Prasinezumab

Net cash used in operating and investing activities was $53.4 million in the first quarter of 2025; quarter-end cash and restricted cash position was $418.8 million Topline results expected in 2Q 2025 from the confirmatory Phase 3 AFFIRM-AL clinical trial of birtamimab in patients with Mayo Stage IV AL amyloidosis being conducted under a SPA agreement with the FDA with a primary endpoint of all-cause mortality (time-to-event) at a statistical significance level of 0.10 Multiple clinical readouts for PRX012, a potential single-injection once-monthly subcutaneous treatment for millions of patients with presymptomatic or early symptomatic Alzheimer’s disease, expected starting around mid-2025 and continuing throughout the year from the ongoing Phase 1 ASCENT clinical trials Results from the Phase 2b PADOVA clinical trial of prasinezumab in patients with early Parkinson’s disease presented at AD/PD 2025 by partner Roche; the totality of the data presented suggest a possible benefit in early-stage Parkinson’s disease; Roche is further evaluating study data and will work together with health authorities to determine next steps around mid-year 2025 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 first quarter of 2025 and provided business highlights. “We continue to meaningfully advance our wholly-owned and partnered programs across our protein dysregulation portfolio during this transformative year for Prothena. Most notably in 2025 we anticipate topline data in 2Q from the confirmatory Phase 3 AFFIRM-AL clinical trial evaluating birtamimab for AL amyloidosis, conducted under a SPA agreement with the FDA with a primary endpoint of time to all-cause mortality at a statistical significance level of 0.10. We also anticipate multiple clinical readouts starting around mid-2025 and continuing throughout the year from the ongoing Phase 1 ASCENT clinical trials in patients with early Alzheimer’s disease for PRX012. We look forward to these clinical milestones, and more, as we move closer to becoming a commercial stage biotech company,” said Gene Kinney, Ph.D., President and Chief Executive Officer, Prothena. “We’re excited to have had a robust presence at AD/PD 2025 with data from our PRX012 program on the diagnostic accuracy of plasma biomarkers and the potential impact on pre-screening for Alzheimer’s Disease clinical trials and two oral presentations from our partner Roche from the Phase 2b PADOVA clinical trial of prasinezumab for early Parkinson’s disease. We’re also anticipating an update on the Phase 2 clinical trial of coramitug for ATTR-CM from Novo Nordisk later this year.” First Quarter, Recent Business Highlights and Upcoming Milestones Neurodegenerative Diseases Portfolio Alzheimer’s Disease PRX012, a wholly-owned potential best-in-class, single-injection once-monthly antibody delivered subcutaneously for the treatment of presymptomatic or early symptomatic Alzheimer’s disease that targets a key epitope at the N-terminus of amyloid beta (Aβ) with high binding potency. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for PRX012 for the treatment of Alzheimer’s disease. Accuracy of plasma biomarkers in predicting Aβ positivity by PET in patients with Alzheimer’s disease presented at AD/PD 2025 Prothena expects to report multiple clinical readouts starting around mid-2025 and continuing throughout the year from the ongoing Phase 1 ASCENT clinical trials Prothena has currently enrolled approximately 260 patients in the ASCENT clinical trials 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 continues to enroll the ongoing Phase 2 TargetTau-1 clinical trial in approximately 475 patients with early Alzheimer’s disease; primary completion expected in 2027 (NCT06268886) Bristol Myers Squibb is responsible for all development, manufacturing, and commercialization PRX123, a wholly-owned potential first-in-class dual Aβ/tau vaccine designed for the treatment and prevention of Alzheimer’s disease, is a dual-target vaccine targeting key epitopes within the N-terminus of Aβ and MTBR-tau designed to promote amyloid clearance and block the transmission of pathogenic tau. The FDA cleared the investigational new drug (IND) application and granted Fast Track designation for PRX123 for the treatment of Alzheimer’s disease. Continuing to optimize capital allocation across our robust R&D pipeline, Prothena expects to update plans for Phase 1 clinical trial by year-end 2025 Parkinson’s Disease 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. Partner Roche presented results for the first time from the Phase 2b PADOVA clinical trial (NCT04777331) of prasinezumab in patients with early Parkinson’s disease in two oral presentations at AD/PD 2025; the totality of the data presented suggests a possible benefit in early-stage Parkinson’s disease including consistent positive trends across primary, secondary and exploratory clinical endpoints; for the first time, a possible biological effect of prasinezumab on MRI biomarkers was also observed Prasinezumab is being investigated in ongoing Open Label Extensions (OLEs) of the Phase 2 PASADENA and Phase 2b PADOVA clinical trials; both clinical trials are being conducted by our partner Roche Roche will continue to evaluate data from