Ptc Therapeutics, Inc. · NASDAQ:PTCT
Ptc Therapeutics — Investor Presentation (November 2021)
53 slides from Ptc Therapeutics's investor presentation, Nov 30, 2021
Slide 1: PTC 2021 Corporate Deck Updated Nov 30, 2021
PTC 2021 Corporate Deck Updated Nov 30, 2021
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 199 5. All statements contained in this release, other than statements of historic fact, are forward -looking statements, including statements with r
Slide 3: Translating Science to Transform Lives
Translating Science to Transform Lives 3
Slide 4: Significant Execution and Value Creation in 2020
Significant Execution and Value Creation in 2020 4 Clinical Regulatory Commercial Financial ✓ Initiated two potential registrational trials with vatiquinone in Mitochondrial Disease Associated Seizures & Friedreich ataxia ✓ Initiated Phase 1 trial of PTC518 in healthy volunteers for Huntington disea
Slide 5: Diversified Platform Drives Strong Portfolio
Diversified Platform Drives Strong Portfolio 5 Clinical Commercial Research Nonsense Mutation LatAm Commercial Deflazacort Gene Therapy Bio-e Metabolic Oncology US Ataluren PTC-AADC Emvododstat AML Unesbulin DIPG Unesbulin LMS Vatiquinone MDAS Vatiquinone FA PTC923 PKU Emvododstat COVID-19 SCA-3 Und
Slide 6: Enduring Innovation Engine
Enduring Innovation Engine 6
Slide 7: Diversified Platform Drives Strong Portfolio
Diversified Platform Drives Strong Portfolio 7 Clinical Commercial Research Nonsense Mutation LatAm Commercial Deflazacort Gene Therapy Bio-e Metabolic Oncology US Ataluren PTC-AADC Emvododstat AML Unesbulin DIPG Unesbulin LMS Vatiquinone MDAS Vatiquinone FA PTC923 PKU Emvododstat COVID-19 SCA-3 Und
Slide 8: 15-Lipoxygenase is a Key Regulator of Inflammation and Oxidative Stress Pathways in CNS Diseases
15-Lipoxygenase is a Key Regulator of Inflammation and Oxidative Stress Pathways in CNS Diseases Glial Cell Activation & Inflammation Oxidative Stress Mediated Membrane Damage 15-Lipoxygenase Alpha-synuclein Oxidation & Aggregation Glutathione Oxidation & Depletion 8 Lipid signaling molecule that re
Slide 9: 15-Lipoxygenase is a Key Regulator in Refractory Epilepsies
15-Lipoxygenase is a Key Regulator of Inflammation and Oxidative Stress Pathways in Refractory Epilepsies 9 O OH O OH O OH Polyunsaturated Fatty Acids Oxidized Fatty Acids Activated Enzyme 15-LO Oxidative stress activates enzyme e e e e ee e e ee e e e e e e e e e e e e e e e e e ee XX O2 - Diseased
Slide 10: Bio-e Platform is a Novel Approach to Treating Rare Disorders
O OH O OH Oxidized Fatty Acids Enzyme Polyunsaturated Fatty Acids O OH Bio-e Platform is a Novel Approach to Treating Rare Disorders Polyunsaturated Fatty Acids Oxidized Fatty Acids Activated Enzyme Oxidative stress cellular viability & neurological function inflammation & oxidative stress decreased
Slide 11: Bio-e Platform is a Novel Approach to Treating Rare Disorders
Enzyme Polyunsaturated Fatty Acids O OH Bio-e Platform is a Novel Approach to Treating Rare Disorders Polyunsaturated Fatty Acids Oxidized Fatty Acids Activated Enzyme Oxidative stress Inhibited 11 PTC Compounds O O HO • Bio-e platform targets a family of oxidoreductase enzymes critical to generatio
Slide 12: MIT-E: Registrational trial of vatiquinone for Mitochondrial Disease Associated Seizures
12 MIT-E: Registrational trial of vatiquinone for Mitochondrial Disease Associated Seizures
Slide 13: Mitochondrial Disease Associated Seizures is a Highly Morbid Disorder with High Unmet Medical Need
Mitochondrial Disease Associated Seizures is a Highly Morbid Disorder with High Unmet Medical Need Disease • Mitochondrial disease associated seizures is the highly morbid condition of refractory seizures in patients with inherited mitochondrial disease Current Treatments • No approved disease modif
Slide 14: Vatiquinone Reduced Seizure Frequency and Improved Neurological Function
