Oral IL-23 Receptor Antagonist JNJ-2113 Achieves Breakthrough Results in Psoriasis Trial—What This Means for Patients

Protagonist Therapeutics and its partner Janssen have made waves with positive Phase 2b data from the FRONTIER 1 clinical trial, showing that JNJ-2113—the first and only oral IL-23 receptor antagonist peptide being developed for moderate-to-severe plaque psoriasis—significantly outperformed placebo in skin clearance metrics. The findings, presented at the World Congress of Dermatology in Singapore, represent a major milestone for oral peptide-based treatments in dermatology.

The Numbers Tell the Story

The trial enrolled 255 patients across six treatment groups, testing different dosages of JNJ-2113 against placebo. The results speak volumes about dose-response effectiveness:

At the highest dose tested (100 mg twice daily), JNJ-2113 demonstrated a 78.6% response rate at PASI 75 (75% skin clearance improvement), compared to just 9.3% for placebo. Even more impressive, 59.5% of patients achieved PASI 90 (90% improvement) and 40.5% reached PASI 100 (complete clearance) at this dosage.

By contrast, even lower doses showed meaningful benefits—the 50 mg daily group achieved 58.1% PASI 75 response, suggesting that effective treatment might be possible with reduced dosing.

Why This Matters: A New Treatment Paradigm

Psoriasis affects millions worldwide, and while existing biologics have helped many patients, an effective oral option—particularly one that’s the first of its kind—could fundamentally change how dermatologists approach the disease. Current IL-23-based treatments typically require injections or infusions, making JNJ-2113’s oral formulation a potential game-changer for patient compliance and quality of life.

The mechanism is straightforward: JNJ-2113 blocks IL-23 signaling, a key driver of the inflammatory cascade in psoriasis. This same pathway also plays a role in other inflammatory conditions like psoriatic arthritis and ulcerative colitis—opening doors for broader applications beyond skin disease.

Safety Profile Looks Solid

A major concern with any new drug is tolerability. The trial showed that adverse events were comparable between JNJ-2113 recipients (52.4% experienced at least one AE) and placebo (51.2%), with no evidence of dose-dependent safety concerns. This is a green flag for advancing into Phase 3 studies.

What Comes Next

Janssen has already announced plans to move forward with Phase 3 development in moderate-to-severe plaque psoriasis and is simultaneously exploring JNJ-2113 in ulcerative colitis. Protagonist remains eligible for up to $855 million in milestone payments if the program succeeds, with immediate payouts of $50 million for Phase 3 advancement and $115 million upon meeting the primary endpoint.

The development trajectory of JNJ-2113—from Protagonist’s discovery platform through collaboration with Janssen to now—demonstrates how oral peptide technology can deliver real clinical value in areas where traditional small molecules and large-molecule biologics have faced limitations. For dermatology patients tired of needle-based treatments, Phase 3 results could usher in a new era of oral options.