Ultragenyx Pharmaceutical Inc. · NASDAQ:RARE
Ultragenyx Pharmaceutical — Q2 2025 Earnings Presentation
42 slides from Ultragenyx Pharmaceutical's earnings presentation, Aug 5, 2025
Slide 1: Corporate Presentation
Corporate Presentation August 2025 Confidential and Proprietary
Slide 2: Forward looking statements
Forward looking statements Cautionary note regarding forward-looking statements: This presentation contains our dependence on Kyowa Kirin for the commercialization of Crysvita in certain major forward-looking statements, including, but not limited to, statements regarding our markets, including the
Slide 3: Who we are
Who we are Next generation rare disease company dedicated to the development and delivery of transformative treatments where none exist 3 Confidential and Proprietary
Slide 4: Our differentiated approach to rare diseases is yielding great results
Our differentiated approach to rare diseases is yielding great results Research Development Commercial Pursue high potential programs Accelerate to drive value Patient-centric approach • Potent biology in severe diseases • Adaptive trial designs • Lean commercial team • Treating underlying cause • N
Slide 5: Creating a successful and profitable rare disease company
Creating a successful and profitable rare disease company 4 commercial products Largest clinical pipeline in rare disease Avery and Addison live with osteogenesis imperfecta 6 Phase 2/3 studies 3 Near-term approvals 5 Confidential and Proprietary
Slide 6: Focused on three therapeutic areas
Focused on three therapeutic areas Late-stage pipeline will leverage successful global commercial organization BONE-ENDOCRINE INBORN ERRORS OF METABOLISM NEUROGENETIC COMMERCIAL LC-FAOD MPS VII XLH & TIO HoFH Ph 3: UX143 for OI Ph 3: UX111 for MPS IIIA Ph 3: GTX-102 for AS CLNICAL PROGRAMS LATE STAG
Slide 7: Diverse late-stage clinical pipeline
Diverse late-stage clinical pipeline Inborn Errors of Therapeutic Area: Bone/Endo Neurogenetic Metabolism Candidate Description Phase 1 Phase 2 Phase 3 Route of Admin Prevalence1 UX143 Anti-Sclerostin Intravenous (IV) monoclonal antibody Osteogenesis Imperfecta (OI) Infusion ~60,000 (setrusumab) ASO
Slide 8: Drivers of value creation in 2025
Drivers of value creation in 2025 1 UX143 for OI Ph3 data readout 2 GTX-102 for AS Ph3 enrollment completion 3 Revenue expansion & near-term launches Amber and her daughter live with Mason lives with Aly lives with XLH osteogenesis imperfecta Angelman syndrome 8 Confidential and Proprietary
Slide 9: UX143 for osteogenesis imperfecta (OI)
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 approve
Slide 10: UX143 for OI: Phase 2 data: 67% reduction in annualized fracture rate
UX143 for OI: Phase 2 data: 67% reduction1 in annualized fracture rate (AFR) P=0.0014 Radiographically Confirmed Fractures1 2 Phase 3 Endpoint (excluding Fingers, Toes, Face, and Skull) Median Annualized Fracture Rate (AFR) P=0.0014 1.5 1 0.5 0.72 0.0 0 Pre- After Setrusumab Treatment2 Initiation 1:
Slide 11: UX143 for OI: Phase 2 data demonstrated increase in lumbar spine BMD and Z-score
UX143 for OI: Phase 2 data demonstrated increase in lumbar spine BMD and Z-score observed at 12 months Lumbar Spine BMD (Mean + SE)1 Lumbar Spine BMD1 as Percent Change from Baseline Z-Score Change from Baseline 22.25 ± 2.71 1.25 ± 0.17 p<0.0001 p<0.0001 0.85 ± 0.13 14.19 ± 2.15 0.58 ± 0.10 9.16 ± 1
Slide 12: UX143 for OI: Younger patients in Phase 2 showed a very large 29% increase
UX143 for OI: Younger patients in Phase 2 showed a very large 29% increase in BMD at Month 12 Lumbar Spine BMD by Age Group1 % Change from Baseline at Month 12 1 Interim data as of May 24, 2024 12 Confidential and Proprietary
Slide 13: UX143 for OI: Phase 2 safety data consistent through Month 14
UX143 for OI: Phase 2 safety data1 consistent through Month 14 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 13 Confidential and Proprietary
Slide 14: Persuasive Phase 2 data support transformational effects of UX143
Persuasive Phase 2 data1 support transformational effects of UX143 Participants in Phase 2 have been on therapy for more than 2 years UX143 builds bone, exactly where needed, increasing bone strength, while improving overall bone health Participants in Phase 2 have reduced fractures, while increasin
