icotrokinra (JNJ-2113) / Protagonist Therap, J&J - LARVOL DELTA

Treatment of Plaque Psoriasis Involving High-Impact Sites With Icotrokinra: Subgroup Analyses of the Phase 3, ICONIC-LEAD Trial (ISDS 2025) - P3 | "Of note, icotronkinra-treated participants achieved substantially greater percent mNAPSI improvement (LS Mean=43.5% vs 2.2%; p=0.005) and f-PGA0/1 (50.4% vs 21.2%; p<0.001)/f-PGA0 (24.1% vs 12.1%; p<0.05) rates vs placebo at Week 16, an early timepoint for nail assessment. Icotrokinra demonstrated high clearance rates for scalp, genitalia, hands/feet, and/or nail PsO in participants with moderate-to-severe plaque PsO."

P3 data • Dermatology • Immunology • Psoriasis • IL23A

Efficacy and Safety of Icotrokinra, a Novel Targeted Oral Peptide, in Adolescents With Moderate-to-Severe Plaque Psoriasis: Subgroup Analyses From the Phase 3 ICONIC-LEAD Study (ISDS 2025) - P3 | "At W16, 50% of ICO and 73% of placebo adolescents had ≥1 adverse event; no safety signals emerged through W24. In adolescents with moderate-to-severe PsO, higher proportions of ICO vs placebo participants achieved clear/almost clear skin at W16, with unprecedented response rates at W24 and a favorable adverse event profile."

Clinical • P3 data • Dermatology • Immunology • Psoriasis • IL23A

Johnson and Johnson Told to Justify Phase III Icotrokinra Trial Design Over Sample Size, Patient Exposure (Medical Dialogues) - "The firm made an online submission presenting phase III clinical trial protocol no. 77242113UCO3001, Amendment 1 dated 24 July 2025. After detailed deliberation, the committee opined that the proposed trial is aimed at studying the safety and efficacy of icotrokinra, an IL-23-receptor antagonist, in patients with moderate to severe ulcerative colitis...The proposal consists of two sub-studies: (i) an induction study (12-week duration) – to evaluate efficacy in inducing disease remission, and (ii) a maintenance study (40 weeks – after the initial induction phase)...The committee highlighted several critical points. (A) On completion of the induction study, all the subjects who received icotrokinra will enter the maintenance study....Accordingly, firm has been asked to submit a response for further review by the committee."

Clinical protocol • Ulcerative Colitis

ANTHEM-UC: Icotrokinra Shows Sustained Efficacy in Moderate-to-Severe Ulcerative Colitis, With Vipul Jairath, MBChB, DPhil (HCPLive) - "The findings were presented at the American College of Gastroenterology (ACG)’s 2025 Annual Scientific Meeting...Among the 252 randomized participants, the mean modified Mayo score (mMS) was 6.63, with 31.9% having mMS >7 and 58.7% presenting with a Mayo endoscopy subscore (MES) of 3, indicating moderate to severe disease activity. Nearly half (43.3%) were biologic, JAK inhibitor, or sphingosine-1-phosphate receptor modulator inadequate responders (BIO/JAKi/S1P-IR). Patients were stratified by prior biologic, JAKi, or S1P receptor modulator inadequate response status (BIO/JAKi/S1P-IR; yes or no [Y/N]) and by MES 2 or 3....By week 16, inadequate response criteria were met by 38.1% of placebo-treated patients (n = 24) compared with 17.2%, 17.7%, and 11.1% of those receiving icotrokinra 100 mg (n = 11), 200 mg (n = 11), and 400 mg (n = 7), respectively."

P2b data • Ulcerative Colitis

Icotrokinra superior to placebo for improving skin symptoms in adolescent psoriasis (Healio) - "According to the researchers, 84.1% of patients who received icotrokinra achieved clear or almost clear skin, as assessed by an investigator’s global assessment (IGA) score of 0 or 1, at week 16 vs. 27.3% in the placebo group (nominal P < .001). Similarly, icotrokinra bested placebo in terms of PASI 90 — 70.5% vs. 13.6% (nominal P < .001)."

