Innate Pharma announces publication in Cell on innovative multifunctional NKp46 NK cell engagers (NKCEs)

• The findings describe potential first-in-class NKp46 NKCEs, a new generation of multifunctional antibody-based molecules for fighting cancer

• The NKCE technology provides a versatile platform to generate formats that co-engage multiple receptors

• Ongoing R&D collaborations for NKCEs with Sanofi and AstraZeneca

“Our multifunctional NKp46 NKCE technology provides a versatile platform to generate formats with the potential to co-engage up to three activating receptors on NK cells and two different tumor antigens on cancer cells,” explains Eric Vivier, Chief Scientific Officer of Innate Pharma, Professor at Aix-Marseille University and lead author of this publication. “These preclinical observations demonstrate the potential of NKp46 NKCEs, which were stable and had promising chemistry and manufacturing profiles compatible with industrial development. Together with a stronger anti-tumor activity in preclinical models than traditional standard therapeutic antibodies, these results support the clinical development of NKCEs for cancer immunotherapy”.

Most attempts in anti-tumor therapy to date have focused on manipulating effector T cells. T cell engager formats are in clinical development, but their use has so far been limited mostly to hematological diseases because of their potential toxicity. In this paper, the authors describe the manipulation of NK cells in cancer via NKCEs based on their anti-tumor effector potential and favorable toxicity profile as compared to T cells.

NKp46 NKCEs binds to one or two antigens at the surface of tumor cells, and engage both CD16 and NKp46 activating receptors on NK cells. The co-engagement of NKp46 synergizes with CD16 to induce full NK cell activation and tumor cell lysis. Further, NKp46 expression is often conserved on infiltrating NK cells in most solid tumors.

In the scope of the expanded oncology R&D collaboration announced in October 2018, AstraZeneca has recently acquired an option to exclusively license a multi-specific NKp46 NK cell engager from Innate Pharma preclinical portfolio.

Innate Pharma is eligible for up to $855 million in opt-in payments, development and commercial milestones and high-single to double-digit tiered royalties on net sales for this molecule if the option is exercised prior to the molecule reaching clinical development. After opt-in and up to the start of a Phase III clinical trial, AstraZeneca will incur all the development costs. Innate retains the right to participate in cost sharing for Phase III clinical trials in order to receive 50% profit and loss sharing within the EU. 

In addition, Innate Pharma has a research collaboration and licensing agreement with Sanofi for the generation and evaluation of up to two bispecific NK cell engagers (one of which is now the IPH61 program), using Innate Pharma’s technology and Sanofi’s technology and tumor targets. Under the terms of this license agreement, Sanofi is responsible for the development, manufacturing and commercialization of products resulting from the research collaboration. Innate Pharma is eligible to receive up to €400m in development and commercial milestone payments as well as royalties on net sales.