Slides
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Confidential and Proprietary Corporate Presentation August 2025
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Forward looking statements Cautionary note regarding forward-looking statements: This presentation contains forward-looking statements, including, but not limited to, statements regarding our expectations, estimates, assumptions, and projections regarding our future operating results and financial performance, including our expectations for profitability in 2027, anticipated cost or expense management, plans with respect to commercializing our product and product candidates, expectations regarding our manufacturing capabilities, 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 or commercializing 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 product 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 achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, fluctuations in buying or distribution patterns from distributors and specialty pharmacies, smaller than anticipated market opportunities for our products 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 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 develop our pipeline product candidates, our ability to achieve our projected development goals in the expected time frames, risks related to reliance on third parties to conduct certain activities on the company's behalf, our limited experience in generating revenue from product sales, our dependence on Kyowa Kirin for the commercialization of Crysvita in certain major markets, including the U.S. and Canada, and for commercial supply of Crysvita in those markets, 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 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, actual results or outcomes may materially differ from our current expectations, estimates, assumptions 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 expectations, estimates, assumptions and projections 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 or outcomes. 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 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, Mepsevii, Dojolvi, Pinnacle PCL and our logo are our trademarks. Any other trademarks appearing in these slides are the property of their respective holders. Confidential and Proprietary2
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Who we are 3 Confidential and Proprietary Next generation rare disease company dedicated to the development and delivery of transformative treatments where none exist
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Our differentiated approach to rare diseases is yielding great results 4 Confidential and Proprietary Pursue high potential programs • Potent biology in severe diseases • Treating underlying cause • Best modality for each disease Accelerate to drive value • Adaptive trial designs • Novel endpoints • High unmet medical need supporting expedited enrollment Patient-centric approach • Lean commercial team • Emphasize patient find/support • Reduced post-approval R&D costs Research Development Commercial Find right opportunities at reasonable cost, develop rapidly with adaptive designs, and commercialize efficiently and effectively
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Creating a successful and profitable rare disease company 5 Confidential and Proprietary 4 commercial products Largest clinical pipeline in rare disease Near-term approvals Phase 2/3 studies6 3 Avery and Addison live with osteogenesis imperfecta
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Focused on three therapeutic areas Late-stage pipeline will leverage successful global commercial organization 6 Confidential and Proprietary LATE STAGE 1 CLNICAL PROGRAMS BONE -ENDOCRINE Ph 3: UX143 for OI INBORN ERRORS OF METABOLISM XLH & TIO COMMERCIAL MPS VIILC-FAOD HoFH Ph 3: UX111 for MPS IIIA Ph 3: DTX401 for GSDIA Ph 3: GTX-102 for AS 1: Clinical pipeline available in Appendix NEUROGENETIC Ph 3: DTX301 for OTC Ph 2: UX701 for WD
