Synlogic DESIGNED FOR LIFE August 2019Corporate Presentation Forward Looking Statements This presentation contains "forward-looking statements" that involve substantial risks and uncertainties for purposes of the safe ha

Synlogic DESIGNED FOR LIFE August 2019Corporate Presentation

Forward Looking Statements This presentation contains "forward-looking statements" that involve

substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this presentation regarding strategy,

future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this presentation, the words "may," "could," "should,"

"anticipate," "believe," "estimate," "expect," "intend," "plan," "predict" and similar expressions and their variants may identify forward-looking statements. Examples of forward-looking statements include, but are not limited to, the approach we

are taking to discover and develop novel therapeutics using synthetic biology; statements regarding the potential of our platform to develop therapeutics to address a wide range of diseases, including: inborn errors of metabolism, inflammatory

and immune disorders, and cancer; the future clinical development of Synthetic Biotic medicines; the potential of our technology to treat phenylketonuria; the expected timing of our anticipated clinical trial initiations; the benefit of orphan

drug and fast track status; the adequacy of our capital to support our future operations and our ability to successfully initiate and complete clinical trials; the results of our collaborations; and the difficulty in predicting the time and cost

of development of our product candidates. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the uncertainties inherent in the preclinical

development process; our ability to protect our intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading "Risk Factors" in our filings with the SEC. The

foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk

factors included in our annual report on Form 10-Q filed with the SEC on August 8, 2019, and in any subsequent filings we make with the SEC. The forward-looking statements contained in this presentation reflect our current views with respect to

future events. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so. These

forward-looking statements should not be relied upon as representing our view as of any date subsequent to the date hereof.

Harnessing nature and technology to create LIVING medicines designed to significantly improve patients'

LIVES Synthetic BioticTM Medicines Designed For Life

v Synthetic BioticTM Medicines A Novel Class of Engineered Living Medicines Designed

genetic circuits to execute biological functionsDegradation of disease-causing metabolitesProduction of therapeutic molecules Bacterial chassisNon-pathogenicAmenable to genetic manipulation PATHWAYS, COMBINATIONS, BIOMARKERS PROGRAMMABLE

POTENCY AND CONTROL LOCAL ACTIVITY, REDUCED SYSTEMIC TOXICITY BIOTIC SYNTHETIC

Synthetic Biotic Portfolio: Breadth and Potential Initial Applications Designed to Target Different

Sites of Action in Metabolic and Immunomodulatory Diseases Oral Administration IMMUNOMODULATION METABOLIC DISEASES Immuno-Oncology Inflammatory and Autoimmune Small or Large Intestine "Cold" Solid Tumors Small or Large Intestine Rare

MetabolicDisease BroadMetabolicDisease

Investing in Development of a Robust Pipeline for a Range of Diseases Research IND-Enabling

Studies Phase 1 Phase 2 Phenylketonuria Additional Rare Metabolic Diseases Inflammatory Bowel Disease Immuno-Oncology Solid Tumors Additional Oncology Applications SYNB1618 SYNB1891 Rare Metabolic

DiseasesImmunomodulation

PKU is a rare inherited amino acid metabolism disorder Causes build up of amino acid phenylalanine (Phe)

in the bodyToday, less than half of adults are at or below target Phe levels of 120-360 mmol / LIf left untreated, symptoms include cognitive impairment, convulsions, behavioral problems, skin rashPatients:16,500 diagnosed in US, similar in

EU5Treatment: Phenylalanine is found in all proteins therefore low protein diet is followed (no meat, dairy, nuts, eggs)KUVAN (sapropterin dihydrochloride): PAH cofactor. 20-40% of patients are respondersPalynziqTM (pegvaliase-pqpz): injectable,

pegylated, bacterial enzyme (phenylalanine ammonia-lyase or PAL) for treatment of adult patients SYNB1618 for Phenylketonuria (PKU) Target Profile to Address Unmet Need:Manage Phe below target levels to prevent irreversible cognitive

damageIncrease natural protein intake: classic PKU patients' natural protein intake is typically less than 10g Oral dosing without systemic toxicity Goal: Managing Plasma Phe Levels

