First-in-class therapeutic candidate antibody inhibiting human Arginase-2

• Lead-optimised antibody that is potent and highly specific to human Arginase-2
• Potent nM inhibition of Arg2 enzymatic activity in vitro and ability to fully reverse Arg2-mediated suppression of T cell proliferation in vitro
• A novel allosteric mechanism of non-competitive Arg2 inhibition as revealed by X-ray crystallographic studies 
• Favourable pharmacokinetics 
• Strong IP position
• Arg2 overexpression documented in various cancer and non-cancer indications

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. Originating from the Cancer Research Horizons–AstraZeneca Antibody Alliance Laboratory, lead-optimised molecule C0021061 was developed using phage display technology, 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). 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.

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, we sought to explore the hypothesis that an Arg2-specific inhibitory monoclonal antibody might restore anti-tumour immunity in cancer patients. Data showing that C0021061 is able to reverse the Arg2-mediated suppression of T cell proliferation in vitro, taken with other information, supports that these original findings indeed seem worth further exploration.