A Randomized, Double-blind, Placebo-controlled, 104-week Proof-of-concept Study to Evaluate the Efficacy of Intravenous Prasinezumab in Participants With Parkinson's Disease Carrying a Severe Mutation in the GBA Gene

This is a proof-of-concept trial to investigate the efficacy of prasinezumab to slow or prevent cognitive decline in people with Parkinson's disease carrying a severe mutation in the GBA (glucocerebrosidase) gene. The duration of the intervention per patient will be 104 weeks with monthly infusions. The investigators plan to enroll 120 participants (60 participants per treatment arm). This study will be conducted across Europe in the following countries: France, Germany, Italy, Luxembourg, Spain, Sweden, UK.

Start Date01 Dec 2025

Sponsor / Collaborator-

NCT07174310

/ RecruitingPhase 3

A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants With Early-Stage Parkinson's Disease

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of prasinezumab compared with placebo in participants with early-stage Parkinson's disease (PD) on stable symptomatic monotherapy with levodopa.

Start Date24 Nov 2025

Sponsor / Collaborator

Roche Holding AG

[+1]

NCT04777331

/ CompletedPhase 2

A Phase IIB, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Intravenous Prasinezumab in Participants With Early Parkinson's Disease

This is a multicenter, randomized, double-blind, placebo-controlled study that will evaluate the efficacy and safety of intravenous (IV) prasinezumab versus placebo in participants with Early Parkinson's Disease (PD) who are on stable symptomatic PD medication.

Start Date05 May 2021

Sponsor / Collaborator

Hoffmann-La Roche, Inc.

[+1]

100 Clinical Results associated with Prasinezumab

100 Translational Medicine associated with Prasinezumab

100 Patents (Medical) associated with Prasinezumab

Literatures (Medical) associated with Prasinezumab

01 Apr 2026·CURRENT OPINION IN NEUROBIOLOGY

The challenges of experimental pharmacology in identifying novel treatments for Parkinson's disease

Review

Author: Huot, Philippe ; Teil, Margaux

An important part of the field of experimental pharmacology encompasses the study of the effects of molecules in animals. In the case of Parkinson's disease (PD), animal models have played an invaluable role in refining our understanding of the disease, in characterizing the effect of new compounds on the illness, and in bringing new treatments to the clinic. Indeed, it is now hardly conceivable that a drug would be tested in humans if several parameters pertaining to safety, toxicology, efficacy, etc. had not previously been evaluated in animal models. Quite unfortunately, efficacy in experimental models of PD does not necessarily guarantee positive clinical outcomes. In this article, which primarily focusses on the past five years, we review drugs that entered clinical trials for the treatment of levodopa-induced dyskinesia, parkinsonism, disease modification, and had previously been assessed in animal models of PD. The drugs discussed are buspirone, JM-010, befiradol, mesdopetam, foliglurax, dipraglurant, tavapadon, prasinezumab, cinpanemab, nilotinib, minzasolmin, exenatide, NLY01, liraglutide, lixisenatide, and semaglutide. For each molecule, we examine how previous preclinical studies succeeded or failed in predicting efficacy in clinical trials and discuss possible ways to optimize animal-model design and selection to maximize the probability of translational success.

01 Mar 2026·JOURNAL OF THE NEUROLOGICAL SCIENCES

α-synuclein monoclonal antibodies in Parkinson's disease: A failed promise or unmet potential?

Review

Author: Mandour, Youssef ; Messak, Mark ; Altalab, Gergis ; Shaker, Omar ; Khattab, Youssef A ; Abdelmageed, Ahmed

BACKGROUND:

Monoclonal antibodies (mAbs) have shown disappointing results in targeting α-synuclein (α-Syn) aggregates in PD, leading us to question whether this therapeutic approach is fundamentally flawed or unrealized potential awaiting better application. This review aims to assess the current evidence, identify key challenges hindering this therapeutic approach, and highlight priorities for future research.

METHODS:

A narrative review of the literature was conducted focusing on available evidence with respect to safety, efficacy, pharmacokinetics, CNS exposure, peripheral and central target engagement, emerging biomarkers and PET scan imaging tracers, and lessons from immunotherapy development in Alzheimer's disease.

FINDINGS:

Five RCTs, three phase-I and two phase-II trials, testing three different forms of mAb (n = 786) were identified. All studies showed that mAbs were generally safe. They demonstrated low but measurable CSF mAb concentration (CSF:Serum = 0.2-0.5%) with limited evidence regarding central target engagement. Phase-II trials failed to meet their primary efficacy endpoints and showed no significant slowing of disease progression (Cinpanemab 250 mg P-value = 0.7, 1250 mg P-value = 0.78, 3500 mg P-value = 0.7; Prasinezumab 1500 mg P-value = 0.24, 4500 mg P-value = 0.72). These disappointing results are attributed to several factors, including late timing of intervention, poor BBB permeability, heterogeneity in α-Syn pathology, not using sensitive tools to detect central target engagement and Delayed PET scan tracers' development.

