Ultragenyx Pharmaceutical Inc. · NASDAQ:RARE
Ultragenyx Pharmaceutical — Investor Presentation (August 2014)
45 slides from Ultragenyx Pharmaceutical's investor presentation, Aug 14, 2014
Slide 1: Transforming good science into great medicine for rare diseases
August 14, 2014 Transforming good science into great medicine for rare diseases Exhibit 99.1
Slide 2: Legal Warning
Cautionary note regarding forward-looking statements: The following information contains forward-looking statements, including statements regarding our expectations regarding the timing of reporting results from our clinical studies of KRN23, rhGUS, triheptanoin (in LC-FAOD and Glut1 DS), and SA-ER;
Slide 3: A rare disease company by design
Ultragenyx Pharmaceutical Inc. A rare disease company by design Serious metabolic genetic disorders Five clinical stage programs Proven team with rare disease expertise Commercialization worldwide Well financed with $182M1 raised year-to-date 1Net proceeds
Slide 4: A Next-Generation Rare Disease Company
A Next-Generation Rare Disease Company Novel approaches to finding and developing products Open minds to undiscovered discoveries Drugs with clear mechanisms Risk-managed development strategies Creative solutions to rare disease challenges Capital efficient and rapid execution Development for rare d
Slide 5: Experienced Management Team
Experienced Management Team Multiple rare disease product approvals Emil Kakkis, MD, PhD, CEO BioMarin (CMO) Tom Kassberg, CBO Proteolix, InterMune, Plexxikon, SUGEN, BMS Shalini Sharp, CFO Agenus, Elan, Goldman, McKinsey Sunil Agarwal, MD, CMO Roche/Genentech, MedImmune, Guilford, Kosan Steve Jungl
Slide 6: Ultragenyx Pipeline
Ultragenyx Pipeline Developing multiple clinical-stage programs in parallel Phase 1/2 or Phase 2 Pre- clinical Candidate Ultragenyx Commercial Rights Phase 3 or Pivotal Phase 1 Indication rhPPCA (UX004) Worldwide Galactosialidosis rhGUS (UX003) MPS 7 Worldwide Triheptanoin (UX007) Glut1 DS Worldwide
Slide 7: KRN23 for X-Linked Hypophosphatemia (XLH)
Phase 2 fully human monoclonal antibody against FGF23 (SC injection) KRN23 for X-Linked Hypophosphatemia* (XLH) *Also known as X-linked hypophosphatemic rickets or vitamin D-resistant rickets
Slide 8: KRN23 MAb Against FGF23 for XLH
KRN23 MAb Against FGF23 for XLH Increases low serum phosphate, which causes bone disease XLH Disease: Excess FGF23* causes excess phosphate loss into urine leading to low serum phosphate and poor bone mineralization Key symptoms: Rickets/deformity, short stature, fractures/pain Diagnosis: Clinical p
Slide 9: KRN23 Increases Phosphate and Vitamin D
KRN23 Increases Phosphate and Vitamin D Phase 1 single-dose data presented at ASBMR* and in JCI** A *At 0.3 – 1 mg/kg, increase in serum Pi > placebo; p < 0.05 Peak at day 8-15, persists ~6-8 weeks Serum Pi (mg/dL) SC administration 1,25 (OH)2D (pg/mL) SC administration a a *At 0.3, 0.6 and 1 mg/kg,
Slide 10: Dose-Escalation Phase 1/2 Data at ENDO
Dose-Escalation Phase 1/2 Data at ENDO* Sustained increase in serum phosphorus with repeat KRN23 *ICE/ENDO; Imel, et al, 2014; The First Multi-Dose Trial of a Human Anti-FGF23 (Fibroblast Growth Factor 23) Antibody (KRN23) in Adults with X-Linked Hypophosphatemia (XLH) Study design and conduct Open-
Slide 11: Dose-Escalation Phase 1/2 Data at ENDO: bone markers and QOL
