Corporate Presentation

Transcription

1 Corporate Presentation May

2 Legal Warning Cautionary note regarding forward-looking statements: This presentation contains forward-looking statements, including, but not limited to, statements regarding our proposed public offering of shares of our common stock, plans with respect to commercializing our product and product candidates, our translational research program, the expected timing of release of additional data for our product candidates, plans to initiate additional studies for product candidates and timing and design of these studies, plans regarding ongoing studies for existing programs, our liquidity position as of the most recent fiscal quarter end, expectations regarding the adequacy of clinical data to support marketing applications and approvals of product candidates, our intent to file marketing applications and the timing of such filings, expectations regarding timing of receiving potential approval of product candidates, and expectations regarding prevalence of patients. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the completion of the proposed public offering on the anticipated terms or at all, our ability to effectively direct the use of the proceeds of our proposed public offering, the uncertainties inherent in the clinical drug development process, such as the regulatory approval process, the timing of our regulatory filings and other matters that could affect sufficiency of existing cash, cash equivalents and short-term investments to fund operations, the availability or commercial potential of our product and product candidates, and our ability to integrate acquired businesses, which are more fully described in our most recent Form 10-Q or Form 10-K under the caption Risk Factors and elsewhere in such reports. Any forward-looking statements made by us reflect our current views with respect to future events or to our future financial performance and involve known and unknown risks, uncertainties, and other factors that may cause our actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by these forward-looking statements. Accordingly, our actual results may materially differ from our current expectations, estimates, and projections. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Any forward-looking statements made by us in this presentation speak only as of the date of this presentation and represent our estimates and assumptions only as of the date of this presentation. Except as required by law, we assume no obligation, and we disclaim any intent, to update these statements to reflect actual results. This presentation concerns drugs that are under preclinical and/or clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (FDA). They are currently limited by Federal law to investigational use, and no representations are made as to their safety or effectiveness for the purposes for which they are being investigated. Ultragenyx, Ultragenyx Pharmaceutical, and our logo are our trademarks. Any other trademarks appearing in these slides are the property of their respective holders. 1

3 Our Strategy Rapidly transforming undiscovered discoveries into effective rare disease products CLEAR BIOLOGY HOW HAVE WE DONE IT? RAPID DEVELOPMENT GLOBAL VISION 2

4 Expanding into New Modalities & Capabilities Optimizing solutions to genetic diseases with clear biology Deep Understanding of Genetic Disease Drug Development Small Molecule Traditional Biologics mrna AAV Gene Therapy Advantages Oral delivery Simple manufacturing High specificity targeting Long half life Ability to target undruggable targets Genomics-based discovery process Potential for onetime treatment for monogenic diseases Current Capabilities In late-stage clinical development: Substrate replacement In late-stage clinical development: Fully human monoclonal antibodies Enzyme replacement therapies In preclinical development: 2 programs using mrna / lipid nanoparticle delivery In early clinical development: 1 AAV gene transfer program in the clinic 2 approaching IND 3

5 Diverse Clinical and Preclinical Pipeline Candidate Description Stage -2 to 0 IND Phase 1 Phase 2 Phase 3 Filed Est d Patients in Dev. World Crysvita Anti-FGF23 monoclonal antibody XLH TIO FDA Approved ~48,000 ~2,000-4,000 CLINICAL Mepsevii UX007 Enzyme replacement Substrate replacement MPS 7 LC-FAOD Glut1 DS FDA Approved ~200 ~8,000-14,000 ~12,000-28,000 TRANSLATIONAL RESEARCH IND READY 4 DTX301 DTX401 UX004 DTX201 DTX701 UX068 Arc-#1 UX001P UX053 Undisclosed DTX501 DTX601 AAV8-OTC Gene Transfer AAV8-G6Pase Gene Transfer rhppca ERT AAV-FVIII Gene Transfer AAV-ATP7B Gene Transfer Substrate replacement mrna/ Lipid Substrate replacement mrna/ Lipid Substrate replacement AAV8-PAH Gene Transfer AAV8-ASS1 Gene Transfer OTC GSDIa Galactosialidosis Creatine Transporter Deficiency GNE Myopathy GSDIII FSHD PKU Hemophilia A Wilson Disease Citrulinemia type I Small Molecule Protein biologic RNA Gene Therapy ~10,000 ~6,000 ~200 ~144,000 >50,000 ~10,000-50,000 >20,000 ~2,000 >10,000 >50,000 ~50,000 ~2,000

