Slides
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Corporate Presentation January 2026 Confidential and Proprietary
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Forward looking statements Confidential and Proprietary2 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.
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Who we are Confidential and Proprietary3 We are leading the future of rare disease with first ever treatments Aly lives with X-Linked Hypophosphatemia
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Our differentiated approach to rare diseases Confidential and Proprietary4 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 Confidential and Proprietary5 4 commercial products Diverse clinical pipeline Potential approvals in 2026 Phase 2/3 programs 5 2 Mason lives with Angelman syndrome
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Focused on three therapeutic areas Late-stage pipeline will leverage successful global commercial organization Confidential and Proprietary6 LATE STAGE 1 CLNICAL PROGRAMS BONE -ENDOCRINE 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 Ph 3: UX143 for OI
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Diverse late-stage clinical pipeline Confidential and Proprietary7 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 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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UX143 (setrusumab) for Osteogenesis Imperfecta Phase 3 Update Confidential and Proprietary
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UX143 for osteogenesis imperfecta Phase 3 results Confidential and Proprietary Neither study achieved primary endpoint of reduction in AFR1 compared to placebo (Orbit) or bisphosphonates (Cosmic) Further understanding will help determine if there is a potential path forward Additional data shows reduction in vertebral fractures and improvements in patient reported outcomes of disease severity, pain/comfort, and daily activities Both studies demonstrated statistically significant increases in bone mineral density (BMD) Data presented at JP Morgan Healthcare Conference 2026 1: Annualized fracture rate 9
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Two randomized Phase 3 studies provide large data set controlled with placebo or active Confidential and Proprietary Orbit Phase 3 Placebo-Controlled Study Design Cosmic Phase 3 Active-Controlled Study Design Orbit Phase 3 Enrollment (2:1) Cosmic Enrollment (1:1) Setrusumab (%) IV-BP (%) Total n 34 (49.3) 35 (50.7) Type 1 12 (35.5) 16 (45.7) Type 3 15 (44.1) 13 (37.1) Type 4 7 (20.6) 6 (17.1) Peds 2 to 7 yo 34 (49.3) 35 (50.7) Screening ≥1 AFR Setrusumab (n=107) Placebo (n=52) Open Label Extension Double-blind treatment period, follow-up 18-24 months 2:1 Randomization Screening ≥1 AFR Setrusumab (n=34) Open Label Extension Active-controlled treatment period, follow-up 18-24 months IV-BP (n=35) 1:1 Randomization 10 Setrusumab (%) Placebo (%) Total n 107 (67.3) 52 (32.7) Type 1 43 (40.2) 21 (40.4) Type 3 43 (40.2) 10 (19.2) Type 4 21 (19.6) 21 (40.4) Peds 5 to <12 yo 44 (41.1) 23 (44.2) Teens 12 to <18 yo 47 (43.9) 21 (40.4) Adults 18 to 26 yo 16 (15.0) 8 (15.4) Data presented at JP Morgan Healthcare Conference 2026
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Baseline fractures are comparable between groups in both studies Orbit: more severe type III/IV patients exited placebo via rescue criteria Confidential and Proprietary Orbit Phase 3 Baseline Historical Fractures1 Setrusumab Placebo Mean / Median Number of fractures 3.2 / 2.0 3.3 / 2.0 Fracture ≤3 Patients Number (%) 71 (66.4) 35 (67.3) Fracture >3 Patients Number (%) 36 (33.6) 17 (32.7) Cosmic Phase 3 Baseline Historical Fractures1 Setrusumab IV-Bisphos. Mean / Median Number of fractures 4.1 / 4.0 4.3 / 3.0 Fracture ≤4 and no FTH Patients Number (%) 4 (11.8) 4 (11.4) Fracture >4 or ≥1 FTH Patients Number (%) 30 (88.2) 31 (88.6) 1: All suspected and radiographically confirmed fractures over prior 2 years 1: All suspected and radiographically confirmed fractures over prior 2 years FTH = Femur, Tibia or Humerus Cosmic had no rescue criteria since it was active treatment controlled • 28 of 31 were more severe Type 3/4 patients • UX143 15/64 (23%) • Placebo 13/31 (42%) A substantially larger number of Placebo patients exited Orbit In Orbit, 31 (19.5%) patients met rescue criteria at 12 months primarily due to fractures 11 Data presented at JP Morgan Healthcare Conference 2026