CONCLUSION:

Although there is strong preclinical evidence supporting the efficacy of mAb in PD, several limitations prevent this from translating into tangible clinical benefit. These limitations do not necessarily indicate a fundamental flaw in the therapeutic concept, but they do highlight the urgent need for future research to prioritize addressing these limitations.

04 Nov 2025·Cureus Journal of Medical Science

Immunotherapy in Early Parkinson's Disease: A Biomarker-Driven Trial Framework for Secondary Prevention

Review

Author: Kniazev, Roman

Parkinson's disease (PD) is characterized by α-synuclein aggregation and progressive dopaminergic neuron loss that begins years before motor symptoms appear. This prolonged premotor phase creates an opportunity for intervention before extensive neurodegeneration. Biomarkers, including α-synuclein seed amplification assays, standardized peripheral tissue biopsies (e.g., skin biopsies for phosphorylated α-syn), neuroimaging, fluid biomarkers, genetics, and digital measures, now detect prodromal PD biology in at-risk individuals and enable secondary-prevention-style trials. Immunotherapy targeting misfolded α-synuclein is a leading disease-modification strategy. Passive approaches (monoclonal antibodies) and active vaccines have shown target engagement in preclinical models and early trials. Phase 1/2 α-synuclein antibody trials have shown mainly mild-to-moderate infusion reactions and no reproducible CNS inflammatory toxicity. Although primary efficacy endpoints have not yet been achieved overall, prasinezumab has indicated exploratory slowing in faster progressors and digital measures. MEDI1341 has demonstrated Phase 1 target engagement with acceptable safety, and Lu AF82422 has shown Phase 1 target engagement, along with promising subgroup trends in MSA, and scheduled Phase 3. Meanwhile, cinpanemab was negative. However, signals of slowed progression in subgroups underscore the importance of treating earlier and selecting patients with biomarker-confirmed pathology. This review synthesizes evidence supporting early, biomarker-anchored intervention and the status of α-synuclein immunotherapies. Treating PD at the prodromal stage aims to preserve vulnerable neurons and alter the disease course; continued advances in biomarkers and trial design are essential to realize this potential. We emphasize biomarkers that verify α-synuclein pathology during the asymptomatic phase and argue for a secondary-prevention model that treats the underlying biology before symptoms to maximize disease-modifying potential. We also propose a practical, biomarker-guided trial blueprint for secondary prevention, with explicit screening funnels and endpoint hierarchies.

News (Medical) associated with Prasinezumab

06 May 2026

·www.biospace.com

ABLi Therapeutics Appoints Industry Veteran Dr. Rachelle S. Doody to its Board of Directors

Dr. Doody joins from Senior Leadership in Neurodegeneration at F. Hoffman-LaRoche LTD and biotech Axxium Life ATLANTA and BOSTON, May 06, 2026 (GLOBE NEWSWIRE) -- ABLi Therapeutics (“ABLi”), a biotechnology company developing therapeutics to address diseases that arise from activation of Abelson Tyrosine Kinases (c-Abl kinases), announces the appointment of world renowned industry veteran in clinical development of neurodegeneration therapeutics, Rachelle S. Doody, MD, PhD, to the ABLi Board of Directors. Dr. Doody has over 10 years of pharmaceutical leadership experience in clinical development of therapeutics to fight neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. She was Global Head of Neurodegeneration in late stage Neuroscience at F. Hoffman-LaRoche (Roche) where she led the development of the monoclonal antibodies Crenezumab and Gantenerumab for familial and sporadic AD; led the late stage development for Tominersin, an antisense oligonucleotide for Huntington’s