Ultragenyx Pharmaceutical Inc. · NASDAQ:RARE

Ultragenyx Pharmaceutical — Investor Presentation (November 2022)

47 slides from Ultragenyx Pharmaceutical's investor presentation, November 2022

  1. Slide 1: Corporate Presentation

    Corporate Presentation November 2022

  2. Slide 2: Forward Looking Statements

    Forward Looking Statements Cautionary note regarding forward-looking statements: This presentation contains forward-looking statements, including, but not limited to, statements regarding our expectations and projections regarding our future operating results and financial performance, anticipated c

  3. Slide 3: Leading the Future of Rare Disease Medicine

    Leading the Future of Rare Disease Medicine Growing  Crysvita, Dojolvi, Mepsevii Commercial  Evkeeza launching in Europe Revenue  Anticipate ~30% revenue growth1  7 clinical programs Strong Clinical  5 ongoing pivotal studies Pipeline  Supporting future revenue growth  Four large value progra

  4. Slide 4: Three Rare Disease Franchises and Five Commercial Programs

    Three Rare Disease Franchises and Five Commercial Programs BONE ENDOCRINE METABOLICS CNS / MUSCLE COMMERCIAL DEVELOPMENT Ph 3 Ph 3 Ph 3 Ph 2/3 Ph 1/2/3 Ph 1/2 Ph 1/2 Setrusumab UX053 UX701 DTX401 DTX301 GTX-102 UX111 for OI for GSDIII for Wilson for GSDIa for OTC for Angelman for MPS IIIA Preclinica

  5. Slide 5: Three Independent Paths to Create Meaningful Value

    Three Independent Paths to Create Meaningful Value Based on Four Large Value Programs Wilson Disease Large Value Opportunity Gene Therapy Programs Clinical proof of concept Commercial scale for GSDIa & OTC to Ph3 manufacturing platform Advancement of GTX-102 to Phase 3 Trials Angelman Syndrome (GTX-

  6. Slide 6: Solid Base of Revenue Growth with Significant Opportunity from Larger Clinical Programs

    Solid Base of Revenue Growth with Significant Opportunity from Larger Clinical Programs 5 Year Revenue ~90% CAGR 400 Growth Driven by: Product Revenue ($M) 300 266 Commercial products provide growing base 200 Pipeline assets further 182 accelerate growth trajectory (Osteogenesis Imperfecta, 103 Ange

  7. Slide 7: Prioritization of High Value Programs Expected to Limit Operating Expenses

    Prioritization of High Value Programs Expected to Limit Operating Expenses and Decrease Net Cash Burn in 2023 1,200 Operating Expenses  Strong capital position: ~$1.0 billion 1,000 in cash and equivalents1 $M 800  One-time expenses refilled pipeline 600 and established the teams needed 628 515 to

  8. Slide 8: Key Upcoming Milestones in 2022 and 2023

    Key Upcoming Milestones in 2022 and 2023 PROGRAM OBJECTIVE TIMING DTX401 Ph 3 LPI Around the end of 2022 GSDIa Ph 3 data readout ~1 year from LPI Ph 2 LPI Early 2023 UX143 Ph 2 data readout and Ph 3 transition Mid-2023 Osteogenesis Imperfecta Initiate young pediatric study 1H23 GTX-102 FPI for Expan

  9. Slide 9: Evkeeza (evinacumab) for Homozygous Familial Hypercholesterolemia (HoFH)

    Evkeeza (evinacumab) for Homozygous Familial Hypercholesterolemia (HoFH) Approved and Launching in Europe

  10. Slide 10: Evkeeza Lowers Cholesterol and Triglycerides by Enhancing an Alternative Lipid Path

    Evkeeza Lowers Cholesterol and Triglycerides by Enhancing an Alternative Short Cut Lipid Path to the Liver  HoFH: Form of familial hypercholesterolemia with dangerously high levels of LDL-C (>400 mg/dL) – Premature atherosclerosis & cardiac events – Most treatments inadequate for HoFH  Prevalence

  11. Slide 11: Patients on Evinacumab Had Substantial LDL-C Reductions

    Patients on Evinacumab Had Substantial LDL-C Reductions on Top of All Ongoing Lipid-lowering Therapy Regardless of Genotype Phase 3 Study (n=65; 2:1 drug:placebo) +1.9% from Baseline (%) Change in LDL-C Placebo Evinacumab -47.1% Raal et al. New England Journal of Medicine, Aug 2020 LDL-C reduced 72%

