Editas Medicine : March 2020 Corporate Presentation

Corporate Presentation

March 4, 2020

P I O N E E R I N G T H E P O S S I B L E

editasmedicine.com

© 2020 Editas Medicine

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Forward Looking Statements

This presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of The Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, contained in this presentation, including statements regarding the Company's strategy, future operations, future financial position, future revenue, projected costs, prospects, plans, and objectives of management, are forward-looking statements. The words ''anticipate,'' ''believe,'' ''continue,'' ''could,'' ''estimate,'' ''expect,'' ''intend,'' ''may,'' ''plan,'' ''potential,'' ''predict,'' ''project,'' ''target,'' ''should,'' ''would,'' and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this presentation include statements regarding the clinical trial timelines for EDIT-101(AGN-151587) and the Company's 2020 priorities, including filing an IND for EDIT-301 by the end of 2020. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward- looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of the Company's product candidates; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; availability of funding sufficient for the Company's foreseeable and unforeseeable operating expenses and capital expenditure requirements; and other factors discussed in the "Risk Factors" section of the Company's most recent Annual Report on Form 10-K, which is on file with the Securities and Exchange Commission, and in other filings that the Company may make with the Securities and Exchange Commission in the future. In addition, the forward-looking statements included in this presentation represent the Company's views as of the date of this presentation. The Company anticipates that subsequent events and developments will cause its views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date of this presentation.

© 2020 Editas Medicine

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Building a Genomic Medicine Leader

CRISPR Gene Editing to Develop Differentiated, Transformational Medicines for High Unmet Need

In Vivo CRISPR Medicines		Engineered Cell Medicines

Leverage AAV-mediated editing with SaCas9		Develop best-in-class medicines for
	hemoglobinopathies using Cas12a and solid
into additional therapeutic areas
	tumors using iPSC-derived cells

Maintain Best-in-class Platform & Intellectual Property, and Advance Organizational Excellence

CRISPR: clustered regularly interspaced short palindromic repeat; SaCas9: Staphylococcus aureus CRISPR-associated protein 9; Cas12a: CRISPR-associated protein 12a; iPSC: induced pluripotent stem cell

© 2020 Editas Medicine

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2019 Achievements

In Vivo CRISPR Medicines

Initiated first ever clinical trial of an in vivo CRISPR medicine with EDIT-101 for Leber congenital amaurosis 10 (LCA10)

Achieved in vivo preclinical proof-of-concept and declared EDIT- 102 development candidate for Usher syndrome 2A (USH2A)

Advanced autosomal dominant retinitis pigmentosa 4 (RP4) program

Expanded into neurological diseases in partnership with AskBio Dose first EDIT-101 patient

Engineered Cell Medicines

Initiated IND-enabling activities and presented preclinical data for EDIT-301, for sickle cell disease and β-thalassemia

C A N C E R F O C U S

Focused collaboration with Bristol-Myers Squibb on αβ T cell medicines

Advanced engineered iPSC-derived NK (iNK) cell medicine for solid tumors using technology from BlueRock Therapeutics

Generated edited NK cells from healthy donors and iPSCs with significantly increased anti-cancer activity

Maintain Best-in-class Platform & Intellectual Property, and Advance Organizational Excellence

Hired Chief Executive Officer,	Grew team to 196 Editors	Added $75M through business
Chief Medical Officer, Chief Financial Officer,		development activity
and Senior Vice President of Operations