PADOVA and will work together with health authorities to determine next steps around mid-year 2025 Neurodegenerative Diseases PRX019, a potential treatment of neurodegenerative diseases in development in collaboration with Bristol Myers Squibb. Bristol Myers Squibb obtained theexclusive global license for PRX019in 2024 Prothena has initiated 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 Phase 1 clinical trial expected to complete in 2026 Rare Peripheral Amyloid Diseases Portfolio AL Amyloidosis Birtamimab, a wholly-owned potential best-in-class anti-amyloid antibody for the treatment of AL amyloidosis designed to directly neutralize soluble toxic light chain aggregates and promote clearance of amyloid that causes organ dysfunction and failure. Among patients with AL amyloidosis, a rare, progressive, and fatal disease, newly diagnosed individuals with cardiac involvement are at the highest risk for early death. Birtamimab has been granted Fast Track designation by the FDA and has been granted Orphan Drug Designation by both the FDA and European Medicines Agency. A significant survival benefit was observed in the post hoc analysis of birtamimab-treated patients categorized as Mayo Stage IV at baseline in the previous Phase 3 VITAL clinical trial (Blood 2023). Presented poster at European Myeloma Network Meeting (EMN) 2025 titled “Mortality Rate of Patients With Mayo Stage IV AL Amyloidosis in Phase 3 VITAL Trial Placebo Arm Is Representative of Real-World Mortality per Matched Mayo Clinic Cohort” The ongoing confirmatory Phase 3 AFFIRM-AL clinical trial is being conducted under a Special Protocol Assessment (SPA) agreement with the FDA with a primary endpoint of all-cause mortality (time-to-event) at a statistical significance level of 0.10 Topline results from confirmatory Phase 3 AFFIRM-AL clinical trial expected in 2Q 2025 (NCT04973137) ATTR Amyloidosis 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. Ongoing Phase 2 signal-detection clinical trial in patients with ATTR-CM is being conducted by Novo Nordisk Phase 2 clinical trial has completed enrollment of approximately 99 patients with trial completion in 1H 2025 and results expected in 2H 2025 (NCT05442047) First Quarter of 2025 Financial Results For the first quarter of 2025, Prothena reported net loss of $60.2 million, as compared to a net loss of $72.2 million for the first quarter of 2024. Net loss per share was $1.12 for the first quarter of 2025, as compared to a net loss per share of $1.34 for the first quarter of 2024. Prothena reported total revenue of $2.8 million for the first quarter of 2025, as compared to total revenue of $0.1 million for the first quarter of 2024. Total revenue for the first quarter 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 first quarter of 2024 was from license fees recognized under a License Agreement with F. Hoffmann-La Roche Ltd. Research and development (R&D) expenses totaled $50.8 million for the first quarter of 2025, as compared to $64.1 million for the first quarter of 2024. The decrease in R&D expenses for the first quarter compared to the same period in the prior year was primarily due to lower clinical trial expenses and lower manufacturing. R&D expenses included non-cash share-based compensation expense of $4.8 million for the first quarter of 2025, as compared to $5.5 million for the first quarter of 2024. General and administrative (G&A) expenses totaled $17.6 million for the first quarter of 2025, as compared to $17.5 million for the first quarter of 2024. G&A expenses included non-cash share-based compensation expense of $6.1 million for the first quarter of 2025, as compared to $6.9 million for the first quarter of 2024. Total non-cash share-based compensation expense was $10.9 million for the first quarter of 2025, as compared to $12.4 million for the first quarter of 2024. As of March 31, 2025, Prothena had $418.8 million in cash, cash equivalents and restricted cash, and no debt. As of May 1, 2025, Prothena had approximately 53.8 million ordinary shares outstanding. 2025 Financial Guidance The Company continues to expect the full year 2025 net cash used in operating and investing activities to be between $168 to $175 million and expects to end the year with approximately $301 million (midpoint) in cash, cash equivalents and restricted cash. The estimated full year 2025 net cash used in operating and investing activities is primarily driven by an estimated net loss of $197 to $205 million, which includes an estimated $41 million of non-cash share-based compensation expense. About Prothena Prothena Corporation plc is a late-stage clinical biotechnology company with expertise in protein dysregulation and a pipeline of investigational therapeutics 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 AL amyloidosis, ATTR amyloidosis with cardiomyopathy, Alzheimer’s disease, Parkinson’s disease and a number of other neurodegenerative diseases. 