Slide 1: APHENITY Topline Results
APHENITY Topline Results Matthew Klein, M.D. CEO May, 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: 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 4: Global Registration-Directed Trial of Sepiapterin Study Design
APHENITY Global Registration-Directed Trial of Sepiapterin Study Design Run-in Placebo-Controlled Part 1 Part 2 Sepiapterin Sepiapterin R Primary Endpoint Placebo Reduction in blood phenylalanine levels 14 Days 42 Days Primary Endpoint 4 APHENITY Topline Results
Slide 5: Part 1 Results Demonstrated Marked Blood Phe Reductions
APHENITY Part 1 Results Demonstrated Marked Blood Phe Reductions Mean % Blood Phe Reduction Mean Absolute Blood Phe Reduction (µmol/L) ≥30% responders ≥30% responders Overall Classical PKU Overall Classical PKU N=103* N=16 N=103* N=16 0% 0 Mean Absolute Blood Phe -10% Reduction (µmol/L) -100 Mean %
Slide 6: Baseline Phe Levels of Classical PKU Patients in Part 1
Baseline Phe Levels of Classical PKU Patients in Part 1 Number of Baseline Phe Patients (µmol/L) >30% responders 16 978.6 15-30% responders 4 1,058.6 <15% responders 15 848.5 Total 35 928.6 6 APHENITY Topline Results
Slide 7: APHENITY Study Population
APHENITY Study Population Patients <2 age 2 patients* Responders ≥30% Reduction in Sepiapterin- Blood Phe from Baseline Primary Responsiveness 103 patients Analysis Evaluated in 66% Population 156 patients Not randomized 98 patients 3 patients 12 Patients with ≥15 – <30% Reduction 110 randomized pat
Slide 8: Global Registration-Directed Trial of Sepiapterin Study Design
APHENITY Global Registration-Directed Trial of Sepiapterin Study Design Run-In Placebo-Controlled Part 1 Part 2 Sepiapterin Sepiapterin R Placebo 14 Days Stratification 42 Days Mean percent reduction in blood Phe levels from Part 1 (≥30% or ≥15 - <30% ) Primary Endpoint Baseline blood Phe level (<60
Slide 9: Primary Analysis Population Includes Full Spectrum of PKU Patients
APHENITY Primary Analysis Population Includes Full Spectrum of PKU Patients Baseline Characteristic Sepiapterin (N=49) Placebo (N=49) Mean age at enrollment (yrs) [min, max] 16.3 [2, 47] 18.1 [4, 54] 2-17 (%) 34 (69.4) 31 (63.3) ≥18 years (%) 15 (30.6) 18 (36.7) F: 46.9 F: 55.1 Sex: %F, %M M: 53.1 M
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 Sepiapterin Placebo Sepiapterin Placebo N=49 N=49 N=6 N=9 10 10 1% 3% 0 0 Mean % Blood Phe Mean % Blood Phe -10 -10 Reduction Reduction -
Slide 11: Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction
Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction Mean Absolute Blood Phe Reduction (µmol/L) Overall Primary Analysis Population Classical PKU Patients Sepiapterin Placebo Sepiapterin Placebo N=49 N=49 N=6 N=9 0 0 16 Mean Absolute Blood Phe 42 Mean Absolute Blood Phe -100
Slide 12: 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 12 APHENITY Topline Results
Slide 13: 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 14: Sepiapterin Demonstrated to be Well Tolerated
Sepiapterin Demonstrated to be Well Tolerated Sepiapterin was well tolerated with no serious adverse events Similar related adverse event frequency between sepiapterin and placebo treatment groups Most common adverse events were headache and diarrhea 14 APHENITY Topline Results
Slide 15: Open-Label Extension Assesses Long Term Safety and Phe Tolerance
APHENITY Open-Label Extension Assesses Long Term Safety and Phe Tolerance Run-in Placebo-Controlled Open-Label Extension Part 1 Part 2 Sepiapterin Study Objectives Sepiapterin Sepiapterin R Placebo Long-term safety Change in dietary Phe/protein consumption 14 Days 42 Days 1 Year 15 APHENITY Topline
Slide 16: Initial Phe Tolerance Data in Open-Label Extension
Prescribed Phe Consumption 16 (mg/kg/day) 20 40 60 80 0 100 120 140 M1 W1-W2 (BL) (N=12) M2 W1-W2 APHENITY Topline Results M2 W3-W4 M3 W5-W6 M3 W7-W8 M4 W9-W10 M4 W11-W12 M5 W13-W14 M5 W15-W16 Increase in Dietary Phe Intake Phe intake M6 W17-W18 M6 W19-W20 Adult recommended M7 W21-W22 (N=4) Mean Blo
Slide 17: 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 17 APHENITY Topline Results 1. NPKUA; h
Slide 18: Overview of Treatment-Emergent Adverse Events
Overview of Treatment-Emergent Adverse Events Sepiapterin Sepiapterin Sepiapterin Sepiapterin Placebo 20 mg/kg 40 mg/kg 60 mg/kg Overall (N = 54) (N=56) (N=56) (N=55) (N=56) N%m N%m N%m N%m N%m All TEAEs 20 (35.7%) 29 7 (12.5%) 10 15 (27.3%) 21 33 (58.9%) 60 18 (33.3%) 33 Treatment-Related TEAEs 5 (
Slide 19: Results Support Potential for Sepiapterin to Address Majority of PKU Segments
APHENITY Results Support Potential for Sepiapterin to Address Majority of PKU Segments Sepiapterin Market Opportunity Therapy Naive Patients Who Patients Who Are Patients Including Have Failed on Not Well Controlled Classical PKU Current Therapies 19 APHENITY Topline Results
Slide 20: 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 20 APHENITY Topline Results
Slide 21: Results Support Next Steps in Regulatory Process and Commercial Planning
APHENITY Results Support Next Steps in Regulatory Process and Commercial Planning Pre-Submission Regulatory Initiate Launch Meetings Submissions Preparation 21 APHENITY Topline Results