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UX143 (setrusumab) Anti-Sclerostin monoclonal antibody Intravenous (IV) Infusion ~60,000 GTX-102 ASO activating paternal expression of UBE3A Intrathecal (IT) Infusion ~60,000 UX111 AAV9 SGSH gene therapy IV Infusion ~3,000 – 5,000 DTX401 AAV8-G6Pase gene therapy IV Infusion ~6,000 DTX301 AAV8-OTC gene therapy IV Infusion ~10,000 UX701 AAV9-ATP7B gene therapy IV Infusion ~50,000 Diverse late-stage clinical pipeline 7 Confidential and Proprietary Candidate Description Phase 1 Phase 2 Phase 3 Route of Admin Prevalence1 Osteogenesis Imperfecta (OI) Sanfilippo Syndrome (MPS IIIA) Glycogen Storage Disease Type Ia (GSDIa) Ornithine Transcarbamylase (OTC) Wilson Disease (WD) Angelman Syndrome (AS) 1: Prevalence in commercially accessible geographies Bone/Endo Inborn Errors of MetabolismNeurogeneticTherapeutic Area:
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Drivers of value creation in 2025 8 Confidential and Proprietary UX143 for OI Ph3 data readout GTX-102 for AS Ph3 enrollment completion Revenue expansion & near-term launches 1 2 3 Amber and her daughter live with osteogenesis imperfecta Mason lives with Angelman syndrome Aly lives with XLH
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UX143 for osteogenesis imperfecta (OI) Fully human monoclonal antibody; Ph3 data readout around the end of the year Osteogenesis Imperfecta: Collagen defect leading to low bone mineral density (BMD) and frequent fractures − Associated with pain and decreased mobility • Treatment: No globally approved therapies; bisphosphonates used off label • Prevalence*: ~60,000 (Types I/III/IV) UX143 Setrusumab: Fully human mAb to inhibit sclerostin and turn on bone production via normal pathway • Phase 3 data expected around the end of the year • Investing in commercial supply • Extensive launch expertise in bone/endocrine from Crysvita • Priority Review Voucher (PRV) eligible Confidential and Proprietary9 *Prevalence in commercially accessible geographies Matthew lives with osteogenesis imperfecta “I have not yet encountered a patient with a fragility fracture while on setrusumab, and this may result from setrusumab’s effects on the skeleton, improving the rate of new bone formation and bone quality.” Gary Gottesman, MD Professor of Pediatrics and Medicine Washington University School of Medicine In reference to October 14, 2023 Phase 2 data presentation
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UX143 for OI: Phase 2 data: 67% reduction1 in annualized fracture rate (AFR) P=0.0014 10 Confidential and Proprietary After Setrusumab Initiation 0.72 0.0 0 0.5 1 1.5 2 P=0.0014 Median Annualized Fracture Rate (AFR) Phase 3 Endpoint (excluding Fingers, Toes, Face, and Skull) Pre- Treatment2 Radiographically Confirmed Fractures1 6 y/o male patient with Type IV OI, increased mobility after 17 months on study 1: Interim data as of May 24, 2024 and includes a mean follow -up of 16 months. 67% reduction = Median(AFR Post -Tx Initiation - Pre-Tx) ÷ Median(AFR Pre-Tx) 2: 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 dose Interim data as of May 24, 2024
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UX143 for OI: Phase 2 data demonstrated increase in lumbar spine BMD and Z-score observed at 12 months 11 Confidential and Proprietary as Lumbar Spine BMD (Mean + SE)1 Percent Change from Baseline Lumbar Spine BMD1 Z-Score Change from Baseline Mean Baseline Z-score of -1.73 goes to -0.49 at 12 months; P-values represent change from Baseline P-values represent change from Baseline 9.16 ± 1.43 14.19 ± 2.15 22.25 ± 2.71 p<0.0001 0.58 ± 0.10 0.85 ± 0.13 1.25 ± 0.17 p<0.0001 1 Interim data as of May 24, 2024 Baseline Month 3 Month 6 Month 12 Baseline Month 3 Month 6 Month 12
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UX143 for OI: Younger patients in Phase 2 showed a very large 29% increase in BMD at Month 12 12 Confidential and Proprietary Lumbar Spine BMD by Age Group1 % Change from Baseline at Month 12 1 Interim data as of May 24, 2024
