Protagonist Therapeutics, Inc.: Q4 FY2025 earnings call

What management said about Q4 FY2025, from the documents filed with the SEC on 25 February 2026: press release. Guidance figures: 3 new, 2 kept. The quarter’s numbers.

Key takeaways

License revenue fell on lower milestones: License and collaboration revenue was $7.4 million in Q4 2025, against $170.6 million a year earlier, and $46.0 million for full year 2025, against $434.4 million. Source
Q4 net loss against prior-year income: The company reported a Q4 2025 net loss of $44.4 million, or $0.69 per share, compared with net income of $131.7 million, or $1.98 per diluted share, in Q4 2024. Source
ICOTYDE U.S. decision expected 2026: A U.S. regulatory decision on ICOTYDE is anticipated in 2026, with commercial launch this year if FDA approval is granted. Source
Rusfertide NDA submitted to FDA: The NDA for rusfertide in polycythemia vera was submitted to the FDA, with potential approval and launch this year, as management stated. Source
Takeda opt-out expected in Q2: Protagonist has the right to opt out of the 50:50 U.S. profit and loss sharing with Takeda in a 90-day period beginning 120 days after the NDA filing; it expects to exercise in Q2 2026. Source
PN-881 Phase 1 completion by mid-2026: The Phase 1 study of PN-881, an oral IL-17 peptide antagonist, is expected to complete by mid-2026, informing subsequent clinical development plans. Source
Cash position at year end: Cash, cash equivalents and marketable securities were $646.0 million at December 31, 2025, against $559.2 million a year earlier and $678.8 million at September 30, 2025. Source

“In 2025, Protagonist reached new heights with multiple successful Phase 3 outcomes and two NDA filings of our partnered assets, ICOTYDE and rusfertide,”
Dinesh V. Patel, Ph.D., the Company’s President and CEO

Guidance

Area	Period	Figure	Against last quarter
Rusfertide partnership opt-out (Takeda) Source	Q2 2026	Expected to exercise opt-out right in Q2 2026	New
ICOTYDE U.S. regulatory decision Source	2026	U.S. regulatory decision anticipated in 2026	Kept
PN-881 Phase 1 study completion Source	By mid-2026	Complete by mid-2026	New
Phase 3 enrollment completion (icotrokinra) Source	2026	Primary endpoint enrollment completion expected in 2026 for two Phase 3 studies	New
Cash runway Source	Through at least end of 2028	Cash runway through at least end of 2028	Kept

What changed from last quarter

New guidance: Management expects to exercise the Takeda opt-out right in Q2 2026; the prior quarter's release did not give this expectation. Source
New: The rusfertide NDA was submitted in December 2025; the prior release had expected filing by year end. Source
New: PN-8047, an oral hepcidin functional mimetic, is named as a new wholly owned candidate; the prior release planned a hepcidin candidate nomination by year end. Source
New: PN-458, a dual GLP-GIP agonist for obesity, is named as a new wholly owned development candidate. Source
New: IL-4Rα and amylin were added as high-priority discovery programs. Source

Results and growth drivers

License revenue fell on lower milestones: License and collaboration revenue was $7.4 million in Q4 2025, against $170.6 million a year earlier, and $46.0 million for full year 2025, against $434.4 million. Source
Prior-year milestones drove the decline: Management attributed the decline mainly to lower milestone and collaboration revenue, which it described as variable and dependent on the timing of regulatory and sales milestones. Source
Q4 net loss against prior-year income: The company reported a Q4 2025 net loss of $44.4 million, or $0.69 per share, compared with net income of $131.7 million, or $1.98 per diluted share, in Q4 2024. Source
Full-year net loss against prior-year income: Full year 2025 net loss was $130.1 million, or $2.05 per share, compared with net income of $275.2 million, or $4.23 per diluted share, in 2024. Source

Partnered programs and milestones

ICOTYDE U.S. decision expected 2026: A U.S. regulatory decision on ICOTYDE is anticipated in 2026, with commercial launch this year if FDA approval is granted. Source
Rusfertide NDA submitted to FDA: The NDA for rusfertide in polycythemia vera was submitted to the FDA, with potential approval and launch this year, as management stated. Source
Takeda opt-out expected in Q2: Protagonist has the right to opt out of the 50:50 U.S. profit and loss sharing with Takeda in a 90-day period beginning 120 days after the NDA filing; it expects to exercise in Q2 2026. Source
Two Phase 3 enrollments to finish 2026: Primary endpoint enrollment completion is expected in 2026 for an ICONIC-ASCEND plaque psoriasis study and a psoriatic arthritis Phase 3 study of icotrokinra. Source