SYNB1618 Mechanism of Action Amino acids from dietary proteins (absorption and

recirculation) Phe PKU Healthy Phenylalanine Hydroxylase (PAH) converts Phe into Tyrosine Tyrosine Accumulation of Phe to toxic levels Impaired PAH SYNB1618 Manage Phe levels When Phe is

not efficiently metabolized (PKU) SYNB1618 provides an alternative mechanismPAL3: produces TCA which is converted to HA in the liver and is excreted in urineLAAD: produces phenylpyruvate (PP) Phenylalanine (Phe) Hippuric Acid (HA) Engineered

Probiotic Bacteria: E. coli NissleComponents of Synthetic Genetic Circuit trans-Cinnamic Acid (TCA) PheP: High-Affinity Uptake trans-Cinnamic Acid (TCA) pheP PAL3 Metabolic

Conversions FNR FNR FNR FNR Phenylalanine LAAD AraC AraC Phenylalanine (Phe) Phenylpyruvate (PP)

SYNB1618 Preclinical Characterization Biomarkers Demonstrate Activity of SYNB1618 in Mouse Model of PKU

and Healthy NHPs IN VIVO EFFICACY IN (PKU) PAHenu2/enu2 MOUSE DOSE RESPONSE IN HEALTHY NHPs Nat. Biotechnol. 2018 Oct;36(9):857-864 Development of synthetic live bacterial therapeutic for the human metabolic disease phenylketonuriaVincent M

Isabella et al, Synlogic, Inc.

SYNB1618 Phase 1/2a Study Design Single Ascending Dose (SAD)6 cohorts, N = 24 Multiple Ascending Dose

(MAD)- TID x 7 days4 cohorts, N = 32 Dose ID Single Dose (SD)N = 4 Multiple Dose (MD)TID x 7 daysN =10 Dose Confirm MTD Part 1: Healthy Volunteers (HV) Part 2: PKU Patients PKU Clinical Trial DesignRandomized, double-blind

placebo-controlled study at multiple sites in the US Primary outcome: establish safety/tolerability following single and multiple doses in HV and PKU patients Secondary outcome: SYNB1618 kinetics in fecesExploratory: change from baseline in

plasma and urinary biomarkers of Phe metabolism Presented in September 2018 New Data

SYNB1618 in the Clinic: Safety There were no treatment-related serious adverse events, no systemic

toxicity or infections Treatment-emergent adverse events were either mild or moderate in severity, and reversible. Most adverse events were GI-relatedSingle dose MTD in healthy volunteers was defined as 2x1011 CFU. Doses above this level were

associated with dose-limiting GI adverse eventsBased on pharmacodynamic data and tolerability profile, a dose of 7x1010 CFU was identified for the second part of the study in PKU patientsDose of 7x1010 CFU TID over seven days was well-tolerated

in PKU patients. There were no discontinuations.All subjects cleared the bacteria (one PKU patient in follow-up). There was no evidence of colonization, and no subject required antibiotics Phase 1/2a SAD/MAD Study Demonstrates Safety and

Clearance in Healthy Volunteers and PKU Patients 56 healthy volunteers, 14 PKU patients Received at least one dose of SYNB1618 or placebo AdultsAge range: 18-62 yrs old

SYNB1618 in the Clinic: Activity Statistically Significant and Equivalent Activity of SYNB1618 in

Healthy Volunteers and Patients SYNB1618 or placebo Protein shake /meal D5-Phe Measure over 6hrs:Plasma:Phe/D5-PheTCA/D5-TCAUrine: HA/D5-HA Key: HA: Hippurate, D5-HA: labeled HA, CFB: change from baseline, CFP: change from

placebo MD URINARY HA AND D5-HA

Modeling: Potential For Phe Reduction in PKU Patients % Blood Phe lowering 7x1010 1x1011 3x1011

5x1011 125100755025 TPP >30% SYNB1618 Dose (CFU) 8-18% 11-26% 34-79% 57-131% Ranges representLow: PAL mechanism only (conservative) High: PAL + LAAD activity (estimates maximum with both pathways)

