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

Clinical Progress

YH004, a potential therapeutic for advanced solid tumors and relapsed/refractory non-Hodgkin’s lymphoma (r/r NHL), is currently undergoing a phase I dose escalation study in Australia as monotherapy. The study was approved under the CTN scheme by the Australian Therapeutic Goods Administration (TGA) in June 2021 and has been officially initiated. The safety assessment of the completed dose groups has not reported any dose-limiting toxicities or drug toxicities exceeding grade 2, indicating that YH004 has been safe and well-tolerated so far. The study is currently ongoing.

Trial #：YH004002
NCT #：NCT05040932

Preclinical studies have yielded several key findings on the potential of YH004 as a therapeutic agent:

1.In an in vivo toxicology study in cynomolgus monkeys, no hepatotoxicity was observed even at the highest tested dose of 30 mg/kg. In the B-h4-1BB syngeneic model, YH004 was significantly safer than urelumab.

2.YH004 had similar antitumor activity to urelumab in the humanized syngeneic 4-1BB MC38 colorectal cancer model at a dose of 1.0 mg/kg. However, YH004 showed better antitumor efficacy than urelumab when used in combination with a PD-1 antibody.

3.YH004 specifically eliminates Tregs, which have high levels of 4-1BB expression, through ADCC.

4.In vitro studies revealed that YH004 has a higher binding affinity to human 4-1BB than urelumab.

5.YH004 promotes the proliferation of CD8+ T cells and the release of IL-2 by activating 4-1BB.

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.

Poster Downloads
AACR2020: Optimization of novel anti-4-1BB antibodies on Biocytogen’s in vivo drug screening platform
AACR2019: Novel in vivo durg screening platform accelerated 4-1BB agonistic antibody development