nPT-CyP

Non-cyclosporin cyclophilin inhibitors for the treatment of hepatitis C infection

Cyclophilin as a target for HCV therapy
Targeting cyclophilin represents a relatively new approach to treating hepatitis C (HCV). Rather than being a part of the virus itself, cyclophilin is a protein naturally expressed in humans (and other animals), which the virus makes use of during its replication. Blocking cyclophilin function inhibits viral replication.

Emergence of resistance to treatment is a major concern with potential new HCV therapies that target viral proteins. Cyclophilin inhibitors are expected to have a different resistance profile from these types of compounds. Targeting cyclophilin may offer a higher barrier to resistance, since there will be no selection pressure on the host target. Because of the differences in resistance profile, cyclophilin inhibitors may combine well with both the current standard of care and with the protease and polymerase inhibitors in clinical development.

Clinically validated target
Inhibition of cyclophilin is a clinically validated approach to treating HCV. Three cyclosporin analogues are in clinical development: Debio-025, NIM-811 and SCY-635). IN HCV patients, they have demonstrated reduction in viral load, alone or in combination with pegylated interferon, validating cyclophilin as a target for HCV therapy. However, cyclosporine analogues have also shown some side effects, including hyperbilirubinemia and thrombocytopenia which may be associated with the class of compounds.  

Biotica’s approach is different
nPT-CyP compounds are based on a polyketide lead structurally unrelated to cyclosporine. They are potent cyclophilin inhibitors and are highly active in the replicon system (an in vitro assay for anti-HCV activity), with a good selectivity index. Biotica’s optimisation programme is focused on generating potent, safe cyclophilin inhibitors with a competitive dosing schedule for the oral treatment of HCV.