Zolucatetide Receives Orphan Drug Designation for Desmoid Tumors

The FDA has granted orphan drug designation to zolucatetide (formerly FOG-001) for the treatment of desmoid tumors, according to a press release from the developer, Parabilis Medicines.¹ This investigational agent is the first and only direct inhibitor of the β-catenin:T-cell factor (TCF) interaction to reach this regulatory milestone.

Previously, in November 2025, the FDA granted fast track designation to zolucatetide for the treatment of patients with desmoid tumors.² Furthermore, supportive results for both indications were shared at the 2025 European Society of Medical Oncology Congress.³

Clinical Context and Supportive Data

The regulatory designation is supported by preliminary clinical data from an ongoing phase 1/2 trial (NCT05919264), which has demonstrated early signs of antitumor activity and a manageable safety profile.

In the trial, a total of 12 patients with desmoid tumors had received treatment with zolucatetide across 3 dose levels. At least 10 of those patients had at least 1 post-baseline scan at the time of data reporting. A disease control rate (DCR) of 100% was observed in all patients across all dose levels. Furthermore, of 5 patients with more than 1 post-baseline scan, the objective response rate (ORR) per RECIST v1.1 was 80%. Notably, responses were noted in patients who were secretase-naïve and secretase-treated.

“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,’” stated Mathai Mammen, MD, PhD, chairman, chief executive officer, and president of Parabilis Medicines, in the release.¹ “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…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.”

Regarding safety data, zolucatetide was well-tolerated, demonstrating an acceptable safety profile in patients with desmoid tumors.

Comprehensive Trial Breakdown: NCT05919264

The ongoing phase 1/2 clinical trial is a multicenter, open-label study designed to evaluate the safety, tolerability, and preliminary efficacy of zolucatetide in patients with advanced solid tumors likely or known to have Wnt pathway–activating mutations.⁴ The study consists of 2 primary phases: a dose-escalation phase to determine the maximum tolerated dose and a dose-expansion phase to further investigate activity in specific tumor cohorts, including desmoid tumors, colorectal cancer, and familial adenomatous polyposis.

Eligible patients also had an ECOG performance status of 0 or 1, and adequate organ and marrow function. Exclusion criteria included known history of bone metastasis, evidence of vertebral compression fracture or non-traumatic bone fracture, uncontrolled inflammatory bowel disease, and unstable/inadequate cardiac function.

Patients enrolled in the desmoid tumor cohort are administered intravenous zolucatetide over continuous 28-day cycles. The primary end points of the trial were incidence and severity of treatment-emergent adverse events, dose-limiting toxicities, ORR, and DCR.

Future Directions

The developers plan to expand the clinical investigation of zolucatetide into broader Wnt-driven indications. The upcoming phase 2 expansion cohorts will prioritize patients with desmoid tumors who are refractory to current therapies. Furthermore, the Helicon peptide platform used to create zolucatetide is being monitored for its ability to target other intracellular protein-protein interactions previously deemed undruggable.

References

1. Parabilis Medicines’ zolucatetide, the first and only direct inhibitor of the elusive β-catenin:TCF interaction, receives FDA orphan drug designation for the treatment of desmoid tumors. News release. Parabilis Medicines. March 11, 2026. Accessed March 12, 2026. https://tinyurl.com/562jzr4c
2. Parabilis Medicines receives FDA fast track designation for FOG-001, the first and only direct inhibitor of the β-catenin:TCF interaction, for the treatment of desmoid tumors. News release. Parabilis Medicines. November 12, 2025. Accessed March 12, 2026. https://tinyurl.com/bdejvb34
3. Parabilis Medicines presents clinical data demonstrating first-ever drugging of key cancer driver with FOG-001. News release. Parabilis Medicines. October 17, 2025. Accessed March 12, 2026. https://tinyurl.com/3x37x9kf
4. FOG-001 in locally advanced or metastatic solid tumors. ClinicalTrials.gov. Updated February 10, 2026. Accessed March 12, 2026. https://tinyurl.com/myk73s4j