Ptc Therapeutics, Inc. · NASDAQ:PTCT
Ptc Therapeutics — Investor Day (July 2023)
58 slides from Ptc Therapeutics's investor day presentation, Jul 19, 2023
Slide 1: PTC Therapeutics PKU Deep Dive
PTC Therapeutics PKU Deep Dive July 19, 2023 Patient Living with PKU
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 1995. All statements contained in this presentation, other than statements of historic fact, are forward-looking statements, including statements wit
Slide 3: Presenters
Presenters Matt Klein Ania Muntau Kylie O’Keefe Chief Executive Officer, Professor of Pediatrics, Chair, Chief Commercial Officer, PTC Therapeutics University Children's Hospital, PTC Therapeutics University Medical Center, Hamburg Eppendorf, Germany 3 PKU Presentation
Slide 4: Agenda
Agenda 1 Overview of PTC and Sepiapterin 2 Clinical Practice in PKU 3 Commercial Landscape for Sepiapterin 4 PKU Presentation
Slide 5: Continued Success Across Our Commercial Portfolio
Continued Success Across Our Commercial Portfolio Distributed in First and only Established market First EMA-approved For treatment of hATTR For treatment 50+ countries with corticosteroid for all US leadership in all major disease-modifying with LATAM patients of FCS and FPL, with continued growth
Slide 6: Strong Commercial Revenue Guidance for 2023
Strong Commercial Revenue Guidance for 2023 $940M-$1B $395 - $435M Other $545 - $565M DMD 6 PKU Presentation
Slide 7: Substantial Pipeline Progress Expected in H2 2023
Substantial Pipeline Progress Expected in H2 2023 Clinical Trials Regulatory Activities* Upstaza BLA Translarna CHMP Translarna FDA Vatiquinone FA FDA Sepiapterin NDA Submission Type II Variation Type C Meeting Type C Meeting Submission Q3 Opinion H2 H2 Q4 Q3 7 PKU Presentation
Slide 8: APHENITY Topline Results
APHENITY Topline Results 8 PKU Presentation
Slide 9: APHENITY Topline Results Demonstrate Clinical and Statistically Significant Benefit
APHENITY Topline Results Demonstrate Clinical and Statistically Significant Benefit Demonstrated substantial Achieved primary endpoint in Phe reduction in both the placebo-controlled portion of overall primary analysis study with statistically population (63%) and the significant (p<0.0001) blood su
Slide 10: Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction
Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction Mean % Blood Phe Reduction Overall Primary Analysis Population Classical PKU Patients 1 Placebo 2 1 2 N=49 N=49 N=6 N=9 10 10 1% 3% 0 0 Mean % Blood Phe Mean % Blood Phe -10 -10 Reduction Reduction -20 -20 -30 -30 -40 -40 4
Slide 11: Vast Majority of Patients Achieved Guidelines Target Blood Phe Levels
Vast Majority of Patients Achieved Guidelines Target Blood Phe Levels US guidelines: all ages EU guidelines: ≥12 years of age EU guidelines: <12 years of age 84% 93% Achieved Achieved <360µmol/L <600µmol/L Blood Phe Blood Phe 11 PKU Presentation
Slide 12: Sepiapterin Part 1 Treatment Effect in Patients Receiving Sapropterin at Study Entry
Sepiapterin Part 1 Treatment Effect in Patients Receiving Sapropterin at Study Entry (N=27 patients) 800 700 Mean Blood Phe (µmol/L) 48% 600 500 400 lower Phe levels following sepiapterin 300 Guideline treatment in those Target 200 patients receiving sapropterin at study 100 entry 0 Mean blood Phe o
Slide 13: Initial Phe Tolerance Data in Open-Label Extension
Initial Phe Tolerance Data in Open-Label Extension Increase in Dietary Phe Intake Blood Phe Levels 140 300 120 Prescribed Phe Consumption 250 100 Mean Blood Phe (mg/kg/day) 200 80 (µmol/L) 60 150 40 Adult recommended Phe intake 100 20 0 50 1 2 3 4 5 6 7 8 9 10 11 12 0 1 2 3 4 5 6 7 8 (N=12) (N=4) (N
Slide 14: Agenda
Agenda 1 Overview of PTC and Sepiapterin 2 Clinical Practice in PKU 3 Commercial Landscape for Sepiapterin 14 PKU Presentation
Slide 15: Overview of Phenylketonuria (PKU)
Overview of Phenylketonuria (PKU) PKU is an inherited, autosomal Variants in PAH, the gene that Both environment (dietary recessive condition1 encodes PAH, lead to impaired intake of Phe) and genotype PAH function and cause PKU 1 are causal components of PKU More than 1,000 variants in the human PAH
