The Albany Gazette - Protagonist Announces Presentations of Clinical Data with Icotrokinra in Plaque Psoriasis and Preclinical Data with PN-881 at the EADV 2025 Congress

Icotrokinra demonstrated superior skin clearance at Weeks 16 and 24 compared to deucravacitinib and similar adverse event rates to placebo in Phase 3 ICONIC-ADVANCE studies

Icotrokinra also showed sustained skin clearance and favorable safety profile in both adults and adolescents at Week 52 in Phase 3 ICONIC-LEAD study

Preclinical proof-of-concept data on PN-881, a first-in-class oral peptide targeting the IL-17 pathway, and part of Protagonist's fully owned development pipeline, including the highly potent and selective binding of IL-17A and IL-17F

NEWARK, CALIFORNIA / ACCESS Newswire / September 17, 2025 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") today announced new data from the Phase 3 ICONIC-ADVANCE 1 and 2 studies which assessed the superiority of icotrokinra, a first-in-class investigational targeted oral peptide that selectively blocks the IL-23 receptor, compared to deucravacitinib in patients with moderate-to-severe plaque psoriasis. These data are being presented at the 2025 European Academy of Dermatology and Venereology (EADV) Congress in Paris, France. Additionally, new long-term 52-week data from the Phase 3 ICONIC-LEAD study investigating icotrokinra in adults and pediatric patients 12 years of age and older (adolescents) with moderate to severe plaque psoriasis will be presented as a late-breaking abstract at EADV.^{1, 2}

Preclinical data on PN-881, a first-in-class oral peptide targeting the IL-17 pathway and fully owned by Protagonist, are also being presented at EADV.³ The Company expects that the first subject will be dosed in the Phase 1 single ascending and multiple ascending dose human clinical study (NCT07153146) in the coming weeks.

"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 Inflammatory and Immunomodulatory (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," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. " Collectively, these data reinforce our ability to innovate and develop oral peptides that could potentially deliver transformative, paradigm shifting outcomes for patients. The first-in-class oral peptides Icotrokinra and PN-881 target the highly relevant biological IL-23 and IL-17 pathways respectively in the I&I space and position Protagonist Therapeutics as an emerging and prominent contributor to this therapeutic field."

ICONIC-ADVANCE 1 and 2 Study Data

The ICONIC-ADVANCE 1 and 2 studies assessed the superiority of icotrokinra compared to deucravacitinib in patients with moderate-to-severe plaque psoriasis. As previously announced, in the studies icotrokinra met both co-primary endpoints compared to placebo at Week 16 with similar adverse event rates and showed superiority to deucravacitinib at multiple timepoints in adult patients.

• Icotrokinra showed superior skin clearance vs placebo (Week 16) and deucravacitinib (Weeks 16 and 24).¹

• A similar proportion of patients experienced adverse events (AEs) between icotrokinra and placebo groups, with no new safety signals identified. Icotrokinra AE rates were numerically lower vs deucravacitinib through Week 24.¹

ICONIC-LEAD Study Data

In the ICONIC-LEAD^b drug withdrawal/re-retreatment study, icotrokinra demonstrated sustained skin clearance and a favorable safety profile through Week 52 with no new safety signals identified.

• At Week 52, adult icotrokinra PASI 90 responders re-randomized to icotrokinra at Week 24 had superior maintenance of PASI 90 response versus those re-randomized to placebo (84% vs 21%; p2,d

• At Week 52, 86% of adolescents who received icotrokinra for the full 52 weeks and 77% of those switched from placebo to icotrokinra at Week 16 achieved PASI 90 response.²

• ICONIC-LEAD Week 16 primary endpoint data was previously presented at the American Academy of Dermatology 2025 Congress.⁴

ASCEND Study Initiated

Protagonist's collaboration partner, Johnson & Johnson, also announced initiation of the Phase 3 ICONIC-ASCEND study,^c the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable biologic, ustekinumab, in psoriasis, representing an important step forward in psoriasis research.

