Corporate Presentation  Designed for life  November 2018  

   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 November 13, 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.  © 2018 Synlogic, Inc. All rights reserved.  2 

         SyntheticDesigned genetic circuits Degradation of disease-causing metabolitesProduction of therapeutic molecules  BioticBacterial chassisNon-pathogenicAmenable to genetic manipulation                  © 2018 Synlogic, Inc. All rights reserved.  Synthetic BioticTM Medicines: A Novel Class of Living Medicines  3  Programmable PotencyPathways, Combinations, Biomarkers  PROGRAMMABLE POTENCY  SWITCHES FOR CONTROL, TUNING  LOCAL, REDUCED SYSTEMIC TOXICITY 

     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  © 2018 Synlogic, Inc. All rights reserved.  Synthetic Biotic Platform Breath and Potential: Pipeline Focused on Three Therapeutic Areas  4  SYNB1891 

 © 2018 Synlogic, Inc. All rights reserved.  5  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 

   © 2018 Synlogic, Inc. All rights reserved.  6  Both diseases are characterized by systemic ammonia accumulation  SYNB1020 for Hyperammonemia Indications    Target Profile to Address Unmet Need:Reduce episodes of hospitalizationImprove cognitive outcomes, QoL  Hepatic Encephalopathy  Urea Cycle Disorders  Neuropsychiatric 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  Genetic 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  Target Profile to Address Unmet Need:Maintain blood ammonia in normal range, avoid crisisProtein liberalization: 50-100% more per dayOral administration 

 © 2018 Synlogic, Inc. All rights reserved.  7  SYNB1020 Mechanism of Action:  Conversion of Toxic Ammonia into Beneficial Arginine for the Treatment of UCD and HE  Under normal conditions, urea cycle metabolizes ammonia into ureaWhere ammonia is not efficiently metabolized via urea cycle, SYNB1020 provides an alternative mechanism 

 © 2018 Synlogic, Inc. All rights reserved.  8  Potent and Efficacious Ammonia Reduction and Improved Survival  SYNB1020 Preclinical Characterization  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   Percent survival at 24h  P<0.0001  p<0.01  p<0.001  p<0.001  In vitro  UCD Model  Arginine as biomarker of strain activity  4.0  0.0  3.0  2.0  1.0  Nissle  SYNB1020  Time  Nissle  SYNB1020  Ammonia (mM)  L-arg (mmoles / 109 cells)  Time 

 © 2018 Synlogic, Inc. All rights reserved.  9  Dose-Dependent Increase in SYNB1020 in Feces, Clearance on Cessation of Dosing  Clinical Data SYNB1020 in Healthy Volunteers 

 © 2018 Synlogic, Inc. All rights reserved.  10  Dose-dependent Production of Plasma and Urinary Nitrate  Nitrate as a Biomarker for SYNB1020 Activity  Plasma Nitrate  Urinary Nitrate 

 © 2018 Synlogic, Inc. All rights reserved.  11  SYNB1020 Clinical Development      2018  2019  Q1  Q2  Q3  Q4  Q1  Q2  Q3  Q4  HE Ph 1b / 2a   UCD Ph 1b / 2a   Program   Urea CycleDisorder  Hepatic Encephalo-pathy      Randomized, double-blind placebo-controlled study ongoing at multiple sites in the US Primary outcome: establish safety/tolerability in hepatic insufficiency - patients with cirrhosis and HESecondary outcome: reduction of ammonia  Hepatic Encephalopathy Study Phase 1b/2a in patients with cirrhosis and elevated ammonia 

 © 2018 Synlogic, Inc. All rights reserved.  12  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 µmol / L, source: NPKUA)Increase natural protein intake (less than 10g typically) Oral dosing without systemic toxicity 

 © 2018 Synlogic, Inc. All rights reserved.  13  SYNB1618 Mechanism of Action  Designed to Convert Toxic Phenylalanine to trans-cinnamic Acid 

 © 2018 Synlogic, Inc. All rights reserved.  14  Preclinical Characterization of SYNB1618  Biomarkers demonstrate activity of SYNB1618 in mouse model of PKU and healthy NHPs 

 © 2018 Synlogic, Inc. All rights reserved.  15  SYNB1618 in the Clinic: Safety  Interim Analysis of Phase 1/2a SAD/MAD Study Demonstrates Safety and Clearance in 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 

 © 2018 Synlogic, Inc. All rights reserved.  16  SYNB1618 in the Clinic: Activity  Statistically significant dose-dependent activity of SYNB1618 in healthy volunteers 

 © 2018 Synlogic, Inc. All rights reserved.  17  SYNB1618 Clinical Development   Phase 1/2a SAD/MAD in Healthy Volunteers with Patient Cohort      2018  2019  Q1  Q2  Q3  Q4  Q1  Q2  Q3  Q4  HV Ph 1 / 2a  Group   PKU Patients  SAD/MADHealthy Volunteers    SD/MD Ph 1/2a    Goal: assess safety, tolerability and kinetics in healthy volunteers across a range of dosesExpansion cohort: PKU patients both SD/MD Secondary Endpoint: trans-Cinnamic acid and Hippuric acid production 

