IPH62 / Innate, Sanofi - LARVOL DELTA

Innate, Sanofi licensing deal gets US antitrust clearance (SeekingAlpha) - "Innate Pharma...and Sanofi...said the expansion of their collaboration on natural killer (NK) cell engagers under a licensing agreement became effective as the waiting period under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 expired. The companies had announced an expansion of their collaboration in December 2022. Under the agreement Sanofi is licensing a NK cell engager program targeting B7H3 from Innate's ANKET (Antibody-based NK Cell Engager Therapeutics) platform. The French pharma giant will also have the option to add up to two additional ANKET targets."

Licensing / partnership • Oncology

Innate Pharma Announces HSR Clearance Regarding Expansion of Its Collaboration With Sanofi on NK Cell Engagers (Businesswire) - "Innate Pharma SA...announced today the expiration of the waiting period under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act of 1976 with respect to the previously announced expansion of its collaboration with Sanofi. The licensing agreement is now effective. As announced on December 19, 2022, Sanofi is licensing a Natural Killer (NK) cell engager program targeting B7H3 from Innate’s ANKET (Antibody-based NK Cell Engager Therapeutics) platform. Sanofi will also have the option to add up to two additional ANKET targets. Upon candidate selection, Sanofi will be responsible for all development, manufacturing and commercialization. Under the terms of the agreement, Innate will receive €25m upfront payment and up to €1.35bn total in preclinical, clinical, regulatory and commercial milestones plus royalties on potential net sales."

Licensing / partnership • Oncology • Solid Tumor

Innate Pharma Announces Publication of Preclinical Data with a Trifunctional NK Cell Engager in Acute Myeloid Leukemia in Nature Biotechnology (Businesswire) - "Innate Pharma SA...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 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)."

Preclinical • Trial status • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

"$IPH $IPHA Innate Pharma has two ongoing partnerships : one with AZN and one with SANOFI, focused on developing multispecific antibodies, oncology oriented; only one target was disclosed : NKp46, the major NK cell specific activating receptor, a favorite of Pr Eric Vivier, CSO" (@oru2day)

Licensing / partnership • Oncology

Cytovia Therapeutics Licenses Productivity-Boosting Manufacturing Technology for Its NK Engager Multifunctional Antibodies From ProteoNic (GlobeNewswire) - "Cytovia Therapeutics, Inc...announced...that it has licensed from ProteoNic BV its 2G UNic™ technology for boosting recombinant protein production, allowing for cost-effective manufacturing at large scale. Under the agreement, Cytovia gains non-exclusive, worldwide commercial rights for application of the technology to the development of a number of its proprietary NK Engager multifunctional antibodies...Cytovia has also licensed NKp46 antibodies from Hebrew University of Jerusalem....'We look forward to bringing our novel cancer therapeutics to clinical trials starting in 2021.'"

Licensing / partnership • New trial • Oncology

IL-21-dependent expansion of memory-like NK cells enhances protective immune responses against Mycobacterium tuberculosis. (PubMed) - Mucosal Immunol - "Using antibodies, short interfering RNA and gene-deleted mice, we found that expansion of memory-like NK cells depends on interleukin 21 (IL-21). NKp46+CD27+KLRG1+ NK cells expanded in healthy individuals with latent TB infection in an IL-21-dependent manner. Our study provides first evidence that memory-like NK cells survive long term, expansion depends on IL-21, and involved in vaccine-induced protective immunity against a bacterial pathogen.Mucosal Immunology advance online publication, 7 December 2016; doi:10.1038/mi.2016.105."

Journal • Biosimilar • Immunology

Essential Role of c-MYC for Natural Killer Cell Development, Proliferation and Anti-Tumor Activity (ASH 2017) - "...Ncr1Cre knock-in mice, in which Cre recombinase was inserted into the Nkp46 locus, was used...Our results also provide a mechanism basis for the potential application of targeting c-Myc in NK cells ex vivo or in vivo expansion, and NK-mediated immunotherapy. Future studies are needed to delineate the underlying mechanisms and explore the applications."

Preclinical • Biosimilar • Leukemia

Group 2 Innate Lymphoid Cells (ILC2s) are Altered in Fatty Liver Disease (AASLD 2016) - "ILC subsets were identified by the expression patterns of c-kit, NKp46 and the IL-33 receptor (ST2). In a murine model of fatty liver disease loss of and/or changes in ILC2s may contribute to chronic inflammation and promote disease progression. This population may represent a potential therapeutic target in the liver."

