PROTHENA CORP PUBLIC LTD CO

Previous wording

Fueled by our deep scientific expertise built over decades of research, we are advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which our ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. These programs include prasinezumab for the potential treatment of Parkinson’s disease and other related synucleinopathies that targets alpha-synuclein in collaboration with Roche. In addition, we have partnered BMS-986446 (formerly PRX005) for the potential treatment for Alzheimer’s disease that targets tau and PRX019 for the potential treatment of neurodegenerative diseases with an undisclosed target in two separate license agreements with Bristol Myers Squibb (BMS). We are also entitled to certain potential milestone payments pursuant to our share purchase agreement with Novo Nordisk pertaining to our ATTR amyloidosis business (inclusive of coramitug, formerly PRX004). Our wholly-owned and unpartnered portfolio includes clinical and preclinical-stage programs that we are exploring strategic interest to further develop.

Current wording

Fueled by our deep scientific expertise built over decades of research, we are advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which our ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. The Company’s pipeline includes both wholly-owned and partnered programs being developed for the potential treatment of diseases including Parkinson’s disease, ATTR amyloidosis with cardiomyopathy, Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS) and a number of other neurodegenerative diseases. Prothena is developing and applying CYTOPE® a novel technology that incorporates a cell-internalizing domain to drive efficient cytosolic delivery with highly specific marcomolecular effectors.

Previous wording

PARAISO is a Phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial to evaluate the efficacy and safety of prasinezumab in approximately 900 participants with early-stage Parkinson's disease on stable symptomatic monotherapy with levodopa. Primary endpoint of the trial is time to confirmed motor progression event on Movement Disorder Society - Unified Parkinson’s Disease Rating Scale (“MDS-UPDRS”) Part III score with a timeframe of at least 104 weeks.

Current wording

In the fourth quarter of 2025, Roche initiated the Phase 3 PARAISO clinical trial (NCT07174310) evaluating prasinezumab as a potential treatment for early Parkinson’s disease. PARAISO is a Phase 3, randomized, double-blind, placebo-controlled, multicenter clinical trial to evaluate the efficacy and safety of prasinezumab in approximately 900 participants with early-stage Parkinson's disease on stable symptomatic monotherapy with levodopa. Primary endpoint of the trial is time to confirmed motor progression event on Movement Disorder Society - Unified Parkinson’s Disease Rating Scale (“MDS-UPDRS”) Part III score at a minimum of 104 weeks.

Previous wording

In December 2024, topline results were announced from the Phase 2b clinical trial (PADOVA) conducted by partner Roche investigating prasinezumab in 586 people with early-stage Parkinson’s disease, treated for a minimum of 18 months while on stable symptomatic treatment. In April 2025, results from the Phase 2b PADOVA trial were presented for the first time in an oral presentation by Roche at the International Conference on Alzheimer’s and Parkinson’s Diseases (“AD/PD 2025”). Prasinezumab showed potential clinical effect in the primary endpoint of time to confirmed motor progression, as assessed by ≥5 point increase in MDS-UPDRS Part III score from baseline, with a HR=0.84 [0.69-1.01] and p=0.0657. The effect of prasinezumab was more pronounced in a pre-specified analysis in the population treated with levodopa (75% of participants), HR=0.79 [0.63-0.99] and nominal p=0.0431. Pre-specified supplementary covariate-adjusted analyses of these endpoints demonstrated nominally significant effects on the primary endpoint (HR=0.81 [0.67-0.98]; nominal p=0.0334) and in the levodopa subgroup (HR=0.76 [0.61-0.95]; nominal p=0.0175). Covariates used for adjustment: medication at baseline, H&Y stage, DaT-SPECT, age, sex, baseline dependent parameter. Consistent positive trends across multiple secondary and exploratory clinical endpoints were also observed. Positive trends towards reduced motor progression at 104 weeks (two years) were observed, showing 30-40% relative reduction versus placebo across the overall and levodopa-treated populations. The PADOVA study also provided the first biomarker evidence of prasinezumab impacting the underlying disease biology. Prasinezumab continues to be well tolerated and no new safety signals were observed in the study.

