H. C. Wainwright 20th Annual Global Investment ConferenceAoife Brennan, M.B., B.Ch., Interim President and CEO, & CMO September 5, 2018 A Novel Class of Living Medicines Synthetic BioticTM medicines to perform and deliver critical therapeutic functions to treat diseases throughout the body

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, liver disease, inflammatory and immune disorders, and cancer; the future clinical development of Synthetic Biotic medicines; the potential of our technology to treat hyperammonemia and 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 quarterly Report on Form 10-Q filed with the SEC on August 9, 2018. 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.

Synthetic BioticTM Medicines: A Novel Class of Living Medicines Synthetic Biology + Bacteria = Synthetic Biotic Medicine Therapeutic delivered locally to treat systemic diseases SyntheticEngineered bacteriaWith designed genetic circuitsTo degrade metabolites that induce disease or synthesize substances to treat disease Biotic: E. coli Nissle as chassis: Widely-used oral probioticLeverage the safety of probioticFound within natural human microbiomeAmenable to genetic manipulation

Advantages of a Synthetic Biotic Approach: Unique Mechanisms to Treat Systemic Metabolic and Immune Dysfunction Can program bacteria to execute an entire metabolic pathway multiple therapeutic functions with potencyand generate biomarkers of activitySwitches provide ability to control or “tune” functions Local delivery of therapeutic function is possible may reduce systemic toxicity Single strain has advantages for rapid understanding and deployment of the platform; and development of robust and reproducible manufacturing processes

Synthetic Biotic Platform Breadth and Potential: Initial Clinical Focus on Orphan Metabolic Diseases Immuno-Oncology (IO) Synthetic Biotic Platform Internal Pipeline Focus Immunomodulation Inflammatory Bowel DiseaseOn-going Partnership Other Inflammation and Immunology Metabolic Diseases Rare Diseases Inborn Errors of Metabolism Liver andObesity-related

Synthetic Biotic Platform Breadth and Potential:Current Pipeline Inborn Errors of MetabolismMetabolic DiseaseImmunomodulation Immuno Oncology 1 Lead Discovery Lead Optimization IND-Enabling Studies Phase I Phase II Hyperammonemia -Urea Cycle Disorder SYNB1020 Phenylketonuria SYNB1618 Organic Acidemias Maple Syrup Urine Disease Inflammatory Bowel Disease Immuno Oncology 2 Hyperammonemia -Hepatic Encephalopathy Immuno Oncology 3 SYNB1020

Initial Synthetic Biotic Programs: Designed to Evaluate Different Sites of Action SYNB1618 for PKU: Site of action = small intestineOther indications:MSUDIVA SYNB1020 for hyperammonemia: Site of action = ColonOther indications:PAMMA Oral Administration Intra-tumoral Administration IO program: Site of action = “Cold” solid tumors

SYNB1020 for Hyperammonemia Indications: Urea Cycle Disorders (UCD) and Hepatic Encephalopathy (HE) Both diseases are characterized by systemic ammonia accumulation Diminished/absent urea cycle activity Ammonia Ammoniabuild up (toxic levels) Urea cycle ! Liver Disease or UCD Urea Cycle DisordersGenetic defects in Urea CycleDeficiency in one of the six enzymes Nitrogen accumulates as toxic ammonia  HE crisisPatients: ~2,000 diagnosed in US; similar in EUTreatment: Ammonia scavengers: buphenyl, Ravicti®Low protein diet with amino acid supplements Hepatic EncephalopathyNeuropsychiatric complication in patients with end-stage liver disease (cirrhosis or hepatitis)Liver dysfunction leads to ammonia accumulationToxic to brain, leading to HE crisis & hospitalizationPatients: 165,000 diagnosed overt patients in USUp to 70% of cirrhotic patients characterized as covert Treatment: Lactulose: laxative - significant side effectsRifaximin reduction in overt HE recurrence Target Profile to Address Unmet Need:Maintain blood ammonia in normal range, avoid crisisProtein liberalization: 50-100% more per dayOral administration Target Profile to Address Unmet Need:Reduce episodes of hospitalizationImprove cognitive outcomes, QoL

SYNB1020 Mechanism of Action:Conversion of Toxic Ammonia into Beneficial Arginine for the Treatment of UCD and HE Urea cycle Ammonia/ NH4Cl Urea Under normal conditions, urea cycle metabolizes ammonia into ureaWhere ammonia is not efficiently metabolized via urea cycle, SYNB1020 provides an alternative mechanism Arginine  Probiotic bacteria: E. coli Nissle Arginine argE argC argB argH argR FNR FNR carA carB argG argl argD argAfbr Ammonia Metabolic Conversions Arginine Glutamate argF SYNB1020

