The FDA has granted fast track designation to FOG-001, an investigational first-in-class inhibitor of β-catenin interactions, for the treatment of patients with desmoid tumors, according to Parabilis Medicines. This designation facilitates development and expedites review of therapies addressing serious conditions with unmet medical needs.
FOG-001 represents a novel approach to targeting the Wnt signaling pathway by directly binding to β-catenin and blocking its interactions with the T-cell factor (TCF) family of transcription factors. Unlike other Wnt/β-catenin pathway modulators, the agent functions by targeting the key oncogenic driver β-catenin directly at the downstream node, regardless of different APC and β-catenin mutations associated with disease.
Clinical Trial Results Show Promising Efficacy
Assessment of FOG-001's safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity is currently underway in a phase 1/2 trial (NCT05919264) among patients with advanced or metastatic solid tumors. Data presented at the European Society for Medical Oncology Congress 2025 demonstrated significant clinical activity in desmoid tumors.
With a data cutoff of mid-August 2025, all 10 evaluable patients with desmoid tumors experienced tumor reductions. Among the 5 patients with more than one postbaseline scan, the objective response rate reached 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.
Favorable Safety Profile Observed
Safety findings revealed no grade 4/5 treatment-related adverse effects or therapy discontinuation following treatment with FOG-001 among the 12 patients treated. Notably, no patients experienced high-grade gastrointestinal or skin toxicities, addressing common concerns associated with Wnt pathway targeting.
"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," stated Fawzi Benzaghou, MD, chief medical officer of Parabilis Medicines. "More than half of patients do not respond to current treatment options, which are also associated with high toxicities."
Broader Development Program Underway
The first-in-human phase 1/2 trial is evaluating FOG-001 both as monotherapy and in combination with other therapies across different dose-escalation and dose-expansion phases. Beyond desmoid tumors, the agent is being assessed in patients with microsatellite-stable colorectal cancer, hepatocellular carcinoma, metastatic castration-resistant prostate cancer, and other disease types.
Primary endpoints include the number and severity of treatment-emergent adverse events, dose-limiting toxicities, objective response rate per RECIST v1.1 guidelines, and the rate of responses with 30% or greater reduction in prostate-specific antigen levels among prostate cancer patients. Secondary endpoints encompass duration of response, progression-free survival, time to progression, and radiographic progression-free survival.
Addressing an Undruggable Target
"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," noted Mathai Mammen, MD, PhD, chairman and CEO of Parabilis Medicines. "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."
Parabilis Medicines plans to present additional clinical data related to FOG-001 in 2026, with further results expected at the Connective Tissue Oncology Society 2025 Annual Meeting demonstrating clinically meaningful antitumor activity in desmoid tumors.
