8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): January 8, 2018

SYNLOGIC, INC.

(Exact Name of Registrant as Specified in its Charter)

Delaware	001-37566	26-1824804
(State of Incorporation)	(Commission File Number)	(IRS EmployerIdentification No.)

200 Sidney St., Suite 320 Cambridge, MA	02139
(Address of principal executive offices, including zip code)	(Zip Code)

Registrant’s telephone number, including area code: (617) 401-9947

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2). 

Emerging Growth Company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒

Item 7.01 Regulation FD Disclosure.

Synlogic, Inc. has prepared an investor presentation to be used in connection with general corporate presentations, a copy which is attached to this Current Report on Form 8-K as Exhibit 99.1.

In accordance with General Instruction B.2 on Form 8-K, the information set forth in this Item 7.01 and the investor presentation attached to this report as Exhibit 99.1 is “furnished” and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section, nor shall such information be deemed incorporated by reference in any filing under the Securities Exchange Act of 1934, as amended, or the Securities Act of 1933, as amended.

Item 9.01 Financial Statements and Exhibits

(d) Exhibits.

99.1   Investor Presentation of Synlogic, Inc., dated January 2018.

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

Dated: January 8, 2018	SYNLOGIC, INC.
	By:	/s/ Todd Shegog
	Name:	Todd Shegog
	Title:	Chief Financial Officer

EX-99.1

Exhibit 99.1

     Corporate Overview  January 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 November 13, 2017. 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 Biotic 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                   

 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 MetabolismUrea Cycle DisorderPhenylketonuriaBranched Chain Amino Acid DisordersOrganic Acidemias  Hepatic EncephalopathyObesityType 2 DiabetesNASHOther Liver Diseases   

       Probiotic bacteria:E. coli Nissle  Correct the deficiency    Ammonia        ✓  Phenylalanine      ✓    Synthetic Biotic        Probiotic bacteria:E. coli Nissle  Conversion of Toxic Ammonia into Beneficial Arginine  PROGRAM 1: SYNB1020Hyperammonemia (UCD and HE)  Degradation of Toxic Phenylalanine to Non-Toxic Amino Acid Metabolites  PROGRAM 2: SYNB1618Phenylketonuria (PKU)  Rare Diseases: Hyperammonemia and Phenylketonuria Programs in Clinical Trials in Patients in 2018  Phase 1 Topline Data Healthy VolunteersProof of mechanism (Nitrate biomarker)Safe and well-toleratedPhase 1 trial in cirrhotic patients with elevated ammonia to begin 1Q2018Plan to initiate Phase 1 trial in UCD patients in 2018Ammonia reduction in vitro & in vivo in UCD and liver disease modelsUS Orphan and Fast Track Designation (UCD)   Degrades phenylalanine (Phe) In Vitro & In VivoBlood Phe reduction demonstrated in 2 speciesBiomarkers identified (blood TCA and urinary Hippurate)Expect to initiate Phase 1 clinical trial in 1H2018 (healthy volunteers and patients)US Orphan Drug Designation                    

 Synthetic Biotic Platform Breadth and Potential:Current Pipeline    Inborn Errors of MetabolismMetabolic DiseaseImmunomodulation  Immuno Oncology 1: STING A/Kyn Consumer      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 

 SYNB1020 for Hyperammonemia Indications: Urea Cycle Disorders (UCD) and Hepatic Encephalopathy (HE)  Both diseases are characterized by systemic ammonia accumulation  Break in cycle / inefficient cycle  Ammonia  x  Ammoniabuild up (toxic levels)  Urea cycle    !    Urea(removed from the body normally)   Urea cycle  Ammonia      Healthy  Diseased  Urea Cycle DisordersGenetic defects in Urea CycleResults in deficiency 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 leading to ammonia accumulationToxic to brain, leading to crisis & hospitalizationPatients: 165,000 diagnosed overt patients in USCovert in up to 70% of cirrhotic patientsTreatment: 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 grams 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  Vehicle  Nissle  5x109  1x1010  1x109   Blood ammonia (mg / dL)  Liver disease model  Normalprotein  SYNB1020High-protein  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  Vehicle  Nissle  SYNB1020  Healthy  Weeks   Percent survival  Liver disease model  p < 0.01 

