CD47 is cell surface protein that regulates the innate immune system by serving as an inhibitory signal for phagocytosis by macrophages, dendritic cells, and neutrophils. We originally identified increased expression of CD47 on AML stem cells, and subsequently identified high expression on many solid tumors including carcinomas, lymphomas, sarcomas, melanomas, and central nervous system tumors. These observations suggested that CD47 inhibits the phagocytosis of cancer cells resulting in immune evasion. Building on this hypothesis, we demonstrated that blocking monoclonal antibodies directed against CD47 enabled the phagocytosis and elimination of AML stem cells and solid tumor cells in mouse pre-clinical models, while having no effect on normal cells and tissues.

On the basis of these studies, together with Irv Weissman, we embarked on a program to develop a humanized anti-CD47 antibody, and with funding from the California Institute for Regenerative Medicine (CIRM) conducted the full pre-clinical development of our own clinical therapeutic including manufacturing, pharmacology, toxicology, clinical protocol design, and regulatory strategy. In summer 2014, we successfully filed an IND with FDA and opened our phase 1 clinical trial in the Stanford Cancer Institute. In fall 2015, we successfully filed an IMPD with MHRA in the UK and opened a second phase 1 clinical trial in the UK. In spring 2016, the CD47 program was licensed to a newly formed biotech company, Forty Seven Inc., who continued the clinical development in multiple cancer indications.

Initial clinical trial results demonstrated that the anti-CD47 antibody, termed Hu5F9-G4, now known as magrolimab, can be safely administered in doses capable of achieving potentially therapeutic serum levels. A phase 1b study in relapsed, refractory non-Hodgkin’s B cell lymphoma demonstrated significant clinical activity in combination with the anti-CD20 antibody rituximab. Separate phase 1b/2 studies in first-line treatment for older individuals with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) demonstrated very high response rates in combination with azacytidine. On the basis of these clinical studies, magrolimab was given fast-track designation by FDA in NHL, MDS, and AML – and breakthrough status for MDS. In 2020, Forty Seven Inc. was acquired by Gilead Sciences, who are continuing the clinical development of magrolimab in these and other indications.