NK: natural killer

© 2020 Editas Medicine

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Pipeline

PROGRAM (OR	DISCOVERY	LEAD	IND ENABLING	EARLY-STAGE	LATE-STAGE	PARTNER	STRUCTURE
DISEASE/CANDIDATE)		OPTIMIZATION		CLINICAL	CLINICAL
IN VIVO CRISPR MEDICINES
	OCULAR
	EDIT-101 (AGN-151587):							Partnered
	Leber Congenital Amaurosis 10
	EDIT-102: Usher Syndrome 2A							Collaboration
	Autosomal Dominant Retinitis							Collaboration
	Pigmentosa 4
	OTHER ORGANS
	Duchenne Muscular Dystrophy							Wholly-owned
	(Muscle)
	Neurological Diseases							Collaboration
ENGINEERED CELL MEDICINES
	HEMATOLOGY
	EDIT-301:							Wholly-owned
	Sickle Cell Disease
	β-Thalassemia							Wholly-owned
	CANCER
	Healthy Donor NK Cells							Collaboration
	iPSC NK Cells							Wholly-owned / Collaboration
	γδ T Cells							Wholly-owned
	αβ T Cells							Collaboration	5
								© 2020 Editas Medicine

2020 Priorities

In Vivo CRISPR Medicines

Dose first EDIT-101 patient in Q1

EDIT-101: complete adult low- and mid-dose cohorts by year-end

Achieve in vivo preclinical proof-of-concept for a neurological indication

Nominate development candidate for RP4

Engineered Cell Medicines

File EDIT-301 IND for sickle cell disease

C A N C E R F O C U S

Initiate IND-enabling studies for an engineered healthy donor NK (HDNK) cell medicine to treat solid tumors

Achieve in vivo preclinical proof-of-concept for an engineered iNK cell medicine to treat solid tumors

Advance αβ T cell medicines in collaboration with Bristol-Myers Squibb

Maintain Best-in-class Platform & Intellectual Property, and Advance Organizational Excellence

Build out clinical and medical affairs organization	Advance manufacturing and operations to support
	clinical activity

© 2020 Editas Medicine

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In Vivo CRISPR Medicines

editasmedicine.com

© 2020 Editas Medicine

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EDIT-101 to Treat Leber Congenital Amaurosis 10

EDIT-101

Remove genetic mutation to restore CEP290 protein and rebuild photoreceptors in patients with

Leber congenital amaurosis 10

DISEASEEPIDEMIOLOGYPROGRAM STATUS

Degeneration of	2-5K	First patient dosed
photoreceptors leading to	patients in US	in Q1 2020
blindness in childhood
and Europe	with potential for data this year

CEP290: centrosomal protein 290

© 2020 Editas Medicine

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EDIT-101 Aims to Rescue Vision in LCA10

LCA10 Photoreceptor

EDIT-101

Rescued Photoreceptor

Outer Segment

Outer Segment

Outer segment	Editing removes	Outer segment
degenerates due to	disease-causing	regenerates with
CEP290 deficiency	mutation	CEP290 protein

© 2020 Editas Medicine

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EDIT-101 Demonstrates Rapid Onset of Therapeutic Editing

CEP290 GENE EDITING
MOUSE FULL-THICKNESS RETINA
100%				1E+13 vg/mL	n = 10 mice
log-Editingscale				1E+12 vg/mL	n = 8 mice	EditingProductivein TransducedRegion
10
1	1	6	11	16	21	26
			Week post dosing

100%			EDIT-101
80			n = 13-75 mice
60
40
20			Therapeutic
0100			Threshold
1010	1011	1012

Vector Dose (vg/mL)

Rapid, therapeutically relevant editing at AAV dose that has been safely administered to humans

AAV: adeno-associated virus		10
Maeder et al. Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10. Nat Med. 2019 Jan 21; 25:229-233	© 2020 Editas Medicine

First In Vivo CRISPR Clinical Trial Initiated

LCA10 PHASE 1/2

CLINICAL TRIAL

Open-label, dose escalation study to evaluate safety, tolerability, and efficacy of EDIT-101(AGN-151587) in patients with CEP290 IVS26 mutation*

STATUS	Enrolling
	Approximately 18 patients, aged 3 years and above
PATIENTS
	Single dose of EDIT-101 administered via subretinal
INTERVENTION
	injection to eye with worse vision
	Patient's own baseline value for each efficacy measure
CONTROL
	• Primary: Safety including frequency and number of adverse
ENDPOINTS
	events related to drug, procedure, and dose limiting toxicities
	• Secondary: Efficacy including visual acuity, mobility course,
	macula thickness, pupillometry, and electroretinogram
	Core measurements every 3 months for 1st year
FOLLOW-UP

