Protagonist Therapeutics, Inc. announced a late-breaking presentation at the American Academy of Dermatology (AAD) 2024 Annual Meeting with positive results from the Phase 2b FRONTIER 2 long-term extension study evaluating JNJ-2113, the first and only investigational targeted oral peptide designed to block the IL-23 receptor, for adult patients with moderate-to-severe plaque psoriasis (PsO). JNJ-2113 is being developed by J&J Innovative Medicine, Inc., under a license and collaboration agreement with Protagonist, and is currently enrolling four pivotal Phase 3 psoriasis studies in the ICONIC clinical development program and one Phase 2b ulcerative colitis study. FRONTIER 2 enrolled patients who completed the 16-week dose ranging FRONTIER 1 Phase 2b study and evaluated patients from Week 17 through Week 52.

In FRONTIER 2, JNJ-2113 maintained high rates of skin clearance through 52 weeks in adults with moderate-to-severe plaque psoriasis, as measured by Psoriasis Area and Severity Index (PASI) response rates of 75%, 90% and 100%. Recently, results from FRONTIER 1 were published in The New England Journal of Medicine and showed superior efficacy of JNJ-2113 at all doses tested and similar safety compared to placebo at Week 16. FRONTIER 2 (NCT05364554) is a Phase 2b multicenter, double-blind, long-term extension, dose-ranging study to evaluate the efficacy and safety of JNJ-77242113 (JNJ-2113) for the treatment of moderate-to-severe plaque psoriasis.

The study evaluated four once-daily and two twice-daily dosages of JNJ-2113 taken orally. The originating study (FRONTIER 1) began with its first participant screened on February 3, 2022. A total of 337 participants were screened of which 255 participants were randomized into six treatment groups (Placebo (n=43), 25 mg daily (n=43), 50 mg daily (n=43), 25 mg twice daily (n=41), 100 mg daily (n=43), 100mg twice daily (n=43)).

At Week 16, a total of 227 participants from FRONTIER 1 entered FRONTIER 2, the long-term extension study, and received at least one dose of study intervention (Placebo switched to 100 mg daily (n=35), 25 mg daily (n=35), 50 mg daily (n=39), 25 mg twice daily (n=40), 100 mg daily (n=40), 100 mg twice daily (n=38)). The first participant in FRONTIER 2 study was dosed on June 10, 2023. The total duration of the trial was 52 weeks.

JNJ-2113 was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and J&J, which retains exclusive worldwide rights to develop JNJ-2113 in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications. The license and collaboration agreement, established in 2017, enabled the companies to work together to discover and develop next-generation compounds that ultimately led to JNJ-2113. Investigational JNJ-2113 is the first targeted oral peptide designed to block the IL-23 receptor, which underpins the inflammatory response in moderate-to-severe plaque psoriasis (PsO) and other IL-23-mediated diseases.

JNJ-2113 binds to the IL-23 receptor with single-digit picomolar affinity and has demonstrated potent, selective inhibition of IL-23 signaling in human T cells. IL-23 plays a critical role in pathogenic T-cell activation in moderate-to-severe plaque PsO and underpins the inflammatory response in PsO and other dermatological, rheumatological and gastroenterological IL-23-mediated diseases.