AVEXEGEN THERAPEUTICS INC. — Department of Health and Human Services SBIR Phase I: 300

Description

ABSTRACT Inflammatory Bowel Disease IBD is a collective name for Crohn s Disease and Ulcerative Colitis UC Both conditions manifest with a pathological inflammation of the bowel that causes breaks in mucosal integrity frank ulceration and the risk of more severe complications While the etiology of IBD is complex and not fully understood the two distinguishing hallmarks of IBD are dysregulation of normal immune function and impaired epithelial repair None of the currently available treatment modalities have a specific targeted effect to retain mucosal integrity or to heal breaches in the gut mucosa Moreover most drugs in development are focused on modifying the local inflammatory response and not on protection and repair of the intestinal epithelium It is highly attractive if a treatment modality could indeed target the damaged gut mucosa as this would complement approaches directed to the abnormal inflammatory response Such a treatment paradigm would retain mucosal integrity and prevent or ameliorate a local breach thereby reducing the impact infiltrating external intra luminal factors may have on the pathophysiological process Additionally it could facilitate healing of breaches in the mucosa and restore integrity Avexegen Therapeutics Inc in collaboration with Mark Frey s group at Children s Hospital Los Angeles CHLA has identified Neuregulin NRG a naturally occurring constituent of human breast milk as a novel mucosal healing peptide NRG leverages physiological mechanisms to both directly protect the intestinal epithelium and to attenuate the inflammatory cascade These actions have been shown to promote mucosal healing and the restoration of the damaged gut barrier in multiple experimental animal models of intestinal inflammation The NRG product platform offers a wide range of product forms for the treatment of IBD Based on the evidence gathered thus far NRG has a high potential for being a stand alone treatment for these disorders or a complement to other treatment approaches In this SBIR Phase I project Avexegen aims to establish a independent confirmation of pre clinical findings from the Frey lab on the therapeutic potential of NRG as a mucosal healing factor This will be done by a week in vitro potency determination study followed by an week dose response study in a DSS mouse model b Proof of concept of efficacy of oral administration in an IBD disease model This will be done by first conducting a week signaling study to demonstrate luminal ErbB receptor activation upon oral NRG administration and in vitro assessment of metabolic stability in a pancreatic digestive enzyme mix Next a month analytical method and formulation development study will be conducted and then followed with an week dose response study in a DSS mouse model using an oral NRG formulation These studies will add to the pre clinical data package for filing the IND and help transform IBD treatment and potentially other gastro intestinal disorders where the repair and retention of intestinal mucosal integrity are key treatment objectives NARRATIVE Inflammatory Bowel Disease IBD affect more than million patients in the US and manifest with a pathological inflammation of the bowel that causes breaks in mucosal integrity frank ulceration and the risk of more severe complications Current treatment approaches have shortcomings Avexegen Therapeutics Inc has identified Neuregulin NRG as a novel physiological mucosal healing peptide that directly promotes healing of inflamed and damaged intestinal tissue and therefore restoration of mucosal integrity Here Avexegen is seeking to advance this compelling new peptide biology to an important new pharmacological application for the treatment of IBD