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First-in-class Arginase 2 inhibitory antibody

The Opportunity: 

We have developed a first-in-class, therapeutic-quality antibody that inhibits human Arginase-2 and are seeking a partner with interest in arginase in tumour immunosuppression and other areas. The rationale for exploring the role of Arginase-2 (Arg2) in tumour immunosuppression is based on Frank Mussai’s early work showing that AML creates an arginase-dependent immunosuppressive microenvironment (1). Since then, dysregulated expression of Arg2 in the tumour microenvironment resulting in an immunosuppressive niche has been reported in other papers as well. As a result of these findings, CRUK sought to explore the hypothesis that an Arg2-specific inhibitory monoclonal antibody might restore anti-tumour immunity in cancer patients. Originating from the CRUK–AstraZeneca Antibody Alliance Laboratory, lead molecule C0021061 was developed using phage display technology (2) and shown to demonstrate potent nM inhibition of Arg2 enzymatic activity in vitro, favourable pharmacokinetics and a novel allosteric mechanism of non-competitive Arg2 inhibition (as revealed by X-ray crystallographic studies). Data showing that C0021061 is able to reverse the Arg2-mediated suppression of T cell proliferation in vitro, taken with other information included in the attached slide deck, supports that these original findings indeed seem worth further exploration.

Intellectual Property: 

PCT/EP2020/073579, filed August 2020

References: 

1) Mussai et al, Acute myeloid leukemia creates an arginase-dependent
immunosuppressive microenvironment. Blood v122 no 5, Aug 2013

2) Chana et al, Extensive sequence and structural evolution of
Arginase 2 inhibitory antibodies enabled by an
unbiased approach to affinity maturation. PNAS, 2 July 2020

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