1CONFIDENTIAL

Designing Optimized Biologics Through Our Expanded Genetic Alphabet Platform

Jefferies 2019 Global Healthcare ConferenceJune 5th, 2019

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Forward-Looking Statements

Statements contained in this presentation regarding matters that are not historical facts are "forward-looking statements" within the meaning of the Private SecuritiesLitigation Reform Act of 1995, including statements associated with the expected ability of Synthorx, Inc. (the “Company”) to undertake certain activities and accomplishcertain goals and objectives. These statements include but are not limited to statements regarding the Company’s business strategy, the Company’s plans to develop andcommercialize its product candidates, the safety and efficacy of the Company’s product candidates, the Company’s plans and expected timing with respect to regulatoryfilings and approvals, and the size and growth potential of the markets for the Company’s product candidates. Because such statements are subject to risks anduncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as "believes," "anticipates," "plans,""expects," "intends," "will," "goal," "potential" and similar expressions are intended to identify forward-looking statements. These forward-looking statements are basedupon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of eventscould differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risksassociated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor ofbuilding a business around such drugs. These and other risks concerning the Company’s development programs and financial position are described in additional detailin the Company’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this presentation speak only as of the date on whichthey were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which theywere made.

The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsementof such products. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food andDrug Administration. No representation is made as to the safety or effectiveness of these product candidates for the therapeutic use for which such product candidatesare being studied.

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Investment Highlights

Leveraging our first-of-its-kind Expanded Genetic Alphabet platform to meet today’s challenges for people suffering from cancer and auto-immune disorders

➢ Initial focus on creating optimized cytokines that target validated mechanisms of action in immuno-oncology and autoimmune disorders where existing therapies have significant drawbacks

➢ Lead product candidate, THOR-707, is a “not-a” IL-2 in development for solid tumors

➢ Second product candidate is an IL-2 variant designed to preferentially expand regulatory T cells (“Tregs”), without expanding conventional T cells (“Tcons”) consisting of CD4+ Th and CD8+ Teff cells

➢ Advancing preclinical cytokine pipeline for cancer and autoimmune disorders

➢ Company well-positioned for success with experienced management team and robust financial position

Our goal is to bring multiple SynthorinsTM to market to positively impact millions of patients worldwide

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Recent Developments at Synthorx

THOR-707 for Solid Tumors

• Oral presentation at the Chinese Society for Clinical Oncology (CSCO) Conference on Immunotherapy demonstrating that

THOR-707 induces strong immunological responses in preclinical models

• AACR 19 poster presentation showing that THOR-707 elicits durable pharmacodynamic responses and efficacy alone and

in combination with an anti-PD-1 therapy in multiple mouse models

• ASCO 19 poster presentation demonstrating expansion of CD8+ T cells without eosinophilia (a measurement of VLS),

regardless of whether THOR-707 is administered every 2, 3 or 4 weeks, and the establishment of persistent, anti-tumor

memory T cell populations in preclinical models

IL-2 for Autoimmune Disorders

• IL-2 AI Synthorin demonstrated to expand Tregs without expanding Tcons in non-human primates “NHP” as well as mice

• Preclinical data to be presented at the 14th World Congress on Inflammation in September 2019

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Expanded Genetic Alphabet Platform

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Our First-of-its-Kind Proprietary Synthetic Biology Platform Utilizes a New DNA Base Pair

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Engineered Cells Install a Novel Amino Acid Utilizing X-Y to Produce at Scale Therapeutic Proteins with Optimized Properties

• Novel amino acid installation provides versatility and diversity to optimize assembled protein (e.g. a dedicated chemical hook at a specific site for bioconjugation)

• Covalent attachment (e.g. polyethylene glycol or PEG) improves drug properties (increased half-life)

• Specific positioning of PEG optimizes receptor selectivity and binding to increase therapeutic activity

• Shields potentially immunogenic epitopes from immunosurveillance

Select Optimized Attributes of a SynthorinProduction System for Synthorins in E. coli

X and YTPs enter via transporter

mRNA with X-Y codon matches with tRNA displaying anticodon

Novel Amino Acid diffuses into cells; used by aminoacyl tRNA synthetase to charge X-Y tRNAs