Disease, and led the late-stage development program for Prasinezumab, an anti-alpha synuclein monoclonal antibody for Parkinson’s disease that is now in Phase 3 development. After leaving Roche in 2024, she joined the biotechnology company Axxium Life as Chief Medical Officer and Director of Development, where she oversees a pipeline of active immunotherapy medications directed against chronic and neurodegenerative diseases. Prior to her tenure at Roche, Dr. Doody was the Effie Marie Cain Chair in Alzheimer’s Disease research at Baylor College of Medicine and is presently a Distinguished Emeritus Professor in Neurology. Dr. Doody trained in internal medicine at McGill University, the Royal Victoria Hospital and the Montreal Neurological Hospital and Institute and did her residency in Neurology at Baylor where she honed her interests and expertise in Alzheimer’s Disease. Her PhD work in cognitive anthropology was completed at Rice University. “The appointment of Dr. Doody brings to the ABLi Board an industry leader in the development of neurodegenerative disease therapeutics,” said Dr. Milton Werner, ABLi’s Chairman and Chief Executive Officer. “Dr. Doody will advise the company on management best practices and clinical trial design as we prepare to launch our Phase 3 programs for Parkinson’s, Multiple System Atrophy (MSA) and Dementia with Lewy Body (DLB).” “Patients with neurodegenerative diseases need more and better treatments than what is available today. I am pleased to join the Board at ABLi to extend my assistance to another promising biotechnology company with the potential to really impact the synucleinopathies, such as Parkinson’s disease, MSA and DLB.” About Risvodetinib (ABLi-148009) Risvodetinib is a potent, selective small-molecule inhibitor of the non-receptor c-Abl kinases, designed for once-daily oral use that targets the underlying biological mechanisms driving Parkinson’s disease initiation and progression. Risvodetinib has been demonstrated to modify the PD pathophysiologic pathway and shown to impact the neurodegenerative and neuroinflammatory disease processes in humans as a once-per-day oral therapy. All marketed therapeutic approaches to treat Parkinson’s disease help manage symptoms, but there are currently no available treatments to slow or stop the disease’s relentless progression. Recently, risvodetinib was the first monotherapy to improve patient quality of life in a randomized, placebo-controlled clinical trial (NCT NCT05424276) and simultaneously reduced the underlying disease pathology and suppressed the underlying disease process in patients with untreated Parkinson’s disease. Risvodetinib currently has intellectual property protection beyond 2036. About ABLi Therapeutics ABLi Therapeutics (“ABLi”) applies innovative medicinal chemistry and a deep understanding of disease biology to develop small molecule therapeutics that target the cause of diseases that arise from activation or dysfunction of the Abelson Tyrosine Kinases (c-Abl). Leveraging its expertise in drug design, ABLi utilizes clinically validated data of kinase inhibitors to design and develop novel product candidates with enhanced penetration into the brain, greater potency and target selectivity, and improved safety to treat diseases in which Abl kinase activation or dysfunction is implicated. The Company’s primary focus is on developing therapeutics for the treatment of neurodegenerative diseases like Parkinson’s disease and the Parkinson’s-related neurodegenerative diseases Multiple System Atrophy and Dementia with Lewy Body that are all associated with Abl kinase activation or dysfunction. For more information visit or follow us on LinkedIn and X. Contacts: For ABLi Therapeutics Milton H Werner PhD Chairman & CEO info@ablitherapeutics.com Investor/Media Mike Moyer Managing Director – LifeSci Advisors mmoyer@lifesciadvisors.com