   © 2018 Synlogic, Inc. All rights reserved.  18  Expand the benefits of immunotherapy broadly across tumor types  Synlogic Vision for Immuno-Oncology  For indications where immune checkpoint inhibitors are indicated, 55-87% of patients fail to respond  Other tumor types show little-to-no response to checkpoint inhibitors, for example:  Colorectal - MSSPancreatic Prostate – castrate resistantBreast – ER+, hormone therapy refractory    Enable broad response and remission through engagement of multiple immunomodulatory pathways to enhance tumor inflammation and promote robust T cell responses  TREATMENT FAILURES  UNRESPONSIVE TUMORS  ORR for Select FDA approved CPI Monotherapy      45%      40%      29%      13-14%  NSCL 1st line  Melanoma 1st line  Bladder 1st line  Cervical / Gastric 2nd line    Non-responders   

   A Tumor Can Evade Multiple Critical Aspects of the Cancer-Immunity Cycle  © 2018 Synlogic, Inc. All rights reserved.  19    Killing  Recognition  Infiltration  Antigen release  Presentation  Priming and activation  T cell trafficking      © 2018 Synlogic, Inc. All rights reserved.  Insufficientactivity/proliferation  Immuno-suppression  Insufficient trafficking  Insufficient priming  Monotherapies Often Fail to Overcome Tumor Evasion Mechanisms  Recognized Need to Combine Mechanisms to Broaden the Benefit of Immunotherapy  Adapted from Chen, Melman; Immunity 2013 

       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.Dr. William B. ColeyImmuno-Oncology Pioneer  “  ”  © 2018 Synlogic, Inc. All rights reserved.  20  Bacteria Recognized as Earliest Immunotherapy  Engineer a Living Solution: Synthetic Biotic Medicines  Reimagining Early Immunotherapy for Combinatorial Effect  Synlogic Vision for Immuno-Oncology  Rationally Designed for Combinatorial EffectLocally Inflame the TME Systemically Drive Tumor-Antigen Specific Immunity Neo-antigen Priming and Sustained Immune Response 

   Elicits innate responses (IL-6 and TNFα) in the tumor, Not circulation  Intra-tumoral Injection of Synthetic Biotic Chassis: Tumor Colonization Without Leakage; Local Innate Immunity  © 2018 Synlogic, Inc. All rights reserved.  21  Robust proliferation in tumor.No significant leakage  Survival/proliferation in tumors 10-15 days post-single dose.Potential for limited injections          30 mins  24 hrs  72 hrs  Image of Tissue  Reporter Signal      Tumor Cross Section  Chassis Distribution  Behavior within TME  in B16.F10 Mice 

   22  Prime for Tumor-Antigen-Specific VaccinationChassis effectProduce lytic factorsProduce agonists for immune cell activation  Promote TraffickingChassis effectProduce cytokines/chemokines  Promote Immune Activation/ProliferationProduce Immunostimulatory MoleculesPromote Immune Cell Survival and Activity  Relieve ImmunosuppressionConsume immunosuppressive metabolitesProduce checkpoint inhibitors (e.g., αPD-1)  VISION: Rational Design to Locally Inflame the TME AND Systemically Drive Tumor-Antigen Specific Immunity  Synthetic Biotic Medicines Engineered for Efficacy      TUMOR  LYMPH NODE  Systemic Tumor-Antigen Specific Immunity           Locally Inflame the TME   © 2018 Synlogic, Inc. All rights reserved. 

   © 2018 Synlogic, Inc. All rights reserved.  23  Synthetic Biotic Medicines Attributes  Platform Flexibility to Maximize Efficacy, Control, and Safety  KEY ATTRIBUTES OF NEXT GEN APPROACHES    SYNTHETIC BIOTIC PLATFORM  Efficacy Drivers  Sustained payload delivery  Persistence in TME    Multiple/combinatorial pro-inflammatory mechanisms  Large gene insert capacity    Enzymatic activity  Cellular bioreactors  Control  Large Engineering Toolkit  Can design to sense / respond to an inducer    Manufacturability  No mammalian cell culture  Safety  Systemic Risk  Initial programs intratumoral    Pathogenic Risk  Non-pathogenic, probiotic chassisAntibiotic deactivation 

 Synthetic biology applied to IO programs to confer activities for efficacy and control for safetySYN-STING designed 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 to produce c-di-AMPDual biosafety featureLearnings inform future combinations    Dual Innate Immune Activator:Synthetic Biotic Medicine Producing STING Agonist (SYN-STING)  © 2018 Synlogic, Inc. All rights reserved.  11 