Increases in bone remodeling markers (P1NP, osteocalcin) support impact of improved phosphate metabolism on bone remodeling Increases in certain QOL measures* in SF-36 & WOMAC physical functioning To be evaluated in future controlled studies Safety No significant changes in parathyroid hormone or ca
Slide 12: KRN23 Development Status and Plan
KRN23 Development Status and Plan Focus on pediatric population with maximum need Complete Phase 2 pediatric study initiated in July 2014 Establish dose range/regimen, preliminary efficacy, and safety Evaluate changes in baseline bone disease/clinical measures Expect 30 prepubertal patients, age 5-1
Slide 13: rhGUS for Mucopolysaccharidosis 7 (MPS 7): Sly Syndrome
Phase 1/2 enzyme replacement therapy (IV infusion) Recombinant Human b-glucuronidase (rhGUS) for Mucopolysaccharidosis 7 (MPS 7): Sly Syndrome
Slide 14: rhGUS ERT in MPS 7: Sly Syndrome
rhGUS ERT in MPS 7: Sly Syndrome Disease and ERT treatment similar to MPS I, II, IVA & VI MPS 7 Disease: Deficiency of lysosomal enzyme b-glucuronidase leads to storage of glycosaminoglycans (GAG) Key symptoms/prognosis Large liver/spleen, airway/pulmonary disease, joint stiffness, etc. Death: teens
Slide 15: Single-Patient eIND Data at LDN World
Single-Patient eIND Data at LDN World* 12 year old patient with recent pulmonary decline Patient treated under emergency IND (eIND) Sponsored by Steven and Alexandra Cohen Children’s Medical Center Symptoms Large liver/spleen, hearing loss, heart valve abnormalities, fatigue Recent worsening pulmona
Slide 16: rhGUS Phase 1/2 Study Interim Results
rhGUS Phase 1/2 Study Interim Results Trial initiated December 2013; 6-12 week data in first 2 subjects Extension Study Screening 12 Week Interim 36 Week Primary Analysis Urinary Chondroitin/Dermatan Sulfate (NREs) Rapidly Decline on Therapy No SAEs up to 12 wks of treatment No IARs in total 13 infu
Slide 17: rhGUS Clinical Program Status
rhGUS Clinical Program Status Continue Phase 1/2 study At 12 weeks assess PK/efficacy/safety Dose titration for dose-response after 12 weeks Decide timing for progression into Phase 3 Phase 3 blind-start design with uGAG primary endpoint Agreed N=12 and uGAG primary endpoint with EMA Start of Phase
Slide 18: Triheptanoin for Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD)
Phase 2 substrate replacement therapy (oral liquid) Triheptanoin for Long-Chain Fatty Acid Oxidation Disorders* (LC-FAOD) *Includes VLCAD, LCHAD, CPT-I, CPT-II, TFP, CACT
Slide 19: Triheptanoin for LC-FAOD
Triheptanoin for LC-FAOD Triglyceride of C7: alternative energy source to long-chain fat LC-FAOD disease mechanism Cannot convert fat into energy due to mitochondrial enzyme deficiency Critical energy shortage during exercise, fasting, and illness Key symptoms/prognosis Hypoglycemia, acute muscle ru
Slide 20: Multi-Symptom Improvement
Multi-Symptom Improvement Historical studies of triheptanoin in LC-FAOD for up to 13 years # Symptomatic Patients* Symptoms Before triheptanoin** After triheptanoin Cardiac 10 1 Muscle rupture 36 15 Weakness/fatigue 44 10 Low blood sugar 24 1 Liver enlargement 26 2 Retinopathy 3 3 *n=48; CPT-I, CPT-
Slide 21: Hospitalization outcomes before and after triheptanoin
______________________________________ 1 Excludes data for 4 infants dosed within first 6 months of life. 2 Excludes hospitalizations with unknown discharge dates. 3 Four infants were dosed within the first 6 months of life. 4 Includes only those patients with hypoglycemia events prior to treatment.