Current wording

In December 2024, topline results were announced from the Phase 2b clinical trial (PADOVA) conducted by partner Roche investigating prasinezumab in 586 people with early-stage Parkinson’s disease, treated for a minimum of 18 months while on stable symptomatic treatment. Prasinezumab showed potential clinical effect in the primary endpoint of time to confirmed motor progression, as assessed by ≥5 point increase in Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (“MDS-UPDRS”) Part III score from baseline, with a HR=0.84 [0.69-1.01] and p=0.0657. The effect of prasinezumab was more pronounced in a pre-specified analysis in the population treated with levodopa (75% of participants), HR=0.79 [0.63-0.99] and nominal p=0.0431. Pre-specified supplementary covariate-adjusted analyses of these endpoints demonstrated nominally significant effects on the primary endpoint (HR=0.81 [0.67-0.98]; nominal p=0.0334) and in the levodopa subgroup (HR=0.76 [0.61-0.95]; nominal p=0.0175). Covariates used for adjustment: medication at baseline, H&Y stage, DaT-SPECT, age, sex, baseline dependent parameter. Consistent positive trends across multiple secondary and exploratory endpoints were also observed. Prasinezumab continues to be well tolerated and no new safety signals were observed in the study. In March 2026, Roche presented an analysis from the ongoing PADOVA open-label extension (OLE)

Previous wording

Prasinezumab is the first anti-alpha synuclein antibody to advance into late-stage development. In March 2022, results from the analysis of part 2 of the Phase 2 PASADENA trial of prasinezumab were presented in an oral presentation by Roche at the International Conference on Alzheimer’s and Parkinson’s Diseases. Results showed that participants with Parkinson’s disease who were treated with prasinezumab for two years (early-start group) showed slower decline of MDS-UPDRS Part III scores relative to participants treated with placebo in the first year and prasinezumab in the second year (delayed-start group), further supporting a potential effect on delaying motor progression in patients. In October 2024, Roche published results in Nature Medicine from the long term open-label extension of the PASADENA trial, which compared the prasinezumab population with a propensity score-balanced cohort of real-world data (“RWD”) Parkinson’s Progression Markers Initiative (“PPMI”). The data suggests that prasinezumab continued to show reduced motor and functional progression in prazinezumab-treated individuals with early-stage Parkinson’s disease compared to a real-world data arm on MDS-UPDRS Part III score (clinician rated motor examination) OFF and ON symptomatic medication state and MDS-UPDRS Part II score (patient-reported motor experiences of daily living). The Phase 2 PASADENA and Phase 2b PADOVA open-label extension studies will continue in order to further explore the observed effects in both studies.

Current wording

Prasinezumab is the first anti-alpha synuclein antibody to advance into late-stage development. In March 2022, results from the analysis of part 2 of the Phase 2 PASADENA trial of prasinezumab were presented in an oral presentation by Roche at the International Conference on Alzheimer’s and Parkinson’s Diseases (“AD/PD 2022”). Results showed that participants with Parkinson’s disease who were treated with prasinezumab for two years (early-start group) showed slower decline of MDS-UPDRS Part III scores relative to participants treated with placebo in the first year and prasinezumab in the second year (delayed-start group), further supporting a potential effect on delaying motor progression in patients. In October 2024, Roche published results in Nature Medicine from the long term open-label extension of the PASADENA trial, which compared the prasinezumab population with a propensity score-balanced cohort of real-world data (“RWD”) Parkinson’s Progression Markers Initiative (“PPMI”). The data suggests that prasinezumab continued to show reduced motor and functional progression in prazinezumab-treated individuals with early-stage Parkinson’s disease compared to a real-world data arm on MDS-UPDRS Part III score (clinician rated motor examination) OFF and ON symptomatic medication state and MDS-UPDRS Part II score (patient-reported motor experiences of daily living). In March 2026, results from the Phase 2 PASADENA open-label extension (OLE) study of prasinezumab were presented in an oral presentation by Roche at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (“AD/PD 2026”). The comparison of PASADENA OLE data with PPMI-based model predictions supports potential disease-modifying efficacy with an estimated two years of ‘time saved’ providing an intuitive measure of long-term benefit. The observed PASADENA OLE outcomes consistently deviated from the model-predicted progression, suggesting a sustained treatment effect. On average, participants were approximately two years less advanced in disease severity five years after the start of the trial compared to the virtual comparator.

Previous wording

Wild-type ATTR (wtATTR) occurs sporadically and primarily involves cardiomyopathy. It is estimated that between 400,000 to 1.4 million patients suffer from ATTR-cardiomyopathy (ATTR-CM).

Current wording

Wild-type ATTR (wtATTR) occurs sporadically and primarily involves cardiomyopathy. It is estimated that between 400,000 to 1.4 million patients suffer from ATTR-cardiomyopathy (ATTR-CM). Within this population, between 130,000 to 490,000 patients are estimated to be moderate-to-advanced and categorized as New York Heart Association Class III and IV.

