Slide 1: Prothena Fourth Quarter and Year-End 2024 Financial Results
Prothena Fourth Quarter and Year-End 2024 Financial Results February 20, 2025
Slide 2: 4Q and FY24 Earnings Call Agenda
4Q and FY24 Earnings Call Agenda Welcome Mark Johnson | Vice President of Investor Relations Opening Remarks Gene Kinney, Ph.D. | President and CEO R&D Update Chad Swanson, Ph.D. | Chief Development Officer Commercial Update Brandon Smith | Chief Operating Officer Financial Results Tran Nguyen | Chi
Slide 3: 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 discovery, preclinical, and clinical pipeline, and expected mil
Slide 4: Opening Remarks
Opening Remarks Gene Kinney, Ph.D. President and CEO
Slide 5: We are Focused on Delivering Life-Saving Therapies
Our Mission Today We are Focused on Delivering Life-Saving Therapies… …for unmet medical needs caused by diseases of protein dysregulation 5
Slide 6: Robust R&D Pipeline
Robust R&D Pipeline FOCUSED ON NEURODEGENERATIVE AND RARE PERIPHERAL AMYLOID DISEASES PROGRAM/ GLOBAL PROTEIN TARGET DISCOVERY PRE-CLINICAL PHASE 1 PHASE 2 PHASE 3 INDICATION PARTNER4 Birtamimab Light Chain SPA1 ODD2 Fast AFFIRM-AL (Phase 3) AL amyloidosis Track3 (Kappa & Lambda) Prasinezumab -Synu
Slide 7: Long-term Value Creation: Wholly-Owned Programs
Long-term Value Creation: Wholly-Owned Programs AL Amyloidosis Alzheimer’s Disease Portfolio Treatment designed to address significant unmet needs Treatments designed to address unmet needs for millions for a rare disease population at high risk of early mortality of presymptomatic and early symptom
Slide 8: Long-term Value Creation: Strategically Partnered Programs
Long-term Value Creation: Strategically Partnered Programs Prasinezumab Coramitug (PRX004) BMS986446 (PRX005) PRX019 Parkinson’s disease ATTR-CM Alzheimer’s disease Neurodegeneration • Potential first-in-class • Potential first-in-class • Potential best-in-class • Potential treatment of anti--synuc
Slide 9: R&D Update
R&D Update Chad Swanson, Ph.D. Chief Development Officer
Slide 10: Birtamimab's Anti-Amyloid Mechanism Designed to Address the Unmet Need for Patients
Birtamimab’s Anti-Amyloid Mechanism Designed to Address the Unmet Need for Patients AL AMYLOIDOSIS PATHOGENIC PATHWAY1-4 CARDIAC DYSFUNCTION & EARLY MORTALITY SOLUBLE TOXIC INSOLUBLE PLASMA CELL DYSCRASIA1,2 LIGHT CHAIN AGGREGATES AMYLOID DEPOSITS Current plasma cell directed Birtamimab’s transforma
Slide 11: Previous Phase 3 VITAL Trial Demonstrated Significant Survival Benefit in Mayo Stage IV
Previous Phase 3 VITAL Trial Demonstrated Significant Survival Benefit in Mayo Stage IV1 Time to All-Cause Mortality (ACM) in Mayo Stage IV Patients2 Post Hoc Analyses of Initial Phase 3 Randomized Trial (VITAL) 1.0 in Mayo Stage IV Patients Birtamimab + SoC (n=38) Efficacy Reduced 0.8 Risk of • Unp
Slide 12: Unmet Need: Early Mortality
Unmet Need: Early Mortality Phase 3 ANDROMEDA Study: Daratumumab (D) + Bortezomib, Cyclophosphamide, and Dexamethasone (VCd) in AL Amyloidosis Patients1 Highlights urgent need to increase early survival for patients with cardiac involvement 12 1 Adapted from presentation by E Kastritis at the 66 th
Slide 13: Birtamimab: Confirmatory Phase 3 AFFIRM-AL Trial Design
Birtamimab: Confirmatory Phase 3 AFFIRM-AL Trial Design Trial Overview (NCT04973137)1 Key Eligibility Criteria Primary Endpoint • Confirmed diagnosis Birtamimab of AL amyloidosis • Time to all-cause mortality (IV Q4W) • Patients with + Standard of Care Secondary Endpoints significant cardiac Randomi
