FDA Fast Tracks FOG-001 After Early Tumor Shrinkage in Desmoid Tumors

The U.S. Food and Drug Administration (FDA) has granted fast track product designation to FOG-001 for the treatment of desmoid tumors, according to a news release from Parabilis Medicines.

This is the first treatment shown to directly block the β-catenin–TCF interaction, a target long considered “undruggable” because it’s been so difficult to hit with medicine.

“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,” Dr. Fawzi Benzaghou, 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. 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.”

Fast track is an FDA program that helps speed up the development and review of treatments for serious conditions when there’s an urgent need for better options.

Early results from an ongoing phase 1/2 study show that FOG-001 has led to measurable tumor shrinkage in patients with desmoid tumors. Among the 10 patients in the trial who could be evaluated for response, every person experienced some level of tumor reduction. For the five patients who had more than one post-baseline scan, the objective response rate was 80%. These responses happened regardless of where the tumor was located, whether patients had previously taken or progressed on gamma secretase inhibitors, or whether they had mutations in CTNNB1 or APC.

As of the mid-August 2025 data cutoff, 12 patients with desmoid tumors had been treated with FOG-001 in this early-phase study. The treatment was generally well tolerated. There were no grade 4 (life-threatening) or 5 (fatal) treatment-related side effects, and no one stopped treatment because of side effects. Investigators also did not see severe gastrointestinal or skin toxicities.

These findings build on preliminary data first shared at an ESMO meeting and being presented again this week at the Connective Tissue Oncology Society 2025 Annual Meeting. Desmoid tumors are rare, locally invasive soft-tissue tumors that form in the body’s connective tissues and can cause pain, limited mobility, changes in appearance and organ problems, as per the release. Although they can significantly affect day-to-day life, there are still no FDA-approved treatments that directly target the biology of this disease.

“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,” Dr. Mathai Mammen, chairman and CEO of Parabilis Medicines, said in the news release. “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.”

Additional Information

FOG-001 is also being studied in several other rare and more common tumors that are driven by changes in the Wnt/β-catenin pathway. Early clinical data have shown that FOG-001 can work on its own in five tumor types where these mutations are the main cause of disease. These include desmoid tumors, adamantinomatous craniopharyngioma, ameloblastoma, salivary gland cancer and solid pseudopapillary neoplasms. Researchers are also exploring whether it may be useful in combination with other treatments for more complex cancers such as microsatellite-stable colorectal cancer. More data are expected in 2026.

FOG-001 is an investigational therapy designed to block a key signaling pathway that helps certain tumors grow. It works inside the cell to disrupt the interaction between β-catenin and the TCF family of transcription factors, which is a central step in the Wnt pathway. Because it targets this pathway directly, FOG-001 is intended to work regardless of the specific APC or β-catenin mutations that may be present.

FOG-001 is currently being tested in a first-in-human Phase 1/2 clinical trial for people with locally advanced or metastatic solid tumors.

Reference

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,” Parabilis Medicines. News Release. Nov. 12, 2025.

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