Spyre Therapeutics, Inc. · NASDAQ:SYRE
Spyre Therapeutics — Aeglea BioTherapeutics — Technical Presentation (April 2019)
14 slides from Spyre Therapeutics's technical presentation, Apr 8, 2019
Slide 1: Sustained Reductions in Plasma Arginine Following Pegzilarginase Administration in ARG1-D
Sustained Reductions in Plasma Arginine Following Pegzilarginase Administration in Patients with Arginase-1 Deficiency are Accompanied by Improvements in Mobility and Adaptive Behavior Diaz GA1, Schulze A2, McNutt MC3, Teles EL4, Merritt II JL5, Enns GM6, Batzios SP7, Conway RL8, Bechter M9, Eckert
Slide 2: Disclosures
Disclosures • Grant/Research Support: Urea Cycle Disorders Consortium, NYCKidSeq Consortium, N-Carbamylglutamate Consortium • Consultant: Aeglea BioTherapeutics, Horizon Pharma, Moderna Therapeutics, Synlogic Therapeutics, Ultragenyx • Major Shareholder: None I will be discussing investigational use
Slide 3: Arginase 1 Deficiency
Arginase 1 Deficiency • ARG1-D Causes Two Key Metabolic Effects − High levels of arginine and arginine-derived metabolites − Impairment of the Urea Cycle• Key Disease Manifestations − Chronic hyperargininemia-related: ▪ spasticity, loss of mobility, deficits in adaptive behavior, intellectual disabi
Slide 4: Year-Old Female with ARG1-D at Baseline
19 Year-Old Female with ARG1-D at Baseline Clinical Presentation Baseline Study Assessments • Diagnosed age 1 after presentation with hyperammonemia • Developed severe lower limb spasticity, speech delay, intellectual disability • Treated with severe protein restriction, essential amino acids, and a
Slide 5: Open-Label, Multi-Center Phase 1/2 Study of IV Pegzilarginase in ARG1-D
Open-Label, Multi-Center Phase 1/2 Study of IV Pegzilarginase in ARG1-DInclusion criteria: • Diagnosis of ARG1-D • >2 years old Exclusion criteria: • Severe, uncontrolled hyperammonemia Completed Part 1 Single Ascending Dose (Q2W) Part 2 8 Repeat Doses (QW) Open Label Extension (QW) Clinical assessm
Slide 6: Baseline Mobility Assessments
Baseline Mobility Assessments6-Minute Walk Test Age/Gender Reference Limits6-Minute Walk Test Age/Gender Reference Limits Berg Balance ScalePROMIS Physical Function / MobilityT-scores (N=14) patient was wheelchair bound. 2 patients were non-English speaking and not assessed for PROMIS1 patient was w
Slide 7: Baseline Adaptive Behavior Assessment
Baseline Adaptive Behavior Assessment Adaptive Behavior Assessment System(ABAS) ≥ 1 SD below mean GAC Conceptual Practical Social GAC Conceptual Practical Social8/10 assessed patients had baseline deficiencies in one or more domains assessed by ABAS Captured deficits in activities of daily living, i
Slide 8: Pegzilarginase Rapidly Reduced and Sustainably Controlled Plasma Arginine
Pegzilarginase Rapidly Reduced and Sustainably Controlled Plasma Arginine• Arginine reduction statistically significant after 1 dose – (n=13 with paired data) • Plasma arginine control improved over time with further significant reduction after 8 weeks of dosing 8 *1-week sample not collected in 1 p
Slide 9: Safety Assessments
• Pegzilarginase was generally well tolerated − > 300 infusions administered − 83% of infusions were ≤ 30 minutes duration • Hypersensitivity reactions were manageable with standard measures and did not lead to treatment discontinuation • Low-titer, emergent ADAs were detected in 8/16 patients; all
Slide 10: Clinically Important Improvements After Only 8 Weeks of Dosing
Clinically Important Improvements After Only 8 Weeks of Dosing9 / 14 patients (64%) demonstrated clinically meaningful improvements in one or more clinical endpoints after only 8 weeks of dosingExceeds MCID Less than MCID 10 Data is for patients who completed Part 2; patients who were within 1 MCID
Slide 11: Continued Improvements in Mobility were Observed at Dose 20
Continued Improvements in Mobility were Observed at Dose 205 / 5 (100%) patients demonstrated clinically meaningful improvements in one or more clinical endpoints at 20 weeks of dosing GMFM enhances the ability to capture objective improvements in mobility14 patients have completed Part 2, and 5 pat
Slide 12: Year-Old Female with ARG1-D on Pegzilarginase
19 Year-Old Female with ARG1-D on PegzilarginaseClinical Presentation• Diagnosed age 1 after presentation with hyperammonemia • Developed severe lower limb spasticity, speech delay, intellectual disability • Treated with severe protein restriction, essential amino acids, and ammonia scavengers • Pro
Slide 13: Conclusions
Conclusions • Pegzilarginase was highly effective in sustainably lowering plasma arginine, a key driver of ARG1-D disease manifestations and progression • Plasma arginine reductions were accompanied by improvements in mobility and adaptive behavior after only 8 weeks of repeat dosing with additional
Slide 14: Acknowledgements
Acknowledgements The 101A/102A Investigators and Research Staff wish to acknowledge and thankthe Patients, their Families, and Caregiversthe Patients, their Families, and CaregiversInformation on the Phase 3 Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints (PEACE) Study for patients
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