CAMBRIDGE, Mass. — Parabilis Medicines said the U.S. Food and Drug Administration has granted Orphan Drug Designation to its investigational therapy zolucatetide for the treatment of desmoid tumors, marking another regulatory milestone for the company’s lead candidate developed using its Helicon peptide platform.
Zolucatetide, previously known as FOG-001, is designed to directly inhibit the β-catenin:TCF interaction, a biological mechanism long considered difficult to target with drugs. The therapy has also received FDA Fast Track Designation for desmoid tumors.
“Patients living with desmoid tumors have lacked therapies that directly address the root biological cause of their disease because that biology, the β-catenin:TCF interaction, has long been considered ‘undruggable,’” said Mathai Mammen, M.D., Ph.D., Chairman, CEO and President of Parabilis Medicines. “With Orphan Drug Designation and Fast Track Designation from the FDA, along with compelling early clinical data showing encouraging evidence of clinical activity, we are building momentum behind zolucatetide as a potential first-in-class therapy that we believe could help redefine the standard of care for patients with desmoid tumors and other tumors driven by the same elusive biology. We are committed to advancing this program with rigor and speed to deliver meaningful impact for patients.”
Desmoid tumors are rare, locally aggressive soft-tissue tumors that form in connective tissue. Although they do not spread to other parts of the body, they can cause severe pain, restricted movement, disfigurement, and organ dysfunction, and they frequently recur after treatment.
Zolucatetide targets the Wnt/β-catenin signaling pathway, which plays a central role in the growth of desmoid tumors. Early clinical data presented at the European Society for Medical Oncology Congress and the Connective Tissue Oncology Society 2025 Annual Meeting showed encouraging activity, including tumor shrinkage and a 100% disease-control rate among 10 evaluable patients who had at least one post-baseline scan. Among five patients with multiple scans, the therapy demonstrated an 80% objective response rate under RECIST 1.1 criteria.
The FDA grants Orphan Drug Designation to therapies intended for rare diseases affecting fewer than 200,000 people in the U.S. The designation provides incentives such as potential tax credits for clinical trial costs, waiver of certain regulatory fees, and up to seven years of market exclusivity following approval.
Beyond desmoid tumors, Parabilis is evaluating zolucatetide in multiple cancers driven by Wnt/β-catenin signaling. Data presented at the AACR-NCI-EORTC 2025 meeting showed single-agent activity in several tumor types in which mutations in the pathway are primary drivers, including adamantinomatous craniopharyngioma, ameloblastoma, salivary gland cancer, and solid pseudopapillary neoplasm. The company has also reported early signals of potential activity in hepatocellular carcinoma and familial adenomatous polyposis.
Zolucatetide is currently being studied in a Phase 1/2 multicenter, open-label clinical trial evaluating safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity in patients with locally advanced or metastatic solid tumors. The study includes both dose-escalation and expansion phases and is testing the therapy as a monotherapy and in combination with other anticancer agents. More than 150 patients have been treated so far, and additional data readouts are expected in 2026.