6 Numerous Catalysts in 2018 Candidate Disease 1H18 2H18 Crysvita Anti-FGF23 monoclonal antibody XLH TIO Positive EC Decision FDA Approval Bone Quality Data Phase 2 48-week Data Peds Phase 3 Data Mepsevii Enzyme Replacement MPS7 CHMP Opinion (Mid18) UX007 LC-FAOD Phase 2 Filing Decision (Mid18) Phase 3 Study Initiation Substrate Replacement Glut1 DS Phase 3 Movement Disorder Data DTX301 AAV8 gene therapy OTC Deficiency Phase 1/2 Cohort 1 Data Phase 1/2 Cohort 2 Data DTX401 AAV8 gene therapy GSDIa IND Filed Phase 1/2 Cohort 1 Data 5 Regulatory Clinical

7 6 Commercial Progress

8 Unique Commercial Model in Place Commercial model and infrastructure designed specifically for the rare disease environment Early & comprehensive patient diagnosis activities including novel dedicated PDL (patient diagnosis liaison) field team Market access strategy focused on optimizing patient access UltraCare, comprehensive in-house patient support in place Mepsevii launch underway in US Rest of World Pre-Launch activities underway Crysvita launched in US and first patient treated with commercial drug 7

9 Field Teams Are Purpose Built to Support Rare Disease Patients Through Deep Coordination Pre-Launch Activities UltraCare Liaison Payer disease education to Top 50 payers Profile institutional & payer formulary review HCP Center logistical readiness assessment Patient Diagnosis Liaison Patient diagnosis confirmation Treater insight and referral patterns Medical Science Liaison Academic centers & key payers Disease education Opinion leader development & mapping Profile confirmed accounts Medical Affairs Teams 8

10 MEPSEVII US Launch Progress and Rest of World Preparation FDA Approval Estimated EMA Decision Estimated Brazil, Mexico, Chile Decision Launch Estimated Launches Named Patient Programs US Launch Progressing Well Product has been available to ship since 11/28 UltraCare Hub continues to receive start forms First patient infused in December Payer meetings and reimbursement approvals progressing well 9

11 DTX301 Program for Ornithine Transcarbamylase (OTC) Deficiency Phase 1/2 study of adeno-associated virus serotype AAV8 vector encoding human OTC 10

12 DTX301 AAV8 for OTC Deficiency AAV8 gene therapy for stable expression of OTC OTC Deficiency: X-linked urea cycle disorder, genetic defect in ammonia detoxification Key symptoms/prognosis: Acute hyperammonemic episodes that can lead to hospitalization, adverse cognitive & neurological effects, death Treatment limited; only curative approach is liver transplantation WW prevalence: ~10,000, 80% late-onset Status: 11 DMC Review of Cohort 1 data complete & proceeding to Cohort 2 Cohort 2 data expected 2H18 Bowing CHILDREN

13 DTX301 AAV8 for OTC Study Design Study Phase Phase 1/2 Study Design Dosing Study Population Sample Size Open-label, multicenter, safety and dose-finding study to determine the safety, tolerability, and efficacy Single intravenous infusion Cohort 1: ^12 GC/kg Cohort 2: ^12 GC/kg Cohort 3: ^13 GC/kg Adults with late-onset OTC deficiency Approximately 6 to 12 patients enrolled sequentially into cohorts 3 patients enrolled in Cohort 1 3 patients will be enrolled in each subsequent cohort Follow-up Period Patients will be followed for 52 weeks after dosing 4-year extension study planned to evaluate the long-term safety and efficacy of DTX301 12

14 Cohort 1: Favorable Initial Safety Profile Safety Summary No infusion-related adverse events No SAEs to date All AE severity graded as 1 or 2 All AEs resolved and unrelated to drug except for elevated liver enzymes (probable relatedness, resolved) Patient 1 Completed 24 weeks Mild elevated liver enzymes between Weeks 4 and 6 (peak 45 IU/L) ALTs returned to normal* after tapering course of corticosteroids 8 AEs (Grade 1 or 2) Patient 2 Completed 20 weeks Mild elevated liver enzymes at Day 36 (peak 118 IU/L) ALTs returned to normal following tapering course of corticosteroids Patient 3 Completed 12 weeks 1 unrelated AE (Grade 1) * Normal ALT levels <40 IU/L

15 Patient 1: Normalization of Ureagenesis % Normal Ureagenesis vs. ALT Patient 1 Rate of Ureagenesis Baseline Activity (% of Normal Ureagenesis) Alternate pathway medications discontinued 2/16/18 Alanine Aminotransferase (U/L) 200 umol/kg/hr 6 weeks 67% increase from baseline to 335 umol/kg/hr 12 weeks 30% increase from baseline to 261 umol/kg/hr 20 weeks 36% increase from baseline to 273 umol/kg/hr 24 weeks 100.8% increase from baseline to 402 umol/kg/hr Normal rate of ureagenesis: ~300 umol/kg/hr 14 Highest prednisone dose of 60mg/day; then tapered

