The Fort Worth Press - Protagonist Announces Icotrokinra Application for Approval in Plaque Psoriasis Submitted to the European Medicines Agency

Icotrokinra is a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor ¹

Filing based on four Phase 3 studies that met all primary and co-primary endpoints. This unprecedented data package includes head-to-head superiority comparisons versus deucravacitinib, adolescent data, and evaluation of difficult to treat skin sites^2,3,4,5,6

Submission underscores that icotrokinra has the potential to offer moderate-to-severe plaque psoriasis patients the combination of complete skin clearance and a favourable safety profile, relative to comparators, with the simplicity of a once-daily tablet. ^2,3,4,5,6

NEWARK, CA / ACCESS Newswire / September 11, 2025 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") today announced the submission of an application to the European Medicines Agency (EMA) by Johnson & Johnson seeking the first approval of icotrokinra, a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor for the treatment of adults and pediatric patients 12 years of age and older (adolescents) with moderate-to-severe plaque psoriasis (PsO).¹Icotrokinra is an investigational targeted oral tablet that is designed to block the IL-23 receptor,which underpins the inflammatory response in PsO and offers potential in other IL-23-mediated diseases.^7,8

The application included data from four Phase 3 studies conducted as part of the ICONIC clinical development program, including ICONIC-LEAD^a, ICONIC-TOTAL^b, and ICONIC-ADVANCE 1 & ICONIC-ADVANCE 2^c. Treatment with icotrokinra met all primary and co-primary endpoints across the development program among adults and adolescents 12 years of age and older with moderate-to-severe PsO, demonstrating significant skin clearance and a favourable safety profile in a once-daily tablet, as previously established in the ICONIC-LEAD and ICONIC-TOTAL clinical studies. ^2,3,4,5,6 Results from the ICONIC-ADVANCE 1 & 2 studies show icotrokinra achieved co-primary endpoints and showed superiority to deucravacitinib in moderate-to-severe PsO.^d,e,5,6 Across all studies, pooled safety data showed a similar proportion of patients experienced adverse events (AEs) between icotrokinra (49.1%) and placebo (51.9%) groups, with no new safety signals identified to date.^2,3,4,5,6

"This EMA submission comes on the heels of a U.S. FDA NDA filing in late July, both of which are supported by a very comprehensive clinical data package demonstrating the significant impact icotrokinra has in the clinical setting, and highlighting its potential to disrupt the current treatment paradigm and transform the approach of plaque psoriasis care," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "We look forward to sharing additional data in ongoing studies, including the ANTHEM ulcerative colitis 12-week data at the upcoming United European Gastroenterology meeting as well as data from the ICONIC-LEAD and ICONIC-ADVANCE trials being presented at the European Academy of Dermatology and Venereology Congress in Paris next week."

Data submitted to the EMA as part of the application include:

• Results from the Phase 3 ICONIC-LEAD study, presented as a late-breaking abstract at the 2025 American Academy of Dermatology (AAD) Annual Meeting, showed that icotrokinra successfully met the co-primary endpoints of an Investigator's Global Assessment (IGA)^d score of 0/1 (clear or almost clear skin) and Psoriasis Area and Severity Index (PASI)^e 90 compared to placebo at Week 16.²

• A subgroup analysis of ICONIC-LEAD, presented at the 2025 World Congress of Pediatric Dermatology (WCPD), which demonstrated 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.³

• Data from the Phase 3 ICONIC-TOTAL study, presented at the 2025 Society for Investigative Dermatology (SID) Annual Meeting, that highlighted the potential of icotrokinra in patients with difficult-to-treat scalp and genital psoriasis.⁴

• Results from the Phase 3 ICONIC-ADVANCE 1 & ICONIC-ADVANCE 2 studies, that further reinforced the overall efficacy profile, met co-primary endpoints of IGA 0/1 and PASI 90 versus placebo at Week 16. Icotrokinra also met all key secondary endpoints at Weeks 16 and 24 that measured superiority to deucravacitinib in patients with moderate-to-severe PsO.^5,6,9

• Long-term data from the ICONIC development program, including at least 52-weeks of treatment for ICONIC-LEAD and ICONIC-TOTAL, and results from a randomized withdrawal analysis evaluating the durability of response, are being prepared for presentation at a future medical meeting.

Editor's notes:

1. ICONIC-LEAD is a Phase 3 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 psoriasis, measuring the percentage of participants who achieve a PASI 90 response and an IGA score of 0/1 with at least a 2-grade improvement as co-primary endpoints. ICONIC-LEAD enrolled 66 adolescent patients.¹⁰

2. ICONIC-TOTAL is a Phase 3 RCT evaluating the efficacy and safety of icotrokinra compared with placebo for the treatment of plaque psoriasis in 311 participants (icotrokinra=208; placebo=103) 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.¹¹

3. ICONIC-ADVANCE 1 & 2 are Phase 3 RCTs evaluating the efficacy and safety of icotrokinra compared with placebo and deucravacitinib in participants with moderate-to-severe plaque psoriasis with PASI 90 and IGA score of 0/1 with at least a 2-grade improvement as co-primary endpoints.^9,12

4. 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.¹³

5. 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.¹⁴ PASI 90 corresponds to an improvement of >=90% in PASI score from baseline.¹⁴

About the ICONIC Clinical Development Programme
The pivotal Phase 3 ICONIC clinical development program of icotrokinra (JNJ-2113) in adult and adolescent individuals with moderate-to-severe plaque psoriasis 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 & Johson company.¹⁵

ICONIC-LEAD (NCT06095115) is a RCT to evaluate the efficacy and safety of icotrokinra compared with placebo in participants with moderate-to-severe plaque psoriasis, with PASI 90 and IGA score of 0 or 1 with at least a 2-grade improvement as co-primary endpoints.¹⁰

