On November 21, 2025 Parabilis Medicines, a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported preliminary clinical data demonstrating the therapeutic potential of its lead investigational Helicon peptide, FOG-001 – the first and only direct inhibitor of the "undruggable" β-catenin:TCF interaction – in adamantinomatous craniopharyngioma (ACP).

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The ACP data, presented today as a mini-oral at the 30th Society for Neuro-Oncology (SNO) Annual Meeting and first shared at last month’s AACR (Free AACR Whitepaper)-NCI-EORTC 2025 "Triple" Meeting, represent the second low-complexity Wnt/β-catenin-driven tumor subgroup – following desmoid tumors – to show tumor reductions in all patients treated to date with FOG-001 monotherapy.

ACP is a rare brain tumor that is often associated with severe endocrine, visual, and neurological complications, where unmet patient needs are high. Due to the location of tumors, surgery and radiation, the mainstays of treatment, can be challenging and carry a high risk of complications, and no approved systemic therapies exist. Nearly all ACP tumors are driven by CTNNB1 mutations and abnormal activation of the Wnt/β-catenin-driven pathway, creating a strong mechanistic rationale for direct inhibition of the β-catenin:TCF interaction, the key node in the Wnt pathway.

"ACPs are devastating tumors associated with high morbidity, and patients have long faced limited treatment options due to the challenges in systemically addressing the underlying disease biology," said Mathai Mammen, M.D., Ph.D., Chairman, CEO and President of Parabilis Medicines. "Our preliminary clinical data demonstrate that FOG-001 can directly inhibit the β-catenin:TCF interaction, which has long been considered ‘undruggable,’ and offer early evidence of meaningful clinical benefit. This has the potential to be a promising advancement for patients confronting this difficult diagnosis for which targeted, effective treatment options are not currently available. More broadly, we continue to see the potential of FOG-001 in treating multiple tumor types, with desmoid and ACP representing just the beginning of what is possible."

In the company’s Phase 1/2 trial, as of the data cutoff date of August 11, 2025, three patients with ACP with visual field impairment had been treated with FOG-001 at doses of 144 mg/m2 (n=1) and 360/m2 mg (n=2), and all patients (n=3) showed tumor reduction with well-managed safety and tolerability. Two patients achieved a partial response with 56.0% and 48.0% reduction in tumor size, and one patient had stable disease with a 19.2% decrease in tumor size. No treatment-related serious adverse events, dose reductions, or treatment discontinuations have been reported.

At the Triple Meeting, Parabilis also reported single-patient activity in three additional low-complexity Wnt/β-catenin-driven tumors, including ameloblastoma, salivary gland cancer, and solid pseudopapillary neoplasm, primarily driven by dysregulated Wnt/β-catenin signaling, as well as preclinical and clinical data supporting further evaluation of rational combinations in more complex tumor types – including microsatellite stable colorectal cancer.

FOG-001 was recently granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors. The Phase 1/2 clinical trial remains ongoing, enrolling patients across a range of Wnt/β-catenin-driven cancers.

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 21, 2025, View Source [SID1234660871])