Calibr-Skaggs advances CLF065, a regenerative GLP-2 therapy, into two Phase 2 IBD studies

LA JOLLA, CA-The Calibr-Skaggs Institute for Innovative Medicines, the nonprofit drug development arm of Scripps Research, today announced two milestones in the clinical advancement of CLF065, its potential best-in-class, long-acting glucagon-like peptide-2 (GLP-2) receptor agonist in development for inflammatory bowel diseases (IBD). Calibr-Skaggs has enrolled the first patient in its Phase 2 study of CLF065 in chronic pouchitis and has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration for a Phase 2, 105-patient study in Crohn's disease. Interest in next-generation GLP-2 analogs has accelerated with active programs from Ironwood, Zealand, and recently Lilly/Hanmi targeting short bowel syndrome. CLF065 is the first long-acting GLP-2 analog to enter Phase 2 trials specifically for IBD, with a pharmacology that supports the potential for once-monthly dosing intervals.

Whereas most approved IBD treatments reduce disease activity through anti-inflammatory or immune-modulating mechanisms, CLF065 targets a key underlying contributor to disease: epithelial barrier dysfunction, the breakdown of the protective intestinal lining that regulates what passes from the gut into the body. By supporting barrier integrity and stimulating regeneration of the gut lining, CLF065 aims to deliver a regenerative, dual-mechanism approach to achieve mucosal healing.

The molecule was created using Calibr-Skaggs' proprietary stapled-peptide technology, which stabilizes the GLP-2 peptide and markedly extends its half-life. In a first-in-human Phase 1 study (N=106 healthy volunteers) completed in 2024, CLF065 was well tolerated across all doses: All treatment-related adverse events were mild and resolved, and no treatment-related serious adverse events were reported. CLF065 demonstrated a half-life supporting once-weekly subcutaneous dosing and produced a sustained, dose-dependent increase in plasma citrulline, an established biomarker of intestinal mucosal growth, that provides a pharmacodynamic basis for monthly dosing intervals.

CLF065 reflects exactly the kind of differentiated science Calibr-Skaggs was built to pursue, using our peptide engineering platform to open up a therapeutic opportunity others have overlooked, said Peter Schultz, PhD, president and chief executive officer of Calibr-Skaggs and Scripps Research. As a nonprofit, our goal is to translate breakthrough biology into medicines for patients with the greatest unmet need. Chronic pouchitis and Crohn's disease are precisely those types of conditions.

The Phase 2 pouchitis study (the OPUS-Pouch Study) is a randomized, placebo-controlled trial that is now enrolling to evaluate the efficacy and safety of CLF065 in patients who continue to experience symptoms after J-pouch surgery related to ongoing intestinal inflammation. The IND filing for the Phase 2 Crohn's disease study (RESET-CD) extends the program into a second IBD indication, which is expected to begin in fall 2026. A positive proof-of-concept in pouchitis-a well-defined population with clear endoscopic and histologic readouts-would also help derisk and inform development across broader IBD phenotypes.

The growing investment in GLP-2 across the industry validates what our science has pointed to for years: GLP-2 receptor biology has therapeutic potential well beyond its origins, said Amy Lightner, MD, MBA, chief medical officer at Calibr-Skaggs and principal investigator of the pouchitis study. Most of the field is focused on short bowel syndrome, but we took CLF065 in a different direction. For people with IBD, today's therapies focus almost entirely on suppressing inflammation, without repairing the damaged intestinal lining that drives the disease. CLF065 is designed to both actively regenerate and repair the gut epithelium, thereby complementing anti-inflammatory agents to change the IBD treatment paradigm.

While chronic pouchitis is not as prevalent or well-known as Crohn's disease, it is the most common long-term complication of J-pouch (ileal pouch-anal anastomosis) surgery, a procedure frequently performed in patients with ulcerative colitis. Approximately 200,000 individuals in the U.S. live with an ileal pouch and up to 30% of this group develop chronic pouchitis, marked by frequent bowel movements, fecal urgency, abdominal pain, dehydration and fatigue. There are no FDA-approved therapies specifically for pouchitis, leaving a substantial unmet need.

The OPUS-Pouch Study and RESET-CD CLF065 are supported by a mission-aligned investment structure, Vx Capital, established in 2026 by Scripps Research to advance three regenerative clinical-stage programs. Scripps Research retains full intellectual property rights and program oversight for the CLF065 Program.

LINK:	https://www.scripps.edu/news-events/news/20260610-calibr-clf065/...
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