Vatiquinone Reduced Seizure Frequency and Improved Neurological Function in Mitochondrial Disease Associated Seizures Patients 14 Disruption of refractory status epilepticus Reduction in seizure frequency Decrease in seizure-related hospitalizations Decrease in disease-related mortality risk Data fr
Slide 15: Vatiquinone Potential for Clinically Differentiated Improvement in Seizures
Vatiquinone has Potential to Show Clinically Differentiated Improvement for Mitochondrial Disease Associated Seizures Patients 15 Primary Endpoint Change from baseline in frequency of observable motor seizures PTC743 (vatiquinone) Placebo N = 30 (planned) 24 weeks R N = 30 (planned) 48 weeks PTC743
Slide 16: MOVE-FA: Registrational trial of vatiquinone for Friedreich Ataxia
16 MOVE-FA: Registrational trial of vatiquinone for Friedreich Ataxia
Slide 17: Friedreich Ataxia is a Highly Morbid, Neuromuscular Disorder with no Approved Therapy
Friedreich Ataxia is a Highly Morbid, Neuromuscular Disorder with no Approved Therapy Disease • Friedreich ataxia (FA) is a rare, inherited, progressive disease resulting from mitochondrial dysfunction that mainly affects the central nervous system and the heart Current Treatments • No approved dis
Slide 18: Vatiquinone Demonstrated Significant Improvement in Friedreich Ataxia Patients
Vatiquinone Demonstrated Significant Improvement in Long-term Disease Severity & Neurological Function in Friedreich Ataxia Patients Clinical Study Summary • Double-blind, placebo-controlled with delayed start • N=63 subjects • Three US clinical sites • Key endpoint: FA disease rating scale (FARS) 1
Slide 19: Vatiquinone has the Potential to Provide Improvement in Neurological Function
Vatiquinone has the Potential to Provide Improvement in Neurological Function 19 Primary and Key Secondary Endpoints Change from baseline in the Modified FA Rating Scale (mFARS) Score at Week 72 Improvement in activities of daily living (FA-ADL) Open-Label Extension Placebo-Controlled PTC743 (vatiqu
Slide 20: Diversified Platform Drives Strong Portfolio
Diversified Platform Drives Strong Portfolio 20 Clinical Commercial Research Nonsense Mutation LatAm Commercial Deflazacort Gene Therapy Bio-e Metabolic Oncology US Ataluren PTC-AADC Emvododstat AML Unesbulin DIPG Unesbulin LMS Vatiquinone MDAS Vatiquinone FA PTC923 PKU Emvododstat COVID-19 SCA-3 Un
Slide 21: APHENITY: Registrational trial of PTC923 for Phenylketonuria (PKU)
21 APHENITY: Registrational trial of PTC923 for Phenylketonuria (PKU)
Slide 22: Phenylketonuria is a Serious Metabolic Condition with High Unmet Medical Need
Phenylketonuria is a Serious Metabolic Condition with High Unmet Medical Need ~58,000 Global prevalence Disease • Phenylketonuria is a metabolic condition caused by mutations to phenylalanine hydroxylase that can lead to cognitive disabilities and seizures Current Treatments • Majority of patients d
Slide 23: Majority of PKU Patients not Addressed by Current Therapies
Majority of PKU Patients not Addressed by Current Therapies 23 ~ 25-30% of diagnosed patients ~60-75% of diagnosed patients Up to 70% of Kuvan Failure Up to 60% of Initial Responders Are Poorly controlled on Kuvan Up to 30% of diagnosed patients
Slide 24: PTC923 Demonstrated Significant Phe Reduction Compared to Kuvan in Phase 2
PTC923 Demonstrated Statistically Significant Differences in Reduction of Phenylalanine (Phe) Compared to Kuvan in Phase 2 Study 24 p< 0.0001
Slide 25: APHENITY is a Global Registrational Trial of PTC923 for Phenylketonuria
APHENITY is a Global Registrational Trial of PTC923 for Phenylketonuria 25 R PTC923 Placebo Primary Endpoint Reduction in blood of phenylalanine levels 42 Days ~12 sites in 15-19 countries Open-Label Extension Placebo-Controlled PTC923 12 Months Primary Endpoint Trial Status • Initiated in 3Q 2021 •
Slide 26: Diversified Platform Drives Strong Portfolio
