Exesso Biopharma Confirms Intestinal Barrier Protection by '3,4-cPP' in IBD Animal Experiments

Exesso Biopharma's new drug candidate '3,4-cPP' has been shown to improve disease activity, weight loss, and colon tissue damage in animal models of inflammatory bowel disease (IBD). Unlike conventional IBD therapies that focus on suppressing immune responses, 3,4-cPP aims to restore both the intestinal mucosa and the vascular barrier, highlighting its potential as a next-generation treatment option.

According to Exesso Biopharma on August 27, the company evaluated the efficacy of 3,4-cPP by intravenously administering it to animal models with acute colitis induced by DSS. The results showed that higher doses of 3,4-cPP were associated with lower disease activity index (DAI) scores. In the high-dose group, weight loss was alleviated, while colon length and histological tissue damage improved as well.

The effects of 3,4-cPP were also observed in tissue staining. In the DSS-only group, clear signs of colon damage were detected, including ulceration, epithelial cell loss, and infiltration of inflammatory cells. However, these types of damage were reduced in the group receiving 3,4-cPP. In particular, the glycocalyx and mucus layer—which serve as protective barriers for the intestinal mucosa—remained intact in this group as well.

3,4-cPP is being developed with a differentiated mechanism of action compared to existing therapies. Some S1P-based therapies suppress inflammation by blocking lymphocyte migration. In contrast, 3,4-cPP aims to continuously activate S1PR1 and induce SIRT1 expression, thereby lowering inflammatory cytokines while simultaneously protecting the intestinal mucosa and the vascular barrier.

The company also conducted a comparative study involving oral administration. Research materials included results comparing 3,4-cPP at 5 mg/kg and the S1PR1 modulator ozanimod at 5 mg/kg, each administered orally, looking at disease activity, weight changes, colon length, and colon weight. Both drugs showed improvement in certain indicators compared to the DSS-only group. Based on these results, the company is preparing follow-up publications.

Pharmacokinetic studies were also carried out to confirm the potential for development as an oral therapeutic. The oral bioavailability of 3,4-cPP ranged from approximately 20.6% to 29.5%. After oral administration, the half-life was about 3.5 hours. With these findings, the company is considering the potential of developing 3,4-cPP as an oral maintenance therapy for IBD patients, who require chronic medication.

Within the IBD treatment market, 'mucosal healing,' or restoring the damaged intestinal mucosa, is recognized as an important therapeutic goal beyond merely suppressing inflammation, which is why there is growing interest in new approaches that protect and restore barrier function itself.

A representative from Exesso Biopharma stated, "For IBD, achieving mucosal healing—restoring the damaged intestinal lining—is a key treatment goal beyond just lowering inflammation. 3,4-cPP could offer a new therapeutic approach that regulates both inflammation and barrier damage without relying on excessive immunosuppression."

The representative added, "We plan to conduct repeated-dose toxicity studies, dose optimization, and formulation development, and we will further specify our clinical development strategy going forward."

This content was produced with the assistance of AI translation services.