Corporate presentation

February 2020Non-confidential

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A fully integrated next generation modular systemic AAV gene therapy company

• Rationally designed next generation capsid

• Cutting edge proprietary CMC platform (Quality, Scale, COGS)

• Clinical and Commercial GMP supply

Functional cures and broad pipeline enabled by high protein expression

High quality potent liver targeted platform

• Lead program in Hemophilia B completing pivotal dose selection

• Second program in Fabry Disease in the clinic

• Gaucher and Hemophilia A in IND-enabling studies

• Cutting edge research enabling reach outside monogenic diseases

Strong Executive team with depth and breath of expertise

• Spanning from Research to Clinical translation and approvals

• Deep CMC and Manufacturing experience

• Strong financial position with $200 mm raised to date and $65 mm on hand

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AAV8 / Mammal / FIX

Current systemic AAV platforms cannot access high protein levels

Estimated therapeutic levels

Inflammatory disorders and

beyond

LSDs – Fabry, Gaucher,

others

Consistent cures in

HaemophiliaPro

tein

pro

du

ced

(p

mo

l/m

l/h

r)

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40% activity assumes Padua

Estimates of therapeutic levels for different endogenous proteins are shown

40% FIX activity level

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AAV8 / Mammal / FIX

Estimated therapeutic levels

Inflammatory disorders and

beyond

LSDs – Fabry, Gaucher,

others

Consistent cures in

HaemophiliaPro

tein

pro

du

ced

(p

mo

l/m

l/h

r)

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Freeline’s proprietary AAVS3 capsid delivers next generation performance

4.3%

24.3%

0%

10%

20%

30%

AAV8 AAVS3

% G

FP p

osi

tive

hu

man

cel

lsAAVS3 high tropism for the human liver verified in

preclinical studies

40% activity assumes Padua

Estimates of therapeutic levels for different endogenous proteins are shown

Dane A et al; abstract 2197, ASH 2018

40% FIX activity level

Programme ResearchIND enabling

studiesPhase 1/2 Next Milestone

Patient No(US & EU5)

Worldwide rights

Haemophilia B FLT180a

Dose Selection 9,000

Fabry FLT190 and

FLT191

Results from dose escalation

9,000

GaucherFLT200 and

FLT201CTA/IND 6,000

Haemophilia A FLT210

CTA/IND 38,000

Undisclosed inflammatory

disordersCandidate Selection 50,000 – 200,000

Proprietary pipeline with two programs in the clinic and two more entering within 24 months

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Haemophilia: epidemiology source: World Federation of Hemophilia 2018.

Fabry Disease epidemiology sources: Metchler et al 2012; Spada et al 2016; Fabry Register; Fabry Outcome Survey; Waldek et al 2009; Deegan et al 2006.

Gaucher Disease epidemiology: Nalysnyk et al 2016; Weinreb et al 2008 & 2013; Charrow et al 2000; National Gaucher Foundation; Orphanet; NIH Technology Assessment Panel on Gaucher; Poorthuis1999; Stirnemann et al 2012; Puopetova2010; Mehta et al 2006.

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Management team of experienced leaders in gene therapy, CMC and rare disease development

Freeline Management Team

Chris HollowoodExecutive Chairman

Amit NathwaniFounder and Chief Scientific Adviser

Markus HörerFounder and Chief Technology Officer

Brian SilverChief Financial Officer & Corporate Development

Jan ThirkettleChief Development Officer

Natalia MisciattelliSVP Strategy

Duncan WhitakerVP Intellectual Property

Romuald CorbauSVP Research

Ged ShortSVP Clinical & Regulatory

Julia P Gregory Non-Executive Director Board of Directors

Chris Hollowood Executive Chairman

Amit Nathwani Founder & Chief Scientific Adviser

Martin Andrews Non-Executive Director

Jeffrey Chodakewitz Non-Executive Director

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Catapult Manufacturing

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Transatlantic organization with footprint in major biotech centres

United Kingdom

United States

Germany

~180 FTEs covering Research, Clinical Development, Process Development, Analytics and GMP Manufacturing

CMC Development & Analytics LabsMunich, Germany

Germany

Corporate OfficeNew York City, NY

ManufacturingBoston, MA

United States

United KingdomHeadquarters & Research Labs Stevenage Bioscience CatalystStevenage, UK

Catapult Manufacturing & QC LabsStevenage, UK

In Vivo LabsLondon Bioscience Innovation CentreLondon, UK

CMC Development & Analytics Labs

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Headquarters & Research Labs

Clinical programs

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Patients, physicians and payers all want the most effective gene therapy for Haemophilia B

• Confidence in a lifetime cure• No need for ERT top up in

any circumstances

Patient aspiration: Parity with general

population

HCP aspiration: Reduction in disease

burden

• Complete relief of clinical symptoms

Payer aspiration: Improved treatment

at lower cost

• Completely eliminate need for expensive and burdensome ERT

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Our Haemophilia B adaptive design has allowed us to find to the therapeutic window

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

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

Low

do

se

Mid

do

se

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h d

ose

Adaptive study design: Allowing titrating to target range between 50 – 150 % FIX

Low dose

4.5e11 vg/kg

Mid dose

1.5e12 vg/kg

High dose

3e12 vg/kg

Lower doses

Final Phase 1/2 dose expansion of patients

Initially 2 patients were evaluated in each of 2 cohorts

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7.5e11 vg/kg

Lower Mid

9.75e11 vg/kg

Not needed

Prophylactic immunosuppression with Corticosteroids + Tacrolimus Transaminitis Strategy

Haem B Low Dose cohort 1 (4.5e11) patients 1 and 2 have shown stable expression over time at 66 and 74 weeks

Patient 1 (low dose)

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0 56 112 168 224 280 336 392 448 504 560 616 672

ALT

Fact

or

IX

Days after Infusion

Pt 2 FIX (Central)

Pt 2 ALT

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ALT

Fact

or

IX

Days after Infusion

Pt 1 FIX (Central)

Pt 1 ALT

Patient 2 (low dose)

Patient 1 (low dose)

Steroid Prophylaxis

Steady state mean 40% +/-5.5 for cohort 1

Prophylactic prednisolone from week 6-12, 60 mg tapered

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Confidential

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EAHAD 2020 presentation shows progress towards dose expected to provide patients with full normalization of Factor IX

Immune management : 1. low dose 4.5e11 vg/kg : Prophylactic corticosteroids. 2. mid dose 1.5e12 vg/kg: Prophylactic corticosteroids & Tacrolimus for breakthrough transaminitis. 3. lower dose 7.5e11 vg/kg: Prophylactic corticosteroids & Tacrolimus for breakthrough transaminitis . 4. lower mid 9.75e11 vg/kg: Prophylactic corticosteroids and tacrolimus

Normal range

2540 37.5 43.5

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150

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Wk3 Wk26 Wk52 Wk78

Mean Factor IX Activity1 (%)Weeks – 3, 26, 52 and 78

Mean Factor IX Activity1 (%)Weeks – 3 and 26

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100

150

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Fact

or

IX A

ctiv

ity

(%)

Fact

or

IX A

ctiv

ity

(%)

Wk3 Wk26

1. Low dose- 4.5e11 vg/kg 2. Mid dose - 1.5e12 vg/kg

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Wk 3 Wk 26

Mean Factor IX Activity (%)at Weeks 3 and 26

109.0

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50

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200Mean Factor IX Activity1 (%)

at Week 3 only

Wk 3

3. Lower dose- 7.5e11 vg/kg 4. lower Mid- 9.75e11 vg/kg

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• Transaminitis was associated with decreased FIX expression in two patients

• Tacrolimus appears to be effective in controlling transaminitis and subsequent loss of FIX expression

• No evidence of neutralising anti-FIX antibodies

• No evidence of infusion reactions

• Evidence of FIX expression in all 8 patients

treated with FLT180a

• Stable FIX activity levels at ~ 40%

maintained for >18 months in the lowest

dose cohort

• Adaptive trial design used to identify dose

required for normal FIX activity levels with

minimal toxicity

• Current focus is to expand Dose level 4

(9.75e11 vg/kg) to establish safety and

efficacy based on early encouraging data

Safety Efficacy

Results of dose finding trial including immune prophylaxis allows continued enrolment for FLT180a

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Patients, physicians and payers all want the most effective gene therapy for Fabry Disease

Patient aspiration: Freedom from

disease progression

HCP aspiration: Reduction in disease

burden

• Effective treatment of clinical manifestations through high GLA levels

• Opportunity for earlier intervention

• Potential for tolerization

Payer aspiration: Improved treatment

at lower cost

• Completely eliminate need for expensive and burdensome ERT

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• Confidence in a lifetime cure

• No need for ERT top up

Fabry Phase 1/2 study MARVEL-1 design allows rapid escalation to the therapeutic dose

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Low dose

0.75e12 vg/kg

Mid dose

1.5e12 vg/kg

High dose

4.5e12 vg/kg

Assessments: Safety and GLA Level Response – 2 week

Initially 1-3 patients per cohortPatients previously treated with ERT

Low

do

se

Mid

do

se

Hig

h d

ose

3 previously ERT untreated patients (PUPs) evaluated

Objective: To assess the safety and efficacy of systemic administration of FLT190 in adult patients

Dose completion with 3 patient from chosen dose

Adaptive Study Design

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FLT190 leads to reversal of kidney and heart disease in GLA KO male mice

WORLD symposia 2019: Jey Jeyakumar et al. Liver-directed gene therapy corrects Fabry disease in mice

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 Heart GLA activity levels

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Clinical trial for FLT190 is underway and first patient at low dose showed positive signal

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Pla

sma

GLA

(n

mo

l/h

r/m

l)

Days post infusion

• First patient dosed at low dose of vector• Infusion well tolerated

• A sustained 3 to 4-fold increase in plasma αGLA activity achieved by week 4 that has persisted through Week 20

• Two SAEs: transaminitis, myocarditis.

• Further patients to be dosed as part of the dose escalation strategy

Early pipeline

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In vivo FLT200 results in uptake into tissues affected in GD patients

FLT200 has been pseudo-typed with AAV8

N a i v e R C - 0 4 - 2 6

1 06

1 07

1 08

1 09

GC

as

e a

ctiv

ity

(

RF

U)

P = 0 . 0 0 0 1

Serum

12 weeks post-infusion 2x1012vg/kg

FLT200

FLT2

00

Freeline has the only Haem A construct that fits in the 4.7KB capacity of an AAV capsid

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Company A Company B Company C Company D

CMC

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Freeline’s iCellis based manufacturing platform delivers highest quality and potency at competitive cost

Upstream in AAV is

paramount

Purity and Quality at

scale

• Downstream processing (DSP) cannot eliminate unwanted packaged DNA

• iCellis is a commercial platform that allows adherent systems at scale

• Adherent cells have higher cell specific productivity than suspension

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Maximised purity

Freeline’s know-how

adds to quality

• Proprietary split plasmid system drives quality and safety

Rep & helper genes

Cap & expression

cassette

DSP

DSP

Unwanted DNA

1 2

0100200300

Mammalianadherent

Mammaliansuspension

3x

E1A % impurity / vg

Capacity secured for pipeline from tox through commercialisation

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Clinical Supply

Commercial Supply

Analytics & Process

Development

GMP manufacture(iCELLis® 500)

Munich, Germany

Tech

no

logy tran

sfer

Stevenage, UK

Cambridge, MA, US

Seneffe, Belgium

Portsmouth, UK

Toxicology Engineering

Conclusion

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PROGRAM 2021

Haemophilia BFLT180a

Gaucher

FLT200/201

2020 2022

Haemophilia A

FLT210

Fabry Disease

FLT190/191

• B-AMAZE dose selection

• Type B meeting

• ECLIPSE enrolment

• GLP Tox• Process Development

• Dose escalation

• RMAT & PRIME

submissions

• ODD (US& EU)

• GLP Tox• Manufacturing • CTA Submission

• Phase 3 started

• Process validation

• Antibody removal study

• CTA / IND• Phase 1/2 start

• 1 year data

• Regulatory path to

market

• Dose selection

• Phase 1/2 start • Initial results• Dose selection

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EOP2: End of Phase 2

RMAT: Regenerative Medicine Advanced Therapy Designation

• Phase 3 complete

• Dose selection

• Phase 3 started

• Phase 3 started

Within 24 months Freeline will have 4 programs in the clinic

Addressable market

Lowest dose, lowest COGS, broadest market opportunities, largest market sizes

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Freeline’s platform creates value across all key strategic domains

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Efficacy Highest safe protein levels

Pipeline Rich set of potential targets to develop 5

Durability Best long term coverage

SafetyLowest dose for necessary expression

=> low level unwanted DNA

Addressable market

Lowest dose, lowest COGS, broadest market opportunities, largest market sizes

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Freeline’s platform creates value across all key strategic domains

freeline.life

Efficacy Highest safe proteins levels

Pipeline Rich set of potential targets to develop 5

Durability Best long term coverage

SafetyLowest dose for necessary expression

=> low level unwanted DNA

Thank you