Prothena Corporation plc · NASDAQ:PRTA
Prothena — Investor Presentation (August 2025)
26 slides from Prothena's investor presentation, Aug 27, 2025
Slide 1: Corporate Overview
CORPORATE OVERVIEW August 2025
Slide 2: Forward-Looking Statements
Forward-Looking Statements This overview contains forward-looking statements. These statements relate to, among other things, the sufficiency of our cash position to fund advancement of a broad pipeline; the continued advancement of our pipeline, and expected milestones in 2026, 2027, and beyond, in
Slide 3: Our Mission Today
Our Mission Today We are Focused on Delivering Life-Saving Therapies… …for unmet medical needs caused by diseases of protein dysregulation 3
Slide 4: Addressing Devastating Proteinopathies Affecting Millions Worldwide
We are Addressing Devastating Proteinopathies Affecting Millions of Patients and Families Worldwide NEURODEGENERATIVE DISEASES RARE PERIPHERAL AMYLOID Alzheimer’s Parkinson’s Transthyretin disease (AD) disease (PD) amyloidosis (ATTR) >80 million >10 million 450,000 People worldwide living with early
Slide 5: Our Biology-Directed Engine Propels Progress Across Broad Pipeline
Our Biology-Directed Engine Propels Prothena’s Progress Across our Broad Pipeline Therapeutics engineered to optimally eliminate pathogenic proteins while preserving normal biology Disease- Driven Multiple Clinical Programs Antibody Two partnered Phase 3 programs Engineering Product Deep candidates
Slide 6: Active Clinical Development Pipeline
Active Clinical Development Pipeline PROGRAM PROTEIN GLOBAL DISCOVERY PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 INDICATION TARGET PARTNER2 Prasinezumab -Synuclein Parkinson’s disease (C-terminus) Roche to initiate Phase 3 development by YE 2025 Coramitug (PRX004) Transthyretin Novo to initiate Phase 3 d
Slide 7: Upcoming Partner Milestones
Upcoming Partner Milestones Up to $105 Million in Clinical Milestones in 2026 Related to the Advancement of Coramitug and PRX0191 2026 2027 2028+ PRX019 BMS-986446 Prasinezumab Coramitug Neurodegenerative Alzheimer’s Parkinson’s ATTR-CM diseases disease disease Ph 1 Trial Ph 2 Trial Ph 3 Trial Ph 3
Slide 8: Partnerships Expected to Generate Meaningful Value Across Programs
Prothena Partnerships Expected to Generate Meaningful Value Across Programs Up to $755 Million in Up to $1.23 Billion in Up to $1.55 Billion in Total Milestones + Total Milestones + Total Milestones Royalties Across Two Clinical Stage Programs Royalties ❑ Upfront Payment + Equity: $150 million2 Pras
Slide 9: Prasinezumab
Prasinezumab Parkinson’s Disease Phase 3 Worldwide Collaboration with Roche
Slide 10: Prasinezumab: Potential First-in-Class Treatment for Parkinson's Disease
Prasinezumab Prasinezumab: Potential First-in-Class Treatment for Parkinson’s Disease Phase 2 Clinical Development Programs: Prasinezumab Parkinson’s Disease • First anti--synuclein antibody to slow progression on measures of PD Status: Phase 3 initiation by YE 2025 • Consistent positive trends acr
Slide 11: Alpha-Synuclein Pathology is Strongly Implicated in Parkinson's Disease
Prasinezumab -Synuclein Pathology is Strongly Implicated in Parkinson’s Disease Accumulation of -Synuclein Neuronal -Synuclein Dopaminergic neurodegeneration is a predominant Symptoms neuropathological feature and Biological or Clinical Measures Functional impairment follows the topological progr
Slide 12: Prasinezumab: Alpha-Synuclein Immunotherapy
Prasinezumab Prasinezumab: -Synuclein Immunotherapy REDUCE NEURONAL TOXICITY AND PREVENT CELL-TO-CELL TRANSMISSION1 Diseased Neuron Protected Neuron -Synuclein as an extracellular target during pathogenesis Aggregated • Caudal-rostral staging, extracellular host-to-graft transfer, -Synuclein vari
Slide 13: Moving into Phase 3 in Parkinson's Disease
Prasinezumab Moving into Phase 3 in Parkinson’s Disease PHASE 2B (PADOVA) AND LONGER FOLLOW-UP DATA SUGGEST CLINICAL BENEFIT IN DELAY OF CONFIRMED MOTOR PROGRESSION Phase 2b (PADOVA) 2.5 years results1 • Multiple endpoints from the PADOVA and OLE study suggest potential clinical benefit of prasinezu