P3 data • Psoriasis

A Study of JNJ-77242113 for the Treatment of Participants With Generalized Pustular Psoriasis or Erythrodermic Psoriasis (clinicaltrials.gov) - P3 | N=19 | Active, not recruiting | Sponsor: Janssen Pharmaceutical K.K. | Trial primary completion date: Apr 2025 ➔ Jan 2025

Trial primary completion date • Dermatology • Immunology • Psoriasis • Pustular Psoriasis

Icotrokinra: “1° endpoint: Clinical response = 63.5%”; Ulcerative colitis (Protagonist Therapeutics) - Corporate Presentation: “2° endpoint: Clinical remission = 30.2%”

P2b data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Icotrokinra: Primary completion of P3 ICONIC-UC trial (NCT07196748) for ulcerative colitis in Jan 2028 (Protagonist Therapeutics) - Corporate Presentation: Primary completion of P3 ICONIC-CD trial (NCT07196722) for Crohn’s disease in Sep 2028

Trial primary completion date • Crohn's disease • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Targeted Oral Peptide Icotrokinra for Psoriasis Involving High-Impact Sites. (PubMed, NEJM Evid) - P3 | "At 16 weeks, significantly higher proportions of participants 12 years of age and over with at least moderate psoriasis involving high-impact sites treated with icotrokinra versus placebo achieved clearance or minimal psoriasis in their skin overall and in the scalp and genital areas, but not in their hands and feet. No safety signals were identified. (Funded by Johnson & Johnson; ClinicalTrials.gov number, NCT06095102.)."

Journal • Dermatology • Immunology • Psoriasis

Oral Icotrokinra for Plaque Psoriasis in Adults and Adolescents. (PubMed, N Engl J Med) - P3 | "Selective blockade of the interleukin-23 receptor with the targeted oral peptide icotrokinra resulted in a significantly higher incidence of skin clearance at week 16 than placebo among adults and adolescents with moderate-to-severe plaque psoriasis. Longer-term data will provide a more complete understanding of the benefit-risk profile of icotrokinra. (Funded by Johnson & Johnson; ICONIC-LEAD ClinicalTrials.gov number, NCT06095115.)See also in NEJM Evidence: Targeted Oral Peptide Icotrokinra for Psoriasis Involving High‑Impact Sites."

Clinical • Journal • Dermatology • Immunology • Infectious Disease • Psoriasis • Respiratory Diseases

Efficacy and Safety of Icotrokinra, a Targeted Oral Peptide That Selectively Blocks IL-23 Receptor Activation, in Ulcerative Colitis: Results From Week 28 of ANTHEM-UC, a Phase 2b Dose-Ranging Trial (ACG 2025) - "Here we report W28 efficacy and safety of ICO from ANTHEM-UC. Participants (pts) had a modified Mayo score (mMS) of 5–9 inclusive, a Mayo endoscopy subscore (MES) ≥2, and inadequate response/intolerance (IR) to TNFα blockers, vedolizumab, ustekinumab, JAK inhibitors, or S1P receptor modulators (BIO/JAKi/S1P-IR) or IR to corticosteroids, AZA, or 6-MP. Analyses included all 252 randomized pts who received study medication: mean mMS, 6.63; mMS >7, 31.9%; MES=3, 58.7%; BIO/JAKi/S1P-IR, 43.3%. W16 inadequate response criteria were met by 24 (38.1%), 11 (17.2%), 11 (17.7%) and 7 (11.1%) pts receiving PBO & ICO 100, 200 and 400 mg.Relative to PBO, all ICO doses demonstrated clinically meaningful rates of clinical response, clinical remission, symptomatic remission, endoscopic improvement, and HEMI at W28 (Figure). Relative to W12 outcomes, rates of clinical response, clinical remission, endoscopic improvement, and HEMI continued to increase through W28 in each ICO dose..."

Clinical • P2b data • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Inflammatory Bowel Disease • Novel Coronavirus Disease • Respiratory Diseases • Tuberculosis • Ulcerative Colitis • IL23A

Is the Future Oral? Towards Sustainable and Patient-Centered Biologic Treatment in Dermatology. (PubMed, Australas J Dermatol) - No abstract available

Journal • Dermatology • Immunology • Psoriasis

Protagonist Announces New Icotrokinra Data in Ulcerative Colitis... (ACCESS Newswire) - "Icotrokinra demonstrated clinically meaningful outcomes at Week 28 in the Phase 2b ANTHEM-UC study in ulcerative colitis, with 31.7% of patients achieving clinical remission and 38.1% showing endoscopic improvement versus placebo."