Slide 16: The Role of PAH in Phe Metabolic Pathway
The Role of PAH in Phe Metabolic Pathway Phenylalanine Hydroxylating System2 GTP PAH catalyzes the first and rate- GTPCH PTPS SR limiting step in the metabolic pathway O2 of Phe, conversion of Phe to Tyr1 NAD+ BH4 Phenylalanine BH4 corrects misfolding and early degradation of PAH and by this DHPR im
Slide 17: Elevated Blood Phe Interferes With Normal Production of Neurotransmitters and Leads to PKU
Elevated Blood Phe Interferes With Normal Production of Neurotransmitters and Leads to PKU Excessive Phe Impact White matter lesion and Formation of amyloid-like reduced myelin production Phe aggregates Elevated blood Phe level and accumulation of Phe in Reduced cerebral glucose Alteration of methyl
Slide 18: PKU Severity Is Associated With Higher Blood Phe Levels and Decreasing Phe Tolerance
PKU Severity Is Associated With Higher Blood Phe Levels and Decreasing Phe Tolerance Normal Mild HPA Mild/Moderate PKU Severe PKU PAH variants Complete associated Normal PAH function Partially inhibited PAH function to near-complete loss with loss of of PAH function PAH function • Patients with PKU
Slide 19: PKU Management Guidelines
PKU Management Guidelines ACMG (US) TREATMENT GUIDELINES1 EU TREATMENT GUIDELINES 2 The treatment of PKU should be initiated as No intervention is required if the blood phenylalanine concentration is less early as possible. than 360 μmol/L. Treatment is recommended up to the age of 12 years if the p
Slide 20: Lifelong Diet Restrictions Remain a Key Requirement for PKU Patients
Lifelong Diet Restrictions Remain a Key Requirement for PKU Patients Types of Barriers to Dietary Treatment Long-Term Continuation Low-protein diet Palatability, lack of variety of PKU diet Prohibitive costs of medicinal foods Phe-free medicinal foods Risk of malnutrition Modified low-protein produc
Slide 21: Diet Restrictions Alone Result in Suboptimal Outcomes
Diet Restrictions Alone Result in Suboptimal Outcomes Suboptimal Outcomes in PKU Treated With Dietary Treatment Alone Despite early and continuous management of diet alone, PKU patients Children and Adolescents Adults may experience cognitive symptoms as • Poor academic performance • Depressed mood
Slide 22: Two Main Goals of Therapy for PKU Patients
Two Main Goals of Therapy for PKU Patients Decreased Blood Increased Dietary Phe Levels Protein Intake (Phe Tolerance) 22 PKU Presentation
Slide 23: Clinician-Reported Challenges With Two Currently Approved Treatments for PKU
Clinician-Reported Challenges With Two Currently Approved Treatments for PKU Indication: Adults who have uncontrolled blood Phe Indication: For adult and pediatric patients ≥1 month (>600 µmol/L) on existing management Clinician Reported Challenges Clinician Reported Challenges1,2 • Sapropterin has
Slide 24: Mechanistic Advantages of Sepiapterin Over Sapropterin
Mechanistic Advantages of Sepiapterin Over Sapropterin GI Tract Plasma Intracellular (liver, brain, kidney) Kidney Clearance Tetrahydrobiopterin (BH4) Synthetic BH4 Co-Factor Therapies (Kuvan® or BH4 Cell Membrane Inefficient sapropterin) Oxidation Cross-Membrane BH2 Active Transport 7.8-Dihydrobiop
Slide 25: Additive Effects of Sepiapterin
Additive Effects of Sepiapterin Sepiapterin is actively transported to misfolded variant PAH tetramers inside a cell and converted to BH4 in pharmacologic concentrations SP SP BH4 Sepiapterin (SP) Tetrahydrobiopterin (BH4) Misfolded PAH Functional PAH 25 PKU Presentation
Slide 26: Additive Effects of Sepiapterin
Additive Effects of Sepiapterin Sepiapterin and BH4 act as pharmacological chaperones by binding to variant PAH, correcting the conformational structure of the tetramer and promoting metabolism of Phe to Tyr SP Sepiapterin (SP) Tetrahydrobiopterin (BH4) Misfolded PAH Functional PAH 26 PKU Presentati
Slide 27: Additive Effects of Sepiapterin
Additive Effects of Sepiapterin SP Sepiapterin (SP) Tetrahydrobiopterin (BH4) Misfolded PAH Functional PAH 27 PKU Presentation
Slide 28: Potential for Sepiapterin to Address Majority of PKU Patients