21 Mar 2026

·ir.prothena.com

Prothena Partners Present Data Supporting Next Generation Treatments for Parkinson’s and Alzheimer’s Disease at AD/PD™ 2026

DUBLIN--(BUSINESS WIRE)-- Prothena Corporation plc (NASDAQ:PRTA), a late-stage clinical biotechnology company with a robust pipeline of investigational therapeutics built on protein dysregulation expertise, today announced partner presentations on clinical updates from prasinezumab for the treatment of Parkinson’s disease and BMS-986446 for the treatment of Alzheimer’s disease at the International Conference on Alzheimer's and Parkinson's Diseases and Related Neurological Disorders (AD/PD™ 2026) in Copenhagen, Denmark, and online. Roche Presentations on Prasinezumab for the Potential Treatment of Parkinson’s Disease Industry Symposium – Pathways to Progress: Exploring Innovations in AD and PD for Future Practice Chair: Malú G. Tansey, Ph.D., Indiana University School of Medicine Stark Neuroscience Institute Date: Tuesday March 17, 2026 This symposium reviewed the evolving understanding of the molecular pathophysiology and disease heterogeneity across Alzheimer's disease (AD) and Parkinson's disease (PD). Explored current and emerging treatment pathways, e.g. alpha-synuclein, amyloid-beta and neuroinflammation; including diagnostics, biomarkers and therapeutics. Considered how the advancing understanding of AD and PD informs innovative clinical development approaches and clinical practice. Oral Presentation – Modeling Parkinson’s Disease Progression to Quantify Long-Term Treatment Effects via the Concept of ‘Time Saved’ Presenter: Benjamin Ribba, Roche Date: Thursday March 19, 2026 The comparison of PASADENA open-label extension (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. Oral Presentation – Prasinezumab in Early-Stage Parkinson’s Disease: Additional Data from the PADOVA Study Presenter: Tania Nikolcheva, M.D., Ph.D., Roche Date: Saturday March 21, 2026 Longer term data from the PADOVA OLE study in early-stage PD showed a sustained effect of prasinezumab in slowing Parkinson’s progression on top of effective symptomatic therapies. The totality of the evidence suggests a possible clinical benefit of prasinezumab and informed the initiation of the Phase III PARAISO study. Poster Presentation – Prasinezumab’s Impact on Neuromelanin- and Iron-Sensitive MRI Biomarkers in Parkinson’s Disease: Findings from the PADOVA Phase IIb Study Exploratory biomarker analysis of PADOVA suggests that prasinezumab is biologically active. This is supported by imaging biomarkers crucial to PD pathology, showing a slowing in the progressive loss of neuromelanin signal in substania nigra pars compacta and reduced iron accumulation in the putamen. Poster Presentation – Sustained Effect on Prasinezumab on Parkinson’s Disease Motor Progression in the Open-Label Extension of the PASADENA Trial, 5-Year Update At Year 5, the combined PASADENA arm (delayed- and early-start groups) showed less disease progression compared to the PPMI cohort. This lower progression was observed across multiple measures. Poster Presentation – Digital Health Technology Detects Group Differences in Practically-Defined OFF L-DOPA State: Results of PADOVA Phase IIb Study of Prasinezumab Post-hoc Digital Health Technology analyses showed consistent trends favoring prasinezumab in digital data collected in the practically-defined OFF L-DOPA state, in line with the PASADENA Phase 2a Simple Sum digital finding and clinical PADOVA readout. Bristol Myers Squibb Presentation on BMS-986446 for the Potential Treatment of Alzheimer’s Disease Oral Presentation – Randomized, Double-Blind, Placebo-Controlled Study Evaluating Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BMS-986446 in Healthy Participants, Including Those of Japanese Ethnicity Presenter: Ilena George, M.D., Bristol Myers Squibb Date: Saturday March 21, 2026 Single-dose BMS-986446 was safe and well tolerated in all participants, including those of Japanese ethnicity. Plasma exposure of BMS-986446 increased dose proportionally. No anti-drug antibodies were detected. These results support BMS-986446 dosing in ongoing clinical studies without adjustments for Japanese ethnicity. About Prasinezumab Prasinezumab is an investigational monoclonal antibody designed to bind aggregated alpha-synuclein and thereby reduce neuronal toxicity. By reducing the build-up of alpha-synuclein protein in the brain, prasinezumab can potentially prevent further accumulation and spreading between cells, which may slow progression of the disease. About Parkinson’s Disease Parkinson’s disease is a chronic, progressive and debilitating neurodegenerative disease characterized by the gradual loss of neurons that make dopamine and other nerve cells. Today, Parkinson’s disease affects over 10 million people worldwide. The prevalence of Parkinson’s disease is increasing, and it has become one of the fastest-growing neurological disorders. Currently, symptomatic treatments that effectively alleviate motor symptoms are available. However, no therapies slow down or stop the clinical progression of Parkinson’s disease. About BMS-986446 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 stop 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. About Alzheimer’s Disease Alzheimer’s disease is a progressive, multifaceted and devastating neurodegenerative disease and the most common type of dementia in adults. Changes in the brain disrupt communication between neurons, impacting memory, cognition and behavior. As a result, Alzheimer’s disease has a significant impact on the day-to-day lives of those it directly affects, as well as on their families, caregivers and friends, resulting in considerable shifts in interpersonal relationships. There remains a critical need for disease-modifying therapies that can slow or delay the progression of Alzheimer’s disease as well as therapies that manage and ease neurobehavioral symptoms. About Prothena Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothena’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 macromolecular effectors. For more information, please visit the Company’s website at www.prothena.com and follow the Company on X (formerly Twitter) @ProthenaCorp. Forward-Looking Statements This press release contains forward-looking statements. These statements relate to, among other things, the treatment potential, designs, proposed mechanisms of action, and potential administration of prasinezumab and BMS-986446; and the continued advancement of our preclinical and clinical pipeline, including the potential and advancement of CYTOPE. These statements are based on estimates, projections and assumptions that may prove not to be accurate, and actual results could differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, as well as those described in the “Risk Factors” sections of our Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 27, 2026, and discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. We undertake no obligation to update publicly any forward-looking statements contained in this press release as a result of new information, future events, or changes in our expectations. Mark Johnson, CFA Senior Vice President, Head of Investor Relations and Corporate Communications 650-837-8550 IR@prothena.com Media@prothena.com

Clinical ResultPhase 2

19 Feb 2026

·ir.prothena.com

Prothena Reports Fourth Quarter and Full Year 2025 Financial Results, and Provides Financial Guidance and Business Highlights