Previous wording

In September 2025, Novo Nordisk initiated the Phase 3 CLEOPATTRA clinical trial evaluating coramitug as a potential treatment for ATTR-CM. CLEOPATTRA is a randomized, double-blind, placebo-controlled, multicenter clinical trial in approximately 1,280 participants with ATTR-CM. Primary endpoint is the number of occurrences of composite endpoint of cardiovascular (CV) deaths and recurrent CV events (CV hospitalizations and urgent heart failure visits) in a timeframe to end of study up to approximately four years.

Current wording

In the fourth quarter of 2025, Novo Nordisk initiated the Phase 3 CLEOPATTRA clinical trial (NCT07207811) evaluating coramitug as a potential treatment for ATTR-CM. CLEOPATTRA is a randomized, double-blind, placebo-controlled, multicenter clinical trial in approximately 1,280 participants with ATTR-CM. Primary endpoint is the number of occurrences of composite endpoint of cardiovascular (CV) deaths and recurrent CV events (CV hospitalizations and urgent heart failure visits) in a timeframe to end of study up to approximately four years.

Previous wording

A Phase 2 clinical trial of coramitug in 105 patients with ATTR amyloidosis with cardiomyopathy was conducted by Novo Nordisk (NCT05442047). Results are planned to be presented at the American Heart Association Scientific Sessions in November 2025.

Current wording

A Phase 2 clinical trial of coramitug in 105 patients with ATTR amyloidosis with cardiomyopathy was conducted by Novo Nordisk (NCT05442047). Top-line results were presented as a late-breaking session at the American Heart Association (AHA) Scientific Sessions in November 2025 and simultaneously published in the AHA journal, Circulation. Treatment with coramitug 60 mg/kg resulted in a statistically significant reduction and improvement from baseline in NT-proBNP levels compared with placebo (–48%; p=0.0017) over 52 weeks and notably with a reduction at in NT-proBNP levels at 12 months from baseline. This favorable reduction was achieved on top of background use of standard-of-care TTR stabilizers in most patients (80% in the coramitug 60 mg/kg group and 85.7% in the placebo group). Coramitug 60 mg/kg showed an estimated treatment difference of 13.45 meters in the six-minute walk test (6MWT) vs. placebo. Statistical significance was not achieved on the 6MWT endpoint, however this was potentially due to the small sample size and relatively short study duration. In addition, across a wide range of echocardiographic parameters, including measures of left ventricle (LV) and right ventricle (RV) systolic function, diastolic function, and estimated pulmonary arterial pressures, coramitug 60 mg/kg was associated with improvements versus placebo, suggestive of favorable cardiac remodeling. Coramitug demonstrated an acceptable safety profile and was generally well tolerated.

Previous wording

Under the terms of the definitive purchase agreement, Novo Nordisk acquired our wholly-owned subsidiary and gained full worldwide rights to the intellectual property and related rights of our ATTR amyloidosis business and pipeline. The aggregate purchase price consists of an upfront paymentand development and sales milestone payments totaling up to $1.23 billion. We have earned approximately $100 million to date.

Current wording

Under the terms of the definitive purchase agreement, Novo Nordisk acquired our wholly-owned subsidiary and gained full worldwide rights to the intellectual property and related rights of our ATTR amyloidosis business and pipeline. The aggregate purchase price consists of an upfront paymentand development and sales milestone payments totaling up to $1.23 billion. We have earned approximately $150 million to date.

Previous wording

BMS-986446 is a humanized monoclonal antibody that targets multiple domains of the microtubule binding region of tau, a highly pathogenic tau fragment associated with neurofibrillary tangle formation and cognitive decline in Alzheimer’s disease. BMS-986446 binds to specific regions of the tau protein (R1–R3 within the microtubule-binding domain) to prevent the cell-to-cell spread of tau and tau uptake into cells. It also activates microglia—the brain’s immune cells—through its Fc receptor function, promoting the clearance of tau via phagocytosis. Neurofibrillary tangles composed of misfolded tau proteins, along with amyloid beta plaques, are pathological hallmarks of Alzheimer’s disease. Cell-to-cell transmission of pathogenic extracellular tau and the accumulation of pathogenic tau also correlate with the progression of symptomatology and clinical decline in patients with Alzheimer’s disease. Recent publications suggest that during the course of Alzheimer’s disease progression, tau appears to spread throughout the brain via synaptically-connected pathways; this propagation of pathology is thought to be mediated by tau “seeds” containing the MTBR of tau. Additionally, it has been recently reported that the presence of MTBR fragments in cerebrospinal fluid correlate with dementia stages and tau tangles in Alzheimer’s disease to a higher degree than fragments of other tau regions. In preclinical research, antibodies targeting this region of tau were superior in blocking tau uptake and neurotoxicity, which has been associated with efficacy in relevant animal models. In these preclinical models, BMS-986446 demonstrated significant reduction of intraneuronal tau pathology and progression protection against behavioral deficit in a tau transgenic mouse model and complete blockade of neuronal tau internalization in vitro.

