Financial Performance - Prothena reported a net loss of $60.2 million for Q1 2025, an improvement from a net loss of $72.2 million in Q1 2024, with a net loss per share of $1.12 compared to $1.34 in the prior year[14]. - Total revenue for Q1 2025 was $2.8 million, significantly up from $0.1 million in Q1 2024, primarily driven by collaboration revenue from Bristol Myers Squibb[15]. - Prothena projects full-year 2025 net cash used in operating and investing activities to be between $168 million and $175 million, with an estimated net loss of $197 million to $205 million[21]. Research and Development - Research and development (R&D) expenses decreased to $50.8 million in Q1 2025 from $64.1 million in Q1 2024, attributed to lower clinical trial and manufacturing expenses[18]. - Prothena expects to report topline results in Q2 2025 from the Phase 3 AFFIRM-AL clinical trial of birtamimab for AL amyloidosis, with a primary endpoint of all-cause mortality[4]. - Multiple clinical readouts for PRX012, a potential treatment for early Alzheimer's disease, are anticipated starting mid-2025 and continuing throughout the year[4]. - Prothena's PRX012 program has received Fast Track designation from the FDA for the treatment of Alzheimer's disease[5]. - The Phase 2b PADOVA clinical trial of prasinezumab for early Parkinson's disease presented data suggesting possible benefits, with further evaluations expected from partner Roche[10]. - Prothena continues to optimize capital allocation across its R&D pipeline and plans to update Phase 1 clinical trial plans by year-end 2025[7]. Financial Position - As of March 31, 2025, Prothena had $418.8 million in cash and cash equivalents, with no debt[20]. - Total assets decreased from $547,108,000 on December 31, 2024, to $495,336,000 on March 31, 2025, representing a decline of approximately 9.5%[26]. - Total current assets fell from $485,412,000 to $436,173,000, a decrease of about 10.1%[26]. - Total liabilities decreased from $60,182,000 to $57,656,000, reflecting a reduction of approximately 4.2%[26]. - Total shareholders' equity declined from $486,926,000 to $437,680,000, a drop of around 10.1%[26]. - Accrued research and development expenses decreased from $13,428,000 to $12,680,000, a reduction of about 5.5%[26]. - Deferred revenue, non-current, decreased significantly from $3,448,000 to $1,622,000, a decline of approximately 53%[26]. - Total current liabilities remained relatively stable, decreasing slightly from $48,501,000 to $48,459,000[26]. - Cash and cash equivalents decreased from $471,388,000 to $417,935,000, a decline of about 11.3%[26]. - Other non-current assets decreased from $47,047,000 to $45,405,000, a reduction of approximately 3.5%[26]. - Property and equipment, net, decreased from $3,081,000 to $2,871,000, a decline of about 6.8%[26].

