Nebokitug was safe and well tolerated through 48 weeks in primary sclerosing cholangitis, with a statistically significant reduction in liver stiffness at week 15 versus placebo in the pre-specified subgroup with moderate/advanced fibrosis. Across the full study, biomarker signals were dose-responsive and most pronounced at 20 mg/kg: numerical reductions in ELF score and PRO-C3 at 15 weeks were sustained through 48 weeks in the open-label extension, and half of patients on 20 mg/kg showed concurrent improvements across ELF, PRO-C3, and liver stiffness, versus none on placebo. The Phase 2 SPRING trial enrolled 76 patients across 33 sites; more than 90% of eligible participants rolled over into the extension.
The core development is that these data, now peer-reviewed in the American Journal of Gastroenterology, underpin Chemomab’s decision to move nebokitug, an anti-CCL24 monoclonal antibody, into a Phase 3 registration program in PSC. The company indicates it is pursuing a single pivotal study with a clinical event-based primary endpoint and holds FDA Fast Track and orphan designations in PSC. The Phase 2 design used IV dosing every three weeks at 10 or 20 mg/kg with safety as the primary endpoint and noninvasive fibrosis and inflammation measures as key secondary readouts.
Strategically, the Phase 3 pivot is an assertive bet that a coherent biomarker package in a difficult-to-treat population can translate into event reduction. PSC remains a space where regulators have pushed sponsors toward hard clinical outcomes and durable signals across heterogeneous disease biology. The strongest SPRING signals sit in patients with higher baseline disease burden (LSM >8.7 kPa) and at the higher dose, which points to an enrichment strategy and dose selection that could increase the probability of success while containing sample size. The lack of broad statistical superiority across secondary endpoints at 15 weeks will keep pressure on the Phase 3 to demonstrate time-to-event benefits with clear effect size rather than rely on surrogate trajectories alone.
For sites and CROs, the operational contours are already visible. Enrollment feasibility in a rare disease was demonstrated across a multi-country footprint, but a Phase 3 event-driven design will extend follow-up and require rigorous endpoint adjudication, elastography standardization, and high retention—particularly given infusion-based therapy. Centralized assays for ELF components and PRO-C3 will be pivotal as stratification and key secondary endpoints, adding lab vendor complexity but offering objective, protocolizable measures. Expect eligibility to skew toward moderate/advanced fibrosis to align with the Phase 2 signal, which may simplify screening if LSM thresholds are used, but it also narrows the funnel and increases competition for the same patient segment.
The near-term watchlist centers on protocol specifics: final dose selection, enrichment based on baseline stiffness or other risk markers, and the precise composition of the clinical event endpoint. Clarity on powering assumptions, geographic dispersion, and site mix will signal recruitment velocity and operational risk. Regulators will look for consistency between biomarker improvements and clinically meaningful outcomes over longer horizons; interim analyses anchored to noninvasive measures may inform adaptation but are unlikely to substitute for event-based evidence. Manufacturing scale-up for repeat IV dosing, immunogenicity monitoring over multi-year exposure, and potential interaction with coexisting IBD care pathways are additional execution variables. If the Phase 3 can convert the fibrosis-centric biomarker signal into fewer clinical events, nebokitug could reset expectations for anti-fibrotic strategies in PSC; if not, the field will again confront the gap between promising noninvasive markers and regulatory-grade outcomes.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