“We see the next 12 to 24 months as a period of significant growth and value creation for Protagonist”
Dinesh V. Patel, Ph.D., the Company’s President and CEO

Costs and operating expense

R&D spend rose on discovery work: R&D expense was $46.4 million in Q4 2025, up $11.5 million, and $159.3 million for the year, up $21.2 million, mainly on drug discovery and preclinical research. Source
G&A rose on professional and personnel costs: G&A expense was $11.4 million in Q4 2025, up $2.5 million, mainly from professional services and personnel-related expenses; full year G&A was $44.9 million. Source
Total operating expense higher year on year: Total operating expense was $57.8 million in Q4 2025, against $43.9 million a year earlier, and $204.1 million for the full year, against $181.6 million. Source

Pipeline and discovery programs

PN-881 Phase 1 completion by mid-2026: The Phase 1 study of PN-881, an oral IL-17 peptide antagonist, is expected to complete by mid-2026, informing subsequent clinical development plans. Source
Preclinical pipeline expanded with PN-477: The pre-clinical pipeline was expanded with PN-477, described as an oral and subcutaneous triple GLP-GIP-GCG agonist, among wholly owned candidates. Source
Discovery focus on IL-17, obesity, hepcidin: The company describes preclinical discovery programs in an oral IL-17 peptide antagonist, obesity dual and triple agonists, and an oral hepcidin functional mimetic. Source

Capital, cash and balance sheet

Cash position at year end: Cash, cash equivalents and marketable securities were $646.0 million at December 31, 2025, against $559.2 million a year earlier and $678.8 million at September 30, 2025. Source
Working capital and deferred revenue lower: Working capital was $532.1 million and total assets $668.2 million at December 31, 2025, against $544.2 million and $744.7 million a year earlier; deferred revenue was $9.55 million, against $30.6 million. Source
Interest income slightly lower: Interest income was $6.8 million in Q4 2025, against $6.9 million a year earlier; full year interest income was $28.8 million, against $26.3 million. Source

Strategy and growth drivers

Growth expected from milestones and royalties: Management said the next 12 to 24 months are expected to bring growth from anticipated regulatory and commercial milestones and royalties from ICOTYDE and rusfertide. Source
Cash and partner revenue fund internal programs: Management stated that cash on hand and potential partnered-asset revenue are expected to fund wholly owned programs to clinical proof-of-concept. Source
Partner leads development after Phase 1: ICOTYDE is licensed to Janssen; Protagonist was primarily responsible for development through Phase 1, and Johnson & Johnson took responsibility from Phase 2 onward. Source

Coming up, as management said on 25 February 2026

ICOTYDE commercial launch this year: Commercial launch of ICOTYDE is expected this year, if FDA approval is granted. Source
Takeda opt-out window opens: The 90-day opt-out window is expected to open in Q2 2026, beginning 120 days after the rusfertide NDA filing. Source
Rusfertide potential launch this year: Potential approval and launch of rusfertide is expected this year, following the NDA submission. Source
PN-881 Phase 1 completion mid-2026: The PN-881 Phase 1 study is expected to be complete by mid-2026, informing subsequent clinical development plans. Source

Figures management reported

Figure	Reported
Pipeline milestone: PN-881 Phase 1 completion Source	Expected by mid-2026
Approval: ICOTYDE U.S. regulatory decision Source	Anticipated in 2026
R&D expense Source	$159.3 million for full year 2025

Risks management discussed

Financial: License and collaboration revenue is highly variable and depends on the timing of regulatory and sales milestones, which may or may not be achieved. Source

Earlier plans management reported on

On track: Management said it remained on track to nominate an oral hepcidin development candidate by year end. The Q4 release names PN-8047 as a new wholly owned candidate.
Not stated: The prior release expected the Takeda-partnered U.S. NDA filing for rusfertide in Q4 2025. The Q4 release states the NDA was submitted in December 2025.

Other quarters

Summarised with AI from the documents the company filed with the SEC. Every point is checked against the filing before it is shown: management’s own words word for word, figures against the line or table row they come from. A point that fails the check is left out. Source opens the filing at that line.

