UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 ______________________________________ FORM 10-K ______________________________________ (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the year ended December 31, 2025 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 001-35676 ______________________________________ PROTHENA CORPORATIO ...

Key Takeaways Prothena reported a Q4 loss of 45 cents per share, while revenues fell sharply year over year.Prothena expects 2026 net cash burn of $50M-$55M and projects up to $105M in milestone payments.Prothena's partnered pipeline includes late-stage studies with Roche and Novo Nordisk through 2029.Prothena Corporation (PRTA) reported fourth-quarter 2025 adjusted loss per share (excluding restructuring costs) of 45 cents, in line with the Zacks Consensus Estimate.In the year-ago quarter, the company had ...

Core Insights - Prothena reported a quarterly loss of $0.44 per share, slightly better than the Zacks Consensus Estimate of a loss of $0.45, and an improvement from a loss of $1.08 per share a year ago, resulting in an earnings surprise of +1.12% [1] - The company generated revenues of $0.02 million for the quarter ended December 2025, missing the Zacks Consensus Estimate by 99.3%, and a significant decline from year-ago revenues of $2.12 million [2] - Prothena's stock has underperformed, losing about 4.8% since the beginning of the year, while the S&P 500 has gained 0.5% [3] Earnings Outlook - The future performance of Prothena's stock will largely depend on management's commentary during the earnings call and the company's earnings outlook, including current consensus earnings expectations for upcoming quarters [4] - The estimate revisions trend for Prothena was mixed ahead of the earnings release, resulting in a Zacks Rank 3 (Hold), indicating expected performance in line with the market [6] - Current consensus EPS estimate for the next quarter is -$0.39 on $5 million in revenues, and for the current fiscal year, it is $0.20 on $148.76 million in revenues [7] Industry Context - The Medical - Biomedical and Genetics industry, to which Prothena belongs, is currently in the top 36% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Compugen, another company in the same industry, is expected to report quarterly earnings of $0.05 per share, reflecting a year-over-year change of +171.4%, with revenues anticipated to be $17.87 million, up 1115.7% from the previous year [9]

Financial Data and Key Metrics Changes - In 2025, Prothena reported a net cash used in operating and investing activities of $163.7 million, which was favorable compared to the guidance range of $170 million to $178 million [37] - The net loss for 2025 was $244.1 million, aligning with the guidance range of $240 million to $248 million [37] - As of December 31, 2025, Prothena had $308.4 million in cash, cash equivalents, and restricted cash, exceeding the guidance of $298 million [38] Business Line Data and Key Metrics Changes - Prothena's clinical pipeline saw significant progress, with two partnered programs, prasinezumab and coramitug, advancing into phase 3 clinical trials [6][7] - The phase 2 clinical trial for BMS-986446 in early Alzheimer's disease was fully enrolled in 2025, with completion expected in the first half of 2027 [8] - The company introduced its CYTOPE technology, demonstrating potential for precise targeting of intracellular disease pathways [9][30] Market Data and Key Metrics Changes - The phase 3 PARAISO trial for prasinezumab is expected to enroll approximately 900 participants, with primary completion anticipated in 2029 [16] - The phase 3 CLEOPATTRA trial for coramitug is intended to enroll about 1,280 ATTR-CM patients, with primary completion also expected in 2029 [23] - Prothena's partnered clinical programs have the potential to deliver up to approximately $3 billion in future milestone payments [12] Company Strategy and Development Direction - Prothena aims to capture value from clinical partnerships, with potential clinical milestone payments of up to $105 million in 2026 [10][40] - The company plans to implement a share redemption program and invest in its preclinical portfolio to support ongoing partnering efforts [40] - Prothena is focused on advancing its knowledge of the preclinical portfolio to explore research collaborations and licensing agreements [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the robust pipeline addressing significant unmet needs for millions of patients [40] - The company highlighted the importance of upcoming milestones and the potential for significant medical advances in areas with high unmet needs [45] - Prothena remains well-capitalized with a strong cash position, focusing on delivering long-term shareholder value [41] Other Important Information - Prothena's collaborations with Bristol Myers Squibb progressed, with BMS-986446 receiving Fast Track designation from the U.S. FDA for Alzheimer's treatment [8] - The company is engaged in research collaborations exploring multiple approaches for applying its CYTOPE technology [11] Q&A Session Summary Question: Key milestones for partnered program trials for PARAISO and CLEOPATTRA - Management outlined expectations for sharing more information on CYTOPE activities and data from the tau program with Bristol Myers Squibb in 2027, along with the phase 3 readouts expected in 2029 for coramitug and prasinezumab [42][44] Question: Keeping the amyloid beta story alive against competitors - Management discussed the advantages of the PRX012 transferrin-based approach, emphasizing its potential for improved amyloid removal and reduced ARIA rates compared to competitors [51][55] Question: Data sharing from the phase one study of PRX019 - Management confirmed that data from the PRX019 study will be shared with Bristol Myers Squibb, who holds global rights to the program [62][68] Question: Data necessary to secure a partnership for the CYTOPE platform - Management highlighted the importance of demonstrating robust CNS activity and specificity in targeting TDP-43 aggregates, which could facilitate partnerships [71][75]

