Prothena Corporation plc · NASDAQ:PRTA
Prothena — Investor Presentation (August 2023)
85 slides from Prothena's investor presentation, August 2023
Slide 1: Corporate Overview August 2023
CORPORATE OVERVIEW August 2023
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 discovery, preclinical, and clinical pipeline, and expected mil
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 NEUROSCIENCE RARE PERIPHERAL AMYLOID DISEASES Amyloid Transthyretin Alzheimer’s Parkinson’s light chain amyloidosis disease (AD) disease (PD) amyloidosis (AL) (ATTR) 55 million 10 million 60,000-120,0
Slide 5: Our Team has Pioneered Multiple Scientific Advances in Protein Dysregulation
Our Team has Pioneered Multiple Scientific Advances in Protein Dysregulation OUR LEGACY INCLUDES FOUNDATIONAL DISCOVERIES IN THE UNDERSTANDING OF ALZHEIMER’S DISEASE Pioneered fundamental discoveries elucidating the roles of beta amyloid (Ab), gamma secretase and beta secretase play in disease1 Firs
Slide 6: Our Biology-Directed Engine Propels Progress Across our 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 Multiple Clinical Programs Ongoing Wholly-owned Phase 3 program Disease- Two partnered Phase 2 programs Driven Two Phas
Slide 7: 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 8: Alzheimer's Disease
Alzheimer’s Disease
Slide 9: Our Legacy Drives Our Vision to Transform the Care of Alzheimer's Disease
Our Legacy Drives Our Vision to Transform the Care of Alzheimer’s Disease With unparalleled protein …We’re uniquely positioned to address Alzheimer’s dysregulation expertise… Disease with a best-in-class portfolio PRX012, anti-Aβ product candidate with potential best-in-class, highly potent binding;
Slide 10: Today's Clinical Science Validates the Mechanism Designed by Our Team
Today’s Clinical Science Validates the Mechanism Designed by Our Team 2020 US FDA ANALYSIS: Aβ has been validated as a disease modifying target in AD1,2 CDR, Clinical Dementia Rating Scale; SUVr, Standardized Uptake Value Ratio. 1 ADUHELM [prescribing information]. Cambridge, Massachusetts: Biogen I
Slide 11: Targeting Alzheimer's Where it Matters
Targeting Alzheimer’s Where it Matters CHANGING THE TREATMENT PARADIGM THROUGH OUR BIOLOGY-DIRECTED ENGINE Dynamic biomarkers of the Alzheimer’s pathological cascade* 11 *Jack, Clifford et al. Hypothetical model of dynamic biomarkers of the Alzheimer’s pathological cascade, 2010 NIH Public Access
Slide 12: PRX012 Alzheimer's Disease
PRX012 Alzheimer’s Disease
Slide 13: 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 HUMANIZED IgG1 monoclonal design and optimization antibody with low immunogenicity campaigns led to… TARGETS all N-terminal epitopes of Aβ protein HIGH AFFINITY AND AVIDITY to Aβ for extended binding tim
Slide 14: PRX012: Promotes Comprehensive Clearance of Amyloid Plaques and Neutralization of Oligomers
PRX012: Promotes Comprehensive Clearance of Amyloid Plaques and Neutralization of Oligomers Designed to target and clear all toxic aggregated forms of Aβ Free/ dispersed Aggregated Microglia PRX012 Aβ plaque Aβ Forms PRX012 elicits microglial-mediated phagocytosis Soluble Insoluble Both unmodified A