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Setrusumab is substantially more effective in increasing BMD Confidential and Proprietary12 *Based on Month 12 timepoint *Based on Month 12 timepoint UX143* 0.70 (0.08) Placebo* -0.25 (0.10) LSmean Diff* 0.95 (0.11) P-value* < 0.0001 UX143* 1.01 (0.22) IV-BP* 0.32 (0.21) LS Mean Diff* 0.69 (0.27) P-value* = 0.0116 Cosmic: UX143 demonstrated clinically and statistically significant increases in BMD vs active comparator Orbit: UX143 demonstrated clinically and statistically significant increases in BMD vs placebo UX143 Placebo 85 47 82 46 83 44 65 33 26 32 UX143 IV-BP 24 29 24 27 23 28 Lumbar Spine BMD Z-Score Mean Change from Baseline Lumbar Spine BMD Z-Score Mean Change from Baseline Baseline Month 6 Month 12 Month 18 Baseline Month 6 Month 12 Month 18 1.0 0.8 0.6 0.4 0.2 0.0 -0.2 -0.4 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 Data presented at JP Morgan Healthcare Conference 2026
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Orbit: UX143 patients showed an increase in fractures over a low placebo rate, but were the same as placebo when all fractures were considered (p=ns) Confidential and Proprietary13 Confirmed fractures by x-ray and skeletal survey Primary Endpoint1 Excl. mVFTFS Key Secondary All Fractures UX143 AFR (n=107) # of fractures 142 191 Mean (SD, SE) 0.92 (1.16, 0.11) 1.22 (1.29, 0.12) Median (Q1, Q3) 0.58 (0.00, 1.53) 0.68 (0.00, 1.82) Placebo AFR (n=52) # of fractures 54 94 Mean (SD, SE) 0.80 (1.48, 0.21) 1.27 (1.96, 0.27) Median (Q1, Q3) 0.00 (0.00, 0.93) 0.61 (0.00, 2.02) Estimated2 UX143 AFR (95% CI) 0.71 (0.50, 0.99) 1.16 (0.90, 1.50) Estimated2 Placebo AFR (95% CI) 0.55 (0.35, 0.86) 1.12 (0.80, 1.57) Rate Ratio2 UX143/Placebo (95% CI) 1.28 (0.80, 2.06) 1.03 (0.71, 1.52) Rate Change2 UX143 Placebo (95% CI) 28.14 (-20.21, 105.79) 3.38 (-29.48, 51.54) P-value2 0.305 0.865 1 Radiographically confirmed fractures, excluding morphometric vertebral fractures and fingers, toes, face, and skull 2 Negative Binomial model Excluding mVFTFS Total Fractures Cumulative Distribution of Primary Endpoint (Excl. mVFTFS) Cumulative Distribution of Key Secondary Endpoint (All fractures) UX143 (N=107) 2x Placebo (N=52) Month on Treatment UX143 (N=107) 2x Placebo (N=52) 0 3 6 9 12 15 18 21 24 Month on Treatment 0 3 6 9 12 15 18 21 24 0 20 40 60 80 100 120 140 160 180 200 0 20 40 60 80 100 120 140 160 Data presented at JP Morgan Healthcare Conference 2026
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Orbit: In setrusumab patients, disease severity (PGIS) in peds/teens reduced and pain/comfort & sports/activity improved Confidential and Proprietary14 Sports/Activity POSNA-PODCI Pain/Comfort POSNA-PODCI Patient Global Impression Scale of Severity (PGIS) -0.37 (-0.68, -0.07) P-value=0.017 -0.40 (-0.77, -0.03) P-value=0.036 -0.26 (-0.57, 0.05) P-value=0.099 Peds/Teens patients constitute 85% of subjects in Orbit Ph3 study (135/159) OI Pain Daily Activities Overall Symptoms 5.79 (-0.94, 12.52) P-value=0.091 9.66(0.26, 19.06) P-value=0.044 12 month assessment is as randomized and most important as no patients had exited due to rescue criteria UX143 Placebo 72 34 68 29 65 30 UX143 Placebo 72 34 68 29 65 30 Baseline Month 6 Month 12 Baseline Month 6 Month 12 -0.4 -0.3 -0.2 -0.1 0.0 0.1 0.2 0.3 0.4 Change from Baseline at Month 12 9 6 3 0 -3 -6 -9 8 6 4 2 0 -2 -4 -6 UX143 (N=75) Placebo (N=35) Pain/Comfort Sub-scale Change from Baseline at Month 12 Spots/Activity Sub-scale Change from Baseline at Month 12 Data presented at JP Morgan Healthcare Conference 2026
