2. Academic Validation
  3. The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075

The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075

  • J Med Chem. 2024 Dec 12;67(23):21126-21142. doi: 10.1021/acs.jmedchem.4c01814.
Sandrine Vendeville 1,  Franck Amblard 2,  Leda Bassit 2,  Leonid N Beigelman 3,  Lawrence M Blatt 3,  Xiaoyuan Chen 4,  Lang Chou 4,  Dieudonné Buh Kum 1,  Sushmita Chanda 3,  Jerome Deval 3,  Xiu Geng 4,  Kusum Gupta 3,  Andreas Jekle 3,  Haiyang Hu 5,  Xiaojuan Hu 5,  Hyunsoon Kang 3,  Cheng Liu 3,  Jyanwei Liu 3,  David C McGowan 1,  Dinah L Misner 3,  Pierre Raboisson 1,  Abel Acosta Sanchez 6,  Vladimir Serebryany 3,  Antitsa D Stoycheva 3,  Julian A Symons 3,  Hua Tan 3,  Hannah Vanrusselt 1,  Caroline Williams 3,  Michael Welch 3,  Liangliang Zhang 5,  Qingling Zhang 3,  Yafeng Zhang 4,  Raymond F Schinazi 2,  David B Smith 3,  Yannick Debing 1
Affiliations

Affiliations

  • 1 Aligos Belgium BV, Gaston Geenslaan 1, 3001 Leuven, Belgium.
  • 2 Center for ViroScience and Cure, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, 100 Woodruff Circle, Atlanta, Georgia 30322, United States.
  • 3 Aligos Therapeutics, Inc., 1 Corporate Dr., Second Floor, South San Francisco, California 94080, United States.
  • 4 WuXi AppTec, 288 Fute Zhong Road Waigaoqiao Free Trade Zone, Pudong New Area, Shanghai, 200131, China.
  • 5 Pharmaron Beijing Co Ltd, 6 Taihe Road, BDA, Beijing 100176, China.
  • 6 Novalix, Gaston Geenslaan 1, 3001 Leuven, Belgium.
PMID: 39575679 DOI: 10.1021/acs.jmedchem.4c01814
Abstract

Chronic hepatitis B (CHB) represents a significant unmet medical need with few options beyond lifelong treatment with nucleoside analogues, which rarely leads to a functional cure. Novel agents that reduce levels of HBV DNA, RNA and Other viral antigens could lead to better treatment outcomes. The capsid assembly modulator (CAM) class of compounds represents an important modality for chronic suppression and to improve functional cure rates, either alone or in combination. GLP-26 is a potent CAM, which in this work was optimized for potency, safety, and Other drug-like properties leading to ALG-001075. ALG-001075 was further advanced through clinical development as the highly soluble prodrug ALG-000184. ALG-000184 is currently being explored in multiple clinical trials in HBV-infected subjects where unprecedented reductions in HBV DNA, RNA and Other viral antigens have been observed, making ALG-000184 a promising candidate to become a cornerstone for future chronic suppressive and combination treatment regimens for CHB.

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