Slide 15: GTX-102 for Angelman syndrome (AS)
GTX-102 for Angelman syndrome (AS) Antisense oligonucleotide; Phase 3 enrollment completed 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 • Prevale
Slide 16: GTX-102 for AS: Overview of Phase 1/2 long-term safety and efficacy
GTX-102 for AS: Overview of Phase 1/2 long-term safety and efficacy 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 con
Slide 17: GTX-102 for AS: Cognition by Bayley-4 GSV and raw scores
GTX-102 for AS: Cognition by Bayley-4 GSV and raw scores show ample power for Phase 3 trial Bayley-4 Cognition GSV scores show significant gains at Ph3 Primary Endpoint: Bayley-4 Cognition raw score Day 338 that continue through Day 506 trend comparable to GSV and is also well powered Bayley-4 GSV S
Slide 18: GTX-102 for AS: Multi-domain responder index
GTX-102 for AS: Multi-domain responder index shows ~80% of participants with clinically meaningful net improvement in ≥ 1 domain at Day 338 Cohorts A&B Day 338 Net Response: +2; p-value: <0.0001 ABC-C Key Takeaways ASA ASA ABC-C Bayley-4 Bayley-4 Total Net Sleep Gross Motor Hyperact/Noncomp Rec Comm
Slide 19: GTX-102 for AS: Safety summary
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 rela
Slide 20: GTX-102 for AS: Phase 3 development plans
GTX-102 for AS: Phase 3 development plans Aurora: Aspire: Phase 3 Study1 Additional Genotype and Ages Study • Randomized, controlled study in deletion patients • Open label • Sample size: ~120 patients; ages 4 to <18 years • Ages <4 and >18 years of age • 48-week primary efficacy period • Non-deleti
Slide 21: UX111 for Sanfilippo syndrome (MPS IIIA)
UX111 for Sanfilippo syndrome (MPS IIIA) AAV9 gene therapy MPS IIIA: Fatal lysosomal storage disease of CNS − Early childhood onset − Rapid neurodegeneration • Treatment: No approved therapies • Prevalence*: ~3,000 to 5,000 * Prevalence in commercially accessible geographies Sadie lives with MPSIIIA
Slide 22: UX111 for MPS IIIA: Substantial reduction in CSF HS exposure
UX111 for MPS IIIA: Substantial reduction in CSF HS1 exposure regardless of age or stage of disease Rapid reduction in CSF HS1 Key Takeaways over 7 to 77 months • > 80% of participants reduced CSF HS by 50% in efficacy set CSF HS Exposure (%) * • Median CSF HS exposure • Efficacy set (N=27): −64.51%
Slide 23: UX111 for MPS IIIA: Improved Bayley-III raw scores compared to natural history
UX111 for MPS IIIA: Treatment with UX111 led to improved Bayley-III raw scores compared to natural history • 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 decli
Slide 24: UX111 for MPS IIIA: Conclusions
UX111 for MPS IIIA: Conclusions • 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 correla
Slide 25: DTX401 for glycogen storage disease type Ia (GSDIa)
DTX401 for glycogen storage disease type Ia (GSDIa) AAV8 gene therapy; BLA submission expected in 4Q-2025, launch 2026 GSDIa: Life-threatening defect in liver’s ability to release glucose due to G6Pase deficiency Daily cornstarch consumption − Severe hypoglycemia − Long-term liver and renal disease
Slide 26: DTX401 for GSDIa: Phase 3 successful across primary and key secondary endpoints
DTX401 for GSDIa: Phase 3 successful across primary and key secondary endpoints p-value Key Takeaways Primary • GSDIa is a severe, life-threatening %∆ daily cornstarch intake <0.0001 metabolic disease, with long term Endpoint complications due to inability to control glucose # of total daily doses o
Slide 27: DTX401 for GSDIa: Phase 3 patients continued improving at last visit
DTX401 for GSDIa: Phase 3 patients continued improving at last visit in crossover and originally treated arms Week 48: Statistically significant reduction (41%) in Week 120: Crossover and original treatment daily cornstarch intake (p < 0.0001) arms continued reducing daily cornstarch (CS) Percent Ch
Slide 28: DTX401 for GSDIa: Reduction in frequency and quantity of cornstarch
DTX401 for GSDIa: Patients treated showed significant reduction in frequency and quantity of day and nighttime cornstarch vs placebo at Week 48 Total Daily Cornstarch (CS) Doses Nighttime Cornstarch (CS) Doses and Grams Placebo DTX401 Placebo DTX401 Total Daily CS Doses (n) N=24 N=20 p-value Nightti