P2b data • Ulcerative Colitis

Icotrokinra long-term results affirm promise of targeted oral peptide with high rates of durable skin clearance and favorable safety profile in difficult-to-treat scalp and genital psoriasis (PRNewswire) - "The ICONIC-TOTAL study, presented at the 2025 Fall Clinical Dermatology Conference...72% of patients with scalp psoriasis achieved a scalp-specific Investigator's Global Assessment (ss-IGA) 0/1 score and 57% achieved ss-IGA 0; 85% of patients with genital psoriasis achieved a Physician's Global Assessment of Genitalia (sPGA-G) 0/1 and 73% achieved sPGA-G 0...In the smaller subset of patients with hand/foot psoriasis, treatment with icotrokinra showed a numerically higher rate of skin clearance at Week 16, which increased through Week 52 with patients achieving a hand and/or foot Physician's Global Assessment (hf-PGA)e score of 0/1 increasing from 42% to 62%."

P3 data • Psoriasis

Efficacy and Safety of Icotrokinra, a Novel Targeted Oral Peptide (IL-23R-Inhibitor), in Adolescents With Moderate-to-Severe Plaque Psoriasis: Subgroup Analyses From a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study (ICONIC-LEAD) (ACR Convergence 2025) - P3 | "In adolescents with moderate-to-severe psoriasis, higher proportions of ICO vs placebo participants achieved clear/almost clear skin at Week 16, with unprecedented response rates at Week 24 and a favorable adverse event profile."

Clinical • P3 data • Dermatology • Immunology • Psoriasis • IL23A

Phase 3 Results From an Innovative Trial Design of Treating Plaque Psoriasis Involving Difficult-to-Treat, High-Impact Sites With Icotrokinra, a Targeted Oral Peptide That Selectively Inhibits the IL-23–Receptor (ACR Convergence 2025) - P3 | "ICO demonstrated significantly higher rates of overall skin, scalp, and genital PsO clearance vs placebo with a favorable safety profile. Basket-like trial designs can be used to efficiently study special skin sites in patients with PsO and other diseases."

P3 data • Dermatology • Immunology • Infectious Disease • Psoriasis • IL23A

Icotrokinra (ICO), a Novel Targeted Oral Peptide, in Patients (Pts) With Psoriatic Disease: Exploratory Assessments From a Phase 2 Psoriasis (PsO) Study Informing a Phase 3 Clinical Program in Psoriatic Arthritis (PsA) (ACR Convergence 2025) - "Exploratory assessments from the Ph 2 FRONTIER 1 study showed comparable ICO PD effects between pts with PsO only, and with PsO+PsA. ICO-treated pts with PsO+PsA reported numerically greater improvements in PsA-relevant PROMIS-29 domains vs PBO. Informed by these post hoc analyses and model-based meta-analyses that bridged data from PsO to PsA, the multicenter, double-blind, PBO-controlled ICONIC-PsA 1 and ICONIC-PsA 2 studies will comprehensively evaluate the novel targeted oral peptide ICO in diverse population of pts with active PsA."

Clinical • P2 data • P3 data • Dermatology • Fatigue • Immunology • Inflammation • Inflammatory Arthritis • Psoriasis • Psoriatic Arthritis • Rheumatology • Seronegative Spondyloarthropathies • IL17A • IL22 • IL23A

Early Systemic and Skin Pharmacodynamic Effects of Icotrokinra in Participants with Moderate-to-Severe Plaque Psoriasis: Results Through Week 24 of the Phase 3, ICONIC-LEAD Study (ACR Convergence 2025) - "Consistent with its mechanism of action of selectively and potently blocking the IL-23R, ICO significantly attenuated systemic and skin biomarkers related to IL-23 pathway activation and PsO disease severity. Findings demonstrated both early and substantial ICO effects, with levels of IL-23 pathway biomarkers of systemic and skin inflammation normalizing to a healthy state. Overall, these comprehensive biomarker findings are consistent with significant skin clearance achieved with this first targeted oral peptide to selectively inhibit IL-23 pathway activation."

