Pfizer terminates Phase Ib trial for CCR6 antagonist PF-07054894 in ulcerative colitis

Pfizer has terminated its Phase Ib clinical trial evaluating PF-07054894, an oral CCR6 antagonist, in adults with ulcerative colitis, according to an update on ClinicalTrials.gov (NCT05549323). The randomized, double-blind, placebo-controlled study was the only patient trial of the investigational compound, which targeted the CCL20/CCR6 chemokine axis.

PF-07054894 was developed under Pfizer’s collaboration with Japan-based Sosei Heptares and functions as an allosteric, insurmountable antagonist of CCR6. The therapeutic rationale was that sustained CCR6 inhibition could prevent recruitment of pathogenic Th17 cells and other CCR6-expressing immune populations into the gut mucosa, potentially interrupting inflammatory signaling in ulcerative colitis.

The study enrolled 44 participants and was structured in two parts, evaluating moderate-to-severe and mild-to-moderate ulcerative colitis populations. Primary endpoints included clinical remission at Week 12 in the higher-severity cohort and percent change in modified Mayo Score in the milder cohort. The trial began in November 2022 and had a planned primary completion date in November 2025.

No efficacy or safety data have been publicly disclosed, and no results have been posted to the registry. The ClinicalTrials.gov entry states the termination reflects a business decision, rather than any safety concerns associated with PF-07054894.

PF-07054894 had previously completed three Phase I first-in-human studies in healthy volunteers. With the discontinuation of the Phase Ib study and no additional patient trials registered, the clinical program appears to have been halted.

The termination leaves the CCR6/CCL20 pathway without an active clinical-stage program in inflammatory bowel disease. The axis has strong biological rationale, with elevated CCL20 expression observed in inflamed colonic tissue and genetic associations linking CCR6 to autoimmune disease susceptibility. However, clinical validation has been limited. GlaxoSmithKline previously evaluated GSK3050002, an anti-CCL20 antibody, in early development, but that program did not advance beyond Phase I.

Ulcerative colitis treatment has expanded in recent years with US FDA approvals of JAK inhibitors, anti-IL-23 antibodies, and S1P receptor modulators. Nonetheless, a substantial proportion of patients fail to achieve durable remission, sustaining interest in novel mechanisms. For now, CCR6 inhibition remains biologically compelling but clinically unproven.