1、42nd AnnualJ.P.Morgan Healthcare ConferenceJanuary 2024Emil D.Kakkis,M.D.,Ph.D.CEO and President Confidential and ProprietaryForward looking statementsCautionary note regarding forward-looking statements:This presentation contains forward-looking statements,including,but not limited to,statements re

2、garding our expectations and projections regarding our future operating results and financial performance,anticipated cost or expense reductions,plans with respect to commercializing our product and product candidates,our translational research program,expectations regarding our manufacturing capabi

3、lities,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

4、,expectations regarding the adequacy of clinical data to support marketing applications and approvals of product candidates,our intent to file,and potential timing and success of,marketing applications and other regulatory approvals,expectations regarding timing of receiving potential approval of pr

5、oduct candidates,expectations regarding prevalence of patients,future regulatory interactions,and the value to be generated by our pipeline.Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs,future results,performance or ach

6、ievements to differ significantly from those expressed or implied by the forward-looking statements.Such risks and uncertainties include,among others,our reliance on our third party partner,Kyowa Kirin Co.,Ltd.,for the supply of Crysvita,fluctuations in buying or distribution patterns from distribut

7、ors and specialty pharmacies,the transition back to Kyowa Kirin of our exclusive rights to promote Crysvita in the United States and Canada and unexpected costs,delays,difficulties or adverse impact to revenue related to such transition,smaller than anticipated market opportunities for our products

8、and product candidates,manufacturing risks,competition from other therapies or products,uncertainties related to insurance coverage and reimbursement status of our newly approved products,our evolving integrated commercial organization,uncertainties in the regulatory approval process and the timing

9、of our regulatory filings,the uncertainties inherent in the clinical drug development process,including the potential for substantial delays and risk that earlier study results may not be predictive of future study results,risks related to adverse side effects,the ability for us to successfully deve

10、lop our pipeline product candidates,our ability to achieve our projected development goals in the expected time frames,the potential for any license or collaboration agreement to be terminated,and other matters that could affect sufficiency of existing cash,cash equivalents and short-term investment

11、s 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-looki

12、ng 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

13、,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 for

14、ward-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 refle

15、ct actual results.This presentation concerns commercial products as well as discussion of investigational 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 Feder

16、al 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,Mepsevii,Dojolvi,Pinnacle PCL and our logo are our trademarks.Any other trademarks appearing in these slides are the property of their r

17、espective holders.Confidential and Proprietary2Most productive rare disease company in the industryConfidential and Proprietary34 products across 5 indications approved in 10 yearsmodes targeting cause of diseaseLargest clinical pipeline in rare diseaselate-stage studies64Product approvals since IPO

18、 exceed other successful,rare disease companies4Confidential and ProprietaryBioMarinBioMarin435GenzymeGenzyme523AlexionAlexion1102AlnylamAlnylam1402VertexVertex2100Years from IPO Years from IPO to 1to 1st st approvalapproval#of approvals#of approvals 10y post10y post-IPOIPO#of approvals#of approvals

19、 15y post15y post-IPOIPOApprovals for rare disease indications*Expected based on current pipeline538-12*Deep scientific understanding increases probability of success82%demonstrate clinical success Fastest development in the industry Avg 5.5 yrs from clinic to approvalFirst ever regulatory and devel

20、opment approachesApproved products based on novel trial designs and endpointsKeys to our success:Experienced team focused on innovation,speed,and execution5Confidential and ProprietaryGlobal commercial organizationTreating patients in 34 countries005002018a2019a2020a2021a2022a2023e2024e20

21、24 revenue growth expected to be 20%driven by Crysvita in the U.S.and Latin AmericaRevenue($M)Annual Revenue Growth11 Preliminary and unaudited2 Total Crysvita revenue,including North America,Latin America,and Europe3 Total Revenue includes Crysvita,Dojolvi,Mepsevii,and Evkeeza$356M$430-435MConfiden

22、tial and Proprietary6$266M$182M$103M$28MProduct2023Preliminary12024GuidanceCrysvita2$325-330M$375-400MDojolvi$70-71M$75-80MTotal Revenue3$430-435M$500-530M16%to 23%growth from 2023 mid-point$500-530M1 Excludes Bayer and Daiichi collaboration revenue and includes preliminary estimates for 2023 and 20

