Editas Medicine, Inc. · NASDAQ:EDIT
Editas Medicine — TIDES 2022
24 slides from Editas Medicine's conference presentation, May 2022
Slide 1: Ongoing Progress in the Phase 1/2 BRILLIANCE Clinical Trial for CEP-290 Retinal Degeneration
Ongoing Progress in the Phase 1/2 BRILLIANCE Clinical Trial for Treatment of CEP-290 Retinal Degeneration In vivo CRISPR gene editing therapies for ocular disease Mark S. Shearman Editas Medicine, Chief Scientific Officer
Slide 2: Disclosure
Disclosure The speaker is an employee and stockholder of Editas Medicine. 2
Slide 3: Presentation Outline
Presentation Outline • Editas Medicine proprietary gene editing technology • EDIT-101 for treating CEP290 mutation-associated LCA-10 • EDIT-103 for treating rhodopsin mutation-associated autosomal dominant Retinitis Pigmentosa • EDIT-102 for treating Usherin mutation-associated Usher Syndrome Type 2
Slide 4: Highly Differentiated Gene Editing and Delivery Technology
Highly Differentiated Gene Editing and Delivery Technology Advanced Bioinformatics Proprietary CRISPR Enzymes Multiple Delivery Solutions and Analytics and RNA Chemistry AAV, RNP, LNP Mastery in design based on Efficient high precision editing delivered in vivo, ex vivo, and proprietary sequencing t
Slide 5: Expansive Pipeline of Gene Editing Medicines for Ocular Diseases
Expansive Pipeline of Gene Editing Medicines for Ocular Diseases EDIT-101: EDIT-103: EDIT-102: Leber Congenital Amaurosis Rhodopsin-associated Usher Syndrome (USH2A) type 10 (LCA-10) autosomal dominant retinitis pigmentosa (RHO-adRP) Gene CEP-290 Rhodopsin Usherin c.2991+1655A>G mutation in Mutation
Slide 6: CEP290-Related Retinal Degeneration: A Rare Cause of Early Onset Loss of Vision
CEP290-Related Retinal Degeneration: A Rare Cause of Early Onset Loss of Vision No Currently Approved Treatments for CEP290-related retinal degeneration • CEP290-related retinal degeneration CEP290-Related Rod Photoreceptor Loss with Increasing Retinal Eccentricity causes progressive vision loss/ bl
Slide 7: CEP290-Related Degeneration: Symptom Burden and Patient Impact
CEP290-Related Degeneration: Symptom Burden and Patient Impact DISEASE SYMPTOMS PATIENT IMPACT PATIENT RETINA & VISION • Inability to adequately navigate NORMAL • Blindness usually diagnosed in infancy or early childhood enclosed spaces • Risk of falls and injury • Severely impaired visual acuity •
Slide 8: The IVS26 Mutation in CEP290 Is a Clearly Defined Target for Gene Editing
The IVS26 Mutation in CEP290 Is a Clearly Defined Target for Gene Editing No protein Protein trafficking trafficking 8
Slide 9: EDIT-101 Allows for Local Delivery of the Editing Complex
EDIT-101 Allows for Local Delivery of the Editing Complex to Specifically Target the Photoreceptors to Be Corrected EDIT-101 CRISPR-Cas9 gene editing EDIT-101 specifically targets the part of the retina containing viable photoreceptors • Photoreceptor-tropic AAV5 vector • Highly specific Guide RNAs
Slide 10: Natural History Study Assessments Informed the Design of the BRILLIANCE Trial
Natural History Study (NHS) Assessments Were Executed to Inform the Design of the Phase 1/2 BRILLIANCE Trial • This study aimed to describe the natural history of an otherwise ill-defined study population and to inform on potential endpoints, trial design, and registrational strategy Eligibility Cri
Slide 11: Natural History Study Identified Feasible, Reliable, and Stable Endpoints
Natural History Study Identified Feasible, Reliable, and Stable Endpoints for Clinical Studies Including VA and FST Scores Stable over Assessment Endpoints Category Feasible Reliable 1 year Optical coherence Thickness of the ONL and integrity of the ellipsoid zone Anatomical tomography (OCT) Pupillo
Slide 12: BRILLIANCE Phase I/II Dose Escalation Trial
BRILLIANCE Phase I/II Dose Escalation Trial Cohort Patients Dose Status/Safety Primary outcomes: Safety Dosing complete LOW Adverse events (AEs) / DLTs 1 (6.0 x 1011 vg/ml) No dose-limiting toxicity (DLTs) Adult, n = 2 No serious adverse events (SAEs) Secondary outcomes: efficacy Dosing complete MID
Slide 13: BRILLIANCE Primary Outcomes: No Reported SAEs or DLTs
