Prothena Corporation FY Conference Summary Company Overview - **Company**: Prothena Corporation (NasdaqGS:PRTA) - **Focus**: Expertise in protein dysregulation with a robust pipeline in neurodegenerative diseases, including Alzheimer's, Parkinson's, and ATTR cardiomyopathy [2][22] Key Programs and Developments - **Phase 3 Programs**: - **Prasunezumab**: Targeting early Parkinson's disease in collaboration with Roche, expected to initiate in Q4 2025 [2][22] - **Coramitug**: Targeting ATTR cardiomyopathy in collaboration with Novo, which has already initiated Phase 3 [2][22] - **Phase 2 Program**: - **PRX019**: Targeting tau in Alzheimer's disease, partnered with Bristol Myers Squibb [2][22] - **Phase 1 Program**: - **PRX012**: An undisclosed target for neurodegeneration, also partnered with Bristol [2][22] Financial Outlook - Prothena anticipates earning up to **$105 million** in clinical milestones in 2026 related to coramitug and PRX019 [2][22] Shareholder Actions - Recently approved a share repurchase program for 2026 to support distributable reserves [2][22] Pipeline Insights - **Alzheimer's Program**: The company is exploring partnerships to advance its amyloid beta program, emphasizing the importance of collaboration for cost efficiency and bandwidth [4][5] - **Transferrin Technology**: Prothena is developing PRX012, which incorporates transferrin technology to enhance blood-brain barrier penetration. Preclinical data is expected in 2026 [7][17][18] Clinical Data and Efficacy - **Amyloid Reduction**: Over **80%** of patients treated with the amyloid beta molecule are reported to be amyloid negative after 18 months [5][6] - **ARIA Rates**: Reported around **40%** for the amyloid beta treatment, with ongoing efforts to mitigate these effects [6][7] - **Coramitug Data**: Recent presentations showed a **50%** difference from placebo in NT-proBNP levels, supporting the move to Phase 3 [24][25] Collaborations and Partnerships - Prothena has established strong collaborations with Roche, Novo, and Bristol Myers Squibb, focusing on scientific dialogue and clinical decision-making [22][26] - The company is actively supporting partner programs as they transition into Phase 3 [26] Regulatory Considerations - The company is preparing for potential IND submissions, with ongoing discussions with the FDA regarding preclinical toxicology requirements [8][9] Market Position and Future Directions - Prothena is positioning itself to leverage its unique constructs in the competitive landscape of Alzheimer's treatments, particularly with its transferrin-based technology [17][40] - The company is closely monitoring developments in the field, including Eli Lilly's studies, to inform its strategic direction [5][40] Conclusion - Prothena Corporation is advancing multiple promising programs in neurodegenerative diseases, with a strong focus on collaboration and innovative technologies to enhance treatment efficacy and patient outcomes [2][22][40]

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Health & Environment - Some doctors suggest that chemicals in the environment, from golf courses to dry cleaners, may be increasing the risk of Parkinson's disease [1] - Parkinson's disease is identified as the fastest-growing neurodegenerative disease globally [1]

Medical Innovation & Treatment - Deep brain stimulation with electrical impulses is used to treat Parkinson's disease, showing immediate improvement in motor skills [1][2] - Personalized treatment plans can provide long-term benefits for patients with Parkinson's disease [3] - Music and other engaging activities can be integrated into brain surgery procedures [4][5] Patient Outcomes & Recovery - A 65-year-old Parkinson's patient regained the ability to play the clarinet after brain surgery [1][2] - Patients experienced immediate improvements in mobility and overall quality of life following the procedure [1][5] - The advancements in modern medicine are making previously unthinkable treatments a new reality for patients [5]

Medical Innovation & Surgical Advancements - The medical field is showcasing innovative surgical techniques, including stimulating the brain with electrical impulses during surgery to improve patient outcomes [1][2] - Personalized treatment plans are being developed to provide long-term relief for patients with conditions like Parkinson's disease [3] - Music and patient engagement, such as playing instruments during brain surgery, are emerging as methods to monitor and enhance surgical precision [4][5] Patient Outcomes & Quality of Life - Patients are experiencing immediate improvements in motor skills and overall quality of life following these advanced surgical procedures [1][5] - The ability to resume cherished activities, like playing musical instruments, signifies a significant return to normalcy for patients [2][5] - Modern medicine is enabling what was once considered impossible, offering renewed hope and a future for patients with debilitating conditions [5][6]

