Corporate Presentation

Fall 2020

Legal Disclaimer

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FIX

αGLA

Proprietary capsid with significantly higher transduction efficiency in the liver

High protein levels at low doses allows us to target diseases perceived as beyond the reach of AAV GT

Potential for a functional cure for Haem B* with FIX expression levels in the normal range

Fabry clinical program demonstrating initial evidence of sustained αGLA activity levels

Leadership Team with deep CMC, development & commercial expertise in GT and rare diseases

Proprietary analytics and CMC capabilities that can deliver high quality at commercial scale

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6 * Certain adult Haem B patients

Clinical-stage, fully integrated, next generation, systemic AAV gene therapy company dedicated to transforming the lives of patients suffering from systemic debilitating diseases

Proprietary potent AAVS3 capsid and platform transduces more liver cells driving high protein expression

Transduction efficiences of AAV capsids in vitro in human hepatocyte:

• UnT Control: 1%

• AAVrh10: 5%

4

0

10

20

30

AAV8 AAV5 AAVS3

Hu

man

hep

ato

cyte

tra

nsd

uct

ion

in v

itro

(% G

FP)

High protein expression

✓

✓

✓

4 to 12 times higher transduction obtained vs.

wildtype AAVs

(n=3)

Our rationally designed AAVS3capsid enables:

Potent liver transduction

Low dose levels and improved safety margin

Lead Haemophilia B program provides validation of approach at low dose levels

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FIX

act

ivit

y le

vel (

%)

50

100

150

AAV82T vg/kgFIX WT1

SPK-90010.5T vg/kgFIX Padua4

Mean: 22%

AMT0605T vg/kgFIX WT2

AMT06120T vg/kgFIX Padua3

Mean: 41%

Mean: 6%

FLT180a0.45T vg/kgFIX Padua

Steady state:38% *

FLT180a0.975T vg/kg

FIX Padua

Mean: 5%

200

Mean: 99% **

FLT180a1.5T vg/kgFIX Padua

Mean: 130%***

AAVS3 enables FIX activity levels in normal range

168%

92%

136%

73%

Normal Range

T= e12

* Stable FIX activity levels at 38% at 52 weeks, and following an additional 52 weeks, or two years after infusion, we have continued to observe a durable response of 38% mean FIX activity in this cohort

** Mean value calculated based on following FIX levels: patient 7 136% (d 21 +/-1), patient 8 82% (d 21 +/-1), patient 9 73% (d 21 +/-1), patient 10 105% (d 21 +/-1)

*** Mean value calculated based on following FIX levels: patient 3 92% (d 21 +/-1), patient 6 168% (d 21 +/-1)

1. Nathwani et al; N Engl J Med 2014; 371:1994-2004

2. Poster presented at The 13th Annual Congress of the European Association for Haemophilia and Allied Disorders, EAHAD 2020

3. Miesback et al; Blood 2018 131:1022-1031

4. George et al; N Engl J Med 2017; 377:2215-2227. and WFH 2018 presentation

= 2= 4= 2= 15= 3

Our platform has the potential to go beyond the reach of other AAV gene therapies

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Protein expression

Haemophilia A&B

LSDs

Inflammatory disorders and beyond

Unserved gene therapy need

Secreted proteins in the genome~1,700

~1,600 Secreted proteins within the packaging limit of AAV

Significantly expands potentially addressable patient population

Programme Research1IND enabling

studies2 Phase 1/2 Phase 3Patient No.US & EU53

Development & WW

Commercial rights4

Haemophilia B FLT180a(RMAT designation)

~ 9,000

Fabry FLT190(Orphan designations)

~ 9,000

GaucherFLT201

~ 6,000

Haemophilia A FLT210

~ 38,000

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Robust pipeline with retained global rights

40,000

1. In the research stage, we conduct in vitroand in vivo preclinical studies to evaluate different product candidates to select thosewith the best tolerability and potency profiles

2. In the IND enabling studies stage, we conduct preclinical in vivo studies in disease-specific mouse models and good laboratory practice, or GLP, toxicity studies in non-human primates and generate the CMC information and analytical data required for an investigational new drug, or IND, submission to the FDA for a clinical trial authorization, or CTA, submission to the EMA

3 These figures represent the total approximate diagnosed population for each indication. The seroprevalence of antibodies against the AAV capsid renders approximately 30-50% of patients ineligible for gene therapy

4. Owned and in-licensed intellectual property rights

Haemophilia epidemiology : World Federation of Hemophilia 2018.

Fabry Disease epidemiology: 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; Poorthuis 1999; Stirnemann et al 2012; Puopetova 2010; Mehta et al 2006.

