antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) of malignant B-cell lines and primary tumor B-cells from patients with acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL). and numerous other subtypes of NHL.
A first-in-human phase 1 study of TG-1801 is ongoing in patients with B-cell lymphoma.