   SYNB1020 Biomarkers of Mechanism:Increase of Plasma and Urinary Biomarkers and Improvement in Urea Cycle in Mice          Plasma L-arginine   Plasma L-citrulline          0.000  0.010  0.020  0.030  SYNB1020  Vehicle  [L-Arg] (mM)  6 hours  SYNB1020  Vehicle  6 hours  [L-Cit] (mM)      Urinary urea  Urinary NOx (nitrite + nitrate)  SYNB1020  Vehicle  6 hours  NOx (nmol)  SYNB1020  Vehicle  Urea mmol  6 hours  *  *  p = 0.0669 

     Urinary nitrate   SYNB1020 Biomarkers in Phase 1 SAD / MAD Study:Significant Dose-Dependent Effect on Plasma and Urinary 15Nitrate     500  1,500  0  1,000  Placebo  6x109  6x1011  1.5x1012  15N-nitrate amount excreted in urine CFB(MPE*mL)  Total daily CFU x 14 days    Plasma nitrate   6  8  4  -4  -2  2  0  Placebo  6x109  6x1011  1.5x1012  Total daily CFU x 14 days  15N-nitrate AUC0-24h CFB(MPE*hr)  p = 0.0519  p = 0.0015  p = 0.267  p = 0.00269 

 SYNB1020 Biomarkers in Phase 1 SAD / MAD Study:Summary of Biomarker Strategy  Healthy humans have a robust urea cycleRapidly convert excess ammonia into ureaMaintain consistent ammonia levelsIn the Phase 1 study of healthy volunteers, an oral dose of 15NH4CL was followed by blood and urine sampling over 24 hours: Tested for 15N-labeled urea, citrulline, nitrateChange in levels compared to baseline as measure of in vivo strain activityIn UCD / HE patients, in vivo activity is expected to translate to lower ammonia levels (vs baseline)     Healthy Subjects      Urea cycle        ~99%  ~1%  SYNB1020  15N - Ammonium Chloride  15N - Arginine  15N - Citrulline  15N - Nitrate  15N - Urea 

     SYNB1020 clearance within 2 weeks following completion of dosing    Dose dependent steady-state SYNB1020 qPCR   SYNB1020 Phase 1 SAD / MAD Study:Safe & Well Tolerated with Dose-dependent Exposure Relationship and Fast Clearance  Steady-state qPCR copy number increases with increasing SYNB1020 dose  Following discontinuation of dosing, fecal qPCR load fell rapidly  2x109  2x1011  5x1011  Median Fecal qPCR Copy Number  Treatment: CFU TID x 14 days                                                  1,000  2,000  5,000  10,000  20,000                    2e+09  2e+11  5e+11  Treatment(CFU TID x 14 days)  Fecal qPCR Copy Number  (Mean within Subject)  Days since last dose 

       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 in 2018  Urea Cycle DisordersDemonstrate safety/tolerability in adults with late onset UCDInitiate Phase 1b/2a in H2 2018 at multiple metabolic clinical sites  Hepatic EncephalopathyIND open, initiating study at multiple sites in the USPhase 1b/2a: Randomized, double-blind placebo-controlledPrimary outcome: establish safety/tolerability in hepatic insufficiency and cirrhosis patients with HESecondary outcome: reduction of ammonia  We are pursuing HE and UCD Ph 1b/2a in 2018 with the goal of obtaining proof of concept data for both indications          

 SYNB1618 for Phenylketonuria (PKU):Facilitating Normalization of Plasma Phe Levels   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 rash, musty body odorTreatment: Low protein diet (no meat, dairy, nuts, eggs)Kuvan: PAH cofactor. 20-40% of patients  Target Profile to Address Unmet Need:Normalize Phe: less than half manage to target (120 - 360 mmol / L, source: NPKUA)Increase protein intake to >25g (vs 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    Normalized levels of Phe      Synthetic Genetic Circuit  Phenylalanine  t-CinnamicAcid      Metabolic Conversions  High-Affinity Uptake  LAAD  FNR  FNR  PAL3  FNR  FNR  pheP  AraC  AraC  t-Cinnamic Acid (TCA)  SYNB1618  When Phe is not efficiently metabolized (PKU) SYNB1618 provides an alternative mechanismProduces TCA which is converted to hippuric acid in the liver  Probiotic bacteria: E. Coli Nissle  Accumulation of Phe to toxic levels 

