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GH21 (also known as HBI-2376) is a selective, orally bioavailable small molecule allosteric inhibitor of SHP2 (Src homology phosphotyrosyl phosphatase 2) developed by Suzhou Genhouse Bio Co., Ltd. SHP2 is a non-receptor protein tyrosine phosphatase that acts as a key signaling node in the RAS-MAPK pathway and is involved in immune suppression downstream of multiple checkpoints, including PD-1. This combination therapy pairs GH21 with a PD-1 inhibitor (a monoclonal antibody) to treat advanced solid tumors that have progressed on prior therapies. The rationale for the combination is to leverage the synergistic effects of SHP2 inhibition and PD-1 blockade to overcome resistance to immunotherapy and enhance anti-tumor immune responses. GH21 is currently being evaluated in Phase 1/2 clinical trials both as a monotherapy and in combination with various targeted and immunotherapies in China and the United States.
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