Corporate presentation

July 2019

Confidential

freeline.life

2

Freeline is a leading clinical stage gene therapy company focused on liver expression for chronic systemic diseases

Proprietary capsid with best-in-class liver transduction profile, allowing for high protein expression levels

Robust pipeline with goal of filing a new IND every year– Fabry Disease program to start dosing 2019– Gaucher and 4th program (undisclosed) to initiate IND enabling studies in 2019– Good progress on research programs for chronic inflammatory diseases

World leading founder and executive team with extensive track record in gene therapy, clinical translation, early and late stage development and global drug approvals

£120m+ raised to date in Series A and B predominantly from Syncona

Industry leading CMC platform at commercial quality and scale, supported by advanced analytics and in-house manufacturing capabilities

Haemophilia B program in phase 1/2 demonstrating activity levels allowing for normalisation of FIX activity levels

Confidential

freeline.life

Amit NathwaniFounder & ChiefScientific Officer

Brian Silver Chief Financial Officer & Corporate Development

Markus HörerFounder & Chief Technology Officer

Ged ShortSVP Clinical & Regulatory

Jan ThirkettleChief Development Officer

Natalia MisciattelliSVP Strategy

Duncan WhitakerVP Intellectual Property

Jane WhitrowVP Business Operations

Romuald CorbauSVP Research

Executive team includes experienced leaders in gene therapy, manufacturing and clinical development

Lyndsay TelakisDirector HR

3

Confidential

freeline.life

4

Successful expansion of global footprint and organisation

130 FTEs covering research, clinical development, process development, analytics and GMP manufacturing

CMC Development & Analytics LabsMunich, Germany

Germany

Corporate Offices, New York, USA

United States

United Kingdom

HQ & Research Labs Stevenage, UK

Manufacturing & QC Stevenage, UK

Animal LabsLondon, UK

Confidential

freeline.life

5

Our technology builds upon the pioneering liver expressing gene therapy in Haemophilia B

NEJM 2011 and 2014

Prof. Amit Nathwani

First to prove long-term sustainable expression of systemic AAV gene

therapy in humans

0.0 0.5 1.0

0

2

4

6

Years

% F

IX a

cti

vit

y

Low (N=2) Mid (N=2) High (N=6)

First generation FIX gene therapy(NEJM 2011 and 2014)

Confidential

freeline.life

6

Prof. Amit Nathwani

First to prove long-term sustainable expression of systemic AAV gene

therapy in humans

Our technology builds upon pioneering liver expressing gene therapy in Haemophilia B

Next Generation

Improve construct with the aim of achieving higher protein expression

Aim for functional cure/normalisation

Create foundation for broad pipeline

Limitations of First Generation constructs

Field set out to replicate the results of Prof. Nathwani with constructs very similar to his original construct:

▪ No change in protein level compared to original construct

▪ Not extendable to pipeline across indications due to low protein levels achieved

Confidential

ITR Promoter Gene Intron ITR

Capsid (S3) Cassette Gene

AAVS3 is a novel, human-selective liver tropic capsid with a high transduction efficiency of human hepatocytes

Best in class liver specific promoter Optimised intron

Codon-optimised geneUtilise gain-of-function mutations, when feasible

freeline.life

7

Our best in class capsid is the foundation of our pipeline

Expression = Cassette x Gene x Capsid

Confidential

freeline.life

8

FRG xenograft mouse model, chimeric human mouse liver model

Dose: 4e12 vg/kg

Source: Poster presented at ASH 2018 – “Preclinical Evaluation of an Engineered AAV Capsid in Non-Human Primates for the Treatment of Haemophilia B”4.3%

24.3%

0%

10%

20%

30%

40%

AAV8 AAVS3

% G

FP p

osi

tive

hu

man

cel

ls

P<0.05

AAVS3 high tropism for the human liver verified in animal studies

Confidential

freeline.life

9

The strength of our proprietary capsid allows continuous development of broad pipeline

Proprietarycapsid

Other diseases treatable by protein replacement

or enhancement

Haemophilia

Lysosomal storage disorders

Chronic inflammatory diseases

Liver directed protein replacement

for monogenic disorders

Confidential

Program Research IND enabling studies Phase 1/2 Next Milestone WW Rights

Haemophilia B FLT180a

Results from next dose cohort

H2 2019

Fabry Disease FLT190

First human dose2019

Gaucher DiseaseFLT200

Initiation of IND enabling studies

UndisclosedHaematology

Initiation of IND enabling studies

UndisclosedInflammation

Lead candidate selection

freeline.life

10

Proprietary and balanced pipeline with two programs in the clinic by 2019

Confidential

FLT180a - Haemophilia B

Confidential

freeline.life

12

Normal blood coagulation occurs in people with FIX activity between 50 and 150%

Normal coagulation >60% needed to ensure coverage during surgery or trauma

Normal50 – 150%

Mild haemophilia 5 – 40%

Prolonged bleeds >15% needed to prevent joint bleeds

Frequent spontaneous bleedsMod/SevHaemophilia <5%

FIX activity %

Uijl et al. 2011. Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity level. Haemophilia (2011), 17, 41–4

WFH Guidelines on the management of haemophilia table 7.1 and 7.2

Confidential

freeline.life

13

Normal blood coagulation occurs in people with FIX activity between 50 and 150%

Normal50 – 150%

Mild haemophilia 5 – 40%

Prolonged bleeds >15% needed to prevent joint bleeds

Frequent spontaneous bleedsMod/SevHaemophilia <5%

FIX activity %

Uijl et al. 2011. Analysis of low frequency bleeding data: the association of joint bleeds according to baseline FVIII activity level. Haemophilia (2011), 17, 41–4

WFH Guidelines on the management of haemophilia table 7.1 and 7.2

Freeline has the potential to deliver the first and only AAV gene therapy capable of normalising FIX levels

Confidential

freeline.life

14

Patients and physicians want normal factor activity levels

World Federation of Hemophilia (WFH). Guidelines on the management of haemophilia table 7.1 and 7.2

KoL advisory board WFH May 2018

Cowen and company 21st annual therapeutics conference topical wrap up.. Equity research 2018

Haemorrhage type

WFH Min. FIX level

Best practice

CNS 60 %100% FIX level by bolus injection followed by continuous infusion maintained at 100% for a week after surgery

Maintain the level over 80% for a further period until discharge.

Throat and neck 60 %

Gastrointestinal 60 %

Joint 40 %

Surgery 60 %

Cowen physician panel October 2018 reported 60% of specialists would like to see gene therapy leading to Factor IX levels within the normal range (50%-150%)

Confidential

freeline.life

15

B-AMAZE is an open label Phase 1/2 study of FLT180a in Haemophilia B

Sponsor: UCL

1 hour infusion

6 months follow up

Long term follow-up in separate protocol

Dose 6e11 equals 4.5e11 with Ph3 standard

Dose 2e12 equals 1.5e12 with Ph3 standard

Prophylactic steroids from week 6 (1st cohort) or week 4 (2nd cohort)

Objective: To assess the safety and efficacy of systemic administration of FLT180a in adult patients with severe haemophilia B

4.5e11 vg/kg (N=2)

Low dose

1.5e12 vg/kg

Mid dose

Adaptive trial design

3e12 vg/kg

Higher dose

7.5e11 vg/kg

Lower dose

Enrolment criteria

▪ Haemophilia B patients aged >=18 years with FIX activity levels <2%

▪ Lack of neutralising antibodies to AAVS3

▪ >50 exposure days to FIX and no history of inhibitors

▪ Normal liver function

▪ No evidence of active Hepatitis B, C, or HIV infection

Assessments

▪ Safety

▪ FIX activity level (one stage clotting assay)

▪ Exogenous FIX concentrate usage

▪ Bleeding frequency

Confidential

16

With FLT180a at a low dose of 4.5e11 stable expression levels of 42-49% were achieved from week 14