Slide 15: Translating Patient Needs Into Antibody Engineering
Translating Patient Needs Into Antibody Engineering PATIENT-CENTRIC DESIGN STRATEGY FOR PRX012 POTENTIAL IMPLICATIONS TARGET PROFILE ANTIBODY DESIGN ATTRIBUTES FOR PATIENTS Maintain From Effectively clear soluble and • N-terminal directed First Generation • Associated with efficacy insoluble aggrega
Slide 16: PRX012 and Surrogate Demonstrate Equivalent Potent Binding Affinity for Aβ
PRX012 and Surrogate Demonstrate Equivalent Potent Binding Affinity for Aβ Surface Plasmon Resonance (SPR) Affinity for Aβ Species Aβ Fibrils Compound Fibril/Plaque N3pE-Aβ 60 Slow off-rate (PRX012 & PRX012s) PRX012 0.070a >67b Response (RU) 40 PRX012s 0.054a >67b Fast biphasic off-rate (aducanumab)
Slide 17: PRX012s Binds Aβ Protofibrils With Very High Affinity
PRX012s Binds Aβ Protofibrils With Very High Affinity Surface Plasmon Resonance Antibody Relative Affinity (KD1) Aβ Protofibrils Lecanemab1 1.97 nM (Tucker et al., 2015) Lecanemab* 1.91 nM dissociation Slower PRX012s 0.0975 nM SPR Binding Kinetics Antibody dissociation ka1 (1/Ms) kd1 (1/s) KD1 Lecan
Slide 18: PRX012s Induced Potent and Robust Clearance of Pyroglutamate-modified Aβ
PRX012s Induced Potent and Robust Clearance of Pyroglutamate-modified Aβ PRX012s PRX012s Abeta Aβ Donanemab Donanemab 40 Reduction %%Reduction ofof N3pE N3pE 20 Study Conditions Post-mortem AD brain tissue (same donor used for Tissue all conditions) Treatment PRX012s, donanemab, or IgG1 isotype cont
Slide 19: PRX012s Promotes Simultaneous Microglia-Mediated Phagocytosis of Aβ and N3pE-Aβ
PRX012s Promotes Simultaneous Microglia-Mediated Phagocytosis of Aβ and N3pE-Aβ in Post-mortem Brain Tissue From AD Subjects Microglia (Iba1) Aβ N3pE-Aβ Merge Microglia Aβ N3pE-Aβ Merge hIgG1 PRX012s Microglia (Iba1: green) simultaneously phagocytose Aβ (red) and pyroglutamate-modified Aβ (AβpE3-42:
Slide 20: PRX012 Phase 1 Study Design
PRX012 Phase 1 SAD Primary Objective: N = ~ 50 total subjects and Phase 1 Study Design: Healthy • To evaluate the safety and Volunteers tolerability of PRX012 when • Randomized, double-blind, (SubQ single placebo-controlled, SAD administered as a single dose Randomize 3:1 study dose) Secondary patie
Slide 21: PRX005 Alzheimer's Disease
PRX005 Alzheimer’s Disease Global Neuroscience Collaboration with Bristol Myers Squibb 21
Slide 22: PRX005: MTBR-Specific Anti-Tau Designed to be Best-in-Class
PRX005: MTBR-Specific Anti-Tau Designed to be Best-in-Class • PRX005, 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 pat
Slide 23: PRX005: Superior in Blocking Cellular Internalization of Tau
PRX005: Superior in Blocking Cellular Internalization of Tau and Downstream Neurotoxicity Compared to Other Anti-Tau Antibodies PRX005 blocks internalization of tau Repeats 1 and 2 defined as the strongest inhibitory regions in screening with cellular 100 internalization and neurotoxicity assays % t
Slide 24: (m)PRX005 Treatment Reduces Pathological Tau in Transgenic Mouse Model