SYNB1020 Preclinical Characterization:Potent and Efficacious Ammonia Reduction and Improved Survival Potency in vitro Arginine as biomarker of strain activity Dose dependent survival and ammonia lowering in vivo 300 400 200 500 0 100 Vehicle 1010 HI 5x109 1x1010 1x109 Vehicle 1010 HI 5x109 1x1010 1x109 Blood ammonia (mg / dL) Normalprotein SYNB1020High-protein Normalprotein SYNB1020High-protein Percent survival at 24h UCD model 4.0 0.0 3.0 2.0 1.0 Nissle SYNB1020 Time Nissle SYNB1020 Ammonia (mM) L-arg (mmoles / 109 cells) Time P<0.0001 p<0.01 p<0.001 p<0.001

Dose dependent steady-state SYNB1020 qPCR Clinical Data SYNB1020 in Healthy Volunteers: Dose-Dependent Increase in SYNB1020 in Feces, Clearance on Cessation of Dosing Steady-state qPCR copy number increases with increasing SYNB1020 dose SYNB1020 clearance within 2 weeks following completion of dosing SYNB1020 Clearance from Feces post-dosing

Nitrate as a Biomarker for SYNB1020 Activity

2018 2019 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 HE Ph 1b / 2a UCD Ph 1b / 2a Program Urea CycleDisorder Hepatic Encephalo-pathy SYNB1020 Clinical Development: Next Steps: HE and UCD Patient Studies – HE study initiated Urea Cycle DisordersDemonstrate safety/tolerability in adults with late onset UCDInitiate Phase 1b/2a at multiple metabolic clinical sites Hepatic EncephalopathyStudy open, initiating multiple sites in the USPhase 1b/2a: Randomized, double-blind placebo-controlledPrimary outcome: establish safety/tolerability in hepatic insufficiency - patients with cirrhosis and HESecondary outcome: reduction of ammonia We are pursuing HE and UCD Ph 1b/2a with the goal of obtaining proof of concept data for both indications

SYNB1618 for Phenylketonuria (PKU):Goal: Managing Plasma Phe Levels to Enable Increased Intake of Natural Protein PKU is a rare inherited amino acid metabolism disorder Causes build up of amino acid phenylalanine (Phe) in the bodyPhenylalanine is found in all proteinsDiagnosed: 16,500 in US, similar in EU5If left untreated, symptoms include cognitive impairment, convulsions, behavior problems, skin rashTreatment: Low protein diet (no meat, dairy, nuts, eggs)Kuvan: PAH cofactor. 20-40% of patientsPalynziq: injectable, pegylated, bacterial enzyme (PAL) (Adults) Target Profile to Address Unmet Need:Manage Phe: Currently < half adults at target (120 - 360 mmol / L, source: NPKUA)Increase natural protein intake (less than 10g typically)Oral dosing without systemic toxicity

SYNB1618 Mechanism of Action:Designed to Convert Toxic Phenylalanine to trans-cinnamic Acid Phe PKU Healthy Amino acids fromdietary proteins [Absorption andRecirculation] Phenylalanine Hydroxylase (PAH): converts Phe into Tyrosine Impaired PAH Tyrosine ! Phenylalanine Hippuric acid (HA) Manage Phe levels Phenylalanine t-CinnamicAcid Metabolic Conversions PheP: High-Affinity Uptake FNR FNR PAL3 FNR FNR pheP LAAD AraC AraC t-Cinnamic Acid (TCA) SYNB1618 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 (PP) Accumulation of Phe to toxic levels Phenylalanine Probiotic bacteria: E. Coli NissleComponents of Synthetic Genetic Circuit Phenylpyruvate (PP)

Preclinical data: Biomarkers demonstrate activity of SYNB1618 in mouse model of PKU and healthy NHPs In vivo activity and efficacy of SYNB1618 in mouse model of (PKU) Pahenu2/enu2 Dose response and PD of SYNB1618 in healthy NHPs

SYNB1618 in the Clinic: SafetyInterim Analysis of Phase 1/2a SAD/MAD Study Healthy Volunteer Cohorts The study enrolled 56 healthy volunteers, all of whom received at least one dose of SYNB1618 or placebo. The subjects were predominantly male Caucasians and the age range of enrolled subjects was 18-62 yearsThere 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 AEs were GI-relatedAll subjects cleared the bacteria. There was no evidence of colonization, and no subject required antibioticsSingle dose MTD 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 was identified for the second part of the study in PKU patients