Diversified Platform Drives Strong Portfolio 26 Clinical Commercial Research Nonsense Mutation LatAm Commercial Deflazacort Gene Therapy Bio-e Metabolic Oncology US Ataluren PTC-AADC Emvododstat AML Unesbulin DIPG Unesbulin LMS Vatiquinone MDAS Vatiquinone FA PTC923 PKU Emvododstat COVID-19 SCA-3 Un
Slide 27: PTC518: Program for Huntington Disease
27 PTC518: Program for Huntington Disease
Slide 28: Huntington Disease is a Debilitating Neurological Disorder with No Available Disease Modifying Treatments
Huntington Disease is a Debilitating Neurological Disorder with No Available Disease Modifying Treatments Disease • Huntington disease is a progressive brain disorder that causes uncontrolled movements and cognitive loss Current Treatments • No approved disease modifying therapies Opportunity • PTC5
Slide 29: Small Molecules Have a Critical Advantage for Pan Brain Distribution
Small Molecules Have a Critical Advantage for Pan Brain Distribution 29 HD Healthy Goh et al. Aus Psychiatry. 2018
Slide 30: Identification of a Novel Approach to Lower HTT
Identification of a Novel Approach to Lower HTT 30 HTT patient Ex 1 Ex Y Ex X Favored mRNA Ex 1 Ex Y Ex X Leads to toxic HTT protein (CAG)>35
Slide 31: Identification of a Novel Approach to Lower HTT
Identification of a Novel Approach to Lower HTT 31 HTT patient Ex 1 Ex Y Ex X Favored mRNA Ex 1 Ex Y Ex X Leads to toxic HTT protein (CAG)>35 Degraded through translation-linked mRNA decay Ex 1 Ex Y Ex X Mutant toxic HTT protein lowering Ex 1 Ex Y Ex X (CAG)>35 Small molecule assisted exon definitio
Slide 32: PTC518 Has Broad Tissue Distribution with Strong Correlation between Brain and Blood
PTC518 Has Broad Tissue Distribution with Strong Correlation between Brain and Blood 32 120 100 80 60 40 20 0 Vehicle 1 3 7 21 63 Brain % HTT Remaining Dose dependent HTT lowering in the brain in BACHD mice Brain and blood HTT lowering Dose (mg/kg) *Data on file from multiple studies Measurements de
Slide 33: The Phase 1 Trial is a 4-Part Study
The Phase 1 Trial is a 4-Part Study 33 Phase 1 trial in healthy volunteers is ongoing Multiple ascending dose • Up to 5 cohorts of 8 healthy volunteers (6 active and 2 placebo) • Evaluate safety & tolerability; HTT mRNA splicing & protein lowering Food effect • Evaluate the effects of food on PTC518
Slide 34: SAD Study: Proof of Mechanism of PTC518 Demonstrated By Dose-Dependent HTT Splicing
34 SAD Study: Proof of Mechanism of PTC518 Demonstrated By Dose-Dependent HTT Splicing Placebo PTC518_45 m g PTC518_90 m g PTC518_135 m g 0 20 40 60 80 100 120 % o f b a s e l i n e H T T R N A ➢ Whole blood HTT splicing in humans ➢ Doses evaluated = 45 mg, 90 mg, and 135 mg ➢ Time – one day; single
Slide 35: MAD Study: Proof of Mechanism of PTC518 Confirmed By Dose-Dependent HTT Splicing
35 MAD Study: Proof of Mechanism of PTC518 Confirmed By Dose-Dependent HTT Splicing ➢ Whole blood HTT splicing in humans ➢ Doses evaluated = 15 mg and 30 mg ➢ Time – Day 14; multiple doses; splicing evaluated 6h post dose on day 14 Placebo PTC518_15 m g PTC518_30 m g 0 20 40 60 80 100 120 % o f b a
Slide 36: Diversified Platform Drives Strong Portfolio
Diversified Platform Drives Strong Portfolio 36 Clinical Commercial Research Nonsense Mutation LatAm Commercial Deflazacort Gene Therapy Bio-e Metabolic Oncology US Ataluren PTC-AADC Emvododstat AML Unesbulin DIPG Unesbulin LMS Vatiquinone MDAS Vatiquinone FA PTC923 PKU Emvododstat COVID-19 SCA-3 Un
Slide 37: Treating Rare Monogenic Disorders with Targeted Gene Therapy
Treating Rare Monogenic Disorders with Targeted Gene Therapy 37 Potential advantages of targeted therapy • Local administration lowers systemic immunogenicity and exposure • Low turnover cells may lead to improved durability • Leveraging stereotactic neurosurgery technologies to enable precise and a
Slide 38: Gene Therapy Has the Potential to Provide Significant Benefit to AADC Patients
Gene Therapy Has the Potential to Provide Significant Benefit to AADC Patients Disease • Aromatic L-amino acid decarboxylase deficiency (AADC-d) is a rare highly morbid and fatal childhood disease. Children with severe AADC deficiency never achieve motor development milestones Current Treatments • N