Pipeline and Clinical Trials - Prothena's pipeline includes investigational therapeutics targeting AL amyloidosis, Alzheimer's disease, and Parkinson's disease, with birtamimab in Phase 3 and prasinezumab in Phase 2b trials[25][45]. - The company is conducting the Phase 3 AFFIRM-AL trial for birtamimab in Mayo Stage IV patients with AL amyloidosis under a Special Protocol Assessment with the FDA[25]. - PRX123, an Alzheimer's disease vaccine program, has received FDA clearance for an investigational new drug application and Fast Track designation[46]. - Prothena's collaboration with Roche focuses on prasinezumab for Parkinson's disease, with topline results expected from the Phase 2b PADOVA trial in December 2024[25][40]. - The Phase 3 AFFIRM-AL clinical trial is expected to enroll up to 220 newly diagnosed, treatment-naïve patients with Mayo Stage IV AL amyloidosis, with topline results anticipated in Q2 2025[55]. - In the Phase 3 VITAL clinical trial, patients treated with birtamimab demonstrated a mean decrease of 0.75 in quality of life (SF-36v2 PCS) at 9 months, compared to a mean decrease of 5.40 for placebo, resulting in a mean difference of 4.65 favoring birtamimab (p=0.046)[57]. - The 6-minute walk test showed a mean distance increase of 15.22 meters for birtamimab-treated patients after 9 months, while placebo patients experienced a mean distance decrease of 21.15 meters, resulting in a mean difference of 36.37 meters favoring birtamimab (p=0.022)[57]. - Prasinezumab showed a potential clinical effect in the Phase 2b PADOVA trial, with a hazard ratio of 0.84 for time to confirmed motor progression (p=0.0657)[63]. - In the Phase 2 PASADENA trial, prasinezumab-treated patients exhibited a 35% reduction in decline of motor function compared to placebo after one year (MDS-UPDRS Part III)[66]. - The Phase 2 PASADENA trial did not meet its primary objective, but signals of efficacy were observed on multiple secondary endpoints, including a hazard ratio of 0.82 for time to clinically meaningful worsening of motor progression[66]. - The Phase 3 AFFIRM-AL trial is designed under a Special Protocol Assessment (SPA) agreement with the FDA, focusing on time to all-cause mortality as the primary endpoint[54]. - Birtamimab has shown a statistically significant survival benefit of 74% for Mayo Stage IV AL amyloidosis patients treated with it plus standard of care, compared to 49% for placebo plus standard of care at 9 months (HR 0.413, p=0.021)[56]. - Prasinezumab demonstrated a statistically significant delay in clinically meaningful worsening of motor progression in Parkinson's disease patients, with a hazard ratio (HR) of 0.82 across pooled dose levels[68]. Research and Development - Prothena's research and development pipeline includes six therapeutic antibody programs currently in clinical development[45]. - The company aims to develop therapies for diseases with unmet medical needs, specifically targeting protein dysregulation in neurodegenerative diseases[35][38]. - Prothena's diverse pipeline includes antibody, small molecule, and vaccine approaches, positioning it to impact a broad spectrum of diseases[47]. - The company is advancing several discovery and preclinical-stage programs for neurological diseases with significant unmet medical needs[104]. - PRX012, an investigational antibody for Alzheimer's disease, has shown approximately 10-fold greater affinity for fibrillar Aβ compared to aducanumab in preclinical studies[96]. - The FDA granted Fast Track designation for PRX012 in April 2022, expediting its development for Alzheimer's disease[97]. - Topline Phase 1 data from the PRX012 trial supports a single-injection, once-monthly subcutaneous treatment regimen, with multiple clinical readouts expected starting mid-2025[97]. - PRX123, a dual Aβ-Tau vaccine, has generated polyclonal responses against key epitopes in preclinical studies, promoting amyloid clearance and tau blockade[99]. - The FDA cleared the IND application for PRX123 in January 2024 and granted it Fast Track designation[100]. - A Phase 1 first-in-human clinical trial for PRX019 was initiated in November 2024 to evaluate its safety and tolerability[103]. Financial Performance - Research and development expenses totaled $222.5 million in 2024, up from $220.6 million in 2023 and $135.6 million in 2022[169]. - The company incurred net losses of $122.3 million, $147.0 million, and $116.9 million for the years ended December 31, 2024, 2023, and 2022, respectively[177]. - As of December 31, 2024, the company had an accumulated deficit of $1.1 billion[177]. - Cash and cash equivalents stood at $471.4 million as of December 31, 2024[179]. - The company anticipates requiring additional capital to fund ongoing research and development activities and potential commercialization of drug candidates[179]. Collaborations and Partnerships - The company leverages external collaborations and business development opportunities to enhance its internal discovery efforts[39][40]. - The License Agreement with Roche includes potential milestone payments totaling up to $755 million, of which $135 million has been earned to date[75]. - Novo Nordisk acquired the ATTR amyloidosis business, including coramitug, for an aggregate purchase price of up to $1.23 billion, with approximately $100 million earned to date[88]. - The collaboration with Roche includes shared development costs allocated 70% to Roche and 30% to the company for prasinezumab in Parkinson's disease[76]. - The company has licensed certain patents and patent applications from Elan and its affiliates, which are worldwide, fully paid, royalty-free, perpetual, and irrevocable[159]. Regulatory and Compliance - The FDA's Fast Track designation allows for frequent interactions during product development and a rolling review of the BLA[118]. - The clinical trial process for biologics can take many years, with no assurance that data will support FDA approval[112]. - The FDA aims to take action on Priority Review applications within six months of the 60-day filing date, compared to ten months for standard reviews[121]. - The FDA may issue a Complete Response Letter if the application is not ready for approval, which may require additional clinical data or trials[122]. - The FDA can impose a Risk Evaluation and Mitigation Strategy (REMS) plan as a condition of approval to mitigate risks associated with the product[123]. - Post-marketing commitments may include Phase 4 clinical trials to further assess the product's safety and effectiveness after commercialization[124]. - The FDA grants orphan drug designation for drugs intended to treat rare diseases, providing financial incentives and a seven-year exclusive marketing period[136]. Market and Competitive Landscape - The pharmaceutical industry is highly competitive, with major international companies posing significant competition[160]. - The company expects to continue incurring substantial losses for the foreseeable future as it develops its drug candidates[177]. - Attracting and retaining qualified personnel is critical for growth, with intense competition potentially affecting business operations[188]. - Collaborators and suppliers require assurances of financial stability; dissatisfaction could adversely impact drug development and business operations[189]. - Business disruptions from epidemics, geopolitical turmoil, or natural disasters could materially affect liquidity and operational timelines[191]. - The COVID-19 pandemic disrupted clinical trials, impacting timelines for drug candidates and access to financial markets[192]. Intellectual Property - The company holds approximately 9 patent families related to AL or AA amyloidosis, with a key patent expected to expire in 2029[154]. - The company has approximately 16 patent families related to passive immunotherapy for Parkinson's disease, with a key patent anticipated to expire in 2032[154]. - The company is required to pay 1% of net sales of any product covered by licensed patents to the University of Tennessee and the University of California, with no royalties incurred to date[157][158]. - The company’s patent term may be extended by up to five years under the U.S. Hatch-Waxman Act, depending on the duration of clinical development and regulatory review[156]. - The company’s intellectual property strategy includes seeking, maintaining, and defending patents, as well as relying on trade secrets and know-how[151]. Risks and Challenges - The company may face significant penalties and legal actions if it fails to comply with extensive healthcare regulations governing pharmaceutical operations, which could impact its business operations and financial results[147]. - The company may face additional costs to ensure compliance with healthcare laws and regulations, which could adversely affect its financial performance and operational capabilities[150]. - Compliance with evolving privacy laws, such as the CCPA and GDPR, may increase operational costs and legal risks[197]. - The EU GDPR imposes significant obligations and potential fines for data breaches, affecting international data transfers and compliance[199]. - The California Privacy Rights Act (CPRA) and similar state laws may increase compliance costs and impact business practices[198]. - The company does not carry earthquake insurance, which could lead to substantial expenses if natural disasters disrupt operations[196]. - The UK GDPR imposes potential fines up to £17.5 million or 4% of the noncompliant company's total annual global turnover for data protection violations[201]. - Compliance with evolving U.S. and foreign data privacy laws may lead to increased operational costs and risks of government investigations or penalties[202]. Future Outlook - The success of the company's business is heavily reliant on the successful discovery, development, and commercialization of drug candidates[203]. - There is no assurance that ongoing clinical trials for birtamimab and prasinezumab will yield positive results necessary for further development[204]. - Regulatory approvals for drug candidates require substantial evidence from well-controlled clinical trials, which can be costly and time-consuming[206]. - The company has not yet marketed or sold any products, and it may take several years before any drug candidates become commercially available[207]. - Delays in clinical trials could significantly impact the ability to commercialize drug candidates and result in increased costs[215]. - Conducting clinical trials in foreign countries presents additional risks, including adherence to clinical protocols and managing regulatory requirements[218].

