Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody
<b>Background/Objectives:</b> Finotonlimab (SCTI10A) is a humanized anti-PD-1 antibody tested in Phase III trials for several solid tumor types. <b>Methods</b>: This study characterized the in vitro and in vivo efficacy, Fc-mediated effector function, and non-clinical PK/PD p...
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MDPI AG
2025-03-01
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| author | Yunqi Yao Xiaoning Yang Jing Li Erhong Guo Huiyu Wang Chunyun Sun Zhangyong Hong Xiao Zhang Jilei Jia Rui Wang Juan Ma Yaqi Dai Mingjing Deng Chulin Yu Lingling Sun Liangzhi Xie |
| author_facet | Yunqi Yao Xiaoning Yang Jing Li Erhong Guo Huiyu Wang Chunyun Sun Zhangyong Hong Xiao Zhang Jilei Jia Rui Wang Juan Ma Yaqi Dai Mingjing Deng Chulin Yu Lingling Sun Liangzhi Xie |
| author_sort | Yunqi Yao |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Finotonlimab (SCTI10A) is a humanized anti-PD-1 antibody tested in Phase III trials for several solid tumor types. <b>Methods</b>: This study characterized the in vitro and in vivo efficacy, Fc-mediated effector function, and non-clinical PK/PD properties of finotonlimab. <b>Results</b>: The results demonstrated that finotonlimab is effective in stimulating human T cell function in vitro and exhibits marked antitumor efficacy in vivo using both PD-1-humanized and PBMC-reconstructed mouse models. Additionally, finotonlimab exhibited minimal impact on the activation of effector cells via Fc receptor-dependent pathways, potentially facilitating PD-1<sup>+</sup> T cell killing. In cynomolgus monkeys, finotonlimab exhibited a nonlinear pharmacokinetic (PK) profile in a dose-dependent manner, and a receptor occupancy rate of approximately 90% was observed at 168 h following a single administration of 1 mg/kg. Finotonlimab’s PK profile (especially C<sub>max</sub>) was better than that of marketed antibodies. Following a 13-week successive administration of finotonlimab, a pharmacodynamic analysis revealed that a sustained mean receptor occupancy of PD-1 molecules on circulating T cells remained at or above 93% for up to 8 weeks, even at a dose of 3 mg/kg, and that there were higher antibody accumulations in different dose groups. <b>Conclusions</b>: Taken together, the preclinical findings are promising and provide the groundwork for evaluating the efficacy and pharmacodynamic characteristics of finotonlimab in clinical trials. |
| format | Article |
| id | doaj-art-92e4c5399fe647fdb737e7330a513cd0 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-92e4c5399fe647fdb737e7330a513cd02025-08-20T02:42:28ZengMDPI AGPharmaceuticals1424-82472025-03-0118339510.3390/ph18030395Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal AntibodyYunqi Yao0Xiaoning Yang1Jing Li2Erhong Guo3Huiyu Wang4Chunyun Sun5Zhangyong Hong6Xiao Zhang7Jilei Jia8Rui Wang9Juan Ma10Yaqi Dai11Mingjing Deng12Chulin Yu13Lingling Sun14Liangzhi Xie15Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaState Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Cancer Biology Center, Frontiers Science Center for New Organic Matter, College of Life Sciences, Nankai University, Tianjin 300071, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, ChinaBeijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China<b>Background/Objectives:</b> Finotonlimab (SCTI10A) is a humanized anti-PD-1 antibody tested in Phase III trials for several solid tumor types. <b>Methods</b>: This study characterized the in vitro and in vivo efficacy, Fc-mediated effector function, and non-clinical PK/PD properties of finotonlimab. <b>Results</b>: The results demonstrated that finotonlimab is effective in stimulating human T cell function in vitro and exhibits marked antitumor efficacy in vivo using both PD-1-humanized and PBMC-reconstructed mouse models. Additionally, finotonlimab exhibited minimal impact on the activation of effector cells via Fc receptor-dependent pathways, potentially facilitating PD-1<sup>+</sup> T cell killing. In cynomolgus monkeys, finotonlimab exhibited a nonlinear pharmacokinetic (PK) profile in a dose-dependent manner, and a receptor occupancy rate of approximately 90% was observed at 168 h following a single administration of 1 mg/kg. Finotonlimab’s PK profile (especially C<sub>max</sub>) was better than that of marketed antibodies. Following a 13-week successive administration of finotonlimab, a pharmacodynamic analysis revealed that a sustained mean receptor occupancy of PD-1 molecules on circulating T cells remained at or above 93% for up to 8 weeks, even at a dose of 3 mg/kg, and that there were higher antibody accumulations in different dose groups. <b>Conclusions</b>: Taken together, the preclinical findings are promising and provide the groundwork for evaluating the efficacy and pharmacodynamic characteristics of finotonlimab in clinical trials.https://www.mdpi.com/1424-8247/18/3/395finotonlimabanti-PD-1 antibodypreclinicalcharacterizationpharmacodynamics |
| spellingShingle | Yunqi Yao Xiaoning Yang Jing Li Erhong Guo Huiyu Wang Chunyun Sun Zhangyong Hong Xiao Zhang Jilei Jia Rui Wang Juan Ma Yaqi Dai Mingjing Deng Chulin Yu Lingling Sun Liangzhi Xie Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody Pharmaceuticals finotonlimab anti-PD-1 antibody preclinical characterization pharmacodynamics |
| title | Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody |
| title_full | Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody |
| title_fullStr | Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody |
| title_full_unstemmed | Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody |
| title_short | Preclinical Characterization of Efficacy and Pharmacodynamic Properties of Finotonlimab, a Humanized Anti-PD-1 Monoclonal Antibody |
| title_sort | preclinical characterization of efficacy and pharmacodynamic properties of finotonlimab a humanized anti pd 1 monoclonal antibody |
| topic | finotonlimab anti-PD-1 antibody preclinical characterization pharmacodynamics |
| url | https://www.mdpi.com/1424-8247/18/3/395 |
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