16 Patients 2 and 3: Ureagenesis and ALT Levels % Normal Ureagenesis vs. ALT Patient 2 Activity (% of Normal) ALT (U/L) Patient 3 Activity (% of Normal) ALT (U/L) 15

17 DTX301 Timeline Cohort 1 DMC Review Complete & Proceeding to Cohort H 1H 2H Cohort 1 12week follow-up DMC Cohort 2 12week follow-up DMC KEY UPDATES DMC review of Cohort 1 complete and proceeding to Cohort 2 March 2018: Opening of Cohort 2 enrollment scheduled 2H18: Data from Cohort 2 expected 16

18 DTX401 AAV8 for GSDIa GSDIa: Autosomal recessive, inborn error of glucose metabolism; deficient glucose-6-phosphatase (G6Pase) Key symptoms/prognosis: Hypoglycemia leading to significant morbidity and mortality Hepatomegaly and nephromegaly; long-term liver and renal disease Hyperlipidemia, hyperuricemia, lactic acidemia in the blood Impaired growth and delayed puberty Severe long-term complications in 70-80% patients incl. hepatocellular adenomas, carcinomas, osteoporosis Limited Treatment Option: Raw cornstarch Prevalence: 6,000 WW 17 Glucose Krebs Cycle GSD I Status: IND and first Patient expected to be enrolled 1H18 GLYCOGEN Gluc-6-Phos Pyruvate Acetyl CoA Uric Acid Lactate Lipids

19 DTX401 AAV8 for GSDIa Second Gene Therapy Program Nearing IND H 2H IND Filing First Patient Dosed Cohort 1 12week follow-up DMC KEY UPDATES IND submission on track for 1H Clinical trial site selection ongoing in US, Canada and EU First patient dosed in clinical trial planned for 1H Cohort 1 data in 2H 18

20 UX007 for Long-Chain Fatty Acid Oxidation Disorders* (LC-FAOD) Phase 2 substrate replacement therapy (oral liquid) *Includes VLCAD, LCHAD, CPT-I, CPT-II, TFP, CACT 19

21 UX007 for LC-FAOD Triglyceride of C7: alternative energy source to long-chain fat LC-FAOD: Inability to convert fat into energy MITOCHONDRIAL ENZYME DEFICIENCIES Key symptoms/prognosis: Hypoglycemia, muscle rupture, heart failure Mortality of ~50% 1 ; a cause of SIDS (newborn screened in US) Standard of care: Diet and MCT 2 oil US prevalence: ~2,000 3,500 Clinical status: Decision on filing based on Phase 2 data mid 2018 Krebs cycle Phase 3 study initiation 2H18 1 J Inherit Metab Dis 2013;36: Medium chain triglycerides 20

22 Phase 2 Data Showed Reduction in Frequency and Duration of Major Clinical Events ALL MAJOR CLINICAL EVENTS (MCEs), N=29 Overall annualized event rate Overall annualized duration rate Mean 48.1% * 50.3% ** Median 50.6% 76.7% * p= ** p= Patient 98.4% REDUCTION IN HYPOGLYCEMIA EVENTS Hospitalization Medical Intervention Days Left of Day 0 shows events in 78 weeks pre-ux007 treatment; Right of Day 0 shows events during UX007 treatment 21

23 Safety Profile as Expected from Prior Studies 5/29 patients discontinued 1 due to diarrhea in wk 1 and considered treatment related 4 withdrew consent (wks 1, 8, 8, 78) for reasons not attributed to UX patients (66%) with treatment-related adverse events (most were mild-to-moderate in nature) Most common treatment-related adverse events were GI-related: diarrhea, abdominal/gi pain, and vomiting Some GI events were managed by adjusting dosing or dosing with food No deaths and 1 treatment related SAE of moderate gastroenteritis with vomiting 22

24 Potential Filing on Phase 2 Data and Finalizing Phase 3 Study Providing additional information to FDA for potential consideration of IND based on Phase 2 data Based on end-of-phase 2 meeting with FDA, Ultragenyx is submitting additional information to support that the improvement demonstrated was likely due to UX007 and not dietary/other changes Decision on potential filing based on Phase 2 data in mid-2018 Completing design of a Phase 3 study Randomized, controlled study Primary endpoint: major clinical events Could be used for registrational or confirmatory purposes Planning to initiate in 2H18 23

