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ResearchIn-Press PreviewHepatologyImmunologyInfectious disease Open Access | 10.1172/jci.insight.196809

Preclinical assessment of oral TLR7 agonist SA-5 in a non-human primate model

Shokichi Takahama,1 Takahiro Tomiyama,1 Sachiyo Yoshio,2 Yuta Nagatsuka,1 Hirotomo Murakami,1 Takuto Nogimori,1 Mami Kochi,3 Shoko Ochiai,3 Hidenori Kimura,3 Akihisa Fukushima,3 Tatsuya Kanto,4 and Takuya Yamamoto1

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Takahama, S. in: PubMed | Google Scholar |

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Tomiyama, T. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Yoshio, S. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Nagatsuka, Y. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Murakami, H. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Nogimori, T. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Kochi, M. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Ochiai, S. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Kimura, H. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Fukushima, A. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Kanto, T. in: PubMed | Google Scholar

1Laboratory of Precision Immunology, Center for Intractable Diseases and Imm, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan

2Department of Human Immunology and Translational Research, National Institute of Global Health and Medicine, Japan Institute for Health Security, Tokyo, Japan

3Research and Development Division, Sumitomo Pharma. Co., Ltd., Osaka, Japan

4Department of Liver Diseases, The Research Center for Hepatitis and Immunol, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan

Find articles by Yamamoto, T. in: PubMed | Google Scholar |

Published November 11, 2025 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.196809.
Copyright © 2025, Takahama et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published November 11, 2025 - Version history
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Abstract

Toll-like receptor 7 (TLR7) agonists are promising immunostimulatory agents for the treatment of chronic infections and cancer. However, their systemic toxicity remains a challenge. In this study, SA-5, a novel liver-targeted, orally available TLR7 agonist, was evaluated for pharmacokinetics, safety, and efficacy in young and aged macaques across 1–10 mg/kg repeated doses. Safety was evaluated through hematologic, biochemical, and flow cytometric profiling, while efficacy was assessed via IFN-α production, gene expression of interferon-stimulated genes, and plasmacytoid dendritic cell activation. A principal component analysis (PCA)-based composite scoring system was used to integrate multimodal parameters. SA-5 induced dose-dependent type I IFN with limited systemic inflammation, with 3 mg/kg showing optimal balance. SA-5 had comparable immunostimulatory activity to GS-9620 but with reduced adverse biomarker shifts. In aged macaques, efficacy was maintained with modestly increased safety responses. These findings support SA-5 as a safer next-generation TLR7 agonist effective across age groups, highlighting integrated biomarker profiling in preclinical immunomodulatory drug development.

Version history
  • Version 1 (November 11, 2025): In-Press Preview
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