# Targeting Irritable Bowel Syndrome (IBS) with astressins

> **NIH NIH R44** · SENTIA MEDICAL SCIENCES, INC. · 2020 · $875,078

## Abstract

Abstract
Sentia seeks to bring to fruition 40 years (1975 - 2015) of NIDDK-funded (P01 DK026741; PIs: W. Vale, C.
Rivier, J. Spiess and J. Rivier) academic research to achieve translational drug candidacy by blocking both
corticotropin-releasing factor (CRF) receptors CRF1/2 with potent astressin peptide antagonists. Present
assets of Sentia include world-wide, patent-protected, "first-in-class" peptide drug candidates and intellectual
property that targets, among others, the regulation of the stress response system. Scientific evidence
documents that potentially dozens of current human ailments can benefit from the use of stress-neutralizing
compounds to achieve temporal or permanent homeostasis. In particular, irritable bowel syndrome (IBS) is well
established to be a stress-sensitive condition with visceral pain being the hallmark. Alleviating visceral pain in
IBS patients is still an unmet need and the market for managing and/or curing the symptoms is conservatively
estimated to be in the $5-10B range. Astressin therapeutics would represent a "first-in-class" opportunity to
safely and effectively treat IBS patients with injectable peptide analogs that could represent a paradigm shift in
therapeutic intervention away from conventional short-acting oral small molecules providing patients a different
option for long-acting relief. In our Phase I SBIR studies, a new Fmoc synthetic process for making astressins
was successfully validated and activity of these drug candidates was demonstrated after acute testing in an IP
CRF-induced model of visceral hypersensitivity. The objective of the Phase II SBIR is to further supply relevant
quantities of astressin CRF1/2 antagonists (compounds 1-3) manufactured following the Fmoc strategy to
support non-GLP chronic pharmacology studies and to evaluate the drug metabolism and pharmacokinetic
(DMPK) and toxicological profile of the compounds. In Aim 1, additional quantities of astressins required for the
proposed non-GLP studies will be synthesized. Synthetic methods will be transferred to a CRO in preparation
for future larger scale synthesis. The goal of Aim 2 will be to develop bioanalytical methods for detection of the
astressin drug candidate as well as to establish the DMPK profile of the compounds and Aim 3 will evaluate
the chronic efficacy of the astressin drug candidates in both prophylactic and therapeutic modalities in a
pharmacological and disease model of IBS, respectively. Aim 4 will assess the in vivo and in vitro toxicological
profile after acute and repeat dosing. The data package will provide sufficient information on efficacy and
therapeutic margins to select a candidate(s) for further evaluation, IND-enabling studies and clinical
development.

## Key facts

- **NIH application ID:** 9925223
- **Project number:** 5R44DK116362-03
- **Recipient organization:** SENTIA MEDICAL SCIENCES, INC.
- **Principal Investigator:** DOMINIC BEHAN
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $875,078
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9925223

## Citation

> US National Institutes of Health, RePORTER application 9925223, Targeting Irritable Bowel Syndrome (IBS) with astressins (5R44DK116362-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9925223. Licensed CC0.

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