Ptc Therapeutics, Inc. · NASDAQ:PTCT
Ptc Therapeutics — Investor Day (July 2023)
59 slides from Ptc Therapeutics's investor day presentation, Jul 19, 2023
Slide 1: PTC Therapeutics PKU Deep Dive
Patient Living with PKU July 19, 2023 PTC Therapeutics PKU Deep Dive
Slide 2: 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 with respect to (i) 2023 total
Slide 3: PKU Presentation Presenters
Matt Klein Chief Executive Officer, PTC Therapeutics Ania Muntau Professor of Pediatrics, Chair, University Children's Hospital, University Medical Center, Hamburg Eppendorf, Germany 3 Kylie O’Keefe Chief Commercial Officer, PTC Therapeutics PKU Presentation Presenters
Slide 4: Agenda
Agenda 4 PKU Presentation Commercial Landscape for Sepiapterin 2 Clinical Practice in PKU 3 1 Overview of PTC and Sepiapterin
Slide 5: Continued Success Across Our Commercial Portfolio
Continued Success Across Our Commercial Portfolio 5 PKU Presentation Distributed in 50+ countries with continued growth from new patients and geographic expansion First and only corticosteroid for all US DMD patients with growth from new patient starts and favorable access Established market leaders
Slide 6: Strong Commercial Revenue Guidance for 2023
Strong Commercial Revenue Guidance for 2023 $395 - $435M Other $545 - $565M DMD 6 PKU Presentation $940M-$1B
Slide 7: Substantial Pipeline Progress Expected in H2 2023
7 PKU Presentation Substantial Pipeline Progress Expected in H2 2023 Translarna FDA Type C Meeting H2 Upstaza BLA Submission Q3 Vatiquinone FA FDA Type C Meeting H2 Sepiapterin NDA Submission Q4 Translarna CHMP Type II Variation Opinion Q3 Clinical Trials Regulatory Activities*
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 Achieved primary endpoint in placebo-controlled portion of study with statistically significant (p<0.0001) blood phenylalanine (Phe) reduction Demonstrated substantial Phe reduction in both the overall primary analys
Slide 10: Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction
Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction -70 -60 -50 -40 -30 -20 -10 0 10 Sepiapterin Overall Primary Analysis Population Classical PKU Patients Mean % Blood Phe Reduction Mean % Blood Phe Reduction N=49 63% 586 464 1% N=49 -70 -60 -50 -40 -30 -20 -10 0 10 Sepiapt
Slide 11: Vast Majority of Patients Achieved Guidelines Target Blood Phe Levels
EU guidelines: ≥12 years of age Vast Majority of Patients Achieved Guidelines Target Blood Phe Levels 93% Achieved <600µmol/L Blood Phe US guidelines: all ages EU guidelines: <12 years of age 84% Achieved <360µmol/L Blood Phe 11 PKU Presentation
Slide 12: Treatment Effect in Patients Receiving Sapropterin at Study Entry
Sepiapterin Part 1 Treatment Effect in Patients Receiving Sapropterin at Study Entry 800 700 600 500 400 300 200 100 0 Mean Blood Phe (µmol/L) (N=27 patients) Mean blood Phe on sapropterin (µmol/L) at study entry Mean blood Phe (µmol/L) following 7-day washout Mean blood Phe (µmol/L) on sepiapterin
Slide 13: Initial Phe Tolerance Data in Open-Label Extension
0 20 40 60 80 100 120 140 M1 W1-W2 (BL) M2 W1-W2 M2 W3-W4 M3 W5-W6 M3 W7-W8 M4 W9-W10 M4 W11-W12 M5 W13-W14 M5 W15-W16 M6 W17-W18 M6 W19-W20 M7 W21-W22 Initial Phe Tolerance Data in Open-Label Extension Prescribed Phe Consumption (mg/kg/day) Adult recommended Phe intake (N=12) (N=4) 0 50 100 150 200
Slide 14: Agenda
Agenda 14 PKU Presentation Commercial Landscape for Sepiapterin 2 Clinical Practice in PKU 3 1 Overview of PTC and Sepiapterin
Slide 15: Overview of Phenylketonuria (PKU)
Overview of Phenylketonuria (PKU) 1. Blau N, et al. The Lancet. 2010;376:1417-1427. 2. Mitchell JJ, et al. Genet Med. 2011; 13:697-707. 3. Hillert, et al. The American Journal of Human Genetics 2020;107,1-17. 15 PKU Presentation Both environment (dietary intake of Phe) and genotype are causal compon
Slide 16: The Role of PAH in Phe Metabolic Pathway