Translation machinery decodes X-Y codons to introduce nAAinto Synthorin proteins

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1st Gen 2nd Gen 3rd Gen

Synthorx is Catalyzing a New Generation of Pegylation Technology

• Random PEG conjugation limited to n-terminus, and lysine and cysteine residues

• Multiple isoforms within product, with varying physicochemical and pharmaceutical properties

• Diversification of PEG derivatives –higher molecular weight polymers, branched structures, reversible bioconjugation chemistry

• PEGylation still limited to N-terminus, and lysine and cysteine residues

• New amino acid placed anywhere in the protein acts as dedicated chemical hook for bioconjugation

• Pegylation occurs only at the new amino acid via click chemistry

• Enables finetuning of cytokine drug half-life and receptor interactions (not-alpha THOR-707)

NKTR-214

Pegilodecakin

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Program Indication(s) DiscoveryLead

OptimizationIND

EnablingPhase 1 Phase 2 Phase 3

THOR-707Not Alpha IL-2

“All-Comers” Solid Tumors

Documented PD-1 Inhibitor Sensitive Solid Tumors

IL-2 Autoimmune Synthorin

AutoimmuneDisorders

IL-10 Synthorin

Immuno-Oncology

IL-15 Synthorin

Immuno-Oncology

Synthorin Cytokines are the Initial Focus of the Company because they are Emerging as Key Therapeutic Agents in Oncology and Autoimmune Disorders

Anticipated Milestones

IND filing 2Q19; Phase 1/2 single agent biomarker POC data in 4Q19

Initiate Phase 1/2 combo trial in 4Q19; Biomarker POC data in 1Q20

Select IND candidate 2019; IND Filing 2020

Select IND candidate 2019

Select IND candidate 2019

Single Agent

Combination with Immune Checkpoint Inhibitor(s)

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THOR-707 A “Not Alpha” IL-2 in Development for Solid Tumors

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IL-2 has a Low Therapeutic Index Due to its Dual Pharmacological Impact on the High Affinity (αβγ) and Intermediate Affinity (βγ) Receptor Complexes

Blood 2014 124:3572-3576

HIGH DOSEAnti-Tumor Activity

Treg

Eosinophil

IL-2

LOW DOSENo Anti-Tumor Activity

Suppressionof tumor immune

response

Toxicityα-receptor mediated innate lymphoid

cell release of IL-5 induces eosinophilia and degranulation that leads to VLS

αβγReceptor

αβγReceptor

Suppressionof tumor immune

response

Treg(CD4+)

αβγReceptor

βγReceptor

Stimulationof tumor immune

response

Teff (CD8+)NK

Vascular Leak Syndrome (VLS)

HypotensionHypoperfusion

Peripheral EdemaRhabdomyolysis

Pulmonary EdemaImpaired Oxygenation

Innate Lymphoid

Cells

Degranulation

Cancer Cell Deathvia anti-tumor immune

response

Tumor

IL-5

Treg(CD4+)

αβγReceptor

Plasma

Hepatorenal Syndrome

Treg Expansion Tmem, NKB Expansion Teff, NKD Expansion

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Single, stable PEG covalently attached to the novel amino acid installed in the “right” place results in a “not alpha” IL-2 protein

• Improved SelectivityReduced CD4+ Treg bias with retained stimulatory activity of CD8+ Teff and NK cells in preclinical studies

• Increased Therapeutic Index for VLSAt least 10 in preclinical NHP studies

• Ease of Use Expected Q2-Q4W dosing

• Reduced Immunogenicity RiskCovalent attachment of stable, “shielding” PEG; amino acid region not rich in MHC-II anchors

THOR-707 is an IL-2 Synthorin Optimized for Use in Immuno-oncology

PEG-IL-2 Synthorin Properties THOR-707’s Key Differentiations

IL-2 binds to the IL-2 receptor αβγ complex

at high affinity because of the α chain

Targeted pegylation of THOR-707 at the novel

amino acid blocks αchain binding

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Single Dose of THOR-707 Increases Lymphocyte Expansion in NHP without Increasing Eosinophils

