HEDGEHOG INHIBITORS IN FIBROSIS

THE HEDGEHOG (HH) PATHWAY IS A SOPHISTICATED CONSERVED CELL SIGNALING PATHWAY THAT PLAYS AN ESSENTIAL ROLE IN CONTROLLING CELL SPECIFICATION AND PROLIFERATION, SURVIVAL FACTORS, AND TISSUE PATTERNING FORMATION DURING EMBRYONIC DEVELOPMENT OF DIFFERENT ORGANS INCLUDING THE LUNGS. 

HH SIGNAL ACTIVITY DOES NOT ENTIRELY DISAPPEAR AFTER DEVELOPMENT AND MAY BE REACTIVATED IN ADULTHOOD WITHIN TISSUE-INJURY-ASSOCIATED DISEASES, INCLUDING IPF.

THE DYSREGULATION OF HH-ASSOCIATED ACTIVATING TRANSCRIPTION FACTORS, GENOMIC ABNORMALITIES, AND MICROENVIRONMENTS IS A CO-FACTOR THAT INDUCES THE INITIATION AND PROGRESSION OF IPF.

NLM-001, IS AN ORAL, SELECTIVE SMALL MOLECULE INHIBITOR OF THE HH PATHWAY, that BINDS TO SMOOTHEN PREVENTING ITS ACTIVATION BY HH LIGANDS. 

IN PRECLINICAL STUDIES OF DIFFERENT FIBROSIS MODELS SUCH AS BLEOMYCIN INDUCED SKIN FIBROSIS OR IPF AND DIET INDUCED HEPATIC FIBROSIS, THE AGENT HAS SHOWN SIGNIFICANT ANTI-FIBROTIC ACTIVITY.