Slide 22: LC-FAOD Phase 2 Study Ongoing
Maintain Current Therapy LC-FAOD Phase 2 Study Ongoing Goal to determine endpoints and patient selection for Phase 3 N = ~30 severe subjects, first patient enrolled in February 2014 Dosed at 25-35% of daily caloric intake Evaluate exercise tolerance (cycle erg, 12MWT, muscle strength, event rate, CK
Slide 23: Triheptanoin for Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Phase 2 substrate replacement therapy (oral liquid) Triheptanoin for Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS)
Slide 24: Triheptanoin for Glut1 DS
Glut1 DS mechanism: Glucose transport defect causes brain energy deficiency Key symptoms/prognosis Seizures Developmental delay Movement disorder Diagnosis: CSF, red cell, genetic tests U.S. prevalence: ~3,000 – 7,000 Standard of care: Ketogenic diet (70-80% of calories in fat, <10% carbs) and anti-
Slide 25: Glut1 DS Phase 2 Study Ongoing
Glut1 DS Phase 2 Study Ongoing Study goal to evaluate potential reduction in seizure frequency Screening Baseline* (6 wks) 1:1 Randomization Randomized, Double-Blind, Placebo-Controlled Treatment Period (8 wks) Placebo Primary analysis at Week 8 evaluating seizure frequency in up to 50 pediatric sub
Slide 26: Sialic Acid Extended Release (SA-ER) for HIBM
Phase 2 substrate replacement therapy (oral tablet) Sialic Acid Extended Release (SA-ER) for Hereditary Inclusion Body Myopathy (HIBM)* *Also known as distal myopathy with rimmed vacuoles (DMRV), Nonaka disease, GNE myopathy
Slide 27: SA-ER Substrate Replacement for HIBM
GNE/MNK Enzyme Defective in HIBM SA-ER Substrate Replacement for HIBM Sialic acid deficiency leads to progressive muscle atrophy HIBM mechanism: Sialic acid deficiency caused by defect in the biosynthetic pathway Key symptoms/prognosis: Onset typically at 18-30 years old Loss of major muscle functio
Slide 28: SA-ER: Positive Phase 2 Results at AAN
Randomized controlled study Placebo, 3g and 6g Cross-over of placebo to 3 or 6g at 24 weeks Biochemistry/PK Muscle strength/dynamometer Upper extremity composite Lower extremity composite Other clinical measures Patient-reported outcomes GNEM-FAS functional scale Safety and tolerability AEs and labo
Slide 29: SA-ER: Phase 2 Results Presented at AAN
SA-ER: Phase 2 Results Presented at AAN Upper extremity muscle strength preserved over 48 weeks on 6g 48 Week Analysis (LS Means) 6g vs Placebo (24 weeks) Combined 6g vs Combined 3g (48 weeks) Combined 6g vs Combined 3g (48 weeks) Predefined subset n/a n/a ≥200M 6MWT at baseline UEC Change +2.33 kg
Slide 30: Patient-Reported Outcomes and Safety Results
Patient-Reported Outcomes Consistent with Preservation of Muscle Strength at 6g Safety Results Indicate SA-ER Is Well-Tolerated No Serious Adverse Events occurred No dose-dependent treatment emergent Adverse Events (AEs) identified in the study Most common AEs: Gastrointestinal-related Procedural pa
Slide 31: Business Summary
Business Summary www.ultragenyx.com 30
Slide 32: Financial Overview
Financial Overview Cash, cash equivalents, and short-term investments as of Q2 2014: $153.3 million Total operating loss for 1H 2014: $24.0 million Completed $60.2 million follow-on in July 20141 Expect existing cash to fund operations through 2016 with current operating plan No debt 1Net proceeds
Slide 33: Five Program Data Readouts in 2014-2015