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UX143 for OI: Phase 2 safety data1 consistent through Month 14 13 Confidential and Proprietary No drug-related hypersensitivity reactions No treatment-related SAEs No unexpected adverse events or safety concerns No patients discontinued treatment for any adverse event 1: As of a May 24, 2024 cutoff
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Persuasive Phase 2 data1 support transformational effects of UX143 14 Confidential and Proprietary UX143 builds bone, exactly where needed, increasing bone strength, while improving overall bone health Participants in Phase 2 have been on therapy for more than 2 years Participants in Phase 2 have reduced fractures, while increasing physical activities and shown improved functional effects 1 Interim data as of May 24, 2024
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GTX-102 for Angelman syndrome (AS) Antisense oligonucleotide; Phase 3 enrollment completed Confidential and Proprietary15 Angelman Syndrome: Loss-of-function of maternal UBE3A gene − Cognitive, communication, motor, behavior, and sleep impairment and seizures − Requires continuous care • Treatment: No approved therapies • Prevalence*: ~60,000 GTX-102: Antisense oligonucleotide (ASO) to activate paternal expression of UBE3A • Phase 3 Aspire Study in deletion patients enrollment completed • Phase 2/3 Aurora study in other genotypes and ages expected to begin in 2H-2025 *Prevalence in commercially accessible geographies “Angelman syndrome affects cognitive and motor function, making walking, communicating, and performing many everyday tasks more difficult…The initiation of the Phase 3Aspire study by Ultragenyx is a significant achievement and something the community should celebrate.” Joint statement from Amanda Moore, chief executive officer at the Angelman Syndrome Foundation (ASF) and Ryan Fischer, chief operating officer at Foundation for Angelman Syndrome Therapeutics (FAST) Conner lives with Angelman syndrome
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GTX-102 for AS: Overview of Phase 1/2 long-term safety and efficacy Data shared via press release on November 9, 2024 16 Confidential and Proprietary Participants have made consistent developmental gains with sustained improvements across multiple symptom domains up to 3 years on therapy No additional cases of lower extremity weakness; safety profile is understood and remains consistent Phase 3 study Aspire enrollment completed in July 2025
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GTX-102 for AS: Cognition by Bayley-4 GSV and raw scores show ample power for Phase 3 trial 17 Confidential and Proprietary Bayley-4 GSV Score Mean (±SE) Change from Baseline GTX-102 Arm Mean (SD) 3x NHS2 Data§ Mean (SD) Hypothesized Difference SD* Power^ (α = 0.045) 10.9 (13.5) 1.2 (9.5) 9.7 13.5 95.5% GTX-102 Arm Mean (SD) 3x NHS2 Data§ Mean (SD) Hypothesized Difference SD* Power^ (α = 0.045) 6.7 (8.6) 0.9 (4.8) 5.8 8.6 92.9% §Natural History data: Linking Angelman and Dup15q Data for Expanded Research (LADDER) at Day 365. *Conservative SD assumption. ^N=108 completers out of 120 randomized (1:1) with 10% drop out rate. Cohort 4-7 and A&B Pts Grey dotted line denotes individual response threshold ≥ 5 for cognitive GSV. Bayley-4 Raw Score Mean (±SE) Change from Baseline 15 10 5 0 40 17 Day 338 Day 506 20 15 10 5 0 40 17 Day 338 Day 506 Data shared via press release on November 9, 2024 Cohort 4-7 and A&B Pts Ph3 Primary Endpoint: Bayley-4 Cognition raw score trend comparable to GSV and is also well powered Bayley-4 Cognition GSV scores show significant gains at Day 338 that continue through Day 506