SYNB1618 in the Clinic: Statistically significant dose-dependent activity of SYNB1618 in healthy volunteers

SYNB1618 in the Clinic:Phase 1/2a SAD/MAD in Healthy Volunteers with Patient Cohort 2017 2018 2019 Q1 Q2 Q3 Q4 Q1 Q2 IND enabling studies SD/MD Patient cohorts SAD / MAD HV Goal: assess safety, tolerability and kinetics in healthy volunteers across a range of dosesIncludes cohorts of SD/MD PKU patientsInterim read: trans-Cinnamic acid and Hippuric acid production in healthy volunteersStudy duration: ~12 months Q4 Q3

Synthetic Biotic Medicines: Applicability Beyond Rare Disease Across Multiple Pathways Short Chain Fatty Acids: ButyrateAcetatePropionate Proteins and PeptidesIL2, IL12, IL15, IL22,IL10IFN, TNF, CXCL10, CD40L, hyaluronidaseGLP1, GLP2 Amino Acid MetabolismBranched Chain AAsTrp, Kyn, indoles, Serotonin, MelatoninArgininePhenylalanine Multiple MoAs in ONE Synthetic Biotic MedicineCombination therapy in a single NME scFv DisplayAnti-PD1Anti-CD47 Degradation ofToxic Metabolites:AmmoniaNucleotides 20 Issued/Allowed Patents 55 Patent Families154 Patent Applications Inflammation MetabolicNeurology MetabolicNeurology MetabolicNeurology Inflammation Immuno Oncology Inflammation Immuno OncologyNeurology Immuno Oncology

Synlogic Vision for Immuno-Oncology: Living Medicines to Turn a “Cold” Tumor “Hot” Dendritic Cells T Cells Tumor antigen-specific, systemic T cell immunity Synthetic Biotic therapyImmune Initiator (innate) + Immune Sustainer (adaptive) Non-inflamed “cold” tumor Inflamed “hot” tumor

Synlogic Vision for Immuno-Oncology: Living Medicines with High Response Rates and Abscopal Effect as Single Agents Immune Initiator Immune Sustainer Concept: 1 Single Drug Antigen Release, Immune Activation & Priming Immune Augmentation & T Cell Expansion 2 mechanistic modules

Design of Initiator SYN-STING and Sustainer SYN-Kyn

Initiator (STING) Module Characterization: STING Agonist Producer with Anti-tumor Activity as Single Agent (B16F10) Dose-dependent inhibition of tumor growth (A20)

Sustainer (Kyn) Module Characterization : Consumes Kynurenine - Arrests Tumor Growth in Combination; Increased Response Rates as Triple Combo Kyn-consuming strain reprograms the tumor microenvironment by depleting kynurenine Time (hr) Kyn (mM) Tumor PD Naive SYN SYN-KYN 0 2 4 7 2 1 6 8 0.0 0.2 0.4 0.6 0.8 2 4 6 8 Metabolite reprogramming in the TME, early T cell activation and reversal of T cell exhaustion drive tumor rejections 0 5 10 15 20 25 0 500 1000 1500 2000 Day on Stud y T u m o r V o l u m e ( m m 3 ) Responders 0% Control 0 10 20 30 0 500 1000 1500 2000 Day on Stud y T u m o r V o l u m e ( m m 3 ) 0 10 20 30 0 500 1000 1500 2000 Day on Stud y T u m o r V o l u m e ( m m 3 ) 0 10 20 30 0 500 1000 1500 2000 Day on Stud y T u m o r V o l u m e ( m m 3 ) SYN/ PD- 1 / CTLA4 SYN-Kyn/ PD- 1 / CTLA4 25% Responders 25% Responders 71% PD- 1 / CTLA4 Responders

Synlogic Development Pipeline:Programs’ Timelines Summary 2018 2019 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SD/MD Patient Cohort HE Ph 1b / 2a IND enabling studies UCD Ph 1b / 2a PKU Program IO UCD HE SAD/MAD HV

GMP manufacturing:Single strainReproducible yieldFormulation & deliveryControl switchesPortfolio applicability Synlogic Synthetic Biotic Platform: Bringing Rational Drug Development to the Microbiome Rational design:Synthetic biology tools appliedEngineer potencyExceed endogenous bacterial activity Pharmacologically tractable:Non-colonizing Measurable dose-response Apply Pharmacological Principles Develop Reliable Manufacturing Build Potency