Financial Data and Key Metrics Changes - In 2025, Prothena reported a net cash used in operating and investing activities of $163.7 million, which was favorable compared to the guidance range of $170 million to $178 million [37] - The net loss for 2025 was $244.1 million, aligning with the guidance range of $240 million to $248 million [37] - As of December 31, 2025, Prothena had $308.4 million in cash, cash equivalents, and restricted cash, exceeding the guidance of $298 million [38] - For 2026, the expected net cash used in operating and investing activities is projected to be between $50 million and $55 million, with an estimated net loss of $67 million to $72 million [38][39] Business Line Data and Key Metrics Changes - Prothena's clinical pipeline saw significant advancements, with two partnered programs, prasinezumab and coramitug, moving into phase III clinical trials [6][7] - The phase II TargetTau-1 clinical trial for BMS-986446 in early Alzheimer's disease was fully enrolled in 2025, with completion expected in the first half of 2027 [8] - The company introduced its CYTOPE technology, demonstrating potential for precise targeting of intracellular disease pathways [9][30] Market Data and Key Metrics Changes - The phase III PARAISO trial for prasinezumab is expected to enroll approximately 900 participants, with primary completion anticipated in 2029 [16] - The phase III CLEOPATRA trial for coramitug is set to enroll around 1,280 ATTR-CM patients, with primary completion also expected in 2029 [23] - Prothena's partnered clinical programs have the potential to deliver up to approximately $3 billion in future milestone payments, in addition to any royalties [12] Company Strategy and Development Direction - Prothena aims to capture value from clinical partnerships, with potential clinical milestone payments of up to $105 million in 2026 [10][41] - The company plans to implement a share redemption program and invest in its preclinical portfolio to support ongoing partnering efforts [10][41] - Prothena is focused on advancing its knowledge of the preclinical portfolio to explore research collaborations and licensing agreements [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the robust pipeline addressing significant unmet needs for millions of patients [40] - The company highlighted the importance of upcoming milestones and the potential for significant medical advances in areas with high unmet needs [46] - Management emphasized the strategic importance of the share redemption program and the potential for clinical milestone payments from partners [47][48] Other Important Information - Prothena's cash position as of year-end 2025 was $308.4 million, allowing for prudent capital utilization to support future potential economics from partner programs [11] - The company is engaged in research collaborations exploring multiple approaches for applying its CYTOPE technology [10] Q&A Session Summary Question: Key milestones for partnered program trials for PARAISO and CLEOPATRA - Management outlined that significant activities are expected in 2026 and 2027, including data from the CYTOPE activities and the phase II tau program with Bristol Myers Squibb [44][46] Question: Keeping the amyloid beta story alive against competitors - Management discussed the advantages of the PRX-012 transferrin-based approach and the potential for improved profiles compared to existing therapies [51][55] Question: Data sharing from the phase I study of PRX-019 - Management indicated that data will be shared with Bristol Myers Squibb, who holds global rights to the program, and will decide on public dissemination [62][68] Question: Data necessary for securing a partnership for the CYTOPE platform - Management highlighted the importance of robust in-vivo data demonstrating the technology's ability to target intracellular disease pathways effectively [71][75]

Financial Data and Key Metrics Changes - In 2025, Prothena reported a net cash used in operating and investing activities of $163.7 million, which was favorable compared to the guidance range of $170 million to $178 million [35] - The net loss for 2025 was $244.1 million, aligning with the guidance range of $240 million to $248 million [35] - As of December 31, 2025, Prothena had $308.4 million in cash, cash equivalents, and restricted cash, exceeding the guidance of $298 million [36] Business Line Data and Key Metrics Changes - Prothena's clinical pipeline saw significant advancements, with two partnered programs, prasinezumab and coramitug, moving into phase 3 clinical trials [5] - The phase 3 PARAISO trial for prasinezumab will evaluate 900 participants with early Parkinson's disease, while the CLEOPATTRA trial for coramitug will enroll approximately 1,280 patients with ATTR-CM [5][17] - The company anticipates potential milestone payments of up to $105 million in 2026 from these partnered programs [9][38] Market Data and Key Metrics Changes - The global market for Parkinson's disease treatment is significant, with over 10 million patients and no approved disease-modifying therapies currently available [13] - The ATTR-CM market represents a multi-billion dollar opportunity, with coramitug expected to capture substantial future milestone payments [18] Company Strategy and Development Direction - Prothena aims to capture value from its clinical partnerships and has a strategic priority to implement a share redemption program in 2026 [9][39] - The company is focused on advancing its preclinical portfolio and exploring research collaborations, particularly around its CYTOPE technology [9][39] - Prothena's strategic priorities are supported by a robust cash position, allowing for prudent capital utilization [10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's execution and resilience in 2025, setting the stage for future growth [39] - The company is optimistic about the potential for significant medical advances in areas with high unmet needs, particularly in neurodegenerative diseases [42] - Management highlighted the importance of upcoming milestones and the potential for substantial clinical milestone payments in 2026 [46] Other Important Information - Prothena's collaborations with Bristol Myers Squibb progressed, with the phase 2 TargetTau-1 trial for BMS-986446 fully enrolled and expected to complete in the first half of 2027 [6] - The company introduced its CYTOPE technology, which aims to enable precise targeting of intracellular disease pathways [27] Q&A Session Summary Question: Key milestones for partnered program trials for PARAISO and CLEOPATTRA - Management outlined that significant activities are expected in 2026 and 2027, including updates on CYTOPE technology and data from the tau program with Bristol Myers Squibb [41][42] Question: Keeping the amyloid beta story alive versus competitors - Management discussed the advantages of the PRX012 transferrin-based approach, emphasizing its potential for robust amyloid removal and improved safety profile [50][52] Question: Data sharing from the phase one study of PRX019 - Management confirmed that data from the PRX019 study will be shared with Bristol Myers Squibb, who holds global rights to the program [61][66] Question: Data necessary for CYTOPE platform partnerships - Management highlighted the importance of demonstrating robust CNS activity and specificity in targeting TDP-43 aggregates to attract partnerships [69][73]