2014 2015 H2 H1 H2 SA-ER rhGUS FAOD Glut1 Phase 1/2 KRN23 Phase 2 (Pediatric) Phase 2 Extension Phase 3 (TBD) Triheptanoin 2014 data points 2015 data points; timing TBD KRN23: Phase 1/2 Adult KRN23: Phase 2 Pediatric rhGUS: Phase 1/2 rhGUS: Phase 3 (TBD) Triheptanoin: Phase 2 FAOD Triheptanoin: Phas
Slide 34: Investment Thesis for Ultragenyx
Investment Thesis for Ultragenyx A rare disease company by design Proven rare disease track record for development Efficiently transforming unrecognized science into effective rare disease products Deep and diversified product pipeline Rich set of value drivers in five programs A next-generation rar
Slide 35: Appendix
Appendix www.ultragenyx.com 34
Slide 36: Rapidly Building a Pipeline and the Company
Rapidly Building a Pipeline and the Company Company founded in 2010; IPO in February 2014 2013 2014 In-licensed from KHK Phase 1 adult data KRN23 rhGUS Triheptanoin SA-ER CTA filing Initiated Phase 1/2 FAOD IND filing FAOD retro data Glut1 IND filing Phase 2 24/48-wk data Initiated DMP IND amend./CT
Slide 37: KRN23 Mechanism of Action
KRN23 Mechanism of Action XLH PATHOPHYSIOLOGY KRN23 MECHANISM OF ACTION
Slide 38: KRN23 Appears Safe and Well-Tolerated
KRN23 Appears Safe and Well-Tolerated Phase 1 single-dose data presented at ASBMR and in JCI Carpenter, et al, IBID 2013 and 2014 No SAEs, deaths, or AEs leading to withdrawal AEs: KRN23 (82%) vs placebo (44%); most were mild Treatment emergent AEs: KRN23 (24/29) vs placebo (4/9). Most common were:
Slide 39: rhGUS Treatment in MPS Mouse
rhGUS Treatment in MPS 7 Mouse Enzyme distribution, urine GAG, and tissue pathology Goal: To verify the enzyme uptake and activity of Ultragenyx’s rhGUS Design: 5 mice/group treated with 0 – 20 mg/kg UX003 IV weekly for 8 weeks Results: Dose-dependent enzyme uptake in wide array of tissues (not show
Slide 40: Triheptanoin for LC-FAOD
Triheptanoin for LC-FAOD Synthetic triglyceride of C7 fatty acids X X X X X X Designed to improve Krebs cycle fat-to-energy conversion Appears to provide TWO substrates Can be converted to glucose unlike MCT
Slide 41: Reduction in Hospital Utilization
Mean Hospitalizations/Year: 36% reduction(1) Reduction in Hospital Utilization Protocol-driven retrospective study of compassionate use patients (1)Excludes 4 infants dosed within 6 months of life (2)Excludes hospitalizations w/unknown discharge dates Mean Hospital Days/Year: 69% reduction(1)(2)
Slide 42: Triheptanoin Mechanism in Glut1 DS
Triheptanoin Mechanism in Glut1 DS Brain energy substrate replacement Glucose Decreased Glucose Uptake Glucose
Slide 43: License and Collaboration with KHK
License and Collaboration with KHK Ultragenyx leads development with costs shared 50/50 Key Terms US and Canada Europe Latin America Commercialization Ultragenyx launches KHK books sales 50/50 profit share for 5 years then tiered revenue share Shared commercial activities over time KHK commercialize
Slide 44: Key Licenses & Intellectual Property
Key Licenses & Intellectual Property Product License Intellectual Property/Royalties KRN23 (XLH) KHK Shared rights to US patents to generic and specific antibodies and use for the treatment of XLH (2022-2029)1 See summary of collaboration rhGUS (MPS 7) St. Louis University IP in progress Low single-
Slide 45: Selected Quarterly Financial Information (Unaudited)
Selected Quarterly Financial Information (Unaudited)
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