Nebokitug maintained favorable safety and sustained biomarker improvement through 48 weeks in the Phase 2 SPRING open-label extension in primary sclerosing cholangitis, with continued reductions in inflammatory and fibrotic signals, including ELF and liver stiffness. Effects were dose-dependent on macrophage-related proteins and strongest in moderate-to-advanced disease at 20 mg/kg, where MST1 expression increased in parallel with improvements in ELF and liver stiffness.
Chemomab is showcasing three AASLD posters flagged as Posters of Distinction: the SPRING open-label extension reporting durability up to 48 weeks, and two mechanistic analyses linking CCL24 blockade to macrophage biology in PSC, including restoration of MST1, a regulator of macrophage activation. Of the 54 eligible patients completing the 15-week double-blind portion, 50 entered the extension for up to 33 additional weeks on nebokitug. Across the set, safety remained acceptable; serum macrophage-associated proteins decreased in a dose-dependent manner compared with placebo-treated patients; and MST1 increased in treated cohorts, correlating with liver stiffness and ELF improvements. The company is positioning 20 mg/kg as the go-forward dose and preparing a single pivotal Phase 3 trial with a clinical event primary endpoint.
Strategically, this is an evidence-building exercise aimed at de-risking a disease-modifying claim in a space where surrogates have struggled to unlock approval. By tying target engagement (CCL24 neutralization) to a coherent macrophage-driven pathophysiology and showing concordant shifts in MST1, Chemomab is laying the pharmacodynamic substrate regulators increasingly expect when sponsors pursue clinical event endpoints. The emphasis on moderate-to-advanced disease and a fixed 20 mg/kg selection signal a pragmatic pivot toward populations and dosing that amplify biologic signal and, potentially, event rates—key for an event-driven Phase 3 in a rare disease with slow progression.
For sites and CROs, the operational read-through is clear. A Phase 3 centered on clinical events will require extended follow-up, rigorous endpoint adjudication, and high retention across a patient population often co-managed with IBD clinics. The biomarker-heavy strategy entails centralized ELF and macrophage panels alongside standardized liver stiffness assessments, with consistent access to MRE or elastography and quality controls. If nebokitug remains an infusion-based, weight-adjusted antibody at 20 mg/kg, infusion capacity, scheduling, and drug accountability will be nontrivial, particularly if enrollment is concentrated among moderate/advanced patients who are more clinically complex. Vendors supporting imaging, central labs, and PD analytics will be central to protocol reliability.
What matters next are the specifics of the Phase 3 architecture: the definition of the clinical event composite, enrichment criteria by disease stage and concomitant IBD, stratification factors, and the geographic footprint needed to hit event targets without overextending site networks. The mechanistic MST1 linkage is promising as a PD marker, but it is not a validated surrogate; whether regulators accept it as supportive evidence will hinge on how tightly it tracks with hard outcomes over time. Watch for durability beyond 48 weeks, immunogenicity, and safety behavior with chronic dosing, and any early signs of subgroup divergence that could drive adaptive enrichment. Finally, manufacturing and cost of goods for a weight-based monoclonal antibody in a chronic indication, as well as infusion logistics, will influence both trial feasibility and eventual commercialization if the Phase 3 signal holds.
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.
