Sanofi To Target Natural Killers In IO With Innate Deal
This article was originally published in Scrip
Sanofi has teamed up with French biotech Innate Pharma to explore natural killer cell engagers in a potential new front in immuno-oncology.
In a new research collaboration and licensing agreement deal worth up to €400m to Innate in milestones as well as royalties on net sales (no other financial details were given), the two companies will develop bispecific antibody formats engaging natural killer (NK) cells to kill tumor cells through the activating receptor NKp46.
The move appears to put Sanofi in pole position in this particular IO race. Being behind in the PD1/L1 section of the checkpoint inhibitor class, despite its $2bn deal with Regeneron last July, like other firms it is looking for other ways to modulate the body's natural immune response to cancer.
Natural killer cells form part of the innate immune response, ie, the body's first non-specific line of defense against potential threats, but the two companies hope to use their respective technologies to boost these cells' cytotoxic effect and to pit it against a specific target.
NKp46 is an activating receptor expressed on all natural killer cells and plays a major role in their recognition of tumor cells. What Sanofi and Innate aim to do is to create bispecific antibodies, dubbed NKp46-bispecific NK cell engagers, to bind with one arm to an antigen at the surface of tumor cells and with the other to the NKp46 receptor on NK cells. This, they say, will lead to activation and specific tumor-killing by NK cells.
Under the deal, Sanofi and Innate Pharma will make and evaluate up to two bispecific NK cell engagers, using technology from Innate Pharma and Sanofi's proprietary bispecific antibody format as well as tumor targets. Under the terms of the agreement, Sanofi will be responsible for the development, manufacturing and commercialization of any resulting products.
There do not seem to be any other products in active development targeting NKp46 in cancer, according to Citeline's Pharmaprojects database.
"There is a lot of excitement around bispecifics in immuno-oncology," said Nicolai Wagtmann, chief scientific officer at Innate Pharma. "By building on our knowledge of the activating receptor NKp46, we have generated a technology to specifically induce tumor killing by NK cells. This new technology platform is complementary to our innovative portfolio of first-in-class antibodies targeting immune checkpoints. We intend to use it for our internal portfolio expansion, as well as through non-exclusive agreements with other companies, such as in this agreement with Sanofi."
Sanofi has also just signed a deal to extend an existing collaboration with Warp Drive Bio in oncology and antibiotics.
Another Innate Deal
Meanwhile, Innate has also signed deal with fellow French company OREGA Biotech, to obtain full worldwide rights to OREGA's program of first-in-class preclinical anti-CD39 checkpoint inhibitors and broaden its IO portfolio.
CD39 is expressed on both regulatory T cells and tumor cells and plays a major role in promoting immunosuppression through the pathway degrading adenosine triphosphate (ATP) into adenosine. It was initially discovered as a checkpoint inhibitor by OREGA's cofounder Dr. Armand Bensussan in collaboration with INSERM.
ATP promotes immune cell-mediated killing of cancer cells within the tumor microenvironment, whereas adenosine accumulation causes immune suppression and dysregulation of immune cell infiltrates resulting in tumor spreading. It is thought that blocking CD39 may stimulate anti-tumor immunity across a wide range of tumors by preventing the production of adenosine and by promoting the accumulation of ATP in the tumor microenvironment.
OREGA Biotech stands to receive upfront payment, milestone payments and royalties, but no details were disclosed. Again, this looks to be the only product against CD39 in development.