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GTX-102 for AS: Multi-domain responder index shows ~80% of participants with clinically meaningful net improvement in ≥ 1 domain at Day 338 18 Confidential and Proprietary Data shared via press release on November 9, 2024 • MDRI is a key secondary endpoint in Phase 3: Sleep, Gross Motor, Behavior (Hyperact./ Noncompl.), Rec. Comm. and Cognition • Ph1/2 data: persuasive statistically significance, capturing meaningful responses • Bayley-4 GSV score to be used for MDRI o MID exists for GSV scores Minimal important difference (MID): ASA: Sleep = ± 1; Gross Motor = ± 1 ABC-C: Hyperactivity/Noncompliance RAW = ± 6 Bayley-4: Receptive Comm GSV = ± 6; Cognition GSV = ± 5 Green color code indicates an improvement: ≥ +1 MID Pink color code indicates a decline: ≤ -1 MID White indicates minimal to no change Last observation used for imputing missing post-baseline data Key Takeaways Cohort A & B (N=28) responder analysis ASA Sleep ASA Gross Motor ABC-C ABC-C Hyperact/Noncomp Bayley-4 Rec Comm Bayley-4 Cognition Total Net Response +5 +5 +4 +4 +4 +4 +3 +3 +3 +3 +3 +2 +2 +2 +2 +2 +2 +2 +1 +1 +1 +1 0 0 0 0 0 -1 Cohorts A&B Day 338 Net Response: +2; p-value: <0.0001
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GTX-102 for AS: Safety summary • Changes in dose administration provided acceptable safety profile • No unexpected serious adverse events • Two patients from Expansion Cohorts (N=53; previously disclosed in April 2024) had serious adverse events of transient lower extremity weakness assessed as related to study treatment • Both resolved rapidly without sequelae and remain in the study without ongoing safety concerns • Patients redosed with multiple doses following resolution of lower extremity weakness • Five original patients from Cohorts 1-3 (previously disclosed in October 2020) safely re-dosed multiple times and are receiving maintenance treatment without recurrence • The Cohort 7 patient (previously disclosed in January 2023) has also re-dosed safely multiple times and is receiving maintenance treatment without recurrence FDA and other regulators notified of safety events; no issues raised and no additional actions requested 19 Confidential and Proprietary Data shared via press release on November 9, 2024
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GTX-102 for AS: Phase 3 development plans Confidential and Proprietary Aspire enrollment completed in July 2025; expect Aurora to initiate in 2H-2025 • Randomized, controlled study in deletion patients • Sample size: ~120 patients; ages 4 to <18 years • 48-week primary efficacy period • Primary Endpoint: Bayley-4 Cognition raw score • Key Secondary: MDRI across cognition, receptive communication, behavior, gross motor, and sleep • Additional, individual secondary endpoints for domains of communication, behavior, gross motor, and sleep Aspire: Phase 3 Study1 Aurora: Additional Genotype and Ages Study • Open label • Ages <4 and >18 years of age • Non-deletion types • Duration, endpoints and other details to be determined with regulatory agencies 20 1: Based on EOP2 meeting with FDA; disclosed July 17, 2024
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UX111 for Sanfilippo syndrome (MPS IIIA) AAV9 gene therapy “It's impressive to see how our study patients treated with UX111 have maintained their communication skills despite being the age in which regression begins to occur…improving behavioral problems and thus family daily life.” Mireia del Toro, M.D. Coordinator of the Metabolic Unit, Pediatric Neurology Department, Hospital Universitari Vall d´Hebron, Barcelona In reference to data presented at WORLDSymposium in February 2024 MPS IIIA: Fatal lysosomal storage disease of CNS − Early childhood onset − Rapid neurodegeneration • Treatment: No approved therapies • Prevalence*: ~3,000 to 5,000 UX111: Gene therapy to restore SGSH gene in CNS and peripheral organs • Actively working to resolve FDA observations in CRL • Priority review granted, PRV eligible • Investing in commercial supply • Leverage existing inborn errors of metabolism field team 21 Confidential and Proprietary * Prevalence in commercially accessible geographies Sadie lives with MPSIIIA