Compared to aldesleukin, THOR-707 shows a strong preference for expanding tumor-fighting lymphocytes vs. eosinophils responsible for VLS

Aldesleukin Induced both Lymphocyte and Eosinophil Expansion1

1. Meyers FJ, et al. Clin Pharmacol Ther. 1991;49:307.

No signs of VLS in NHP with THOR-707 up to 1,000 mcg/kg (highest dose level tested)

THOR-707 Single Dose Leukocyte Subpopulations High Lymphocytes, No Eosinophils

0

Days-1 2 4 6 8 10 12 14 16 18 20

White blood cellsLymphocytesEosinophils

10

20

30

40

Ce

ll C

ou

nts

x 1

03/µ

L

Dose

0

10

20

30

40

Pre Treatment Post Treatment

Ce

ll C

ou

nts

x 1

03/µ

L

Lymphocytes

Eosinophils

Aldesleukin dosing limited in people (37 mcg/kg) and NHP by VLS (25 mcg/kg and higher)

300 mcg/kg of THOR-707

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-1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

0

20

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Days

Ki6

7+

% in

CD

8+T

cel

ls

dose

Vehicle

30 mcg/kg

300 mcg/kg

100 mcg/kg

dose dose

1,000 mcg/kg

Ki-

67

+%

in C

D8

+ T

cells

100

80

60

0

Days-1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Dose Dose Dose

Vehicle

30 mcg/kg

100 mcg/kg

300 mcg/kg

1,000 mcg/kg

40

20

THOR-707 Induces CD8+ Teff Cell Ki67 Levels at or Above the 60% Level Required to Support Cell Proliferation

Peripheral CD8+ Teff CellProliferation in NHP

Peripheral CD8+ TeffCells Ki67 Expression in NHP

-1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

0

20

40

60

Days

CD

8+%

in s

ing

lets

Vehicle

30 mcg/kg

300 mcg/kg

100 mcg/kg

dose dose dose

1,000 mcg/kg

CD

8+

% in

sin

glet

s

6

4

2

0

Days-1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Dose Dose Dose

Vehicle

30 mcg/kg

100 mcg/kg

300 mcg/kg

1,000 mcg/kg

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Updated and New Preclinical Findings Presented at ASCO

• THOR-707, as a single agent, elicits CD8 T cell tumor infiltration, activation of effector and memory T cells, and improved survival. In combination with anti-PD-1, THOR-707 leads to durable anti-tumor responses and rejection upon re-challenge

• THOR-707 does not significantly expand Tregs

• THOR-707 + anti-PD1 increases T Cell Receptor-mediated IFNg release which suggests that the combination strongly activates effector T cells. IFNg is a key inducer of tumor antigen presentation

• On the other hand, Pembrolizumab did not increase the relatively low level of IFNg release observed with THOR-707 in the periphery demonstrating a low risk to exacerbate auto-immune effects of anti-PD-1’s

• THOR-707 +/- anti-PD-1 does not induce release of cytokines associated with CRS

• Similar exposure levels observed vs re-dosing: no indication of ADAs

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The Tumor Microenvironment is Re-Programmed Following Treatment with THOR-707 and Enhanced when Combined with an anti-PD-1

➢ Induction of multiple markers of IL-2 response and T cell activation, including the IL-2 receptor chains, CD28, 4-1BB

➢ Elevated expression of the checkpoint inhibitory receptors PD-1 and CTLA4, and the PD-1 ligands PD-L1 and PD-L2

➢ Induction of genes reporting on IFNg signaling pathways

RNA is not expressed

RNA is expressed

ControlTHOR-707

Anti-PD-1Combo

Key Findings

Methodology

• CT-26 tumor samples were profiled via mRNAseq (Omniseq) and analyzed by GeneCentric to identify cell and molecular signatures of lymphocyte infiltration and activation

• Nomenclature shown for human ortholog genes

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THOR-707 Is Efficacious as a Single Agent and when Combined With a PD-1 Inhibitor in the CT-26 Mouse Tumor Model

THOR-707 Single Agent Study, Day 17 Combination Study Overall Survival (n=14)

*P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001

0

1000

2000

3000

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Treatment groups QW x 3 IV

Tu

mo

r V

olu

me (

mm

3)