Prothena Fourth Quarter and Year-End 2025 Financial Results 4Q and FY25 Earnings Call Agenda | Welcome | Mark Johnson Vice President, Head of Investor Relations | | --- | --- | | Opening Remarks | Gene Kinney, Ph.D. President and CEO | | Clinical Programs | Chad Swanson, Ph.D. Chief Development Officer | | Preclinical Programs | Philip Dolan, Ph.D. Vice President, Head of Discovery Research | | Financial Results | Tran Nguyen Chief Strategy Officer and Chief Financial Officer | | Closing Remarks | Gene Kinn ...

Exhibit 99.1 PRESS RELEASE Prothena Reports Fourth Quarter and Full Year 2025 Financial Results, and Provides Financial Guidance and Business Highlights DUBLIN, Ireland, February 19, 2026-- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today reported financial results for the fourth quarter and full year 2025. In addition, the Company provided business highlights and 2026 fi ...

Core Viewpoint - Prothena Corporation (PRTA) has experienced a significant decline in share price, dropping 36.8% over the past year, primarily due to setbacks in its pipeline, particularly the failure of its candidate birtamimab in a late-stage study [1][6]. Financial Performance - The company has reported inconsistent earnings over the last four quarters, with losses widening due to increased research and development expenses and the impact of pipeline setbacks, including the discontinuation of birtamimab [2]. - Prothena's earnings have missed estimates in each of the last four quarters, with an average negative surprise of 26.72% [2]. Pipeline Setbacks - In May 2025, Prothena announced the discontinuation of birtamimab after the AFFIRM-AL study failed to meet its primary endpoint, removing a near-term value driver [3]. - The termination of birtamimab has significantly reduced near-term catalysts for the stock and shifted the company's strategic focus toward earlier-stage assets like PRX012, which are several years away from potential commercialization [4]. Workforce and Cost Management - In June, Prothena announced a 63% workforce reduction to streamline operating costs while ensuring continued support for its wholly owned programs and partnered program obligations [7]. Partnered Programs Progress - Prothena's pipeline progress is largely driven by partnered assets rather than wholly owned programs [8]. - Partner Novo Nordisk is evaluating coramitug in the phase III CLEOPATTRA program for ATTR cardiomyopathy, which could earn Prothena up to $1.23 billion in development and sales milestones [9]. - Roche has initiated the phase III PARAISO study on prasinezumab for early-stage Parkinson's disease, indicating ongoing commitment to this collaboration [10]. Collaboration Agreements - Prothena has a worldwide collaboration agreement with Roche, having received $135 million to date, with potential for up to $620 million in additional milestone payments and royalties on future sales [11]. - Bristol Myers Squibb is conducting a phase II study for its anti-tau antibody BMS-986446 in Alzheimer's disease, with primary completion expected in 2027 [12]. Ongoing Development - Prothena has initiated an early-stage first-in-human study on PRX019, with completion expected in 2026 [14].

Core Viewpoint - Prothena (PRTA) has received a Zacks Rank 2 (Buy) upgrade, indicating a positive outlook for its earnings estimates, which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Price Movement - The Zacks rating system emphasizes the correlation between changes in earnings estimates and stock price movements, driven by institutional investors who adjust their valuations based on these estimates [4]. - An increase in earnings estimates typically leads to higher fair value for a stock, prompting institutional investors to buy or sell, which subsequently affects stock prices [4]. Prothena's Earnings Outlook - Prothena is projected to earn -$4.60 per share for the fiscal year ending December 2025, which remains unchanged from the previous year [8]. - Over the past three months, the Zacks Consensus Estimate for Prothena has increased by 119%, reflecting a positive trend in earnings estimates [8]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with Zacks Rank 1 (Strong Buy) stocks historically generating an average annual return of +25% since 1988 [7]. - Prothena's upgrade to Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, indicating strong potential for market-beating returns in the near term [10].