Current wording

BMS-986446 is designed to be a best-in-class anti-tau antibody that specifically binds with high affinity the R1, R2, and R3 repeats within the microtubule binding region (“MTBR”) of tau and targets both 3R and 4R tau isoforms. MTBR-tau has been shown in preclinical studies to be involved in the pathological spread of tau. Neurofibrillary tangles composed of misfolded tau proteins, along with amyloid beta plaques, are pathological hallmarks of Alzheimer’s disease. Cell-to-cell transmission of pathogenic extracellular tau and the accumulation of pathogenic tau also correlate with the progression of symptomatology and clinical decline in patients with Alzheimer’s disease. Recent publications suggest that during the course of Alzheimer’s disease progression, tau appears to spread throughout the brain via synaptically-connected pathways; this propagation of pathology is thought to be mediated by tau “seeds” containing the MTBR of tau. Additionally, it has been recently reported that the presence of MTBR fragments in cerebrospinal fluid correlate with dementia stages and tau tangles in Alzheimer’s disease to a higher degree than fragments of other tau regions. In preclinical research, antibodies targeting this region of tau were superior in blocking tau uptake and neurotoxicity, which has been associated with efficacy in relevant animal models. In these preclinical models, BMS-986446 demonstrated significant reduction of intraneuronal tau pathology and progression protection against behavioral deficit in a tau transgenic mouse model and complete blockade of neuronal tau internalization in vitro.

Previous wording

In the first quarter of 2024, BMS advanced the anti-tau program BMS-986446 with the initiation of the Phase 2 TargetTau-1 clinical trial (NCT06268886). TargetTau-1 is a randomized, double-blind, placebo-controlled, global Phase 2 proof-of-concept study designed to evaluate the efficacy, safety and tolerability of multiple doses of BMS-986446 in approximately 310 participants with early Alzheimer’s disease. The study aims to determine whether targeting MTBR-tau can modify disease progression. In addition to clinical outcome measures, the trial integrates a comprehensive biomarker strategy to assess tau and amyloid-beta biology. The primary outcome measure is change from baseline in brain tau deposition as measured by tau positron emission tomography (PET) at 76 weeks.

Current wording

In the first quarter of 2024, BMS advanced the anti-tau program BMS-986446 with the initiation of a Phase 2 TargetTau-1 clinical trial (NCT06268886). This is a randomized, double-blind, placebo-controlled, global, Phase 2 clinical trial designed to evaluate the efficacy, safety, and tolerability of BMS-986446, an anti-MTBR tau monoclonal antibody, in approximately 310 participants with early Alzheimer's disease. Participants will be randomized into one of three treatment arms including placebo, BMS-986446 Dose A, and BMS-986446 Dose B. The primary outcome measure is change from baseline to week 76 in brain tau deposition as measured by tau positron emission tomography (PET). Secondary endpoints include change from baseline to week 76 in Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score and in the integrated Alzheimer’s Disease Rating Scale (iADRS) score.

Previous wording

A multiple ascending dose (MAD) portion of the Phase 1 clinical trial was ongoing at the time BMS acquired the global rights to the program and control of the Phase 1 trial.

Current wording

A multiple ascending dose (MAD) portion of the Phase 1 clinical trial was ongoing at the time BMS acquired the global rights to the program and control of the Phase 1 trial. All program updates going forward, including results from ongoing and any future BMS-986446 clinical trials, will be reported by BMS.

Previous wording

In the second quarter of 2025, BMS initiated a Phase 1 clinical trial to assess drug levels, tolerability and absolute biological availability of single subcutaneous dose of BMS-986446 in healthy participants. This is a Phase 1, randomized, open-label, parallel, single-dose clinical trial to assess the pharmacokinetics, tolerability, and absolute bioavailability of subcutaneous administration of BMS-986446, an anti-MTBR tau monoclonal antibody, in approximately 46 healthy participants.