SE

M

*** p<=0.001

Veh

icle

1 m

g/kg

3 m

g/kg

6 m

g/kg

9 m

g/kg

***

***

***

Treatment Group QW x 3 IV

Vehicle 1 mg/kg 3 mg/kg 6 mg/kg 9 mg/kg

2000

1000

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Tum

or

Vo

lum

e (

mm

3)

±SE

M

0 0 20 40 60 80 1000

25

50

75

100

Study Day

Perc

en

t su

rviv

al

Vehicle

anti PD-1 (10 mg/kg)

THOR-707 (6 mg/kg)

THOR-707 + anti PD-1

**

* #

• 5/14: complete regression (last THOR-707 dose Day 14)• All 5 mice remained tumor-free by Day 100 (36%)

Across two studies, 9 mice treated with THOR-707 (QW x 3) and anti-PD-1 (Q3D x 6) showed complete tumor regression beyond 100 days

THOR-707LAST DOSE

PD-1LAST DOSE

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The Mice Showing Complete Regression were Re-challenged with Tumor cells and Remained Tumor-free with no Additional Treatment

These data demonstrate activation of memory T cells leading to durable anti-tumor responses, which was observable in the blood of re-challenged animals

Control 2nd re-challenge

****(p<0.0001)

CD

3+T

me

m%

in

blo

od

CD

3+

T ce

lls

50

40

30

20

10

0 CD

8+T

me

m%

in

blo

od

CD

8+

T ce

lls

****(p<0.0001)

Control 2nd re-challenge

30

20

10

0

CT26 Control2nd re-challenge

100 110 120 130 140 150 160 170 180 190

0

500

1000

1500

2000

2500

Days

Me

an

Tu

mo

r V

olu

me

(m

m3

SE

M)

Control (N=7)Re-challenged (N=7)

1st rechallenge 2nd rechallenge

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THOR-707 + PD-1 Inhibitor Potentiates Tumor Antigen-Driven T Cell Receptor Responses in T Effector Cells

45.720

200

400

600

800

1000

THOR 707 (ng/mL)

IFNg

(pg/

mL)

Control

Nivo (5 ng/mL)

Nivo (50 ng/mL)

Nivo (500 ng/mL)

45.72 411.520

10000

20000

30000

40000

50000

THOR 707 (ng/mL)

IFNg

(pg/

mL)

Nivo (0ng/ml)

Nivo (5ng/ml)

Nivo (50ng/ml)

Nivo (500ng/ml)

In this study using an mixed lymphocyte reaction model, anti-PD-1 works synergistically with THOR-707 to increase T cell receptor-mediated IFNg release

THOR-707 + Nivolumab Effect After 5 Days (Ex vivo)

(15.7%) (62.6%)

(Receptor occupancy at CD8+ Teff Cells)

20

0

1000

2000

3000

IFNg

0

5

10

15

IL-6 TNFa IL-5

THOR-707 is Unlikely to Exacerbate the Auto-Immune Effects of Anti-PD-1 and THOR-707 +/- Anti-PD-1 has Decreased risk for Cytokine Release Syndrome

mcg/mL THOR-707 -/+ 90 mg/mL pembrolizumab

pg

/mL

mcg/mL THOR-707 -/+ 90 mcg/mL pembrolizumab

pg

/mL

Concentrations tested reach ~1.5X of maximal Cmax levels observed in non-GLP studies (29 mcg/mL) and cover a receptor engagement range between EC37.9 – 99.5

Pembrolizumab did not increase the relatively low level of IFNgrelease observed with THOR-707 from human whole blood (relative to control anti-CD3, 10 mg/mL)

THOR-707 +/- pembrolizumab did not induce significant release of the cytokines associated with cytokine release syndrome (IL-6 and TNFa) or vascular leak syndrome (IL-5)

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Dose Escalation and Expansion of THOR-707 as a Single Agent, in Combination with a PD-1 Inhibitor

Part 1Single Agent Dose Escalation

Part 2Combination Dose Escalation

Cohort 1 Cohort 2 Cohort 3

Additional Cohorts

Cohort 1 Cohort 2 Cohort 3

Maximum Tolerated Dose and/or Recommended Phase 2 Dosing

• “All-Comers” Populations (3+3 Design, 3-6 subjects)• THOR-707 IV Administered Q2W or Q3W