BRILLIANCE Primary Outcomes: No Reported SAEs or DLTs Primary Outcomes: Safety and DLTs Cohort 1 Cohort 2 Adult Low dose Adult Mid Dose • No DLTs or SAEs observed to date in first two (n = 2) (n = 4) cohorts AEs 26 (22 Mild, 4 Moderate) 25 (23 Mild, 2 Moderate) • To date, no observed treatment-relat
Slide 14: BRILLIANCE Secondary Outcomes: Mid-dose Cohort Demonstrates Early Signs of Efficacy
BRILLIANCE Secondary Outcomes: Mid-dose Cohort Demonstrates Early Signs of Efficacy Baseline After Six Months BRVT What the patient can Berkeley now see Rudimentary Vision Test LogMar 2.7 (20 / 10,000) LogMar2.0 (20 / 2,000) PASS at 500 lux PASS at 63 lux Navigation How the Commercial Light Low Ligh
Slide 15: EDIT-101 Summary To Date
EDIT-101 Summary To Date EDIT-101 for treatment of CEP290-related retinal degeneration is the first clinically investigated in vivo CRISPR gene editing therapy, including first pediatric patient to be dosed To date, no dose-limiting toxicities or serious adverse events have been reported Early effic
Slide 16: Rhodopsin-Associated Autosomal Dominant Retinitis Pigmentosa (RHO-adRP)
Rhodopsin-Associated Autosomal Dominant Retinitis Pigmentosa (RHO-adRP) Rhodopsin (RHO) • Light-sensitive receptor protein, located in outer segments, involved in phototransduction in rod photoreceptors • Approximately 30% of adRP caused by RHO dominant mutations (US and UK) • >150 mutations identif
Slide 17: RHO-adRP: Symptom Burden and Patient Impact
RHO-adRP: Symptom Burden and Patient Impact DISEASE SYMPTOMS PATIENT IMPACT PATIENT VISION TUNNEL VISION IN RHO-adRP • Night blindness beginning in • 7,500 patients in US childhood and adolescence 12,100 patients in EU and UK2 • Blind spots in peripheral vision • Impaired academic performance • Prog
Slide 18: EDIT-103: Dual AAV-based Knockout and Replace Therapeutic Strategy
EDIT-103: Dual AAV-B ed “ n c ut nd e l ce” Therapeutic Strategy • Agnostic to any RHO mutation – thus will knockout any dominant gain-of-function rhodopsin mutant • Step 1: Both mutant and normal endogenous RHO will be knocked out in the treated area • Step 2: Exogenous normal RHO (resistant to edi
Slide 19: EDIT-103: Proof-of-Concept in Non-Human Primates
EDIT-103: Proof-of-Concept in Non-Human Primates EDIT-103 is a highly specific “knock out & replace” system for treating RHO-adRP with near 100% editing efficiency EDIT-103 shows near 100% editing and functional RHO replacement 95% *** 37% 25% 125125 *** 50 (compared to NHP RHO in Vehicle) * Product
Slide 20: RHO Protein Expression and Retinal Morphology Preserved in EDIT-103-Treated NHP Retinas
RHO Protein Expression and Retinal Morphology Preserved in EDIT-103-Treated Versus KO-Treated NHP Retinas Vehicle KO (3E12 vg/ml) EDIT-103 (3E12 vg/ml) IS/OS IS/OS RPE IS/OS ONL ONL ONL RHO protein / Cas9 genome IS/OS IS/OS IS/OS ONL ONL ONL H&E staining AAV ratio: 1:1; Injection volume: 100 μL; Tim
Slide 21: Retinal Function Preserved in EDIT-103 Treated Versus KO-Treated NHP Eyes
Retinal Function Preserved in EDIT-103 Treated Versus KO-Treated NHP Eyes Retinal layers RPE 150 ✱✱✱ a-wave 150 b-wave IS/OS ✱✱✱ ✱ (compared to vehicle) (compared to vehicle) % of b-wave a-wave % of a-wave ONL 100 100 OPL INL b-wave 50 50 IPL GCL 0 0 NFL Vehicle KO EDIT-103 EDIT-103 Vehicle KO EDIT-
Slide 22: Usher Syndrome (USH2A): Symptom Burden and Patient Impact
Usher Syndrome (USH2A): Symptom Burden and Patient Impact DISEASE SYMPTOMS PATIENT IMPACT PATIENT RETINA & VISION • Most common form of • Affects approximately 4 -17 syndromic retinitis per 100,000 persons pigmentosa • Accounts for 50% of all • Severe loss of vision, hereditary deaf-blindness progre
Slide 23: EDIT-102: Gene Editing for USH2A with Optimized AsCas12a Increases Productive Editing
EDIT-102: Gene Editing for USH2A with Optimized AsCas12a Increases Productive Editing • Development of an AsCas12a in vivo editing • Large patient population platform outperforms prior EDIT-102 construct • Ability to edit gene with either SaCas9 or AsCas12a • Improved gRNA and AsCas12a activity. nuc
Slide 24: Summary
Summary • Editas Medicine utilizes proprietary technology with an expansive pipeline of gene editing medicines in ophthalmology, hemoglobinopathies and oncology • EDIT-101 achieved in vivo proof-of-concept in 2021 for treating CEP290 retinal degeneration ‒ BRILLIANCE data provide clinical evidence o