Net cash used in operating and investing activities was $23.3 million and $163.7 million for the fourth quarter and full year of 2025, respectively; quarter-end cash and restricted cash position was $308.4 million Prothena expects the full year 2026 net cash used in operating and investing activities to be $50 to $55 million and expects to end the year with approximately $255 million in cash (midpoint). Financial guidance does not include the potential to earn up to $105 million in aggregate clinical milestone payments from strategic partners in 2026 Roche initiated the Phase 3 PARAISO trial evaluating prasinezumab in early-stage Parkinson’s disease in 4Q 2025; primary completion expected in 2029 Novo Nordisk initiated the Phase 3 CLEOPATTRA trial evaluating coramitug in ATTR amyloidosis with cardiomyopathy in 4Q 2025; primary completion expected in 2029 Bristol Myers Squibb fully enrolled the Phase 2 TargetTau-1 trial evaluating BMS-986446 in early Alzheimer’s disease with primary completion expected in 1H 2027, completed a Phase 1 trial evaluating a subcutaneous formulation of BMS-986446 and obtained Fast Track designation from the U.S. FDA for BMS-986446 for the treatment of Alzheimer’s disease Prothena presented preclinical data on its TDP-43 CYTOPE® program at Neuroscience 2025 (SfN) and at the International Symposium on ALS/MND demonstrating the potential of Prothena’s CYTOPE® technology to target intracellular disease pathways At the Extraordinary General Meeting on November 19, 2025 Prothena obtained shareholder approval to reduce share capital to create distributable reserves to support a share redemption program to be conducted in 2026 if deemed appropriate Potential to earn up to $105 million in aggregate clinical milestone payments by end of 2026 related to the advancement of both coramitug for ATTR amyloidosis with cardiomyopathy by Novo Nordisk and PRX019 for neurodegenerative diseases by Bristol Myers Squibb DUBLIN--(BUSINESS WIRE)-- 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 financial guidance. “In 2025, our partner Roche initiated the Phase 3 PARAISO clinical trial evaluating prasinezumab in early Parkinson’s disease and Novo Nordisk initiated the Phase 3 CLEOPATTRA clinical trial evaluating coramitug in ATTR amyloidosis with cardiomyopathy, both with primary completions expected in 2029. In addition, we expect our partner Bristol Myers Squibb to decide on the potential advancement of PRX019 in 2026 and to complete the ongoing Phase 2 TargetTau-1 clinical trial evaluating BMS-986446 in early Alzheimer’s in 1H 2027. These partnered programs have the potential to earn up to approximately $3 billion in future aggregate milestones in addition to potential future royalties,” said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. “We also unveiled our proprietary CYTOPE® technology with presentations at scientific congresses highlighting preclinical data from our TDP-43 CYTOPE® program. In addition, we are evaluating PRX012-TfR, our once-monthly, subcutaneous anti-Aβ antibody combined with transferrin receptor technology for the treatment of Alzheimer’s in preclinical studies. We expect to share more data from our preclinical programs later this year.” 2025 Business Highlights and Upcoming Milestones Updates on Active Clinical Development Portfolio Prasinezumab, a potential first-in-class antibody for the treatment of Parkinson’s disease that is designed to target a key epitope within the C-terminus of alpha-synuclein and is the focus of a worldwide collaboration with Roche. Roche is evaluating prasinezumab in the ongoing Phase 3 PARAISO clinical trial in ~900 participants with early-stage Parkinson's disease; primary completion expected in 2029 ( NCT07174310) Roche has stated that prasinezumab has peak sales potential greater than $3.5 billion (unadjusted) and could be the first disease-modifying treatment for a condition that affects 10 million people worldwide Coramitug (formerly PRX004), a potential first-in-class amyloid depleter antibody for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM) designed to deplete the pathogenic, non-native forms of the transthyretin (TTR) protein, is being developed by Novo Nordisk as part of its up to $1.2 billion acquisition of Prothena’s ATTR amyloidosis business and pipeline. Novo Nordisk is evaluating coramitug in the ongoing Phase 3 CLEOPATTRA clinical trial in ~1280 participants with ATTR-CM; primary completion expected in 2029 ( NCT07207811) Novo Nordisk presented Phase 2 results during a late-breaking session at the American Heart Association Scientific Sessions on November 10, 2025 Potential to earn a clinical milestone in 1H 2026 when prespecified enrollment criteria are met in ongoing Phase 3 clinical trial by Novo Nordisk BMS-986446 (formerly PRX005), a potential best-in-class antibody for the treatment of Alzheimer’s disease that specifically targets a key epitope within the microtubule binding region (MTBR) of tau, a protein implicated in the causal pathophysiology of Alzheimer’s disease. Bristol Myers Squibb is conducting the Phase 2 TargetTau-1 clinical trial in approximately 310 patients with early Alzheimer’s disease; primary completion expected in 1H 2027 ( NCT06268886) Bristol Myers Squibb conducted a Phase 1 open-label single-dose clinical trial to assess a subcutaneous administration ( NCT06955741) BMS-986446 granted Fast Track designation by U.S. FDA as a treatment for Alzheimer’s disease PRX019, a potential treatment of neurodegenerative diseases in development in collaboration with Bristol Myers Squibb. Bristol Myers Squibb obtained the exclusive global license for PRX019 in 2024 Prothena is conducting a Phase 1 first-in-human clinical trial to evaluate the safety, tolerability, immunogenicity, and pharmacokinetics of single ascending and multiple doses in healthy adults with completion expected in 2026 Potential to earn a clinical milestone by end of 2026 should Bristol Myers Squibb decide to further develop PRX019 Updates on Active Preclinical Development Portfolio TDP-43 CYTOPE, a proprietary preclinical program enabling precision intracellular targeting of TDP-43 pathology, a defining pathogenic feature of ALS and other TDP-43 proteinopathies. TDP-43 