The data point to the potential of JNJ-2113 as a first-in-class drug candidate in multiple IL-23 driven-diseases.

Protagonist Therapeutics and Janssen Biotech, Inc.'s oral IL-23 receptor antagonist, JNJ-2113, performed well in Phase 1 and Pre-clinical Studies.

JNJ-2113 is a macrocyclic peptide that binds to the IL-23 receptor with single digit picomolar affinity and demonstrated potent, selective inhibition of IL-23 signaling in human T cells.

The results were  presented at the International Societies for Investigative Dermatology (ISID) 2023 meeting in Tokyo, Japan. 

Although peptides typically have low oral bioavailability, the high potency of JNJ-2113, along with its oral stability, indicated potential for systemic activity beyond the gastrointestinal tract in rat models of inflammation and colitis.

In a rat trinitrobenzene sulfonic acid (TNBS)-induced colitis model, efficacy was observed as measured by attenuation of weight loss and colon inflammation with oral doses of JNJ-2113 as low as 0.3 mg/kg/day.

In an IL-23-induced rat skin inflammation model, orally dosed JNJ-2113 achieved inhibition of inflammation equivalent to an IL-23 antibody, along with reduction of IL-17 and IL-22 cytokines.

Oral treatment with JNJ-2113 provided selective systemic IL-23 pathway inhibition in pre-clinical models that successfully translated to systemic pharmacodynamics activity in healthy human volunteers, indicating potential for JNJ-2113 as a first-in-class oral therapy targeting IL-23-mediated diseases.

"JNJ-2113 is a potential first-in-class drug candidate in multiple aspects, such as with respect to its biological target, the IL-23 receptor; its oral mode of drug delivery; and its chemical modality as a peptide, representing a major breakthrough in the field of innovative oral peptide-based therapeutics," says Dinesh V. Patel, Ph.D., President and CEO of Protagonist, in a news release. "These data demonstrated pre-clinical proof-of-concept in skin inflammation and colitis disease models, highlighting JNJ-2113's potential for therapeutic utility in both psoriasis and inflammatory bowel diseases implicated in the IL-23 pathway. We look forward to the presentation of the Phase 2b FRONTIER 1 study data in adults with moderate-to-severe plaque psoriasis later this year."

Positive topline results from the FRONTIER 1 study of JNJ-2113 in moderate-to-severe plaque psoriasis became available in March 2023, with further details to be shared at medical meetings starting in the second quarter of 2023.