BackMaplirpacept (TTI-622/PF-07901801)
Maplirpacept (TTI-622/PF-07901801) is an investigational compound. Its safety and efficacy have not been established.
Overview + Rationale
- Maplirpacept (TTI-622/PF-07901801) is a fusion protein designed to enhance phagocytosis and antitumor activity by preventing CD47 from delivering its inhibitory signal as well as generating a moderate pro-phagocytic signal via IgG4 Fc
- Maplirpacept minimally binds to human red blood cells
RATIONALE FOR CANCER TYPE
- CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a “don’t eat me” signal to prevent phagocytosis
- CD47 is overexpressed in various hematological malignancies and its interaction with Signal Regulatory Protein (SIRP)α on phagocytic cells prevents phagocytosis of cancer cells
- Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes
- CD47 blockade promotes both innate (macrophage phagocytosis) and adaptive immunity (T cell responses)
- Tumor cells frequently overexpress CD47 and exploit this pathway to evade macrophage-mediated destruction
Mechanism of Action
Maplirpacept (TTI-622/PF-07901801) consists of the CD47-bindingdomain of human SIRPα and is linked to the Fc region of IgG4
- The IgG4 Fc delivers a moderate “eat” signal through FcγRs
Stage of Development
R/R Diffuse Large B-Cell Lymphoma (DLBCL)Transplant Ineligible
Phase 1b/2 Combination*