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
Updated ANTHEM-UC data support Phase 3 clinical development of icotrokinra in both moderately to severely active ulcerative colitis and Crohn’s disease
In areas of high impact, 72% of patients with scalp psoriasis and 85% with genital psoriasis treated with icotrokinra achieved site-specific clear or almost clear skin at Week 52 in Phase 3 ICONIC-TOTAL study
Further, 67% of patients treated with icotrokinra in the ICONIC-TOTAL study achieved overall rates of clear or almost clear skin by Week 24, which was maintained through Week 52
NEWARK, CALIFORNIA / ACCESS Newswire / October 27, 2025 / Protagonist Therapeutics, Inc. (“Protagonist” or the “Company”) today announced new data from two studies of icotrokinra, a first-in-class investigational targeted oral peptide that precisely blocks the IL-23 receptor, presented at two recent medical conferences.
Week 28 data from the Phase 2b ANTHEM-UC study of icotrokinra will be presented at the 2025 American College of Gastroenterology Annual Scientific Meeting (ACG), demonstrating sustained and clinically meaningful results, with all doses (100 mg, 200 mg and 400 mg) showing higher rates of clinical response a , clinical remission b , endoscopic improvement c and histologic-endoscopic mucosal improvement (HEMI) d at Week 28 compared to placebo. [1] These outcomes build on Week 12 data that was recently presented at United European Gastroenterology (UEG) Week 2025.
|
Icotrokinra 400 mg once daily |
Week 12 |
Week 28 |
Placebo (at Week 28) |
|
Clinical response 1 |
63.5% |
66.7% |
25.4% |
|
Clinical remission 1 |
30.2% |
31.7% |
9.5% |
|
Endoscopic improvement 1 |
36.5% |
38.1% |
11.1% |
|
HEMI rates 1 |
28.6% |
33.1% |
11.1% |
Based on results from the Phase 2b ANTHEM-UC study, Johnson & Johnson has initiated the ICONIC-UC Phase 3 protocol in adults and adolescents with moderately to severely active UC, as well as the ICONIC-CD Phase 2b/3 protocol in adults with moderate to severely active Crohn’s disease.
Additionally, new long-term 52-week data from the Phase 3 ICONIC-TOTAL study e , presented last week at the 2025 Fall Clinical Dermatology Conference, show icotrokinra demonstrated high and durable rates of site-specific psoriasis clearance affecting these high-impact and difficult-to-treat areas of the body. [2]
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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 f
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85% of patients with genital psoriasis achieved a Physician’s Global Assessment of Genitalia (sPGA-G) 0/1 and 73% achieved sPGA-G 0 g
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) h score of 0/1 increasing from 42% to 62%.
Overall response rates among patients treated with once-daily icotrokinra were maintained through Week 52, with 67% of patients treated with icotrokinra achieving clear or almost clear skin (Investigator’s Global Assessment (IGA) i 0/1) and 44% achieving completely clear skin (IGA 0) at Week 52. The overall response rates were also comparable among patients who received icotrokinra for all 52 weeks and those who transitioned from placebo to icotrokinra at Week 16 (67% versus 68% achieved IGA0/1, respectively). Across treatment groups, adverse event and serious adverse event rates were similar through Week 52 compared to those through Week 16, with no new safety signals identified.
“Additional data from Phase 2b ANTHEM-UC and Phase 3 ICONIC-TOTAL studies continue to show a strong durability of response and clinical benefit of icotrokinra treatment in a range of inflammatory and immunological diseases,” said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. “We are very pleased to see that the ICONIC development program now includes both ICONIC-UC, a Phase 3 study in adults with moderately to severely active UC, and ICONIC-CD, a Phase 2b/3 study in adults with moderate to severely active Crohn’s disease. Our goal continues to be delivering well-differentiated oral targeted therapy treatments for patients as we continue to advance our oral peptides-based scientific and innovation leadership in the I&I field.”
Editor’s notes:
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Clinical response was defined as a decrease from baseline in the modified Mayo score by greater than or equal to (>=) 30 percent (%) and >=2 points, with either a >=1-point decrease from baseline in the rectal bleeding subscore or a rectal bleeding subscore of 0 or 1.
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Clinical remission was defined as a stool frequency subscore of 0 or 1, a rectal bleeding subscore of 0, and an endoscopy subscore of 0 or 1.
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Endoscopic improvement was defined as an endoscopy subscore of 0 or 1.
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Histologic-endoscopic mucosal improvement (HEMI) was defined as histologic remission (absence of neutrophils from the mucosa in both lamina propria and epithelium, no crypt destruction, and no erosions, ulcerations, or granulation tissue according to the Geboes grading system) and endoscopic improvement (MES of 0 or 1).
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ICONIC-TOTAL evaluates the efficacy and safety of icotrokinra compared with placebo in participants with at least moderate scalp, genital, and/or hand/foot PsO with once-daily icotrokinra or placebo, with placebo-to-icotrokinra transition at Week 16.
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The ss-IGA is a five-point scale where scalp lesions are assessed in terms of clinical signs of redness, thickness, and scaliness on a severity score ranging from 0 to 4, where 0 indicates absence of disease, 1 is very mild, 2 is mild, 3 is moderate and 4 indicates severe disease.
