Slide 1: APHENITY Topline Results
Patient Living with PKU Matthew Klein, M.D. CEO May, 2023 APHENITY Topline Results
Slide 2: Forward-Looking Statements
Forward-Looking Statements 2 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 w
Slide 3: APHENITY Topline Results Demonstrate Clinical and Statistically Significant Benefit
APHENITY Topline Results Demonstrate Clinical and Statistically Significant Benefit 3 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 anal
Slide 4: Global Registration-Directed Trial of Sepiapterin Study Design
APHENITY Global Registration-Directed Trial of Sepiapterin Study Design 4 Primary Endpoint Reduction in blood phenylalanine levels Primary Endpoint Sepiapterin Placebo 42 Days Placebo-Controlled Sepiapterin Run-in Part 1 Part 2 R 14 Days APHENITY Topline Results
Slide 5: APHENITY Part 1 Results Demonstrated Marked Blood Phe Reductions
-70% -60% -50% -40% -30% -20% -10% 0% Overall Classical PKU APHENITY Part 1 Results Demonstrated Marked Blood Phe Reductions 5 Mean Absolute Blood Phe Reduction (µmol/L) ≥30% responders Mean % Blood Phe Reduction ≥30% responders Mean % Blood Phe Reduction Mean Absolute Blood Phe Reduction (µmol/L) N
Slide 6: Study Population Sepiapterin-Responsiveness Evaluated in 156 patients
APHENITY Study Population 6 Sepiapterin-Responsiveness Evaluated in 156 patients Patients <2 age 2 patients* Not randomized 3 patients Primary Analysis Population 98 patients 12 Patients with ≥15 – <30% Reduction 110 randomized patients Responders ≥30% Reduction in Blood Phe from Baseline 103 patien
Slide 7: Global Registration-Directed Trial of Sepiapterin Study Design
APHENITY Global Registration-Directed Trial of Sepiapterin Study Design 7 Primary Endpoint Sepiapterin Placebo 42 Days Placebo-Controlled Sepiapterin Run-In Part 1 Part 2 R 14 Days Stratification Mean percent reduction in blood Phe levels from Part 1 (≥30% or ≥15 - <30% ) Baseline blood Phe level (<
Slide 8: APHENITY Primary Analysis Population Includes Full Spectrum of PKU Patients
8 APHENITY Primary Analysis Population Includes Full Spectrum of PKU Patients APHENITY Topline Results 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) Sex: %F, %
Slide 9: Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction
Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction 9 APHENITY Topline Results Mean % 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% 58
Slide 10: Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction
-600 -500 -400 -300 -200 -100 0 Sepiapterin Placebo Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction 10 -600 -500 -400 -300 -200 -100 0 Sepiapterin Placebo Overall Primary Analysis Population Classical PKU Patients Mean Absolute Blood Phe Reduction (µmol/L) Mean Absolute
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 11 93% Achieved <600µmol/L Blood Phe US guidelines: all ages EU guidelines: <12 years of age 84% Achieved <360µmol/L Blood Phe APHENITY Topline Results
Slide 12: Sepiapterin Treatment Effect in Patients Receiving Sapropterin at Study Entry
Sepiapterin Part 1 Treatment Effect in Patients Receiving Sapropterin at Study Entry 12 800 700 600 500 400 300 200 100 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 sepiapter
Slide 13: Sepiapterin Demonstrated to be Well Tolerated
Sepiapterin Demonstrated to be Well Tolerated 13 Most common adverse events were headache and diarrhea Sepiapterin was well tolerated with no serious adverse events Similar related adverse event frequency between sepiapterin and placebo treatment groups APHENITY Topline Results
Slide 14: Open-Label Extension Assesses Long Term Safety and Phe Tolerance
APHENITY Open-Label Extension Assesses Long Term Safety and Phe Tolerance 14 R Sepiapterin Placebo 42 Days Placebo-Controlled Open-Label Extension Sepiapterin 1 Year Sepiapterin Run-in Part 1 Part 2 Study Objectives Long-term safety Change in dietary Phe/protein consumption 14 Days APHENITY Topline
Slide 15: 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 15 APHENITY Topline Results Prescribed Phe Consumption (mg/kg/day) Adult recommended Phe intake (
Slide 16: Commercial Pillars for Success Already Established
Commercial Pillars for Success Already Established 16 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 APHENITY Topline Results 1. NPKUA; h
Slide 17: Results Support Potential for Sepiapterin to Address Majority of PKU Segments
APHENITY Results Support Potential for Sepiapterin to Address Majority of PKU Segments 17 APHENITY Topline Results Sepiapterin Market Opportunity Therapy Naive Patients Including Classical PKU Patients Who Are Not Well Controlled Patients Who Have Failed on Current Therapies
Slide 18: PTC Global Commercial Infrastructure Will Allow for Rapid Worldwide Launch
PTC Global Commercial Infrastructure Will Allow for Rapid Worldwide Launch 18 KOL/ Payor Relationships PAG Relationships Patient Support Dedicated Customer Facing Teams EAP/ Access & Reimbursement Plug and Play in PKU APHENITY Topline Results
Slide 19: Results Support Next Steps in Regulatory Process and Commercial Planning
APHENITY Results Support Next Steps in Regulatory Process and Commercial Planning 19 Pre-Submission Meetings Regulatory Submissions APHENITY Topline Results Initiate Launch Preparation