Biotica adds nPT-CyP, a series of polyketide cyclophilin inhibitors for HCV, to its pipeline
Cambridge, UK: 25 June 2009
Biotica, the leader in discovery of polyketide therapeutics, today announces the progression of the nPT-CyP project into its pipeline. The series of non-cyclosporin cyclophilin (CyP) inhibitors is under evaluation for the treatment of hepatitis C virus (HCV) infection. Its progression builds upon Biotica’s strategy of developing polyketide therapeutics whose target is clinically validated in an indication of high clinical and commercial importance.
Compounds in the bPT-CyP series have demonstrated excellent activity in the replicon system (an in vitro assay for activity against HCV), and a good selectivity index. Because CyP is a host target, the compounds are expected to combine advantageously with both the current standard of care for HCV (pegylated interferon-alpha plus ribavirin) and the protease and polymerase inhibitors that dominate the HCV clinical pipeline. Furthermore, the barrier to emergence of resistance may be higher than for compounds with viral targets.
Selection of this project for progression into the pipeline is based upon a rigorous evaluation process. Clinical validation of the target comes from the cyclosporin-based CyP inhibitors, such as Debio-025 (DebioPharm), NIM-811 (Novartis) and SCY-635 (Scynexis). In HCV patients, Debio-025 has demonstrated significant reduction in viral load. However, the cyclosporin analogues have also shown some side effects, including hyperbilirubinemia and thrombocytopenia, which may be associated with the chemical class.
Biotica worked closely with expert advisors to define a target product profile and development plan for nPT-CyP. This includes early proof-of-concept studies with well-defined go/no go criteria for progression of the compounds. Meeting these criteria will ensure that the nPT-CyP compounds are well-differentiated in their safety and efficacy profile against existing HCV therapies and the clinical-stage cyclosporin-based cyclophilin inhibitors.
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
CyP 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 poor bioavailability and 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 Wyeth), 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