 Dual Innate Immune Activator  © 2018 Synlogic, Inc. All rights reserved.  25  TUMOR  CDN-STINGActivation  1  SYN-STING  Naked STING Agonist    Gram-negative BacteriaE.Coli Nissle   TLR4              IFN-b1  Type 1 IFN  P    IRF3  Phagosome  CDNs3’3’-cGAMPc-di-GMBC-di-AMP  STING          Bacterial TLR/MyD88 Signaling  TNF, others  4  CYTOSOL  NUCLEUS    Gram-negative BacteriaE.Coli Nissle   TLR4      IL-6,  p50  p65  NF-κB  APC      Bacterial Intracellular TLR4 Signaling  TLR4  3    Gram-negative BacteriaE.Coli Nissle       IFN-b1  Type 1 IFN  P    IRF3  Phagosome  TRIF  TRAM      Promotes Trafficking, Immune Activation/Proliferation, Priming  Bacterial cGAS-STING Activation  2    Gram-negative BacteriaE.Coli Nissle   TLR4            IFN-b1  Type 1 IFN  P    IRF3  2’3’-cGAMP  STING    cGAS  dsDNA(pathogen, host)          © 2018 Synlogic, Inc. All rights reserved.  25 

   © 2018 Synlogic, Inc. All rights reserved.  In Vitro Characterization of SYNB1891  Interferon Production Across Multiple Human STING Alleles Greater than Naked STING AgonistAdditional Proinflammatory Pathways Engaged  26    Control  SYNB1891-PT2  Naked Agonist  Reporter THP-1  Primary DCs  Synthetic Biotic  Soluble Ligand  Synthetic Biotic  Soluble Ligand  CDA(nmol/well)  CDA(nmol/well)  Naked CDA  SYNB1891  STING Knockout  Human STING Alleles 

   In vitro: STING Agonist Induction by SYN-STING Results in Dose-Dependent Production of IFN-b      © 2018 Synlogic, Inc. All rights reserved.  13  Note: RAW cells  27 

   In vivo: SYN-STING Strain Delivers Robust Anti-tumor Activity as Single Agent in B16.F10 Model  Initial robust Type I IFN production leads to early innate activation at 2 days  Followed by an adaptive T cell response at 9 days, including production of granzyme B and IL-15  IFNb1  IL-6  Sequence of activation following intratumoral injection of SYN-STING  © 2018 Synlogic, Inc. All rights reserved.  15  Key: Saline SYN SYN-STING  28 

 © 2018 Synlogic, Inc. All rights reserved.  SYN-STING Drives Dose-Dependent Tumor Control in A20 Lymphoma Model  Control  SYN-STING 1e7  SYN-STING 5e7  SYN-STING 1e8  Tumor Growth Inhibition  14  29 

   In Vivo Characterization of SYNB1891  SalineSYNB1891-PT1Naïve Control          Re-challenge  SYNB1891-PT1 dose  SYNB1891 Prototype Strain Leads to Systemic Anti-tumor Immunity  © 2018 Synlogic, Inc. All rights reserved.  22      Day on Study  Tumor Volume (mm3)    Saline  SYNB1891-PT1  Naïve Control 

   In Vivo Characterization of SYNB1891  Day 2  Day 9  Saline  SYNB  SYNB1891-PT2  Gated on live CD8+ T cells  H2-kb (Trp2)  CD8α  d1  109 cfu, i.t..YN or SYN-STING)  B16-F10 tumors ~100 mm3, randomize groups  d2  d4  d9  Tumor Draining LN (Flow)  (SYNB or SYNB1891-PT2)  SYNB1891 Prototype Strain Leads to Generation of Tumor Antigen-specific T Cell  CD8a  © 2018 Synlogic, Inc. All rights reserved.  23 

   © 2018 Synlogic, Inc. All rights reserved.  32  Promise Over Other Approaches  STING Agonism in Natural ContextActivation of Multiple Innate Immune PathwaysLow Systemic Risk  Progress Towards the Clinic  Tumor Colonization without LeakageEnhanced Activity vs. Naked STING AgonistIntracellular Activation of STING and Bacterial-Induced Immune Pathways Within APCsDose-dependent Anti-tumor ActivityImmunological MemoryIND Submission 2H19  Dual Innate Immune Activator SYNB1891  A STING Agonist-producing Synthetic Biotic Designed to Locally Inflame the TME and Systemically Drive Tumor Antigen-Specific Immunity 

   © 2018 Synlogic, Inc. All rights reserved.  33  Prime for Tumor-Antigen-Specific Vaccination  Promote TraffickingChassis effectCXCL10Hyaluronidase  Promote and Sustain Immune ActivationIL-15; IL-12Arg Production4-1BBLOX40L  Relieve ImmunosuppressionKyn ConsumptionAde ConsumptionαPD-1 scFv  Additional Synthetic Biotic Effectors  Chassis effect5FC5FUSTINGαCD40 scFv/CD40L  TNFαIFNγαCD47 ScFv / SirpαGM-CSF  VISION: Rational Design to Locally Inflame the TME AND Systemically Drive Tumor-Antigen Specific Immunity      TUMOR  LYMPH NODE  Systemic Tumor-Antigen Specific Immunity           Locally Inflame the TME  

       © 2018 Synlogic, Inc. All rights reserved.  34  Broad Ambitions in Immuno-Oncology  Vision: Expand and Exceed the Effect of Cancer Immunotherapies          SYNB1891  DISCOVERY PORTFOLIO  COMBINATIONS  HARNESS THE MICROBIOME  ORAL  INTRATUMORAL 

 © 2018 Synlogic, Inc. All rights reserved.