FDA Grants Fast Track Designation to FOG-001 for Desmoid Tumors

The FDA has granted fast track designation to FOG-001 for the treatment of patients with desmoid tumors.1

The investigational helicon peptide FOG-001 is the first direct inhibitor of the β-catenin:T-cell factor (TCF) interaction, according to a news release from Parabilis Medicines. In targeting this interaction, FOG-001 is designed to block the Wnt signaling pathway regardless of the presence of APC and β-catenin mutations, which are known to drive desmoid tumors.

“Obtaining fast track designation for FOG-001 reinforces our confidence in its potential to offer meaningful clinical benefit to patients with desmoid tumors, who today have no therapies that directly address the underlying disease biology,” Fawzi Benzaghou, MD, chief medical officer of Parabilis Medicines, stated in a news release. “More than half of patients do not respond to current treatment options, which are also associated with high toxicities. By inhibiting the β-catenin:TCF interaction, FOG-001 has the potential to intervene at the source of disease and marks an important step forward in advancing our mission to drug the undruggable.”

Data from a phase 1/2 trial (NCT05919264) presented at the 2025 ESMO Congress demonstrated that in response-evaluable patients with desmoid tumors (n = 10) who underwent at least 1 post-baseline scan, FOG-001 generated a disease control rate (DCR) of 100%, with tumor reductions observed across all dose levels.2 Those who underwent more than 1 post-baseline scan (n = 5) achieved an overall response rate (ORR) of 80%. Notably, responses were experienced by patients who were naive to and previously exposed to gamma-secretase inhibitors.

Regarding safety, 83.3% patients treated with FOG-001 at doses of 72 mg/m2, 240 mg/m2, or 480 mg/m2 (n = 12) experienced at least 1 any-grade treatment-related adverse effect (TRAE). The rate of grade 3 or higher TRAEs was 16.7%. The most common any-grade TRAEs included fatigue (58.3%), alopecia (50.0%), increased aspartate aminotransferase levels (41.7%), nausea (41.7%), increased alanine aminotransferase levels (33.3%), increased blood bilirubin levels (33.3%), epistaxis (33.3%), and hypoaldosteronism (25.0%). Notably, no TRAEs led to treatment discontinuation.

What is the design of the phase 1/2 trial investigating FOG-001?

The multicenter, open-label, non-randomized, dose-escalation and -expansion phase 1/2 study is examining FOG-001 both as monotherapy and in combination with other anticancer agents in patients with locally advanced or metastatic solid tumors that are likely or known to have Wnt pathway activating mutations.3 Patients must be at least 18 years of age to enroll. Both the dose-escalation and -expansion phases of the study include cohorts for patients with desmoid tumors with aggressive fibromatosis. Key inclusion criteria for all patients include an ECOG performance status of 0 or 1, and adequate organ and bone marrow function.

Patients are being excluded if they have a history of bone metastases, other than patients with metastatic castration-resistant prostate cancer; evidence of vertebral compression fracture or non-traumatic bone fracture within 12 months of enrollment; osteoporosis; uncontrolled inflammatory bowel disease; unstable/inadequate cardiac function; or known meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases.

In the desmoid tumor cohorts, FOG-001 is being administered intravenously in continuous 28-day cycles.

Safety, the incidence of dose-limiting toxicities, ORR, and DCR are serving as the trial’s primary end points. Secondary end points include pharmacokinetics, duration of response, and progression-free survival.

“The Wnt/β-catenin pathway is implicated in millions of cancer cases each year, yet remains unaddressed by any approved therapies despite decades of effort,” Mathai Mammen, MD, PhD, chairman and chief executive officer of Parabilis Medicines, added in a news release.1 “FOG-001 demonstrates that our helicon peptides can unlock disease biology once considered completely inaccessible—opening a new path to drug targets long thought out of reach and medicines with the potential to fundamentally transform outcomes for patients.”

References

1. 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 November 12, 2025. https://parabilismed.com/press-release/parabilis-medicines-receives-fda-fast-track-designation-for-fog-001-the-first-and-only-direct-inhibitor-of-the-%ce%b2-catenintcf-interaction-for-the-treatment-of-desmoid-tumors/
2. Cote GM, Cecchini M, Papadopoulos KP, et al. A phase I/II trial of FOG-001, a first-in-class direct β-catenin:TCF4 inhibitor - safety and preliminary antitumor activity in patients with desmoid tumors. Ann Oncol. 2025; 36(suppl2): S1435-S1436. doi: 10.1016/j.annonc.2025.08.3
3. FOG-001 in locally advanced or metastatic solid tumors. ClinicalTrials.gov. Updated October 24, 2025. Accessed November 12, 2025. https://clinicaltrials.gov/study/NCT05919264