Parabilis Medicines (NASDAQ:PBLS) presented updated interim phase I/II data for investigational beta-catenin/TCF inhibitor zolucatetide in desmoid tumors at the European Society for Medical Oncology Congress in Madrid, reporting tumor responses, disease control and an FDA-aligned plan for a registrational phase III study.
The data were preliminary as of a June 22, 2026 cutoff, and zolucatetide is not approved for any use. Chief Executive Officer Mathai Mammen said the company expects to begin its PEDESTAL phase III trial in the first half of 2027 and report top-line results in 2029.
Updated Efficacy Results
The dataset included 48 patients who started at 450 mg or higher, including two patients who began at 900 mg but had dose reductions resulting in average exposure roughly comparable with the company’s planned induction regimen. Parabilis said responses were seen in both patients previously treated with gamma-secretase inhibitors, or GSIs, and in GSI-naive patients.
Mammen said responses continued to deepen over time and that the company used landmark analyses because patients had spent substantially different amounts of time on treatment. The company said its updated data included 76 treated patients overall, roughly double the number reported in its February data cutoff.
Parabilis compared its results with published data from approved and investigational GSI studies, while emphasizing that the trials were not head-to-head comparisons. The company said published phase III studies reported response rates of 41% for nirogacestat and 55.7% for varegacestat at their primary analyses after longer follow-up periods. Using estimates derived from published swim-lane plots, Parabilis estimated response rates at 24 weeks of about 25% for nirogacestat and 22% for varegacestat.
Safety and Selected Regimen
At the planned 450 mg weekly induction dose, Parabilis said adverse events were predominantly low grade, with fatigue, alopecia and nausea among the most common events. The company reported no treatment discontinuations due to treatment-related adverse events, or TRAEs, across all 76 patients.
The company said zolucatetide had not been associated with ovarian toxicity or high-grade diarrhea or rash, adverse effects commonly associated with GSIs. At the 450 mg starting dose, 13% of patients experienced a grade 3 event, according to the presentation.
Across the 76 patients, the company reported two serious adverse events: a transient grade 1 fever and grade 2 peripheral sensory neuropathy that it believes was related to tumor compression of a nearby nerve rather than treatment. Parabilis also reported one grade 4 treatment-related transient creatine phosphokinase increase at the 150 mg weekly dose; the asymptomatic laboratory abnormality resolved in about a week without intervention.
Parabilis selected a regimen of 450 mg weekly for four months followed by 300 mg every two weeks for maintenance in phase III. The regimen was informed by an arm using 450 mg weekly induction followed by 150 mg weekly maintenance. Mammen said the every-two-week schedule is intended to provide comparable exposure with half as many maintenance infusions.
FDA Discussion and Phase III Plan
Mammen said the company recently completed an end-of-phase II meeting with the Food and Drug Administration and aligned on key elements of the PEDESTAL trial. The planned study will be placebo-controlled, enroll a broad population including both pre-GSI and post-GSI patients, and use progression-free survival as its primary endpoint.
During the question-and-answer session, Mammen said the FDA wants a randomized controlled trial despite discussion at ESMO about whether the data might support a single-arm registration approach. He also said the company expects desmoid tumor treatment to be chronic or semi-chronic, although patients who achieve substantial responses could potentially take treatment breaks.
Helen Ho, Parabilis’ chief business and strategy officer, said the company believes the U.S. desmoid market is underpenetrated. Management said approximately 30,000 people in the U.S. are living with desmoid tumors, about 11,000 are under active management, and about 1,000 are currently receiving GSI therapy.
Parabilis plans to develop a self-administered formulation for commercial use. Mammen said the company is conducting preclinical formulation work and intends to test bioequivalence in humans, with a potential additional patient study if requested by the FDA.
Beyond desmoid tumors, Parabilis said it initiated a dose-ranging study of zolucatetide in familial adenomatous polyposis and expects additional data in that indication during the first quarter of 2027. The company also expects data in adamantinomatous craniopharyngioma and hepatocellular carcinoma during the first half of 2027, and said its cash runway extends into 2030.
About Parabilis Medicines (NASDAQ:PBLS)
Parabilis Medicines Inc is a clinical-stage biopharmaceutical company built to develop transformative medicines addressing some of the most consequential, yet historically undruggable, protein targets driving human disease. Parabilis Medicines Inc is based in CAMBRIDGE, Mass.