As filed with the SEC

Open the filing on EDGAR

Protagonist Reports Fourth Quarter and Full Year 2025 Financial Results and Provides Corporate Update

NDA for rusfertide submitted to the US Food and Drug Administration (FDA), with potential approval and launch this year

Company expects to opt-out of the 50:50 profit and loss sharing arrangement for rusfertide with Takeda during a 90-day window expected to open in Q2

U.S. regulatory decision for ICOTYDE™ (icotrokinra) anticipated in 2026 with potential launch this year

PN-881 Phase 1 completion expected by mid-2026

Pre-clinical pipeline expanded with novel wholly-owned candidates PN-477, an oral and s.c. triple GLP-GIP-GCG agonist and PN-458, an oral and s.c. dual GLP-GIP agonist, and PN-8047, an oral hepcidin functional mimetic

Cash, cash equivalents and marketable securities of $646 million as of December 31, 2025, anticipated to provide cash runway through at least end of 2028

NEWARK, Calif., February 25, 2026 - Protagonist Therapeutics (Nasdaq: PTGX) (“Protagonist” or “the Company”) today reported financial results for the fourth quarter and full year ended December 31, 2025 and provided a corporate update.

“In 2025, Protagonist reached new heights with multiple successful Phase 3 outcomes and two NDA filings of our partnered assets, ICOTYDE and rusfertide,” said Dinesh V. Patel, Ph.D., the Company’s President and CEO. “We see the next 12 to 24 months as a period of significant growth and value creation for Protagonist, driven by a combination of the anticipated regulatory and commercial milestones and royalties from ICOTYDE and rusfertide and the continued advancement of our robust R&D pipeline comprised of the oral IL-17 peptide antagonist, our obesity dual and triple agonists, and our oral hepcidin functional mimetic. We are well equipped to fund all our internal wholly owned programs to clinical proof-of-concept with the cash on hand and potential revenue from the partnered assets.”

Fourth Quarter 2025 Recent Developments and Upcoming Milestones

Rusfertide

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 a New Drug Application with the FDA for Rusfertide for polycythemia vera. We currently expect to exercise that right in the second quarter of 2026.

ICOTYDE™ (Icotrokinra)

A U.S. regulatory decision 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 (NCT06934226).
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 (NCT06878404).

Clinical Programs

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

Discovery Programs

Recently, Protagonist 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.
Additionally, the Company added IL-4Rα and amylin as high-priority discovery programs to further expand and strengthen its pipeline.

Fourth Quarter and Full Year 2025 Financial Results

Cash, Cash Equivalents and Marketable Securities: 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.

	Three Months Ended		Twelve Months Ended
	December 31,		December 31,
(in thousands, except per share amounts)	2025	2024	2025	2024
	(Unaudited)
License and collaboration revenue	$7,437	$170,638	$46,016	$434,433
Research and development expense	$46,358	$34,904	$159,290	$138,128
General and administrative expense	$11,434	$8,954	$44,853	$43,462
Net (loss) income	$(44,384)	$131,674	$(130,149)	$275,188
Basic earnings (loss) per share	$(0.69)	$2.11	$(2.05)	$4.47
Diluted earnings (loss) per share	$(0.69)	$1.98	$(2.05)	$4.23

Revenue: License and collaboration revenue is derived from the Company’s License and Collaboration Agreement with JNJ, (the “JNJ Agreement”), and its License and Collaboration Agreement with Takeda (the “Takeda Agreement”).

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 we provided during the period under the Takeda Agreement. License and collaboration revenue of $170.6 million for the fourth quarter of 2024 included (i) achievement of a non-refundable $165.0 milestone under the JNJ Agreement, and (ii) development services we provided during the period under the Takeda Agreement.
License and collaboration revenue of $46.0 million for the full year 2025 was comprised of (i) proportional recognition of a $25.0 million milestone earned from Takeda in Q1 25, and (ii) development services we provided during the period under the Takeda agreement. License and collaboration revenue of $434.4 million for the full year 2024 included (i) $254.1 million of the $300.0 million initial transaction price for the Takeda Agreement allocated to the rusfertide license upon effectiveness of the agreement, (ii) achievement of a non-refundable $165.0 milestone under the JNJ Agreement earned in Q4 24, and (iii) development services we provided during the period under the Takeda Agreement.