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Cumulative Distribution of Primary Endpoint Cumulative Distribution of Key Secondary Endpoint Cosmic: Setrusumab treatment shows reduced fractures over IV-BP (p=ns) Confidential and Proprietary15 80 Confirmed fractures by x-ray and skeletal survey Primary Endpoint Total fractures Key Secondary1 Excl. mVFTFS UX143 AFR (n=34) # of fractures 102 82 Mean (SD, SE) 1.87 (1.69, 0.29) 1.53 (1.53, 0.26) Median (Q1, Q3) 2.02 (0.00, 3.04) 1.42 (0.00, 2.53) IV-BP AFR (n=35) # of fractures 132 99 Mean (SD, SE) 2.6 (3.19, 0.54) 1.97 (2.90, 0.49) Median (Q1, Q3) 1.38 (0.55, 4.06) 0.67 (0.00, 3.04) Estimated2 UX143 AFR (95% CI) 0.91 (0.51, 1.60) 0.68 (0.34, 1.35) Estimated2 IV-BP AFR (95% CI) 1.15 (0.65, 2.04) 0.79 (0.39, 1.61) Rate Ratio2 UX143/IV-BP (95% CI) 0.79 (0.48, 1.28) 0.86 (0.47, 1.57) Rate Change2 favoring UX143 (95% CI) -21.27 (-51.75, 28.47) -14.27 (-53.07, 56.61) P-value2 0.338 0.616 Excluding mVFTFS 1 Radiographically confirmed fractures, excluding morphometric vertebral fractures and fingers, toes, face, and skull 2 Negative Binomial model Month on Treatment 0 3 6 9 12 15 18 21 24 0 20 40 60 100 120 UX143 (N=34) IV-BP (N=35) Month on Treatment 0 3 6 9 12 15 18 21 24 80 0 20 40 60 100 120 Data presented at JP Morgan Healthcare Conference 2026 UX143 (N=34) IV-BP (N=35) Total Fractures 140
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Cosmic: Large reduction in vertebral fractures on setrusumab (p-value 0.081) Despite MORE severe type III/IV patients on UX143 (65% UX143 vs 54% to IV-BP) Cosmic Phase 3 Radiographically confirmed fractures Total fractures All types Vertebral Fractures UX143 IV-BP UX143 IV-BP All fractures 102 132 19 46 All fractures (Excluding mV1) 84 104 1 18 All fractures (Excluding mVFTFS 2) 82 99 1 18 mVertebral fractures (Tertiary endpoint) 18 28 18 28 Setrusumab 59% fewer vertebral fractures of all types Setrusumab 94% fewer non-morphometric vertebral fractures Radiographically Confirmed Fracture Type (comparing 19 vs 46 vertebral fractures*) All Vertebral Fractures Negative Binomial Model (95% CI) Est UX143 AFR (95% CI) 0.14 (0.04, 0.51) Est IV-BP AFR (95% CI) 0.33 (0.10, 1.12) Ratio UX143/IV-BP (95% CI) 0.44 (0.18, 1.11) Rate Change favoring UX143 (%) (95% CI) -56.00 (-82.48, 10.53) P-value 0.081 Radiographically Confirmed Fracture Type (Tertiary endpoint) Morphometric Vertebral Fractures, Only Negative Binomial Model (95% CI) Est UX143 AFR (95% CI) 0.15 (0.04, 0.51) Est IV-BP AFR (95% CI) 0.24 (0.07, 0.79) Ratio UX143/IV-BP (95% CI) 0.64 (0.26, 1.61) Rate Change favoring UX143 (%) (95% CI) -35.87 (-74.43, 60.86) P-value 0.344 * Post hoc analysis Confidential and Proprietary16 Data presented at JP Morgan Healthcare Conference 2026 1: Morphometric vertebral fractures 2: Morphometric vertebral fractures and fingers, toes, face, and skull
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No new safety concerns identified, reported TEAEs are consistent with the anticipated safety profile for setrusumab Confidential and Proprietary17 Treatment emergent adverse events (TEAE) • No serious-related TEAE’s • Low incidence (<2%) severe-related TEAE’s • Low incidence (<3%) TEAE’s leading to treatment or study discontinuation Adverse events of special interest (AESI) • No ischemic CV Events • No hypersensitivity reactions related to UX143 • 1 TEAE in neurologic effect due to bony overgrowth o Radial nerve injury following a surgical procedure No Deaths Orbit* Cosmic* Treatment emergent adverse events (TEAE) • No serious related TEAE’s • Low incidence (<3%) severe related TEAE • No TEAE’s leading to treatment discontinuation or study discontinuation Adverse events of special interest (AESI) • No ischemic CV events • No hypersensitivity reactions related to UX143 • No neurologic sequalae due to bony overgrowth No Deaths *Data presented above is representative of setrusumab arm only *Data presented above is representative of setrusumab arm only Data presented at JP Morgan Healthcare Conference 2026