(m)PRX005 Treatment 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 b
Slide 25: PRX123 Alzheimer's Disease
PRX123 Alzheimer’s Disease
Slide 26: Vaccine Constructs: Potential Best-in-class Dual Aβ/Tau Vaccine
Vaccine Constructs: Potential Best-in-class Dual Aβ/Tau Vaccine for the Treatment & Prevention of AD PROTHENA IS PIONEERING THE DEVELOPMENT OF DUAL AΒ/TAU VACCINE CANDIDATE PRX123 • Synergistic mechanism designed for increased efficacy over single-target vaccines Cleavage Site Ab MTBR of tau – Stron
Slide 27: Desirable Attributes of Aβ/Tau Vaccines and Prothena's Design Strategies
Desirable Attributes of Aβ/Tau Vaccines and Prothena’s Design Strategies Design Strategy Desirable Output • Linear peptides, proprietary ✓ Optimal antigen presentation RESPONSE cleavable linkers with persistent immune response 1 Antibody levels, balanced • Optimal carriers, immunization ✓ Overcomes
Slide 28: Prothena's Dual Aβ/Tau Vaccines Demonstrate Desirable Quantity, Quality and Safety
Prothena’s Dual Aβ/Tau Vaccines Demonstrate Desirable Quantity, Quality and Safety Quantity Quality Safety Unable to induce measurable cytotoxic T-cell activity against Aβ and tau in Non-human primates (ELISpot) Prothena’s Dual Vaccine Positive Control Aβ Tau ✓ Epitope, affinity, Aβ clearance, ✓ Avo
Slide 29: Rare Peripheral Amyloid Diseases
Rare Peripheral Amyloid Diseases
Slide 30: AL Amyloidosis: A Rare, Progressive, and Fatal Disease
AL Amyloidosis: A Rare, Progressive, and Fatal Disease PATHOGENIC PATHWAY The four stages (Mayo Stages I–IV) of AL amyloidosis: life expectancy decreases as the disease progresses 4,5 Protein HEART Misfolding Restrictive Biomarkers Life cardiomyopathy Mayo Stage Heart failure Impacted* Expectancy I
Slide 31: AL Amyloidosis Treatments Are at a Roadblock
AL Amyloidosis Treatments Are at a Roadblock Currently available AL treatments have not shown survival benefit in AL patients • Most are re-purposed multiple myeloma treatments1 • Cardiotoxic and unsuitable for people with advanced disease and heart damage2,3 UNMET NEED: Newly • No reduction of amyl
Slide 32: Birtamimab AL Amyloidosis
Birtamimab AL Amyloidosis
Slide 33: Birtamimab: Pioneering a New Class of Amyloid-Depleting Therapies
Birtamimab: Pioneering a New Class of Amyloid- Depleting Therapies for Advanced AL Amyloidosis Addresses acute unmet needs in Mayo Stage IV BINDS only to misfolded light AL amyloidosis chain isoforms; leaves normal proteins intact • Ongoing Phase 3 trial designed per FDA Special Protocol Assessment
Slide 34: Birtamimab: Only Clinical Candidate Demonstrating Survival Benefit in Stage IV AL Amyloidosis
Birtamimab: The Only Clinical Candidate Demonstrating a Significant Survival Benefit in Stage IV AL Amyloidosis* Survival Rates of Birtamimab vs Placebo for • More than 300 patients dosed Stage 4 AL Amyloidosis Patients** 1.0 • Post hoc analyses of initial Phase 3 RCT Birtamimab + SoC (VITAL Study):
Slide 35: AFFIRM-AL Study: Confirmatory Phase 3 Trial Underway