CYTOPE preclinical data demonstrates the potential of Prothena’s CYTOPE technology to target intracellular disease pathways. Prothena presented a poster at Neuroscience 2025 (Society for Neuroscience) and the International Symposium of ALS/MND demonstrating the potential of TDP-43 CYTOPE in multiple preclinical models PRX012-TfR, a preclinical program combining PRX012, our wholly-owned, single-injection, once-monthly antibody delivered subcutaneously with transferrin receptor technology to potentially improve its product profile. Phase 1 ASCENT clinical program preliminary results demonstrated that patients on the 400 mg dose level of PRX012 for 18 months reached a mean centiloid (CL) level of ~16.0 CL and 9 of 12 achieved amyloid negativity (defined as <24.1 CL). However, the robust plaque clearance was associated with non-competitive rates of ARIA-E. Based on the totality of the results, Prothena is developing PRX012-TfR (transferrin receptor) in preclinical studies while exploring potential partnership opportunities Upcoming Investor Conference Members of the senior management team will present and participate in investor meetings at the following upcoming investor conference: The Citizens Life Sciences Conference on Wednesday, March 11, 2026; fireside chat at 10:10 a.m. ET in Miami, FL Fourth Quarter and Full Year of 2025 Financial Results For the fourth quarter and full year of 2025, Prothena reported net loss of $21.6 million and $244.1 million, respectively, as compared to a net loss of $58.0 million and $122.3 million for the fourth quarter and full year of 2024, respectively. The full year of 2025 net loss includes $30.1 million of restructuring charges associated with the discontinuation of the birtamimab program and the reduction in workforce announced in June 2025, and a $43.2 million net non-cash income tax expense to book a full valuation allowance against its federal deferred tax assets. Net loss per share was $0.40 and $4.53 for the fourth quarter and full year of 2025, respectively, as compared to a net loss per share of $1.08 and $2.27 for the fourth quarter and full year of 2024, respectively. Prothena reported total revenue of $21 thousand and $9.7 million for the fourth quarter and full year of 2025, respectively, as compared to total revenue of $2.1 million and $135.2 million for the fourth quarter and full year of 2024, respectively. Total revenue for the fourth quarter and full year of 2025 was primarily from collaboration revenue from Bristol Myers Squibb related to the partial performance of our PRX019 Phase 1 clinical trial obligation. Total revenue for the full year of 2024, was primarily from collaboration revenue from Bristol Myers Squibb including revenue recognized from the execution of the PRX019 Global License Agreement by Bristol Myers Squibb, which included an $80 million upfront payment in 2024. Research and development (R&D) expenses totaled $14.6 million and $134.9 million for the fourth quarter and full year of 2025, respectively, as compared to $50.2 million and $222.5 million for the fourth quarter and full year of 2024, respectively. The decrease in R&D expenses for the fourth quarter and full year of 2025 compared to the same periods in the prior year was primarily due to lower clinical trial expenses, lower personnel expenses, lower manufacturing and lower consulting expenses. R&D expenses included non-cash share-based compensation expense of $2.1 million and $14.1 million for the fourth quarter and full year of 2025, respectively, as compared to $4.7 million and $20.9 million for the fourth quarter and full year of 2024, respectively. General and administrative (G&A) expenses totaled $12.6 million and $59.4 million for the fourth quarter and full year of 2025, respectively, as compared to $16.8 million and $67.2 million for the fourth quarter and full year of 2024, respectively. The decrease in G&A expenses for the fourth quarter and full year of 2025 compared to the same periods in the prior year was primarily due to lower personnel expenses and lower consulting expenses. G&A expenses included non-cash share-based compensation expense of $5.0 million and $21.5 million for the fourth quarter and full year of 2025, respectively, as compared to $5.8 million and $25.0 million for the fourth quarter and full year of 2024, respectively. Total non-cash share-based compensation expense was $7.1 million for the fourth quarter of 2025 and $37.6 million for the full year of 2025 which included $2.1 million in non-cash share-based compensation expense related to restructuring charges, as compared to $10.5 million and $46.0 million for the fourth quarter and full year of 2024, respectively. As of December 31, 2025, Prothena had $308.4 million in cash, cash equivalents and restricted cash, and no debt. As of February 12, 2026, Prothena had approximately 53.8 million ordinary shares outstanding. 2026 Financial Guidance The Company expects its full year net cash used in operating and investing activities to be $50 to $55 million and to end the year with approximately $255 million (midpoint) in cash, cash equivalents, and restricted cash. The estimated full year 2026 net cash used from operating and investing activities is primarily driven by an estimated net loss of $67 to $72 million, which includes an estimated $24 million of non-cash share-based compensation expense. This financial guidance does not include the potential to earn up to $105 million of aggregate clinical milestone payments from strategic partners in 2026 related to the advancement of both coramitug for ATTR amyloidosis with cardiomyopathy by Novo Nordisk and PRX019 for neurodegenerative diseases by Bristol Myers Squibb. Share Redemption Program Prothena convened an Extraordinary General Meeting of shareholders on November 19, 2025 at which shareholders voted to approve a reduction in Prothena’s share capital to create distributable reserves, which was subsequently confirmed by the Irish High Court. The creation of distributable reserves provides flexibility for the Board of Directors to potentially return capital to shareholders via a share redemption program through open market purchases or other permissible means in 2026. Any such program