SYNB1618 Potential to Address Unmet Need Across Patient Groups 360 mmol /L Uncontrolled

Adults Partially Controlled Adults(Adults on Kuvanand/or low-Phe Diet) Pediatric Patients (controlled / partially controlled) (Pediatric patients on Kuvan and / or low-Phe diet Phe Natural protein Phe Phe Initial Focus

Development of Lyophilized SYNB1618 Improved fermentation process enables production of a solid

formulation of SYNB1618 with: Minimal impact on cell viability and activitySimilar activity to frozen liquid as measured by Phe consumption and biomarker productionImproved quality attributesPatient and commercialization-friendly

presentationStability profile at 2-8 C and room temperatureProcess is robust and reproducible at 30 L production scaleGMP cleanroom build-out has been completed, and lyophilized SYNB1618 material has been manufactured and released for clinical

Batch to Batch Consistency of SYNB1618 Solid Formulation Viability Activity in WT mice

Stability of SYNB1618 Solid Formulation

Upcoming Milestones and Path Forward Established new solid formulation and manufacturing process Completed

EPO1 interactions with FDA to align on program plans (clinical, manufacturing, toxicology) Completed Phase 1/2a study (healthy volunteers and PKU patients)Initiate bridging study with solid formulation in Q3 2019Phase 2 study in PKU patients to

assess Phe lowering to start in 1H 2020

RESERVED. CONFIDENTIAL | 20

CHECKPOINT INHIBITORS HAVE TREATMENT FAILURES Synlogic Vision for Immuno-Oncology Expand the

Benefits of Immunotherapy Broadly Across Tumor Types Other tumors, where CPIs are not indicated, show little-to-no response to checkpoint inhibitors Failure Rates for Select FDA Approved CPI Monotherapy 55% NSCL 1st

line 60% Melanoma 1st line 71% Bladder 1st line 87% Cervical / Gastric 2nd line Non-responders For indications where immune checkpoint inhibitors are indicated, 55-87% of patients fail to respond Nature often gives us hints

to her profoundest secrets, and it is possible that she has given us a hint in which, if we will but follow, may lead us on to the solution of this difficult problem. " " Bacteria Recognized as Earliest Immunotherapy DR. WILLIAM B.

COLEYIMMUNO-ONCOLOGY PIONEER Enable broad response and remission through engagement of multiple immunomodulatory pathways to enhance tumor inflammation and promote robust T cell responses

Dual Innate Immune Activator:Synthetic Biotic Medicine Producing STING Agonist (SYNB1891) Synthetic

biology applied to confer activities for efficacy and control for safetyDesigned as a dual innate immune activator: combined benefit of bacterial chassis and STING agonistThe dacA gene is integrated into genome under the control of inducible

promoter (Pfnr) to produce c-di-AMP (CDA)Dual biosafety feature via auxotrophies - no proliferation in tumor, systemic circulation or environmentLearnings inform future combinations ANAEROBIC ENVIRONMENT dacA Pfnr ATP

+ATP Cyclic-di-AMP(STING Agonist) 02 AuxotrophiesDiaminopimelic acid (DAP)Thymidine

SYNB1891 In Vitro Characterization Interferon Production Across Multiple Human STING Alleles - Activity

Greater than Naked STING Agonist HUMAN PRIMARY DENDRITIC CELLS REPORTER HUMAN MONOCYTIC LINE Human STING Alleles STING Knockout

SYNB1891 In Vivo Characterization d1 107, 5x107 or 108 CFU, i.t. (SYNB1891-PT1) A20 tumors ~100 mm3,

randomize groups d7 d4 d18 Dose-dependent Anti-tumor Activity of SYNB1891 Prototype Strain (PT1) as a Single Agent Control Control SYNB1891-PT1 (1 x 107) SYNB1891-PT1 (5 x 107) SYNB1891-PT1 (1 x 108) = Dose

SYNB1891 In Vivo Characterization SYNB1891 Prototype Strain (PT1) Leads to Systemic Anti-tumor

Immunity SYNB1891-PT1 dose Re-challenge d1 108 CFU, i.t. (Bacteria) A20 tumors ~80-100 mm3, randomize groups d7 d4 d35 d63 Rechallenge (2e5 A20 cells) d1