Research and Development Expenses: Increased by $11.5 million and $21.2 million for the fourth quarter and full year 2025, respectively, from the prior year periods. The increases were due primarily to increases in drug discovery and pre-clinical research expenses, including expenses related to our IL-17 product candidate PN-881 and our obesity product candidates.

General and Administrative Expenses: Increased by $2.5 million for the three months ended December 31, 2025, from the prior year period primarily due to increases in professional services and personnel-related expenses. The increase of $1.4 million for the full year 2025 as compared to the prior year was primarily due to increases in professional services and personnel-related expenses, partially offset by $4.6 million in one-time advisory and legal fees in 2024 related to the Takeda Agreement.

Net (Loss) Income: Net loss was $44.4 million, or $0.69 per basic share and diluted share, for the fourth quarter of 2025 as compared to net income of $131.7 million, or $2.11 per basic share and $1.98 per diluted share, for the fourth quarter of 2024. Net loss was $130.1 million, or $2.05 per basic share and diluted share, for the full year 2025, as compared to net income of $275.2 million, or $4.47 per basic share and $4.23 per diluted share, for the full year 2024.

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 a New Drug Application (NDA) for ICOTYDETM (icotrokinra) under review at the FDA and an NDA for rusfertide submitted in December 2025. ICOTYDE 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 ICOTYDE's joint discovery by Protagonist and Johnson & Johnson scientists pursuant to the companies' IL-23R collaboration, Protagonist was primarily responsible for the development of Icotyde 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 development for the rare blood disorder polycythemia vera. Rusfertide is being co-developed and may be co-commercialized with Takeda Pharmaceuticals pursuant to a worldwide collaboration and license agreement under which the Company was 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 an oral IL-17 peptide antagonist, obesity dual and triple agonists, an oral hepcidin functional mimetic, and the recently announced IL-4 and amylin programs.

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

Forward-looking statements notice

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 potential timing of regulatory actions, clinical trial results and potential revenue from the Company’s collaborations with Takeda and Johnson & Johnson. 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.

Consolidated Statements of Operations

(Amounts in thousands except share and per share data)

	Three Months Ended		Twelve Months Ended
	December 31,		December 31,
	2025	2024	2025	2024
License and collaboration revenue	$7,437	$170,638	$46,016	$434,433
Operating expense:
Research and development	46,358	34,904	159,290	138,128
General and administrative	11,434	8,954	44,853	43,462
Total operating expense	57,792	43,858	204,143	181,590
Loss (income) from operations	(50,355)	126,780	(158,127)	252,843
Interest income	6,761	6,853	28,789	26,315
Other (expense) income, net	(124)	31	27	250
(Loss) income before income tax expense	(43,718)	133,664	(129,311)	279,408
Income tax expense	666	1,990	838	4,220
Net (loss) income	$(44,384)	$131,674	$(130,149)	$275,188
Net (loss) income per share, basic	$(0.69)	$2.11	$(2.05)	$4.47
Net (loss) income per share, diluted	$(0.69)	$1.98	$(2.05)	$4.23
Weighted-average shares used to compute net (loss) income per share, basic	64,031,592	62,328,468	63,573,048	61,566,989
Weighted-average shares used to compute net (loss) income per share, diluted	64,031,592	66,406,817	63,573,048	65,077,722

(1) Amount includes non-cash stock-based compensation expense.

Stock-based Compensation

(In thousands)

	Three Months Ended		Twelve Months Ended
	December 31,		December 31,
	2025	2024	2025	2024
Research and development	$6,121	$5,322	$26,422	$20,919
General and administrative	4,580	3,771	19,552	16,635
Total stock-based compensation expense	$10,701	$9,093	$45,974	$37,554

PROTAGONIST THERAPEUTICS, INC.

Selected Consolidated Balance Sheet Data

(In thousands)

	December 31,	December 31,
	2025	2024
Cash, cash equivalents and marketable securities	$646,002	$559,165
Working capital	532,133	544,243
Total assets	668,188	744,725
Deferred revenue	9,550	30,567
Accumulated deficit	(470,671)	(340,522)
Total stockholders' equity	614,707	675,295

Contacts
Corey Davis, Ph.D.
LifeSci Advisors cdavis@lifesciadvisors.com +1 212 915 2577
Virginia Amann ENTENTE Network of Companies virginiaamann@ententeinc.com +1 833 500 0061 ext 1
PROTAGONIST THERAPEUTICS, INC.