Ultragenyx Pharmaceutical Inc. · NASDAQ:RARE
Ultragenyx Pharmaceutical — J.P. Morgan 2023 Healthcare Conference
33 slides from Ultragenyx Pharmaceutical's conference presentation, January 2023
Slide 1: JP Morgan 2023 Healthcare Conference
JP Morgan 2023 Healthcare Conference Emil Kakkis, M.D., Ph.D. President and CEO Confi dential a nd Proprietary
Slide 2: Forward looking statements
Forward looking statements Cautionary note regarding forward-looking statements: This presentation contains the timing of our regulatory filings the uncertainties inherent in the clinical drug forward-looking statements, including, but not limited to, statements regarding our development process, in
Slide 3: Our mission since 2010
Our mission since 2010 Going beyond every day... to transform the lives of people 4 approved therapies >3,200 patients globally 5 indications treated including living with rare disease. commercial & expanded use ~70% success rate 7 clinical programs from clinic to approval (5 in pivotal studies) Wel
Slide 4: Our specialized approach to drug development
Our specialized approach to drug development Match deep understanding of with the right drug informed by disease biology modality and tools patient experience For X-linked hypophosphatemia (XLH) AAV gene therapy for glycogen storage disease 1a (left to right) Alison, her son Caden, her niece Macy an
Slide 5: Driving revenue growth and key clinical data generation while increasing operational leverage
Driving revenue growth and key clinical data generation while increasing operational leverage Operational • Focus on large / pivotal programs • Leverage current pipeline and infrastructure efficiency • Financial discipline & alignment of resources Revenue growth Data generation Expanding current ma
Slide 6: Reaching patients around the world
Reaching patients around the world Commercial Compassionate use 6 Confi dential a nd Proprietary
Slide 7: Growing base of revenue driven by established and expanding commercial portfolio
Growing base of revenue driven by established and expanding commercial portfolio Growing Product Revenue $425-450M 2022 2023 Product 400 Estimate1 Guidance $352-356M Crysvita2 $277-279M $325-340M Product Revenue ($M) 300 $266M Dojolvi $55-56M $65-75M 200 $182M $103M Total Product $352-356M $425-450M
Slide 8: Strong balance sheet and operational efficiency provide runway
Strong balance sheet and operational efficiency provide runway to execute on value creating programs Uses 1 700 of Cash 600 Cash and equivalents3 of 500 ~$900M as of Dec 31, 2022 400 300 200 100 2023 Cash Used in Operations 0 2021 2022 2023 less than $400M Estimated 2 Cash Used in Operations GTMF Ca
Slide 9: Leverage and focused investments to grow value, manage cash use
Leverage and focused investments to grow value, manage cash use Mature, integrated rare disease company Growing revenue base and reducing cash use Driving value through advancement of large and late-stage clinical programs Increasing leverage from operational and program investments: • Established g
Slide 10: Key upcoming clinical catalysts
Key upcoming clinical catalysts PROGRAM OBJECTIVE EXPECTED TIMING Ph 2 LPI Early 2023 UX143 Ph 2 data readout and Ph 3 transition Mid-2023 Osteogenesis Imperfecta Initiate young pediatric study 1H23 GTX-102 FPI for Expansion Cohorts 1H23 Angelman syndrome Ph 1/2 data readout 2023 DT
Slide 11: UX143 (setrusumab) for Osteogenesis Imperfecta
UX143 (setrusumab) for Osteogenesis Imperfecta (OI) Abnormal bone metabolism leads to increased bone resorption, inadequate bone production Confi dential a nd Proprietary
Slide 12: UX143 for osteogenesis imperfecta: reverses abnormal bone biology
UX143 for osteogenesis imperfecta (OI) Reverses abnormal bone biology, repressing excess resorption • WW prevalence: ~60,000 (targeting types Mechanism of Anti-Sclerostin Mechanism Antibody of Anti-Sclerostin Antibody I/III/IV) • No approved treatments: bisphosphonates anti-resorptive treatments are
Slide 13: Anti-sclerostin antibody increases bone formation on all bone surfaces
Anti-sclerostin antibody increases bone formation on all bone surfaces Osteoporotic Monkey Model (12mo Tx) Vehicle Sclerostin-Ab Femur Diaphysis Red bone formed on the important sites: the bone surface and middle of the bone Ominsky et al 2017 13 Confi dential a nd Proprietary
Slide 14: UX143 can normalize bone mass and strength in brittle OI mice
UX143 can normalize bone mass and strength in brittle OI mice even if collagen still mutated • UX143 (5wks) restored Femur Diaphysis Femur Diaphysis Lumbar Vertebra cortical bone geometry 0.25 30 * 50 * & strength in Brtl/+ mice * +6% to WT levels 0.20 40 +28% -1% Maximum Load (N) Maximum Load (N) •
Slide 15: UX143 makes stronger bone than bisphosphonates
UX143 makes stronger bone than bisphosphonates 5wk UX143 vs 12wk Alendronate in Brittle Mouse OI Model BONE MASS INDICES BONE STRENGTH INDICES CSMI Cortical Thickness Maximum Load Stiffness 120 * 120 120 120 * 100 * * +20% % of WT mean % of WT mean % of WT mean 100 100 100 %WT mean UX143 80 -1% +5%
Slide 16: Phase 2b adult ASTEROID study: UX143 well tolerated
Phase 2b adult ASTEROID study: UX143 well tolerated BMD and bone strength dose-dependently improved Mean % ∆ UX143 UX143 UX143 from BL at 12 mos 20 mg/kg 8 mg/kg 2 mg/kg 8.97 6.65 2.35 Lumbar spine aBMD (p<0.001) (p<0.001) (p<0.05) BMD increases 2.48 2.69 1.99 consistent across Total
