Slide 1: Prothena Fourth Quarter and Year-End 2025 Financial Results
Prothena Fourth Quarter and Year-End 2025 Financial Results February 19, 2026
Slide 2: 4Q and FY25 Earnings Call Agenda
4Q and FY25 Earnings Call Agenda Welcome Mark Johnson | Vice President, Head of Investor Relations Opening Remarks Gene Kinney, Ph.D. | President and CEO Clinical Programs Chad Swanson, Ph.D. | Chief Development Officer Preclinical Programs Philip Dolan, Ph.D. | Vice President, Head of Discovery Res
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 our pipeline, and the potential to advance, initiate, and complete preclinical and IND enabling studies for our ea
Slide 4: Opening Remarks
Opening Remarks Gene Kinney, Ph.D. President and CEO
Slide 5: 2025 Achievements Shape Pipeline Progress
2025 Achievements Shape Pipeline Progress PROGRAM GLOBAL 2025 ACHIEVEMENTS STATUS INDICATION (MODALITY) RIGHTS4 PARTNERED CLINICAL PROGRAMS Prasinezumab Roche advanced to Phase 3 based on data from two Phase 2 trials & OLEs Parkinson’s disease (mAb) Phase 3 Target: α-Syn (C-terminus) presented at
Slide 6: 2026 Strategic Priorities
2026 Strategic Priorities CAPTURE VALUE EMBEDDED IN PARTNERSHIPS & OPTIMIZE CAPITAL STRUCTURE All partnered assets originated from Prothena’s R&D engine & drive meaningful long-term value • Up to $105 MILLION in clinical milestones by YE 2026 • Coramitug potential milestone after prespecified enroll
Slide 7: Future Partner Catalysts
Future Partner Catalysts Up to $105 Million in Clinical Milestones by YE 2026 Related to the Advancement of Coramitug and PRX0191 2026 2027 2028+ Coramitug PRX019 BMS-986446 Prasinezumab Coramitug ATTR-CM Neurodegenerative Alzheimer’s disease Parkinson’s disease ATTR-CM diseases Eligible for Ph 3 Ph
Slide 8: Clinical Programs
Clinical Programs Chad Swanson, Ph.D. Chief Development Officer
Slide 9: Prasinezumab: Potential First-In-Class Treatment for Parkinson's Disease
Prasinezumab Prasinezumab: Potential First-In-Class Treatment for Parkinson’s Disease Clear Addressable Unmet Need Current Status • > 10 million Parkinson’s patients globally, fastest • Roche advanced prasinezumab into the growing neurodegenerative disease1 Phase 3 PARAISO clinical trial in ~900 pat
Slide 10: Moving into Phase 3 in Parkinson's Disease
Prasinezumab Moving into Phase 3 in Parkinson’s Disease Phase 2b (PADOVA) 2 Year Results L-DOPA-treated population ~40% relative reduction in progression at week 104 vs. placebo p=0.01771 • More pronounced effect in L-DOPA treated patients (~75% of population) • Results consistent across both PADOVA
Slide 11: Phase 3 PARAISO Trial Design
Prasinezumab Phase 3 PARAISO Trial Design PARAISO Trial Overview (NCT07174310) Key Inclusion Criteria Primary Endpoint • Ages 50 – 85 years • Time to Confirmed Motor Prasinezumab Progression Event on • Diagnosis of idiopathic IV infusion Movement Disorder Society - Parkinson’s disease based on MDS c
Slide 12: Coramitug: Potential First-in-Class Depleter Treatment for ATTR-CM
Coramitug Coramitug: Potential First-in-Class Depleter Treatment for ATTR-CM Clear Addressable Unmet Need Current Status • 450,000 patients estimated globally with wild-type or • Novo Nordisk advanced coramitug into the hereditary ATTR-CM1-3 Phase 3 CLEOPATTRA clinical trial in ~1280 patients with A
Slide 13: Moving into Phase 3 in ATTR-CM
Coramitug Moving into Phase 3 in ATTR-CM Phase 2 Results1-2 105 patients / 3-arms / 12 months Coramitug 60 mg/kg reduced NT-proBNP levels from baseline at 12 months and by 48% vs. placebo p=0.0017 • Coramitug 60 mg/kg showed a treatment difference of 13.45 m in 6MWT vs. placebo at 12 months • Corami
Slide 14: Phase 3 CLEOPATTRA Trial Design
Coramitug Phase 3 CLEOPATTRA Trial Design CLEOPATTRA Trial Overview (NCT07207811) (NCT07207811) Key Inclusion Criteria Primary Endpoint • 18 years and older • Number of occurrences of Coramitug + SOC composite endpoint of CV • Diagnosis of ATTR-CM1 deaths and recurrent CV IV infusion events (CV hosp
Slide 15: BMS-986446: Potential First-In-Class anti-Tau mAb for Alzheimer's Disease
BMS-986446 BMS-986446: Potential First-In-Class anti-Tau mAb for Alzheimer’s Disease Clear Addressable Unmet Need Current Status • > 80 million Alzheimer’s patients globally1 • Bristol completed enrollment in the Phase 2 TargetTau-1 clinical trial in ~310 patients with Differentiated Mechanism of Ac
Slide 16: Microtubule Binding Region (MTBR) of Tau
