pNew icotrokinra (JNJ-2113) data from a subgroup analysis of ICONIC-LEAD, a phase III registrational study in moderate-to-severe plaque psoriasis.- Protagonist

Protagonist Therapeutics, Inc. announced new icotrokinra (JNJ-2113) data from a subgroup analysis of ICONIC-LEAD, the first ever Phase III registrational study in moderate-to-severe plaque psoriasis (PsO) to assess efficacy and safety of an orally delivered systemic therapy in adolescents and adults simultaneously.

Data from an oral presentation at the 2025 World Congress of Pediatric Dermatology (WCPD) Annual Meeting show adolescents treated with once daily icotrokinra achieved higher rates of clear or almost clear skin at Week 16 compared to patients receiving placebo, with no new safety signals identified. Icotrokinra is a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor and is being studied in adults and adolescents 12 years of age and older with moderate-to-severe plaque PsO.

Key findings from the adolescent cohort of the ICONIC-LEAD study:

• i. At week 16, 84.1% of adolescent patients treated with once daily icotrokinra achieved an Investigator's Global Assessment (IGA) score of 0/1 (clear or almost clear skin) and 70.5% achieved a Psoriasis Area and Severity Index (PASI)^c 90 response, compared to 27.3% and 13.6% receiving placebo, respectively.
• ii. Response rates continued to improve through Week 24 where 86.4% of adolescents achieved IGA 0/1 and 88.6% achieved PASI 90.
• iii. At week 24, 75% of adolescents achieved IGA 0 (completely clear skin) and 63.6% achieved PASI 100.
• iv. Icotrokinra demonstrated a favorable safety profile, with 50% of adolescents treated with icotrokinra experienced ≥1 adverse event (AE), compared to 73% of adolescents receiving placebo at 16 weeks. No new safety signals were identified.

"We are thrilled with the data from the Phase III ICONIC LEAD subgroup analysis, which suggests icotrokinra may provide a novel first line treatment option for moderate-to-severe plaque psoriasis in adolescents who have not yet received an advanced injectable therapy," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "Icotrokinra offers a unique combination of complete skin clearance and favorable safety profile in a once-daily pill that aligns with the needs and preferences of adolescent patients struggling with the challenges of the visible and uncomfortable nature of psoriasis. The icotrokinra data continue to demonstrate the potential to become a first-line therapy for plaque psoriasis."

Editor's notes:

1. ICONIC-LEAD is a Phase III randomized controlled trial (RCT) evaluating the efficacy and safety of icotrokinra compared with placebo in 684 participants (icotrokinra=456; placebo=228) 12 years of age or older with moderate-to-severe plaque PsO, with the higher efficacy bar of PASI 90 and IGA score of 0/1 with at least a 2-grade improvement as co-primary endpoints. ICONIC-LEAD enrolled 66 adolescent patients.
2. The IGA is a five-point scale with a severity score ranging from 0 to 4, where 0 indicates clear, 1 is minimal, 2 is mild, 3 is moderate, and 4 indicates severe disease.
3. The PASI score grades the amount of surface area on each body region that is covered by psoriasis plaques and the severity of plaques for their redness, thickness and scaliness.³ PASI 90 corresponds to an improvement of >=90% in PASI score from baseline.

About the ICONIC Clinical Development Program The pivotal Phase III ICONIC clinical development program of icotrokinra (in adult and adolescent individuals with moderate-to-severe plaque PsO was initiated with two studies in Q4 2023 - ICONIC-LEAD and ICONIC-TOTAL - pursuant to the license and collaboration agreement between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., a Johnson & Johnson company. The ICONIC program is being conducted by Johnson & Johnson.

ICONIC-LEAD (NCT06095115) is a randomized controlled trial (RCT) to evaluate the efficacy and safety of icotrokinra compared with placebo in participants with moderate-to-severe plaque PsO, with PASI 90 and IGA score of 0 or 1 with at least a 2-grade improvement as co-primary endpoints.

ICONIC-TOTAL (NCT06095102) is a RCT to evaluate the efficacy and safety of icotrokinra compared with placebo for the treatment of PsO in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or hands and feet) with overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.

Other Phase III studies in the development program include ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604), which are evaluating the efficacy and safety of icotrokinra compared with both placebo and deucravacitinib in adults with moderate-to-severe plaque PsO.  ICONIC-ASCEND will evaluate the efficacy and safety of icotrokinra compared with placebo and ustekinumab in participants with moderate-to-severe plaque psoriasis. ICONIC-PsA 1 (NCT06878404) and ICONIC-PsA 2 (NCT06807424) will evaluate the efficacy and safety of icotrokinra compared to placebo in participants with active psoriatic arthritis.