Stopping Fibrosis in MASH Before It’s Too Late

Our next-generation therapy is designed to halt fibrotic progression in MASH, offering a timely and effective solution to preserve liver function and improve long-term outcomes

AD64 | A breakthrough small molecule anti-fibrotic therapy for MASH

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver condition marked by fat buildup in the liver, accompanied by inflammation and liver cell injury. MASH can occur with or without fibrosis and may advance to cirrhosis, liver failure, or liver cancer in its later stages. MASH falls under the broader category of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), which includes a spectrum of liver disorders.

Our preclinical study in MASH demonstrated promising improvements in key metabolic and liver health markers. Administered orally, our investigational therapy led to significant enhancements in liver histopathology. Furthermore, we achieved MASH resolution, underscoring the potential of our approach to address both inflammation and scarring in liver disease

About Akeso

Pathophysiology

Pathophysiology

Challenge

Currently, there is no widely accessible pharmacologic treatment for MASH, aside from a recently USFDA-approved therapy with limited availability. Existing options have limited global accessibility, highlighting the urgent need for effective and accessible treatment strategies.

Akeso was envisioned to empower individuals living with MASH (Metabolic Associated Steatohepatitis), offering innovative solutions to proactively manage their condition and prevent disease progression. By addressing unmet medical challenges, we focus on creating pharmacological products that enhance well-being for improved health outcomes. As part of our commitment, we are broadening our portfolio with specialized attention to MASH, ensuring a comprehensive approach to tackling this complex condition.

If left untreated, MASH is associated with an increased risk of cirrhosis and hepatocellular carcinoma. Beyond the liver, it contributes to a range of multisystemic disorders, including type 2 diabetes, chronic kidney disease, cardiovascular diseases, metabolic syndrome (characterized by abdominal obesity, elevated blood pressure, and high triglyceride levels), and various non-hepatic cancers such as colorectal, esophageal, gastric, and pancreatic cancers.

Obesity Icon

51.3% with MASLD
81.8% with MASH
have Obesity

Mechanism of action

AD64 is proposed to exert therapeutic effects in Metabolic Dysfunction-Associated Steatohepatitis (MASH) through the modulation of key intracellular signaling pathways.

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MASLD/MASH Prevalence
Prevalence Chart 1
Prevalence Chart 2

References

  1. Cariou B, et al. Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review. Diabetes Obes Metab. 2021 May;23(5):1069-1083.
  2. https://www.jmcp.org/doi/epdf/10.18553/jmcp.2024.30.9-a.s1
  3. Sangro P, de la Torre Aláez M, Sangro B, D’Avola D. Metabolic dysfunction–associated fatty liver disease (MAFLD): an update of the recent advances in pharmacological treatment. Journal of physiology and biochemistry. 2023 Nov;79(4):869-79.
  4. https://pubmed.ncbi.nlm.nih.gov/37363821/
  5. Loomba R, Wong VW. Implications of the new nomenclature of steatotic liver disease and definition of metabolic dysfunction-associated steatotic liver disease. Aliment Pharmacol Ther. 2024 Jan;59(2):150-156. doi: 10.1111/apt.17846. PMID: 38153279; PMCID: PMC10807722.
  6. Harvey BE. NASH: regulatory considerations for clinical drug development and U.S. FDA approval. Acta Pharmacol Sin. 2022 May;43(5):1210-1214. doi: 10.1038/s41401-021-00832-z. Epub 2022 Jan 21. PMID: 35110697; PMCID: PMC9061714.
  7. Golabi P, Sayiner M, Fazel Y, Koenig A, Henry L, Younossi ZM. Current complications and challenges in nonalcoholic steatohepatitis screening and diagnosis. Expert Rev Gastroenterol Hepatol. 2016;10(1):63-71. doi: 10.1586/17474124.2016.1099433. Epub 2015 Oct 15. PMID: 26469309.
  8. Kalligeros M, Henry L, Younossi ZM. Metabolic dysfunction-associated steatotic liver disease and its link to cancer. Metabolism. 2024 Nov;160:156004. doi: 10.1016/j.metabol.2024.156004. Epub 2024 Aug 23. PMID: 39182603.
  9. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023 Apr 1;77(4):1335-1347. doi: 10.1097/HEP.0000000000000004. Epub 2023 Jan 3. PMID: 36626630; PMCID: PMC10026948.
  10. https://pubmed.ncbi.nlm.nih.gov/29886156/
  11. Sharma B, John S. Nonalcoholic Steatohepatitis (NASH) [Updated 2023 Apr 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470243/
  12. https://www.mdedge9-ma1.mdedge.com/gihepnews/article/265554/liver-disease/masld/mash-and-weight-loss
  13. https://pubmed.ncbi.nlm.nih.gov/29886156/