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Forty Seven to Gilead: “Eat me”

Gilead’s latest cancer immunotherapy acquisition, a $4.9 billion buyout of Forty Seven, gives the biotech giant access to a pipeline of CD47-targeted monoclonal antibodies (mAbs) and other related binding molecules to fight cancer.

Forty Seven’s lead drug is magrolimab, a mAb against CD47, the ‘do-not-eat-me’ cue that tumor cells use to evade the immune system’s macrophage-mediated killing. The mAb blocks recognition between CD47 on tumor cells and its binding partner, signal regulatory protein (SIRP)-α, on macrophages.

Forty Seven is a spinout of Stanford University; it went public in 2018. In December, the company announced results from a phase 1b trial for magrolimab in combination with the chemotherapeutic agent azacytidine, for myelodysplastic syndrome and acute myeloid leukemia, at the American Society of Hematology meeting. The combination therapy was “highly active and well-tolerated” in both groups of patients.

The acquisition further boosts Gilead’s cancer immunotherapy pipeline, mostly obtained from its purchase of Kite Pharma in 2017, before the first approval of its chimeric antigen receptor (CAR)-T cell therapy Yescarta. Former Kite cancer immunotherapy assets KTE-X19, KITE-718 and KITE-439 are in clinical testing by Gilead. “Magrolimab complements our existing work in hematology, adding a non-cell therapy program that complements Kite’s pipeline of cell therapies for hematological cancers,” says Gilead chairman and CEO Daniel O’Day.

Forty Seven has plans to advance two experimental medicines into clinical testing that target other parts of the same immune signaling pathway. One approach is to target cKIT, a cell growth factor found on hematopoietic stem cells, which blocks an ‘eat-me’ signal to macrophages. Forty Seven’s anti-cKIT antibody, FSI-174, has shown anticancer effects in combination with magrolimab in animal testing. The other is anti-SIRPα antibody FSI-189, which is expected to enter phase 1 testing this year.

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Forty Seven to Gilead: “Eat me”. Nat Biotechnol 38, 389 (2020). https://doi.org/10.1038/s41587-020-0496-1

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