Biotica achieves preclinical proof-of-concept in its nPT-CyP hepatitis C programme

Cambridge, UK: 6 April 2010

Biotica today announces that nPT-CyP, its non-cyclosporin cyclophilin (CyP) inhibitor programme for the treatment of hepatitis C virus (HCV), has reached preclinical proof of concept.

The nPT-CyP series of compounds is based on a polyketide with a naturally high affinity to CyP. Biotica has applied its novoPT™ technology to generate proprietary analogues with improved activity in the replicon system. While the polyketide lead has an EC50 of 300nM, new compounds in the series are significantly more potent in the replicon system, at an EC50 of approximately 40nM. The proprietary compounds are extremely selective, with a selectivity index (CC50/EC50) approaching 1000. Furthermore, in comparison with the original polyketide lead, these compounds are much more drug-like, displaying improved water solubility and oral bioavailability.

No CyP inhibitors are approved for HCV, but three cyclosporin-based CyP inhibitors have demonstrated clinical activity alone and/or in combination, validating the target for HCV treatment. Biotica’s nPT-CyP programme is expected to be well-differentiated from these pathfinder compounds. It is based on very different chemistry, and Biotica’s novoPT™ technology enables generation of compounds that lack the liabilities associated with cyclosporin-based compounds.

The most promising compounds in the nPT-CyP series are now being evaluated for further advancement as drug candidates. In parallel, Biotica continues to apply its novoPT™ technology to expand the chemical diversity within the series. More detailed information, including the chemical structure of the lead, will be released in future scientific publications.

Biotica Technology Ltd
Dr Edward E. Hodgkin, CEO
Tel: +44 1799 532920
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About Hepatitis C
There is significant unmet medical need for new anti-HCV treatments as the current standard of care (pegylated interferon-alpha plus ribavirin) is only effective in about half of the patients treated and is associated with serious side effects. WHO estimates that there are in excess of 180 million chronic carriers of HCV infection and, globally, there are approximately 3-4 million new cases of HCV infection each year. There is no vaccine available for HCV. Approximately 70%–85% of infected patients develop chronic HCV infection and are thus at high risk to develop liver cirrhosis and hepatocellular carcinoma. In developed countries more than half of all cases of liver cancer and two-thirds of all liver transplants are due to chronic HCV infection.

About Cyclophilin
Cyclophilin (CyP) is an important new target for the treatment of HCV. It is a human peptidyl prolyl isomerase which is required for HCV replication. CyP inhibitors represent a promising alternative class of anti-HCV drugs that can be combined in future antiviral cocktails for the treatment of HCV infection. They have been shown to exhibit potent antiviral efficacy and a higher barrier to the development of resistance is noted for compounds that do not target viral enzymes. However, the CyP inhibitors currently under clinical development are all derivatives of the cyclic peptide cyclosporin A. They suffer from chemical class-related bioavailability issues and have been seen to exhibit side-effects including hyperbilirubinemia and thrombocytopaenia.

About Biotica
Biotica is a privately-held biotechnology company that discovers and develops polyketide therapeutics. It has a growing pipeline of novel therapeutic programmes supported by clinical validation. These include nPT-mTOR (unique mTOR inhibitors partnered with Pfizer), nPT-CLN (potent calcineurin inhibitors for inhaled use in asthma), nPT-CyP (cyclophilin inhibitors for HCV) and nPT-ery (erythromycin analogues partnered with GlaxoSmithKline). All of Biotica’s projects employ its proprietary novoPT™ technology, which enables it to select from the many known polyketides with biological activity and make a range of derivatives that are either difficult or impossible to make by medicinal chemistry methods. For additional information visit http://www.biotica.com