FOG-001 Earns FDA Fast Track Designation in Desmoid Tumors

The FDA has granted fast track designation to FOG-001, an investigational inhibitor of β-catenin interactions, as a treatment for patients with desmoid tumors, according to a press release from the developer, Parabilis Medicines.¹

Developers engineered the first-in-class agent to directly target β-catenin interactions with the T-cell factor (TCF) family of transcription factors, thereby blocking the Wnt signaling pathway regardless of different APC and β-catenin mutations associated with disease. Unlike other Wnt/β-catenin pathway modulators, FOG-001 functions by binding directly to the key oncogenic driver β-catenin and blocking the Wnt pathway at the key downstream node.

“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 the press release.¹ “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.”

Assessment of the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of FOG-001 among those with advanced or metastatic solid tumors is currently underway in a phase 1/2 trial (NCT05919264). Investigators previously presented data from the study at the European Society for Medical Oncology Congress 2025 in Berlin, Germany.²

With a data cutoff of mid-August 2025 and 12 patients with desmoid tumors who received FOG-001 at the time of analysis, all evaluable patients (n = 10) experienced tumor reductions. Among those with more than 1 postbaseline scan, the objective response rate (ORR) was 80% per RECIST v1.1 criteria. Investigators reported responses regardless of prior treatment with γ-secretase inhibitors, progressive disease on prior γ-secretase inhibitors, tumor locations, or CTNNB1 or APC mutations.

Safety findings revealed no grade 4/5 treatment-related adverse effects (AEs) or therapy discontinuation following treatment with FOG-001. No patients had high-grade gastrointestinal or skin toxicities.

Developers plan to present additional clinical data related to FOG-001 in 2026.

Investigators of the first-in-human phase 1/2 trial are assessing FOG-001 alone and in combination with other therapies for patients with solid tumors that may harbor Wnt pathway–activating mutations across different dose-escalation and dose-expansion phases. Beyond desmoid tumors, the novel agent is being evaluated in patients with microsatellite-stable colorectal cancer, hepatocellular carcinoma, metastatic castration-resistant prostate cancer, and other disease types.³

The trial’s primary end points include number and severity of treatment-emergent AEs, dose-limiting toxicities, ORR per RECIST v1.1 guidelines, and the rate of responses with a 30% or greater reduction in prostate-specific antigen levels from baseline among those with prostate cancer. Secondary end points include duration of response, progression-free survival (PFS), time to progression, and radiographic PFS.

Patients 18 years or older with an ECOG performance status of 0 or 1 and adequate organ and marrow function were eligible for enrollment in the trial; those with desmoid tumors were eligible to enter parts 1d and 2d of the trial. Those with a known history of bone metastases or uncontrolled inflammatory bowel disease were ineligible to enroll.

“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. 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,” Mathai Mammen, MD, PhD, chairman and CEO of Parabilis Medicines, concluded.¹

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://tinyurl.com/ye279ca3
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(suppl 2):S1435-1436. doi:10.1016/j.annonc.2025.08.3299
3. FOG-001 in locally advanced or metastatic solid tumors. ClinicalTrials.gov. Updated October 24, 2025. Accessed November 12, 2025. https://tinyurl.com/m56cbk4f