Innate Pharma SA announced the publication in Nature Biotechnology of preclinical data showing the control of acute myeloid leukemia (AML) cells by a trifunctional NKp46-CD16a-NK cell engager (NKCE) targeting CD123. The studies were conducted by Innate and Sanofi and published in Nature Biotechnology on January 12, 2023. The study shows that expression of CD64 on AML blasts confers resistance to anti-CD123 antibody-dependent cell cytotoxicity (ADCC) and redirecting NK cells against cancer targets through binding to CD16a and NKp46 circumvents this resistance.

Moreover, through their binding to NKp46, CD123-NKCE specifically target NK cells and has potent antitumor activity against primary AML blasts; it induces NK cell activation and cytokine secretion only in the presence of AML cells. In vivo, its antitumor activity in a mouse tumor model exceeds that of the comparator anti-CD123 antibody. The efficacy of CD123-NKCE in vitro in human peripheral blood mononuclear cells and in vivo in nonhuman primates was associated with the induction of low pro-inflammatory cytokine release and no signs of toxicity.

These results support clinical development of CD123-NKCE. A Phase 1/2 clinical trial by Sanofi is ongoing, evaluating IPH6101/SAR'579 (SAR443579), the first NKp46/CD16-based CD123-targeted ANKET NK cell engager, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL) or high-risk myelodysplastic syndrome (HR-MDS).