Background

It is estimated that in the USA alone, some 4 million people have been infected with Hepatitis C with 2.7 million suffering from chronic infection. Worldwide, 180 million people are infected. Hepatitis C virus (HCV) causes inflammation of the liver, which may lead to fibrosis and cirrhosis, liver cancer and, ultimately, liver failure. Existing drugs for HCV have toxicity issues and limited effectiveness, with approximately 50% of infected people not responding to current therapies, leaving a significant need for new therapies that directly target and halt replication and production of the virus in patients.

P7 Inhibitor

Biotron’s HCV program is focused on developing drugs to target the HCV p7 protein. HCV p7 is highly conserved and present in all 6 clades, with a critical role in virus assembly and release, and is a potential new target for therapeutic intervention. BIT225 is a novel small molecule viral assembly inhibitor that targets p7 and is in development for treatment of chronic HCV infection.

Preclinical data

• Identified as “hit” in HCV p7 bacterial assay
• Inhibits p7 (HCV 1a) ion channel in planar lipid bilayers
• Inhibits infectious clone JFH1 (HCV 2a)
• Also inhibits HCV model viruses GBV-B & BVDV
• Synergy with IFN, IFN/ribavirin, and polymerase inhibitors in BVDV in vitro
• High barrier to antiviral resistance in vitro
• Good preclinical safety and toxicology data
• Phase 1b data showed antiviral efficacy against genotype 1-3
• Viral assembly inhibitor with antiviral kinetics that suggest efficacy increases with treatment duration
  

Clinical data

Phase 1a safety trial (BIT225-001) in healthy volunteers was completed in late 2007.

Phase 1b, repeat-dose monotherapy study (BIT225-003) in HCV-infected patients was completed in late 2009. The results demonstrated that BIT225 showed antiviral efficacy against genotype 1-3, significantly reducing viral loads compared to placebo, and that the drug was well tolerated. The antiviral kinetics suggested that efficacy increased with treatment duration.

Phase 2a, 28-day, repeat-dose, combination trial (BIT225-005) of BIT225 with standard of care (pegylated interferon and ribavirin) in treatment-naive, genotype 1 HCV-infected patients commenced in Sept 2010, and concluded in August 2011. Preliminary headline results were released in October 2011, and demonstrated that BIT225 is able to significantly reduce viral loads over and above that seen with standard of care. Data from the trial is anticipated to be presented at the HepDART conference in December 2011.

Advantages

BIT225 has the following advantages:

• First-in-class, new mode of action drug
• Novel p7 inhibitor with the potential to increase the potency of current anti-HCV therapy
• Highly synergistic with ribavirin and rIFNa-2b
• Potential for use in HCV and HIV-1 co-infected patients.