Current wording

In 2025, BMS completed a Phase 1 clinical trial to assess drug levels, tolerability and absolute biological availability of single subcutaneous dose of BMS-986446 in healthy participants. This was a Phase 1, randomized, open-label, parallel, single-dose clinical trial to assess the pharmacokinetics, tolerability, and absolute bioavailability of subcutaneous administration of BMS-986446, an anti-MTBR tau monoclonal antibody, in approximately 46 healthy participants.

Previous wording

In July 2021, we entered into an exclusive US license agreement for BMS-986446 and we received an associated option exercise fee of $80 million. In July 2023, we entered into an exclusive global license agreement for BMS-986446, which as discussed above supersedes and replaces the US license agreement in its entirety and we received an associated option exercise fee of $55 million. We are eligible to receive regulatory and sales milestone payments of up to $563 million, as well as tiered royalties on annual, worldwide net sales. In October 2025, Bristol Myers Squibb announced that the FDA granted Fast Track designation for BMS-986446 for the treatment of Alzheimer’s disease. The FDA’s Fast Track designation program is designed to expedite the development and review of drugs intended to treat a serious condition, such as Alzheimer’s disease, with evidence demonstrating the potential to address an unmet medical need.

Current wording

In July 2021, we entered into an exclusive US license agreement for BMS-986446 and we received an associated option exercise fee of $80 million. In July 2023, we entered into an exclusive global license agreement for BMS-986446, which supersedes and replaces the US license agreement in its entirety and we received an associated option exercise fee of $55 million. We are eligible to receive regulatory and sales milestone payments of up to $563 million, as well as tiered royalties on annual, worldwide net sales. In October 2025, we announced that Bristol Myers Squibb obtained Fast Track designation from the U.S. FDA for BMS-986446 for the potential treatment of Alzheimer’s disease.

Previous wording

In December 2023, the FDA cleared the IND application for PRX019. In May 2024, we entered into an exclusive global license agreement for PRX019 and we received an associated option exercise fee of $80.0 million. We are eligible to receive development, regulatory, and sales milestone payments of up to $617.5 million as well as tiered royalties on annual, worldwide net sales.

Current wording

In December 2023, the FDA cleared the IND application for PRX019. In May 2024, we entered into an exclusive global license agreement for PRX019 and we received an associated option exercise fee of $80 million. We are eligible to receive development, regulatory, and sales milestone payments of up to $617.5 million as well as tiered royalties on annual, worldwide net sales.

Previous wording

We have a portfolio of unpartnered discovery and preclinical-stage programs for diseases with significant unmet medical needs.

Current wording

We are also advancing several early-stage programs for neurological diseases with significant unmet medical needs. If promising, we expect to advance our discovery and preclinical programs to clinical development. New target discovery will focus on areas where we can bring potential new therapies to patients expeditiously through our internal expertise and resources. Existing late discovery-stage or preclinical-stage programs may be partnered or out-licensed.

Previous wording

There were no significant changes to our critical accounting policies and estimates during the nine months ended September 30, 2025, from the critical accounting policies and estimates disclosed in Management's Discussion and Analysis of Financial Condition and Results of Operations in our 2024 Form 10-K.

Current wording

There were no significant changes to our critical accounting policies and estimates during the three months ended March 31, 2026, from the critical accounting policies and estimates disclosed in Management's Discussion and Analysis of Financial Condition and Results of Operations in our 2025 Form 10-K.

Previous wording

Except as described in Note 2 to the Condensed Consolidated Financial Statements under the heading “Recent Accounting Pronouncements”, there have been no new accounting pronouncements or changes to accounting pronouncements during the nine months ended September 30, 2025, as compared to the recent accounting pronouncements described in our 2024 Form 10-K, that are of significance or potential significance to us.

Current wording

Except as described in Note 2 to the Condensed Consolidated Financial Statements under the heading “Recent Accounting Pronouncements”, there have been no new accounting pronouncements or changes to accounting pronouncements during the three months ended March 31, 2026, as compared to the recent accounting pronouncements described in our 2025 Form 10-K, that are of significance or potential significance to us.

Previous wording

Comparison of three and nine months ended September 30, 2025 and 2024

Current wording

Comparison of three months ended March 31, 2026 and 2025

Previous wording

Total revenue was$2.4 million and$1.0 million for the three months ended September 30, 2025 and 2024, respectively, and$9.7 million and $133.0 million for the nine months ended September 30, 2025, and 2024, respectively.

Current wording

Total revenue was $51.1 million and $2.8 million for the three months ended March 31, 2026 and 2025, respectively.