The Role of PAH in Phe Metabolic Pathway Blau N, et al. 2010 Phenylalanine Hydroxylating System2 GTP GTPCH PTPS SR NAD+ DHPR NADH H2O PCD q-dihydrobiopterin 4a-hydroxy-BH4 Fe+2 O2 Tyrosine Phenylalanine BH4 LIVER PAH PAH catalyzes the first and rate-limiting step in the metabolic pathway of Phe, con
Slide 17: Elevated Blood Phe Interferes With Normal Production of Neurotransmitters
Elevated Blood Phe Interferes With Normal Production of Neurotransmitters and Leads to PKU 17 PKU Presentation Excessive Phe Impact Elevated blood Phe level and accumulation of Phe in the brain is toxic to the central nervous system and impairs neurological functions White matter lesion and reduced
Slide 18: PKU Severity Is Associated With Higher Blood Phe Levels
PKU Severity Is Associated With Higher Blood Phe Levels and Decreasing Phe Tolerance • Patients with PKU are intolerant of dietary intake of the essential amino acid Phe11 18 PKU Presentation Blood Phe level Normal Mild HPA Mild/Moderate PKU Severe PKU Dietary Phe tolerance 50–110 µmol/L 120–600 µmo
Slide 19: PKU Management Guidelines
PKU Management Guidelines ACMG (US) TREATMENT GUIDELINES1 EU TREATMENT GUIDELINES 2 The treatment of PKU should be initiated as early as possible. No intervention is required if the blood phenylalanine concentration is less 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
Types of Dietary Treatment Barriers to Long-Term Continuation Lifelong Diet Restrictions Remain a Key Requirement for PKU Patients Low-protein diet Phe-free medicinal foods Modified low-protein products Glycomacropeptide High concentration of LNAA Palatability, lack of variety of PKU diet Prohibitiv
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 may experience cognitive symptoms as well as emotional and behavioral problems Adults • Depressed mood • Generaliz
Slide 22: Two Main Goals of Therapy for PKU Patients
Two Main Goals of Therapy for PKU Patients 22 PKU Presentation Decreased Blood Phe Levels Increased Dietary Protein Intake (Phe Tolerance)
Slide 23: Clinician-Reported Challenges With Two Currently Approved Treatments for PKU
Clinician-Reported Challenges With Two Currently Approved Treatments for PKU 23 PKU Presentation Indication: For adult and pediatric patients ≥1 month Indication: Adults who have uncontrolled blood Phe (>600 µmol/L) on existing management Clinician Reported Challenges • Sapropterin has a limited res
Slide 24: Mechanistic Advantages of Sepiapterin Over Sapropterin
Mechanistic Advantages of Sepiapterin Over Sapropterin GI Tract Plasma Co-Factor Therapies Cell Membrane Intracellular (liver, brain, kidney) Synthetic Sepiapterin (PTC923) Rapid Cross-Membrane Active Transport Sepiapterin Sepiapterin reductase Oxidation Synthetic BH4 (Kuvan® or sapropterin) BH4 BH2
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 25 PKU Presentation SP SP BH4 Sepiapterin (SP) Tetrahydrobiopterin (BH4) Misfolded PAH Functional PAH
Slide 26: Additive Effects of Sepiapterin
Additive Effects of Sepiapterin 26 PKU Presentation 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 P
Slide 27: Additive Effects of Sepiapterin
Additive Effects of Sepiapterin 27 PKU Presentation SP Sepiapterin (SP) Tetrahydrobiopterin (BH4) Misfolded PAH Functional PAH
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 Including Classical PKU Patients Who Are Not Well Controlled Patients Who Have Failed on 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 Sepiapterin has potential advantages over both sapropterin and Palynziq and can potentially treat a broader range of PKU patients PKU leads to a toxic accumulation of Phe in the brain and must be treated from birth Current th
Slide 30: Agenda
Agenda 30 PKU Presentation Commercial Landscape for Sepiapterin 2 Clinical Practice in PKU 3 1 Overview of PTC and Sepiapterin