   SYNB1618 Preclinical Characterization in Mice: Efficient Phe Degradation and Hippuric Acid Excretion    Dose-responsive urinary hippuric acid production in Pahenu2     Reduced plasma Phe in Pahenu2 mice  3.13x109  6.25x109  1.25x1010  2.5x1010  5x1010  1x1011  1x1011  Urinary HA / cage (mmol)  SYNB1618    Nissle  1.0  0.0  0.5  SYNB1618  Nissle    Serum Phe (mM)  p = 0.002  Following SQ Phe administration to PKU mouse in the presence of SYNB1618    

   SYNB1618 Preclinical Characterization in Healthy NHPs: Proof of Mechanism - Metabolizes Phe Whether Administered Orally or Systemically    Phe (oral administration) metabolism with a Synthetic Biotic medicine    13C Phe (systemically administered) metabolism to 13C HA with Synthetic Biotic medicine  0.10  0.20  0  SYNB  Control  Phe (mM)  Time (h)  1.0  0.0  3.0  2.0  4.0  2  5  3  4  1  Total urinary 13C-HA (mMoles)  NHP subjects 

   300  100  200  0  SYNB1618 Preclinical Characterization in Healthy NHPs:Phe Metabolism is Dose Responsive     Dose dependent excretion of urinary HA  0  3x109  1.1x1010  2.3x1010  4.5x1010  9x1010  1.8x1011  3.6x1011  7.2x1011  HA (mmoles)  Dose dependent conversion of Phe to plasma TCA  0  3x109  1.1x1010  2.3x1010  4.5x1010  9x1010  1.8x1011  3.6x1011  7.2x1011  0.04  0.00  0.02  Plasma TCA AUC 6 hrs post-dose period 

   SYNB1618 Preclinical Characterization in Healthy NHPs:Phe Metabolism is Clinically Relevant  PKU patients: restricted to <10g protein/dayExtrapolation from highest dose in NHPs: Supports a minimum of 25g of dietary protein intake in humans~50% of daily recommended protein intake (US RDA) or 2.5x increase in protein intakeClinical target for SYNB1618 up to US RDA    PKU subjects  Dietary protein (g) recommended levels  0  25  50  <10g  Protein restricted diet  NHP Projection  US RDA  Target for SYNB1618 

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

 SYNB1020 and SYNB1618:What We Have Learned     Preclinical  Clinical  Regulatory  Manufacturing  Successful Regulatory interactions: Established a development path: requirements for preclinical and clinical testing and manufacturing of a live biotherapeutic  Completed Phase I study in 52 healthy volunteers for SYNB1020Safety: safe and well-tolerated; nausea and vomiting is dose-limiting toxicityEfficacy: Dose responsive effect on systemic metabolite through programmed mechanism which is active in the gut Bacteria are active in vivo, can survive transit through the GI tract, and be metabolically active in fecesClearance: bacteria behave in a consistent and predictable way; clearance within 2 weeks following completion of dosing in all subjects   Established mechanism of action (MoA) for ammonia and phenylalanine lowering in plasmaCorrelated MoA with efficacy and survivalIdentified biomarkersDemonstrated dose-dependent changes in systemic metabolite levels based on activity in the gutIn ex-vivo human GI models demonstrated survival, resident time and potencyCompleted preclinical / tox program for 2 biotics  Operationalized manufacturing for a human trial with an LBPDeveloped process to manufacture 3,000 – 5,000 doses of active drug 