P3 data • PK/PD data • Dermatitis • Dermatology • Immunology • Inflammation • Psoriasis • IL17A • IL22 • IL23A • NFKBIA

ICOTROKINRA, A TARGETED ORAL PEPTIDE THAT SELECTIVELY BLOCKS IL-23 RECEPTOR ACTIVATION, IN MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: WEEK 12 RESULTS FROM THE PHASE 2B, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, TREAT-THROUGH, DOSE-RANGING ANTHEM-UC TRIAL (UEGW 2025) - "Aims & Eligible participants with moderately to severely active UC defined as a modified Mayo score (mMS) of 5–9 (inclusive) and a Mayo endoscopy subscore (MES) ≥2 and history of inadequate response or intolerance (IR) to TNFα blockers, vedolizumab, ustekinumab, JAK inhibitors, or S1P modulators (BIO/JAKi/S1Pi-IR) or IR to corticosteroids (CS), azathioprine, or mercaptopurine were randomized 1:1:1:1 to once-daily (qd) oral icotrokinra 100 mg, 200 mg, 400 mg, or placebo (PBO). Icotrokinra, the first-in-class targeted oral peptide that selectively blocks IL-23R activation, demonstrated efficacy and a favorable safety profile in participants with moderately to severely active UC."

Clinical • P2b data • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Infectious Disease • Inflammatory Bowel Disease • Respiratory Diseases • Tuberculosis • Ulcerative Colitis • IL23A

Johnson & Johnson in talks to acquire Protagonist Therapeutics, source says (Yahoo Finance) - "Shares of Protagonist surged more than 30% in afternoon trading. The company had a market capitalization of $4.2 billion as of Thursday's close....The two companies are working on the development of an oral treatment, icotrokinra, for immune diseases, including plaque psoriasis and ulcerative colitis, with J&J holding the exclusive rights to commercialize the product."

M&A • Stock price • Psoriasis • Ulcerative Colitis

Icotrokinra data in ulcerative colitis show potential for a standout combination of therapeutic benefit and a favorable safety profile in once-daily pill (J&J Press Release) - "At Week 12, patients treated with 400 mg of icotrokinra once-daily achieved a clinical response rate of 63.5% versus 27% for placebo (p<0.001), while patients treated with 200 mg and 100 mg of icotrokinra once-daily achieved 58.1% and 54.7% response rates, respectively...Across multiple secondary endpoints, in the 400 mg icotrokinra group, significantly greater proportions of patients achieved clinical remission, symptomatic remission and endoscopic improvement at Week 12 compared to placebo....Similar proportions of participants reported adverse events and serious adverse events through Week 12 across all icotrokinra dose groups and the placebo group."

P2b data • Ulcerative Colitis

ICONIC-CD: A Study of Icotrokinra in Participants With Moderately to Severely Active Crohn's Disease (clinicaltrials.gov) - P2/3 | N=1092 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Crohn's disease • Gastroenterology • Genetic Disorders • Immunology • Inflammatory Bowel Disease

ICONIC-UC: A Protocol of Icotrokinra Therapy in Adult and Adolescent Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P3 | N=882 | Recruiting | Sponsor: Janssen Research & Development, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Maintenance of Response With Icotrokinra, a Targeted Oral Peptide, for the Treatment of Moderate-to-Severe Plaque Psoriasis: Randomized Treatment Withdrawal in Adults (Weeks 24-52) and Continuous Treatment in Adolescents (Through Week 52) From the Phase 3, ICONIC-LEAD Trial (EADV 2025) - P3 | "1. Bissonnette R. AAD Annual Meeting; March 8, 2025; Orlando, FL, USA."

Clinical • Late-breaking abstract • P3 data • Dermatology • Immunology • Psoriasis • IL23A

ICONIC-UC: A Protocol of Icotrokinra Therapy in Adult and Adolescent Participants With Moderately to Severely Active Ulcerative Colitis (clinicaltrials.gov) - P3 | N=882 | Not yet recruiting | Sponsor: Janssen Research & Development, LLC

New P3 trial • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis