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