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 32 of patients are well-controlled on Kuvan Less than patients globally 58,000 10% 60% poorly controlled 40% well controlled Up to 70% fail ~30% respond PKU Presentation 1. BioMarin first quarter 2021 presentation 1Q 2021. 2. Third party reports prepared for PTC 30% t
Slide 33: The PKU Patient Journey Begins at Birth and Continues Throughout Life
The PKU Patient Journey Begins at Birth and Continues Throughout Life 33 PKU Presentation Newborn Screening Geneticist/Pediatric Metabolic Specialist & Dietitian Life-long Protein Restriction, Medical Foods & Formulas Social Isolation, Anxiety, Depression, Fatigue
Slide 34: Key Issues in PKU Management
Key Issues in PKU Management 34 PKU Presentation The consequences of lack of effective Phe control can be devastating to the quality of life for these patients and irreversible in terms of intellectual disability A large majority of PKU patients are not well-controlled on any approved treatment or c
Slide 35: Two Main Goals of Therapy for PKU Patients
Two Main Goals of Therapy for PKU Patients 35 PKU Presentation Decreased Blood Levels Phe Increased Dietary Protein Intake (Phe Tolerance) Decreased Blood Phe Levels
Slide 36: Significant Correlation Between Blood Phe Level and IQ
Significant Correlation Between Blood Phe Level and IQ 36 PKU Presentation 1 Waisbren et al. Mol Genet Metab (2007) Sep-Oct;92(1-2):63-70 Correlations between Phe level and intelligence quotient (IQ) were extracted from 40 studies and confirmed a significant correlation between blood Phe level and I
Slide 37: Two Main Goals of Therapy for PKU Patients
Two Main Goals of Therapy for PKU Patients 37 PKU Presentation Decreased Blood Levels Phe Dietary Protein Increase (Phe Tolerance) Increased Dietary Protein Intake (Phe Tolerance)
Slide 38: Keeping a Strict Diet Is the Largest Burden
Keeping a Strict Diet Is the Largest Burden and Makes Patients Constantly Feel Frustrated and Extremely Limited 38 TRINITY US Qualitative Interviews (N=20 HCPs; N=10 PKU Patients) Patients were asked their current feelings about their dietary restrictions • Patients currently feel limited, frustrate
Slide 39: Diet for Non PKU Patient vs 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 =1.25g § side salad = 2.2g § piece of bread wit
Slide 40: The Burden of a PKU Diet is Substantial
The Burden of a PKU Diet is Substantial 40 What is in 5-10g of protein a day? 2g of protein 1-2g of protein 6g of protein PKU Presentation Avoid all high protein foods Limited natural protein: under 10g/day Very low protein foods allowed Protein substitute – must be taken at least 3 times daily Spec
Slide 41: Patient Perspective
Patient Perspective 41 PKU Presentation
Slide 42: . . - ee aid
. x * . . - ee aid ‘ | Weeertbeaict lot of children and ~ myself included, like in teenage years tend to struggle with staying on diet. It can be alittle bit tricky ABIGAIL when you're trying to deal with peer pressure and just growing up inthe community where everyone’ 's different from you. You’ r
Slide 43: So that's why it’s really important
So that's why it’s really important when you're younger, when your brain is developing, to have such a strict SAM diet because that's when your brain is, is developing. And nowit's still important because when | have high blood levels, |have bad memory. My hands gst sh ky. Ih have brain fog.
Slide 44: 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 44 Decreasing Importance TRINITY US Qualitative Interviews (N=20 HCPs; N=10 PKU Patients) • Patients mentioned that ease of use includes route of administration, dosing option
Slide 45: Physician Perspective
Physician Perspective 45 PKU Presentation
Slide 46: Dr. Drago Bratkovic: Massive unmet need in PKU
\GOEZ There is very mucha massive unmet need in PKU. The diet onits own, whilst you can get good Phe levels with it, Dr. Drago Bratkovic takes a lot of work and we do need other therapies that are easier to undertake Head of Metabolic Unit and also maintain throughout the . “a lifespan of a patient.
