nPT-CLN

A series of potent calcineurin inhibitors for local administration in inflammatory indications.

Project overview
The target of the nPT-CLN series is calcineurin, a protein which stimulates components of the immune system, in particular cytokines, and activates T-cells. Biotica’s compounds are based on tacrolimus (FK506), a powerful immunosuppressant drug which acts by inhibiting calcineurin. Using novoPT™, Biotica has created create analogues with novel chemistry that are absorbed and active at the site of application, but which have minimal systemic bioavailability. This limits side effects while maximizing efficacy at the site of inflammation.

Development in asthma
The rationale for development of calcineurin analogues in asthma is especially strong. Asthmatic patients have elevated numbers of T-cells, and T-cell activation correlates with severity. Furthemore, tacrolimus itself has shown clinical efficacy in the indication, but has not been approved, possibly due to its side effects. By optimising for inhaled use and reducing systemic bioavailability, Biotica can generate more effective and safer new treatment options for severe asthma patients.

Up to 20% of adult asthma patients suffer from severe, persistant asthma. These patients are not well controlled by inhaled steroids and they have very few treatment options, making this an indication of high unmet need.

Opportunities in other inflammatory indications
Inflammatory bowel disease and skin conditions such as atopic dermatitis and psoriasis are also associated with overactivity of immune system components, and are sometimes treated clinically with tacrolimus. These indications are also suitable for local delivery of the active agent, making them potential development indications for compounds arising from Biotica’s nPT-CLN programme.