would be subject to the discretion of the Board of Directors and Prothena’s then-current financial condition. Conference Call Details Prothena management will discuss these results and its 2026 financial guidance during a live audio conference call today, Thursday, February 19, 2026, at 4:30 PM ET. The conference call will be made available on the Company's website at www.prothena.com under the Investors tab in the Events and Presentations section. Following the live audio webcast, a replay will be available on the Company's website for at least 90 days. To access the call via dial-in, please dial +1 (800) 715-9871 (U.S. and Canada toll free) or +1 (646) 307-1963 (international) five minutes prior to the start time and refer to conference ID number 1706941. A replay of the call will be available until February 26, 2026, via dial-in at +1 (800) 770-2030 (U.S. and Canada toll free) or +1 (609) 800-9909 (international), Conference ID Number 1706941. About Prothena Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation with the potential to change the course of devastating neurodegenerative and rare peripheral amyloid diseases. Fueled by its deep scientific expertise built over decades of research, Prothena is advancing a pipeline of therapeutic candidates for a number of indications and novel targets for which its ability to integrate scientific insights around neurological dysfunction and the biology of misfolded proteins can be leveraged. Prothena’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 its proprietary CYTOPE® technology to target a broad spectrum of intracellular disease pathways in the brain and periphery. For more information, please visit the Company’s website at www.prothena.com and follow the Company on X (formerly Twitter) @ProthenaCorp. Forward-Looking Statements This press release contains forward-looking statements. These statements relate to, among other things, the sufficiency of our cash position to fund advancement of our pipeline and completion of our ongoing clinical trials; the continued advancement of our preclinical and clinical pipeline, including the potential and advancement of our CYTOPE technology and expected milestones in 2026, 2027, and beyond; the treatment potential, designs, proposed mechanisms of action, and potential administration of prasinezumab, coramitug, BMS-986446, PRX019, TDP-43 CYTOPE, and PRX012-TfR; plans for ongoing and future clinical trials of prasinezumab, coramitug, BMS-986446, and PRX019; the expected timing of reporting data from preclinical studies and clinical trials; projections regarding peak sales and patient population for prasinezumab; timing of and amounts we may receive under our collaborations with Novo Nordisk and Bristol Myers Squibb; our anticipated net cash burn from operating and investing activities for 2026 and expected cash balance at the end of 2026; our estimated net loss and non-cash share-based compensation expense for 2026; and the potential to return capital to shareholders via a share redemption program or other permissible means. These statements are based on estimates, projections and assumptions that may prove not to be accurate, and actual results could differ materially from those anticipated due to known and unknown risks, uncertainties and other factors, including but not limited to uncertainties related to the completion of operational and financial closing procedures, audit adjustments and other developments that may arise that would require adjustments to the preliminary financial results included in this press release, as well as those described in the “Risk Factors” sections of our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on November 6, 2025, discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC, and our Annual Report on Form 10-K to be filed with the SEC for our fiscal year 2025. We undertake no obligation to update publicly any forward-looking statements contained in this press release as a result of new information, future events, or changes in our expectations. PROTHENA CORPORATION PLC CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited - amounts in thousands except per share data) Three Months Ended December 31, Year Ended December 31, 2025 2024 2025 2024 Collaboration revenue $ 21 $ 2,123 $ 9,634 $ 135,107 Revenue from license and intellectual property — — 50 50 Total revenue 21 2,123 9,684 135,157 Operating expenses: Research and development 14,586 50,172 134,852 222,519 General and administrative 12,646 16,848 59,392 67,199 Restructuring costs (3,008 ) — 30,080 — Total operating expenses 24,224 67,020 224,324 289,718 Loss from operations (24,203 ) (64,897 ) (214,640 ) (154,561 ) Other income, net 2,624 5,396 13,811 25,631 Loss before income taxes (21,579 ) (59,501 ) (200,829 ) (128,930 ) Provision for (benefit from) income taxes 10 (1,545 ) 43,263 (6,620 ) Net loss $ (21,589 ) $ (57,956 ) $ (244,092 ) $ (122,310 ) Basic and diluted net loss per ordinary share $ (0.40 ) $ (1.08 ) $ (4.53 ) $ (2.27 ) Shares used to compute basic and diluted net loss per share 53,831 53,815 53,829 53,772 PROTHENA CORPORATION PLC CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited - amounts in thousands) December 31, 2025 2024 Assets Cash and cash equivalents $ 307,531 $ 471,388 Prepaid expenses and other current assets 7,662 14,024 Total current assets 315,193 485,412 Property and equipment, net 2,144 3,081 Operating lease right-of-use assets 8,125 10,708 Restricted cash, non-current 860 860 Other non-current assets 482 47,047 Total non-current assets 11,611 61,696 Total assets $ 326,804 $ 547,108 Liabilities and Shareholders’ Equity Accrued research and development $ 4,329 $ 13,428 Deferred revenue, current 2,664 8,850 Restructuring liability 13,303 — Lease liability, current 2,886 2,610 Other current liabilities 17,661 23,613 Total current liabilities 40,843 48,501 Deferred revenue, non-current — 3,448 Lease liability, non-current 5,487 8,233 Total non-current liabilities 5,487 11,681 Total liabilities 46,330 60,182 Total shareholders’ equity 280,474 486,926 Total liabilities and shareholders’ equity $ 326,804 $ 547,108 Mark Johnson, CFA, Vice President, Investor Relations 650-837-8550 IR@prothena.com Media@prothena.com

