ANKET™ (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for developing next-generation, multi-specific 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 a cytokine (IL-2 variant) in a single molecule. This innovation is built on our existing tri-specific NK cell engager technology, which has demonstrated potent NK cell activation, cytotoxicity and efficient control of tumor growth in preclinical models.
In preclinical studies, Innate's tri- and tetra-specific technology has demonstrated potent NK cell activation, cytotoxicity and efficient control of tumor growth in preclinical models.
Tetra-specific ANKET demonstrated in vitro the ability to induce human NK cell proliferation, cytokine production and cytolytic activity against cancer cells expressing the targeted antigen. Tetra-specific ANKET also demonstrated in vivo anti-tumor efficacy in several tumor models, allowing regression of established tumors as well as control of metastasis, associated with increased NK cell infiltration, cytokine and chemokine production at the tumor site. ANKET showed also pharmacodynamic effect, low systemic cytokine release and a manageable safety profile in non-human primates.
Innate’s pipeline includes four preclinical drug candidates born from the ANKET platform:
- Two developed in collaboration with Sanofi, including IPH6101/SAR443579 currently in new drug (IND)-enabling studies
- One under an option agreement with AstraZeneca (IPH62)
- One fully proprietary (IPH65)
NKp46 is the most specific marker of human NK cells and its expression is conserved on tumor-infiltrating NK cells. No statistically significant downregulation of NKp46 was observed in several cancer conditions.
Because NK cells are not expected to produce a cytokine storm and NKp46 is not downregulated in tumor infiltrating NK cells, ANKET may overcome the limitations of both ADCC inducing antibodies and T-cell engagers.
Mechanistically, incorporating NKp46, CD16 and IL-2 receptor-binding moieties in the same molecule, is essential for strong activity. In non-human primates, ANKET resulted in valuable PK and PD with minimal systemic cytokine release and no clinical sign of toxicity. Tetra-functional ANKET including an IL-2v thus constitutes a synthetic technological platform combining the induction of NK cell proliferation and effector functions without toxicity, supporting its clinical development for next-generation cancer immunotherapies.
Gauthier, et al, Multifunctional Natural Killer Cell Engagers Targeting NKp46 Trigger Protective Tumor Immunity. Cell 2019. 177: 1701-1713 e1716.
Demaria, et al, Natural killer cell engagers in cancer immunotherapy: Next generation of immuno-oncology treatments. European Journal of Immunology 2021. https://doi.org/10.1002/eji.202048953
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