Slide 17: UX143 program next steps
UX143 program next steps Phase 2/3 Orbit study in patients ages 5-25 initiated April 2022 • Phase 2: identify dose strategy based on increases Osteogenesis in collagen production using serum P1NP levels imperfecta • Phase 3 transition: expected to initiate in mid-2023; treatment leverages evaluate f
Slide 18: GTX-102 Program for Angelman Syndrome
GTX-102 Program for Angelman Syndrome (AS) Neurogenetic disorder caused by loss of expression of UBE3A gene Confi dential a nd Proprietary
Slide 19: GTX-102 for Angelman syndrome: ASO activates UBE3A
GTX-102 for Angelman syndrome (AS) Antisense oligonucleotide (ASO) activates UBE3A • Devastating neurodevelopmental disorder • WW prevalence: ~60,000 • No approved treatments • Currently in Phase 1/2: dose titration and expansion • Provided promising interim data in July 2022 with acquisition of Gen
Slide 20: Study dosing schematic for GTX-102 in U.K. and Canada
Study dosing schematic for GTX-102 in U.K. and Canada Day 58 Day 128 PMD ~Day 170 PMD ~Day 254 Baseline Evaluation Evaluation Evaluation Evaluation Evaluation Next Dose Major Next Dose Next Dose Increase or not? Assessment Increase or not? Increase or not? Dose 1 Dose 2 Dose 4 Dose 3 Dose 5 Dose 6 M
Slide 21: Increases in receptive and expressive communication
Increases in receptive and expressive communication Exceeds threshold to be significant Bayley-4 GSV1 Bayley-4 is an established measure Latest Assessment Change from Baseline2 • Administered by psychologist Receptive Expressive • A score of +/-6 or greater is statistically larger than Communication
Slide 22: Substantial, clinically meaningful changes in sleep domain
Substantial, clinically meaningful changes in sleep domain1 Cohort 4 : AS Sleep Change in Severity Comments from Caregivers on Sleep Less Severe -6 Patient 7 (cohort 4): Her sleep has improved which is humongous, and very helpful for me and our whole family. -4 -4 -3 Patient 11 (cohort 4): Before [t
Slide 23: GTX-102 safety profile under amended protocol
GTX-102 safety profile under amended protocol 23 patients dosed: loading doses range from 2 mg to 10 mg, maintenance up to 14 mg • Ten patients with 6 to 12 months exposure and five with >12 months Common AEs: COVID-19 infection, vomiting, upper respiratory infection One AE of special interest (AESI
Slide 24: Encouraging signs of clinical activity
Encouraging signs of clinical activity Successfully redosing three of original five U.S. patients • Clinical responses at lower loading doses (Cohorts 4-7) • Continuing dose exploration with higher loading doses For the first time in their life, Patient • Patients showing clinical activity and furth
Slide 25: GTX-102 program next steps
GTX-102 program next steps In discussions with FDA to harmonize U.S. study with U.K. / Canada Next program update Enrolling Phase 1/2 expansion cohorts based on a larger number of patients in the program Phase 3 planning and endpoints 25 Confi dential a nd Proprietary
Slide 26: Our gene therapy franchise
Our gene therapy franchise Leading clinical and manufacturing expertise Confi dential a nd Proprietary
Slide 27: Large advanced gene therapy portfolio in rare disease
Large advanced gene therapy portfolio in rare disease Candidate Description Pre-Clinical IND Phase 1 Phase 2 Phase 3 Approved UX111 AAV9 Mucopolysaccharidosis Type IIIA (MPS IIIA) (ABO-102) Gene Therapy AAV8-G6Pase DTX401 Gene Therapy Glycogen Storage Disease Type Ia (GSDIa) AAV8-OTC DTX301 Gene The
Slide 28: Four pivotal gene therapy programs
Four pivotal gene therapy programs DTX401 for GSDIa UX111 for MPS IIIA • WW prevalence: 6,000 • WW prevalence: 3,000-5,000 • Phase 3 fully enrolled • Phase 1/2/3 ongoing • Data anticipated by 1H24 • Meeting with FDA to discuss filing path 1H23 DTX301 for OTC UX701 for Wilson disease • WW prevalence:
Slide 29: Gene therapy technology & manufacturing facility provide control over quality and COGS
Our gene therapy technology & manufacturing facility provide control over quality and COGS Pinnacle PCL™ platform Manufacturing facility in Bedford, MA • Efficient, reliable production of AAV • Improved product quality and yield • Lower cost and increased speed of production • Potentially improved s
Slide 30: Foundation for value generation
Foundation for value generation Confi dential a nd Proprietary
Slide 31: Three parallel opportunities to meaningful value
Three parallel opportunities to meaningful value 2023 milestones Expected data generation Angelman ~60,000 • FPI for Syndrome patients expansion • Phase 1/2 data in 2023 cohorts • Phase 3 Osteogenesis ~60,000 transition • Phase 2 data mid-2023 Imperfecta patients • Initiate young pediatric study ~50
Slide 32: We are leading the future of rare disease medicine
We are leading the future of rare disease medicine One of the most robust and diverse clinical pipelines in rare Broad global commercial footprint and expertise History of strong clinical and commercial execution Inspired and urgent mission to transform as many lives as possible 32 Confi dential a n
Slide 33: Thank you
Thank you IR@ultragenyx.com Confi dential a nd Proprietary
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