A novel approach to treating hepatitis B

A novel approach to treating hepatitis B

Partnering opportunity in infectious disease:

A novel approach to treating hepatitis B

 

Team

Professor Marc Pellegrini, Dr Greg Ebert

Background

Hepatitis B virus (HBV) is a global public health problem. It is estimated there are two billion people infected worldwide, and 600,000 deaths each year from HBV-related liver failure and liver cancer.

Current antiviral treatments are adequate in suppressing virus production, however they do not effectively eliminate HBV-infected cells, and thus patients become indefinitely dependent on antiviral therapies.

Cellular inhibitors of apoptosis proteins (cIAPs) have become important targets in cancer due to their ability to convert TNF-induced self-destruction signals into pro-survival signals through NFkB. Drug inhibitors of cIAPs, also known as Smac mimetics, were developed as cancer therapeutics to promote TNF-mediated tumour killing.

Our researchers have discovered that cIAPs also inhibit the death of HBV-infected cells and thus clearance of HBV infection by blocking the TNF signalling pathway. This has provided us with a novel strategy to eliminate HBV-infected cells.

The technology

Using an immunocompetent model of chronic HBV infection, our researchers have shown that Smac mimetics are able to rapidly reduce serum HBV DNA and serum HBV surface antigen, and promote the elimination of hepatocytes containing HBV core antigen.

Markers of cell death were not detected in untreated and uninfected models; meaning cell death is preferentially targeted to HBV-infected hepatocytes. Treatment with Smac mimetics enhances the efficacy of antiviral Entecavir to reduce viral DNA production in HBV-infected models, and this combination showed no overt evidence of toxicity. Further, Smac mimetics promote seroconversion, or the ability to generate an immune response against future infection.

Applications

The primary application is HPV infection. However our findings also show that Smac mimetics can be used to treat other infectious diseases such as tuberculosis and HIV, which represent similar market sizes worldwide.

Intellectual property

We hold a patent application published as WO2014205516A1 relating to the use of Smac mimetics as therapeutics in chronic human infectious diseases.

Opportunity for partnership

This work is currently in Phase I clinical trials. We seek a partner to co-invest in the continuation of trials, as well as in the development of novel Smac mimetics for use in clearing chronic infections.

Key publications

  • Ebert G. et al. Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus. Proc Natl Acad Sci U S A. 2015 May 5;112(18):5797-802 PMID: 25902529
  • Ebert G. et al. Eliminating hepatitis B by antagonizing cellular inhibitors of apoptosis. Proc Natl Acad Sci U S A. 2015 May 5;112(18):5803-8 PMID: 25902530

Contact

Dr Lauren Giorgio, Business Development Associate

Phone: +61 3 9345 2779 Email: giorgio.l@wehi.edu.au

 

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