Slide 29: UX701 for Wilson disease (WD)
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 GT manufacturing facility in Bedf
Slide 30: UX701 for WD: Clinical activity observed in Stage 1
UX701 for WD: Clinical activity observed in Stage 1 with 6 of 15 patients completely off chelators and/or zinc therapy1 • 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 ca
Slide 31: 2025 total revenue expected to grow 14-20%
2025 total revenue expected to grow 14-20% Annual Revenue Growth1 700 $640-670M 2024 2025 Product 600 Actuals Guidance $560M $460-480M 500 Crysvita1 $410M 12-17% $433M Revenue ($M) 400 $356M $90-100M Dojolvi $88M 2-13% 300 $266M TIO Total $640-670M 200 $182M $560M Revenue2 14-20% XLH $103M 100 $28M
Slide 32: Project full year GAAP profitability in 2027
Project full year GAAP profitability in 2027 Core Assumptions • 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
Slide 33: Key clinical and regulatory catalysts
Key clinical and regulatory catalysts PROGRAM OBJECTIVE ANTICIPATED TIMING UX143 Phase 3 Orbit final analysis (threshold: p<0.04) Around end of 2025 Osteogenesis imperfecta Phase 3 Aspire study initiation GTX-102 Phase 3 Aspire enrollment completion Angelman syndrome Phase 2/3 Aurora study init
Slide 34: We are creating a successful and profitable rare disease company
We are creating a successful and profitable rare disease company History of outstanding clinical and outstanding commercial execution Near-term catalysts from 6 Phase 2/3 studies and 3 potential approvals Revenue growth and new launches plus expense management to achieve expected full-year GAAP prof
Slide 35: Appendix
Appendix Confidential and Proprietary
Slide 36: Key licenses & intellectual property – commercial products
Key licenses & intellectual property – commercial products Product License United States Intellectual Property Rights/Royalties • Anti-FGF23 antibodies and use for treatment of XLH and TIO (2028-2032)1 CRYSVITA® Kyowa Kirin Co. (KKC) • Q2W dosing for treatment of FGF23-associated hypophosphatemic di
Slide 37: Key licenses & intellectual property – clinical programs
Key licenses & intellectual property – clinical programs Product License US Intellectual Property Rights/Royalties + Milestones • Setrusumab antibody (2028) UX143 • Use of anti-sclerostin antibodies including setrusumab for treatment of OI (2037) (Osteogenesis Mereo Biopharma • Tiered double-digit r
Slide 38: Crysvita partnership revenue recognition
Crysvita partnership revenue recognition Product Sales: Revenue in Profit-Share Royalty revenue in Latin America & Türkiye Territory: U.S. and Canada European Territory Commercialization Ultragenyx KKC KKC KKC books sales and pays Ultragenyx books sales and revenue share calculated KKC books sales a
Slide 39: CRYSVITA® exclusivity summary
CRYSVITA® exclusivity summary XLH Orphan TIO Orphan Biologics Crysvita CoM Q2W Exclusivity Exclusivity Exclusivity Patent Dosing Patent United States 2025 2027 2030 2032* 2035 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2028 2033* 2035 XLH Orphan + Crysvita CoM Q2W Europe D&M Exclusivity Paten
Slide 40: DOJOLVI® exclusivity summary
DOJOLVI® exclusivity summary NCE LC-FAOD Orphan Dojolvi CoM Ultrapure Dojolvi Exclusivity Exclusivity Patent (Pending) United States 2025 2027 2029* 2034 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2034 Ultrapure Dojolvi Europe (Pending) *Includes US PTE award 40 Confidential and Proprietary
Slide 41: MEPSEVII® exclusivity summary
MEPSEVII® exclusivity summary MPS7 Orphan Biologics Mepsevii Exclusivity Exclusivity CoM Patent United States 2024 2029 2035 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2028 2035 MPS7 Orphan + Mepsevii Europe D&M Exclusivity CoM Patent 41 Confidential and Proprietary
Slide 42: EVKEEZA® exclusivity summary
EVKEEZA® exclusivity summary Data & Marketing Evkeeza Exclusivity Ab Patent Europe 2031 2036* 2022 2024 2026 2028 2030 2032 2034 2036 2038 2040 Exemplary additional patent applications pending: • Evkeeza w/ PCSK9 Ab • Evkeeza w/ statins • Evkeeza formulations Projected expiration dates between 2037-
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