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Overall data suggest an impact of setrusumab on OI disease but missed primary AFR endpoints are a challenge Confidential and Proprietary18 Further understanding will help determine if there is a potential path forward UX143 IV-BP All fractures 19 46 All fractures (Excluding mV1) 1 18 Reduced Vertebral fractures Improved functional outcomes •Decreased bone pain •Improved functional ability •Improved walking ability The largest BMD improvements found in the lumbar spine BMD are associated with reduced vertebral fractures and improved pain and functional outcomes in pediatric patients Data presented at JP Morgan Healthcare Conference 2026 1: Morphometric vertebral fractures Improved Lumbar Spine BMD
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2026 potential approvals and data readouts Confidential and Proprietary
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UX111 for Sanfilippo syndrome (MPS IIIA) AAV9 gene therapy; expect to resubmit BLA in early 2026 Confidential and Proprietary20 “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 • Expect to resubmit BLA in early-2026, up to 6-month review1 • Investing in commercial supply • Leverage existing inborn errors of metabolism field team • PRV eligible * Prevalence in commercially accessible geographies Sadie lives with MPSIIIA 1: As required by FDA regulations
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UX111 for MPS IIIA: Substantial reduction in CSF HS1 exposure regardless of age or stage of disease Confidential and Proprietary21 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 Confidential and Proprietary22 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 Confidential and Proprietary23 • 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; rolling BLA submission completed in December 2025 Confidential and Proprietary24 “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 submitted Dec-2025, expect PDUFA date in 3Q-20261 • Manufacturing in-house at our Bedford, MA plant • Leverage existing inborn errors of metabolism field team • PRV eligible *Prevalence in commercially accessible geographies Daily cornstarch consumption 1: As required by FDA regulations
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DTX401 for GSDIa: Phase 3 successful across primary and key secondary endpoints Confidential and Proprietary25 %∆ 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) 0.131 Week 48 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 Data presented via conference call on May 30, 2024
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DTX401 for GSDIa: Phase 3 crossover and original treatment arm continued reducing daily cornstarch through Week 96 Confidential and Proprietary26 Week 96 Daily cornstarch (CS) reductions • Patients in the original DTX401 group and Crossover patients, previously treated with placebo, both demonstrated a 61% reduction in daily CS at Week 96 – Patients able to titrate CS much more rapidly once treatment confirmed with DTX401 and with timely, direct access to their glucose levels • DTX401 demonstrated a consistent and acceptable safety profile as of the data cut-off Statistically significant and clinically meaningful cornstarch reductions continued in crossover period Data presented at ICIEM September 2025 Week
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DTX401 for GSDIa: Statistically significant reductions in frequency and quantity of day and nighttime CS vs placebo at Week 48 that continued to Week 96 Confidential and Proprietary27 Nighttime Cornstarch (CS) Doses and Grams Nighttime CS Doses (n) DTX4011 Placebo / Crossover2 p-value Baseline Mean (SE) 1.7 (0.3) 1.7 (0.2) ∆ BL to W48 Mean (SE) -0.4 (0.2) +0.5 (0.4) 0.0105 ∆ BL to Week 96 Mean (SE) -0.8 (0.2) -1.1 (0.5) Changes from baseline for patients who required nighttime CS at baseline Nighttime CS Intake (g) DTX4011 Placebo / Crossover2 p-value Baseline Mean (SE) 85.8 (9.2) 100.4 (20.6) %∆ BL to W48 Mean (SE) -42.5 (7.8) +15.2 (27.7) 0.0132 %∆ BL to W96 Mean (SE) -70.2 (10.0) -75.1 (7.6) Total Daily CS Doses (n) DTX4011 Placebo / Crossover2 p-value Baseline Mean (SE) 5.8 (0.3) 5.1 (0.3) ∆ BL to Week 48 Mean (SE) -1.1 (0.2) -0.1 (0.1) 0.0011 ∆ BL to Week 96 Mean (SE) -1.9 (0.4) -1.6 (0.5) 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 Data presented at ICIEM September 2025 1: N = 24; 2: N=20 for patients initially treated with placebo and N=19 for patients who crossed over to DTX401. Crossover group was re-baselined at Week 48 and change in Crossover group reflects change from Week 48. 1: N = 15; 2: N=15 for patients initially treated with placebo and N=13 for patients who crossed over to DTX401. Crossover group was re-baselined at Week 48 and change in Crossover group reflects change from Week 48.