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The sPGA-G is a six-point scale used to evaluate the severity of genital psoriasis at a given time point ranging from 0 to 5, where 0 indicates clear, 1 is minimal, 2 is mild, 3 is moderate, 4 is severe and 5 indicates very severe disease. [3]
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The Physician’s Global Assessment of Psoriasis on the Hands and/or Feet (hf-PGA) assesses the severity of hand and foot psoriasis using a 5-point scale to score the plaques on the hands and feet as: clear (0), almost clear (1), mild (2), moderate (3) and severe (4). [4]
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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. [5]
About ANTHEM-UC
ANTHEM-UC ( NCT06049017 ) is a Phase 2b multicenter, randomized, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of icotrokinra (JNJ-77242113, JNJ-2113) in patients with moderately to severely active ulcerative colitis who had an inadequate response or intolerance to conventional therapy (e.g., thiopurines or corticosteroids), prior biologics (TNF antagonists or vedolizumab) and/or ozanimod or approved JAK inhibitors. The study is evaluating three once-daily dosages of icotrokinra taken orally. Participants who complete the Week 28 assessments and have achieved clinical response at Week 28 and who, in the opinion of the investigator, will continue to benefit from treatment with study intervention will continue in the 48-week long term extension (LTE) period and receive the same treatment up to Week 76.
About Ulcerative Colitis
Ulcerative colitis (UC) is a chronic disease of the large intestine, also known as the colon, in which the lining of the colon becomes inflamed and develops tiny open sores, or ulcers, that produce pus and mucus. It is the result of the immune system’s overactive response.Symptoms vary but may typically include loose and more urgent bowel movements, rectal bleeding or bloody stool, persistent diarrhea, abdominal pain, loss of appetite, weight loss, and fatigue.
About the ICONIC Clinical Development Program
The pivotal Phase 3 ICONIC clinical development program of icotrokinra (JNJ-2113) in adult and pediatric patients 12 years of age and older 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.
ICONIC-LEAD ( NCT06095115 ) is a 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 3 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.
Johnson & Johnson has also initiated the ICONIC-UC Phase 3 protocol in adults and adolescents with moderately to severely active UC as well as the ICONIC-CD Phase 2b/3 protocol in adults with moderate to severely active Crohn’s disease.
About Plaque Psoriasis
Plaque psoriasis (PsO) is a chronic immune-mediated disease resulting in overproduction of skin cells, which causes inflamed, scaly plaques that may be itchy or painful. It is estimated that 8 million Americans and more than 125 million people worldwide live with the disease. Nearly one-quarter of all people with plaque PsO have cases that are considered moderate-to-severe.Plaques typically appear as raised patches with a silvery white buildup of dead skin cells or scales.Plaques may appear red in lighter skin or more of a purple, gray or dark brown color in patients with darker skin tones. Plaques can appear anywhere on the body, although they most often appear on the scalp, knees, elbows, and torso.Living with plaque PsO can be a challenge and impact life beyond a person’s physical health, including emotional health, relationships, and handling the stressors of life. Psoriasis on highly visible areas of the body or sensitive skin, such as the scalp, hands, feet, and genitals, can have an increased negative impact on quality of life.
About Protagonist
Protagonist Therapeutics is a discovery through late-stage development biopharmaceutical company. Two novel peptides derived from Protagonist’s proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application (NDA) for icotrokinra submitted to the FDA in July and in the NDA submission for rusfertide expected by end of 2025. Icotrokinra (formerly, JNJ-2113), is a first-in-class investigational targeted oral peptide that precisely blocks the Interleukin-23 receptor (“IL-23R”) which is licensed to Janssen Biotech, Inc., a Johnson & Johnson company. Following icotrokinra’s joint discovery by Protagonist and Johnson & Johnson scientists pursuant to the companies’ IL-23R collaboration, Protagonist was primarily responsible for the development of icotrokinra through Phase 1, with Johnson & Johnson assuming responsibility for development in Phase 2 and beyond. Rusfertide, a mimetic of the natural hormone hepcidin, is currently in Phase 3 development for the rare blood disorder polycythemia vera (PV). Rusfertide is being co-developed and will be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement entered in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of preclinical stage drug discovery programs addressing clinically and commercially validated targets, including IL-17 oral peptide antagonist PN-881, obesity triple agonist peptide PN-477, and the oral hepcidin program.
More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company’s website at https://www.protagonist-inc.com/ .
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of icotrokinra, and expectations regarding the icotrokinra development program. In some cases, you can identify these statements by forward-looking words such as “anticipate,” “believe,” “may,” “will,” “expect,” or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreements with Johnson & Johnson and Takeda, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading “Risk Factors” contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release.
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References:
[1] Jairath V., et al. 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. Poster 1066 at ACG Annual Scientific Meeting 2025. October 2025.
[2] Lain, E et al. Durability of Response to the Targeted Oral Peptide Icotrokinra for High-Impact Site Psoriasis: 1-Year ICONIC-TOTAL Findings. Oral presentation (Presentation FC01.1G) at the 2025 Fall Clinical Dermatology Conference. October 2025.
[3] Merola JF, Bleakman AP, Gottlieb AB, et al. The Static Physician’s Global Assessment of Genitalia: a clinical outcome measure for the severity of genital psoriasis. J Drugs Dermatol . 2017;16(8):793-799
[4] Goldblum O, et al. Validation of the physician’s global assessment of psoriasis of the hands and/or feet as a clinical endpoint. J Am Acad Dermatol. 2013:68(4)Supplement1:AB218.
[5] Simpson E, Bissonnette R, Eichenfield LF, et al. The validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD™): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis [published online April 25, 2020]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2020.04.104. Accessed April 2025.
SOURCE: Protagonist Therapeutics
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