Financial Performance - Prothena Corporation reported a fourth-quarter 2024 loss per share of $1.08, which was wider than the Zacks Consensus Estimate of a loss of $1.02, but improved from a loss of $1.26 per share in the year-ago quarter [1][2] - Revenues for the fourth quarter totaled $2.1 million, missing the Zacks Consensus Estimate of $14 million, and significantly up from $316,000 in the fourth quarter of 2023 [2][3] - For the full year 2024, revenues reached $135.1 million, an increase from $91.4 million in 2023, with a loss per share of $2.27, improving from a loss of $2.76 in 2023 [13] Expense Management - Research and development (R&D) expenses decreased by 19% year over year to $50.2 million, attributed to lower clinical trial and manufacturing costs [3] - General and administrative expenses were slightly reduced to $16.8 million from $16.9 million in the previous year [3] Cash Position - As of December 31, 2024, Prothena had $472.2 million in cash, cash equivalents, and restricted cash, with no debt [3] Pipeline Developments - Prothena is evaluating PRX012 for Alzheimer's Disease, currently enrolling approximately 260 patients in the ASCENT clinical trials, with expected clinical readouts starting mid-2025 [4] - The company is advancing BMS-986446 in collaboration with Bristol Myers, with approximately 475 patients enrolled in a phase II study expected to complete in 2027 [5][6] - PRX019, a potential treatment for neurodegenerative diseases, is in a phase I trial expected to complete in 2026 [7] - Prothena is developing a dual Aβ-Tau vaccine, PRX123, for Alzheimer's Disease, which has received Fast Track designation from the FDA [8] - The company is also evaluating prasinezumab for Parkinson's disease in collaboration with Roche [9][10] - Birtamimab, a potential treatment for AL amyloidosis, is in a confirmatory phase III study with top-line results expected in Q2 2025 [11] - Novo Nordisk acquired Prothena's Coramitug, a potential treatment for ATTR amyloidosis, with an ongoing phase II study expected to complete in 2025 [12] 2025 Guidance - Prothena expects a net cash burn from operating and investing activities in the range of $168-$175 million for 2025, with a projected year-end cash position of approximately $301 million [14] - The net loss for 2025 is projected to be in the range of $197-$205 million [14]