Dose 6e11 vg/kg equals 4.5e11 vg/kg with Ph3 standard

Prophylactic prednisolone week 6-12, 60 mg tapered

Source: ASH 2018 Oral Presentation by Prof. Nathwani: “A Single Intravenous Infusion of FLT180a Results in Factor IX Activity Levels of More Than 40% and Has the Potential to Provide a Functional Cure for Patients with Haemophilia B”

FIX activity level % ALT (IU/l)

Weeks post vector infusion

Pt 1: 42%

Pt 2: 49%

Pt 2

Pt 1

freeline.lifeConfidential

Confidential

freeline.life

17

No spontaneous bleeding episodes during 9 and 6 months, respectively, of observation

pre-GT post -GT0

50000

100000

150000

200000

250000F

IX C

on

c U

sa

ge

IU/ 9 m

on

ths

pre-GT post -GT0

2

4

6

Ble

ed

ra

tes

No

/9 m

on

ths

Prophylactic infusion Day 2

Cut finger, no FIX infusion

pre-GT post -GT0

50000

100000

150000

FIX

Co

nc

Us

ag

e

IU/6

mo

nth

s

Patient 1 Patient 2

FIX usage

Number of bleeds

pre-GT post -GT

0

1

2

3

Ble

ed r

ates

No

/6 m

on

ths

Dose 6e11 vg/kg equals 4.5e11 vg/kg with Ph3 standard

Prophylactic prednisolone from week 6-12, 60 mg tapered

Source: ASH 2018 Oral Presentation by Prof. Nathwani: “A Single Intravenous Infusion of FLT180a Results in Factor IX Activity Levels of More Than 40% and Has the Potential to Provide a Functional Cure for Patients with Haemophilia B”

Pre -GT Post -GT Confidential

Confidential

Clinical superiority

Rapid progression

Clear regulatory pathway

freeline.life

18

FLT180a has the potential to be the first Haemophilia B gene therapy to provide normalisation of FIX levels

B-AMAZE Phase 1/2 data points to first gene therapy providing normalisation in haemophilia B

Optimised development plan with ongoing natural history study

and use of surrogate endpoint allows for rapid progression to market

Potential qualification for accelerated regulatory review FDA Draft guidance for industry. Human Gene Therapy For Haemophilia –July 2018

Confidential

FLT190 – Fabry disease

Confidential

freeline.life

20

The manifestations of Fabry Disease are broad and debilitating with significant unmet needs

Disease characteristics

– X-linked – men and women

– Alpha-galactosidase A (GLA) deficiency

– Accumulation of globotriaosylceramide (Gb3) primarily in vascular wall

– Affects a range of organs

– Renal and cardiac failure most common cause of morbidity

– Stroke is a common feature

Confidential

freeline.life

21

ERTs may stop progression but do not heal organ damage

High use of pain medicines due to peaks and troughs in ERT

Ab development limiting treatment response

Treatment barrier high leading to advanced disease

ERTs do not prevent stroke

Role of high expressing gene therapyUnmet needs

Prevent disease progression Rapid Gb3 clearance -> improved renal function

Elimination of pain and GI symptoms

High expression level expected to lead to tolerization

Earlier and simple interventionbefore organ damage

Stroke risk likely to be reduced

Continuous high expression gene therapy holds potential for better treatment outcomes than ERTs

Confidential

freeline.life

22

FLT190 leads to reversal of kidney disease in GLA KO mice

Jeyakumar et al. Liver-directed gene therapy corrects Fabry disease in mice. Molecular Genetics and Metabolism 2019 Feb;126(2): Page S1, Poster #180

FLT190 vector genome pseudo-typed with AAV8 in GLA KO mice; Dose: 2e12 vg/kg. Error bars: Mean ± SD

Time point: 16 week disease development prior to treatment; analysis 14 weeks post-treatment. Gb3/Lyso-Gb3 data (n=4, 2 males and 2 females)

Kidney GLA activity

Fa

br

y U

T

Fa

br

y T

re

at e

d

W

i l d t y

pe

s

0

5 0 0 0

1 0 0 0 0

1 5 0 0 0

K i d n e y G b 3

Gb

3

(n

g/m

g t

ot

al p

ro

te

in

)

