Slide 1: Prothena Fourth Quarter and Year-End 2023 Financial Results
Prothena Fourth Quarter and Year-End 2023 Financial Results February 15, 2024
Slide 2: 4Q and FY23 Earnings Call Agenda
4Q and FY23 Earnings Call Agenda Welcome Mark Johnson | VP of Investor Relations Opening Remarks Gene Kinney, Ph.D. | President and CEO Pre-Commercial Planning Brandon Smith | Chief Operating Officer Clinical Progress Hideki Garren, M.D., Ph.D. | Chief Medical Officer Financial Results Tran Nguyen |
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 expected timing of reporting data from clinical trials of PRX012, birtamimab, prasinezumab,
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/ PROTEIN COMMERCIAL DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PHASE 3 INDICATION TARGET RIGHTS Birtamimab Kappa & Lambda AFFIRM-AL (Phase 3 clinical trial, under SPA1 agreement with FDA) AL amyloidosis Light Ch
Slide 7: Potential Upcoming Clinical Readouts
Potential Upcoming Clinical Readouts WHOLLY OWNED STRATEGICALLY PARTNERED NEURODEGENERATIVE PRX012 Prasinezumab Alzheimer’s disease Parkinson’s disease DISEASES • Potential best-in-class, next generation, • Potential first-in-class anti-α-synuclein antibody subcutaneous anti-Aβ antibody • Phase 2b P
Slide 8: Pre-Commercial Planning
Pre-Commercial Planning Brandon Smith Chief Operating Officer
Slide 9: Birtamimab: Differentiated Approach to AL Amyloidosis
Birtamimab: Differentiated Approach to AL Amyloidosis Ongoing Phase 3 AFFIRM-AL (NCT04973137) Birtamimab • Trial designed per FDA Special Protocol AL Amyloidosis Assessment (SPA) with unprecedented significance level of P ≤ 0.10 Anti-Amyloid Mechanism of Action • Primary Endpoint: Time to all-cause
Slide 10: Defined Patient Population and Consolidated Prescriber Base Enable Birtamimab Market Penetration
Defined Patient Population and Consolidated Prescriber Base Enable Birtamimab Market Penetration with Focused Launch Significant Defined Consolidated Unmet Need Patient Population2-6 Prescriber Base • Urgent need for immediate • 60 – 120 K Mayo Stage IV • ~75% US and EU Mayo Stage IV intervention in
Slide 11: Clinical Progress
Clinical Progress Hideki Garren, M.D., Ph.D. Chief Medical Officer
Slide 12: Significant Survival Benefit in Mayo Stage IV AL Amyloidosis
Significant Survival Benefit in Mayo Stage IV AL Amyloidosis in Randomized Clinical Trial1 Survival Rates of Birtamimab vs Placebo for Mayo Stage IV AL Amyloidosis Patients2 • Post hoc analyses of initial Phase 3 1.0 randomized clinical trial (VITAL): Birtamimab + SoC – Survival benefit in Mayo Stag
Slide 13: Birtamimab: Confirmatory Phase 3 AFFIRM-AL Trial Design
Birtamimab: Confirmatory Phase 3 AFFIRM-AL Trial Design FDA Fast Track Designation SPA agreement with FDA Primary Endpoint • Based on VITAL results in this Birtamimab • Time to All-Cause population, SPA agreement with FDA (IV q28d) Mortality at unprecedented significance level of + SoC Randomize 2:1
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 SAD Design
PRX012 Phase 1 SAD Design SINGLE ASCENDING DOSE (SAD) COHORTS Healthy Volunteer Cohorts Trial Design • Age 20 – 45 years 70 mg 200 mg • Phase 1, randomized 3:1, double-blind, placebo-controlled, n= ~8 n= ~8 single ascending dose trial (3:1) (3:1) • 1 subcutaneous dose of PRX012 • Evaluate the safety
Slide 16: PRX012 Phase 1 MAD Design
PRX012 Phase 1 MAD Design MULTIPLE ASCENDING DOSE (MAD) COHORTS Early Alzheimer’s Disease “A” Cohorts Trial • Ages 55 – 85 years Design • Amyloid PET positive • Phase 1, randomized 3:1, 45 mg 70 mg 200 mg 400 mg double-blind, placebo-controlled, • MMSE ≥ 18 n= ~32 n= ~32 n= ~32 n= ~32 MAD trial (3:1
Slide 17: Prasinezumab: Potential First-in-Class Treatment for Parkinson's Disease
Prasinezumab: Potential First-in-Class Treatment for Parkinson’s Disease Prasinezumab Ongoing Phase 2b PADOVA (NCT04777331) Parkinson’s Disease • N = 586 early Parkinson’s disease patients • Primary Endpoint: Time to confirmed motor Anti-α-synuclein Antibody progression event • Preferentially binds
Slide 18: NNC6019: Potential First-in-Class Treatment for ATTR Amyloidosis
NNC6019: Potential First-in-Class Treatment for ATTR Amyloidosis NNC6019 Ongoing Phase 2 (NCT05442047) ATTR Amyloidosis • N = 99 ATTR-CM patients, 3 arms Differentiated Depleter Mechanism of Action • Participants receive IV infusion Q4W of 10 mg/kg or 60 mg/kg of NNC6019 or placebo added to SOC unti
Slide 19: Financial Results
Financial Results Tran Nguyen Chief Strategy Officer and Chief Financial Officer
Slide 20: 2023 Actual vs. Guidance
2023 Actual vs. Guidance FY 2023 Actuals FY 2023 Guidance Commentary Net Cash Used in Operating and Investing Activities $136.7 M $148 –161 M Favorable Net Loss $147.0 M1 $153 –171 M Favorable Year End Cash Balance2 $621.0 M $600 M Favorable 1 Includes non-cash share-based compensation expense of $4
Slide 21: 2024 Financial Guidance
2024 Financial Guidance FY 2024 Guidance Net Cash Used in Operating and Investing Activities $208 – 225 M Net Loss $229 – 255 M1 Year End Cash Balance2 (midpoint) $405 M 1 Includes an estimated $51 million of non-cash share-based compensation expense; 2 Includes cash, cash equivalents, and restricte
Slide 22: Closing Remarks
Closing Remarks Gene Kinney, Ph.D. President and CEO
Slide 23: Upcoming Potential Milestones
Upcoming Potential Milestones TRANSFORMATIONAL PERIOD AHEAD Wholly-owned Programs Birtamimab for potential treatment of AL amyloidosis 4Q24 – 2Q25 Confirmatory Phase 3 AFFIRM-AL topline data (NCT04973137) PRX012 for potential treatment of Alzheimer’s disease 2024 Ongoing Phase 1 trial update PRX
Slide 24: Q&A
Q&A