AFFIRM-AL Study: Confirmatory Phase 3 Trial Underway FDA Fast Track Designation Primary Endpoint SPA agreement with FDA • All-Cause Mortality on trial design Birtamimab (IV q28d) Randomize 2:1 • Based on VITAL results in this Secondary population, SPA agreement with FDA + SoC Endpoints Orphan Drug N
Slide 36: Mayo Stage IV Patients are Primarily Treated in Amyloidosis Centers
Mayo Stage IV Patients are Primarily Treated in Amyloidosis Centers TREATMENT SETTING MAYO STAGE IV PATIENTS Amyloidosis Centers of 15-27% ~75% of US and EU Excellence (COEs) patients primarily treated in ~500 Amyloidosis Specialty Amyloidosis COE 43-51% Academic Centers and specialty centers Commun
Slide 37: NNC6019 (formerly PRX004) ATTR Amyloidosis
NNC6019 (formerly PRX004) ATTR Amyloidosis ATTR Business Acquired by Novo Nordisk
Slide 38: NNC6019: Potential First-in-Class Treatment for ATTR Amyloidosis
NNC6019 (formerly PRX004): Potential First-in-Class Treatment for ATTR Amyloidosis • Differentiated depleter uniquely designed for NON-PATHOGENIC patients at high risk of early mortality PATHOGENIC PATHWAY PATHWAY • mPRX004 (murine form of PRX004) preclinical HEART results:1 Protein Restrictive Misf
Slide 39: Parkinson's Disease
Parkinson’s Disease
Slide 40: Prasinezumab Parkinson's Disease
Prasinezumab Parkinson’s Disease Worldwide Collaboration with Roche
Slide 41: Prasinezumab: a-Synuclein Immunotherapy
Prasinezumab: a-Synuclein Immunotherapy REDUCE NEURONAL TOXICITY AND PREVENT CELL-TO-CELL TRANSMISSION1 • a-Synuclein pathology is strongly implicated in PD – Accumulation of a-synuclein is a predominant neuropathological feature and follows the topological progression of disease Aggregated extracel
Slide 42: Upcoming Milestones
Upcoming Milestones
Slide 43: Upcoming Potential Milestones
Upcoming Potential Milestones TRANSFORMATIONAL PERIOD AHEAD PRX012 for potential treatment of Alzheimer’s disease YE22 ✓ Phase 1 multiple ascending dose study initiation 1Q23 ✓ Oral presentation of preclinical data showing superior binding characteristics of PRX012 at AD/PD 2023 YE23 ❑ Topline Phase
Slide 44: Appendix
APPENDIX
Slide 45: Birtamimab Supplemental Information
Birtamimab Supplemental Information
Slide 46: Birtamimab Demonstrated Significant Amyloid Clearance and Prolonged Survival in Preclinical Model
Birtamimab* Demonstrated Significant Amyloid Clearance and Prolonged Survival in Preclinical Model Birtamimab* Removes Amyloid In Vivo Birtamimab* Prolongs Survival in Transgenic Mouse Model 100% survival with birtamimab* p < 0.0025 100 80 Percent survival 60 40 Control mAB 20 Birtamimab* 0 0 10 20
Slide 47: Phase 3 VITAL Study Overview
Phase 3 VITAL Study Overview* • Global, randomized, double-blinded, placebo-controlled study − Sample size and randomization • 30% of patients ▪ N=260 enrolled in VITAL ▪ 1:1 (N=77) were − Key eligibility criteria characterized as ▪ Confirmed diagnosis of AL amyloidosis Mayo Stage IV at ▪ Newly diag
Slide 48: Birtamimab Survival Benefit Adjusted for Key Baseline Variables
Birtamimab Survival Benefit Adjusted for Key Baseline Variables for Mayo Stage IV Patients 48 Gertz et al; Birtamimab plus standard of care in light chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial; Blood; June 27, 2023.