*Intervening sequence 26 in CEP290 gene containing the c.2991+1655A>G mutation

© 2020 Editas Medicine

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EDIT-102 to Treat Usher Syndrome 2A

EDIT-102

Rescue vision by restoring USH2A protein leveraging

same proprietary SaCas9 enzyme, vector, and promoter as EDIT-101

DISEASEEPIDEMIOLOGYPROGRAM STATUS

Progressive vision loss	4K	EDIT-102
leading to blindness due	patients with target	development candidate
to degeneration of
mutation	declared
photoreceptors
Additional
	10K
	potentially addressable

© 2020 Editas Medicine

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EDIT-102: Editing Restores Functional Usherin Protein

Deleting exon 13
USH2A Gene
	c.2299delG
Ex12	*Ex13	Ex14
Gene editing to
remove exon13
Ex12	Ex14

			increases USH2A mRNA					and restores
			lacking exon 13					functional protein
			human cell line at 4 days		human retinal organoids at 120-140 days
Productive Editing	∆13 USH2A mRNA
100%				100%							Healthy retina

				USH2A retina
		47%	61%
	0%		1%	Edited
0		USH2A retina
		0
	Unedited	USH2A	Unedited USH2A
		Edited	Edited	Usherin Protein Complex
		n = 2 technical replicates	Photoreceptor Protein

© 2020 Editas Medicine

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Autosomal Dominant Retinitis Pigmentosa 4 (RP4)

AUTOSOMAL DOMINANT RETINITIS PIGMENTOSA 4 (RP4)

Preventing blindness by replacing defective rhodopsin

using same proprietary SaCas9 enzyme and vector as EDIT-101

DISEASEEPIDEMIOLOGYPROGRAM STATUS

Progressive decline in	26K	Development
peripheral vision, and	patients with target	candidate
night vision, followed by
eventual blindness	mutation	by year-end
due to degeneration of
photoreceptors

© 2020 Editas Medicine

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In Vivo CRISPR Medicine Opportunities

		Central nervous system
	Peripheral nervous system	Cardiology
Ocular	Neuromuscular	Additional therapeutic areas

• LCA10
• USH2A
• RP4

Liver

• AAV delivery enabled by development of proprietary SaCas9
• Leverage ocular experience to expand into neurological diseases and other therapeutic areas

© 2020 Editas Medicine

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Engineered Cell Medicines

editasmedicine.com

© 2020 Editas Medicine

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EDIT-301: Potential Best-in-Class Hemoglobinopathy Medicine

EDIT-301

Editing hematopoietic stem cells to increase fetal hemoglobin

to durably alleviate morbidity and mortality

	DISEASE			EPIDEMIOLOGY		PROGRAM STATUS
cells causing anemia, pain crises,	42-47 years	File IND
Deformed and diminished blood
organ failure, and mortality	median life expectancy	by year-end
	Over
				100K
			hospitalizations annually
				in US alone

© 2020 Editas Medicine

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EDIT-301: Potential Best-in-Class Hemoglobinopathy Medicine

						EDIT-301 (HBG1/2 Editing)		BCL11Ae Editing	Lentiviral Gene Therapy
						+++ HbF		++ HbF	++ HbA-T87Q
EFFICACY			Reduces sickle globin		Reduces sickle globin	No impact on sickle globin
						Strongly supported by		Not supported by human
						human genetics		genetics
					No lineage skewing in mice		Lineage skewing in mice
SAFETY
						Targeted genetic change		Targeted genetic change	Random integration with
									some cells >20 VCN

© 2020 Editas Medicine

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Editing Profile Expected to Sustain Higher Fetal Hemoglobin

Identified key regulatory region in β-globin locus consistent with human genetics implying human safety

