Slide 1: Six Month Results of the Phase I Study of RGX-314 Gene Therapy in nAMD
Six Month Results of the Phase | Study to Evaluate Safety & Tolerability of RGX-314 Gene Therapy in nAMD Subjects Jeffrey Heier, MD Peter Campochiaro, MD, Allen Ho, MD, Albert Maguire, MD, David M. Brown, MD, Jorge Calzada, MD, Robert Avery, MD, Szilard Kiss, MD Stephen Yoo, MD, Sherri Van Everen, P
Slide 2: Disclosures
Disclosures Research grants: Aerpio, Apellis, Clearside, Corcept, Daiichi Sankyo, Genentech, Genzyme, Hemera, Janssen R&D, Kalvista, Kanghong, Novartis, Ocudyne, Ophthotech, Optovue, Regeneron, REGENXBIO, Scifluor, Tyrogenex Scientific Advisor: 4DMT, Adverum, Aerie, Aerpio, Akros, Allegro, Apellis,
Slide 3: RGX-314: Optimized NAV Gene Therapy for Wet AMD
RGX-314: Optimized NAV® Gene Therapy for Wet AMD Gene Encoding for NAV AAVB Vector Sone ETE Cell a anti-VEGF RGX-314 is Designed fab Protein to Deliver a Gene Encoding for an anti-VEGF fab Protein
Slide 4: Utilizing AAV8 for Higher Protein Expression in NHPs
RGX-314: Utilizing AAV8 for Higher Protein Expression in NHPs "Vandenberghe ea 2011 Scion Tansotena Medkeine
Slide 5: Design
RGX-314 Phase | Trial: Design nin eor Pen reese nestor mare Weeks t t t ea Safety Safety Safet 3x10? GCleye review! 1x10" GCleye review! «x10 GCleye review! —-1.6x10" GCeye Dosing Completed in Four Cohorts
Slide 6: Standardized Automated Subretinal Delivery Procedure
RGX-314: Standardized Automated Subretinal Delivery Procedure Step 1 — Vitrectomy Step 2 — Subretinal Injection wt MicroDose™ be i Kit Mecone MicroDose nge y to per i i bleb area a core vitrectomy ina healthy area of retina ifneeded 2DA away from the fovea Air fluid exchange and then Sub-conj steroi
Slide 7: Outcome Measures and Eligibility Criteria
RGX-314 Phase | Trial: Outcome Measures and Eligibility Criteria ee incae 3) Objectives Prima Key Inclusion Criteria ry = To determine the safety and tolerability of RGX-314 in patients with nAMD though 6 months. 2 go 2 2 = Expression of RGX-314 protein in the eye = Documented nAMD with response to
Slide 8: Anti-VEGF Rescue Injection Criteria
RGX-314 Phase | Trial: Anti-VEGF Rescue Injection Criteria Anti-VEGF may be given beginning 4 weeks post-treatment and PRN every 4 weeks thereafter per investigator’s discretion if one or more of the criteria apply: Vision loss of 25 letters CNV-related increased, associated w/ new, or persistent fl
Slide 9: Baseline Demographics for Cohorts 1-3
RGX-314 Phase | Trial: Baseline Demographics for Cohorts 1-3 Variabl Cohort 1 (n=6) | Cohort 2(n=6) | Cohort 3 (n=6) Total (n=18) g Mean Age (Years) 782 78.0 80.0 78.7 = & Female (Number, %) 4 (66.7%) 3 (60.0%) 2 (83.3%) 9 (60.0%) 3 3 3 Caucasian, no. (%) 6 (100.0%) 6 (100.0%) 6 (100.0%) 18 (100.0%)
Slide 10: Safety for Cohorts 1-3
RGX-314 Phase | Trial: Safety for Cohorts 1-3* = RGX-314 was well-tolerated (n=18) = No drug-related AEs or drug-related SAEs = Most AEs were assessed as mild (Grade 1 — 83%) = No observed clini: immi drug-related ocular inflammation, or any post-surgical inflammation beyond what is expected followi
Slide 11: Protein Levels at One Month for Cohorts 1-3
RGX-314 Phase | Trial: Protein Levels at One Month for Cohorts 1-3 As measured from aqueous samples by ECL-based assay ZF 1000 — 160.2 ng/ml £ ra Ss 100 os 8 ae 12.8 ng/ml no i CI oO 4 € § 8 = 1 r : 1 Cohort 4 Cohort 2 Cohort 3 3x10® GCleye 1x10" GCleye 6x10" GCleye N=6 N=6 N=6 RGX-314 Dose
Slide 12: Mean Change in BCVA, CRT and Average Injections Over Six Months, by Cohort
RGX-314 Phase | Trial: Mean Change in BCVA, CRT and Average Injections Over Six Months, by Cohort Best Corrected Visual Acuity (BCVA) 2 2 Or oe rma Ma a as Dr oe wt a ms a ms Tine Tine Or 08 Mt Ms Ma MS we Tine Average Injections: 4.7 Average Injections: 3.8 Average Injections: 1.3 Cohort 1 Cohort 2
Slide 13: Summary of Interim Results Through Six Months
RGX-314 Phase | Trial: Summary of Interim Results Through Six Months Mean Aqueous. RGX-314 Protein ‘One Month Posttreatment Mean # of Anti-VEGF |Mean Change inCRT| Mean Change -2 letters** 2.4 ngiml 47 inj (181 to +92 4m) ——-(-8 to +10 letters) +26 pm +7 letters 12.8 ng/ml 3.8 inj (7t0 +62 pm) (ato
Slide 14: Sustained Protein Levels at Six Months
RGX-314 Phase | Trial: Sustained Protein Levels at Six Months All Subjects (N=6) in Cohort 3 1000 160.2 ng/ml 217.8 ngim 100 10 1+ Month 1 Month 6 Mean RGX-314 Protein (ng/mL) (log scale) “One subject ecaved an ant VEGF rescue injection 1 month porto sample. “
Slide 15: Sustained Protein Levels at Six Months
RGX-314 Phase | Trial: Sustained Protein Levels at Six Months Subjects with in Cohort 100 Mean RGX-314 Protein (ng/mL) (log scale) Month 1 Month 6
Slide 16: Mean Change in BCVA and CRT Over Six Months
RGX-314 Phase | Trial: Mean Change i in Pah — Over Six Months in Cohort 3 Subj with No R ij Best Corrected Visual Acuity (BCVA) ™ “otal Ltrs Read or os co we us wa us 6 Tene Central Retinal Thickness (CRT) on SD-OCT or os ms a us wa us 6 Tine Cohort 3 with 16
Slide 17: Phase I Trial Interim Results at Six Months Conclusions
RGX-314: Phase | Trial Interim Results at Six Months Conclusions = RGX-314 was well-tolerated at all doses = Dose-dependent RGX-314 protein expression = Cohort 3: sustained RGX-314 protein at six months with stability in vision and anatomy despite few to no injections = Cohort 4: a higher dose recen
Slide 18: Acknowledgments
RGX-314 Acknowledgments = Robert Avery, MD (Santa Barbara, CA) Univorsity of = David Brown, MD (Houston, TX) aes, oe = Peter Campochiaro, MD (Baltimore, MD) BN tall a is ye nit, = Jorge Calzada, MD (Memphis. TN) Paiodeba,P een Johns Hopkins = Jeff Heier, MD (Boston, MA) “pe Stl atn pee ine = Allen H