nPT-CyP

Non-cyclosporin cyclophilin inhibitors for the treatment of hepatitis C

Cyclophilin as a target for HCV therapy
Targeting cyclophilin (CyP) represents a relatively new approach to treating hepatitis C (HCV). Blocking CyP function inhibits viral replication but, critically, CyP is a host (i.e. human) protein. As a result, CyP inhibitors are expected to have a different resistance profile from HCV therapeutics against viral targets, including potentially slower development of resistance. Therefore, CyP inhibitors may combine well with both the current standard of care in HCV and with the protease and polymerase inhibitors in clinical development.

nPT-CyP series characteristics
The nPT-CyP series is based on a polyketide with a naturally high affinity to CyP, to which Biotica has applied its novoPT™ technology to generate improved proprietary compounds. These compounds are highly active, with EC50 of approximately 40nM in the replicon system (an in vitro assay for anti-HCV activity) and a selectivity index (CC50/EC50) approaching 1000. These compounds are undergoing additional profiling as possible candidate drugs, and Biotica continues to use the novoPT technology to generate additional compounds for investigation.

Biotica’s approach is different
CyP is validated as an HCV target by three cyclosporin-based CyP inhibitors, which have demonstrated clinical activity alone and/or in combination. Biotica’s nPT-CyP programme is well differentiated from these pathfinder compounds. It is based on very different chemistry, and Biotica is using the novoPT™ technology to generate compounds without the liabilities which may be associated with cyclosporin-based compounds.