Ultragenyx Pharmaceutical Inc. · NASDAQ:RARE
Ultragenyx Pharmaceutical — Technical Presentation (October 2023)
22 slides from Ultragenyx Pharmaceutical's technical presentation, Oct 16, 2023
Slide 1: GTX-102 for Angelman Syndrome Phase 1/2 Clinical Study Update
GTX-102 for Angelman Syndrome Phase 1/2 Clinical Study Update © 2023 Ultragenyx Pharmaceutical Inc. | Confidential and Proprietary Exhibit 99.3
Slide 2: GTX-102 for Angelman syndrome (AS)
GTX-102 for Angelman syndrome (AS) Antisense oligonucleotide (ASO) activates UBE3A Confidential and Proprietary Devastating neurodevelopmental disorder Prevalence*: ~60,000 No approved treatments Phase 1/2: enrolling and dosing expansion cohorts Targeting highly conserved region across multiple spec
Slide 3: GTX-102 Phase 2 Update
GTX-102 Phase 2 Update © 2023 Ultragenyx Pharmaceutical Inc. | Confidential and Proprietary Multiple domains improved in Loading and Maintenance Phase compared to natural history, where available Clinical changes associated with quantitative changes in EEG Extension cohorts and redosed patients have
Slide 4: Key Angelman Syndrome Domain Evaluations
© 2023 Ultragenyx Pharmaceutical Inc. | Confidential and Proprietary Key Angelman Syndrome Domain Evaluations Domains Evaluation Natural History Comparison1 Cognition Bayley-4 Yes Sleep Angelman Severity Assessment for Sleep (ASA) -- Receptive Communication Bayley-4 Yes Behavior ASA for Behavior --
Slide 5: Angelman Severity Assessment (ASA) Rating Scales
Angelman Severity Assessment (ASA) Rating Scales © 2023 Ultragenyx Pharmaceutical Inc. | Confidential and Proprietary ASA rate the severity of the patient’s symptoms The ratings are: 1 – Not at all impaired 2 – Borderline, slightly impaired 3 – Mildly impaired 4 – Moderately impaired 5 – Markedly im
Slide 6: Interim Phase Data on Extension Cohorts
Confidential and Proprietary Interim Phase 2 Data on Extension Cohorts No additional events of lower extremity weakness or other safety signals Cohorts 4-7 Enrolled outside of the U.S. n=15 patients Loading doses from 3.3 - 7.5 mg Maintenance from 10 - 14 mg 11 patients on therapy greater than 12 mo
Slide 7: Study Dosing Schematic for GTX-102
Study Dosing Schematic for GTX-102 Loading phase through Day 254 Month 1 … PMD2 PMD1 Month 4 Month 2 Month 3 Baseline Evaluation Day 58 Evaluation Day 128 Evaluation Day 254 Evaluation Dose 1 Dose 2 Dose 3 Dose 4 Dose 5 Dose 6 Monthly loading doses Maintenance dosing every 3 months © 2023 Ultragenyx
Slide 8: Natural History as Comparator for GTX-102 Phase Data
© 2023 Ultragenyx Pharmaceutical Inc. | Confidential and Proprietary Natural History as Comparator for GTX-102 Phase 2 Data Comparable to GTX-102 study population age and genotype 1Sadhwani et al., 2021; Keute et al., 2021; Gentile et al., 2010 2Linking Angelman and Dup15q Data for Expanded Research
Slide 9: Cognition by Bayley-4 Improved Rapidly Compared to Natural History
Cognition by Bayley-4 Improved Rapidly Compared to Natural History GTX-102 treated patients showed positive response at Day 254 Natural history through Day 730 15 15 12 0 128 254 Day Patients -2 0 2 4 6 8 10 12 Bayley-4 Cognition GSV LS Mean (SE) -5 0 365 730 254 Patients 64 62 47 Bayley-4 Cognition
Slide 10: EEG Showed Rapid Positive Change for Patients on GTX-102
Natural History EEG data shows pathologically increased relative delta power (den Bakker et al., 2018) Relative delta power reliably predicts cognitive function, as assessed by the Bayley (Ostrowski et al., 2021) EEG Showed Rapid Positive Change for Patients on GTX-102 Reduction in delta relative po
Slide 11: Sleep by ASA Scores Improved in Parallel with Increased Sleep Spindle Duration
Sleep by Angelman Severity Assessment (ASA) Scores Improved in Parallel with Increased Sleep Spindle Duration on EEG den Bakker H et al. (2018) Mol Autism 9: 32. Ostrowski LM et al. (2021). Ann Clin Transl Neurol 8(7): 1433-1445. ASA-Sleep improved for GTX-102 treated patients through Day 254 EEG sh