TSS:-130

Cas12a SpCas9

TSS:-92

CCAGCCTTGCCTTGACCAATAGCCTTGACAAGGCAAAC GGTCGGAACGGAACTGGTTATCGGAACTGTTCCGTTTG

Large deletions induce		Large NHEJ deletions, but
higher HbF in cultured cells		not MMEJ, are maintained in vivo
40%		100%
Gγ		Indels	59%	67%	NHEJ
				MMEJ
0			22%	13%
		0
≤3bp	>3bp		Pre-infusion	Bone marrow
				at 16 weeks
			n = 2 healthy human donors in NBSGW mice
NHEJ: non-homologous end joining; MMEJ: microhomology mediated end joining

	Cas12a induces more large
	NHEJ deletions than SpCas9
100%				11%
Indels	49%		24%
30%
		65%
0	22%
SpCas9	Cas12a (Cpf1)
	<=3bp	>3bp MMEJ	>3bp NHEJ
				© 2020 Editas Medicine	19

Editing HBG1/2 Maintains Erythroid Output In Vivo

HBG1/2 EDITING		BCL11Ae EDITING
EDITAS MEDICINE STRATEGY		COMPETING STRATEGY

SIMILAR LEVELS OF	SIMILAR LEVELS
ERYTHROID OUTPUT	OF CELL DEATH

REDUCED

ERYTHROID OUTPUT

INCREASED

CELL DEATH

120%			6%
Control (Erythroid)	100			Caspase+ Cells
80			4
60	100%	106%
40		2
20
	0	Unedited	HBG1/2		0
			Edited

2%

2%

Unedited HBG1/2 Edited

120%			***
(Erythroid)	100
80
60			100%
Control	40
20
									20%
	0
		Unedited BCL11Ae
											Edited

6%					***
Cells	4
Caspase+	2			5%
				2%
	0
		Unedited BCL11Ae
									Edited

n = 5 healthy human donors in NBSGW mice at 16 weeks

***p<0.001		20
Chang et al., Genome Editing of HBG1/2 Promoter Leads to Robust HbF Induction In Vivo While Editing of BCL11A Erythroid Enhancer Shows Erythroid Defect, 60th ASH Annual Meeting & Exposition	© 2020 Editas Medicine

Editing HBG1/2 Induces Robust Fetal Hemoglobin In Vivo

Robust HbF in human CD34+ cells in vivo

	100%
+ HbA)	80
60
/ (HbF
40
HbF
	52%
	20
	4%
	0
	Unedited	HBG1/2
		Edited

High pan-cellular human HbF in red blood cells

100%
Cells	80
Blood	60
Red	40	89%
HbF+
20
	4%
	0
	Unedited	HBG1/2
		Edited

n = 5 healthy human donors in NBSGW mice at 16 weeks

HbF: fetal hemoglobin; HbA: adult hemoglobin

© 2020 Editas Medicine

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Potential for Rapid Innovation in Cell Medicines for Cancer

		1	2	3
CELL SOURCE	Patient Donor	Healthy Donor	Universal (iPSC)
ABILITY TO MULTIPLEX	Lower	Medium	Higher
COST	Higher	Medium	Lower

© 2020 Editas Medicine

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Potential Cell Types for Allogeneic Cell Medicines

Pluripotent

Stem Cell

CD34+ Cells

		αβ T cells			γδ T cells		NK cells
Immune System
	ADAPTIVE						INNATE
Tumor Recognition	•	αβ T cell receptor		•	γδ T cell receptor	•	Innate receptors
	•	CAR		•	Innate receptors	•	Antibody-directed
					•	CAR	•	CAR
Graft-vs-Host Risk		Higher					Lower

CAR: chimeric antigen receptor

© 2020 Editas Medicine

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NK Therapeutic Strategy for Treating Solid Tumors

Multiple

innate receptors

NK CELL	Antibody-directed
	cellular cytotoxicity
	(ADCC)

		Multiple
		innate receptors
Multiple	NK CELL
innate receptors	CARs
NK CELL		ADCC
ADCC	CRISPR editing

