Core Viewpoint - Prothena Corporation plc announced disappointing results from the Phase 3 AFFIRM-AL clinical trial for birtamimab, leading to the decision to discontinue its development [3][4]. Group 1: Clinical Trial Details - The Phase 3 AFFIRM-AL trial involved 207 newly diagnosed patients, with birtamimab administered every 28 days at a dose of 24 mg/kg, not exceeding 2500 mg [2]. - Both active and control groups received a bortezomib-containing chemotherapy regimen, with the use of daratumumab permitted [2]. Group 2: Trial Outcomes - The trial did not meet its primary endpoint of time to all-cause mortality (HR=0.915, p-value=0.7680) [3][4]. - Secondary endpoints, including the 6-minute walk test distance (nominal p-value=0.5288) and Short Form-36 version 2 Physical Component Score (nominal p-value=0.9597), were also not met [5]. Group 3: Company Response and Future Plans - Prothena's CEO expressed surprise and disappointment at the trial results, stating that discontinuing birtamimab's development was the most appropriate action [4]. - The company plans to reduce spending, including a substantial workforce reduction, and will evaluate business options to benefit shareholders [6]. - Upcoming data from the Phase 1 ASCENT clinical trials on PRX012 in Alzheimer's disease is expected in August, with additional program updates from partners anticipated in the coming years [6]. Group 4: Market Reaction - Following the announcement, Prothena's stock (PRTA) fell by 26.80%, trading at $4.82 during the premarket session [7].

Core Viewpoint - Prothena Corporation reported a wider-than-expected loss per share for Q1 2025, despite improvements in year-over-year performance due to higher revenues and lower expenses [1][5]. Financial Performance - The loss per share for Q1 2025 was $1.12, compared to the Zacks Consensus Estimate of a loss of $0.92, and an improvement from a loss of $1.34 per share in the same quarter last year [1]. - Revenues for Q1 2025 totaled $2.8 million, significantly missing the Zacks Consensus Estimate of $21 million, and a notable increase from $0.1 million in Q1 2024 [2]. - Research and development (R&D) expenses decreased by 20.7% year over year to $50.8 million, attributed to lower clinical trial and manufacturing costs [5]. - General and administrative expenses were $17.6 million, slightly down from $17.5 million in the previous year [5]. - As of March 31, 2025, Prothena had $418.8 million in cash and equivalents, with no debt [5]. - The company expects a net cash burn of $168-$175 million for 2025, with a projected year-end cash balance of approximately $301 million [15]. Stock Performance - Prothena's shares have declined by 48.7% year to date, in contrast to a 7.4% decline in the industry [4]. Pipeline Developments - Prothena is evaluating PRX012, a single-injection antibody for Alzheimer's Disease, with approximately 260 patients enrolled in the ASCENT clinical trials, expecting multiple readouts starting mid-2025 [6]. - The company is advancing BMS-986446, an anti-tau antibody for Alzheimer's, with about 475 patients enrolled in a phase II study expected to complete in 2027 [7]. - PRX019, a potential treatment for neurodegenerative diseases, is in phase I trials, expected to complete in 2026 [8]. - Prothena is developing PRX123, a dual Aβ-Tau vaccine for Alzheimer's, which has received Fast Track designation from the FDA [9][10]. - The company is also evaluating prasinezumab for Parkinson's disease in collaboration with Roche, which is conducting ongoing studies [10][12]. - Prothena is assessing birtamimab for AL amyloidosis, with a phase III study initiated and top-line results expected in Q2 2025 [13]. Guidance - Prothena projects a net loss for 2025 in the range of $197-$205 million [15].

分组1 - Prothena reported a quarterly loss of $1.12 per share, which was worse than the Zacks Consensus Estimate of a loss of $0.92, and an improvement from a loss of $1.34 per share a year ago, indicating an earnings surprise of -21.74% [1] - The company generated revenues of $2.83 million for the quarter ended March 2025, missing the Zacks Consensus Estimate by 86.72%, compared to revenues of $0.05 million in the same quarter last year [2] - Prothena's shares have declined approximately 47.4% since the beginning of the year, contrasting with the S&P 500's decline of -4.3% [3] 分组2 - The earnings outlook for Prothena is mixed, with the current consensus EPS estimate for the upcoming quarter at -$0.94 on revenues of $21.05 million, and for the current fiscal year at -$3.60 on revenues of $80.55 million [7] - The Medical - Biomedical and Genetics industry, to which Prothena belongs, is currently ranked in the top 33% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8]