Haemophilia B & AThe Freeline mission: To be life changers

Adaptive B-AMAZE trial in Haemophilia B designed to establish a dose that demonstrates normal range of FIX activity

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Adaptive dose escalation design:Aim is to establish effective dose (50 – 150% FIX)

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

Haemophilia B

4.5e11 vg/kg

1.5e12 vg/kg

7.5e11 vg/kg

9.75e11 vg/kg

Results to date have informed our optimised immune management strategy with the potential to prevent loss of

factor IX expression during the critical period of 4 to 16 weeks

= Bookends of normal range

*Immune management includes initiation of Prednisolone and Tacrolimus at week 3 with rapid taper of steroids until discontinuation at month 3; continue tacrolimus until discontinuation up to month 5. Immune management treatment includes patient monitoring for 9 months, followed by annual monitoring of FIX activity levels.

Assessments: Safety; FIX activity level (one stage clotting assay); Exogenous FIX concentrate usage; Bleeding frequency

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

Oral treatment with Prednisolone and Tacrolimus at day 21 (post dosing) and continuing through month 3 for Prednisolone and up to month 5 for Tacrolimus*

Established dose response with multiple cohorts achieving normalisation of FIX activity

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250

FIX

act

ivit

y le

vel (

%)

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20

30

40

50

60

70

80

90

100

110

120

130

140

150

FLT180a7.5e11 vg/kg

FIX Padua

Week 52: 60%*

FLT180a9.75e11 vg/kg

FIX Padua

200

Normal Range

Mean week 3: 99%**

FLT180a1.5e12 vg/kg

FIX Padua

Mean week 3: 130%***

AAVS3 enables FIX activity levels in normal range

168%

92%

160

136%

73%

* Based on 1 data point, patient 5 at week 52. Patient 4 on 7.5e11 had ALTs

** Mean value calculated based on following FIX levels: patient 7 136% (d 21 +/-1), patient 8 82% (d 21 +/-1), patient 9 73% (d 21 +/-1), patient 10 105% (d 21 +/-1)

*** Mean value calculated based on following FIX levels: patient 3 92% (d 21 +/-1), patient 6 168% (d 21 +/-1)

= 2= 4= 1

Durable FIX activity achieved beyond 2 years

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20

30

40

50

60

70

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90

100

0 56 112 168 224 280 336 392 448 504 560 616 672 728 784

FIX

act

ivit

y le

vel (

%)

Years

Pt 1 FIX (Local)

Pt 2 FIX (Local)

Steady state indicator

Data as of 15th June 2020

Normal rangeImmune management Durability

4.5e11 vg/kg - with short duration prophylactic steroid

NormalRange

✓

Patient 1

Patient 2

1 2

Durable FIX activity levels in the normal range

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Immune management includes initiation of Prednisolone and Tacrolimus at week 3 with rapid taper of steroids until discontinuation at month 3; continue tacrolimus until discontinuation up to month 5. Immune management treatment includes patient monitoring for 9 months, followed by annual monitoring of FIX activity levels.

Data as of 15th June 2020

9.75e11 vg/kg cohort - patient 7: Immune management had not been optimised and therefore patient was not on prophylactic optimised steroid and tacrolimus programme.

9.75e11 vg/kg - with prophylactic steroid and tacrolimus

Immune management Durability ✓✓✓

No bleeds requiring supplemental FIX to date ✓

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50

100

150

200

250

300

350

0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250

Days after Infusion

Pt 8 FIX (Local)

Pt 9 FIX (Local)

Pt 10 FIX (Local)

FIX

act

ivit

y le

vel (

%)

Patient 8

Patient 9

Patient 10

NormalRange

Normal range

FLT180a has demonstrated a favourable safety profile

Most common SAE was transaminitis. SAEs recorded (excluding transaminitis): Patient six: Pulmonary Sepsis & AV fistula thrombosis; Patient four: appendicitis; Patient nine: Blood creatinine increased; Patient ten: abdominal pain upper

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Most common drug related SAE was transient transaminitis. Manifests as a decrease in expression and is not a safety signal

No evidence of neutralising antibody formation against FIX

No infusion reactions observed to date

✓

✓

✓

Safety

H1 2021H2 2020 H1 2022 H1 2023

Planning to file BLA in 2023

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PHASE 1/2

Fully enrolled

Enrolling

EOP2 meeting

Patients 1 to 10FIX activity at 6 months

H2 2023

Long term safety study

File BLA Accelerated

ApprovalEDS

DSDS

EDS = Safety = Durability = Efficacy

Run in study 6 months baseline

PHASE 2b/3

Haemophilia AThe Freeline mission: To be life changers

Platform able to package shortened FVIII gene within the wild type AAV capacity

Note: Haem A candidate nomination reached. Toxicology, CMC and disease animal model confirmation work ongoing

Sources of construct sizes:

1. As presented at ASGCT (2016) and WFH (2020)

2. As documented in patent (int. patent number: WO 2016/025764 A2)

3. McIntosh J, Lenting PJ, Rosales C, et al. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant. Blood. 2013;121(17):3335-3344.

4. Bunting S, Zhang L, Xie L, et al. Gene Therapy with BMN 270 Results in Therapeutic Levels of FVIII in Mice and Primates and Normalization of Bleeding in Hemophilic Mice. Mol Ther. 2018;26(2):496-509.

