On November 12, 2025 Parabilis Medicines, a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track product designation to FOG-001 for the treatment of desmoid tumors, reflecting significant unmet need and the potential of this first-in-class therapy to transform patient care. FOG-001, Parabilis’s lead investigational Helicon peptide, is the first and only direct inhibitor of the "undruggable" β-catenin:TCF interaction.
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The FDA’s Fast Track designation is intended to help facilitate the development and expedite the review of new therapies for serious conditions that address an unmet medical need. A therapy may qualify if it targets a disease with no existing treatments, or if it offers a meaningful advantage over available options – such as showing superior effectiveness, avoiding serious side effects, or decreasing toxicities that frequently cause discontinuation of treatment. Fast Track designation enables more frequent interactions with the FDA throughout development and provides eligibility for features like Rolling Review and potential Priority Review, helping promising medicines reach patients sooner.
"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," said Fawzi Benzaghou, M.D., 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."
This designation follows preliminary data, first released at ESMO (Free ESMO Whitepaper) and to be presented this week at the Connective Tissue Oncology Society (CTOS) 2025 Annual Meeting, demonstrating that FOG-001 has shown evidence of clinically meaningful antitumor activity in desmoid tumors. Desmoid tumors are rare, locally invasive soft-tissue tumors that form in the connective tissues of the body, often causing pain, limited mobility, disfigurement, and organ dysfunction. Despite its impact on quality of life, there are no FDA-approved therapies that directly target the underlying biology of the disease.
In the company’s ongoing Phase 1/2 trial, as of the mid-August 2025 data cutoff, 12 patients with desmoid tumors had been treated with FOG-001. Tumor reductions were seen in all response-evaluable patients (n=10), and an 80% objective response rate (ORR) was seen in patients with more than one post-baseline scan (n=5), per RECIST 1.1. These responses were irrespective of prior exposure to gamma secretase inhibitors, progression on gamma-secretase inhibitors, tumor location, or mutations in CTNNB1 or APC. FOG-001 also demonstrated an acceptable safety and tolerability profile, with no Grade 4/5 treatment-related adverse events or discontinuations. No high-grade gastrointestinal (GI) or skin toxicities were observed.
"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," said Mathai Mammen, M.D., Ph.D., 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 and medicines with the potential to fundamentally transform outcomes for patients."
Beyond desmoid tumors, FOG-001 is being evaluated across a broad range of rare and common Wnt/β-catenin-driven tumor types. Clinical data presented recently at the AACR (Free AACR Whitepaper)-NCI-EORTC 2025 meeting showed FOG-001 had single-agent activity in five low-complexity tumor types where Wnt/β-catenin mutations are the primary drivers of disease – including desmoid, adamantinomatous craniopharyngioma (ACP), ameloblastoma, salivary gland cancer, and solid pseudopapillary neoplasm (SPN) – with strong scientific rationale for combination therapy in more complex cancers such as microsatellite-stable colorectal cancer (MSS CRC).
Parabilis plans to share additional FOG-001 data in 2026.
About FOG-001
FOG-001 is an investigational first-in-class competitive inhibitor of β-catenin interactions with the T-cell factor (TCF) family of transcription factors and is currently in clinical development. By directly targeting the β-catenin:TCF protein-protein interaction, FOG-001 is intended to block the Wnt signaling pathway irrespective of the various APC and β-catenin mutations that typically drive disease.
FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the key downstream node, disrupting the interaction between β-catenin and the TCF transcription factors, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis.
FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors.
About the Phase 1/2 trial of FOG-001
FOG-001 is being evaluated in a first-in-human Phase 1/2 multicenter, open-label study (NCT05919264) assessing its safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity. The trial includes dose-escalation and dose-expansion phases and is testing FOG-001 both as a monotherapy and in combination with other anticancer agents in patients with advanced or metastatic solid tumors likely or known to harbor a Wnt pathway–activating mutation (WPAM).
(Press release, Parabilis Medicines, NOV 12, 2025, View Source;cateninTCF-Interaction-for-the-Treatment-of-Desmoid-Tumors [SID1234659859])