CRISPR editing

Improved ADCC, persistence, and tumor micro-environment (TME) resistance

Improved ADCC, persistence, and additional TME resistance

Improved recognition of tumor cells lacking T cell antigens for PD-1 nonresponding tumors with innate receptors and CARs

© 2020 Editas Medicine

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Editing Increases Tumor Killing by Healthy Donor NK Cells

Pooled healthy	NK cells	Edited NK Cells
donor blood

Efficient editing of HDNK cells

100%
	80
Editing	60
40	85%	83%
	20
	0	Single KO	Double KO

improves tumor killing

100%
	80
Cytolysis	60
40	74%
	20
	20%
	0
	Unedited	Double KO

n = 3 healthy human donors; editing and tumor cell killing measured 4 days after electroporation

KO: knock-out

© 2020 Editas Medicine

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Advancing Universal Allogeneic Cell Medicines to Treat Cancer

Differentiated	iPSC	Edited clonal iPSC line			iNK cells
somatic cell
				Editing +
	Dedifferentiate					Differentiate
		clonal identification

0

Technology from

High editing efficiency

Developing a

Highly engineered line

Infinitely renewable

BlueRock Therapeutics

with engineered Cas12a

proprietary, scalable

Genome

Defined genome

differentiation method

Low COGs

characterization builds

Off-the-shelf

on in vivo editing

capabilities

© 2020 Editas Medicine

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Advancing Universal Allogeneic Cell Medicines to Treat Cancer

Differentiated	iPSC	Edited clonal iPSC line	iNK cells
somatic cell

Efficient knock out of multiple genes in iNKs	Editing iNKs increases tumor killing
100%						100%
Editing	80	100%	100%	75%	74%	70%	Cytolysis	80		74%
60	60
	40							40
	20							20	2%
	0							0
	KO 1	KO 2	KO 3	KO 4	KO 5		Unedited	Single KO
		DNA harvested from cells 4 days after electroporation

© 2020 Editas Medicine

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Strong Foundation for Long-Term Leadership

PARTNERS

OCULAR MEDICINES		ENGINEERED CELL MEDICINES FOR CANCER

PATENTS

BROAD & DEEP PORTFOLIO OF CRISPR IP

DEVELOPMENT & COMMERCIALIZATION

Option to license up to 5 ocular programs

$90 million upfront plus > $1 billion contingent milestones and tiered royalties; option for 50/50 profit split in US on 2 programs

αβ T cell medicines to treat cancer and autoimmune diseases

$100 million in upfront and amendment payments to date plus potential

for milestones & tiered royalties

Exclusive access to foundational Cas9 and Cas12a patent estates

NEUROLOGICAL MEDICINES ENGINEERED CELL MEDICINES FOR CANCER

				Sandhill
				Therapeutics
RESEARCH	Collaboration bringing	Collaboration to create novel,	Collaboration using BINATE
COLLABORATION	leading capsid development,	allogeneic pluripotent stem cell	technology to develop
		clinical stage AAV vector	(PSC) lines using BlueRock's	engineered HDNK cell
		delivery system, and	induced pluripotent stem cell	medicines
		manufacturing expertise	(iPSC) platform to develop
			engineered iNK cell medicines

Exclusive access to multiple species and engineered forms of Cas9 and Cas12a

Over 70 issued patents and over 600 patent applications pending

Issued patents covering EDIT-101

Allergan terms per March 2017 agreement; Juno terms per May 2015 agreement as restated and amended in May 2018 and November 2019

© 2020 Editas Medicine

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Building a Genomic Medicine Leader

CRISPR Gene Editing to Develop Differentiated, Transformational Medicines for High Unmet Need

In Vivo CRISPR Medicines		Engineered Cell Medicines

Leverage AAV-mediated editing with SaCas9		Develop best-in-class medicines for
	hemoglobinopathies with Cas12a and solid
into additional therapeutic areas
	tumors using iPSC-derived cells

Maintain Best-in-class Platform & Intellectual Property, and Advance Organizational Excellence

© 2020 Editas Medicine

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