Prothena Corporation (NasdaqGS:PRTA) FY Conference Summary Company Overview - Prothena Corporation is focused on developing therapies for neurodegenerative diseases, with a robust pipeline of partnered programs and a strategic approach to clinical milestones and business development opportunities [1][2][4]. Pipeline Strategy - The company has two late-stage programs in Phase 3: - **Prasinezumab** for early Parkinson's disease, partnered with Roche, with a trial initiation expected in Q4 2025 [2][6]. - **Coramitug** for ATTR cardiomyopathy, partnered with Novo, which has already initiated its Phase 3 trial [2][20]. - Prothena aims to achieve $105 million in clinical milestones from Coramitug and PRX019 in the near term [3][49]. Key Programs Prasinezumab - Prasinezumab targets alpha-synuclein, a protein implicated in the progression of Parkinson's disease, and aims to be the first disease-modifying therapy for this condition [6][7]. - The Phase 3 trial design incorporates learnings from previous Phase 2 studies, focusing on time to motor progression as the primary endpoint [10][11]. - Roche estimates a market opportunity of approximately $3.5 billion for this asset [12]. Coramitug - Coramitug targets the deposited forms of transthyretin in ATTR cardiomyopathy, differentiating itself from existing therapies that either inhibit synthesis or stabilize the protein [17][18]. - The Phase 2 data showed a significant reduction in NT-proBNP levels, indicating cardiac health improvement, and a potential for rapid effects [19][23]. - Novo has initiated a Phase 3 study with a primary endpoint focused on cardiovascular events [27][28]. PRX019 - This program targets Tau in Alzheimer's disease and is currently in Phase 1, with potential for significant market opportunity in the multi-billion dollar range [46][48]. Financial Aspects - Prothena has received $135 million in upfront and clinical milestone payments from Roche for Prasinezumab, with an additional $620 million in potential milestone payments remaining [15][34]. - The partnership with Novo includes $100 million in milestone payments, with a total remaining potential of $1.13 billion, structured to avoid future taxes [34][36]. Business Development and Future Outlook - Prothena is exploring unpartnered programs and technologies, such as CyTOPE, to enhance shareholder value through potential partnerships [4][50]. - The company plans to announce a share repurchase program in 2026, reflecting a commitment to financial prudence [4][49]. - The upcoming milestones and data readouts from ongoing studies are expected to create significant value for investors over the next few years [48][49]. Conclusion - Prothena Corporation is strategically positioned with a strong pipeline and partnerships, focusing on innovative therapies for neurodegenerative diseases. The company is set to achieve key clinical milestones and explore further business development opportunities, making it a compelling prospect for investors looking towards 2026 and beyond [1][4][50].

Pipeline and Milestones - Prothena has multiple clinical programs ongoing, including one partnered Phase 3 program, two partnered Phase 2 programs, one partnered Phase 1 program, and one wholly-owned Phase 1 program[13] - Prothena is eligible to receive up to $1.23 billion in total consideration from Novo Nordisk for coramitug and the broader ATTR amyloidosis program[13, 16] - Prothena anticipates up to $105 million in clinical milestones in 2026, including completion of Phase 3 development for prasinezumab and initial data from the Phase 1 ASCENT trial for PRX012[18] Partnerships and Financials - Prothena's partnerships are expected to generate meaningful value, with up to $755 million in total milestones and royalties for prasinezumab, up to $1.23 billion for coramitug, and up to $1.55 billion across two clinical-stage programs (BMS-986446 and PRX019)[20] - Bristol Myers Squibb (BMS) owns approximately 2.2% of Prothena's outstanding shares as of March 3, 2025[21] Alzheimer's Disease Programs - PRX012, Prothena's anti-Aβ candidate, has approximately 10X greater binding potency to fibrillar Aβ vs aducanumab and approximately 20X greater binding potency against protofibrils vs lecanemab[24] - BMS-986446 (formerly PRX005), an anti-tau candidate, has the potential to reduce pathogenic tau spread in Alzheimer's disease[27] - PRX123, a dual Aβ/tau vaccine candidate, is designed for both treatment and prevention of Alzheimer's disease, and its IND has been cleared[27] Parkinson's Disease Program - Roche will initiate Phase 3 development for prasinezumab in early-stage Parkinson's disease[15, 111] - The Parkinson's disease affects >10 million people worldwide and represents an overall economic burden of $52 billion in the US[5] ATTR Amyloidosis Program - Coramitug (formerly PRX004) is in Phase 2 development for ATTR amyloidosis with cardiomyopathy (ATTR-CM)[15, 142] - An estimated 450,000 patients worldwide have wtATTR or ATTRv[8]