Potential for Sepiapterin to Address Majority of PKU Patients Sepiapterin Patient Segments Therapy-Naive Patients Who Patients Who Are Patients Including Have Failed on Not Well Controlled Classical PKU Current Therapies 28 PKU Presentation
Slide 29: Unmet Need Remains in PKU That Can Potentially Be Addressed by Sepiapterin
Unmet Need Remains in PKU That Can Potentially Be Addressed by Sepiapterin PKU leads to a toxic accumulation of Phe in the brain and must be treated from birth Current therapies are not suitable for all PKU patients, and a large unmet need remains Sepiapterin has potential advantages over both sapro
Slide 30: Agenda
Agenda 1 Overview of PTC and Sepiapterin 2 Clinical Practice in PKU 3 Commercial Landscape for Sepiapterin 30 PKU Presentation
Slide 31: Unmet Need in PKU
Unmet Need in PKU 31 PKU Presentation
Slide 32: Large Unmet Need Remains in PKU
Large Unmet Need Remains in PKU Up to 70% 70% fail tried Kuvan Less than 58,000 patients globally ~30% 40% well controlled 10% of patients are 60% poorly well-controlled respond controlled on Kuvan 30% therapy naïve including classical PKU 32 PKU Presentation 1. BioMarin first quarter 2021 presentat
Slide 33: The PKU Patient Journey Begins at Birth and Continues Throughout Life
The PKU Patient Journey Begins at Birth and Continues Throughout Life Geneticist/Pediatric Metabolic Specialist & Dietitian Life-long Protein Restriction, Medical Foods & Formulas Newborn Screening Social Isolation, Anxiety, Depression, Fatigue 33 PKU Presentation
Slide 34: Key Issues in PKU Management
Key Issues in PKU Management The majority of PKU patients A large majority of PKU The consequences of lack of on diet alone do not achieve patients are not well-controlled effective Phe control can be effective Phe control by early on any approved treatment or devastating to the quality of adulthood
Slide 35: Two Main Goals of Therapy for PKU Patients
Two Main Goals of Therapy for PKU Patients Decreased Blood Increased Dietary Levels Phe Levels Phe Protein Intake (Phe Tolerance) 35 PKU Presentation
Slide 36: Significant Correlation Between Blood Phe Level and IQ
Significant Correlation Between Blood Phe Level and IQ Correlations between Phe level Each 100 µmol/l and intelligence quotient (IQ) increase in Phe predicted a were extracted from 40 studies and confirmed a significant correlation between blood Phe level and IQ1 1.9 to 4.1 point reduction in IQ 36
Slide 37: Two Main Goals of Therapy for PKU Patients
Two Main Goals of Therapy for PKU Patients Decreased Blood Increased Dietary Protein Dietary Levels Phe Protein Increase Intake (Phe Tolerance) 37 PKU Presentation
Slide 38: Keeping a Strict Diet Is the Largest Burden and Makes Patients Constantly Feel Frustrated
Keeping a Strict Diet Is the Largest Burden and Makes Patients Constantly Feel Frustrated and Extremely Limited Controlled Stressed Limited Patients were asked their current feelings about their dietary restrictions • Patients currently feel limited, frustrated, and Frustrated anxious regarding thei
Slide 39: Diet for Non PKU Patient Diet for PKU Patient
Diet for Non PKU Patient Diet for PKU Patient Breakfast 2 eggs scrambled with cheese = 18g 2 pieces of bacon = 6g ½ cup breakfast potatoes = 2.3g Lunch turkey wrap = 24g Lays potato chips = 2g chocolate chip cookie = 1.5g Diet Coke = 0g Dinner grilled chicken = 55g ½ cup broccoli =
Slide 40: The Burden of a PKU Diet is Substantial
The Burden of a PKU Diet is Substantial Avoid all high Limited natural protein: Very low protein protein foods under 10g/day foods allowed What is in 5-10g of protein a day? Some fruit and veg Special low protein prescription foods 2g of protein 1-2g of protein 6g of protein Protein substitute – mus
Slide 41: Patient Perspective
Patient Perspective 41 PKU Presentation
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Slide 43: Patients Want a Treatment That Allows Them to Liberalize Their Diet
Patients Want a Treatment That Allows Them to Liberalize Their Diet While Decreasing the Inconveniences of Some Side Effects Efficacy Safety Ease of Use • Patients want a treatment that will • Patients are concerned about • Patients mentioned that ease of use reduce the Phe levels significantly pote
