Comprehensive Report on Tulisokibart (MK-7240/PRA023): An Investigational Anti-TL1A Monoclonal Antibody

1. Executive Summary

Tulisokibart, an investigational humanized IgG1 kappa monoclonal antibody, represents a novel therapeutic approach targeting Tumor Necrosis Factor-like Cytokine 1A (TL1A). Originally developed by Prometheus Biosciences under the designation PRA023 and now advanced by Merck & Co., Inc. as MK-7240, Tulisokibart is in late-stage clinical development primarily for inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD).[1] Phase 2 clinical trials (ARTEMIS-UC for ulcerative colitis and APOLLO-CD for Crohn's disease) have demonstrated statistically significant and clinically meaningful efficacy in inducing clinical remission and endoscopic improvement in patients with moderately to severely active disease, many of whom had failed previous conventional or advanced therapies.[1]

The mechanism of Tulisokibart involves the specific inhibition of TL1A, a cytokine implicated in both pro-inflammatory and pro-fibrotic pathways. This dual action is a key differentiator, suggesting potential benefits beyond symptomatic relief, particularly in conditions characterized by tissue remodeling and fibrosis, such as Crohn's disease and Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD).[1] The therapeutic strategy for Tulisokibart includes the co-development of a companion diagnostic (CDx) aimed at identifying patients with a genetic predisposition to increased TL1A expression, thereby potentially enhancing treatment response through a precision medicine approach.[1] While the CDx has shown some predictive value, its role and optimization are still under evaluation.