YH004 is a recombinant humanized agonistic 4-1BB IgG1 monoclonal antibody with a favorable safety profile. It effectively eliminates Treg cells with high expression of 4-1BB through ADCC effects and activates CD8+ T cells.

Clinical Progress

A Phase I dose-escalation study of YH004 as a monotherapy in patients with advanced solid tumors is being conducted in Australia and China. This study marks the first-in-human trial of YH004, with the first patient dosed in December 2021. As of June 30, 2024, a total of 17 patients have been enrolled and treated with YH004 at doses of 0.01 mg/kg (n=1), 0.03 mg/kg (n=1), 0.1 mg/kg (n=3), 0.3 mg/kg (n=3), 1.0 mg/kg (n=3), 3.0 mg/kg (n=3), and 6.0 mg/kg (n=3), administered intravenously every three weeks (iv q3W). To date, YH004 monotherapy has demonstrated good safety and tolerability at doses up to 6.0 mg/kg.

Trial #：YH004002

NCT #：NCT05040932

4-1BB Target

4-1BB is a member of the tumor necrosis factor receptor superfamily (TNFRSF) and is expressed in activated T cells within the tumor microenvironment. Antibody-mediated stimulation of 4-1BB can enhance the release of CD8+ T cell effectors through costimulatory signals, promote cell proliferation while inhibiting apoptosis, and ultimately improve the anti-tumor immune response.

Bristol-Myers Squibb's urelumab (BMS-663513) is the first therapeutic drug targeting 4-1BB that has entered clinical trials. However, there are currently no 4-1BB drugs on the market.