  12. Slide 12: Evkeeza Well-Positioned in High Unmet Need HoFH

    Evkeeza Well-Positioned in High Unmet Need HoFH Evkeeza high potency and monthly dosing compares well  Competition for HoFH with low LDLR activity – Juxtapid/Lojuxta (lomitapide) Poor tolerability issues with persistence/compliance issues – Apheresis to remove LDL with frequent and long sessions, s

  13. Slide 13: GTX-102 Program for Angelman Syndrome

    GTX-102 Program for Angelman Syndrome Positive interim Phase 1/2 efficacy data from ASO program in Angelman syndrome

  14. Slide 14: GTX-102 for Angelman Syndrome

    GTX-102 for Angelman Syndrome Large neurodevelopmental disorder  Angelman syndrome: Neurogenetic disorder caused by loss of expression of UBE3A gene  Devastating Neuro Disease: Motor dysfunction, lack of speech, cognitive impairment, sleep disorder  GTX-102: Antisense oligonucleotide (ASO) that c

  15. Slide 15: Study Dosing Schematic for GTX-102 in U.K. and Canada

    Study Dosing Schematic for GTX-102 in U.K. and Canada Dose of 10-12mg tolerated well in young and older cohorts PMD PMD Baseline Day 58 Day 128 ~Day 170 ~Day 254 Dose in mg Evaluation Evaluation Evaluation Evaluation Evaluation Next dose increased or not? Next dose increased or not? Next dose increa

  16. Slide 16: Increases in Receptive and Expressive Communication

    Increases in Receptive and Expressive Communication Exceeds Threshold to be Significant; Comparable to first 5 patients Receptive Comm Expressive Comm Bayley-4 GSV1 Bayley-4 GSV1  Psychologist administered Latest Assessment2 Latest Assessment2  A score of +7 or higher is Change from Baseline Chang

  17. Slide 17: Sleep Domain: Substantial, clinically meaningful changes

    Sleep Domain: Substantial, clinically meaningful changes Comments from Caregivers on Sleep Cohort 4 : AS Sleep Change in Severity  103-003: “Her sleep has improved which is humongous, and very helpful for me and our whole family. She's more rested, we're all more rested. So everyone's able to funct

  18. Slide 18: GTX-102 Safety Profile Under Amended Protocol

    GTX-102 Safety Profile Under Amended Protocol Improved administration procedure  No adverse events of leg weakness  Patients treated for over 1 year  Starting doses range from 2 mg to 10 mg with escalation up to 14 mg  Total of 71 doses administered  Cumulative doses up to 61 mg  2 patients re

  19. Slide 19: UX143 (setrusumab) for Osteogenesis Imperfecta

    UX143 (setrusumab) for Osteogenesis Imperfecta Enrolling pivotal Phase 2/3

  20. Slide 20: UX143 for Osteogenesis Imperfecta (OI)

    UX143 for Osteogenesis Imperfecta (OI) Large genetic bone disorder with positive Phase 2b adult data Mechanism of Anti-Sclerostin Antibody  OI: Reduced or abnormal collagen causes increased bone resorption and inadequate bone production – Leads to decreased bone mass, strength & fractures  No appr

  21. Slide 21: Anti-Sclerostin Antibody Increases Bone Formation on All Bone Surfaces

    Anti-Sclerostin Antibody Increases Bone Formation on All Bone Surfaces OVX Monkeys (12mo Tx) Vehicle Scl-Ab Femur Diaphysis 21 Ominsky et al 2017

  22. Slide 22: Setrusumab can normalize bone mass and strength in Brittle OI mice

    Setrusumab can normalize bone mass and strength in Brittle OI mice even if collagen still mutated  Setrusumab (5wks) Femur Diaphysis Femur Diaphysis Lumbar Vertebra restored cortical bone 0.25 30 * 50 * geometry & strength in * +6% Brtl/+ mice to WT levels 0.20 Maximum Load (N) Maximum Load (N) -1%

  23. Slide 23: Setrusumab makes better bone than bisphosphonates

    Setrusumab makes better bone than bisphosphonates 5wk Setrusumab vs 12wk Alendronate BONE MASS INDICES BONE STRENGTH INDICES CSMI Cortical Thickness Maximum Load Stiffness SETRUSUMAB 120 * * 120 * 120 * 120 100 +20% 100 100 100 ^ +5% +6% ^ %of WT mean %of WT mean %of WT mean ^ -1% ^ %WT mean 80 80 8

