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 noveltechnology 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.

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Mark Johnson, CFA

Senior Vice President, Head of Investor Relations and Corporate Communications

650-837-8550

IR@prothena.com

Media@prothena.com

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