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 a broad pipeline and completion of our ongoing clinical trials; the continued advancement of our discovery, preclinical, and clinical pipeline, and expected milestones in 2025, 2026, and beyond; the treatment potential, designs, proposed mechanisms of action, and potential administration of PRX012, BMS-986446/PRX005, PRX123, prasinezumab, PRX019, birtamimab, and coramitug/PRX004; plans for ongoing and future clinical trials of PRX012, BMS-986446/PRX005, PRX123, prasinezumab, PRX019, birtamimab, and coramitug/PRX004; the expected timing of reporting data from clinical trials, including multiple clinical readouts starting in mid-2025 and continuing throughout the year from our ongoing Phase 1 clinical trials evaluating PRX012 and topline study results for our Phase 3 AFFIRM-AL clinical trial in 2Q 2025; our anticipated net cash burn from operating and investing activities for 2025 and expected cash balance at the end of 2025; and our estimated net loss and non-cash share-based compensation expense for 2025. 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 May 8, 2025, 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. PROTHENA CORPORATION PLC CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (unaudited - amounts in thousands except per share data) Three Months Ended March 31, 2025 2024 Collaboration revenue $ 2,778 $ — Revenue from license and intellectual property 50 50 Total revenue 2,828 50 Operating expenses: Research and development 50,811 64,114 General and administrative 17,598 17,464 Total operating expenses 68,409 81,578 Loss from operations (65,581 ) (81,528 ) Other income, net 4,208 7,088 Loss before income taxes (61,373 ) (74,440 ) Benefit from income taxes (1,178 ) (2,201 ) Net loss $ (60,195 ) $ (72,239 ) Basic and diluted net loss per ordinary share $ (1.12 ) $ (1.34 ) Shares used to compute basic and diluted net loss per share 53,827 53,714 PROTHENA CORPORATION PLC CONDENSED CONSOLIDATED BALANCE SHEETS (unaudited - amounts in thousands) March 31, December 31, 2025 2024 Assets Cash and cash equivalents $ 417,935 $ 471,388 Prepaid expenses and other current assets 18,238 14,024 Total current assets 436,173 485,412 Property and equipment, net 2,871 3,081 Operating lease right-of-use assets 10,027 10,708 Restricted cash, non-current 860 860 Other non-current assets 45,405 47,047 Total non-current assets 59,163 61,696 Total assets $ 495,336 $ 547,108 Liabilities and Shareholders’ Equity Accrued research and development 12,680 13,428 Deferred revenue, current 7,898 8,850 Lease liability, current 2,628 2,610 Other current liabilities 25,253 23,613 Total current liabilities 48,459 48,501 Deferred revenue, non-current 1,622 3,448 Lease liability, non-current 7,575 8,233 Total non-current liabilities 9,197 11,681 Total liabilities 57,656 60,182 Total shareholders’ equity 437,680 486,926 Total liabilities and shareholders’ equity $ 495,336 $ 547,108 Investors Mark Johnson, CFA, Vice President, Investor Relations 650-417-1974, mark.johnson@prothena.com Media Michael Bachner, Senior Director, Corporate Communications 609-664-7308, michael.bachner@prothena.com

– New trontinemab data continue to support rapid and deep, dose-dependent reduction of amyloid plaques in Phase Ib/IIa Brainshuttle™ AD study – – Data on the Elecsys ® pTau181 plasma test demonstrate potential to accurately rule out amyloid pathology, one of the hallmarks of Alzheimer’s disease – – A Phase III program for trontinemab later this year will be initiated based on totality of data – SOUTH SAN FRANCISCO, CA, USA I April 03, 2025 I Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that new data were presented at the AD/PD 2025 International Conference on Alzheimer’s and Parkinson’s Diseases in Vienna, Austria. Highlights included presentations from the ongoing trontinemab Phase Ib/IIa Brainshuttle™ AD study demonstrating dose-dependent rapid amyloid depletion from the brain and the potential of the Elecsys ® pTau181 plasma test to rule out amyloid pathology. A Phase III program for trontinemab will be initiated later this year. “We are pleased with the progress across our Alzheimer’s portfolio as we move ahead with a Phase III trontinemab program and continue to expand our diagnostic solutions,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Well over 55 million people worldwide are living with dementia, of which around 70% have Alzheimer’s. Moreover, up to three-quarters of people experiencing symptoms of Alzheimer’s remain undiagnosed. This growing population needs more accurate, less invasive diagnostic approaches paired with effective disease-modifying treatments to slow neurodegeneration as early as possible.” Trontinemab Preliminary results for trontinemab from 114 participants in the 1.8 or 3.6 mg/kg double-blind period suggest rapid and deep, dose-dependent reduction of amyloid plaques in the brain as measured by amyloid positron emission tomography (PET). Trontinemab reduced amyloid levels below the 24 centiloid threshold in 81% of participants (n=21/26) in the 3.6 mg/kg dose group after 28 weeks. Based on data in the field, both the speed of amyloid lowering, and the ability to lower below the amyloid positivity threshold early on, are important to achieve clinically meaningful benefit in early Alzheimer’s disease. These data were reinforced by early and significant reductions in fluid biomarkers of Alzheimer’s disease including total tau, phosphorylated Tau (pTau)181, pTau217 and neurogranin measured in cerebrospinal fluid (CSF) and