Preclinical • Biosimilar • Immunology • Obesity

Innate Lymphoid Cells in Mouse Models of HCC and NASH (VCUHC 2017) - "...Flow cytometry was performed and group 1 ILCs weredetermined as CD45+, lineage-, NKp46+ and NK1.1+ or Tbet+...NK cells represent a major population in the liver of mice and human. ILC1s are closely related to NK cells and their plasticity but also their function in the setting of liver disease and HCC is not understood."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

NK cell phenotypic and functional shifts coincide with specific clinical phases in the natural history of chronic HBV infection. (PubMed) - Antiviral Res - "This depicts a shift in NK cell characteristics between the immune active, under heavy viral or immune pressure, and inactive carrier phases, that coincides with HBeAg seroconversion. Although these changes in NK cells do not appear to be completely responsible for differences in liver damage characteristic of specific clinical phases, they could provide a step toward understanding immune dysregulation in chronic HBV infection."

Journal • Biosimilar • Immunology

Natural Killer cells contribute to hepatic injury and help in viral persistence during progression of HBeAg-negative chronic HBV infection. (PubMed) - Clin Microbiol Infect - "Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+)T-cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells by enhanced TRAIL and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced IFN-γ secretion and perforin-mediated CD4(+)T-cell lysis contribute to progression of e(-)CHI."

Journal • Biosimilar • Fibrosis • Immunology

Differentiation and function of group 3 innate lymphoid cells, from embryo to adult. (PubMed) - "After birth, the NCR(-) and NCR(+) ILC3 contribute to the maintenance of health but also to inflammation in mucosal tissues. This review will describe the differentiation pathways of ILC3, their involvement in the development of the adaptive immune system and their role in the establishment and maintenance of gut immunity."

Journal • Biosimilar • Immunology • Inflammation

The Beneficial Effects of mTOR Inhibitors on Liver Resident Natural Killer Cells. (ATC 2017) - "...Expression of NKp46 and CD69 was also higher on liver resident NK cells from the mTORi-treated group than that from the untreated group (NKp46: 117.65±3.7 vs 96.16±3.45, CD69: 54.1±6.04 vs 46.8±12.15, respectively)...Spleen NK cells and PB-NK cells showed no effect by mTORi-treatment.(Conclusion) The mTOR inhibitor has ability to enhance the liver NK cell activity. This result suggested that mTOR inhibitor is might be useful to maintain anti-microbe and anti-tumor immunity after transplantation."

Preclinical • Biosimilar • Graft versus Host Disease • Oncology

Zbtb1 controls NKp46+ ROR-gamma-T+ innate lymphoid cell (ILC3) development. (PubMed, Oncotarget) - "Finally, absence of NKp46+ILC3 cells combined with the absence of T-cells in Zbtb1-deficient mice, led to a transient susceptibility to C. rodentium infections. Altogether, these results establish that Zbtb1 is essential for the development of NKp46+ ILC3 cells."

Journal • Biosimilar • Immunology

Strategic partnership aims to develop cancer immunotherapies targeting natural killer cells (GlobeNewswire) - "Yissum...announced today a strategic collaboration in the development of precision medicines for both blood cancers and solid tumors. Under the collaboration, Cytovia will sponsor a research program for the development of multi-specific antibodies targeting both NK cells and the tumor antigen...Prof. Mandelboim’s team has recently demonstrated that the NK activating receptor, NKp46, influences the FN1 expression by tumors, ultimately affecting its metastatic ability..."

Licensing / partnership

Multifunctional natural killer cell engagers targeting NKp46 trigger protective tumor immunity (SITC 2019) - "Trifunctional NKCEs targeting CD19, CD20 or EGFR as tumor antigens triggered tumor killing by human primary NK cells in vitro. In vivo, they induced NK cell accumulation in tumors and promoted tumor clearance in preclinical mouse models of solid and invasive cancers. Our multispecific technology provides a versatile platform with many different format options and the potential to co-engage up to three activating receptors on NK cells and two different tumor antigens on cancer cells."

IO Biomarker • EGFR

"#InnatePharma announces publication in Cell on innovative multifunctional #NKp46 #NKCellEngagers (#NKCEs) https://t.co/PvvI8itrfO" (@1stOncology)

"*SLIDE SET 5* Dr Mathieu Blery #immunologist @InnatePharma @Immunopole talks @ #TIMO2019 #Halle switching to #NKp46 #bispecific/NK-engager/preclinical model human Raji cells/Role of Fc important/Fc optimized @sitcancer #FinishCancer @AstraZeneca @univamu @Inserm" (@BernardAFox)

Preclinical