O046 - A NOVEL LONG-ACTING GLP-2 ANALOG FT1 ATTENUATES CHEMOTHERAPY-INDUCED DIARRHEA VIA MUCOSAL RESTORATION: PRECLINICAL EVIDENCE FROM RODENT MODELS

O046

A NOVEL LONG-ACTING GLP-2 ANALOG FT1 ATTENUATES CHEMOTHERAPY-INDUCED DIARRHEA VIA MUCOSAL RESTORATION: PRECLINICAL EVIDENCE FROM RODENT MODELS

K. Fan^1,*, Q. Chen¹, K. Wu¹, Y. Peng¹, Y. He¹, Y. He¹, J. Sun¹

¹Chongqing Peg-Bio Biopharm Co., Ltd., Chongqing, China

Rationale: Chemotherapy-induced diarrhea (CID) remains a dose-limiting complication compromising anticancer efficacy. Mechanistic studies implicate intestinal mucosal injury in CID pathogenesis through impaired absorption. Based on the intestinal regenerative properties of GLP-2, we developed FT1, a long-acting GLP-2 analog with sustained exposure, to explore mucosal repair-based strategies for CID prevention.

Methods: Sprague-Dawley rats (n=8/group) received afatinib (30 mg/kg/day orally, days 8-21) to induce CID. Preventive interventions (days 1-21) included vehicle (s.c., twice weekly), FT1 (0.5/1.5/4.5 mg/kg, s.c., twice weekly), teduglutide (1.5 mg/kg/day, s.c.), and loperamide hydrochloride (10 mg/kg/day orally, days 8-21). Outcome measurements included daily diarrhea scores, body weight and food intake. Histopathological assessment included villus height, crypt depth, mucosal thickness, and intestine weight. Plasma citrulline levels were quantified as a functional biomarker.

Results: FT1 dose-dependently attenuated diarrhea severity (p<0.001, all doses vs vehicle). Mucosal restoration was demonstrated through increased intestinal weight, mucosal thickness and crypt depth (p<0.001 vs vehicle). Functional improvement correlated with dose-dependent citrulline elevation (p<0.001 vs vehicle). Notably, the comparable protection potential of FT1 was also observed in 5-fluorouracil-induced mice CID model.

Conclusion: FT1 demonstrates preclinical CID prevention efficacy through sustained mucosal repair capacity. The pharmacokinetic properties of FT1 enable intermittent dosing while maintaining therapeutic activity, suggesting potential translational advantages. These findings support further development of FT1 as a CID preventive agent for high-risk chemotherapy.

Disclosure of Interest: None declared