Therapeutic area

P144

P144 is a transforming growth factor beta 1 (TGF-B1) inhibitor peptide, derived from TGF-B1 type III receptor sequence. TGF-B1 develops a wide range of biological effects like cellular proliferation, immunomodulation, angiogenesis, fibrogenesis, etc. One of the more characteristic effects of TGF-B1 concerns to its contribution to the excessive production of collagen and other extracellular matrix components, related to different pathologies. TGF-B1 inhibition could be an effective approach to the treatment of different serious diseases (scleroderma, idiopathic lung fibrosis, kidney failure, cardiac fibrosis and hepatic cirrhosis) with fibrosis development as a common fact. However there are many other pathologies (queloid scars, burns, surgical scars, cornal fibrosis, etc) less serious from the patient point of view but with capacity to affect the quality life in a significant way. Besides, fibrosis is one of the main cutaneous manifestations of systemic diseases, like scleroderma before mentioned. Nowadays there are no proved efficacy drugs to inhibit the fibrotic process, so an available product to treat these situations could significantly improve the patients’ life quality.

P144 have developed excellent results in different animal models related to fibrotic processes like chronic liver damage and a silicone prostheses postimplantation reactive fibrosis in rats. Moreover the immunomodulation effect of this peptide has been probed in different immune system response models, where TGF-B1 has an important regulator role. We are now testing the antifibrogenis effect of P144 and P17 in animal models of corneal and retina fibrosis. The establish fibrosis in these ocular structures is the final stage of alterations related to inflammatory processes and scarring, this fibrosis could imply a partial or total lose of vision.

P144 have shown promising results, through topical application, in a mice scleroderma model in which fibrosis is induced by bleomicyn subcutaneous injections. In this model P144 is able to significantly reduce the dermal fibrosis in prevention as well as in treatment. DIGNA Biotech is administrating wide resources in the toxicological-pharmacokinetics study and galenic development of P144 in different formulations to carry out the clinical and pharmaceutical possible applications of this peptide with antifibrotic activity.

At present, a galenic cream formulation of P144 has been developed that allows for topical treatment; the preclinical development of the product is currently being completed, and it is expected that the first phase I/II trials with the substance will begin in the first trimester of 2006.