Slide 49: Mayo Stage IV Patients in Major Markets
Mayo Stage IV Patients in Major Markets TARGETED OPPORTUNITY IN ORPHAN POPULATION AL Amyloidosis ~13,000 ~17,500 ~4,500 ~30,500 ~6,800 Dx Prevalence Urban Only Mayo Stage IV ~3,900 ~5,200 ~1,300 ~9,100 ~2,000 Dx Prevalence 49 Kyle Mayo Clin Proc. 2019; Kyle Blood 1992; Quock Blood Adv. 2018; Shimaza
Slide 50: Improvements in Hematological Response Have Not Been Shown to Impact Survival
Improvements in Hematological Response Have Not Been Shown to Impact Survival in AL Amyloidosis Table 3. Univariate and multivariate analysis for OS 50
Slide 51: Primary Results from the Daratumumab Phase 3 ANDROMEDA Study
Primary Results from the Daratumumab Phase 3 ANDROMEDA Study, Presented at EHA June 2020 51
Slide 52: Primary Results from the Daratumumab Phase 3 ANDROMEDA Study
Primary Results from the Daratumumab Phase 3 ANDROMEDA Study, Presented at EHA June 2020 52
Slide 53: Primary Results from the Daratumumab Phase 3 ANDROMEDA Study
Primary Results from the Daratumumab Phase 3 ANDROMEDA Study, Presented at EHA June 2020 53
Slide 54: The Path Leading to AFFIRM-AL
The Path Leading to AFFIRM-AL VITAL results Collaboration and analyzed alignment with FDA • Results analyzed with • Multiple in-depth • Confirmatory Phase 3 global input from external discussions with FDA study of birtamimab in Mayo advisors and KOLs Stage IV patients with AL • VITAL data enables •
Slide 55: NNC6019 (formerly PRX004) Supplemental Information
NNC6019 (formerly PRX004) Supplemental Information
Slide 56: PRX004: Designed to Deplete Amyloid
PRX004: 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 vivo
Slide 57: Prothena Developed PRX004 to Target an Epitope Exposed on Pathogenic Forms of TTR
Prothena Developed PRX004 to Target an Epitope Exposed on Pathogenic Forms of TTR1 TTR89-97 Epitope recognized by PRX004 is hidden in the TTR tetramer, but exposed in monomeric and aggregated forms of both ATTRv and wtATTR2 1-GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT WEPFASGKTS-50 51-ESGELHGLTT EE
Slide 58: PRX004 Phase 1 Study Design
PRX004 Phase 1 Study Design NCT03336580 Escalation Phase Long Term Extension Phase* • 3+3 study design • 6 Dose levels: 0.1, 0.3, 1, 3, 10, & 30 mg/kg • Up to 15 additional doses IV q28d for 3 months IV q28d Primary Objectives: • Evaluate safety, tolerability, PK and target engagement (misTTR assay)
Slide 59: Observed Improvement in Neuropathy with PRX004
Observed Improvement in Neuropathy with PRX004 • NIS for each of the 7 evaluable patients was more favorable than published historical data • 3 of these 7 patients demonstrated improvement in neuropathy with a mean change in NIS of –3.33 points PRX004 Phase 1 Natural Patisiran2 All PRX004 Alone Hist
Slide 60: Observed Improvement in Cardiac Systolic Function with PRX004
Observed Improvement in Cardiac Systolic Function with PRX004 • Improvement in GLS in all 7 evaluable patients • In the 3 patients who improved on NIS, GLS improvement was more pronounced, with a mean change of –1.51% PRX004 Phase 1 Natural Patisiran2 All PRX004 Alone History1 ΔGLS mean* –1.21% –2.1
Slide 61: NYHA Classification Remained Stable with PRX004
NYHA Classification Remained Stable with PRX004 NYHA • Classification at baseline: PATIENT SYMPTOMS CLASS – NYHA I (n=6) – NYHA II (n=1) No limitation of physical activity. Ordinary I physical activity does not cause undue fatigue, palpitation, dyspnea • All patients (n=7) were stable at their last
Slide 62: Trend for Survival Does Not Show Clear Separation Until ~18 Months After Start of Tafamidis