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UX111 for MPS IIIA: Substantial reduction in CSF HS1 exposure regardless of age or stage of disease 22 Confidential and Proprietary Data presented at WORLDSymposium 2025 • > 80% of participants reduced CSF HS by 50% in efficacy set • Median CSF HS exposure • Efficacy set (N=27): −64.51% (p<0.0001) • mITT set (N=17): −65.96% (p<0.0001) • Maximum reduction: ~79% • * One patient with immune response lost expression and cognitive function CSF HS Exposure (%) Rapid reduction in CSF HS1 over 7 to 77 months Months since UX111 Administration Key Takeaways * 1: cerebral spinal fluid (CSF) heparan sulfate (HS)
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UX111 for MPS IIIA: Treatment with UX111 led to improved Bayley-III raw scores compared to natural history 23 Confidential and Proprietary Data presented at WORLDSymposium 2025 • Model-based est'd LS mean (SE) of change from ages 24 to 60 mths in BSITD-III Cognitive Raw Score – mITT participants improved by +16.0 (2.9) points – Untreated Natural History patients declined by - 6.8 (2.3) points – Treatment effect: +22.7 points (p <0.0001) • Statistically significant improvement in receptive & expressive communication raw scores (not shown) • Numerical improvement in fine motor and gross motor scores (not shown) – Gross motor function is generally lost later in the disease process, and longer-term follow-up may be needed to see statistically significant changes
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UX111 for MPS IIIA: Conclusions 24 Confidential and Proprietary • UX111 led to substantial and sustained reductions in CSF HS exposure over time, irrespective of age or stage of disease progression at the time of treatment • Reduction in CSF HS exposure correlated with improved Bayley-III Scores • Statistically significant correlations between CSF HS exposure and estimated yearly change were seen for all 5 Bayley-III subdomains • Younger participants treated early in disease progression showed gains in cognitive skills, expressive and receptive communication, and fine motor skills compared to natural history • Older participants treated at more advanced stages of disease showed retention of key functions of communication, feeding, and ambulation • UX111 was generally well tolerated across all doses, including the highest dose of 3.0 × 10 13 vg/kg, and observed adverse reactions were manageable Data presented at WORLDSymposium 2025
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DTX401 for glycogen storage disease type Ia (GSDIa) AAV8 gene therapy; BLA submission expected in 4Q-2025, launch 2026 “I don't think people can understand how fast the blood sugars fall. And the stress that these families have, knowing that if you oversleep or you miss your alarm clock, your child can die or have a seizure.” David Weinstein Former Director-Glycogen Storage Disease Program Connecticut Children's Medical Center GSDIa: Life-threatening defect in liver’s ability to release glucose due to G6Pase deficiency − Severe hypoglycemia − Long-term liver and renal disease • Treatment: Modified diet, cornstarch slurries every few hours around the clock, or liver transplantation • Prevalence*: ~6,000 DTX401: Gene therapy to express G6Pase-α • BLA submission expected in 4Q-2025, launch 2026 • Manufacturing in-house at our Bedford, MA plant • Leverage existing inborn errors of metabolism field team • PRV eligible 25 Confidential and Proprietary *Prevalence in commercially accessible geographies Daily cornstarch consumption
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DTX401 for GSDIa: Phase 3 successful across primary and key secondary endpoints %∆ daily cornstarch intakePrimary Endpoint Key Secondary Endpoints p-value <0.0001 # of total daily doses of cornstarch 0.0011 %∆ glucose values in hypoglycemic range (<70 mg/dL), assessed for non-inferiority <0.0001 Patient Global Impression of Change score at Week 48 (median) 0.132 Key Takeaways • GSDIa is a severe, life-threatening metabolic disease, with long term complications due to inability to control glucose • Phase 3 data demonstrated DTX401 significantly reduced patients dependance on cornstarch, while maintaining glucose control • Substantial unmet need and we have extensive experience commercializing rare disease medicines 26 Confidential and Proprietary Data presented via conference call on May 30, 2024
