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Abalone Bio has identified novel cannabinoid receptor 2 (CB2)-specific agonist antibodies, AB110, AB120 and AB150 using its proprietary Functional Antibody Selection Technology (FAST) platform. This innovative approach leverages yeast expressing human GPCRs to directly select for antibodies with desired functional properties, bypassing the need for initial affinity-based selection. CB2 is predominantly expressed on immune cells such as macrophages, microglia, and Kupffer cells. Activating CB2 effectively suppresses the activation of these cell types, leading to reductions in inflammation and fibrosis. While several small molecule CB2 agonists have been evaluated in clinical trials, their development has been hindered by off-target effects on the CB1 receptor. AB110, AB120, and AB150 effectively reduce mouse and human macrophage activation in vitro and attenuate the expression of fibrotic markers in an ex vivo precision cut liver slice model of fibrosis. Additionally, AB120 and AB150 reduce fibrosis in a therapeutic model of F4 stage liver fibrosis. This model recapitulates advanced liver cirrhosis and is a high bar for potential therapeutics. These CB2 agonists also significantly alleviate behavioral hypersensitivity to mechanical and cold stimulation in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN) induced by the taxane, paclitaxel.

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