Dual Innate Immune Activator SYNB1891 Designed to Locally Inflame the TME and Systemically Drive Tumor

Antigen-Specific Immunity Tumor Colonization without LeakageEnhanced Activity vs. Naked STING AgonistIntracellular Activation of STING and Bacterial-Induced Immune Pathways Within APCsDose-dependent Anti-tumor ActivityImmunological

MemoryAtezolizumab supply agreement in placeIND Cleared by FDAPhase 1 monotherapy data expected in 2020 STING Agonism in Target Cells that Drive EfficacySparing Cells Where STING Agonism is DetrimentalActivation of Multiple Innate Immune

PathwaysLow Systemic Risk PROMISE OVER OTHER APPROACHES PROGRESS TOWARDS THE CLINIC

A Tumor Can Evade Multiple Critical Aspects of the Cancer-Immunity

Cycle Killing Recognition Infiltration Antigen release Presentation Priming and activation T cell trafficking Insufficientactivity/proliferation Immuno-suppression Insufficient trafficking Insufficient priming Recognized Need to

Combine Mechanisms to Broaden the Benefit of Immunotherapy Adapted from Chen, Melman; Immunity 2013 MONOTHERAPIES OFTEN FAIL TO OVERCOME TUMOR EVASION MECHANISMS Rationally Designed for Combinatorial EffectLocally Inflame the tumor

microenvironment (TME)Systemically Drive Tumor-Antigen Specific Immunity In Situ Vaccination: Neo-antigen Priming and Sustained Immune Response ENGINEER LIVING SOLUTIONS: SYNTHETIC BIOTIC MEDICINES

Additional Synthetic Biotic Effectors VISION: Rational Design to Locally Inflame the TME AND Systemically

Drive Tumor-Antigen Specific Immunity Chassis effectCXCL10Hyaluronidase Kyn ConsumptionAde Consumption PD-1 scFv Chassis effect5FC 5FUSTING CD40 scFv/CD40L TNF IFN CD47 ScFv / Sirp GM-CSF TUMOR LYMPH NODE Systemic Tumor-Antigen

Specific Immunity Locally Inflame the TME IL-15; IL-12Arg Production4-1BBLOX40L RELIEVE IMMUNOSUPRESSION PROMOTE AND SUSTAIN IMMUNE ACTIVATION PRIME FOR TUMOR-ANTIGEN-SPECIFIC VACCINATION PROMOTE TRAFFICKING

Broad Ambitions in Immuno-Oncology SYNB1891 DISCOVERY PORTFOLIO INTRATUMORAL Vision: Expand and

Exceed the Effect of Cancer Immunotherapies COMBINATIONS HARNESS THE MICROBIOME ORAL

Synlogic Internal GMP Manufacturing Capabilities In-house Process Development and Clinical Manufacturing

for Early & Mid-Stage Trials Biotherapeutic Manufacturing Candidate Selection & Process Dev. Testing (in vitro and in vivo) Strain Engineering OptimizedProcess Scale-up Process development and lab scale

production MicrobioreactorsHigh throughput strain screening & process development Fermentation DownstreamHarvest/Formulation Lyophilization, milling, & capsule fill Discovery Lead Optimization Pre-IND Phase 1 Mid-Stage

Trials Analytical Methods Development and Validation

Builds off validated pilot program initiated in 2017 Provides access to Ginkgo's industrial scale,

high-throughput strain optimization and screeningEnables screening and identification of higher quality optimized candidates, increasing potential for success Delivers novel tools for increased candidate potencyIncludes equity investment at a

premium, extending runway through multiple milestones Platform Collaboration to Accelerate Development of Synlogic's Synthetic Biotic Medicines

2019 Progress and Milestones SYNB1618 in PKUCompleted Phase 1/2a study in healthy volunteers and

patients, top-line data presentedFull data presentation Sept. 2019 (SSIEM)Bridging study initiatedSYNB1020 in HyperammonemiaPreclin. and HV clin. data published in Sci. Transl. Med.Completed Phase 1b/2a study in patients with cirrhosis (program