Editas Medicine, Inc. · NASDAQ:EDIT
Editas Medicine — TIDES 2021
33 slides from Editas Medicine's conference presentation, Sep 23, 2021
Slide 1: IND-enabling Small-Scale Guide RNA Production Under GMP for CRISPR Based Cell Therapies
IND-enabling Small-Scale Guide RNA Production Under GMP for CRISPR Based Cell Therapies Sept 23rd 2021 Keith Jarvis Senior Director, Process Chemistry editasmedicine.com © 2021 Editas Medicine 1
Slide 2: Disclosure
Disclosure § I am an employee and shareholder of Editas Medicine © 2021 Editas Medicine 2
Slide 3: IND-enabling Small-Scale Guide RNA Production Under GMP for CRISPR Based Cell Therapies
IND-enabling Small-Scale Guide RNA Production Under GMP for CRISPR Based Cell Therapies This presentation will focus on the appropriate scale, final purity release specifications and GMP compliance for internal small-scale guide RNA production necessary to support our pre-clinical programs. It will
Slide 4: Overview
Overview Editas Medicine Research Pipeline Cas12a advantage and how it relates to guide RNA production Large scale manufacturing advantage of ~40/60mers vs 100mers Strategy to create internal guide RNA manufacturing at the appropriate scale for our programs Quality Systems to support GMP manufacturi
Slide 5: Editas Research and Pipeline
Editas Research and Pipeline In Vivo Gene Edited Medicines Ex Vivo Gene Edited Cell Medicines Cellular Therapy Medicines © 2021 Editas Medicine 5
Slide 6: In Vivo Research Pipeline
In Vivo Research Pipeline © 2021 Editas Medicine 6
Slide 7: Ex Vivo Research Pipeline
Ex Vivo Research Pipeline © 2021 Editas Medicine 7
Slide 8: Ex Vivo and Cell Therapy Medicines
Ex Vivo and Cell Therapy Medicines § Remove an individual’s cells, edit them, then reintroduce them to the patient. EX VIVO § Create a universal cell population that can be edited and then given to any patient who needs it, without CELL THERAPY needing the patient to donate cells first. © 2021 Edita
Slide 9: Overview: Cas12a advantage and guide RNA production
Overview Editas Medicine Research Pipeline Cas12a advantage and how it relates to guide RNA production Large scale manufacturing advantage of ~40/60mers vs 100mers Strategy to create internal guide RNA manufacturing at the appropriate scale for our programs Quality Systems to support GMP manufacturi
Slide 10: Cas12a/Cpf1 vs Cas9
Cas12a/Cpf1 vs Cas9 • Programmable protein that specifically • gRNA has differences in protospacer locates, binds to and edits the DNA of adjacent motifs targeted genes • Staggered DNA cuts increase efficiency • Pairs with a guide RNA molecule that and accuracy for gene repair recognizes and initiat
Slide 11: AsCas12a Higher Intrinsic Specificity and Sequence Fidelity in Shorter Guide RNA
The AsCas12a Nuclease has Higher Intrinsic Specificity and Higher Sequence Fidelity in the Shorter Chemically Synthesized Guide RNA Specificity: Guide RNA synthesis: Matched Target Site (20-Ns): Chemical synthesis of gRNAs occurs in the 3’ à 5’ direction and purity TTTVNNNNNNNNNNNNNNNNNNNNNGG and yi
Slide 12: Overview: Large scale manufacturing advantage of ~40/60mers
Overview Editas Medicine Research Pipeline Cas12a advantage and how it relates to guide RNA production Large scale manufacturing advantage of ~40/60mers vs 100mers Strategy to create internal guide RNA manufacturing at the appropriate scale for our programs Quality Systems to support GMP manufacturi
Slide 13: Ex Vivo Gene Edited Cell Medicine
Ex Vivo Gene Edited Cell Medicine + gRNA Nuclease (~40-60mer) (Cas12a) RNP RNP Active Pharmaceutical Ingredient Sterile Fill Engineered Patient Cell Patient Cell © 2021 Editas Medicine 13
Slide 14: Chemistry of guide RNA
Chemistry of guide RNA RNA targeting region DNA 2’Omethyl modifications PS/PO ~40 to 60mers © 2021 Editas Medicine 14
Slide 15: Effect of coupling efficiency on yield
Effect of coupling efficiency on yield yield ~ (% coupling efficiency)n where n = # of bases coupling length 90% 95% 99% 34 2.8% 17% 71% 66 0.1% 3.4% 51% 100 <0.01% 0.6% 36% shorter sequences: q superior fidelity q higher maximum yield © 2021 Editas Medicine 15
Slide 16: Typical Guide RNA Crude
Typical Guide RNA Crude • 631 µmol scale synthesis • Crude gross yield: 81700 ODU • Crude full-length purity by UPLC: 51% • Adjusted crude yield: 41667 ODU / 1287.02 mg • Full length mass confirmed © 2021 Editas Medicine 16
Slide 17: Typical Guide RNA Final
Typical Guide RNA Final OLI # Batch# Length (A260-blank) Pthlngth Dil'n Fctr Extinction Coefficient moles/liter uM uL pmol nmol mg 40735 D 41 0.649 1 200 420700 0.00030853 308.53 98000 30236272.88 30236.27 392.91 • 631 µmol scale synthesis • Final yield: ~393 mg • Final purity by UPLC: ~85% • Full l
Slide 18: Overview: Strategy for internal guide RNA manufacturing