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4.5

4.6

4.7

4.8

4.9

5

5.1

5.2

SB-525 SPK-8011/SPK-8016

BMN270 FLT210

kb

Vector size comparison

Standard 4.7 kbp

AAVcapacity

Delivery of more functional intact transgenes and

predictable, less variable expression

Key attributes of FLT210:

Smallest known liver specific promoter

Shortened FVIII gene to reduce expression cassette size

Allows expression cassette to fit within the natural capacity of AAV capsid

✓

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Fabry & Gaucher disease

The Freeline mission: To be life changers

Fabry mouse model demonstrates increased GLA expression and reduction in pathologic substrate

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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 levels Heart GLA activity levels

Electron microscopy x5000

0

100

200

300

wt Untreated Treated

GLA

in

Kid

ney

(nm

ol/

hr/

mg)

0

100

200

300

400

wt Untreated Treated

GLA

in

Hea

rt(n

mo

l/h

r/m

g)Electron microscopy x5000

Adaptive Phase I/II dose finding study in previously treated and naive patients with Fabry disease

190.75e12 vg/kg

1.5e12 vg/kg

4.5e12 vg/kg

Dose finding plan:For patients with prior ERT therapy

1.5e13 vg/kg

FLT190 demonstrated durable increases in plasma GLA in Patient 1 at lowest dose

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0.0

0.4

0.8

1.2

1.6

0 7 14 21 28 35 42 49 56 63 70 77 84

Pla

sma

GLA

nm

ol/

hr/

ml

Days post infusion

Data as of 15th June 2020

* Normal range for GLA in plasma is 5-9 nmol/ hr/ ml

Below 1 nmol/hr/ml is diagnostic for Fabry disease

Baseline - Patient 1

Steady state – Patient 1

5.0

9.0

Patient 1 results

Normal Range*

Increase patient 1

GaucherThe Freeline mission: To be life changers

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1

2

3

4

Naïve FLT200 FLT201

Pla

sma

GC

ase

leve

l (m

U/m

l)

Plasma

Low doses of longer acting FLT201 result in high uptake in tissues commonly affected by Gaucher Disease

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FLT200 and FLT201 have been pseudo-typed with AAV8 for evaluation in mouse

• Better substrate clearance vs. standard of care (velaglucerase alfa) in Gaucher mice

• Novel GCase variant, FLT201 has a greater than 20-fold longer half-life than wild-type protein

Conclusion

LungBone marrowSpleen

Anti-GCase – DAB, Haematoxylin counterstain, AAV8

Time post infusion (min)

GC

ase

leve

l (n

mo

l/h

/ml)

0 2040 60 2000 4000 6000 8000 100000

5

10

15

20

VPRIV (60 U/kg)

FLT200 (2x1012 vg/kg)

P< 0.0001

CMC, Manufacturing & Supply

The Freeline mission: To be life changers

Platform built on deep AAV expertise enables supply of pipeline of products with the goal of maximising safety and efficacy

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What we have

✓ Product safety built into manufacturing design from the start

✓ High product potency enabling lower dose

✓ Increased predictability and longevity

✓ Enhanced production yield and low cost of goods

✓ Agile supply allowing fast response to changing business needs

Proprietary analytics and characterisation

algorithms

Why it’s important

Proprietary mammalian production system

Proprietary promoters and construct designs

Capacity secured for product candidates

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Multiple supply chains running same commercial-scale production platform

Long term clinical/ commercial facility planned

Clinical SupplyCommercial

SupplyToxicology

Haemophilia B

Fabry

Pipeline

Commenced

GMP manufacture(iCELLis® 500)

Cambridge, MA, USHaem B

Fabry

Stevenage, UK

Gaucher, Haem A, future pipeline

Seneffe, BE

MilestonesThe Freeline mission: To be life changers

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Haem B - Completed enrollment anddosing for Phase 1/2 study✓

Haem B - Initiated baseline screening study✓

Fabry - Complete dose escalation inPart 1 of Phase 1/2 study

Platform - Secured Brammer capacity for potential Haem B product candidate commercialisation

✓

Haem B - Initiate pivotal study

Haem B - Present durability data up to 3 years

Fabry - Resume dosing Gaucher - Initiate Phase 1/2 study

Platform - Further develop plans for Freeline manufacturing facility

Haem A - Complete preclinical proof of concept study

Haem B - Present longer durability data from Phase 1/2 study

Fabry - Submit IND

Multiple near-term value-creating milestones expected

20212020

✓

ConclusionThe Freeline mission: To be life changers

Clinical-stage, fully integrated, next generation, systemic AAV gene therapy company dedicated to transforming the lives of patients suffering from systemic debilitating diseases

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Potent capsid & high protein levels

Durable efficacy in the normal range

Broad proprietary pipeline

Committed to functional cures

Quality driven by CMC & Analytics

Leadership with deep expertise

Thank you