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Week 120: Crossover and original treatment arms continued reducing daily cornstarch (CS) DTX401 for GSDIa: Phase 3 patients continued improving at last visit in crossover and originally treated arms 27 Confidential and Proprietary • Crossover patients, previously treated with placebo, demonstrated a 64% reduction in daily CS at their last visit • 69 week mean follow-up post-DTX401 treatment • Patients able to titrate CS much more rapidly once treatment confirmed with DTX401 and with timely, direct access to their glucose levels • Patients in the original DTX401 group demonstrated a 60% reduction in daily CS at their last visit • 120 week mean follow-up • DTX401 demonstrated a consistent and acceptable safety profile as of the data cut-off Week 48: Statistically significant reduction (41%) in daily cornstarch intake (p < 0.0001) Placebo DTX401 Percent Change from Baseline in Daily Cornstarch (CS) Intake (g) Week 120 data presented via press release on May 6, 2025
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DTX401 for GSDIa: Patients treated showed significant reduction in frequency and quantity of day and nighttime cornstarch vs placebo at Week 48 Nighttime Cornstarch (CS) Doses and Grams Nighttime CS Doses (n) Placebo N=17 DTX401 N=17 p-value Baseline Mean (SD) 1.8 (1.1) 1.7 (0.7) ∆ BL to W48 Mean (SD) +0.3 (1.4) -0.4 (0.6) ∆ BL to W48 LS Mean (SE) +0.4 (0.3) -0.4 (0.3) 0.0410 Changes from baseline for patients who required nighttime CS at baseline Nighttime CS Intake (g) Placebo N=17 DTX401 N=17 p-value Baseline Mean (SD) 100 (74.4) 87.4 (37.0) %∆ BL to W48 Mean (SD) +8.5 (69.3) -42.4 (29.3) %∆ BL to W48 LS Mean (SE) +6.9 (14.5) -44.1 (15.0) 0.0091 Total Daily CS Doses (n) Placebo N=24 DTX401 N=20 p-value Baseline Mean (SD) 5.1 (1.4) 5.8 (1.4) ∆ BL to W48 Mean (SD) -0.1 (0.6) -1.1 (0.9) ∆ BL to W48 LS Mean (SE) -0.2 (0.2) -1.1 (0.2) 0.0011 Total Daily Cornstarch (CS) Doses Changes from baseline for patients who required nighttime CS at baseline “With these Phase 3 results, the significant reduction in cornstarch intake with continued management of glucose control has the potential to offer meaningful benefit to patients while improving quality of life on a daily basis.” Rebecca Riba-Wolman, M.D. Director of the Glycogen Storage Disease Program & Disorders of Hypoglycemia at Connecticut Children’s Medical Center and investigator on the study 28 Confidential and Proprietary Data presented via conference call on May 30, 2024
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UX701 for Wilson disease (WD) AAV9 gene therapy; Stage 1, Cohort 4 Enrollment Completion in 2H-2025 Wilson disease: Life-threatening defect in liver’s ability to metabolize copper due to ATP7B mutation − Liver failure − Neurologic deterioration − Death, if untreated • Treatment: Modified diet, chelation therapy, or liver transplantation • Prevalence*: ~50,000 UX701: Gene therapy designed for stable expression of ATP7B gene • Stage 1, Cohort 4 enrollment completion expected in 2H-2025 • Manufacturing in-house at our Bedford, MA plant 29 Confidential and Proprietary *Prevalence in commercially accessible geographies GT manufacturing facility in Bedford, MA
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UX701 for WD: Clinical activity observed in Stage 1 with 6 of 15 patients completely off chelators and/or zinc therapy1 30 Confidential and Proprietary • Clinical activity observed across all three dose cohorts in Stage 1 • 6 of 15 patients completely off chelators and/or zinc therapy • 1 additional patient tapering standard of care • In responders, non-ceruloplasmin bound copper (NCC) stabilized to normal, healthy levels • Some patients demonstrated increased ceruloplasmin-copper activity consistent with improved loading of copper on ceruloplasmin by ATP7B function • UX701 well tolerated, with no unexpected related treatment emergent adverse events 1: Data disclosed in press release on October 3, 2024 Plan to enroll additional cohort at moderately increased dose and with optimized immunomodulation