Previous wording

Collaboration revenue was$2.4 million and$9.6 million for thethree and nine months ended September 30, 2025, compared to$1.0 million and$133.0 million for thethree and nine months ended September 30, 2024. Collaboration revenue forthree and nine months ended September 30, 2025 was related to the partial performance of our PRX019 Phase 1 Clinical Trial Obliga tion. Collaboration revenue of$133.0 million for thenine months ended September 30, 2024 included $107.9 million from the PRX019 Global License Agreement and PRX019 Phase 1 Clinical Trial Obligation and $25.0 million was related to BMS’s material rights for the US Rights and Global Rights for the TDP-43 Collaboration Target that expired unexercised on May 24, 2024 as a result of the expiration of the research term of the Collaboration Agreement.

Current wording

Collaboration revenue was $1.0 million for thethree months ended March 31, 2026, compared to $2.8 million for thethree months ended March 31, 2025. Collaboration revenue forthree months ended March 31, 2026 and 2025 was related to the partial performance of our PRX019 Phase 1 Clinical Trial Obliga tion.

Previous wording

As of September 30, 2025, the Company has$2.7 million of deferred revenue related to the remaining performance obligations under the PRX019 Global License Agreement relatedto PRX019 Phase 1 Clinical Trial Obligations. See Note 7, “Significant Agreements” to the Condensed Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information.

Current wording

As of March 31, 2026, the Company has$1.6 million of deferred revenue related to the remaining performance obligations under the PRX019 Global License Agreement relatedto PRX019 Phase 1 Clinical Trial Obligations. See Note 7, “Significant Agreements” to the Condensed Consolidated Financial Statements regarding the Collaboration Agreement with BMS for more information.

Previous wording

License and intellectual property revenue for the nine months ended September 30, 2025, and 2024 included $50,000 in each period, respectively, in license fees recognized under the License Agreement entered into on March 1, 2020, between the Company's wholly owned subsidiary, Prothena Biosciences Limited, and F. Hoffmann-La Roche Ltd.

Current wording

Intellectual property revenue for thethree months ended March 31, 2026, included$50.0 million in a milestone payment from Novo Nordiskfor the continued advancement of coramitug in the Phase 3 CLEOPATTRA clinical trial. See Note 7, “Significant Agreements” to the Condensed Consolidated Financial Statements regarding the Novo Nordisk Share Purchase Agreement for more information. For thethree months ended March 31, 2026, and 2025, license revenue included $50 thousand in each period, respectively, in license fees recognized under the License Agreement entered into on March 1, 2020, between the Company's wholly owned subsidiary, Prothena Biosciences Limited, and F. Hoffmann-La Roche Ltd.

Previous wording

Total opera ting expenses consist of R&D expenses, general and administrative (“G&A”) expenses, and restructuring costs. Our operating expenses were $42.7 million and $67.5 million for the three months ended September 30, 2025 and 2024, respectively, and $200.1 million and $222.7 million for thenine months ended September 30, 2025, and 2024, respectively.

Current wording

Total opera ting expenses consist of research and development (“R&D”) expenses, general and administrative (“G&A”) expenses, and restructuring costs. Our operating expenses were $21.0 million and $68.4 million for thethree months ended March 31, 2026 and 2025, respectively.

Previous wording

Our research activities are aimed at developing new drug products. Our development activities involve the translation of our research into potential new drugs. Our R&D expenses primarily consist of personnel costs and related expenses, including share-based compensation and external costs associated with clinical activities and drug development related to our drug programs, and preclinical activities related to our discovery programs. We also incurred wind down costs for programs that we are no longer advancing, including birtamimab and PRX012.

Current wording

Our research activities are aimed at developing new drug products. Our development activities involve the translation of our research into potential new drugs. Our R&D expenses primarily consist of personnel costs and related expenses, including share-based compensation and external costs associated with clinical activities and drug development related to our drug programs, and preclinical activities related to our discovery programs. We also incurred clinical trial wind down costs for programs that we are no longer advancing in clinical development, including birtamimab and PRX012.

Previous wording

Our R&D expense decreased by $21.8 million or 43% for the three months ended September 30, 2025 and decreased by $52.1 million or 30% for the nine months ended September 30, 2025, compared to the same periods in the prior year. The decrease for thethree and nine months ended September 30, 2025, compared to the same periods in the prior year, wasprimarily due to lower clinical trial expenses primarily related to PRX012 wind down, lower personnel expenses and lower manufacturing and consulting expenses.

