EPICERTIN for Mucosal Healing in Ulcerative Colitis

Project Summary
We have developed a candidate product that induces colon epithelial repair in ulcerative colitis (UC) models. UC
comprises a major type of inflammatory bowel disease and is characterized by chronic and relapsing
inflammation in the gastrointestinal (GI) tract. UC develops in the innermost mucosal layer of the distal GI tract
in a continuous manner, usually starting at the rectum and spreading into the colon. The etiology of UC remains
elusive; genetic and environmental factors appear to trigger dysregulated mucosal immune responses, leading
to chronic inflammation, disrupted intestinal barrier function and epithelial damage in the colon. Lacking a
definitive cause, no preventative or curative therapies have been developed for UC. Conventional treatments
aim to blunt inflammation, establish and maintain clinical remission, mucosal healing, decrease the risk of
complications and improve quality of life. Achieving mucosal healing is recognized as an important clinical
endpoint 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 do
not effectively induce mucosal healing because merely inhibiting inflammation will not necessarily facilitate tissue
repair, which is a complex and dynamic process that must involve the restoration of the intestinal barrier function
along with alleviation of detrimental inflammation. Thus, development of an epithelial wound repair agent will
fill an important gap for the management of UC.
Our lead product, EPICERTIN, is a recombinant protein derived from cholera toxin B subunit that has been
modified genetically with a C-terminal peptide containing the KDEL endoplasmic reticulum retention signal. This
simple modification instills in EPICERTIN the colon epithelial wound healing activity. EPICERTIN is our lead
active 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) and
therapeutic effects in acute and chronic animal models of colitis. The MOA involves an unfolded protein
response, and all preliminary studies have underscored high safety and tolerability upon oral or colonic
administrations to animals. We have initiated pre-IND discussions with FDA and have received initial Agency
guidance, which has substantially reduced regulatory risk. Following FDA’s and NIH reviewers’
recommendations, UofL and its commercial partner GROW Biomedicine LLC are initiating product-focused
development of EPICERTIN through this Phase I STTR project with the goals of: (1) further exploring dose-effect
relationships 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 using
the results of the two aims to revise our nonclinical development plan and seek further Agency input to support
a future IND submission for a first-in-human clinical study.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 Biomedicineandapos;s first-in-
class, wound-healing biotherapeutic for UC.