We have developed a candidate product that induces colon epithelial repair in ulcerative colitis (UC) models. UCcomprises a major type of inflammatory bowel disease and is characterized by chronic and relapsinginflammation in the gastrointestinal (GI) tract. UC develops in the innermost mucosal layer of the distal GI tractin a continuous manner, usually starting at the rectum and spreading into the colon. The etiology of UC remainselusive; genetic and environmental factors appear to trigger dysregulated mucosal immune responses, leadingto chronic inflammation, disrupted intestinal barrier function and epithelial damage in the colon. Lacking adefinitive cause, no preventative or curative therapies have been developed for UC. Conventional treatmentsaim to blunt inflammation, establish and maintain clinical remission, mucosal healing, decrease the risk ofcomplications and improve quality of life. Achieving mucosal healing is recognized as an important clinicalendpoint in UC treatment, as it is closely associated with sustained clinical remission, improved quality of life,fewer surgical interventions and cancer incidence, as shown in clinical studies. However, current UC drugs donot effectively induce mucosal healing because merely inhibiting inflammation will not necessarily facilitate tissuerepair, which is a complex and dynamic process that must involve the restoration of the intestinal barrier functionalong with alleviation of detrimental inflammation. Thus, development of an epithelial wound repair agent willfill an important gap for the management of UC.Our lead product, EPICERTIN, is a recombinant protein derived from cholera toxin B subunit that has beenmodified genetically with a C-terminal peptide containing the KDEL endoplasmic reticulum retention signal. Thissimple modification instills in EPICERTIN the colon epithelial wound healing activity. EPICERTIN is our leadactive pharmaceutical ingredient for managing UC via epithelial barrier recovery. University of Louisville (UofL)researchers invented EPICERTIN and extensively characterized its biological mode of action (MOA) andtherapeutic effects in acute and chronic animal models of colitis. The MOA involves an unfolded proteinresponse, and all preliminary studies have underscored high safety and tolerability upon oral or colonicadministrations to animals. We have initiated pre-IND discussions with FDA and have received initial Agencyguidance, which has substantially reduced regulatory risk. Following FDA's and NIH reviewers'recommendations, UofL and its commercial partner GROW Biomedicine LLC are initiating product-focuseddevelopment of EPICERTIN through this Phase I STTR project with the goals of: (1) further exploring dose-effectrelationships in vivo in a rat model of UC to support future pharmacodynamic and toxicity studies, and (2)expanding the range of applications of our bioanalytical method to quantify the drug in canine plasma, and usingthe results of the two aims to revise our nonclinical development plan and seek further Agency input to supporta future IND submission for a first-in-human clinical study.
Public Health Relevance Statement: Narrative
Investigators at University of Louisville (UofL; academic institution) have partnered with GROW Biomedicine LLC
(small business company) to develop a rectal enema containing the potent wound-healing and tissue-repair
protein EPICERTIN as a candidate biologic for the non-immunosuppressive management of ulcerative colitis
(UC). In pre-IND communications, FDA requested additional structural and biologic characterization of
EPICERTIN including dose optimization in vivo, expansion of analytical capabilities and a revision of our
nonclinical study plan, as prerequisites to future clinical development of this novel product. The goal of this
project is to address FDA's recommendations and provide some of the key data needed to support a future first-
in-human clinical study, thereby accelerating commercial development of UofL/GROW Biomedicine's first-in-
class, wound-healing biotherapeutic for UC.
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