Regenxbio Inc. · NASDAQ:RGNX
Regenxbio — WORLDSymposium 2021
17 slides from Regenxbio's conference presentation, Feb 11, 2021
Slide 1: RGX-121 Gene Therapy for Severe MPS II: Interim Results of an Ongoing First in Human Trial
RGX-121 Gene Therapy for Severe Mucopolysaccharidosis Type II (MPS II): Interim Results of an Ongoing First in Human Trial 11 February 2021 Marie-Laure Névoret, MD Senior Clinical Development Lead - REGENXBIO
Slide 2: Disclosures
Disclosures Marie-Laure Névoret is an employee of REGENXBIO 2
Slide 3: Objectives
Objectives Mucopolysaccharidosis Type II (MPS II) and RGX-121 as a therapeutic candidate Overview of RGX-121-101 First in Human Study Biochemical and Clinical Interim Analysis Conclusions and Program Outlook of Gene Therapy for MPS II 3
Slide 4: Mucopolysaccharidosis Type II (MPS II)
Mucopolysaccharidosis Type II (MPS II) Incidence MPS II is also known as Hunter syndrome 1 in 100,000 to Rare X-linked recessive genetic disease (predominantly occurs in males) 1 in 170,000 Caused by a deficiency of iduronate-2-sulfatase (I2S), an enzyme required for the degradation of the glycosami
Slide 5: RGX-121-101: MPS II Phase 1/2 Clinical Study Summary
RGX-121-101: MPS II Phase 1/2 Clinical Study Summary NCT03566043 on ClinicalTrials.gov RGX-121 AAV9 + IDS Patients Cohorts (dose levels) Data Genome copies/g brain mass Approximately 12 MPS II patients Cohort 1: 1.3 x 1010 Primary endpoint is safety; (≥ 4 months to ˂ 5 years of age) Cohort 2: 6.5 x
Slide 6: RGX-121-101: Patient overview
RGX-121-101: Patient overview ▪ No SAEs related to study drug as of 04 January 2021 ▪ Immunosuppression discontinued per protocol in first 4 patients ▪ 8 patients dosed to date ▪ Ages at dosing: 5 months to 59 months ▪ Mutations among patients: 3 missense, 2 gene inversions, 3 frameshifts Dose Follo
Slide 7: Cerebral spinal fluid (CSF) Biomarker: Heparan Sulfate (HS)
Cerebral spinal fluid (CSF) Biomarker: Heparan Sulfate (HS) Consistent Heparan Sulfate decrease in the CSF after RGX-121 dosing ▪ The median change from baseline at week 8 (N=6) is -30.3% and p-value is 0.03* ▪ The median change from baseline at the last available timepoint (N=6) is -35.8% and p-val
Slide 8: HS Digestion with Heparinase
HS Digestion with Heparinase Heparan Sulfate (HS) Heparinase ▪ I2S enzyme cleaves sulfates from HS in the lysosome ▪ Absence of I2S causes long chains of fully sulfated D2S6 to accumulate in I2S6 HS ▪ Quantitative measurement of D2S6 is reflective of I2S enzyme activity level D2S6 I2S6 and D2S6 are
Slide 9: CSF Biomarker: HS D2S6 Disaccharide
CSF Biomarker: HS D2S6 Disaccharide ▪ HS sulfation has been correlated with pathogenesis in neurodegenerative disorders1-3 Consistent decrease in CSF D2S6, a correlate of neuropathology phenotype in severe MPS II 4-6 ▪ The median change from baseline at week 8 (N=6) is -44.2% and p-value is 0.03* ▪
Slide 10: Neurodevelopment Function: Age Equivalence (Cognitive)
Neurodevelopment Function: Age Equivalence (Cognitive) Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) ▪ Patients 1, 3 and 5 demonstrate continued cognitive development within a normal range ▪ Patients 2 and 4 presented with significant cognitive delay at baseline – Patient 2
Slide 11: Neurodevelopment Function: Language and Motor Domains
Neurodevelopment Function: Language and Motor Domains BSID-III Expressive Communication Receptive Communication Gross Motor Fine Motor Continued language and/or motor skills acquisition in patients with > 6 months of follow-up 11
Slide 12: Systemic Efficacy: Urine Total GAGs ERT-Treated Patients
Systemic Efficacy: Urine Total GAGs ERT-Treated Patients Sustained decrease in urine GAG levels across all patients receiving ERT 12
Slide 13: Systemic Efficacy: Urine Total GAGs ERT Naïve and ERT Discontinued Patients
Systemic Efficacy: Urine Total GAGs ERT Naïve and ERT Discontinued Patients ERT Withdrawal ERT Withdrawal Rapid decrease in urine GAGs in ERT-naïve patients after RGX-121 administration; absence of urine GAG rebound post ERT withdrawal 13
Slide 14: Systemic Efficacy: Plasma I2S Enzyme Concentration
Systemic Efficacy: Plasma I2S Enzyme Concentration I2S Enzyme Concentration, Plasma (pg/mL) General increase in plasma I2S enzyme levels in 5 out of 6 patients after RGX-121 administration 14
Slide 15: Systemic Efficacy: Liver and Spleen Ultrasounds
Systemic Efficacy: Liver and Spleen Ultrasounds ERT Naïve Patient ▪ Hepatosplenomegaly occurs almost universally in untreated MPS II1 ▪ Patient 6, who never received ERT, demonstrated clear reduction in liver and spleen dimensions 24 weeks after receiving RGX-121 Liver Spleen Spleen Spleen Follow-Up
Slide 16: RGX-121-101: Summary of Results
RGX-121-101: Summary of Results RGX-121 appeared to be well tolerated ▪ 8 patients dosed with no SAEs related to study drug (as of 04January2021) ▪ Immunosuppression discontinued in first 4 patients according to protocol Biomarker and neurodevelopmental function indicate encouraging RGX-121 CNS acti
Slide 17: Acknowledgements
Acknowledgements The study coordinators (Jill, Jodi, Katherine, and Larissa), research assistants, and study teams at the clinical study sites MPS II patients and The study principal investigators: their families • Dr Maria Escolar, University of Pittsburgh, USA • Dr Can Ficicioglu, Children’s Hospi