Slide 14: PRX012: Leading a Paradigm Shift in the Treatment of Alzheimer's Disease
PRX012: Leading a Paradigm Shift in the Treatment of Alzheimer’s Disease 300+ iterative antibody design and optimization campaigns led to… Key Antibody Design Attributes HUMANIZED IgG1 monoclonal antibody with low immunogenicity TARGETS a key epitope at the N-terminus of Aβ protein HIGH AFFINITY AND
Slide 15: PRX012 Phase 1 Multiple Dose Design
PRX012 Phase 1 Multiple Dose Design Trial Overview1 Key Inclusion Dose Escalation: “A” and “B” Cohorts2,3 Dose Expansion Key Objectives Criteria • Evaluate the safety, 45 mg A Cohort (n~32) • Patients with tolerability, and SC 6X Q4W early AD immunogenicity 70 mg A Cohort (n~32) • Effect on brain •
Slide 16: PRX123: Potential Best-in-class Dual Aβ/Tau Vaccine for the Treatment & Prevention of AD
PRX123: Potential Best-in-class Dual Aβ/Tau Vaccine for the Treatment & Prevention of AD Mechanism of Action: Need for Dual Targets Cleavage Site A MTBR of tau • PRX123 targets key epitopes within the N-terminus of Peptide Aβ and MTBR of tau designed to promote amyloid clearance and block the trans
Slide 17: Commercial Update
Commercial Update Brandon Smith Chief Operating Officer
Slide 18: Established Patient Population and Consolidated Prescriber Base Enable Birtamimab Market Penetration
Established Patient Population and Consolidated Prescriber Base Enable Birtamimab Market Penetration with Focused Launch Established Consolidated Regulatory and IP Patient Population1-6 Prescriber Base6 Positioning Treated AL amyloidosis patients with • 75% US + EU patients primarily ✓ SPA agreement
Slide 19: Birtamimab: Large Global Market Opportunity
Birtamimab: Large Global Market Opportunity Birtamimab has the potential to be the first anti-amyloid MOA to address significant unmet needs in AL amyloidosis, positioning it as 1L and critical component of SOC $ Multi-Billion Only treatment to demonstrate early survival Market Potential benefit in
Slide 20: Alzheimer's Pipeline: Well-Positioned to Address Presymptomatic & Early AD Patient Population
Alzheimer’s Pipeline: Well-Positioned to Address Presymptomatic & Early AD Patient Population Alzheimer’s Disease Continuum “Early AD” ~315M global ~69M global ~16M global (~40M U.S.) (~5.5M U.S.) (~2.5M U.S.) MCI Due to Mild Moderate Severe Presymptomatic AD AD AD AD AD Stage 1 Stage 2 Stage 3 Stag
Slide 21: Financial Results
Financial Results Tran Nguyen Chief Strategy Officer and Chief Financial Officer
Slide 22: 2024 Actual vs. Guidance
2024 Actual vs. Guidance FY 2024 Actuals FY 2024 Guidance Commentary Net Cash Used in Operating $150.3 M $148 –160 M In-line and Investing Activities Net Loss $122.3 M1 $120 –135 M In-line Year End Cash Balance2 $472.2 M $468 M In-line 1 Includes non-cash share-based compensation expense of $46 mill
Slide 23: 2025 Financial Guidance
2025 Financial Guidance FY 2025 Guidance Net Cash Used in Operating and Investing $168 – 175 M Activities Net Loss $197 – 205 M1 Year End Cash Balance2 $301 M (midpoint) 1 Includes an estimated $41 million of non-cash share-based compensation expense; 2 Includes cash, cash equivalents, and restricte
Slide 24: Closing Remarks
Closing Remarks Gene Kinney, Ph.D. President and CEO
Slide 25: Meaningful Clinical Catalysts Ahead
Meaningful Clinical Catalysts Ahead Wholly-owned Programs Partnered Programs Coramitug (PRX004) Birtamimab ATTR-CM AL Amyloidosis Completion and results of ongoing 2025 Phase 2 trial (NCT05442047) Topline results from confirmatory Phase 3 2Q25 AFFIRM-AL with SPA agreement of P ≤ 0.1 Prasinezumab (NC
Slide 26: Q&A
Q&A