Problem Statement & Impact - Neurological conditions create emotional weight on families and patients, isolating individuals and limiting their interaction with the world [6] - In the US, over 1 million people are living with Parkinson's disease, with 90,000 new diagnoses annually [8][9] - Medications for Parkinson's can cost up to $2,500 per person, and therapeutic surgeries can exceed $100,000 [9] Proposed Solutions & Technologies - Brain Machine Interfaces (BMIs) can recreate the sense of touch and allow users to control devices with their thoughts [13][14] - Haptic feedback, the science of recreating the sense of touch, can be implemented in BMIs and prosthetics to enhance the user experience [17][18] - Engineering and science can be combined with humanities to create effective and deeply human treatments for neurological conditions [10][21] Call to Action & Vision - The industry should focus on thriving, not just surviving, by creating connections for people with neurological diseases [20] - There is a need to blend STEM fields with humanities to develop treatments that are not only effective but also deeply human [19][21] - The industry should shift focus from complex technologies like AI and robots to simpler solutions that enhance the simple joys of life [22][23]

Parkinson's Disease & Engineering Solutions - Parkinson's disease is a neurodegenerative disease impacting movement, specifically causing freezing of gait [2] - Freezing of gait leads to falls, loss of independence, and fractures [3] - Engineering solutions, such as a small stimulus, could potentially prevent freezing of gait [3] - A key challenge is overcoming the stigma associated with assistive devices [4] - Adoption of external technology and regulatory hurdles are significant considerations [5] - The development of a biocompatible device is crucial [5] Vibration Device & Patient Outcomes - A small wearable device was developed to address freezing of gait using gentle pulses of vibration [5][6] - A retired colonel with Parkinson's disease regained his mobility and independence through the use of the device [6] - Gentle vibration can reset the compass, restoring mobility and independence [7]

Core Viewpoint - Umecrine Cognition's drug candidate golexanolone shows promise in reversing neuroinflammation in a Parkinson's disease model, indicating its potential as a chronic treatment option [1][3]. Company Overview - Karolinska Development AB holds a 73% ownership stake in Umecrine Cognition prior to dilution, emphasizing its significant investment in innovative medical solutions [4]. - The company focuses on identifying and developing breakthrough medical innovations in the Nordic region, aiming to create and grow companies that advance these innovations into commercial products [5][6]. Research Findings - A preclinical study demonstrated that golexanolone completely reverses the activation of immune cells responsible for neuroinflammation in the brain, which is crucial for controlling voluntary movement and posture [3]. - The treatment with golexanolone not only reversed the increase of inflammation-promoting proteins but also provided robust protection against neuroinflammation as early as three weeks after disease onset [3]. - After nine weeks, golexanolone continued to counteract inflammation and aided in restoring protective immune cells, indicating a sustained effect on harmful brain inflammation [3]. Academic Collaboration - The study was conducted in collaboration with academic partners at Centro de Investigación Príncipe Felipe in Valencia, Spain, highlighting the importance of academic partnerships in advancing medical research [4].

Health Risk - Studies indicate individuals residing within approximately one mile of golf courses face a 126% increased risk of Parkinson's disease [1] - The ingestion of pesticides, rather than inhalation, is considered a primary concern due to water source contamination [2] - Pesticides like rotinone and parakquat, known mitochondrial toxins, are implicated in inducing Parkinson's disease [2] Environmental Concerns - Pesticide runoff from golf courses can contaminate local water sources [2] - Contaminated water sources expose residents to pesticides through drinking water [2] Causation - Pesticide exposure is a known factor in the development of Parkinson's disease [3] - The study suggests a link between living near golf courses, pesticide exposure, and the increased incidence of Parkinson's disease [1][2]

Parkinson's Disease Overview - Parkinson's disease affects 1 in 15 men in the Western world [4] - Parkinson's disease is growing 20% faster than Alzheimer's disease, making it the most common and fastest-growing neurological condition [5] - The biggest breakthrough in Parkinson's medication occurred over 60 years ago in 1961 [6] - Levodopa remains the standard treatment for Parkinson's disease [8] Treatment and Management - Deep brain stimulation (DBS), involving electrodes in the skull connected to a battery pack in the chest, is a treatment option [11] - DBS can significantly reduce tremors associated with Parkinson's [16] Resilience and Coping Strategies - Resilience is key to dealing with life's challenges [19] - Key traits of resilient people include having choices, being optimistic, and having goals [22] - Resilience is built over time through experience [24][25] - Creating healthy habits, both physical and mental, can foster resilience [28][29]