Protagonist Therapeutics has reported new clinical and preclinical data at the European Academy of Dermatology and Venereology (EADV) 2025 Congress in Paris, highlighting progress with its oral peptide pipeline in psoriasis.

Phase 3 results from the ICONIC-ADVANCE 1 and 2 trials showed icotrokinra, an oral peptide targeting the IL-23 receptor, outperformed Bristol Myers Squibb’s deucravacitinib in patients with moderate to severe plaque psoriasis. The drug achieved superior skin clearance at weeks 16 and 24 while maintaining adverse event rates similar to placebo. No new safety signals were observed.

Longer-term findings from the ICONIC-LEAD study demonstrated sustained efficacy over 52 weeks in both adults and adolescents. At week 52, 84% of adults who remained on icotrokinra maintained a PASI 90 response compared with 21% of those switched to placebo. In adolescents, 86% achieved PASI 90 after one year of treatment.

Johnson & Johnson, Protagonist’s development partner, has also initiated ICONIC-ASCEND, a head-to-head Phase 3 trial comparing oral icotrokinra with injectable ustekinumab, making it the first study of its kind to pit an oral pill directly against a biologic in psoriasis.

Alongside the late-stage clinical updates, Protagonist presented preclinical data on PN-881, an oral peptide designed to block IL-17. PN-881 demonstrated high binding affinity to IL-17A and IL-17F, metabolic stability across multiple species, and dose-dependent efficacy in animal models of psoriasis. The company expects to begin a Phase 1 trial of PN-881 in the coming weeks.

Dinesh Patel, president and chief executive officer at Protagonist, said: “The data presented at EADV demonstrate the potential for icotrokinra to set a new standard of treatment for psoriasis patients with a once-daily targeted oral therapy that selectively blocks the IL-23R. Additionally, the preclinical data on our next drug candidate in the I&I space, PN-881, being presented at the conference highlight its potential as a first-in-class oral peptide antagonist targeting the three therapeutically relevant dimeric forms of IL-17.”

Protagonist is positioning its portfolio as a new generation of oral therapies that could challenge biologics in inflammatory diseases. With icotrokinra moving through Phase 3 and PN-881 approaching human trials, the company is expanding its footprint in dermatology and inflammatory medicine.