The Albany Gazette - Protagonist Announces Submission of NDA for First Icotrokinra U.S. FDA Approval Aiming to Revolutionize Treatment Paradigm for Adults and Adolescents with Plaque Psoriasis

NEWARK, CALIFORNIA / ACCESS Newswire / July 21, 2025 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) by Johnson & Johnson seeking the first approval of icotrokinra, a first-in-class investigational targeted oral peptide for the treatment of adults and pediatric patients 12 years of age and older with moderate to severe plaque psoriasis (PsO). Icotrokinra is uniquely designed to block the IL-23 receptor,which underpins the inflammatory response in plaque PsO and offers potential in other IL-23-mediated diseases.^{[1], [2], [3]} Icotrokinra was jointly discovered and is being developed pursuant to the license and collaboration agreement between Protagonist and Johnson & Johnson.

The NDA includes data from four pivotal Phase 3 studies conducted as part of the ICONIC clinical development program, including ICONIC-LEAD, ^a ICONIC-TOTAL,^b ICONIC-ADVANCE 1 and ICONIC-ADVANCE 2.^c Treatment with icotrokinra met all primary and co-primary endpoints across the development program among adults and pediatric patients 12 years of age and older with moderate-to-severe plaque PsO, demonstrating significant skin clearance and a favorable safety profile in a once-daily pill. Results from the ICONIC-ADVANCE 1 & 2 studies show icotrokinra achieved co-primary endpoints and showed superiority to deucravacitinib in moderate-to-severe plaque PsO. Across all studies, pooled safety data showed a similar proportion of patients experienced adverse events between icotrokinra (49.1%) and placebo (51.9%) groups, with no new safety signals identified to date.^{[4], [5], [6], [7], [8]}

"The very comprehensive clinical data package included in the NDA filing demonstrate that icotrokinra has the potential to disrupt the current treatment paradigm and transform how physicians and patients approach plaque psoriasis care," said Dinesh V. Patel, Ph.D., President and Chief Executive Officer at Protagonist. "All four pivotal Phase 3 trials achieved impressive efficacy results and favorable safety profile with a convenient, targeted once-a-day oral peptide therapy. We look forward to additional data in the ongoing studies that may expand the future application of icotrokinra in indications such as psoriatic arthritis, ulcerative colitis, and Crohn's disease."

"This NDA marks a first for an asset discovered at Protagonist and further validates the potential of our peptide discovery and development platform. It's a testament to great innovation and perseverance, and an outstanding long-term collaboration with Johnson & Johnson," said Dr. Patel. "Protagonist is at the forefront of discovery and development of novel peptide therapeutics that offer the efficacy and specificity of injectable biologics with the convenience of oral delivery in various disease areas including inflammation, immunomodulatory and metabolic diseases."

Data submitted to the FDA as part of the NDA 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 icotrokinra successfully met the co-primary endpoints of 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 16.⁴

• A subgroup analysis of ICONIC-LEAD, presented at the 2025 World Congress of Pediatric Dermatology (WCPD), which demonstrated that pediatric patients 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.⁵

• Data from the Phase 3 ICONIC-TOTAL study, presented at the 2025 Society for Investigative Dermatology (SID) Annual Meeting, highlighted the potential of icotrokinra in patients with difficult-to-treat scalp and genital psoriasis.⁶

• 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 plaque PsO.^7,8 Comprehensive results are being prepared for presentation at a future medical meeting.

• 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.

Johnson & Johnson has also initiated the Phase 3 ICONIC-ASCEND^f study, the first-ever head-to-head study seeking to demonstrate the superiority of an oral pill, icotrokinra, compared to an injectable biologic, ustekinumab, representing an important step forward in psoriasis research.

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 pediatric patients.

2. ICONIC-TOTAL is a Phase 3 RCT evaluating the efficacy and safety of icotrokinra compared with placebo for the treatment of plaque PsO 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.

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 PsO with PASI 90 and IGA score of 0/1 with at least a 2-grade improvement as co-primary endpoints.

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.^[9]

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.^[10] PASI 90 corresponds to an improvement of >=90% in PASI score from baseline.¹⁰

6. 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.

About the ICONIC Clinical Development Program
The pivotal Phase 3 ICONIC clinical development program of icotrokinra (in adult and pediatric 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. The ICONIC program is being conducted by Johnson & Johnson.^[11]

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. ^[12]

ICONIC-TOTAL (NCT06095102) is an 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.^[13]

Other Phase 3 studies in the development program include ICONIC-ADVANCE 1 (NCT06143878) and ICONIC-ADVANCE 2 (NCT06220604), which evaluate the efficacy and safety of icotrokinra compared with both placebo and deucravacitinib in adults with moderate-to-severe plaque PsO. ^{[14], [15]} 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.^[18] It is estimated that 8 million Americans and more than 125 million people worldwide live with the disease.^[19] 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.¹⁹ On skin of color, the plaques may appear darker, 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.^[20] 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.^[21] 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.^{18, [22]}

About Icotrokinra (JNJ-77242113, JNJ-2113)
Investigational icotrokinra is the first targeted oral peptide designed to selectively block the IL-23 receptor,¹ which underpins the inflammatory response in moderate-to-severe plaque PsO, ulcerative colitis, and offers potential in other IL-23-mediated diseases.^2,3 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.^[23] 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 oral peptide IL-23 receptor antagonists that ultimately led to icotrokinra.^[24]

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.^{[25], [26], [27]}

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 have completed Phase 3 clinical development, with one New Drug Application submitted to the FDA in 2025 and a second NDA submission expected in the fourth quarter of 2025. An NDA for the treatment of psoriasis has been submitted for icotrokinra (formerly, JNJ-2113). Icotrokinra 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. Protagonist and Johnson & Johnson scientists jointly discovered icotrokinra under the companies' IL-23R research 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, recently completed Phase 3 development for the rare blood disorder polycythemia vera (PV). An NDA is expected to be submitted in the fourth quarter of 2025. 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 drug discovery programs addressing clinically and commercially validated targets, including IL-17 oral peptide antagonist PN-881, obesity triple agonist peptide PN-477, and oral hepcidin.

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 in psoriasis and other potential indications and our expectations regarding icotrokinra clinical development. 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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SOURCE: Protagonist Therapeutics

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(M.Scott--TAG)