CAMBRIDGE, Mass. — Parabilis Medicines reported preliminary clinical evidence that its investigational drug zolucatetide may reduce polyp burden in patients with familial adenomatous polyposis (FAP), according to early findings presented at the 11th Biennial Meeting of the International Society for Gastrointestinal Hereditary Tumours.
The Cambridge-based clinical-stage biopharmaceutical company said the data come from an ongoing Phase 1/2 trial evaluating zolucatetide, a direct inhibitor of the β-catenin:TCF interaction designed to target a key molecular driver of the disease.
In the trial, a patient with FAP and an associated desmoid tumor experienced significant improvement in duodenal polyposis after 60 weeks of treatment with zolucatetide. Researchers observed substantial reductions in both the number and size of polyps compared with a pre-treatment assessment conducted nearly two years earlier. The improvement corresponded with a downstaging of disease severity from Spigelman stage II to stage I.
The patient also showed a 52.2 percent reduction in desmoid tumor diameter during treatment. According to the company, no treatment-related serious adverse events or treatment discontinuations were reported.
Complementary preclinical research also showed dose-dependent inhibition of β-catenin transcriptional activity in APC mutant tumor cells. In a mouse model of FAP, the therapy reduced polyp formation at exposure levels similar to those used in the ongoing clinical trial.
“Patients with FAP face a lifetime of intensive surveillance and often prophylactic colectomy, yet there are no approved therapies,” said Mathai Mammen, M.D., Ph.D., Chairman, CEO and President of Parabilis Medicines. “These early findings suggest that directly inhibiting β-catenin, the key driver of tumor formation in FAP, may offer a new way to intervene at the source of disease. Our goal is to move beyond managing polyp burden and toward altering the course of disease for patients suffering from FAP.”
Familial adenomatous polyposis is a rare inherited disorder affecting an estimated 34,000 people in the United States. The condition is caused by mutations in the APC gene that lead to continuous activation of Wnt/β-catenin signaling and the formation of hundreds to thousands of precancerous colorectal adenomas. Without treatment, the disease almost inevitably progresses to colorectal cancer.
Management typically involves intensive surveillance and prophylactic colectomy, often performed at a young age. However, the surgery does not prevent other manifestations of the disease, including duodenal polyposis, rectal polyposis, and desmoid tumors.
Zolucatetide is designed to directly inhibit the interaction between β-catenin and T-cell factor transcription factors, blocking a key step in the Wnt signaling pathway that drives tumor formation. The investigational therapy is being evaluated across multiple rare and common tumors driven by Wnt/β-catenin signaling.
The company said the drug has shown early single-agent activity in desmoid tumors and is also being studied in conditions including adamantinomatous craniopharyngioma and hepatocellular carcinoma. The therapy received Fast Track Designation from the U.S. Food and Drug Administration for the treatment of desmoid tumors.
Parabilis Medicines said more than 150 patients have been treated with zolucatetide across its ongoing Phase 1/2 clinical trial, with additional data readouts expected in 2026.
