Protagonist Therapeutics announces presentations of icotrokinra data

Protagonist Therapeutics (PTGX) announced new data from the Phase 3 ICONIC-ADVANCE 1 and 2 studies which assessed the superiority of icotrokinra, a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor, compared to deucravacitinib in patients with moderate-to-severe plaque psoriasis. These data are being presented at the 2025 European Academy of Dermatology and Venereology Congress in Paris, France. Additionally, new long-term 52-week data from the Phase 3 ICONIC-LEAD study investigating icotrokinra in adults and pediatric patients 12 years of age and older with moderate to severe plaque psoriasis will be presented as a late-breaking abstract at EADV. Preclinical data on PN-881, a first-in-class oral peptide targeting the IL-17 pathway and fully owned by Protagonist, are also being presented at EADV.3 The Company expects that the first subject will be dosed in the Phase 1 single ascending and multiple ascending dose human clinical study in the coming weeks. The ICONIC-ADVANCE 1 and 2 studies assessed the superiority of icotrokinra compared to deucravacitinib in patients with moderate-to-severe plaque psoriasis. As previously announced, in the studies icotrokinra met both co-primary endpoints compared to placebo at Week 16 with similar adverse event rates and showed superiority to deucravacitinib at multiple timepoints in adult patients. Icotrokinra showed superior skin clearance vs placebo and deucravacitinib. A similar proportion of patients experienced adverse events between icotrokinra and placebo groups, with no new safety signals identified. Icotrokinra AE rates were numerically lower vs deucravacitinib through Week 24. In the ICONIC-LEADb drug withdrawal/re-retreatment study, icotrokinra demonstrated sustained skin clearance and a favorable safety profile through Week 52 with no new safety signals identified. At Week 52, adult icotrokinra PASI 90 responders re-randomized to icotrokinra at Week 24 had superior maintenance of PASI 90 response versus those re-randomized to placebo. At Week 52, 86% of adolescents who received icotrokinra for the full 52 weeks and 77% of those switched from placebo to icotrokinra at Week 16 achieved PASI 90 response.2 ICONIC-LEAD Week 16 primary endpoint data was previously presented at the American Academy of Dermatology 2025 Congress. Protagonist’s collaboration partner, Johnson & Johnson, also announced initiation of the Phase 3 ICONIC-ASCEND study,c the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable biologic, ustekinumab, in psoriasis, representing an important step forward in psoriasis research. Preclinical data on PN-881, the next generation IL-17 oral peptide antagonist for psoriasis will also be presented at the conference, key takeaways included: Exhibited in vitro potency comparable to bimekizumab, and superior to secukinumab, in the nanomolar to picomolar range. 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. Oral dosing showed dose-dependent efficacy with significant reduction in skin thickness in a 5-day rat IL-23 induced skin inflammation model.