C21 as a new therapy for idiopathic pulmonary fibrosis

Up-regulated angiotensin II type 2 receptor (AT2R) expression has been demonstrated in models of fibrosis and lung injury. However, the lack of selective and potent AT2R agonists has hampered the assessment of the effects of AT2R activation. C21, a highly selective and potent AT2R agonist has demonstrated anti-fibrotic features of AT2R activation, including decreased TGF-levels and/or reduced collagen accumulation for several pathological conditions in different experimental models in vitro as well as in vivo. In animal models of pulmonary fibrosis administration of C21 both prevented and reversed induced pulmonary fibrosis efficiently as well as decreased the TGF-?levels. In addition, nonclinical toxicology and safety studies with C21 have revealed few adverse effects at relevant dose levels. A phase I program is already in progress. The main pilar of the H2020 application is thus the pivotal phase 2 study, which in addtion to providing clinical proof-of-concept (cPoC), also will be powered to suggest expected efficacy rates. The cPoC study will be the main pilar of teh proposal and detail will be clrear only after scientific advice meeting with EMA. The main outline of the study design is: (1) Population of patients with idiopathic pulmonary fibrosis; (2) Randomised, double-blind, placebo-control, on top of standard-of-care, 6 months treatment (3)Efficacy variables included: Forced vital capacity, the six-minute walk test, hospitalisation, mortality and patient reported outcome. In the case of compelling phase 2 results, a compassionate use progrem must be explored, and conditional marketing authorisation may be obtained. Regulatory affaires work to prepare such applications are therefore included in the work packages.