Financial Performance & Guidance - Prothena's net cash used in operating and investing activities for FY 2024 was $150.3 million, aligning with the guidance of $148 - $160 million[54] - The company's net loss for FY 2024 was $122.3 million, including $46 million in non-cash share-based compensation expense, which was in line with the guidance of $120 - $135 million[54, 55] - Prothena's year-end cash balance for 2024 was $472.2 million, consistent with the guidance of $468 million[54] - For FY 2025, Prothena anticipates net cash usage in operating and investing activities between $168 million and $175 million[56] - The projected net loss for FY 2025 is between $197 million and $205 million, which includes an estimated $41 million in non-cash share-based compensation expense[56, 57] - The company forecasts a year-end cash balance of $301 million for 2025 (midpoint)[56] Pipeline Development - Topline results from the Phase 3 AFFIRM-AL trial of birtamimab in AL amyloidosis are expected in Q2 2025[10, 60] - Multiple data readouts from the Phase 1 ASCENT clinical trials of PRX012 for Alzheimer's disease are anticipated starting in mid-2025 and continuing throughout the year[11, 60, 62] - Completion and results of the ongoing Phase 2 trial of coramitug (PRX004) in ATTR-CM are expected in 2025[14, 61] - Roche will determine the next steps for prasinezumab in Parkinson's disease in 2025[14, 61] - The Phase 2 trial of BMS-986446 (PRX005) in Alzheimer's disease is expected to be completed in 2027[14, 61] - The Phase 1 trial of PRX019 in neurodegeneration is expected to be completed in 2026[14, 61] Birtamimab Market Opportunity - Birtamimab has multi-billion dollar global market potential in AL Amyloidosis[10, 48] - Approximately 5,000 patients in the US and over 5,000 in the EU are Mayo Stage IV patients, representing a target population for Birtamimab[42]