ICONIC-TOTAL (NCT06095102) is a RCT to evaluate the efficacy and safety of icotrokinra compared with placebo for the treatment of psoriasis in participants with at least moderate severity affecting special areas (e.g., scalp, genital, and/or hands and feet) with an overall IGA score of 0 or 1 with at least a 2-grade improvement as the primary endpoint.¹¹

Other Phase 3 studies in the development programme 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 psoriasis.^9,12

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. ^16,17

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. On Caucasian skin, plaques typically appear as raised, red patches covered with a silvery white buildup of dead skin cells or scale. On skin of color, the plaques may appear darker and thicker, and more of a purple, gray, or dark brown color. 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 Icotrokinra (JNJ-77242113, JNJ-2113)
Investigational icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor, which underpins the inflammatory response in moderate-to-severe plaque PsO, ulcerative colitis, and offers potential in other IL-23-mediated diseases. Icotrokinra binds to the IL-23 receptor with single-digit picomolar affinity and demonstrates potent, selective inhibition of IL-23 signaling in human T cells. The license and collaboration agreement established between Protagonist Therapeutics, Inc. and Janssen Biotech, Inc., a Johnson & Johnson company, in 2017 enabled the companies to work together to discover and develop next-generation compounds that ultimately led to icotrokinra.

Icotrokinra was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and Johnson & Johnson. Johnson & Johnson retains exclusive worldwide rights to develop icotrokinra in Phase 2 clinical trials and beyond, and to commercialize compounds derived from the research conducted pursuant to the agreement against a broad range of indications.

Icotrokinra is being studied in the pivotal Phase 3 ICONIC clinical development program in moderate-to-severe plaque psoriasis and active psoriatic arthritis and the Phase 2b ANTHEM-UC study in moderately to severely active ulcerative colitis.

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 selectively 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 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 pre-clinical 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 Janssen 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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¹ Bissonnette R, et al. Data presentation. A phase 2, randomized, placebo-controlled, dose-ranging study of oral JNJ-77242113 for the treatment of moderate-to-severe plaque psoriasis: FRONTIER 1. Presented at WCD 2023, July 3-8.

² Bissonnette, R et al. Icotrokinra, a Targeted Oral Peptide That Selectively Blocks the Interleukin-23-Receptor, for the Treatment of Moderate-to-Severe Plaque Psoriasis: Results Through Week 24 of the Phase 3, Randomized, Double-blind, Placebo-Controlled ICONIC-LEAD Trial. Late-breaking research presentation (Abstract #66708) at the American Academy of Dermatology (AAD) 2024 Annual Meeting. Accessed July 2025.

³ Eichenfield, L et al. 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). Presented at the World Congress of Pediatric Dermatology (Abstract #0054). Accessed July 2025.

⁴ Gooderham, M.J. et al. 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. Presented at the 2025 Society for Investigative Dermatology (Abstract #LB1142). Accessed July 2025.

⁵ Data on file (RF-454780). JNJ-77242113 Topline Results: Study 77242113PSO3002. Accessed July 2025.

⁶ Data on file (RF-454781). JNJ-77242113 Topline Results: Study JNJ77242113PSO3004. Accessed July 2025.

⁷ Razawy W, et al. The role of IL‐23 receptor signaling in inflammation‐mediated erosive autoimmune arthritis and bone remodeling. Eur J Immunol. 2018 Feb; 48(2): 220-229.

⁸ Tang C, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012 Feb; 135(2): 112-124.

⁹ Clinicaltrials.gov. A Study of JNJ-77242113 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis (ICONIC-ADVANCE 2). Identifier NCT06220604. https://clinicaltrials.gov/study/NCT06220604. Accessed July 2025.

¹⁰ Clinicaltrials.gov. A study of JNJ-2113 in adolescent and adult participants with moderate-to-severe plaque psoriasis (ICONIC-LEAD). Identifier NCT06095115. https://classic.clinicaltrials.gov/ct2/show/NCT06095115. Accessed July 2025.

¹¹ Clinicaltrials.gov. A study of JNJ-2113 for the treatment of participants with plaque psoriasis involving special areas (scalp, genital, and/or palms of the hands and the soles of the feet) (ICONIC-TOTAL). Identifier NCT06095102.

¹² Clinicaltrials.gov. A Study of JNJ-77242113 for the Treatment of Participants With Moderate to Severe Plaque Psoriasis. Identifier NCT06143878. https://clinicaltrials.gov/study/NCT06143878?term=jnj-77242113&rank=10. Accessed July 2025.

¹³ 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 July 2025.

¹⁴ Thompson Jr, D. How the Psoriasis Area and Severity Index works. Everyday Health. Available at: https://www.everydayhealth.com/psoriasis/living-with/how-the-pasi-index-works. Accessed July 2025.

¹⁵ Protagonist Therapeutics. Press release. Protagonist announces advancement of JNJ-2113 across multiple indications. Available at: https://www.accesswire.com/791174/protagonist-announces-advancement-of-jnj-2113-across-multiple-indications. Accessed July 2025.

¹⁶ Clinicaltrials.gov. A Study to Evaluate the Efficacy and Safety of JNJ-77242113 (Icotrokinra) in Biologic-naïve Participants With Active Psoriatic Arthritis (ICONIC-PsA 1). Identifier NCT06878404. https://clinicaltrials.gov/study/NCT06878404

¹⁷ A Study to Evaluate the Efficacy and Safety of Icotrokinra (JNJ-77242113) in Biologic-experienced Participants With Active Psoriatic Arthritis (ICONIC-PsA 2). Identifier NCT06807424. https://clinicaltrials.gov/study/NCT06807424

SOURCE: Protagonist Therapeutics

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L.Holland--TFWP