• PD-1 Inhibitor Sensitive Populations (3+3 Design, 3-6 subjects)• THOR-707 IV Administered Q3W in combination with a PD-1 inhibitor

Measure PD markers of anti-tumor immune response, such as pSTAT5, Ki67 expression and CD8+ T cell count

Maximum Tolerated Dose and/or Recommended Phase 2 Dosing

Purpose: Determine safety and tolerability of THOR-707 as a single agent and in combination with a PD-1 inhibitor

• Emerging “Checkpoint Deserts” (e.g. 2L NSCLC in combination with standard of care chemotherapy or TKIs)

• Low Tumor Mutational Burden (TMB) (suboptimal antigen presentation due to IFN-γ insensitivity)

• Later Line RCC and Melanoma (monotherapy)

• High Tumor Burden/Disseminated Disease (e.g. liver, brain, visceral metastases, all potentially low TMB)

• Viral-mediated Malignancies (e.g. HCC)

Additional Cohorts

Part 3Dose Expansion – Potential

Populations of Interest

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Clinical Endpoints and Biomarkers for THOR-707 Phase 1 Single Agent and Combination Trial

Safety(Primary Endpoint)

Efficacy(Secondary Endpoints)

Key Biomarkers(Readout: 1Q20 Single Agent, 2Q20 Combo)

• RP2D Recommended Phase 2 Dose (RP2D) as single agent and in combination with a PD1 inhibitor

• Maximum Tolerated Dose (MTD) of THOR-707 as a single agent and in combination with a PD-1 inhibitor

• Dose-limiting Toxicity (DLT)

• Overall Response Rate (ORR) determined by RECIST v1.1

• Time to Response (TTR)

• Duration of Response (DoR)

• Progression Free Survival (PFS)

• Overall Survival (OS)

• pSTAT5 expression in peripheral blood lymphocytes

• Ki67 expression levels in peripheral blood lymphocytes

• CD8+ T cell counts

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IL-2 AI IL-10 IO IL-15 IO

Status YE 2018

✓ Dose-dependent peripheral CD4+ Treg expansion in mice

✓ No expansion of CD8+ T cells✓ Additional Synthorins in

testing

✓ Production of dimerized (fully active) IL-10 with high purity

✓ Synthorin IL-10 constructs completed or in progress

✓ “Not alpha” and “half-life extended” IL-15 Synthorins identified

✓ Synthorin IL-15 constructs completed or in process

2019 Milestones✓ Expansion of Treg in monkey• Selection of IND candidate

✓ Evaluation of SAR; in vitro and ex vivo

• In vivo testing of leads

• Selection of IND candidate

✓ Evaluation of “not alpha” vs. “half-life extended” biology

• In vivo evaluation

• Selection of IND candidate

Development Highlights

• DTH incorporated into single ascending dose study in healthy volunteers for POC

• Multiple autoimmune indications

• Single agent and combo

• IL-10/IL-2 combo

• IL-10/IL-2/PD-1 triplet

• Take advantage of unique IL-15 roles vs. IL-2 (e.g. survival of CD8+ Tmems, blocks the ability of TGFβ to suppress the activation of T cells)

• Single agent and combo

Update on Cytokine Pipeline

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Summary

Leveraging our first-of-its-kind Expanded Genetic Alphabet platform to meet today’s challenges for people suffering from cancer and auto-immune disorders

➢ Initial focus on creating optimized cytokines that target validated mechanisms of action in immuno-oncology and autoimmune disorders where existing therapies have significant drawbacks

➢ Lead product candidate, THOR-707, is a “not-a” IL-2 in development for solid tumors

➢ Second product candidate is an IL-2 variant designed to preferentially expand Tregs without expanding Tcons consisting of CD4+ Th and CD8+ Teff cells

➢ Advancing preclinical cytokine pipeline for cancer and autoimmune disorders

➢ Company well-positioned for success with experienced management team and robust financial position

Our goal is to bring multiple SynthorinsTM to market to positively impact millions of patients worldwide

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Thank you