Financial Data and Key Metrics Changes - Prothena reported a net cash used in operating and investing activities of $150.3 million for 2024, at the low end of the guidance range of $148 million to $160 million [56] - The net loss for 2024 was $122.3 million, also at the low end of the guidance range of $120 million to $135 million [56] - As of December 31, 2024, Prothena had $472.2 million in cash, cash equivalents, and restricted cash, aligning with the guidance of $468 million [58] Business Line Data and Key Metrics Changes - The company has four wholly-owned and four partnered programs across various stages of clinical development, focusing on neurodegenerative and rare peripheral amyloid diseases [10][11] - Birtamimab is positioned as a potential multi-billion dollar global commercial opportunity, with expectations for a BLA submission to the FDA by the second half of 2026 if positive results are achieved in the ongoing Phase 3 AFFIRM-AL trial [13][44] Market Data and Key Metrics Changes - In the U.S., there are approximately 16,000 diagnosed and treated AL amyloidosis patients, with around 13,000 having cardiac involvement, which is the segment at highest risk for early mortality [45] - The estimated diagnosed and treated population of Mayo Stage IV patients is close to 5,000 in the U.S. and over 5,000 in major European markets [46] Company Strategy and Development Direction - Prothena aims to create transformational therapies for significant unmet medical needs, leveraging partnerships to advance treatments while maintaining financial upside [10][11] - The company is focused on building commercial capabilities to support birtamimab as its first potential commercial product, with plans for independent commercialization in the U.S. [43][49] Management's Comments on Operating Environment and Future Outlook - Management highlighted 2025 as a transformational year with significant clinical readouts expected from both wholly-owned and partnered programs [62] - The company remains well-capitalized with a robust cash position, focusing on advancing clinical programs to become a fully integrated commercial biotechnology company [62] Other Important Information - Prothena received an $80 million payment from Bristol Myers Squibb for the exclusive global license of PRX019 in 2024 [57] - The company has a simple capital structure with zero debt, which supports its financial stability [58] Q&A Session Summary Question: What is considered the best and worst-case scenario for the Phase 3 AFFIRM-AL trial? - Management emphasized the significant unmet need in AL amyloidosis and the opportunity for birtamimab to demonstrate survival benefits, with a best-case scenario being a p-value of 0.10% or less [70][71] Question: Can you discuss the baseline characteristics of patients enrolled in AFFIRM-AL? - Approximately 80% of subjects in the AFFIRM-AL trial are on daratumumab, with a focus on Mayo Stage IV patients who are at the highest risk of early mortality [81] Question: What visibility do you have on long-term mortality trends beyond the randomized phase of the trials? - Management noted that while there were no ongoing trials for long-term follow-up, data from previous trials indicated significant survival benefits for patients treated with birtamimab [88] Question: How does the control arm in AFFIRM-AL compare to the control arm in ANDROMEDA? - The control arm in AFFIRM-AL is expected to behave similarly to the VITAL trial, with a median survival of around 8.3 months, and daratumumab's inclusion does not seem to impact early mortality [112][114] Question: Can you elaborate on the rationale for the 200 mg expansion cohort in PRX012? - The expansion cohort was created to meet patient demand, as enrolling the B cohorts requires screening a large number of patients due to the low prevalence of APOE homozygous carriers [124]

Prothena (PRTA) came out with a quarterly loss of $1.08 per share versus the Zacks Consensus Estimate of a loss of $1.02. This compares to loss of $1.26 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of -5.88%. A quarter ago, it was expected that this drug developer would post a loss of $1.18 per share when it actually produced a loss of $1.10, delivering a surprise of 6.78%.Over the last four quarters, the company has surpassed ...

Exhibit 99.1 PRESS RELEASE Prothena Reports Fourth Quarter and Full Year 2024 Financial Results, and Provides Financial Guidance and Business Highlights DUBLIN, Ireland, February 20, 2025-- 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 2024. In addition, the Company provided business highlights and 2025 fi ...

Core Viewpoint - Kuehn Law, PLLC is investigating potential breaches of fiduciary duties by officers and directors of Prothena Corporation PLC, focusing on possible self-dealing that may affect shareholders [1]. Group 1 - The investigation by Kuehn Law concerns whether certain officers and directors of Prothena Corporation PLC have engaged in self-dealing, which could lead to damages and corporate governance reforms for shareholders [1]. - Shareholders of Prothena Corporation PLC are encouraged to contact Kuehn Law for a free consultation regarding their rights and potential claims [2]. - The firm emphasizes the importance of shareholder participation in maintaining the integrity and fairness of financial markets [3].

A month has gone by since the last earnings report for Prothena (PRTA) . Shares have lost about 17.9% in that time frame, underperforming the S&P 500.Will the recent negative trend continue leading up to its next earnings release, or is Prothena due for a breakout? Before we dive into how investors and analysts have reacted as of late, let's take a quick look at the most recent earnings report in order to get a better handle on the important drivers. Prothena Q3 Earnings Beat Estimates, Pipeline Progress in ...

Prothena Corporation (PRTA) reported a loss per share of $1.10 per share in the third quarter of 2024, narrower than the Zacks Consensus Estimate of a loss of $1.18.In the year-ago quarter, the company posted earnings of 38 cents per share, driven by higher revenues.Third-quarter 2024 revenues totaled $1 million, which missed the Zacks Consensus Estimate of $2 million. PRTA recorded revenues of $85 million in the third quarter of 2023 on the back of collaboration revenues from partner Bristol Myers Squibb ( ...