Current wording

Our R&D expense decreased by $38.2 million or(75)% for thethree months ended March 31, 2026, compared to the same period in the prior year. The decrease for the three months ended March 31, 2026, compared to the same period in the prior year, was primarily due to lower clinical trial expenses primarily related to PRX012 and birtamimab wind down, lower personnel expenses, lower manufacturing, and lower consulting expenses .

Previous wording

The following table sets forth the R&D expenses for our major programs (specifically, programs with successful first dosing in a Phase 1 clinical trial and have material expenditures in the periods presented), which were birtamimab, PRX012, PRX019, and other R&D expenses for the three and nine months ended September 30, 2025, and 2024, (in thousands):

Current wording

The following table sets forth the R&D expenses for our major programs (specifically, programs with successful first dosing in a Phase 1 clinical trial and have material expenditures in the periods presented), which were birtamimab, PRX012, PRX019, and other R&D expenses for the three months ended March 31, 2026, and 2025, (in thousands):

Previous wording

Our G&A expenses decreasedby$3.5 million or 21% for the three months ended September 30, 2025 and decreased by$3.6 million or 7%for thenine months ended September 30, 2025, compared to the same periods in the prior year primarily due to lower personnel expense.

Current wording

Our G&A expenses decreasedby $4.9 million or(28)% for thethree months ended March 31, 2026, compared to the same period in the prior year primarily due to lower G&A consulting and lower personnel expense.

Previous wording

In June 2025, we commenced a restructuring plan following our decision in May 2025 to discontinue further development of birtamimab. We have incurred aggregate restructuring charges of approximately $0.5 million and $33.1 million for thethree and nine months ended September 30, 2025.

Current wording

In June 2025, we commenced a restructuring plan following our decision in May 2025 to discontinue further development of birtamimab. Our restructuring liability has reduced by approximately $4.2 million for the three months ended March 31, 2026, primarily due to a reduction in estimated contract termination costs associated with one or more third-party vendors.

Previous wording

Restructuring charges incurred under this plan primarily consist of employee termination benefits in connection with the reduction in force announced in June 2025 and contract termination costs. Employee termination benefits include severance costs, employee-related benefits, and noncash share-based compensation expense related to the acceleration of the vesting of certain stock options. Substantially all of the cash payments are expected to be paid out by the end of the fourth quarter of 2025. We may also incur additional costs not currently contemplated due to events that may occur as a result of, or that are associated with, the restructuring plan. See Note 11, “Restructuring” to the Condensed Consolidated Financial Statements for more information.

Current wording

Restructuring charges incurred under this plan primarily consist of employee termination benefits in connection with the reduction in force announced in June 2025 and contract termination costs. Employee termination benefits include severance costs, employee-related benefits, and noncash share-based compensation expense related to the acceleration of the vesting of certain stock options. We may also incur additional costs not currently contemplated due to events that may occur as a result of, or that are associated with, the restructuring plan. See Note 11, “Restructuring” to the Condensed Consolidated Financial Statements for more information.

Previous wording

Interest income decreased by $3.4 million or 50% for the three months ended September 30, 2025 and decreased by $8.9 million or 44% for the nine months ended September 30, 2025, compared to the same periods in the prior year primarily due to lower interest income from our cash and money market accounts resulting from lower cash balances and lower yields.

Current wording

Interest income decreased by $1.9 million or(44)% for thethree months ended March 31, 2026, compared to the same period in the prior year primarily due to lower interest income from our cash and money market accounts resulting from lower cash balances and lower yields.

Previous wording

Other expense, net for thethree and nine months ended September 30, 2025, was primarily foreign exchange losses from transactions with vendors denominated in euros.

Current wording

Other income (expense), net for thethree months ended March 31, 2026, was primarily due to foreign exchange gains from transactions with vendors denominated in euros.

Previous wording

No tax benefit has been recorded related to tax losses recognized in Ireland or the U.S. and any deferred tax assets for those losses are offset by a valuation allowance.

Current wording

The Company maintains a full valuation allowance on its deferred tax assets. No tax benefit has been recorded related to tax losses recognized in Ireland or the U.S. and any deferred tax assets for those losses are offset by a valuation allowance.

Previous wording

Working capital was$288.5 million as of September 30, 2025, a decrease of $148.4 million from working capital of$436.9 million as of December 31, 2024. This decrease in working capital during the nine months ended September 30, 2025, was primarily attributable to cash used in operating activities of $140.3 million.

Current wording

Working capital was $306.7 million as of March 31, 2026, an increase of $32.3 million from working capital of $274.4 million as of March 31, 2025. This increase in working capital during the quarter ended March 31, 2026, was primarily attributable to the$50.0 million milestone payment from Novo Nordisk.

