CAMBRIDGE, Mass.—Parabilis Medicines, a clinical-stage biopharmaceutical company developing innovative treatments for cancer, announced at the ESMO Congress 2025 the first-ever clinical evidence that its investigational therapy FOG-001 has successfully targeted and inhibited β-catenin:TCF—a critical cancer-driving interaction within the Wnt/β-catenin pathway that has long been considered “undruggable.”
In the ongoing Phase 1/2 trial of FOG-001 in patients with Wnt/β-catenin-driven tumors, as of mid-August 2025, 12 patients with desmoid tumors were treated across three dose levels. Among the 10 patients who had undergone at least one post-baseline scan, tumor reductions were observed at all dose levels, resulting in a 100 percent disease-control rate. Of the five patients with more than one post-baseline scan, an objective response rate of 80 percent (4 out of 5) was achieved per RECIST 1.1. Responses were recorded in both gamma secretase-naive and -treated patients. FOG-001 showed meaningful anti-tumor activity alongside a favorable safety and tolerability profile.
FOG-001 is the lead candidate from Parabilis’s Helicon peptide platform and works by disrupting the interaction between β-catenin and T-cell factor (TCF) transcription factors—the core mechanism driving tumor growth in cancers activated by the Wnt pathway. The results support continued development of FOG-001 in desmoid tumors and suggest the therapy could provide a more direct and durable approach than currently available treatments by addressing the root cause of the disease.
“For decades, scientists believed the Wnt/β-catenin:TCF interaction couldn’t be drugged, but our data prove otherwise,” said Mathai Mammen, M.D., Ph.D., Chairman, CEO, and President of Parabilis Medicines. “FOG-001 demonstrates what bold science can achieve—taking on one of cancer’s most central drivers and opening the door to an entirely new class of therapies. This milestone validates the potential of our Helicon peptide platform and represents a transformative moment for patients and oncology research alike.”
The Wnt/β-catenin pathway, discovered more than 30 years ago, plays a central role in cancer biology and is implicated in millions of cases annually. It is involved in both common cancers—such as colorectal, hepatocellular, and gastric cancers—and in rare diseases like desmoid tumors and adamantinomatous craniopharyngioma. Despite numerous attempts, prior efforts to directly inhibit the β-catenin:TCF interaction had failed until FOG-001.
The company’s proprietary Helicon platform uses stabilized α-helical peptides capable of penetrating cells and binding to challenging, flat protein surfaces that small molecules cannot easily target. Through this approach, Parabilis has achieved what decades of cancer research had not—successfully drugging the “undruggable.”
Additional presentations on FOG-001’s potential across a range of Wnt/β-catenin-driven solid tumors will be made at upcoming scientific meetings, including the AACR-NCI-EORTC International Conference on Molecular Targets (October 22–26, Boston, MA), the Connective Tissue Oncology Society Annual Meeting (November 12–15, Boca Raton, FL), and the Society for Neuro-Oncology Annual Meeting (November 19–23, Honolulu, HI). The company will also present new preclinical data from its androgen receptor (ARON) and ERG degrader programs for prostate cancer at AACR-NCI-EORTC and the Prostate Cancer Foundation Scientific Retreat (October 23–25, Carlsbad, CA).
