Slide 1: 1 Year Data from First in Human Study of Pegzilarginase for ARG1-D
Dr Ravi M Rao, MD PhD Chief Medical Officer, Aeglea BioTherapeutics On behalf of the 101A/102A Investigators and Research Staff 1 Year Data from First in Human Study of Pegzilarginase for the Treatment of Arginase 1 Deficiency (ARG1-D) Diaz GA1, Bechter MW2, Sloan LS2, Rao RM2, Zori RT3 Exhibit 99.2
Slide 2: Disclosures
Bechter MW, Sloan LS, Rao RM are full time employees of Aeglea BioTherapeutics Diaz GA, Zori RT have performed as consultants and received travel support from Aeglea BioTherapeutics The investigational use of pegzilarginase will be discussed during this presentation Disclosures
Slide 3: Arginase 1 Deficiency (ARG1-D)
Arginase 1 Deficiency (ARG1-D) Autosomal recessive disorder of arginine metabolism due to ARG1 enzyme deficiency Recent genetic prevalence data suggests > 2500 patients worldwide1 >700 patients in Europe >250 patients in US Typically presents at ~2-4 years of age, can be later2,3 Developmental delay
Slide 4: Current Disease Management Fails To Adequately Control Plasma Arginine Levels
Current Disease Management Fails To Adequately Control Plasma Arginine Levels Improved catalytic activity and serum stability Substituted metal cofactor (Mn2+ replaced with Co2+ ) Pegzilarginase is Engineered to Robustly Control Plasma Arginine Even with strict dietary restriction, plasma arginine l
Slide 5: Open-Label, Multi-Centre Phase 1/2 Study of Pegzilarginase in ARG1-D
Inclusion criteria: Diagnosis of ARG1-D >2 years old Exclusion criteria: Severe, uncontrolled hyperammonaemia Key Objectives Primary endpoint: Safety and tolerability Secondary endpoints: Effect on: Plasma arginine (p[Arg]) Plasma guanidino compound (GC) levels Evaluation of clinical outcome assessm
Slide 6: Baseline Characteristics and Safety Summary
Baseline Characteristics (n=16) *Values are median (range) unless stated otherwise. Arg, arginine; ARG1, arginase 1; BL, baseline; NH3, ammonia; 6MWT, 6-minute walk test; GMFM-D/E, Gross Motor Function Measure Part D/E; Pt, patient ** 1 patient non-assessable (wheelchair bound) Safety Summary Pegzil
Slide 7: Pegzilarginase Markedly Reduces and Sustainably Controls Plasma Arginine
Baseline p[Arg] on standard disease management was markedly elevated Significant and sustained reductions in p[Arg] were achieved from baseline to week 1, week 8, week 20 and week 56 At the week 56 analysis: the median p[Arg] was 99µM (40-115µM) 10/13 patients achieved a p[Arg] within normal range (
Slide 8: Clinically Impactful Improvements at Patient Level with Pegzilarginase
Clinically Impactful Improvements at Patient Level with Pegzilarginase Assessment Normal Population Baseline 20 Week Analysis 56 Week Analysis Plasma arginine 40 - 115µM 363µM 108.5µM* 88.2µM* 6MWT 310 - 664m 174m 176m 209m* GMFM-D Max = 39 21 27* 28* GMFM-E Max = 72 27 35* 34* Teenage girl diagnose
Slide 9: Pegzilarginase Demonstrates Sustained Improvements in Six Minute Walk Test
Pegzilarginase Demonstrates Sustained Improvements in 6 Minute Walk Test 6MWT by Patient at 56 Week Analysis Mean Change from Baseline in 6MWT Change from Baseline (m) 6MWT – Six Minute Walk Test; MCID=9% 8 Week Analysis Mean Change from Baseline (m) 20 Week Analysis 56 Week Analysis Individual Pati
Slide 10: Patients in GMFCS Levels II and III also Show Improvement in Mobility
GMFM-D Change from Baseline 56 Week Analysis (n=6) GMFM-E change from Baseline 56 Week Analysis (n=6) Patients in GMFCS Levels II and III also Show Improvement in Mobility MCID for GMFM Part D is 3.3 and 1.5 for GMFCS Levels II and III, respectively; MCID for GMFM Part E is 2.8 and 1.8 for GMFCS Lev
Slide 11: Pegzilarginase Demonstrates Durable Clinical Response
Pegzilarginase Demonstrates Durable Clinical Response at 56 Week Analysis *MCID for 6MWT = 9%; MCID for GMFM Part D is 2.4, 3.3, and 1.5 for GMFCS Levels I, II and III, respectively; MCID for GMFM Part E is 4.0, 2.8, and 1.8 for GMFCS Levels I, II and III, respectively. Maximum values for GMFM-D and
Slide 12: Conclusions
Conclusions Arginase 1 Deficiency (ARG1-D) is a debilitating, progressive, inherited, metabolic disease driven by the accumulation of arginine and its metabolites, which results in prominent neurological manifestations including progressive spastic diplegia and early mortality Delays in diagnosis ar
Slide 13: Acknowledgements
The 101A/102A Investigators and Research Staff wish to acknowledge and thank the Patients, their Families, and Caregivers for their dedication to these studies Acknowledgements Information on the ongoing Phase 3 Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints (PEACE) Study for pati