BMS-986446 Microtubule Binding Region (MTBR) of Tau N1 N2 Proline-rich domain R1 R2 R3 R4 1 45 104 151 244 275 306 338 371 441 N-terminus Microtubule-binding domain C-terminus Rationale for Targeting Microtubule Binding Region (MTBR) of Tau: • Pathology: MTBR is central to fibril formation, seeding
Slide 17: Phase 2 TargetTau-1 Trial Design
BMS-986446 Phase 2 TargetTau-1 Trial Design TargetTau-1 Trial Overview (NCT06268886) Key Inclusion Criteria Primary Endpoint • Ages 50 – 80 years Placebo • Change from baseline in brain tau deposition as measured • MCI due to AD or mild by tau-PET at 76 weeks AD dementia Randomized BMS-986446 4:3:3
Slide 18: PRX019: Potential Treatment of Neurodegenerative Diseases
PRX019 PRX019: Potential Treatment of Neurodegenerative Diseases Current Status Upcoming Milestones • Phase 1 clinical trial being conducted by Prothena • Phase 1 trial primary completion expected in 2026 (NCT06699680) • Eligible for potential milestone at time of BMS decision to further develop PRX
Slide 19: Preclinical Programs
Preclinical Programs Philip Dolan, Ph.D. VP, Head of Discovery Research
Slide 20: CYTOPE: A Breakthrough in Intracellular Therapeutics
CYTOPE® CYTOPE®: A Breakthrough in Intracellular Therapeutics CYTOPE® is an innovative intracellular drug targeting technology designed at Prothena to reach virtually any cell-type, enable precise targeting of intracellular disease pathways, and to unlock therapeutic access to targets where conventi
Slide 21: pTDP-43 is a Core Driver of ALS Pathogenesis that is an Undruggable Target
CYTOPE® pTDP-43 is a Core Driver of ALS Pathogenesis that is an Undruggable Target with Current Modalities pTDP-43: Hallmark of ALS Pathology Challenges in Targeting pTDP-43 • ~97% of ALS cases show TDP-43 nuclear-to-cytoplasmic • Delivery: Intracellular target expressed broadly in CNS & mislocaliza
Slide 22: TDP-43 CYTOPE is Designed to Address Toxic Gain-of-Function and Loss-of-Function Pathology
CYTOPE® TDP-43 CYTOPE® is Designed to Address Toxic Gain-of-Function and Loss-of-Function Pathology Toxic Gain-of-Function Loss-of-Function TDP-43 CYTOPE® Specifically degrades pTDP-43 aggregates in the 1 cytoplasm, addressing toxic gain-of-function pathology TDP-43 CYTOPE TDP-43 CYTOPE was designed
Slide 23: TDP-43 CYTOPE Preclinical Data Demonstrates Potential of CYTOPE Technology
CYTOPE® TDP-43 CYTOPE® Preclinical Data Demonstrates Potential of CYTOPE Technology 1 Addresses Toxic Gain-of-Function: 2 Addresses Loss-of-Function: Significantly Reduced pTDP-43 Aggregates Attenuated ALS-Related Splicing Defects Motor Cortex Skeletal Muscle Human Neuronal Cells rNLS8 Mice (Left) %
Slide 24: Potential of TfR for PRX012
PRX012-TfR Potential of TfR for PRX012 Rationale for Transferrin Receptor Technology: • The addition of transferrin targeting to gantenerumab has been demonstrated to: • Significantly decrease the time required to achieve meaningful amyloid reduction • Substantially lower risk of ARIA-E associated w
Slide 25: PRX012-TfR for Alzheimer's Disease
PRX012-TfR PRX012-TfR for Alzheimer’s Disease PRX012 Antibody Profile • Phase 1 ASCENT top-line results1 support once- PRX012-TfR Antibody monthly, subcutaneous PRX012 with dose- and • PRX012-TfR may lower the risk of ARIA, time-dependent reductions in amyloid plaque lower dose level of PRX012, and
Slide 26: Financial Results
Financial Results Tran Nguyen Chief Strategy Officer and Chief Financial Officer
Slide 27: 2025 Actual vs. Guidance
2025 Actual vs. Guidance FYE 2025 FYE 2025 Performance Actuals Guidance Net Cash Used in Operating $163.7 M $170 – 178 M Favorable and Investing Activities Net Loss $244.1 M1 $240 – 248 M In-line Year End Cash Balance2 $308.4 M $298 M Favorable 1 Includes non-cash share-based compensation expense of
Slide 28: 2026 Financial Guidance
2026 Financial Guidance FYE 2026 Guidance Net Cash Used in Operating and Investing $50 – 55 M Activities Net Loss $67 – 72 M1 Year End Cash Balance2 $255 M2 (midpoint) Financial guidance does not include the potential to earn up to $105 million of aggregate clinical milestone payments from strategic
Slide 29: Closing Remarks
Closing Remarks Gene Kinney, Ph.D. President and CEO
Slide 30: 2026 Strategic Priorities
2026 Strategic Priorities CAPTURE VALUE EMBEDDED IN PARTNERSHIPS & OPTIMIZE CAPITAL STRUCTURE All partnered assets originated from Prothena’s R&D engine & drive meaningful long-term value • Up to $105 MILLION in clinical milestones by YE 2026 • Coramitug potential milestone after prespecified enroll
Slide 31: Q&A
Q&A