Merck (NYSE: MRK) reported positive topline results from the Phase III ATLAS-UC Study 2, making tulisokibart (MK-7240) the first anti-TL1A monoclonal antibody to demonstrate clinical remission at 12 weeks in moderately to severely active ulcerative colitis in a Phase III setting. The result makes tulisokibart the first anti-TL1A antibody to report positive Phase III induction data in ulcerative colitis..
The ATLAS-UC Study 2 is a randomized, double-blind, placebo-controlled induction-only trial evaluating high-dose and low-dose IV tulisokibart against placebo. The primary endpoint — clinical remission per Modified Mayo Score at Week 12 — was met, as were key secondary endpoints including endoscopic improvement, clinical response, and histologic-endoscopic mucosal improvement. No specific numerical data were disclosed; full results will be presented at an upcoming scientific congress alongside data from Study 1, the parallel induction and maintenance trial. No safety concerns were identified, consistent with previously reported Phase II findings.
Tulisokibart targets TL1A, a TNF superfamily cytokine that drives both intestinal inflammation and fibrosis — a process Merck terms "immuno-fibrosis." By binding both soluble and membrane-bound TL1A, the antibody is designed to address not only mucosal inflammation but also the deeper transmural fibrotic changes increasingly recognized in UC pathology. This distinguishes it mechanistically from approved biologics targeting TNF, IL-12/23, IL-23p19, or gut integrins, and from JAK inhibitors and S1P modulators, none of which directly address the fibrotic component.
Competitive context
The anti-TL1A class is now entering its first Phase III readout period, but competition within it is real. Sanofi and Teva's duvakitug is in Phase III for both UC and Crohn's disease, with Phase IIb maintenance data previously reporting 58% clinical remission at 44 weeks in UC induction responders. Waltham, Massachusetts-based Spyre Therapeutics' (Nasdaq: SYRE) SPY002, an extended half-life anti-TL1A antibody, recently reported a statistically significant 10.7-point reduction in Robarts Histopathology Index at Week 12 in Phase II — the largest histopathology result reported for any anti-TL1A molecule in UC to date, though in an uncontrolled setting. Roche's afimkibart is also in Phase III, with a regulatory submission expected by 2027. Cross-trial comparisons across these programs are limited by differences in study design, patient populations, and the absence of head-to-head data.