Parabilis reports 72% response rate for zolucatetide in desmoid

Parabilis Medicines has presented updated Phase 1/2 data for zolucatetide in desmoid tumours at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid, reporting an objective response rate (ORR) of 72.2% and a disease control rate (DCR) of 100% among response-evaluable patients receiving a starting dose of 450 mg or above.

The data, cut off on 22 June 2026, covered 76 patients enrolled across dose escalation and dose optimisation cohorts. Of the 46 response-evaluable patients who began treatment at the threshold dose, all showed disease control with no evidence of progression. Among the 18 patients who had scans at the 32-week landmark, 13 met RECIST 1.1 response criteria. Responses were observed regardless of prior gamma-secretase inhibitor (GSI) exposure or CTNNB1 or APC mutation status.

Mechanism and differentiation

Zolucatetide is described by Parabilis as the first direct inhibitor of the interaction between beta-catenin and the TCF family of transcription factors, a node in the Wnt/beta-catenin signalling pathway that has historically resisted drug development. The company says its Helicon peptide platform, which generates alpha-helical peptides capable of engaging intracellular proteins, underpins this approach. Because zolucatetide targets a downstream node, the company argues it can address pathway activation driven by different upstream mutations, potentially broadening the treatable population relative to approaches that target earlier steps.

Mrinal Gounder, sarcoma medical oncologist at Memorial Sloan Kettering Cancer Center and the presenting author, said the "magnitude and apparent rapidity of tumour responses observed to date" were encouraging, adding that therapies capable of achieving meaningful tumour shrinkage with acceptable tolerability "remain an important clinical goal." Dr Gounder has disclosed financial interests related to Parabilis.

On safety, treatment-related adverse events were predominantly low-grade. The most commonly reported were fatigue, alopecia and nausea. No patients discontinued due to treatment-related adverse events, and the drug was not associated with the ovarian toxicity or high-grade gastrointestinal and skin toxicities reported with GSIs, the current standard-of-care class.

Phase 3 path and competitive context

Following end-of-Phase 2 discussions, the FDA has aligned with Parabilis on a dose and regimen of 450 mg weekly for four induction cycles followed by 300 mg every two weeks for maintenance, a placebo-controlled study design, and progression-free survival as the primary endpoint. The randomised, double-blind PEDESTAL trial is planned to begin in the first half of 2027, with topline results anticipated in 2029.

Desmoid tumours are locally invasive soft-tissue tumours arising predominantly in young adults, with an estimated 30,000 patients in the United States, approximately 11,000 of whom are actively managed. No approved therapy currently targets the underlying Wnt/beta-catenin biology directly, leaving GSIs, non-steroidal anti-inflammatory drugs, and systemic chemotherapy as the principal treatment options.

The competitive landscape in this rare indication has attracted increasing interest. Nirogacestat, a GSI approved by the FDA in 2023 for desmoid tumours, is the only currently approved targeted agent; Parabilis is positioning zolucatetide as differentiated by its tolerability profile relative to that class. Zolucatetide carries both Fast Track and Orphan Drug Designations from the FDA. Investors and clinicians will look to the full Phase 1/2 dataset, including duration of response and longer follow-up, before drawing firm conclusions ahead of the PEDESTAL readout.