23、24Capital allocation focused on key clinical and commercials programs 005006007002022a2023e2024eCash Used in OperationsGTMF CapEx/Non-recurringUses of Cash1Preliminary cash and equivalents2 of$776M as of Dec 31,2023Declining YoY Cash Used in Operations expected to be less than less than$4

24、00M in 20241 Cash used in operations,Gene Therapy Manufacturing Facility(GTMF)Capital Expenses and select non-recurring uses of cash;estimated values for 2023 and 20242 Preliminary,unaudited cash,cash equivalents,and available-for-sale investments as of December 31,2023Confidential and Proprietary7O

25、ngoing revenue growth and continued expense management create path to path to profitability in 2026profitability in 2026Focused on three therapeutic areas8Confidential and ProprietaryXLHXLHTIOTIOCOMMERCIALDEVELOPMENTBONE ENDOCRINEBONE ENDOCRINEUX143UX143Osteogenesis ImperfectaPh 3Ph 3CNS/MUSCLECNS/M

26、USCLEGTXGTX-102 102 Angelman SyndromePh 2Ph 2UX810 UX810 DuchenneUX055UX055CDDPreclinicalPreclinical(Disclosed)MPS VIIMPS VIILCLC-FAODFAODINBORN ERRORS OF METABOLISMINBORN ERRORS OF METABOLISMDTX401DTX401GSDIaPh 3Ph 3DTX301DTX301OTCPh 3Ph 3UX701UX701WilsonPh 2Ph 2HoFHHoFHUX111UX111MPS IIIAPh 3Ph 3Di

27、verse commercial and clinical pipeline9Confidential and ProprietaryCandidateDescriptionPre-ClinicalINDPhase 1Phase 2Phase 3ApprovedPrevalence1Kyowa KirinAnti-FGF23Monoclonal Antibody50,000Enzyme Replacement200RegeneronAnti-ANGPTL3Monoclonal Antibody23,000 5,0003Mereo BiopharmaUX143(setrusumab)Anti-S

28、clerostinMonoclonal Antibody60,000Substrate Replacement8,000 14,000UX111(ABO-102)AAV9 Gene Therapy3,000 5,000DTX401AAV8-G6Pase Gene Therapy6,000DTX301AAV8-OTCGene Therapy10,000UX701AAV9-ATP7BGene Therapy50,000UX055AAV9Gene Therapy20,000 30,000UX810MicrodystrophinGene Therapy40,000GTX-102AntisenseOli

29、gonucleotide60,000X-Linked Hypophosphatemia(XLH)&Tumor-Induced Osteomalacia(TIO)Mucopolysaccharidosis Type VII(MPS VII)Homozygous Familial Hypercholesterolemia(HoFH)Osteogenesis Imperfecta(OI)Long-Chain Fatty Acid Oxidation Disorders(LC-FAOD)Sanfilippo Syndrome(MPS IIIA)Glycogen Storage Disease Type

30、 Ia(GSDIa)Ornithine Transcarbamylase(OTC)DeficiencyWilson Disease(WD)CDKL5 Deficiency Disorder Angelman Syndrome(AS)Small MoleculeProtein BiologicGene TherapyNucleic AcidKey1:Prevalence in commercially accessible geographies2:Ultragenyx licensed ex-US rights to Evkeeza from Regeneron3:Excludes the U

31、S,where Regeneron has rights2Duchenne Muscular DystrophyThree opportunities for significant near-term value creation10Confidential and ProprietaryAngelman SyndromeWilson DiseaseOsteogenesis ImperfectaUX143(setrusumab)for osteogenesis imperfecta:Phase 2 data showed 67%reduction in AFR post-treatment1

32、1Confidential and ProprietaryAfter Setrusumab Initiation0.720.000.511.52P=0.042Median Annualized Fracture Rate(AFR)Phase 3 Endpoint(excluding Fingers,Toes,Face,and Skull)Pre-Treatment2Radiographically Confirmed Fractures16 y/o male patient with Type IV OI,increased mobility after 17 months on study1

33、:Data presented at the companys Analyst Day on October 16,20232:Pre-Treatment period includes fractures in the two years before screening based on medical record review and patient report,and fractures between screening and first doseGTX-102 for Angelman syndrome:Phase 1/2 showed meaningful and impr