  24. Slide 24: Phase 2b Adult OI study: Large Effects of Setrusumab

    Phase 2b Adult OI study: Large Effects of Setrusumab BMD and bone strength were dose-dependently improved Mean % ∆ Setrusumab Setrusumab Setrusumab from BL at 12 mos 20 mg/kg 8 mg/kg 2 mg/kg Lumbar spine aBMD 8.97 6.65 2.35 (p<0.001) (p<0.001) (p<0.05) Total hip aBMD 2.48 2.69 1.99 BMD Increases (p<

  25. Slide 25: ORBIT Phase 2/3 Study Schema

    ORBIT Phase 2/3 Study Schema Phase 2 biomarker data expected in mid-2023 Phase 2 Single Blind Treatment Period Phase 3 Double-Blind Treatment Period Stratified for Peds/Adults Phase 3 Dose Selection Setrusumab Setrusumab at Selected Dose (n = 130) New Patients Randomization Randomized 20 mg/kg (n=12

  26. Slide 26: UX143: Next Steps

    UX143: Next Steps  Phase 2/3 Orbit study in patients 5-25 years old initiated in April 2022 – Phase 2 portion: identify optimal dose strategy based on increases in collagen production using serum P1NP levels – Phase 3 transition: expected to initiate in mid-2023; evaluate fractures over 15-24 month

  27. Slide 27: Gene Therapy Platform

    ultra Gene Therapy Platform

  28. Slide 28: Diverse and Late-Stage Gene Therapy Pipeline

    Diverse and Late-Stage Gene Therapy Pipeline Pre- Est’d Patients in Candidate Description IND Phase 1 Phase 2 Phase 3 Approved Clinical Dev. World UX111 AAV9 Mucopolysaccharidosis Type IIIA (MPS IIIA) ~3,000–5,000 (ABO-102) Gene Therapy AAV8-G6Pase DTX401 Glycogen Storage Disease Type Ia (GSDIa) ~6,

  29. Slide 29: Sanfilippo Syndrome Type A (MPS IIIA)

    Sanfilippo Syndrome Type A (MPS IIIA) Lysosomal storage disease leading to early neurocognitive decline & death  MPS IIIA: Severe lysosomal storage disease due to an enzyme deficiency, causing abnormal accumulation of heparan sulfate (HS) – Progressive cognitive decline begin at age 1-2 to devastat

  30. Slide 30: Mullen Cognitive Age-Equivalent Data

    Mullen Cognitive Age-Equivalent Data Patients treated at an early age track along normal development range Cognitive Age Equivalent • Black solid line and gray data points: Typical developmental pattern for children with MPS IIIA per natural history data • DQ60 and DQ100 lines: Expected development

  31. Slide 31: Summary of Transpher A Results and Next Steps

    Summary of Transpher A Results and Next Steps Pivotal study data with UX111  Patients track along normal development range, showing continuous improvements  Cohort 3 (highest dose, n=10), stabilization or increase in cortical gray matter, total cerebral, and amygdala volumes  Statistically signif

  32. Slide 32: DTX401: AAV8 for Glycogen Storage Disease Type Ia

    DTX401: AAV8 for Glycogen Storage Disease Type Ia Patient 3 Cornstarch when Travelling  GSDIa: Defect in liver’s ability to release glucose to the circulation due to G6Pase deficiency – Severe life-threatening hypoglycemia – Long-term liver and renal disease – Severe long-term complications (70-80%

  33. Slide 33: All Patients Sustained Reduction in Cornstarch Therapy

    All Patients Sustained Reduction in Cornstarch Therapy While Maintaining or Improving Time in Euglycemia Cornstarch Rx is a critical repetitive oral glucose infusion required to keep patients from hypoglycemia crashes and consequences. It’s a “gun to the head” every day and night their entire lives,

  34. Slide 34: Enrollment and Dosing Ongoing in Phase 3 Study

    Enrollment and Dosing Ongoing in Phase 3 Study Expect to complete enrollment around end of 2022 Phase 3 Study Design  50 patients, randomized 1:1 DTX401 (1.0 x 1013 GC/kg) to placebo – Patients on placebo will cross over to gene therapy arm  48-week duration – Longer-term Phase 1/2 data to be incl

  35. Slide 35: DTX301: AAV8 for OTC Deficiency

    DTX301: AAV8 for OTC Deficiency AAV8 gene therapy for stable expression of OTC Amino Protein  OTC Deficiency: X-linked urea cycle disorder, genetic Acids Breakdown defect in ammonia detoxification  Key symptoms/prognosis: – Acute hyperammonemic episodes – Adverse cognitive & neurological effects 

