Protagonist Reports 2025 Results, Advances Two NDAs and Expands Pipeline

Protagonist Therapeutics reported financial results for the fourth quarter and full year ended December 31, 2025, announcing that NDAs for rusfertide and ICOTYDE (icotrokinra) have been submitted to the FDA, with potential approvals and launches anticipated in 2026. Two novel peptides derived from Protagonist's proprietary discovery platform are currently in advanced Phase 3 clinical development.

The company submitted a New Drug Application to the FDA for rusfertide for polycythemia vera. Under the terms of its License and Collaboration Agreement with Takeda Pharmaceuticals USA, Inc., Protagonist has the right to opt out of the 50:50 profit and loss sharing arrangement in the U.S. during the 90-day period beginning 120 days after filing of the NDA. The company currently expects to exercise that right in the second quarter of 2026.

A U.S. regulatory decision for ICOTYDE (icotrokinra) is anticipated in 2026, followed by commercial launch this year, if FDA approval is granted. Primary endpoint enrollment completion is expected in 2026 for the Phase 3 ICONIC-ASCEND multicenter, randomized, double-blind, placebo-controlled, and ustekinumab active comparator-controlled study to evaluate the efficacy and safety of icotrokinra for the treatment of participants with moderate to severe plaque psoriasis. Primary endpoint enrollment completion is also expected in 2026 for the Phase 3 multicenter, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of icotrokinra for the treatment of biologic-naïve participants with active psoriatic arthritis.

The company is progressing Phase 3 trials in partnership with large pharmaceutical companies, including Johnson & Johnson and Takeda. Johnson & Johnson has pursued Protagonist Therapeutics in a multibillion-dollar transaction centered on peptide-based therapies.

The company expects its Phase 1 study of PN-881 to be complete by mid-2026, informing subsequent clinical development plans.

Protagonist recently announced two new wholly owned development candidates: PN-458, a novel dual GLP-GIP agonist for obesity, and PN-8047, an oral hepcidin functional mimetic complementing rusfertide, an injectable hepcidin mimetic. The company also announced PN-477, an oral and subcutaneous triple GLP-GIP-GCG agonist. Additionally, the company added IL-4Rα and amylin as high-priority discovery programs to further expand and strengthen its pipeline.

Cash, cash equivalents, and marketable securities as of December 31, 2025, were $646.0 million as compared to $559.2 million in the previous year. The company anticipates this will provide cash runway through at least end of 2028.

License and collaboration revenue is derived from the company's License and Collaboration Agreement with Johnson & Johnson and its License and Collaboration Agreement with Takeda. License and collaboration revenue decreased by $163.2 million from $170.6 million for the fourth quarter of 2024 to $7.4 million for the fourth quarter of 2025. License and collaboration revenue decreased by $388.4 million from $434.4 million for the full year 2024 to $46.0 million for the full year 2025. The decrease in revenue was primarily attributable to lower milestone and collaboration revenue, which is highly variable and dependent upon factors such as the timing of when regulatory and sales milestones are achieved, if at all, and the accounting for any upfront payments associated with any existing or new agreements.

License and collaboration revenue of $7.4 million for the fourth quarter of 2025 was comprised of development services provided during the period under the Takeda Agreement.

The stock closed at $81.49, with a 3 year return of 404.0% and a 1 year return of 110.7%, even as returns over the past week, month, and year to date show declines of 3.6%, 4.4%, and 6.5% respectively.