Slide 39: PTC-AADC Treated Patients Make Significant and Sustainable Progress
PTC-AADC Treated Patients Make Significant and Sustainable Progress 39 Age 2 Age 3 Age 4.5 Untreated Post-Treatment
Slide 40: Preparing for PTC's First Gene Therapy Launch
Preparing for PTC’s First Gene Therapy Launch 40 US Regulatory PTC-AADC BLA submission expected in 1Q22 Treatment Centers Identification and preparation of expert pediatric neurosurgical centers Patient Finding Ongoing patient finding targeting 300 patients identified at launch EU Regulatory The CHM
Slide 41: Providing Patients Access to Transformative Treatments
Providing Patients Access to Transformative Treatments 41
Slide 42: Global Geographic Presence Supports Growing Product Portfolio
Global Geographic Presence Supports Growing Product Portfolio 42 >1,000 employees Offices in 20 countries Footprint in >50 countries
Slide 43: DMD Commercial Franchise – A Growing Global Business
DMD Commercial Franchise – A Growing Global Business 43
Slide 44: DMD Commercial Franchise – A Growing Global Business
DMD Commercial Franchise – A Growing Global Business 44 • YE 2020 net product revenue of $192M • Treatment for nonsense mutation DMD for ages 2 and older • Distributed in over 50 countries worldwide • Data from Study 041 expected 3Q22
Slide 45: DMD Commercial Franchise – A Growing Global Business
DMD Commercial Franchise – A Growing Global Business 45 • YE 2020 net product revenue of $192M • Treatment for nonsense mutation DMD for ages 2 and older • Distributed in over 50 countries worldwide • Data from Study 041 expected 3Q22 • YE 2020 net product revenue of $139M • First and only corticost
Slide 46: Continued Strong DMD Franchise Growth
Continued Strong DMD Franchise Growth USD millions 34 81 145 171 190 29 92 101 2019 2020 2017 2015 2016 2018 263 174 331 +58% 291 Emflaza Net Sales Translarna Net Sales 139 192 46
Slide 47: Evrysdi's Strong Global Launch Brings Therapy to SMA Patients
Evrysdi’s Strong Global Launch Brings Therapy to SMA Patients with High Unmet Need 47 Patients treated across all SMA types Patients are treatment-naïve or switching from both Spinraza and Zolgensma Broadest range of age treated Differentiated product for SMA patients • The first at-home, oral treat
Slide 48: Multiple Platforms Provide Opportunity to Treat Over 500,000 Patients by 2030
Multiple Platforms Provide Opportunity to Treat Over 500,000 Patients by 2030 48 DMD SMA AADC ~50K ME ~20K PKU ~58K FA ~25K HD ~135K GBA-PD ~190K AS ~75K 2021 2030 AADC
Slide 49: Strong Financial Performance Supports Future Growth
Strong Financial Performance Supports Future Growth 49 Net Product Revenue $333M DMD Franchise Net Product Net Revenue $331M $1.1B Year-end Cash Position 2020
Slide 50: Strong Financial Performance Supports Future Growth
Strong Financial Performance Supports Future Growth 50 DMD Franchise Net Product Revenue Guidance $400-420M OPEX Guidance* $715-735M Net Product Revenue $333M DMD Franchise Net Product Net Revenue $331M 2020 2021 $1.1B Year-end Cash Position *Non-GAAP measure which excludes estimated non-cash, stock
Slide 51: 2021 Potential Milestones to Generate Value
2021 Potential Milestones to Generate Value 51 PTC857 Data PTC518 Data Evrysdi CHMP Opinion PTC518 Phase 2 Study Initiation Unesbulin LMS and DIPG Data PTC923 PKU P3 Trial Emvododstat COVID-19 Enrollment Complete 1H 2021 2H 2021
Slide 52: PTC has Built a Strong, Sustainable Company to Execute on our Mission
PTC has Built a Strong, Sustainable Company to Execute on our Mission 52 Proven groundbreaking science Enduring innovation engine Providing patients access to transformative treatments Culture Operational Excellence
Slide 53: Translating Science to Transform Lives
Translating Science to Transform Lives 53
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