plasma. Trontinemab continues to show a favorable safety and tolerability profile. Amyloid-related imaging abnormalities-edema/effusion (ARIA-E) were observed in <5% (n=3/114) of participants (blinded data), which were radiographically mild, and there was one case associated with mild symptoms. Trontinemab is currently being studied in the Phase Ib/IIa Brainshuttle AD study assessing the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of trontinemab in participants with Alzheimer’s disease. Diagnostics Results from 604 participants in a multicenter study of Roche’s Elecsys pTau181 plasma test were presented, demonstrating its potential to accurately rule out amyloid pathology, a hallmark of Alzheimer’s disease, in people with cognitive impairment. The Elecsys pTau181 test is a minimally invasive blood test that measures pTau181 protein in plasma. By ruling out those without signs of amyloid pathology, the test can help to avoid unnecessary testing using CSF or PET, which are more invasive and often come with long waiting times and high costs. This can result in further delays to diagnosis and cost to healthcare systems. Roche anticipates tests being available in Europe by late 2025, with the U.S. following after. Other activities at the AD/PD 2025 International Conference Parkinson’s disease Results from the Phase IIb PADOVA study were presented for the first time, investigating prasinezumab in 586 people with early-stage Parkinson’s disease while on stable symptomatic treatment. Although the study missed its primary endpoint, the totality of data suggest possible benefit in early-stage Parkinson’s disease. Prasinezumab showed potential clinical efficacy in the primary endpoint of time to confirmed motor progression with a hazard ratio (HR)=0.84 [0.69-1.01] and p=0.0657, missing statistical significance. In a pre-specified analysis, the effect of prasinezumab was more pronounced in the population treated with levodopa (75% of participants), HR=0.79 [0.63-0.99]. Consistent positive trends across multiple secondary and exploratory clinical endpoints were also observed, in addition to a potential biological effect of prasinezumab on MRI biomarkers. Prasinezumab continues to be well tolerated and no new safety signals were observed in the study. Given the high level of unmet need for these patients, Roche is further evaluating study data to determine next steps. About trontinemab Trontinemab is an investigational Brainshuttle™ bispecific #2+1 amyloid-beta antibody specifically engineered for enhanced access to the brain to enable rapid reduction of amyloid in people with Alzheimer’s disease. Trontinemab is designed for the efficient transport across the blood-brain barrier to target aggregated forms of amyloid beta and remove amyloid plaques in the brain. The uniqueness of trontinemab is based on Roche’s proprietary Brainshuttle technology combining an amyloid beta-binding monoclonal antibody with a transferring receptor (TfR1) shuttle module. As a result, high central nervous system (CNS) exposure of trontinemab may be achieved at low doses, leading to a rapid and deep amyloid clearance. Due to its unique properties, trontinemab might unlock the full potential of disease-modifying monoclonal antibodies by effectively penetrating the brain and potentially leading to slowing of disease progression. About prasinezumab Prasinezumab is an investigational monoclonal antibody designed to selectively bind aggregated alpha-synuclein (α-syn) and reduce neuronal toxicity. By targeting the build-up of α-syn protein in the brain, prasinezumab can potentially prevent further accumulation and spreading between cells, thereby slowing down the progression of the disease. The evidence supporting targeting α-syn aggregates as a mechanism of action in Parkinson’s disease is based on a wide range of scientific evidence in the field. Prasinezumab is currently being assessed in ongoing open-label extensions of the Phase II PASADENA and Phase IIb PADOVA studies. The safety database for prasinezumab consists of data from more than 900 Parkinson’s disease study participants that have been treated with the investigational medicine, including more than 500 who were treated over 1.5-5 years. Roche entered into a Licensing, Development, and Commercialization agreement with Prothena in December 2013 to develop and commercialize monoclonal antibodies targeting α-syn, such as prasinezumab, for the treatment of Parkinson’s disease. About Genentech in Neuroscience Neuroscience is a major focus of research and development at Genentech. Our goal is to pursue groundbreaking science to develop new treatments that help improve the lives of people with chronic and potentially devastating diseases. Genentech and Roche are investigating more than a dozen medicines for neurological disorders, including multiple sclerosis, spinal muscular atrophy, neuromyelitis optica spectrum disorder, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Duchenne muscular dystrophy. Together with our partners, we are committed to pushing the boundaries of scientific understanding to solve some of the most difficult challenges in neuroscience today. About Genentech Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com . SOURCE: Genentech