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0 100 200 300 400 500 600 700 2017 2018 2019 2020 2021 2022 2023 2024 2025e 2025 total revenue expected to grow 14-20% Annual Revenue Growth1 1 Total Crysvita revenue, including North America, Latin America, and Europe 2 Total Revenue includes Crysvita, Dojolvi, Mepsevii, and Evkeeza $356M $433M Confidential and Proprietary31 $266M $103M $28M Product 2024 Actuals 2025 Guidance Crysvita1 $410M $460-480M 12-17% Dojolvi $88M $90-100M 2-13% Total Revenue 2 $560M $640-670M 14-20% $560M 1 Excluding Bayer and Daiichi collaboration revenue, estimates for 2025. Logos indicate launch year. $0.5M $182M TIO Revenue ($M) XLH $640-670M
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Project full year GAAP profitability in 2027 Confidential and Proprietary32 • Revenue: Continued double-digit growth from current products and contribution from three upcoming launches • Operating expense: Continued expense management, incorporating select investments to maximize launch success • Cash: • Planned monetization of PRVs from UX111, DTX401, and UX143 • $538M in cash, cash equivalents, and marketable debt securities as of June 30, 2025 Core Assumptions
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Key clinical and regulatory catalysts 33 Confidential and Proprietary PROGRAM OBJECTIVE ANTICIPATED TIMING UX143 Osteogenesis imperfecta Phase 3 Orbit final analysis (threshold: p<0.04) Around end of 2025 GTX-102 Angelman syndrome Phase 3 Aspire study initiation Phase 3 Aspire enrollment completion Phase 2/3 Aurora study initiation 2H-2025 UX111 Sanfilippo syndrome Resubmit BLA To be updated DTX401 GSDIa BLA filing 4Q-2025 UX701 Wilson disease Stage 1, Cohort 4 enrollment completion 2H-2025 DTX301 OTC deficiency Phase 3 enrollment completion
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We are creating a successful and profitable rare disease company Confidential and Proprietary34 History of outstanding clinical and outstanding commercial execution Revenue growth and new launches plus expense management to achieve expected full-year GAAP profitability in 2027 and beyond Near-term catalysts from 6 Phase 2/3 studies and 3 potential approvals
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Appendix Confidential and Proprietary
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Key licenses & intellectual property – commercial products 36 Confidential and Proprietary Product License United States Intellectual Property Rights/Royalties CRYSVITA® (XLH, TIO) Kyowa Kirin Co. (KKC) • Anti-FGF23 antibodies and use for treatment of XLH and TIO (2028-2032)1 • Q2W dosing for treatment of FGF23-associated hypophosphatemic disorders (2035) • See discussion of KKC license and collaboration in annual report for royalty summary MEPSEVII® (MPS7) St. Louis University (Know-How) • Low single-digit royalty until expiration of orphan drug exclusivity N/A (IP Owned by Ultragenyx) • Recombinant human GUS (rhGUS) and use for treatment of MPS7 (2035) DOJOLVI® (LC-FAOD) Baylor Research Institute (BRI) • Compositions comprising triheptanoin (2025-2029)1 • Mid single-digit royalty N/A (IP Owned by Ultragenyx) • Ultrapure triheptanoin and use in treatment of FAOD (Pending; 2034) Product License Europe Intellectual Property Rights/Royalties + Milestones EVKEEZA® (HOFH) Regeneron • Evkeeza antibody and use for treatment of HOFH (2036)2 • Evkeeza antibody in combination with other agents for treatment of HOFH (Pending; 2037) • Stabilized formulations of Evkeeza (Pending; 2041) • Regeneron supplies product and charges Ultragenyx a transfer price from the low 20% range up to 40% on net sales • Ultragenyx to pay up to $63M in potential regulatory and sales milestones 1Includes granted U.S. patent term extension 2Includes projected extension via supplementary protection certificates (SPCs)
