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ResearchIn-Press PreviewHematologyImmunology Open Access | 10.1172/JCI205864

Pegtarazimod limits acute graft-versus-host disease mortality and severity in mice and is tolerated in patients

Verena Holzmüller,1 Jana Gawron,1 Ann-Cathrin Burk,1 Anna-Verena Stell,1 Anna-Sophia Baur,1 Alexander Zähringer,1 Viktor Fetsch,1 Annika Mäder,1 Alina Hartmann,1 Nana Talvard-Balland,1 Neel Krishna,2 Kenji Cunnion,2 Ulrich Thienel,3 Paolo Martini,2 Lindsey Glenn,2 James L.M. Ferrara,4 Monzr M. Al Malki,5 Hannah Choe,6 José Antonio Pérez-Simón,7 Annette Schmitt-Graeff,8 Joerg Buescher,9 Natalie Köhler,1 Zohreh Mansoori Moghadam,10 Philipp Henneke,11 Geoffroy Andrieux,12 Melanie Boerries,13 and Robert Zeiser14

1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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1Department of Internal Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

2ReAlta Life Sciences, Norfolk, United States of America

3UT Partners, New York, United States of America

4Icahn School of Medicine at Mount Sinai, New York, United States of America

5City of Hope National Medical Center, Duarte, United States of America

6Division of Hematology, James Cancer Hospital and Solove Research Institute at The Ohio State University, Columbus, United States of America

7Hospital Universitario Virgen del Rocío, Seville, Spain

8University of Freiburg, Freiburg, Germany

9Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany

10Institute for Infection Control and Prevention, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

11CIBSS – Centre for Integrative Biological Signalling Studies, University of Freiburg, Freiburg, Germany

12Institute of Medical Bioinformatics and Systems Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

13German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center – University of Freiburg, Freiburg, Germany

14Department of Internal Medicine I, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany

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Published August 4, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI205864.
Copyright © 2026, Holzmüller 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 August 4, 2026 - Version history
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Abstract

The success of allogeneic hematopoietic cell transplantation (allo-HCT) is limited by acute graft-versus-host disease (aGVHD). We have previously reported that neutrophils can exacerbate tissue damage caused by conditioning regimens. Pegtarazimod is a synthetic peptide, derived from the capsid protein of human astrovirus serotype 1, that was shown to reduce neutrophil effector functions. Therefore, we evaluated the therapeutic activity of pegtarazimod against aGVHD. Pegtarazimod significantly reduced aGVHD-related mortality, histological aGVHD severity, and pro-inflammatory cytokines in multiple in vivo mouse models, while maintaining the anti-leukemia effect. Mechanistically, pegtarazimod reduced inflammation by decreasing ROS production as investigated using allo-HCT recipient mice with genetic inactivation of NADPH oxidase (NOX2) in the bone marrow. In addition to the anti-inflammatory effect, pegtarazimod protected intestinal organoids against TNF-induced toxicity and oxidative DNA damage. In the phase-2 clinical trial AURORA, pegtarazimod treatment was well-tolerated in patients with corticosteroid-refractory (SR) aGVHD (NCT06343792) with an overall response rate (ORR) of 4/7 patients at day 28. In summary, pegtarazimod reduced aGVHD in mice by suppressing pro inflammatory neutrophil effector functions and preserving enterocyte integrity. The clinical trial data support tolerability of pegtarazimod in aGVHD patients and further studies are needed to determine efficacy.

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