Akeso Publishes Preclinical Results of PD-1/LAG-3 Bi-specific Antibody（AK129）at the American Association for Cancer Research (AACR) 2022 Annual Meeting

HONG KONG,April 14,2022 --Akeso,Inc. (9926.HK) ( "Akeso" ),a China-based biopharmaceutical company focusing on the development and commercialization of innovative therapeutic antibodies for Oncology & Immunology,announced the publication of preclinical results of its PD-1/LAG-3 bi-specific antibody (AK129) at the American Association for Cancer Research (AACR) Annual Meeting 2022. Both in vitro and in vivo preclinical data demonstrated that AK129 has enhanced T cell activation activity with robust anti-tumor activity compared to PD-1 and LAG-3 antibody combo.

Abstract: AK129,an anti-PD1/LAG-3 bi-specific antibody for cancer therapy

https://www.abstractsonline.com/pp8/#!/10517/presentation/17739

AK129,a bi-specific antibody,acts by co-blocking two immune checkpoint molecules co-expressed on T cells,PD-1 and LAG-3. Signaling through PD-1/PD-L1 exerts major effects on cytokines production by T cells,inhibiting the production of IFN-γ and IL-2. LAG-3 is a cell surface molecule expressed on effector T cells and Tregs,which plays a vital role in regulating T cell function to promote tumor immune escape. LAG-3 and PD-1 mediate different signaling pathways,but they may act synergistically to cause effector T cells inactivation and exhaustion. AK129 is being investigated as a cancer immunotherapeutic agent.

Results and observations from AK129's preclinical study support the development of AK129 as a cancer immunotherapeutic agent in the clinic：

AK129 showed good antigen binding to PD-1 and LAG-3. Coinsidently,AK129 potently inhibited the binding of LAG-3 to its ligand MHC-II,and the binding of PD-1 to its ligand PD-L1,thus blocking downstream immune suppression.

At the individual target level,AK129 demonstrated a similar PD-1 blocking activity compared to penpulimab,and similar LAG-3 blocking activity compared to relatlimab. Importantly,at the whole cell level,the enhancement effect of AK129 is stronger than the combination of penpulimab and relatlimab,as evidenced by significantly higher level of IL-2 and IFN-γ secretion from PBMCs.

AK129 showed favorable anti-tumor activity in BALB/c-hPD1/hLAG3 mice CT26.WT tumor model,with tumor growth inhibition values reaching 99.27% and 89.48% in high dose (20 mg/kg) and low dose (4 mg/kg) group of AK129,respectively.

Reference

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