Editas Medicine, Inc. · NASDAQ:EDIT
Editas Medicine — Technical Presentation (May 2022)
15 slides from Editas Medicine's technical presentation, May 16, 2022
Slide 1: Exploratory Immuno-Safety Profile of EDIT-101, a First-in-Human In Vivo CRISPR Gene Editing Therapy
Exploratory Immuno-Safety Profile of EDIT-101, a First-in-Human In Vivo CRISPR Gene Editing Therapy for CEP290-Related Retinal Degeneration Brian R. Duke, Saleh El-Husayni, Michael C. Jaskolka, Amanda Erlwein, Rene Myers, Mark E. Pennesi, Eric Pierce, Mark S. Shearman, Kate Zhang, Swati Mukherjee 16
Slide 2: Disclosures
Disclosures Brian R. Duke, Saleh El-Husayni, Michael C Jaskolka, Amanda Erlwein, Rene Myers, Mark S. Shearman, Kate Zhang, and Swati Mukherjee are all employees of Editas Medicine 2
Slide 3: CEP290-related retinal degeneration: A leading cause of early onset vision loss
CEP290-related retinal degeneration: A leading cause of early onset vision loss Currently no approved treatments for CEP290-related retinal degeneration • Leber Congenital Amaurosis Type 10 (LCA10) is a rare, autosomal recessive inherited disorder that causes progressive vision loss in children with
Slide 4: EDIT-101 is designed to specifically edit CEP290 within photoreceptors
EDIT-101 is designed to specifically edit CEP290 within photoreceptors AAV5 with DNA encoding two gRNAs and SaCas9 delivered subretinally as a single dose EDIT-101 • Photoreceptor-tropic AAV5 vector AAV5-CRISPR-Cas9 gene editing • Highly specific Guide RNAs • Restricted SaCas9 expression in photorec
Slide 5: EDIT-101 is designed to specifically edit CEP290 within photoreceptors
EDIT-101 is designed to specifically edit CEP290 within photoreceptors AAV5 with DNA encoding two gRNAs and SaCas9 delivered subretinally as a single dose No protein trafficking AAV5: adeno-associated virus type 5; SaCas9: Staphylococcus aureus CRISPR associated protein 9; hGRK1: human G-coupled Rec
Slide 6: BRILLIANCE Trial
BRILLIANCE Trial Phase 1/2, open-label, single ascending dose study for EDIT-101 (NCT03872479) Screening 2 Year Extension with Option Baseline 12 Months Following Single Sub-Retinal Treatment in Worse Eye for 12 Years of Follow-up Adult Low Dose (6 x 1011 vg/ml) N=2 Primary Objective: Safety Adult M
Slide 7: AAV gene therapy based clinical trials require monitoring adaptive immunity
AAV gene therapy based clinical trials require monitoring adaptive immunity AAV5 Memory B Cell MHCII TCR TCR MHCII CD4 DC T Cell B Cell Target MHCI TCR CD8 cell T cell CD4 CD4 Plasma Peptide cell CD8 Antibodies Perforin/granzyme AAV5: adeno-associated virus type 5; BAB: binding antibody; CD: cluster
Slide 8: Cell mediated and humoral immune responses are being monitored in the BRILLIANCE trial
Cell mediated and humoral immune responses are being monitored in the BRILLIANCE trial AAV5 Memory Memory BBCell Cell MHCII TCR TCR MHCII CD4 CD4 DC DC TTCell BB Cell Cell Cell Target MHCI TCR CD8 cell T cell CD4 CD4 Plasma Plasma Peptide cell CD8 cell Perforin/granzyme A Antibodies B A. Cell Mediat
Slide 9: Profile of subjects with pre-existing immune response to AAV5 and SaCas9
Profile of subjects with pre-existing immune response to AAV5 and SaCas9 Pre-existing Immune Responses • Pre-existing humoral immunogenicity to AAV5 was seen to AAV5 and SaCas9 at screening in 3 of 11 subjects dosed. Only 1 subject’s 8 pre-existing antibodies were neutralizing 6 # Positive Subjects
Slide 10: SaCas9 and AAV5 humoral response: Binding Antibodies
SaCas9 and AAV5 humoral response: Binding Antibodies SaCas9 BAB Titer AAV5 BAB Titer 10 5 10 5 10 4 10 4 10 3 10 3 Titer Titer 10 2 10 2 10 1 10 1 10 0 10 0 g g 2 4 8 2 4 8 3 6 12 3 6 12 n n k k k k k k th th th th ni ni ee ee ee ee ee ee th th on on on on e e on on W W W W W W re re M M M M M M Sc
Slide 11: Most antibody responses to AAV5 are neutralizing
Most antibody responses to AAV5 are neutralizing AAV5 BAB Titer AAV5 nAb Titer LD1 10 5 10 5 LD2 HD1 10 4 10 4 MD1 HD2 MD2 HD3 10 3 10 3 MD3 Titer Titer HD4 10 2 10 2 MD4 MD5 10 1 10 1 10 0 10 0 g 2 4 8 3 6 12 g 2 4 6 8 3 on 6 12 in k k k th th n k k k k th th en ee ee ee h ni n n nt ee ee ee ee th
Slide 12: No subject developed post-treatment cell mediated responses to EDIT-101
No subject developed post-treatment cell mediated responses to EDIT-101 Cell CellMediated MediatedResponse ResponseDetection Detection AAV5 SaCas9 Cell mediated responses to Subject Latest Timepoint Pre-Existing/Post-Treatment Pre-Existing/Post-Treatment AAV5 capsid and SaCas9 LD1 Month 6 -/- -/- we
Slide 13: Conclusions
Conclusions Our data and patient profile indicate EDIT-101 has a favorable immunogenicity profile Some subjects across all cohorts exhibit pre-existing immunity to AAV5 and/or SaCas9 No subject developed post-treatment cellular or humoral immunogenicity to SaCas9 EDIT-101 treatment resulted in AAV5
Slide 14: Acknowledgements
Acknowledgements We would like to acknowledge and thank all patients in the BRILLIANCE clinical trial and their families! Additional thanks to clinical and translational operations, data management, our external PIs, the clinical sites, our partner CROs, and the Foundation Fighting Blindness 14
Slide 15: Questions?
Questions? 15