Slide 14: Roche's Phase 3 Go Decision Based on Meeting the Bar Criteria
Prasinezumab Roche’s Phase 3 Go Decision Based on Meeting the Bar Criteria INSIGHTS FROM PHASE 2B (PADOVA) AND OPEN LABEL EXTENSION WILL INFORM ROCHE’S PH 3 TRIAL DESIGN Peak sales potential >$3B (unadjusted) DMT: Disease modifying therapy; OLE: Open label extension; PD: Parkinson’s disease. 14 Slid
Slide 15: Coramitug (formerly PRX004)
Coramitug (formerly PRX004) ATTR Amyloidosis with Cardiomyopathy Phase 3 ATTR Business Acquired by Novo Nordisk
Slide 16: Coramitug: Potential First-in-Class Treatment for ATTR-CM
Coramitug Coramitug (formerly PRX004): Potential First-in-Class Treatment for ATTR-CM Phase 2 Signal Detection Trial (NCT05442047): Coramitug • Trial complete ATTR amyloidosis with • N = 105 ATTR-CM patients, 3 arms cardiomyopathy (ATTR-CM) • Participants received IV infusion Q4W of 10 mg/kg or 60 S
Slide 17: Differentiated Mechanism for ATTR-CM
Coramitug Differentiated Mechanism for ATTR-CM NON-PATHOGENIC PATHWAY PATHOGENIC PATHWAY HEART Protein Misfolding Restrictive cardiomyopathy Heart failure PERIPHERAL NERVES Loss of sensation LIVER FREE MONOMER, SOLUBLE Loss of reflex TETRAMER AGGREGATE Muscle weakness AMYLOID FIBRILS Coramitug: Curr
Slide 18: Designed to Deplete Amyloid
Coramitug Designed to Deplete Amyloid SUMMARY OF PRECLINICAL EFFECTS OF mPRX004 mPRX004 (murine ✓ Inhibits fibril formation form of PRX004) ✓ Specifically binds to pathogenic TTR preclinical results:1 ✓ Reacts to amyloid deposits in multiple organs in both wtATTR and ATTRv patients ✓ Promotes in viv
Slide 19: BMS-986446 (formerly PRX005)
BMS-986446 (formerly PRX005) Alzheimer’s Disease Phase 2 Global Neuroscience Collaboration with Bristol Myers Squibb
Slide 20: BMS-986446: Potential Best-in-Class Anti-Tau Antibody for Alzheimer's Disease
BMS-986446 BMS-986446: Potential Best-in-Class anti-Tau antibody for Alzheimer’s Disease Phase 2 Trial (NCT06268886): Ongoing BMS-986446 Alzheimer’s disease • Global, double-blind, placebo-controlled Status: Phase 2, completion 2027 • 310 participants with early AD Anti-Tau Mechanism of Action • Ran
Slide 21: BMS-986446: MTBR-Specific Anti-Tau Antibody
BMS-986446 BMS-986446: MTBR-Specific Anti-Tau Antibody BMS-986446, a differentiated tau antibody that targets an optimal tau region within the MTBR • Recent publications strongly suggest that tau appears to spread throughout the brain via synaptically-connected pathways1 • This propagation of pathol
Slide 22: Superior in Blocking Cellular Internalization of Tau and Neurotoxicity
BMS-986446 BMS-986446 (PRX005): Superior in Blocking Cellular Internalization of Tau and Downstream Neurotoxicity PRX005 blocks internalization of tau Repeats 1 and 2 defined as the strongest inhibitory regions in screening with cellular 100 internalization and neurotoxicity assays % tau positive ce
Slide 23: (m)PRX005 Reduces Pathological Tau and Ameliorates Behavioral Deficit
BMS-986446 (m)PRX005 Reduces Pathological Tau and Ameliorates Behavioral Deficit in Transgenic Tau Mouse Model All values are mean ± SE (n=15-20) Reduction of tau pathological markers Delay of behavioral deficit *p<0.05 *p<0.05 pTau-199/202 in brainstem (% area) * * Chronic dosing start pTau-212 in
Slide 24: BMS-986446: TargetTau-1 Phase 2 Trial Design
BMS-986446 BMS-986446: TargetTau-1 Phase 2 Trial Design TargetTau-1 Trial Overview (NCT06268886)1 Key Inclusion Criteria Primary Endpoint • Ages 50 – 80 years Placebo • Change from baseline in brain tau deposition as measured • MCI due to AD or by tau PET at 76 weeks mild AD dementia Randomized BMS-
Slide 25: PRX019
PRX019 Neurodegenerative Diseases Phase 1 Global Neuroscience Collaboration with Bristol Myers Squibb
Slide 26: PRX019: Potential Treatment of Neurodegenerative Diseases
PRX019 PRX019: Potential Treatment of Neurodegenerative Diseases Phase 1 Trial: Ongoing PRX019 Neurodegenerative diseases • Phase 1 clinical trial being conducted by Prothena Status: Phase 1, completion 2026 • Single ascending dose and multiple ascending dose in healthy adults Global Rights Deal for