Parabilis Medicines Announces Compelling Preliminary Clinical Results for FOG-001 in Adamantinomatous Craniopharyngioma at SNO 2025
Parabilis Medicines, a clinical-stage biopharmaceutical company dedicated to developing transformative therapies for patients with cancer, announced new preliminary clinical data highlighting the therapeutic promise of its lead investigational Helicon™ peptide, FOG-001. As the first and only direct inhibitor of the historically “undruggable” β-catenin:TCF protein–protein interaction, FOG-001 represents a novel therapeutic strategy for targeting tumors driven by dysregulation of the Wnt/β-catenin signaling pathway.
The newly released findings focus on patients with adamantinomatous craniopharyngioma (ACP), a rare brain tumor with high morbidity and no approved systemic treatments. The data were delivered as a mini-oral presentation at the 30th Annual Meeting of the Society for Neuro-Oncology (SNO) and build on insights first shared publicly at the AACR-NCI-EORTC 2025 “Triple” Meeting the month prior. Importantly, ACP is now the second low-complexity, Wnt/β-catenin-driven tumor type—following desmoid tumors—in which all patients treated to date have demonstrated measurable tumor reduction with FOG-001 monotherapy.
A Significant Step Forward in a Tumor with High Unmet Need
ACP is a rare but highly challenging intracranial tumor, frequently leading to endocrine dysfunction, visual deterioration, cognitive impairment, and neurological deficits. Because these tumors are located deep within the brain and often near Parabilis Medicines critical neurovascular structures, treatment typically relies on surgery and radiation, both of which can result in substantial and sometimes irreversible complications. Despite ongoing clinical research, patients currently have no systemic therapeutic options that reliably and safely address the biology of ACP.
Nearly all ACP tumors are characterized by mutations in CTNNB1, the gene encoding β-catenin, which subsequently leads to persistent activation of the Wnt/β-catenin signaling pathway. This dysregulation plays a central role in tumor formation and maintenance. The abnormal activation of signaling through the β-catenin:TCF complex, a critical node within the pathway, provides the scientific rationale behind FOG-001’s mechanism. By directly disrupting this core interaction, FOG-001 aims to inhibit the transcriptional activity that drives tumor proliferation and survival in ACP and similar Wnt-activated tumor types.
Leadership Perspective: A Potential Breakthrough in an “Undruggable” Space
According to Mathai Mammen, M.D., Ph.D., Chairman, CEO, and President of Parabilis Medicines, these early findings reflect a meaningful step forward for a population long underserved in neuro-oncology.
“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 Dr. Mammen. “Our preliminary clinical data demonstrate that FOG-001 can directly inhibit the β-catenin:TCF interaction—long believed to be ‘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 therapeutic potential of FOG-001 across multiple tumor types, with desmoid and ACP representing only the beginning of what is possible.”
His remarks underscore the broader implications of this program: ACP is not an isolated opportunity. Instead, ACP adds to an emerging list of tumor types in which FOG-001 is showing activity, strengthening the case for Wnt-pathway interference as a viable therapeutic modality.
Early Clinical Findings: Tumor Reductions in All ACP Patients Treated
The new ACP data come from Parabilis Medicines’ ongoing Phase 1/2 clinical trial, which is evaluating FOG-001 across a spectrum of Wnt/β-catenin-driven cancers. As of the data cutoff on August 11, 2025, three patients with ACP and documented visual field impairment had received FOG-001 monotherapy at doses of 144 mg/m² (n=1) and 360 mg/m² (n=2). Remarkably, all three patients experienced tumor shrinkage, accompanied by a favorable safety profile and strong overall tolerability.
Key findings include:
- Two patients achieved partial responses, with tumor reductions of
– 56.0%, and
– 48.0% - The third patient achieved stable disease, with a 19.2% decrease in tumor size
- No treatment-related serious adverse events, dose reductions, or treatment discontinuations were reported
These Parabilis Medicines early results are significant not only because all treated patients responded with some degree of tumor reduction, but also because such reductions were achieved without compromising patient safety. In a tumor type where treatment-related morbidity is common, the favorable tolerability profile is an important component of FOG-001’s therapeutic promise.
Reinforcing the Role of Wnt/β-Catenin in Cancer Biology
The ACP data align with a growing body of evidence supporting the role of FOG-001 across tumor types with low-complexity Wnt/β-catenin pathway activation. Data shared earlier at the 2025 Triple Meeting revealed single-patient clinical activity in additional tumor types primarily driven by Wnt/β-catenin dysregulation, including:
- Ameloblastoma
- Salivary gland cancers
- Solid pseudopapillary neoplasm (SPN)
These findings extend the relevance of FOG-001 beyond desmoid tumors and ACP, suggesting that tumors with simpler or more direct Wnt-pathway drivers may be particularly susceptible to β-catenin:TCF inhibition.
Moreover, Parabilis Medicines reported preclinical and emerging clinical evidence suggesting that FOG-001 may be effective in rational combination strategies for more genomically complex tumors. One such example is microsatellite stable colorectal cancer (MSS-CRC), a tumor type for which therapeutic progress has been slow and new mechanistic strategies are urgently needed. By integrating FOG-001 with complementary targeted agents or immunotherapies, Parabilis aims to extend the benefit of Wnt-pathway inhibition into broader oncologic settings.
Regulatory Momentum: Fast Track Designation for Desmoid Tumors
In addition to generating compelling early clinical data, FOG-001 has also achieved a key regulatory milestone. The Parabilis Medicines drug candidate was recently granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for the treatment of desmoid tumors. This designation reflects the agency’s recognition of FOG-001’s potential to address a serious disease with significant unmet need, and it may help streamline development through enhanced FDA engagement and eligibility for accelerated approval pathways.
Although the Fast Track designation currently applies to desmoid tumors, the consistency of responses seen in ACP and other Wnt-driven cancers enhances the program’s overall momentum and could strengthen rationale for future regulatory discussions across multiple indications.
A Growing Clinical Program with Broad Potential
The ongoing Phase 1/2 study continues to enroll patients across a diverse set of Wnt/β-catenin-driven malignancies, reflecting Parabilis Medicines’ ambition to establish FOG-001 as a foundational therapy within this mechanistically defined class of tumors. As more data emerge, the company aims to refine the therapeutic profile of FOG-001, identify optimal dose levels, and explore both monotherapy and combination approaches tailored to tumor biology.
While these ACP results represent early findings from a small number of patients, they meaningfully contribute to a rapidly Parabilis Medicines expanding dataset illustrating the drug’s biological activity and clinical promise. For a tumor type with limited therapeutic options and high patient burden, the possibility of a targeted, disease-modifying treatment marks an important turning point for the field.
A Promising New Chapter in Wnt-Targeted Therapeutics
The Parabilis Medicines preliminary ACP data presented at SNO 2025 underscore the potential of FOG-001 to transform the treatment landscape for patients with tumors driven by dysregulated Wnt/β-catenin signaling. With measurable tumor reductions in all ACP patients treated to date—paired with a favorable safety profile—the findings provide early validation of Parabilis Medicines’ novel approach to targeting the β-catenin:TCF interaction.
As clinical development continues to expand, FOG-001 may represent a first-in-class opportunity to address multiple cancers long considered resistant to systemic therapy. For patients living with ACP and other rare Wnt-pathway-driven diseases, these findings offer new hope for meaningful clinical breakthroughs.
Source Link: https://www.businesswire.com/