Slide 47: Prof. Nicola Longo: Unmet need for PKU patients
‘6 There is an unmet need for PKU patients in finding some oral Prof. Nicola Longo medication that can really control better phenylalanine level to allow alittle bit more diet liberalisation. Having the capacity to eat normal food for them is very important and any step that we can take in this d di
Slide 48: 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 48 TRINITY US Qualitative Interviews (N=20 HCPs; N=10 PKU Patients) The goal of PKU treatment is to get patient’s Phe levels into a target range (120-360µM/L) Physicians place high importance on Phe tolerance due to issues
Slide 49: Physicians Expect 30%-50% Phe Reduction from Baseline
0% 10% 20% 30% 40% 50% 60% 70% 80% Physicians Expect 30%-50% Phe Reduction from Baseline for a First-Line PKU Therapy 49 Percent Change of Phe Reduction from Baseline Response Rate Minimum Value Ideal Value PKU Presentation TRINITY US Qualitative Interviews (N=20 HCPs; N=10 PKU Patients) (Data on Fi
Slide 50: Commercial Launch Strategy
Commercial Launch Strategy 50 PKU Presentation
Slide 51: APHENITY Results Support Potential for Sepiapterin to Address Majority of PKU Segments
APHENITY Results Support Potential for Sepiapterin to Address Majority of PKU Segments Therapy-Naive Patients Including Classical PKU Patients Who Are Not Well Controlled Patients Who Have Failed on Current Therapies 51 Sepiapterin Addressable Population PKU Presentation ~15-30% Target PKU Patients
Slide 52: Commercial Pillars for Success Already Established
Commercial Pillars for Success Already Established Newborn screening with ~58,000 patients worldwide1,2,3 Well-known metabolic centers of excellence worldwide Connected and coordinated patient advocacy community Disease pathology well understood and documented 52 PKU Presentation 1. NPKUA; https://w
Slide 53: PTC Global Commercial Infrastructure Will Allow for Rapid Worldwide Launch
PTC Global Commercial Infrastructure Will Allow for Rapid Worldwide Launch KOL/ Payor Relationships PAG Relationships Patient Support Dedicated Customer Facing Teams EAP/ Access & Reimbursement Plug and Play in PKU 53 PKU Presentation
Slide 54: Understanding the Cross-Functional Team at PKU Clinics
Understanding the Cross-Functional Team at PKU Clinics 54 Patients Dietitian Geneticist Pediatric Metabolic Specialist Nurse Practitioners Endocrinologist Neurologists PKU Presentation
Slide 55: 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 55 For each US HCP we have visibility into: • First/Last Name • Provider taxonomies and demographics • Affiliation Hierarchy • Institutional vs Professional claim types, with differentiation of treatment settings • Line-item charg
Slide 56: Initial Areas for New Treatment Consideration Have Been Identified
Initial Areas for New Treatment Consideration Have Been Identified 56 ~60 HCPs Kuvan and/or Palynziq Writers With Lapsed Patients Real-world data reveals a valuable opportunity among clinicians with lapsed Kuvan & Palynziq users Patients per Zip 1 4 Lapsed Kuvan Patients Lapsed Palynziq Patients Pre
Slide 57: Key Professional Associations & Patient Advocacy Groups
Key Professional Associations & Patient Advocacy Groups Scientific Medical Associations: Dietitian/Nutritionist Associations: Patient Advocacy Groups: 57 PKU Presentation
Slide 58: Setting the Launch Strategy for an Effective PKU Treatment
Setting the Launch Strategy for an Effective PKU Treatment That Works for More Patients 58 • Amplify strong clinical data and MOA • Physician and Patient Education Programs • Leverage advocates • Provide superior patient support • Pricing/reimbursement strategy • Early access programs Build Confiden
Slide 59: APHENITY Results Support Next Steps in Regulatory Process and Commercial Planning
APHENITY Results Support Next Steps in the Regulatory Process and Commercial Planning Pre-Submission Meetings Regulatory Submissions Initiate Launch Preparation 59 PKU Presentation