Slide 44: Physician Perspective
Physician Perspective 44 PKU Presentation
Slide 45: The Clinician Perspective
The Clinician Perspective 45
Slide 46: Blood Phe Reduction and Phe Tolerance Are the Most Important Drivers for HCPs
Blood Phe Reduction and Phe Tolerance Are the Most Important Drivers for HCPs Blood Phe Reduction Phe Tolerance Quality of Life The goal of PKU treatment is Physicians place high to get patient’s Phe levels into importance on Phe tolerance a target range (120-360µM/L) due to issues with outcomes fro
Slide 47: Physicians Expect 30%-50% Phe Reduction from Baseline for a First-Line PKU Therapy
Physicians Expect 30%-50% Phe Reduction from Baseline for a First-Line PKU Therapy 0% 10% 20% 30% 40% 50% 60% 70% 80% Percent Change of Phe Reduction from Baseline Response Rate Minimum Value Ideal Value APHENITY Topline Results 47 PKU Presentation TRINITY US Qualitative Interviews (N=20 HCPs; N=10
Slide 48: Commercial Launch Strategy
Commercial Launch Strategy 48 PKU Presentation
Slide 49: APHENITY Results Support Potential for Sepiapterin to Address Majority of PKU Segments
APHENITY Results Support Potential for Sepiapterin to Address Majority of PKU Segments Sepiapterin Addressable Population Therapy-Naive Patients Who Patients Who Are Patients Including Have Failed on Not Well Controlled Classical PKU Current Therapies ~15-30% Target PKU Patients 49 PKU Presentation
Slide 50: Commercial Pillars for Success Already Established
Commercial Pillars for Success Already Established Newborn Well-known Disease pathology Connected and screening with metabolic centers well understood coordinated ~58,000 patients of excellence and documented patient advocacy worldwide1,2,3 worldwide community 50 PKU Presentation 1. NPKUA; https://w
Slide 51: PTC Global Commercial Infrastructure Will Allow for Rapid Worldwide Launch
PTC Global Commercial Infrastructure Will Allow for Rapid Worldwide Launch EAP/ Access & Reimbursement Patient Dedicated Support Customer Facing Teams KOL/ Payor PAG Relationships Relationships Plug and Play in PKU 51 PKU Presentation
Slide 52: Understanding the Cross-Functional Team at PKU Clinics
Understanding the Cross-Functional Team at PKU Clinics Neurologists Dietitian Geneticist Patients Pediatric Metabolic Specialist Nurse Practitioners Endocrinologist 52 PKU Presentation
Slide 53: We Have a Deep Understanding of US PKU Treaters and How to Reach Them
We Have a Deep Understanding of US PKU Treaters and How to Reach Them ~500 HCPs ~150 HCPs For each US HCP we have visibility into: Kuvan Writers Palynziq Writers • First/Last Name Treating ~3,000 PKU patients Treating ~1,000 PKU patients • Provider taxonomies and demographics Other Specialties Psych
Slide 54: Initial Areas for New Treatment Consideration Have Been Identified
Initial Areas for New Treatment Consideration Have Been Identified Real-world data reveals a valuable opportunity among clinicians with lapsed Kuvan & Palynziq users 1 HCPs ~60 HCPs 6 HCPs 3 HCPs 5 HCPs 1 HCPs 2 HCPs 3 HCPs 1 HCPs 2 HCPs 1 HCPs 2 HCPs Kuvan and/or Palynziq 3 HCPs 1 HCPs 2 HCPs 5 HCP
Slide 55: Key Professional Associations & Patient Advocacy Groups
Key Professional Associations & Patient Advocacy Groups Scientific Medical Associations: Dietitian/Nutritionist Associations: Patient Advocacy Groups: 55 PKU Presentation
Slide 56: Setting the Launch Strategy for an Effective PKU Treatment That Works for More Patients
Setting the Launch Strategy for an Effective PKU Treatment That Works for More Patients Build Confidence Establish Differentiation Ensuring Access in the efficacy and through the clinical to the broadest range of safety of sepiapterin at body of evidence PKU patients launch • Amplify strong clinical
Slide 57: APHENITY Results Support Next Steps in the Regulatory Process and Commercial Planning
APHENITY Results Support Next Steps in the Regulatory Process and Commercial Planning Pre-Submission Regulatory Initiate Launch Meetings Submissions Preparation 57 PKU Presentation
Slide 58: PTC Therapeutics PKU Deep Dive
PTC Therapeutics PKU Deep Dive July 19, 2023 Patient Living with PKU