Trend for Survival Does Not Show Clear Separation Until ~18 Months After Start of Tafamidis Treatment 62 Source: Maurer M et al. 2018
Slide 63: ATTR-ACT Phase 3 Study: Tafamidis Showed Little/No Effect in NYHA Class III
ATTR-ACT Phase 3 Study: Tafamidis Showed Little/No Effect in NYHA Class III ATTR Amyloidosis Patients 63 Source: Maurer M et al. 2018
Slide 64: Preclinical PK/PD Dose Selection Model, Confirmed in PRX004-101
Preclinical PK/PD Dose Selection Model, Confirmed in PRX004–101 Preclinical PK/PD Model Clinical Confirmation of Preclinical PK/PD Model 3 10 30 mg/kg Variables 3 10 30 mg/kg Variables • Binding kinetics and • Reduction in free non- immunoreactivity to native TTR by PRX004 patient derived (P1), acco
Slide 65: Prasinezumab Supplemental Information
Prasinezumab Supplemental Information
Slide 66: Phase 2b PADOVA Study
Phase 2b PADOVA Study (NCT04777331) Early Parkinson’s Primary Objective: Disease Patients: • Time to meaningful progression on motor signs as Placebo assessed by ≥5 point increase in MDS-UPDRS Part III • A diagnosis of PD for at least 6 (IV q4W) score from baseline months to maximum 3 years at scree
Slide 67: Phase 2 PASADENA Study Summary of Part 1 & 2 Results
Phase 2 PASADENA Study Summary of Part 1 & 2 Results PRASINEZUMAB IN EARLY PARKINSON’S DISEASE • First anti-a-synuclein antibody to significantly slow progression on measures of PD; results support the potential of prasinezumab to slow underlying disease pathophysiology and clinical decline in patie
Slide 68: PASADENA Phase 2 Study
PASADENA Phase 2 Study (NCT03100149) Part 1 – Complete Part 2 - Ongoing 52-week double- 52-week complete blind treatment prasinezumab 1500 Primary Objective: Early Parkinson’s mg IV q4W • Evaluate efficacy using MDS-UPDRS at Week 52 Disease Patients: Placebo • A diagnosis of PD for 2 IV q4W Secondar
Slide 69: Progression of MDS-UPDRS Total Over 1 Year is Mostly Driven by Part III
Progression of MDS-UPDRS Total Over 1 Year is Mostly Driven by MDS-UPDRS Part III in an Early-Stage Population (PPMI study) Change in MDS-UPDRS over 1 year in PPMI study MDS-UPDRS Total Score MDS-UPDRS Part III MDS-UPDRS Part II MDS-UPDRS Part I 69 MDS-UPDRS, Movement Disorder Society-Unified Parkin
Slide 70: PASADENA Phase 2: Significantly Slowed Progression of MDS-UPDRS Part III
PASADENA Phase 2 SIGNIFICANTLY SLOWED PROGRESSION OF MDS-UPDRS PART III MDS-UPDRS Part III – central rating* SECONDARY ENDPOINT: Change in total MDS-UPDRS Part III from baseline to Week 52 *Patients who started symptomatic PD treatment contribute until the last visit before symptomatic PD treatment
Slide 71: PASADENA Phase 2: Delayed Time to Worsening of Motor Function
PASADENA Phase 2 SIGNIFICANTLY DELAYED TIME TO WORSENING OF MOTOR FUNCTION, CONFIRMED BY DIGITAL MEASURES OF PROGRESSION Exploratory Endpoint: Time to worsening of Exploratory Endpoint: Digital PASADENA motor function (≥5 points MDS-UPDRS Part III) motor score from baseline to Week 52 Cumulative Fre
Slide 72: PASADENA Phase 2: Improvement in Cerebral Blood Flow in the Putamen
PASADENA Phase 2 IMPROVEMENT IN CEREBRAL BLOOD FLOW IN THE PUTAMEN Placebo Prasinezumab* 50 Baseline Exploratory Week 52 endpoint: change in cerebral blood flow in the brain 20 regions from N=2 N=4 baseline to Week 2 7 52 (MRI-ASL) Images from a subset of all individuals treated with prasinezumab (L
Slide 73: Opportunity to Detect Treatment Effect is Increased in Fast-Progressing Individuals
