The Fort Worth Press - Icotrokinra Results Show 75% of Adolescents with Plaque Psoriasis Achieved Completely Clear Skin and Demonstrate Favorable Safety Profile with a Once Daily Pill

NEWARK, CA / ACCESS Newswire / April 10, 2025 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced new icotrokinra (JNJ-2113) data from a subgroup analysis of ICONIC-LEAD^a, the first ever Phase 3 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.¹ 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:

• At week 16, 84.1% of adolescent patients treated with once daily icotrokinra achieved an Investigator's Global Assessment (IGA)^b 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.¹

• Response rates continued to improve through Week 24 where 86.4% of adolescents achieved IGA 0/1 and 88.6% achieved PASI 90.

• At week 24, 75% of adolescents achieved IGA 0 (completely clear skin) and 63.6% achieved PASI 100.

• 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.¹

"We are thrilled with the data from the Phase 3 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 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.

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.²

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.³

About the ICONIC Clinical Development Program
The pivotal Phase 3 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.⁴ 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.⁵

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.⁶

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.^7,8 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.

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.⁹ It is estimated that 8 million Americans and more than 125 million people worldwide live with the disease.¹⁰ Nearly one-quarter of all people with plaque PsO have cases that are considered moderate to severe.¹¹ On Caucasian skin, plaques typically appear as raised, red patches covered with a silvery white buildup of dead skin cells or scale.¹¹ On skin of color, the plaques may appear darker and thicker and more of a purple, gray or dark brown color.¹² Plaques can appear anywhere on the body, although they most often appear on the scalp, knees, elbows, and torso.¹² 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.¹² 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.^12,13

About Icotrokinra (JNJ-77242113, JNJ-2113)
Investigational icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor,¹⁴ which underpins the inflammatory response in moderate-to-severe plaque PsO, ulcerative colitis and offers potential in other IL-23-mediated diseases.^15,16 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.¹⁷ 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.¹⁸

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.^19,20,21

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, icotrokinra and rusfertide, derived from Protagonist's proprietary discovery platform are currently in advanced Phase 3 clinical development, with New Drug Application submissions to the FDA expected in 2025. Icotrokinra (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 into in 2024 under which the Company remains primarily responsible for development through NDA filing. The Company also has a number of pre-clinical stage oral drug discovery programs addressing clinically and commercially validated targets, including the IL-17 oral peptide antagonist PN-881, an oral hepcidin program, and an oral obesity program.

More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at 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.

Investor Relations Contact

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¹ 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). April 2025.

² 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.

³ 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 April 2025.

⁴ 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 April 2025.

⁵ 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 April 2025.

⁶ 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 April 2025.

⁷ 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 April 2025.

⁸Clinicaltrials.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 April 2025.

⁹ National Psoriasis Foundation. About Psoriasis. Available at: https://www.psoriasis.org/about-psoriasis. Accessed April 2025.

¹⁰ National Psoriasis Foundation. Psoriasis Statistics. Available at: https://www.psoriasis.org/content/statistics. Accessed April 2025.

¹¹ National Psoriasis Foundation. Plaque Psoriasis. Available at: https://www.psoriasis.org/plaque/.Accessed April 2025.

¹² National Psoriasis Foundation. Life with Psoriasis. Available at: https://www.psoriasis.org/life-with-psoriasis/. Accessed April 2025.

¹³ National Psoriasis Foundation. High Impact Sites. Available at: https://www.psoriasis.org/high-impact-sites/. Accessed April 2025.

¹⁴Bissonnette 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.

¹⁵ 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.

¹⁶ Tang C, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012 Feb; 135(2): 112-124.

¹⁷ Pinter A, et al. Data Presentation. JNJ-77242113 Treatment Induces a Strong Systemic Pharmacodynamic Response Versus Placebo in Serum Samples of Patients with Plaque Psoriasis: Results from the Phase 2, FRONTIER 1 Study. Presented at EADV 2023, October 11-14.

¹⁸ Johnson & Johnson. Press release. Janssen enters into worldwide exclusive license and collaboration agreement with Protagonist Therapeutics, Inc. for the oral Interlukin-23 receptor antagonist drug candidate for the treatment of Inflammatory Bowel Disease. Available at: https://www.jnj.com/media-center/press-releases/janssen-enters-into-worldwide-exclusive-license-and-collaboration-agreement-with-protagonist-therapeutics-inc-for-the-oral-interlukin-23-receptor-antagonist-drug-candidate-for-the-treatment-of-inflammatory-bowel-disease. Accessed April 2025.

¹⁹ Protagonist Therapeutics. Press release. Protagonist Therapeutics announces amendment of agreement with Janssen Biotech for the continued development and commercialization of IL-23 antagonists. Available at: https://www.protagonist-inc.com/press-releases Pg. 20. Accessed April 2025.

²⁰ Protagonist Therapeutics. Press release. Protagonist Reports positive results from Phase 1 and pre-clinical studies of oral Interleukin-23 receptor antagonist JNJ-2113. Available at: https://www.protagonist-inc.com/press-releases Page 7. From May 12 2023. Accessed April 2025.

²¹ Protagonist Therapeutics. Press release. Protagonist Therapeutics announces positive topline results for Phase 2b FRONTIER 1 clinical trial of oral IL-23 receptor antagonist JNJ-2113 (PN-235) in psoriasis. Available at: https://www.protagonist-inc.com/press-releases Page 7. From March 7 2023. Accessed April 2025.

SOURCE: Protagonist Therapeutics

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N.Patterson--TFWP