Ultragenyx Pharmaceutical Inc. · NASDAQ:RARE

Ultragenyx Pharmaceutical — Technical Presentation (2016)

16 slides from Ultragenyx Pharmaceutical's technical presentation, 2016

  1. Slide 1: Randomized, Open-label, Dose-finding, Phase 2 Study of KRN23 in Children with XLH

    Randomized, Open-label, Dose-finding, Phase 2 Study of KRN23, a Human Monoclonal Anti-FGF23 Antibody, in Children with X-linked Hypophosphatemia (XLH) Thomas Carpenter Yale University School of Medicine, New Haven, Connecticut E. Imel, A. Boot, W. Högler, A. Linglart, R. Padidela, W. van’t Hoff, M.

  2. Slide 2: Disclosures

    Disclosures • Dr. Carpenter: grant support and travel fees from Ultragenyx Pharmaceuticals Inc. (Ultragenyx) • Drs. Imel, Boot, Linglart, Högler, van’t Hoff, and Portale: travel and/or consulting fees from Ultragenyx. Dr. Padidela has received consulting fees from Ultragenyx and Alexion Pharmaceutic

  3. Slide 3: Excess FGF23 in XLH Leads to Phosphate Wasting and Chronic Hypophosphatemia

    Excess FGF23 in XLH Leads to Phosphate Wasting and Chronic Hypophosphatemia PHEX mutation Serum FGF23 Defective mineralization Renal Tubule Cell Capillary Urine 1- hydroxylase and delayed ossification NaPi-2a 1,25(OH)2D NaPi-2c NaPi2a/NaPi2c FGFR Cotransporters FGF23 Downregulated -KLOTHO Phosphat

  4. Slide 4: KRN23 Is Designed to Inhibit FGF23 to Improve Phosphate Homeostasis

    KRN23 Is Designed to Inhibit FGF23 to Improve Phosphate Homeostasis PHEX KRN23 Inhibits mutation Serum FGF23 Proposed KRN23 Mechanism of Action Improved mineralization and bone disease expected Urine Renal Tubule Cell Capillary 1- hydroxylase NaPi-2a 1,25(OH)2D NaPi-2c NaPi2a/NaPi2c FGFR Cotranspor

  5. Slide 5: Pediatric Phase 2 Study Design (UX023-CL201)

    Pediatric Phase 2 Study Design (UX023-CL201) Study Design Key Endpoints Biweekly (Q2W) Dose Group • Pharmacodynamics: Titration serum P,1,25(OH)2D, Treatment Period Period 16 Weeks 48 Weeks TmP/GFR N = 52 Age 5-12 yrs Extension • Rickets -- graded by two Monthly (Q4W) Dose Group Study Tanner ≤2 scor

  6. Slide 6: Baseline Demographics and Characteristics

    Baseline Demographics and Characteristics KRN23 KRN23 KRN23 Q2W Q4W Overall (N = 18) (N = 18) (N = 36) Age, yrs 8.3 (1.6) 8.1 (2.1) 8.2 (1.8) Male 9 (50%) 9 (50%) 18 (50%) White 16 (89%) 16 (89%) 32 (89%) Weight, kg 31.5 (17.6, 47.2) 24.4 (14.7, 55.2) 28.8 (14.7, 55.2) Height Z score -1.6 (1.0) -2.2

  7. Slide 7: Improvement in Serum Phosphate, TmP/GFR, and 1,25(OH)2D

    Improvement in Serum Phosphate, TmP/GFR, and 1,25(OH)2D 3.8 Q2W Q4W Serum Phosphorus 3.4 (mg/dL) 3.0 • All post-baseline values 2.6 were significant (p<0.05) 2.2 compared with baseline 1.8 unless denoted as not 4.2 significant (NS) 3.6 • Mean dose (SD) at Week 40: TmP/GFR (mg/dL) 3.0 • Q2W: 2.4  0.