Overview Editas Medicine Research Pipeline Cas12a advantage and how it relates to guide RNA production Large scale manufacturing advantage of ~40/60mers vs 100mers Strategy to create internal guide RNA manufacturing at the appropriate scale for our programs Quality Systems to support GMP manufacturi
Slide 19: New Boulder Facility
New Boulder Facility 7,669 sf Phase 1 Office Space Phase 2 PD/AD Lab Phase 3 GMP Manufacturing © 2021 Editas Medicine 19
Slide 20: New PD/AD Lab
New PD/AD Lab © 2021 Editas Medicine 20
Slide 21: Production Overview
Production Overview Supply Cleavage & Crude Planning Reagent Prep Synthesis Deprotection Workup* Suspension and Batch Sterile Purification* Ultrafiltration* Lyophilization Filtration* Pooling* Aseptic Fill Final Release and Finish Packaging Testing Shipment * denotes an in-process testing point © 20
Slide 22: gRNA GMP Manufacturing
gRNA GMP Manufacturing Aseptic Fill and Finish Synthesis Purification • Formulation • AktaTM OligopilotTM 100 • Gilson Reverse Phase • Sterile Filtration synthesizer Prep System • Lyophilization • Cleavage and • Ultrafiltration • Located in Clean Room Deprotection within enclosed hood space • Locate
Slide 23: First GMP batch initiation expected in Q1 2022
Boulder GMP Cleanroom In-Process QC analysis PD Lab Process Steps: Cleanroom Process Steps: will be completed at • Synthesis • Purification Editas. • Cleavage / • Final Ultrafiltration Deprotection • Lyophilization • Crude Ultrafiltration • Final Fill & Finishing Final release testing will be comple
Slide 24: Dual Duty: Lead Guide PD/AD and Synthesis Upstream Processing
Dual Duty: Lead Guide PD/AD and Synthesis Upstream Processing PROCESS DEVELOPMENT/ANALYTICAL SYNTHESIS UPSTREAM PROCESSING DEVELOPMENT – Guide process optimization once a lead is declared by research – Phosphoramidite and Reagent Prep – Phosphoramidite and Reagent Prep – Synthesis – Synthesis – Clea
Slide 25: Boulder GMP Cleanroom
Boulder GMP Cleanroom • CNC area (ISO 9) • First airlock (ISO 8) • Purification room (ISO 7) • Fill / Finish Room (ISO 7) • BSC (ISO 5) © 2021 Editas Medicine 25
Slide 26: Current gRNA Internal Analyses
Current gRNA Internal Analyses Category Attribute Method Current Acceptance Criteria LCMS Identity Molecular Weight Consistent w/ Theor. Mass ±0.2% (TM-0001) Assay % w/w (anhydrous) by A260 UV/Vis Strength Report Results UV Assay (TM-0002) IP-RP-UHPLC Final product: ≥ typically 80.0% Purity (TM-0001
Slide 27: GMP guide RNA Testing (at CRO)
GMP guide RNA Testing (at CRO) Category Attribute Method Current Acceptance Criteria Bioburden USP <61> ≤100 CFU/100 mg TAMC/ TYMC Safety Endotoxin USP <85> ≤ 0.25 EU/mg (to two decimal places) White to off-white solid, free of visible Appearance Agilent QC-GNM-6005 particulates General pH USP <791>
Slide 28: Overview: Quality Systems to support GMP manufacturing
Overview Editas Medicine Research Pipeline Cas12a advantage and how it relates to guide RNA production Large scale manufacturing advantage of ~40/60mers vs 100mers Strategy to create internal guide RNA manufacturing at the appropriate scale for our programs Quality Systems to support GMP manufacturi
Slide 29: GMP Systems Implementation for gRNA Production
GMP Systems Implementation for gRNA Production Materials Management System • Procure appropriate grade of materials for gRNA production • Create Internal Material Specifications • Procedures for receipt and disposition of incoming raw materials • Vendor Qualification for suppliers/manufacturers Prod
Slide 30: GMP Systems Implementation for gRNA Production
GMP Systems Implementation for gRNA Production Environmental Monitoring Program and Qualification • HVAC operation • Monitoring of particulates and air sampling • Aseptic conditions Equipment • Operation, Calibration and Maintenance procedures • IQ/OQs Data Integrity • Data backup Validation • CSV f
Slide 31: Overview: Internal GMP manufacturing will accelerate pre-clinical programs
Overview Editas Medicine Research Pipeline Cas12a advantage and how it relates to guide RNA production Large scale manufacturing advantage of ~40/60mers vs 100mers in terms of cost, purity and time Strategy to create internal guide RNA manufacturing at the appropriate scale for our programs Quality
Slide 32: Internal GMP Manufacturing Accelerates our Pre-Clinical Programs
Internal GMP Manufacturing Accelerates our Pre-Clinical Programs Appropriate scale customized to actual need 6 to 12 month lead time required to hold a manufacturing slot Ability to prioritize internal and collaborative programs based on evolving research timelines All IP retained internally (every
Slide 33: Process Chemistry Team Acknowledgement
Process Chemistry Team Acknowledgement Medicinal Chemistry • Vy Le (Scientist) • Austin McFarlin (Research Associate) Research Scale Guide RNA Production • McKenzie Weiss (Research Associate) • Mark Jones (Research Associate) • Shelby Beer (Research Associate) • Research Associate Process Developmen