34、oving changes across multiple domains at longer timepoints112Confidential and ProprietaryEnrollment in Phase 1/2 complete with 74 patients enrolled Enrollment in Phase 1/2 complete with 74 patients enrolled across Cohorts 1 to 7 and A through Eacross Cohorts 1 to 7 and A through EQuantitative improv

35、ements in Bayley-4 far exceeding natural history Cognition Receptive Communication Gross MotorImprovements in ASA show meaningful reductions in severity Sleep BehaviorSupportive data from EEG delta power and sleep spindle1:Data presented at the companys Analyst Day on October 16,2023GTX-102:Multi-Do

36、main Responder Index(MDRI)captures broad clinical benefit across five domains and multiple endpointsPatient(n=11)ASA SleepASA BehaviorBayley-4 ReceptiveCommBayley-4 Gross MotorBayley-4 CognitionTotalNet Responses*354004364075823711210n/an/a21511

37、10034161DeclineImprovementMinimal Important Difference(MID)ASA-Sleep+/-1 ASA-Behavior+/-1 Bayley-4 Receptive Communication+/-6 Bayley-4 Gross Motor+/-5 Bayley-4Cognition+/-5*P-value is from a sign test13Confidential and Proprietary Median Total Net Responses+2 Net Responses 0p*=0.001p*=0.001*Day 338

38、Data presented at the companys Analyst Day on October 16,2023UX701 for Wilson Disease:Four of five in Cohort 1 tapering SOC,including two completely off chelators and/or zinc therapyCohort 2 dosing completed;4Cohort 2 dosing completed;4 of of 5 patients in Cohort 3 patients dosed5 patients in Cohort

39、 3 patients dosedCohort 1Weeks on StudyReduction of SOC Chelator and/or zinc therapyCopper TraffickingPatient 1820%IndeterminatePatient 270100%Reduced urinary copper and improved trafficking by copper oxidase assayPatient 344100%Reduced urinary copper and improved trafficking by copper oxidase assay

40、Patient 42033%Reduced urinary copper;pending trafficking assessmentPatient 51650%Reduced urinary copper;pending trafficking assessmentConfidential and Proprietary14Data as of October 8,2023Four pivotal gene therapy programsDTX401 for GSDIa HEK293 manufacturing process Phase 3 fully enrolled Data ant

41、icipated in 1H24UX111 for MPS IIIA HEK293 manufacturing process Updated pivotal data to be presented at WORLDSymposiumTM in February 2024 Seeking accelerated review path with FDADTX301 for OTC HEK293 manufacturing process Phase 3 FPI in February 2023 Expect Ph3 to be fully enrolled in 1H24UX701 for

42、Wilson disease Pinnacle PCLTM manufacturing process Phase 1/2/3 study ongoing Stage 1 enrollment completion expected in January 2024&data expected 1H24Confidential and Proprietary15Gene therapy platform built on best-in-class manufacturing capabilitiesConfidential and Proprietary16Pinnacle PCL platf

43、orm Efficient,reliable production of AAV Improved product quality and yield Lower cost and increased speed of production Potentially improved safety of AAV therapy at higher dosesManufacturing facility in Bedford,MAFacility capable of running both HEK and Pinnacle PCLFacility capable of running both

44、 HEK and Pinnacle PCLNear-term key clinical catalysts17Confidential and ProprietaryPROGRAM OBJECTIVETIMINGUX143Osteogenesis ImperfectaComplete enrollment of Phase 3 Orbit study(5-25 y/o)Complete enrollment of Phase 3 Cosmic study(2-5 y/o)Further Phase 2 data update1Q 20241H 20242024GTX-102Angelman S

45、yndromeLPI for Expansion CohortsPhase 1/2 Expansion dataEnd of Phase 2 Discussion with FDA1H 2024Mid-2024UX701Wilson DiseaseStage 1 enrollment completionStage 1 safety and initial efficacy dataInitiation of randomized,placebo-controlled Stage 2January 20241H 20242H 2024DTX401GSDIaPhase 3 data1H 2024

46、DTX301OTC deficiencyPhase 3 enrollment completion1H 2024We are leading the future of rare disease medicineConfidential and Proprietary18Most productive rare disease company in the industryNear-term catalysts for key clinical programsExpect multiple blockbuster product approvals in 2-3 yearsRevenue growth and expense management support path to profitabilityThank youConfidential and Proprietary