Clinical Trials and Investigational Therapies - Prothena's investigational therapeutic birtamimab has shown a statistically significant survival benefit of 74% for Mayo Stage IV AL amyloidosis patients treated with birtamimab plus standard of care compared to 49% for placebo plus standard of care at 9 months [165]. - The Phase 3 AFFIRM-AL clinical trial for birtamimab 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 [164]. - Prasinezumab, an investigational antibody for Parkinson's disease, demonstrated a potential clinical effect with a hazard ratio of 0.84 in the primary endpoint of time to confirmed motor progression in the Phase 2b PADOVA trial [169]. - In the PADOVA trial, prasinezumab showed a more pronounced effect in the levodopa-treated subgroup with a hazard ratio of 0.79, indicating a significant reduction in motor progression [169]. - Coramitug, designed for the treatment of ATTR amyloidosis, targets non-native TTR to improve organ function and has shown promise in preclinical studies for inhibiting amyloid fibril formation [172][177]. - The Phase 3 VITAL clinical trial results indicated that birtamimab-treated patients had a mean decrease of 0.75 in quality of life compared to a mean decrease of 5.40 for placebo, demonstrating a significant quality of life advantage [166]. - A Phase 2 clinical trial for BMS-986446 is being conducted with approximately 475 participants with early Alzheimer's disease, initiated in Q1 2024 [186]. - PRX123, a dual Aβ-tau vaccine, is in development for the potential treatment and prevention of Alzheimer's disease, with preclinical studies showing promising results [190]. - The Phase 1 clinical trial for PRX019 was initiated in November 2024 to evaluate its safety and pharmacokinetics in healthy adults [195]. Financial Performance - Total revenue for the three months ended March 31, 2025, was $2.8 million, a significant increase from $0.1 million in the same period of 2024, representing a 5,556% growth [200]. - Collaboration revenue for the three months ended March 31, 2025, was $2.8 million, compared to nil for the same period in 2024, attributed to the PRX019 Phase 1 Clinical Trial [201]. - Total operating expenses for the three months ended March 31, 2025, were $81.6 million, a decrease of 16% from $68.4 million in the same period of 2024 [205]. - Research and development expenses decreased by $13.3 million for the three months ended March 31, 2025, primarily due to lower clinical trial expenses related to PRX012 [208]. - R&D expenses totaled $50.8 million for the three months ended March 31, 2025, a decrease of 20.6% from $64.1 million in the same period of 2024 [209]. - Interest income decreased by $2.8 million to $4.3 million, a decline of 39% compared to $7.2 million in the prior year, primarily due to lower yields and cash balances [210]. - The benefit from income taxes decreased by $1.0 million or 46%, from $2.2 million in 2024 to $1.2 million in 2025, mainly due to a decrease in capitalized deferred tax assets [212]. Cash and Liabilities - Working capital decreased by $49.2 million to $387.7 million as of March 31, 2025, primarily due to cash used in operating activities of $53.4 million [214]. - Cash and cash equivalents were $417.9 million as of March 31, 2025, sufficient to meet obligations for at least the next twelve months [215]. - Net cash used in operating activities was $53.4 million for the three months ended March 31, 2025, with total operating expenses of $68.4 million [221]. - Total liabilities were $57.7 million as of March 31, 2025, a slight decrease from $60.2 million as of December 31, 2024 [214]. - Contractual obligations included minimum cash payments under operating leases of $11.3 million and purchase obligations of $15.6 million as of March 31, 2025 [226]. - The company expects full year 2025 net cash used in operating and investing activities to be approximately $168 million to $175 million [229]. Regulatory Designations and Collaborations - The company has received Fast Track Designation and Orphan Drug Designation from the FDA for birtamimab, emphasizing its potential as a critical treatment option for AL amyloidosis [159]. - Prothena's partnered programs include prasinezumab for Parkinson's disease in collaboration with Roche, and BMS-986446 for Alzheimer's disease in collaboration with Bristol Myers Squibb [156]. - The FDA granted Fast Track designation for PRX012 in April 2022, aimed at expediting its development for Alzheimer's disease [189]. - The FDA cleared the IND application for PRX019 in December 2023, with potential milestone payments of up to $617.5 million [194]. Investment and Credit Risk - The company places cash and cash equivalents with high credit quality financial institutions [234]. - The investment policy limits credit exposure with any one financial institution [234]. - Deposits held with banks exceed federally insured limits [234]. - The company has not experienced any losses on deposits of cash and cash equivalents [234]. - Credit risk exposure is recorded on the Condensed Consolidated Balance Sheets [234].

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 ...