25 UX007 for Glucose Transporter Type 1 Deficiency Syndrome (Glut1 DS) Phase 3 substrate replacement therapy (oral liquid) 24

26 UX007 for Glut1 Deficiency Syndrome Alternative energy source for the brain Mechanism: Glucose transport defect causes brain energy deficiency Less Glucose Uptake (red color) in Glut1 DS Key symptoms: Seizures, movement disorder, developmental delay Standard of care: Ketogenic diet (70-80% of calories in fat, <10% carbs) U.S. prevalence: ~3,000 7,000 Clinical status: Phase 3 movement disorder study enrollment complete (44 patients); data expected 2H18 Normal Glucose Uptake Glut1 DS Glucose Uptake 25 Ann Neurol 2002

27 Glut1 DS Movement Disorder Ph3 Study Design STUDY DESIGN KEY ENDPOINTS Runin Titration Period Titration Period UX007 Placebo Wash-out Titration Period Titration Period Placebo UX007 UX007 OLE Extension Frequency of disabling paroxysmal movement disorder events: daily electronic diary Week Children and Adults with Glut1 DS 44 patients (1:1 randomization) Experiencing disabling movement disorder events Not on KD Duration of disabling paroxysmal movement disorder events: daily electronic diary 26

28 Crysvita Launch Progress and Rest of World Preparation U.S. FDA EU Conditional Approval Marketing Authorization Estimated Canada Decision Estimated Chile, Mexico, Colombia, Brazil, Argentina, Switzerland*, Decisions Launch* US Launch Named Patient Programs Various EU launches throughout the year* 27 *Denotes territories where KKI has commercial responsibility

29 28 Finance and Business Summary

30 Financial Overview Cash 1 (as of March 31, 2018): $571.3 million Operating loss (three months ended March 31, 2018): $96.5 million Cash used in operations (three months ended March 31, 2018): $89.5 million No debt (as of March 31, 2018) 29 1 Cash, cash equivalents, and investments

31 Investment Thesis Diverse, robust company Able to execute One approved therapy; second launch on horizon Four modalities to optimize treatment of rare diseases 14+ programs spanning preclinical to commercial 3 Phase 3 programs 2 clinical-stage gene therapy programs 10+ translational research programs Deep domain expertise and high-quality team Rapid execution and innovation in clinical and regulatory strategy Capital-efficient well resourced business model Commercial-stage with global reach 30

32 31 Appendix

33 License and Collaboration with KHK Ultragenyx leads development with costs shared 50/50 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 commercializes and books sales Ultragenyx commercializes and books sales Royalties After 5 years, tiered revenue share in mid to high 20% range to Ultragenyx after profit share period Up to 10% royalty to Ultragenyx Low single-digit royalty to KHK Commercial supply KHK supplies; price is doubledigit percentage of net sales NA KHK supplies; price is double-digit percentage of net sales 32

34 Disease Burden Survey in Adult XLH Patients Online survey of 165 adults in 13 countries Adults can experience progressively debilitating complications that cause pain and negatively impact functional independence, quality of life despite longterm treatment in childhood with conventional therapy Majority of patients receiving treatment 69% receiving current treatment 50% receiving oral phosphate/vitamin D 71% taking medication for bone or joint pain > 1x/wk 47% had a bone fracture Significant pain, stiffness, physical functioning impairment Bone pain (75%), joint pain (90%), joint stiffness (87%) Restricted range of motion, gait disturbance, muscle pain/weakness (70%) WOMAC pain, stiffness, physical function scores well below normal Calcification outside the bone was commonly reported Osteophytes (46%); enthesopathy (32%); nephrocalcinosis (23%); spinal stenosis (23%); kidney stones (16%) 33

35 Key Licenses & Intellectual Property Product License Intellectual Property/Royalties Burosumab (XLH, TIO) KHK Shared rights to US patents to generic and specific antibodies and use for treatment of XLH ( ) 1 See summary of collaboration Vestronidase Alfa (MPS 7) UX007 (LC-FAOD) UX007 (Glut1 DS) DTX301 (OTC Deficiency) St. Louis University Composition and use for treatment of MPS 7 (2035) Low single-digit royalty Baylor Research Institute (BRI) Composition ( ) 2 Use for treatment of LC-FAOD (2020) Mid single-digit royalty BRI & UniQuest Composition ( ) 2 Use for treatment of Glut1 DS associated movement disorders (2033) Mid single-digit royalty Sub-License from REGENXBIO of UPENN IP Composition and use for treatment of OTC Deficiency ( ) Low to mid single-digit royalty 1 Without patent term extension of up to fourteen years from approval 2 Without patent term extension of up to five years 39