Protagonist Therapeutics achieved a significant regulatory milestone in July 2025 with the submission of its first New Drug Application (NDA) for icotrokinra, targeting moderate to severe plaque psoriasis in adults and adolescents 12 years of age and older. The filing marks a breakthrough accomplishment for the Newark, California-based biopharmaceutical company, which is advancing multiple novel peptide therapeutics through late-stage development.
Icotrokinra Advances Through Regulatory Process
The icotrokinra NDA submission, announced jointly with partner Johnson & Johnson on July 21st, included data from four pivotal Phase 3 studies conducted as part of the ICONIC clinical development program: ICONIC-LEAD, ICONIC-TOTAL, and ICONIC-ADVANCE 1 & 2. Icotrokinra (formerly JNJ-2113) represents a first-in-class investigational targeted oral peptide that selectively blocks the Interleukin-23 receptor (IL-23R).
The drug candidate has demonstrated efficacy across challenging patient populations. Data from the Phase 3 ICONIC-TOTAL study in difficult-to-treat scalp and genital psoriasis was presented at the Society for Investigative Dermatology Annual Meeting in May, while results from the adolescent cohort of the ICONIC-LEAD study were presented at the 2025 World Congress of Pediatric Dermatology in April.
Beyond psoriasis, icotrokinra showed promise in ulcerative colitis, with positive top-line results from the Phase 2b ANTHEM trial in moderately to severely active disease announced in March. The full data set is scheduled for oral presentation at the 33rd United European Gastroenterology Week on October 7th.
Rusfertide Gains Momentum in Rare Blood Disorders
Protagonist's rusfertide program reached a prestigious milestone when the full Phase 3 VERIFY trial data set was presented during the plenary session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting on June 1st. The subcutaneous injectable hepcidin mimetic is being developed for polycythemia vera and other blood disorders.
Partner Takeda Pharmaceuticals is expected to file a U.S. NDA for rusfertide in the treatment of patients with polycythemia vera in Q4 2025. The collaboration agreement, established in 2024, positions Protagonist to remain primarily responsible for development through NDA filing, with co-development and co-commercialization responsibilities shared with Takeda.
Pipeline Expansion with Novel Mechanisms
The company expanded its development pipeline with two promising early-stage candidates. In June, Protagonist announced the selection of PN-477, a potential best-in-class GLP-1, GIP, GCG receptor triple agonist peptide with both oral and subcutaneous routes of administration, as a development candidate for obesity treatment.
Preclinical data on PN-881, a first-in-class oral IL-17 peptide antagonist, was presented at the Society for Investigative Dermatology Annual Meeting in May. Key findings demonstrated that PN-881 potently and selectively binds IL-17A and -17F, blocking the three dimeric forms of the cytokine, with nanomolar to picomolar in vitro potency comparable to bimekizumab and superior (70-fold) to secukinumab.
The compound showed metabolic stability across several species, making it suitable for oral delivery, and demonstrated dose-dependent efficacy with significant reduction in skin thickness in a 5-day rat IL-23 induced skin inflammation model after oral dosing.
Financial Position and Performance
Protagonist reported cash, cash equivalents and marketable securities of $673.0 million as of June 30, 2025, compared to $559.2 million as of December 31, 2024. The company anticipates this provides cash runway through at least the end of 2028.
The second quarter 2025 financial results showed a net loss of $34.8 million, or $0.55 per basic and diluted share, compared to a net loss of $30.6 million, or $0.50 per basic and diluted share, for the second quarter of 2024. License and collaboration revenue reached $5.5 million for Q2 2025, comprised of development services provided under the Takeda collaboration agreement.
Research and development expenses increased to $37.0 million in Q2 2025 from $33.5 million in the prior year period, primarily due to increases in pre-clinical and drug discovery research expenses for new product candidates PN-881 and PN-477, partially offset by decreases in rusfertide expenses related to the Phase 3 VERIFY clinical trial.
"Thus far, 2025 has been a year of breakthrough accomplishments for Protagonist, as we saw rusfertide the topic of the prestigious ASCO Plenary Session in May, the announcement of an oral and injectable triple agonist anti-obesity peptide development candidate in June, and most recently the first ever NDA filing of icotrokinra for psoriasis last month," said Dinesh V. Patel, Ph.D., the Company's President and CEO.