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Key licenses & intellectual property – clinical programs 37 Confidential and Proprietary Product License US Intellectual Property Rights/Royalties + Milestones UX143 (Osteogenesis Imperfecta) Mereo Biopharma • Setrusumab antibody (2028) • Use of anti-sclerostin antibodies including setrusumab for treatment of OI (2037) • Tiered double-digit royalty on ex-EU sales and clinical, regulatory, and commercial milestones to Mereo • Fixed double-digit royalty on EU sales to Ultragenyx DTX401 (GSDIa) NIH (Non-Exclusive) • Recombinant vectors comprising codon-optimized G6Pase gene (2034) • Low single-digit royalty UX111 / ABO-102 (MPS IIIA) Nationwide Children’s Hospital (NCH) • Recombinant vectors comprising SGSH gene (Pending; 2032) • Development milestones up to $1M plus low single-digit royalty Abeona Therapeutics • Commercial milestones up to $30M plus tiered royalty up to 10% DTX301 (OTC Deficiency) Sub-License from REGENXBIO of UPENN IP • Recombinant vectors comprising codon-optimized OTC gene (2035) • Low to mid single-digit royalty and development milestones UX701 (Wilson Disease) Sub-License from REGENXBIO of UPENN IP • AAV9 Capsid (2026) • Mid to high single-digit royalty and up to $9M in development milestones UPENN • Recombinant vectors comprising certain regulatory and coding sequences packaged in UX701 (2039) • Development up to $5M and commercial milestones up to $25M plus low to mid single-digit royalty N/A (IP Owned by Ultragenyx) • Recombinant vectors expressing a novel truncated version of ATP7B protein produced by UX701 (Pending; 2040) GTX-102 (Angelman Syndrome) Texas A&M University • Use of UBE3A-ATS antisense oligonucleotides including GTX-102 for treatment of AS (2038) • Development and commercial milestones plus mid single-digit royalty GeneTx • Development, regulatory, and commercial milestones up to $190M plus mid to high single-digit royalty
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Crysvita partnership revenue recognition 38 Confidential and Proprietary Product Sales: Latin America & Türkiye Revenue in Profit-Share Territory: U.S. and Canada Royalty revenue in European Territory Commercialization Ultragenyx KKC KKC Revenue Ultragenyx books sales and pays low single-digit royalty to KKC on Latin America revenue KKC books sales and pays revenue share calculated using annual revenue tiers ranging from the mid-20% up to 30% to Ultragenyx KKC books sales and pays up to 10% royalty to Ultragenyx Product supply KKC supplies; price is double- digit percentage of net sales recorded to cost of sales NA NA
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CRYSVITA® exclusivity summary 39 Confidential and Proprietary Q2W Dosing Patent United States Europe 20362018 20342032203020282026202420222020 Q2W Dosing Patent Crysvita CoM Patent Crysvita CoM Patent XLH Orphan + D&M Exclusivity Biologics Exclusivity TIO Orphan Exclusivity XLH Orphan Exclusivity *Includes US PTE and EU SPC awards 2035 20352033* 2032* 2028 203020272025
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DOJOLVI® exclusivity summary 40 Confidential and Proprietary Ultrapure Dojolvi (Pending) 20362018 20342032203020282026202420222020 Ultrapure Dojolvi (Pending) Dojolvi CoM Patent LC-FAOD Orphan Exclusivity NCE Exclusivity United States Europe *Includes US PTE award 2034 2034 2029*20272025
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MEPSEVII® exclusivity summary 41 Confidential and Proprietary Mepsevii CoM Patent 20362018 20342032203020282026202420222020 Mepsevii CoM Patent MPS7 Orphan + D&M Exclusivity MPS7 Orphan Exclusivity United States Europe 2035 20352028 2024 Biologics Exclusivity 2029
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EVKEEZA® exclusivity summary 42 Confidential and Proprietary Evkeeza Ab Patent 20402022 20382036203420322030202820262024 Data & Marketing Exclusivity Exemplary additional patent applications pending: • Evkeeza w/ PCSK9 Ab • Evkeeza w/ statins • Evkeeza formulations Projected expiration dates between 2037-2041 Europe 2036*2031 *Includes EU SPC award