MeiraGTx Holdings plc · NASDAQ:MGTX
MeiraGTx — ARVO Annual Meeting 2023
10 slides from MeiraGTx's conference presentation, April 2023
Slide 1: Humoral Immune Response to AAV5-RPGR Gene Therapy in RPGR-associated XLRP
Humoral Immune Response to AAV5- RPGR (Botaretigene Sparoparvovec) Gene Therapy in RPGR-associated X-linked Retinitis Pigmentosa Eleni Caratzas,1,* Michael Clark,1 Albert Fung,1 Tong-Yuan Yang,1 Anastasios Georgiadis,2 Carrie Page,2 Michel Michaelides,3,4 Pansy Minnick,1 Douglas Steinbach1 1Janssen
Slide 2: Background
Background • XLRP is a severe form of retinitis pigmentosa that leads to progressive vision loss1 • AAV5-RPGR (botaretigene sparoparvovec) is being developed as a subretinal gene therapy for patients with XLRP caused by mutations in the RPGR gene • Immunogenicity is a potential concern with AAV-base
Slide 3: MGT009: Phase 1/2 Trial of AAV5-RPGR
MGT009: Phase 1/2 Trial of AAV5-RPGR Open-label study of an AAV5-RPGR gene therapy (NCT03252847) conducted at 5 sites in the United States and the United Kingdom Dose-escalation Dose confirmation Expansion cohort Adults Children Adults and children Low dose Intermediate dose Followed for 12 months (
Slide 4: Methods
Multitiered Approach Methods Used for Assessment of Antibodies1 Sensitive screening assay • Titers were only quantified on samples that were confirmed positive No No • Neutralizing antibodies to the capsid were only assessed in Positive further participants identified as treatment-emergent positive
Slide 5: Summary of Immunogenicity Results
Summary of Immunogenicity Results Baseline Antibodies to AAV5, Neutralizing Antibodies Treatment-emergent Antibodies to AAV5, to AAV5, and Antibodies to RPGR Neutralizing Antibodies to AAV5, and Antibodies to 100 100 RPGR Through Week 26* 90 90 80 80 70 70 60 60 Total, % Total, % 50 44.4% 50 46.7% 4
Slide 6: Time to AAV5 Capsid Treatment-emergent Antibodies
Time to Treatment-emergent Antibodies to AAV5 Capsid All 45 Participants Stratified by Dose Level 100 Strata All 100 Strata Low Intermediate High Positive participants for treatment- Positive participants for treatment- emergent antibodies to AAV5, % emergent antibodies to AAV5, % 75 75 50 50 25 25
Slide 7: Time to Treatment-emergent Neutralizing Antibodies to AAV5 Capsid
Time to Treatment-emergent Neutralizing Antibodies to AAV5 Capsid All 21 Positive for Treatment-emergent Antibodies to AAV5 Participants Stratified by Dose Level 100 Strata All 100 Strata Low Intermediate High treatment-emergent neutralization treatment-emergent neutralization Positive participants
Slide 8: Time to RPGR Treatment-emergent Antibodies
Time to Treatment-emergent Antibodies to RPGR All 45 Participants Stratified by Dose Level treatment-emergent antibodies to RPGR, % treatment-emergent antibodies to RPGR, % 100 Strata All 100 Strata Low Intermediate High Positive participants for Positive participants for 75 75 50 50 25 25 0 0 0 4 1
Slide 9: Conclusions
Conclusions • There was no apparent association between treatment-emergent antibody status and dose • Findings did not seem to deviate from those reported for voretigene neparvovec1-3 1. US Food and Drug Administration. LUXTURNA® Biologics License Application Clinical Review Memorandum. https://www.
Slide 10: Acknowledgments
Acknowledgments • Participants and families • Referring clinicians and collaborators • Trial managers, coordinators, and technicians • Reading centers in Belfast, OHSU, and MCW • Other supporting institutions: Kellogg Eye Center (University of Michigan), Moorfields Eye Hospital (NHS Foundation Trust