PN-881 Study Data

Preclinical data on PN-881, the next generation IL-17 oral peptide antagonist for psoriasis will also be presented at the conference, key takeaways included: ³

• Exhibited in vitro potency comparable to bimekizumab, and superior (70-fold) to secukinumab, in the nanomolar to picomolar range.

• Showed metabolic stability in several matrices across several species, making it a suitable candidate for oral delivery.

• Demonstrated PD-based target engagement in a mouse IL-17 challenge model after oral dosing.

• Oral dosing showed dose-dependent efficacy with significant reduction in skin thickness in a 5-day rat IL-23 induced skin inflammation model.

Editor's notes:

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

2. 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 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 12 years of age and older.

3. ICONIC-ASCEND is a Phase 3 RCT and the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable biologic, ustekinumab in moderate-to-severe plaque PsO.⁵

4. 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. PASI 90 means a 90% reduction in baseline PASI score.

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.⁶

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.⁷

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.⁸

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.^{9, 10} 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.^{11, 12}

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 demonstrated 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 PN-881

PN-881 is a potential first- and best-in-class oral peptide IL-17 antagonist which has demonstrated robust activity against all three therapeutically relevant dimeric forms of the IL-17 ligand in preclinical testing. It demonstrates potency that is orders of magnitude better than an anti-IL-17 oral small molecule analog, and better than, or on par with, various approved or developmental stage injectable antibody or nanobody therapeutic agents. Planned clinical studies include a Phase 1 single ascending dose (SAD) and multiple ascending dose (MAD) study expected to begin in the fourth quarter of 2025 (NCT07153146). Results of the Phase 1 trial will inform the design and dosing of a subsequent dose-ranging Phase 2 psoriasis trial. Rapid expansion into other IL-17 mediated diseases, including psoriatic arthritis, hidradenitis suppurativa, and axial spondyloarthropathies, will be based on initial results observed in psoriasis studies.

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, Inc. 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 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 PN-881, and expectations regarding the icotrokinra and PN-881 development programs. 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.

Investor Relations Contact

Corey Davis, Ph.D.
LifeSci Advisors
+1 212 915 2577
[email protected]

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ENTENTE Network of Companies
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¹ Stein Gold, L et al. Icotrokinra Demonstrated Superior Responses Compared with Placebo and Deucravacitinib in the Treatment of Moderate-to-Severe Plaque Psoriasis : Results Through Week 24 of the Phase 3 ICONIC-ADVANCE 1&2 Studies. Oral presentation (Presentation FC01.1G) at the European Academy of Dermatology and Venereology Congress (EADV). September 2025.

² Soung, J et al. Maintenance of Response with Icotrokinra, a Targeted Oral Peptide, for the Treatment of Moderate-to-Severe Psoriasis: Randomized Treatment Withdrawal in Adults (weeks 24-52) and Continuous Treatment in Adolescents (Through Week 52) From the Phase 3, ICONIC-LEAD Trial. Late-breaking research oral presentation (Presentation #D1T01.2B) at the European Academy of Dermatology and Venereology Congress (EADV). September 2025.

³ Manrique, M et al. PN-881: First-in-class oral IL-17 antagonist peptide for potential treatment of psoriatic diseases. Presented at the European Academy of Dermatology and Venereology Congress (EADV) (Abstract #2155). September 2025.

⁴ 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. March 2025.

⁵ Clinicaltrials.gov. A Study to Assess Efficacy and Safety of JNJ-77242113 Compared to Placebo and Ustekinumab in Participants with Moderate to Severe Plaque Psoriasis (ICONIC-ASCEND). Identifier NCT0693422. https://clinicaltrials.gov/study/NCT06934226?term=iconic-ascend&rank=1. Accessed July 2025.

⁶ 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.

⁷ 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.

⁸ 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. https://classic.clinicaltrials.gov/ct2/show/NCT06095102. Accessed July 2025.

⁹ 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.

¹⁰ 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.

¹¹ 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

¹² 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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(T.Brown--TAG)