Opportunity to Detect Treatment Effect is Increased in Fast-Progressing Individuals Sub-phenotype progression in PPMI population1 In the PASADENA study population, the following subgroups* were defined for further analyses: Mild motor Diffuse malignant (n=59) Intermediate predominant Score on motor
Slide 74: Slowing of Clinical Decline More Evident in Faster Disease Progression
Slowing of Clinical Decline with Prasinezumab was More Evident in Individuals with Faster Disease Progression MDS-UPDRS Part III* Total population (N=316) MAO-B inhibitor treated (n=115) Diffuse malignant (n=59) Change at Week 52 (placebo) = 5.57 points Change at Week 52 (placebo) = 6.82 points Chan
Slide 75: Slowing of Clinical Decline More Evident in Digital Motor Measures
Slowing of Clinical Decline with Prasinezumab was More Evident in Individuals with Faster Progression in Digital Motor Measures PASADENA Digital Motor Score Total population (N=316) MAO-B inhibitor treated (n=115) Diffuse malignant (n=56) Pooled: –0.030, 80% CI=(–0.050, –0.010); –25.0% Pooled: –0.03
Slide 76: Summary of Effects of Prasinezumab in Preclinical Models of Synucleinopathy
Summary of Effects of Prasinezumab in Multiple Preclinical Models of Synucleinopathy Prasinezumab (murine form of 9E4) Lowering of Blockade of cell-to-cell demonstrated in multiple in vivo and a-Syn Pathology transmission cellular a-synucleinopathy models to:1–3 IgG1 PRX002 IgG1 PRX002 PRX002 ✓ Redu
Slide 77: Pharmacokinetic/Pharmacodynamic Framework
Pharmacokinetic/Pharmacodynamic Framework BOTH PHASE 2 DOSE LEVELS SATURATE THE TARGET Aggregated a- Syn occupancy by Monomeric prasinezumab (%) a-Syn a-Syn Elements determining > 400-fold target-occupancy in CNS selectivity Anticipated exposure in CSF for Low and • Relative concentrations of prasin
Slide 78: PASADENA Phase 2 Baseline Demographics
PASADENA Phase 2 Baseline Demographics PRESENTED AT AAT-AD/PD, APRIL 2020 Baseline data (1/2) 78
Slide 79: PASADENA Phase 2 Baseline Demographics
PASADENA Phase 2 Baseline Demographics PRESENTED AT AAT-AD/PD, APRIL 2020 Baseline data (2/2) 79
Slide 80: PASADENA Phase 2 Overview of Safety Data
PASADENA Phase 2 Overview of Safety Data PLACEBO LOW DOSE HIGH DOSE ALL PATIENTS (N=105) (N=105) (N=106) (N=316) Total number of AEs* 411 428 549 1388 Total number of AE with fatal outcome 0 0 0 0 (Grade 5)* Total number of patients with at least one (%): † AE 87 (82.9) 98 (93.3) 97 (91.5) 282 (89.2
Slide 81: NNC6019/PRX004 Supplemental Information
NNC6019/PRX004 Supplemental Information
Slide 82: Summary of Phase 1 Study Results
Summary of Phase 1 Study Results PRX004* IN ATTR AMYLOIDOSIS • First clinical results from a depleter mechanism of action in ATTR amyloidosis – 223 total doses administered through the end of the study – Patient received between 3 – 17 doses • All six dose levels of PRX004 found to be generally safe
Slide 83: Partnerships and Collaboration Details
Partnerships and Collaboration Details
Slide 84: Global Neuroscience R&D Collaboration with Bristol Myers Squibb
Global Neuroscience R&D Collaboration with Bristol Myers Squibb INCLUDES PRX005 (TAU), TDP-43 AND PRX019 Preclinical to Phase 1 Phase 2 to Commercial Prothena Leads and Funds BMS Leads and Funds Upfront US License Option Global License Regulatory and Commercial Equity Purchase Royalties Payment Paym
Slide 85: Worldwide Collaboration with Roche
Worldwide Collaboration with Roche Total Milestones $755M $-- ✓ Upfront, P1, P2 and P2b milestones 135M* -- Clinical, regulatory & first sale 290M -- U.S. sales milestones 155M -- Ex-U.S. sales milestones 175M – • Up to double digit • Leads clinical • U.S. teen royalties development • U.S. co-