Protagonist announces icotrokinra data from Phase 3 ICONIC-TOTAL study

Protagonist Therapeutics (PTGX) announced new clinical data from the Phase 3 ICONIC-TOTAL a study investigating icotrokinra, the first-in-class oral peptide antagonist targeting IL-23 receptor and preclinical characterization of PN-881, the first-in-class oral peptide antagonist blocking the three dimeric forms of IL-17, were presented separately today at the 2025 Society for Investigative Dermatology (SID) Annual Meeting in San Diego, CA. The ICONIC-TOTAL study, conducted by Protagonist’s collaboration partner, Johnson & Johnson, evaluated adults and adolescents 12 years of age and older with body surface area as low as 1% and at least moderate plaque psoriasis affecting high-impact skin sites. Key findings from the high-impact skin sites cohort of the icotrokinra ICONIC-TOTAL study: At week 16, 57% of patients treated with once daily icotrokinra achieved the study’s primary endpoint with an Investigator’s Global Assessment b score of 0/1 and a greater than or equal to2-grade improvement from baseline at Week 16 compared to 6% of patients receiving placebo. 66% of patients with scalp psoriasis achieved a scalp-specific Investigator’s Global Assessment c score of 0/1 compared to 11% receiving placebo at 16 weeks. 77% of patients with genital psoriasis achieved a static Physician’s Global Assessment of Genitalia d score of 0/1 compared to 21% receiving placebo at 16 weeks. In the smaller subset of patients with hand/foot psoriasis, patients showed a numerically higher rate of skin clearance at Week 16 with 42% achieving a hand and/or foot Physician’s Global Assessment e score of 0/1 compared to 26% receiving placebo. Icotrokinra demonstrated a favorable safety profile. A similar proportion of patients experienced adverse events and serious adverse events in icotrokinra and placebo respectively through Week 16, with no new safety signals identified. PN-881 represents Protagonist’s next generation of oral peptides for psoriasis. Key takeaways from the pre-clinical characterization of the IL-17 oral peptide antagonist PN-881: Exhibited nanomolar to picomolar in vitro potency comparable to bimekizumab and superior to secukinumab. Showed metabolic stability in several matrices across several species, making it a suitable candidate for oral delivery. Demonstrated PD-based target engagement in a mouse IL-17 challenge model after oral dosing. Demonstrated dose-dependent efficacy with significant reduction in skin thickness in a 5-day rat IL-23 induced skin inflammation model after oral dosing.