Shanghai Jeyou Pharmaceutical Technology Co., Ltd. (hereinafter referred to as “Jeyou Pharmaceutical”) announced that JYB1907 for injection, which the company developed independently, has been approved by the National Medical Products Administration to proceed with clinical trials for the treatment of advanced malignant solid tumors.

JYB1907 is an innovative, recombinant humanized monoclonal antibody targeting GARP/TGF-β1, independently developed by the Jeyou Pharmaceutical Macromolecular Innovation Institute. It holds proprietary intellectual property rights and is classified as a Class 1 new biological product. It is intended for the treatment of locally advanced or metastatic solid tumors and demonstrates excellent drug candidate properties and clinical therapeutic potential. It received clinical trial authorization from the U.S. FDA on December 17, 2022, making it the first GARP/TGF-β1 monoclonal antibody drug developed in China to be approved for clinical trials in the United States.

Glycoprotein-A repetitions predominant (GARP) is a type I transmembrane cell surface receptor for latent transforming growth factor-β1 (LTGF-β1) and is highly expressed on activated regulatory T cells (Tregs) and platelets. GARP mediates the release of transforming growth factor-β1 (TGF-β1). Within tumors, TGF-βs, particularly TGF-β1, stimulate stromal cell proliferation, angiogenesis, cancer cell metastasis, and inhibit immune cell infiltration [1][2]. Recent studies have revealed that TGF-β is the primary cause of resistance to immune checkpoint inhibitors in the tumor microenvironment. Consequently, GARP/TGF-β1 represents one of the core mechanisms underlying the immunosuppressive function of Treg cells. Inhibiting the release of TGF-β1 by GARP on the surface of Treg cells in the tumor microenvironment constitutes the primary drug-development mechanism for this target and is a promising target for precision immunotherapy against tumors [3].

JYB1907 specifically binds to GARP/TGF-β1, blocking GARP-mediated TGF-β1 release, thereby reversing immunosuppressive effects in the tumor microenvironment and enhancing antitumor immune responses. Preclinical study results demonstrate good safety and efficacy. In various animal models of human tumor cells and humanized PBMC tumors, JYB1907 demonstrated varying degrees of tumor growth inhibition; notably, in the ZR-75-1 human breast cancer model, complete tumor regression was observed in more than half of the mice. When JYB1907 was co-administered with a PD-L1 antibody in the A375 human melanoma model, it induced complete tumor regression in some mice, significantly outperforming the tumor-suppressing effect of the PD-L1 antibody alone, demonstrating a synergistic effect of the combination therapy.

In the future, Jeyou Pharmaceuticals plans to rapidly advance this drug into Phase I clinical trials to bring benefits to patients as soon as possible.

References:

[1] Metelli, Alessandra et al. “Immunoregulatory functions and the therapeutic implications of GARP-TGF-β in inflammation and cancer.” Journal of hematology & oncology. 2018, 11(1): 24

[2] Satoh, Kazuki et al. “Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.” International immunology. 2021, 33(8): 435-446.

[3] Cuende, Julia, et al. "Monoclonal antibodies against GARP/TGF-β1 complexes inhibit the immunosuppressive activity of human regulatory T cells in vivo." Science translational medicine. 2015, 7(284): 284ra56.