Phase 1Clinical ResultPhase 3Phase 2Financial Statement

100 Deals associated with Prasinezumab

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KEGG	Wiki	ATC	Drug Bank
D11420	-	-	DB14788

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Parkinson Disease	Phase 3	United States	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	China	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	Australia	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	Austria	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	Brazil	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	Canada	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	Denmark	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	France	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	Germany	Roche Holding AG	24 Nov 2025
Parkinson Disease	Phase 3	Italy	Roche Holding AG	24 Nov 2025

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04777331 (PADOVA, CTgov)	Phase 2	Parkinson Disease	586	placebo+prasinezumab (DBT Period: Placebo)	fkjqhoekaj(mqsaiwaudj) = qdqxakflus zqtccnfwri (gcqynpmqhy, uniirhnszf - almmietlmb) View more	-	02 Dec 2025
				Prasinezumab (DBT Period: Prasinezumab)	fkjqhoekaj(mqsaiwaudj) = bnewrjeqxh zqtccnfwri (gcqynpmqhy, tudmfnhhuj - rlscebllyo) View more
NCT04777331 (PADOVA, MDS2025)	Phase 2	Parkinson Disease	589	Prasinezumab	wdmcglacci(fqsalsqxwd): Difference in adjusted means = -2.18 (95.0% CI, -3.87 to -0.49), P-Value = 0.0117 View more	Positive	05 Oct 2025
				Placebo
NCT04777331 (PADOVA, Company_Website) Manual	Phase 2	Parkinson Disease	586	Prasinezumab	qzgqatrwnl(eewesfcfvh): HR = 0.84 (95% CI, 0.69 - 1.01), P-Value = 0.0657 Not Met	Negative	18 Dec 2024
				Placebo
NCT03100149 (PASADENA, AAN2023)	Phase 2	Parkinson Disease alpha-synuclein	316	Prasinezumab 1500 mg	czfbhphhlt(vidhtgbuol) = xdzcovpjcx pgqfrngfgd (elejlqzomk ) View more	-	25 Apr 2023
				Placebo+Prasinezumab 1500 mg	czfbhphhlt(vidhtgbuol) = gmtuhnjkuw pgqfrngfgd (elejlqzomk ) View more
NCT03100149 (PASADENA, MDS2022)	Phase 2	Parkinson Disease α-synuclein	-	Prasinezumab 1500 mg	jvnkqejzds(rqjbqwowgz) = bvglvabudq iyzshoclwv (injjfarnko ) View more	-	15 Sep 2022
				Prasinezumab 4500 mg	jvnkqejzds(rqjbqwowgz) = xpkqphawbl iyzshoclwv (injjfarnko ) View more
NCT03100149 (PASADENA, Pubmed \| N Engl J Med)	Phase 2	Parkinson Disease α-synuclein	316	Prasinezumab 1500 mg	eypmvyccsh(ghwascsdwx) = infusion reactions occurred in 19.0% and 34.0%, respectively zlyinmgikb (tgnqrmdptq ) View more	Negative	04 Aug 2022
				Prasinezumab 4500 mg
NCT03100149 (PASADENA, CTgov)	Phase 2	Parkinson Disease	316	Placebo (Part 1: Placebo)	ghalenmuht(hpmmanuhze) = qajigkhidj bimpoyczwo (xhjjnrrfdm, 1.221) View more	-	08 Feb 2021
				RO7046015 (Part 1: RO7046015 Low Dose)	ghalenmuht(hpmmanuhze) = ykgpuatqou bimpoyczwo (xhjjnrrfdm, 1.225) View more
NCT03100149 (PASADENA, Pubmed \| Front Neurol)	Phase 2	Parkinson Disease	316	Prasinezumab 1,500 mg	nshijjxlzh(qwznnnrjvs) = usfvftytcr gelshbajfz (rusikitlsa )	-	01 Jan 2021
				Prasinezumab 4,500 mg	nshijjxlzh(qwznnnrjvs) = kotkjaanfg gelshbajfz (rusikitlsa )
NCT02157714 (Pubmed \| JAMA Neurol) Manual	Phase 1	Parkinson Disease	80	PRX002	jdaypjasrp(ulineuztpx) = iwmezwjuxa lueqaxspaa (ncmlcxayvl ) View more	Positive	01 Oct 2018
				Placebo	jdaypjasrp(ulineuztpx) = scuxbrqbtm lueqaxspaa (ncmlcxayvl )
EAN2017	Phase 1	Parkinson Disease alpha-synuclein	80	PRX002 0.3 mg/kg	pqajlcyfes(xnmddmuqxl) = TEAEs experienced by â¥5% of patients and >placebo were constipation ribtewpped (ulwceycbry ) View more	Positive	13 Jul 2017
				PRX002 1 mg/kg

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