Data show control of acute myeloid leukemia by a trifunctional NKp46-CD16a-NK cell engager targeting CD123
These results support clinical development of CD123-NKCE; A Phase 1/2 clinical trial by Sanofi is ongoing
Innate Pharma SA (Euronext Paris: IPH; Nasdaq: IPHA) (“Innate” or the “Company”) announced today 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 ANKETTM 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).
Eric Vivier, DVM, PhD, Chief Scientific Officer of Innate Pharma:
“The activity, safety, pharmacokinetic and pharmacodynamics data provided here demonstrate the superiority of CD123-NKCEs over comparator cytotoxic antibodies in terms of antitumor activity, and their favorable safety profiles relative to T cell therapies for the treatment of AML. IPH6101/SAR’579 is a multi-specific NKCE targeting CD123 currently in a Phase 1 trial in AML sponsored by Sanofi. At Innate Pharma, we are developing a broad portfolio of NK Cell Engager programs via our proprietary platform ANKETTM that can address different types of cancer.”
Valeria Fantin, Ph.D., Global Head of Oncology Research at Sanofi:
“At Sanofi, we are building a diverse oncology portfolio including next-generation NK-based assets and bringing new approaches to fighting cancer. We're pleased with our productive collaboration with Innate Pharma, and data like this reinforce our confidence in proceeding to clinical evaluation of this novel NK cell engager."
ANKETTM (Antibody-based NK cell Engager Therapeutics) is Innate's proprietary platform for developing next-generation, multi-specific natural killer (NK) cell engagers to treat certain types of cancer.
This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce synthetic immunity against cancer. It leverages the advantages of harnessing NK cell effector functions against cancer cells and also provides proliferation and activation signals targeted to NK cells.
Our latest innovation, the tetra-specific ANKET molecule, is the first NK cell engager technology to engage activating receptors (NKp46 and CD16), a tumor antigen and an interleukin-2 receptor (via an IL-2 variant, IL-2v) via a single molecule.