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Hepatitis B infection model

Model description - HBV model​

Nova’s hepatitis B disease (HBV) model accounts for the virus pathophysiology, including viral replication within hepatocytes and antiviral immune response in chronically infected patients. Nova's chronic hepatitis B model for exploring and predicting efficacy for novel HBV treatments.

Structure of the HBV model. The patho-physiology model includes an intra-hepatocyte viral cycle submodel coupled with a cellular level chronic hepatitis B submodel for the dynamics of infected and healthy hepatocytes as well as immune cells and cytokines. Entecavir and peg-interferon alpha treatments models are coupled to the patho-physiology model to allow simulating patient’s response to treatments.

💊 Drugs that can be tested​

  • Nucleos(t)ide analogs (NUC) (eg.

  • entecavir, tenofovir)

  • Direct antivirals (including small interfering RNA, entry inhibitors, capsid assembly modulators)

  • Indirect antivirals (including immunomodulators such as peg-interferon alfa, recombinant vaccines, FXR agonist)

👥 Model Populations of interest​

  • Adult chronic HBV population
  • Treatment naive or NUC-controlled
  • HBe antigen positive or negative
  • Single of co-infection with HDV
  • (Hepatitis Delta)
  • Various HBV genotypes

📍Possible clinical endpoints​

  • Viral markers (HBV DNA, HBsAg, HBeAg, HBV RNA) in serum

  • Immune markers (cytokines eg. IL-10, immune cells eg. CD8+ T cells, NKC)

  • Possible extension: liver cirrhosis, hepatic carcinoma, liver failure

Biological submodels​

  • HBV replication & excretion
  • Bile acid metabolism
  • Cholesterol synthesis and intake
  • Impact of HBV on hepatocytes
  • Immune system
  • Drug model of your treatment
  • Drug models of Standard of Care (entecavir, peg-IFN-alpha)

Early insights to optimize your trial design - HBV model​

Drug Regimen​

  • What is the impact of the dose per administration of an investigational treatment on pharmacodynamics markers?
  • What is the impact of treatment duration?
  • What is the best follow-up duration to assess efficacy?

Combination of treatments​

  • What is the difference in efficacy of an investigational treatment dose when combining it with IFN treatment?
  • What is the impact of adding ETV on top of the other 2 treatments?
  • What is best between a full combination therapy approach and a sequential / alternating treatment

Patient selection​

  • What is the impact of various inclusion criteria (BeAg status, Hepatitis B viral genotype, age...)?

"Generating such insights upstream within a few months instead of many years reduces the risks, and make our drug development strategies eventually more successful."

Pietro SCALFARO
Chief Medical Officer, ENYO Pharma