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DTX401 for GSDIa: Patients reported meaningful improvements in disease management at Week 48 and Week 96 Confidential and Proprietary28 Patient Global Impression of Change (PGIC) • Week 48: 79% (15/19) reported improved GSDIa in DTX401-treated group versus 52% (12/23) Placebo • Week 96: (end of Double-blind Crossover Period) improved GSDIa reported in: – 83% (10/12) DTX401 group – 95% (18/19) Crossover DTX401 group Patient interviews • Week 48: 39% reported improved ability to self-regulate blood sugar levels (e.g., feeling of a “safety net”) in DTX401 versus 18% Placebo • DTX401-treated participants most frequently reported: – Reductions in cornstarch intake, hypoglycemia, tiredness – Improvements in physical function, social, and diet/daily regimen impacts Data presented at ICIEM September 2025
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GTX-102 for Angelman syndrome (AS) Antisense oligonucleotide; Phase 3 Aspire data expected in 2H-2026 Confidential and Proprietary29 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 • Enrollment completed in Phase 3 Aspire Study in deletion patients • Enrollment underway in Phase 2/3 Aurora study in other genotypes and ages • Phase 3 Aspire data expected in 2H-2026 *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: Two global studies enrolling broad age range and genotypes Confidential and Proprietary30 Aspire Phase 3 Sham-Controlled Study Aurora Open Label Study GTX-102 Sham Open Label Extension 48-week primary efficacy period 129 Patients; 1:1 Randomization Cohort A Open Label Extension Screening Screening Cohort B Cohort C Cohort D • Randomized, controlled study in deletion patients • Enrollment: 129 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 Cohort Age (years) Genotype Primary Endpoint A ≥1 to <4 Deletion Bayley-4 Cognitive raw score B ≥4 to <18 UPD/ICD MDRI C ≥18 to <65 All MDRI D ≥4 to < 18 Mutation MDRI • Global study will enroll ~60 participants • Open label, 48-week primary efficacy period
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UX701 for Wilson disease (WD) AAV9 gene therapy; Stage 1, dose finding data expected in 1H-2026 Confidential and Proprietary31 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 completed in August 2025 • Stage 1, dosing finding data expected in 1H-2026 • Manufacturing in-house at our Bedford, MA plant *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 Confidential and Proprietary32 • 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 Enrollment completed in fourth cohort with moderately increased dose and with optimized immunomodulation
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Commercial revenue grew approximately 20% in 2025 Confidential and Proprietary33 0 100 200 300 400 500 600 700 800 2017 2018 2019 2020 2021 2022 2023 2024 2025e Total Revenue* 1 Total Revenue includes Crysvita, Dojolvi, Mepsevii, and Evkeeza 2 Total Crysvita revenue, including North America, Latin America, and Europe 3 Preliminary, unaudited estimate $356M $266M $103M $28M Product 2025 Flash Estimate3 2026 Guidance Total revenue 1 $672 - 674M ~20% growth Expect to be shared on 4Q/FY25 earnings call Crysvita2 $480 - 482M ~17% growth Dojolvi $95 - 97M ~9% growth $560M * Excluding Bayer and Daiichi collaboration revenue and potential future launches. Estimate for 2025. $0.5M $182M TIO Revenue ($M) XLH $672 - 674M $433M
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Planning significant expense and headcount reductions to support path to profitability in 2027 Confidential and Proprietary34 • Revenue: Continued double-digit growth from current products, plus contribution from upcoming launches • Operating expense: Significant expense and headcount reductions as a result of the UX143 data readout, while investing in launches for UX111, DTX401, and GTX-102 (e.g., pre-launch inventory) • Cash: • Planned monetization of PRVs from UX111 and DTX401 • ~$735M in cash and investments1 as of 12/31/2025 Profitability assumptions 1 Preliminary, unaudited estimate of cash, cash equivalents, and marketable securities