Previous wording

As of September 30, 2025, we had $330.8 million in cash and cash equivalents. Based on our current business plans, we believe that our existing cash and cash equivalents at September 30, 2025 are sufficient to meet our obligations for at least the next twelve months. To operate beyond such period, or if we elect to increase our spending on research and development programs significantly above current long-term plans or enter into potential licenses and/or other acquisitions of complementary technologies, products or companies, we may need additional capital. Additionally, in order to develop and obtain regulatory approval for our potential products we will need to raise substantial additional capital. We expect to continue to finance future capital needs that exceed our existing cash and cash equivalents, payments pursuant to our agreements with Roche, BMS, and Novo Nordisk, and, to the extent necessary, other collaboration agreements with corporate partners, or other arrangements, and through proceeds from public or private equity or debt financings, and loans, including pursuant to the Amended Distribution Agreement (See Note 8, “Shareholders’ Equity” to the Condensed Consolidated Financial Statements for more information). We cannot assume that such additional financings will be available on acceptable terms, if at all, and such financings may only be available on terms dilutive to our shareholders.

Current wording

As of March 31, 2026, we had $329.5 million in cash and cash equivalents. Based on our current business plans, we believe that our existing cash and cash equivalents at March 31, 2026 are sufficient to meet our obligations for at least the next twelve months. To operate beyond such period, or if we elect to increase our spending on research and development programs significantly above current long-term plans or enter into potential licenses and/or other acquisitions of complementary technologies, products or companies, we may need additional capital. Additionally, in order to develop and obtain regulatory approval for our potential products we will need to raise substantial additional capital. We expect to continue to finance future capital needs that exceed our existing cash and cash equivalents, payments pursuant to our agreements with Roche, BMS, and Novo Nordisk, and, to the extent necessary, other collaboration agreements with corporate partners, or other arrangements, and through proceeds from public or private equity or debt financings, and loans. We cannot assume that such additional financings will be available on acceptable terms, if at all, and such financings may only be available on terms dilutive to our shareholders.

Previous wording

In managing our liquidity needs in Ireland, we do not rely on unrepatriated earnings as a source of funds. As of September 30, 2025, $215.8 million of our outstanding cash and cash equivalents related to U.S. operations are considered permanently reinvested. We do not intend to repatriate these funds. However, if these funds were repatriated back to Ireland, we would incur a withholding tax from the dividend distribution.

Current wording

In managing our liquidity needs in Ireland, we do not rely on unrepatriated earnings as a source of funds. As of March 31, 2026, $224.0 million of our outstanding cash and cash equivalents related to U.S. operations are considered permanently reinvested. We do not intend to repatriate these funds. However, if these funds were repatriated back to Ireland, we would incur a withholding tax from the dividend distribution.

Previous wording

Cash Provided by (Used in) Financing Activities

Current wording

Cash Provided by (Used in) Operating Activities

Previous wording

Net cash used in operating activities was$140.3 million for the nine months ended September 30, 2025, which was primarily due to ongoing research and development activities, general and administrative expenses to support those activities (adjusted to exclude non-cash charges for share-based compensation expense) and payments related to our restructuring activities, partially offset byinterest income on investments.

Current wording

Net cash provided by operating activities was$28.9 million for thethree months ended March 31, 2026, which was primarily due to $50 million milestone payment from Novo Nordisk, interest income, partially offset by ongoing research and development activities, general and administrative expenses to support those activities (adjusted to exclude non-cash charges for share-based compensation expense) and payments related to our restructuring activities.

Previous wording

Net cash used in investing activities was $138 thousand for thenine months ended September 30, 2025, which consisted of expenditures to purchase property and equipment.

Current wording

Net cash used in investing activities was null for the three months ended March 31, 2026.

Previous wording

Net cash used in financing activities was$139 thousand for thenine months ended September 30, 2025, which consisted of expenditures related to our at-the-market offering.

Current wording

Net cash used in financing activities was$6.9 million for the three months ended March 31, 2026, which consisted of cash used to repurchase our ordinary shares.

Previous wording

Refer to “Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations — Liquidity and Capital Resources” in our third quarter 2024 Quarterly Report on Form 10-Q for a discussion of the cash flows for the nine months ended September 30, 2024.

Current wording

Refer to “Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations — Liquidity and Capital Resources” in our first quarter 2025 Quarterly Report on Form 10-Q for a discussion of the cash flows for the three months ended March 31, 2025.