5000

10000

15000

wtTreatedUntreated

Kidney Gb3

Gb

3(n

g/m

g t

ota

l pro

tein

)

0

Fa

br

y U

T

Fa

br

y T

re

at e

d

W

i ld

ty

pe

s

0

5 0

1 0 0

1 5 0

2 0 0

K i d n e y L y s o - G b 3

Ly

so

-G

b3

(n

g/m

g t

ot

al p

ro

te

in

) Kidney Lyso-Gb3

Lyso

-Gb

3(n

g/m

g to

tal p

rote

in)

200

150

100

50

0

wtTreatedUntreated

EM x5000

Confidential

freeline.life

…as well as reversal of heart disease in GLA KO mice

Jeyakumar et al. Liver-directed gene therapy corrects Fabry disease in mice. Molecular Genetics and Metabolism 2019 Feb;126(2): Page S1, Poster #180

FLT190 vector genome pseudo-typed with AAV8 in GLA KO mice; Dose: 2e12 vg/kg. Error bars represent mean ± SD

Time point: 16 week disease development prior to treatment; analysis 14 weeks post-treatment. Gb3/Lyso-Gb3 data (n=4, 2 males and 2 females)

Fa

br

y U

T

Fa

br

y T

re

at e

d

W

i l d t y

pe

s

0

1 0 0 0

2 0 0 0

3 0 0 0

H e a r t G b 3

Gb

3

(n

g/m

g t

ot

al p

ro

te

in

)

Gb

3(n

g/m

g t

ota

l pro

tein

)

3000

2000

1000

0

Heart Gb3

Fabry U

T

Fabry T

reate

d

Wild

types

0

5

10

15

Heart Lyso-Gb3

Lyso

-Gb3

(ng/

mg

tota

l pro

tein

)Ly

so-G

b3

(ng/

mg

tota

l pro

tein

)

15

10

5

0

Heart Lyso-Gb3

23

wtTreatedUntreated

wtTreatedUntreated

Heart GLA activity levels

EM x5000

Confidential

Strong preclinical data

High performing manufacturing process

Phase 1/2 ready for FHD 2019

freeline.life

24

FLT190 ready for first human dose in H1 2019

In-vitro and in-vivo data support achievement of therapeutic levels in humans

CMC building on learnings from Haemophilia B programme

MARVEL1 Phase 1/2 ready for dosing 2019

Confidential

Platform technologies

Confidential

freeline.life

26

Freeline has addressed the multiple steps to building a gene therapy platform delivering high systemic expression

Cassetteoptimisation

Gain-of-function

Humanoptimised

capsid

Product potency and quality

ScalableCMC process

Confidential

freeline.life

27

Our differentiated AAV manufacturing platform provides flexibility in readiness for commercial demands

SPEED TO GMP

Class-leading pipeline progression from candidate selection to GMP

manufacture and commercialisation

MAXIMISED POTENCY

High product potency achieved through optimised cell line, plasmids and transfection system

AGILE SUPPLY

Single manufacturing platform meets demand from tox to commercial with

low cost of goods

HIGHEST QUALITY

Quality built-in to product using proprietary technology and supported by world class analytics

Confidential

freeline.life

28

Multiple value creating milestones with two programs in the clinic in 2019

2018PROGRAM 2019H1 H2

2020

Haemophilia BFLT180a

Fabry DiseaseFLT190

Gaucher FLT200

B-AMAZE results

B-AMAZE cohort 1 results at ASH 2018

EOP2 meetings

Ph 3 enrolment

Preclinical data WORLD 2019

FPFV MARVEL1

CTA approved for MARVEL1 (Ph 1/2)

MARVEL1 initial clinical results

Complete dose escalation PTPs

Lead candidate selection

FHD Ph 1/ 2IND enabling studies initiated

EOP2: End of Phase 2

FHD: First Human Dose

PTPs: Previously Treated Patients

Generation of multiple candidates

ASGCT: CMC platform presentations