Slide 12: GTX-102 Maintenance Phase
GTX-102 Maintenance Phase Confidential and Proprietary
Slide 13: Cognition by Bayley-4 Continued to Improve During Maintenance Phase
Cognition by Bayley-4 Continued to Improve During Maintenance Phase GTX-102 treated patients showed positive response through Day 506 Patients 15 0 15 128 12 254 11 338 9 422 8 506* Day 25 20 15 10 5 0 -5 *Doses at D506 between 10mg and 14mg Bayley-4 Cognition GSV LS Mean (SE) Natural history throug
Slide 14: Receptive Communication by Bayley-4 Showed Sustained Improvement During Maintenance
Receptive Communication by Bayley-4 Showed Sustained Improvement During Maintenance Treated patients showed sustained improvements through Day 506 Natural history through Day 730 15 12 8 0 128 422 15 11 9 338 506 254 -2 0 2 4 6 8 10 12 Patients 0 365 730 Day 506 Bayley-4 Receptive Communication GSV
Slide 15: Gross Motor by Bayley-4 Showed Continued Improvement Compared to Natural History
Gross Motor by Bayley-4 Showed Continued Improvement Compared to Natural History Gross Motor Bayley-4 showed steady improvement through Day 506 Response threshold of ≥5 based on Bayley-4 administration manual. The estimated values are from a GEE model which includes all available data as the depende
Slide 16: Sleep by ASA Show Continued Improvement During Maintenance
Sleep by ASA Show Continued Improvement During Maintenance The estimated values are from a GEE model which includes all available data as the dependent variable and baseline age as a covariate, with exchangeable correlation structure. Day Patients ASA-Sleep improved for patients treated with GTX-102
Slide 17: Behavior by ASA Showed Continued Improvement During Maintenance
Behavior by ASA Showed Continued Improvement During Maintenance 15 12 7 0 128 422 Day 15 9 9 254 338 506 Patients 14 170 The estimated values are from a GEE model which includes all available data as the dependent variable and baseline age as a covariate, with exchangeable correlation structure. ASA
Slide 18: Multi-Domain Responder Index (MDRI) Captures Broad Clinical Benefit Across Five Domains
Multi-Domain Responder Index (MDRI) Captures Broad Clinical Benefit Across Five Domains in Patients Treated with GTX-102 Patient (n=11) ASA Sleep ASA Behavior Bayley-4 Receptive Comm Bayley-4 Gross Motor Bayley-4 Cognition Total Net Responses* 1 1 0 1 0 3 1 2 3 2 7 3 17 4 3 1 1 16 5 20 5 4 0 0 14 3
Slide 19: Quantitative Analysis of Multiple Domains Showed Meaningful Improvement
© 2023 Ultragenyx Pharmaceutical Inc. | Confidential and Proprietary Quantitative Analysis of Multiple Domains Showed Meaningful Improvement Improvements far exceeding natural history Cognition Receptive Communication Gross Motor Supportive data from EEG delta power and sleep spindle Improvements in
Slide 20: Emergence of New Developmental Skills Gained, Lost and Regained in Redosed Patients
Emergence of New Developmental Skills Gained, Lost and Regained in Redosed Patients Patient A Patient B Patient C 103-004 Init dose Off-tx Re-dose Init dose Off-tx Re-dose Init dose Off-tx Re-dose Receptive Communication Responds to name No issue Follows 1-step directions Follows 2-step or complex d
Slide 21: Interim Safety Evaluation including Extension and Expansion Cohorts
Interim Safety Evaluation including Extension and Expansion Cohorts Most Common Adverse Events Reported Phase 1/2 Patients (n=58) Vomiting (anesthesia related) 18 (31%) Pyrexia (Fever) 10 (17%) Nasopharyngitis 8 (14%) Coronavirus infection 6 (10%) Fall 5 (9%) Post-lumbar puncture syndrome 5 (9%) No
Slide 22: Next Steps
Next Steps Phase 2 Expansion Cohort Update © 2023 Ultragenyx Pharmaceutical Inc. | Confidential and Proprietary >30 patients enrolled across Cohorts A-E (Expansion Cohorts) 25 sites active across 8 countries Next data update planned for at least 20 patients with 6 months of data by 1H24 Expected FDA
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