  8. Slide 8: Two Rickets Scoring Systems Utilized

    Two Rickets Scoring Systems Utilized Thacher Rickets Severity Score (RSS) Radiographic Global Impression of • Total 0-10: wrist (0-4) plus knee (0-6) Change (RGI-C) • Read centrally by an expert blinded to • 7-point scale describing changes at dose and patient wrist, knee, and leg during treatment •

  9. Slide 9: Mean Change from Baseline to Week 40 in RSS

    Mean Change from Baseline to Week 40 in RSS All Patients (N=36) Baseline RSS Total Score ≥1.5 (N = 18) 44% 14% 30% 59% 33% 47% p=0.013 p=0.3 p=0.008 p<0.0001 p=0.008 p<0.0001 2.44 Mean RSS Total Score ± SE at Week 40 2.5 2.5 2.17 2.31 2 1.53 2.0 1.44 1.33 1.43 1.5 1.5 1.22 1.14 0.86 1.00 1.00 1 1.0

  10. Slide 10: Mean RGI-C Global Score at Week 40

    Mean RGI-C Global Score at Week 40 All Patients (N=36) Baseline RSS Total Score ≥1.5 (N = 18) +2.5 +2.5 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 2.00 1.85 Mean RGI-C Score ± SE at Week 40 +2.0 +2.0 1.70 1.56 1.38 +1.5 1.20 +1.5 +1.0 +1.0 +0.5 +0.5 0.0 0.0 Q2W (N=18) Q4W (N=18) All (N=36

  11. Slide 11: Proportion of Subjects with Substantial Healing (RGI-C ≥2.0) at Week 40

    Proportion of Subjects with Substantial Healing (RGI-C Global Score ≥2.0) at Week 40 All Patients (N=36) Baseline RSS Total Score ≥1.5 (N = 18) 100 89% (8/9) 90 80 67% Percent of Subjects 70 (12/18) 56% 60 (10/18) 42% 44% 50 (15/36) (4/9) 40 28% (5/18) 30 20 10 0 Q2W Q4W All Q2W Q4W All

  12. Slide 12: Radiographic Appearance of Rickets at Baseline and Follow-up

    Radiographic Appearance of Rickets at Baseline and Follow-up Knee X-rays in 12 yr-old girl before (left) and after 40 wks (center) and 64 wks (right) of KRN23 therapy for XLH. Noted the improved rachtic findings at the growth plate.

  13. Slide 13: Change in Serum Alkaline Phosphatase

    Change in Serum Alkaline Phosphatase Mean ± SE Alkaline Phosphatase (U/L) 520 500 480 460 440 420 400 380 * 360 0 4 8 16 24 40 Week Q2W Q4W * p=0.01; p value calculated from paired t test based on baseline and Week 40 value

  14. Slide 14: Summary of Safety Measures

    Summary of Safety Measures KRN23 KRN23 KRN23 Subject Incidence Q2W Q4W Overall (%) (N = 18) (N = 18) (N = 36) Any Adverse Events (AEs) 18 (100%) 18 (100%) 36 (100%) Drug-related AEs* 13 (72%) 13 (72%) 26 (72%) Injection Site Reaction 7 (39%) 7 (39%) 14 (39%) Erythema 4 (22%) 3 (17%) 7 (19%) Swelling

  15. Slide 15: PTH and Urine Calcium

    PTH and Urine Calcium 70 65 Q2W Q4W 60 iPTH (pg/mL) 55 • No meaningful increases in 50 45 serum PTH levels 40 35 30 100 24 H Urine Calcium Exc. 90 80 • No increases in serum or Rate (mg/day) 70 urinary calcium levels were 60 observed 50 40 30 0 8 16 20 28 40 Week

  16. Slide 16: Summary

    Summary • KRN23, an investigational product, improved P homeostasis and rickets in children with XLH previously treated for a mean of 6.6 years • Greater improvement in rickets scores occurred with Q2W dosing and in subjects with more severe baseline rickets (RSS total score ≥1.5) • KRN23 was well-t

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