  36. Slide 36: Seven of Eleven Patients Show Durable Metabolic Control

    Seven of Eleven Patients Show Durable Metabolic Control and Sustained Responses up to 4.5 years Patient # Dose Ammonia Levels (Gender); Current Response Status Cohort (baseline → after treatment) Follow-Up 1 1 (M); 234 wks Normal levels maintained Complete responder 2 4 (M); 182 wks Normal levels ma

  37. Slide 37: DTX301: Phase 3 Design

    DTX301: Phase 3 Design Phase 3 Study Design  50 patients, randomized 1:1 DTX301 (1.7 x 1013 GC/kg) to SOC/placebo – Patients on SOC/placebo will cross over to gene therapy arm  64-week duration – Longer-term Phase 1/2 data to be included in submission to support durability  Primary endpoints – Co

  38. Slide 38: UX701: AAV9 for Wilson Disease

    UX701: AAV9 for Wilson Disease Second clinical program to utilize PCL manufacturing system  Wilson Disease: Causes copper to accumulate in liver, brain and other vital organs  Key symptoms/prognosis: Liver failure, neurological deterioration, death Untreated KO Mice 1x1011 GC Treated Mice  Standa

  39. Slide 39: Broad and Diverse Clinical Pipeline to Build on Strong Commercial Foundation

    Broad and Diverse Clinical Pipeline to Build on Strong Commercial Foundation Stable & Growing Significant Clinical Catalysts Revenue Base over Next Few Years >$300M revenue in 2022 from Diversified across modalities and current commercial portfolio smaller and larger indications Osteogenesis Imperfe

  40. Slide 40: Appendix

    ultra Appendix

  41. Slide 41: Diverse Clinical Pipeline with Larger Indications to Drive Long-Term Growth

    Diverse Clinical Pipeline with Larger Indications to Drive Long-Term Growth Pre- Est’d Patients in Candidate Description IND Phase 1 Phase 2 Phase 3 Approved Clinical Dev. World Anti-FGF23 X-Linked Hypophosphatemia (XLH) & Tumor-Induced Osteomalacia (TIO) ~50,000 Monoclonal Antibody Enzyme Replaceme

  42. Slide 42: Key Licenses & Intellectual Property – Commercial Products

    Key Licenses & Intellectual Property – Commercial Products Product License US Intellectual Property Rights/Royalties CRYSVITA® Kyowa Kirin Co. (KKC)  Anti-FGF23 antibodies and use for treatment of XLH and TIO (2022-2032)1 (XLH, TIO)  Q2W dosing for treatment of FGF23-associated hypophosphatemic di

  43. Slide 43: Key Licenses & Intellectual Property – Clinical Programs

    Key Licenses & Intellectual Property – Clinical Programs Product License US Intellectual Property Rights/Royalties UX143 Mereo Biopharma  Setrusumab antibody (2028) (Osteogenesis Imperfecta)  Use of anti-sclerostin antibodies including setrusumab for treatment of OI (2037)  Tiered double-digit ro

  44. Slide 44: CRYSVITA Exclusivity Summary

    CRYSVITA® Exclusivity Summary XLH Orphan TIO Orphan Biologics Crysvita Q2W Exclusivity Exclusivity Exclusivity CoM Patent Dosing Patent United States 2025 2027 2030 2032* 2035 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2028 2033* 2035 Europe XLH Orphan + Crysvita CoM Q2W Dosing D&M Exclusivit

  45. Slide 45: DOJOLVI Exclusivity Summary

    DOJOLVI® Exclusivity Summary NCE LC-FAOD Orphan Dojolvi CoM Ultrapure Dojolvi Exclusivity Exclusivity Patent (Pending) United States 2025 2027 2029* 2034 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2034 Europe Ultrapure Dojolvi (Pending) 45 *Includes projected US PTE award

  46. Slide 46: MEPSEVII Exclusivity Summary

    MEPSEVII® Exclusivity Summary MPS7 Orphan Biologics Mepsevii Exclusivity Exclusivity CoM Patent United States 2024 2029 2035 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2028 2035 Europe MPS7 Orphan + Mepsevii D&M Exclusivity CoM Patent 46

  47. Slide 47: EVKEEZA Exclusivity Summary

    EVKEEZA® Exclusivity Summary Data & Marketing Evkeeza Exemplary additional patent Exclusivity Ab Patent applications pending: • Evkeeza w/ PCSK9 Ab 2031 20361 • Evkeeza w/ statins Europe • Evkeeza formulations Projected expiration dates between 2037-2041 2022 2024 2026 2028 2030 2032 2034 2036 2038

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