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Key clinical and regulatory catalysts Confidential and Proprietary35 PROGRAM OBJECTIVE ANTICIPATED TIMING DTX401 GSDIa BLA filing PDUFA decision date 3Q-2026 UX111 Sanfilippo syndrome Resubmit BLA PDUFA decision date Early in 2026 TBD UX701 Wilson disease Stage 1 dose finding data (Cohorts 1-4) 1H-2026 GTX-102 Angelman syndrome Phase 3 Aspire data 2H-2026
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We are leading the future of rare disease with first ever treatments Confidential and Proprietary36 History of consistent and ongoing revenue growth from base business Revenue growth and new launches plus expense management to reach profitability in 2027 and beyond Near-term catalysts from 5 Phase 2/3 programs and 2 potential approvals
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Appendix Confidential and Proprietary
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Key licenses & intellectual property – commercial products 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 (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 • Treatment of HOFH-associated atherosclerosis and use in combination with LDL-C lowering regimen (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 granted extensions via supplementary protection certificates (SPCs) 38
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Key licenses & intellectual property – clinical programs Confidential and Proprietary39 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 for treatment of MPS IIIA (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) UPENN • Recombinant vectors comprising certain regulatory and coding sequences packaged in UX701 (2039) • Development milestones 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 (2042) 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 Confidential and Proprietary40 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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Illustration of Crysvita Royalty Monetization Confidential and Proprietary41 Europe U.S. / Canada % of RARE Royalty Interest OMERS = +25% • RARE receives annual tiered royalty up to 30% on KKC’s U.S./Canada revenue • RARE received $500M from OMERS for 30% of RARE royalties up to 1.45x • Payments began April 2023 • RARE received $400M from OMERS for addtl 25% of RARE royalties and an extension of prior deal after its cap is hit up to a total of 1.55x • Payments to OMERS begin in January 2028 • RARE receives 10% royalty on KKC’s European revenue • RARE received $320M cash from RP for 100% of RARE royalties up to 1.9x by December 2030 or 2.5x • Payments began January 2020 % of RARE Royalty Interest Royalty Pharma = 100% Apr 2023 Jan 2028 Dec 2019 Capped at 1.9x by Dec 2030 or 2.5x OMERS = 30% Capped at 1.55x Capped at 1.45x
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CRYSVITA® exclusivity summary Confidential and Proprietary42 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 Regulatory Exclusivity Issued Patents
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DOJOLVI® exclusivity summary Confidential and Proprietary43 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 Pending Patent ApplicationsRegulatory Exclusivity Issued Patents
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MEPSEVII® exclusivity summary Confidential and Proprietary44 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 Regulatory Exclusivity Issued Patents
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EVKEEZA® exclusivity summary Confidential and Proprietary45 Evkeeza CoM Patent 20402022 20382036203420322030202820262024 Data & Marketing Exclusivity Europe 2036*2031 *Includes EU SPC award Atherosclerosis Treatment Patent 2037 Formulation Patent (Pending) 2041 Pending Patent ApplicationsRegulatory Exclusivity Issued Patents