 Strain engineeringFast - >40 in 3 yearsSwitch technology enables productive biomass  In vitro testingSmall scale manufacture- ambr® 15In-house testing of:Strength – CFUsPotency – micro well plate assays  Discovery and Preclinical  Drug Substance  Clinical suppliesStandard process for consistent biomass and potencyPhase 1 scale 150-200L fermentation - ambr® 250CMO producing lead program supplies  Commercial suppliesProbiotics at massive scale, lyophilizedPrebiotic formulation for energetics, survival, and switchesUnder evaluation: Large scale CMOs, lyophilization, spray dry  Drug Product  Clinical suppliesLiquid/oral formulationUnder developmentSolid oralInjectable for intratumoral  Commercial suppliesProbiotics are solid oralSolid dose CMO capabilities under evaluationEvaluating: Capsules, sachet, enteric coating      Tox and In vivo lots3,000 dose lotsCMO currently producingIn-house in 2018    Manufacture of Drug Substance and Drug ProductFrom Flask to Fermenter to the Clinic   

         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 

 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 41 Patent Families122 Patent Applications    Inflammation MetabolicNeurology    MetabolicNeurology    MetabolicNeurology    Inflammation Immuno Oncology    Inflammation Immuno OncologyNeurology     Immuno Oncology 

 SYN-MSUD for Maple Syrup Urine Disease (MSUD):Degradation of toxic branched-chain amino acids  Branched-chain amino acids (BCAA)        Valine  Leucine  Isoleucine  BCAA aminotransferase  Branched-chain ketoacids  Branched-chain Acetyl-CoAs  Mutation in branched-chain a-keto acid dehydrogenase complex (BCKD)   ATP    Accumulation of α-ketoacids Leucine is the toxic metabolite responsible for pathology    !  Genetic AminoacidopathyEnzyme defect in catabolic pathway of branched-chain amino acids (BCAAs)Incidence: 1:185,000; higher in certain population e.g Mennonites 1:176Diagnosis via newborn screening programSymptoms: lethargy, hypotonia, seizures, hypoglycemia, ketoacidosis, pancreatitis, coma, neurological declineTreatment: No therapeutic optionsLong term dietary management: restriction of BCAAs  Target Profile to Address Unmet Need:Maintain target leucine levelsPrevention of acute episodes 

 SYN-MSUD In Vivo: Lowers Plasma and Brain Leu Levels      Plasma Leu significantly reduced on Day 3Trend for Leu lowering in the brain      Plasma  Brain  Protective effect on iMSUD animals fed high-protein chow 

     Metabolite production, consumption, transformation   Neurotransmitter or hormone production/consumption,Toxin consumption,Neuroprotectant production  Bianconi et al., Atlas of Human Biology 2013Sender et al, PLoS Biology 2016  Engineered Probiotics to Modulate Cross-talk between the Gut and the Liver or Brain                Chassis  Pathway  Preclinical      Translation    Delivery   Engineerability Effectiveness Safety  Pharmacology, modelingDoseToxicityBioavailabilityPotency Residence TimeConversion Efficiency  ManufacturabilityDrug Substance and Drug Product Manufacturing:     High Throughput Strain EngineeringEnzyme optimization Pathway balancingIndustrial scale gene synthesisAutomated and Parallel TestingMutli-dimensional analyticsIntegrated manufacturabilityPredictive translational  Understand disease pathology Identify mechanisms to restore healthDesignBioinformaticsPathway enumerationIn silico designSystems-level characterization  Unprecedented Engine for Rational Drug Development of Living Medicines 

   HORIZON 3    HORIZON 2    Test simple synthetic biology concepts in the local tumor microenvironment  Harness microbiome metabolomics to widen response to cancer immunotherapies  Rationally build full minimal genomes solely designed for wide therapeutic use in cancer      HORIZON 1    Synlogic Mission: To Re-define Medicine through Synthetic BiologyBringing Minimal Therapeutic Genomes to Oncology       

   Synlogic Vision for Immuno-Oncology: One Drug, 2 Mechanistic Modules to Turn Cold Tumors to Hot, Driving High Response Rates and Abscopal Effect      STING Agonist  KYNConsumer  SYNB0828: Lead IO Program  Immune Initiator: Antigen Release, Activation & Priming  Immune Sustainer: Immune Augmentation & T Cell Expansion    SYN-Kyn with PD-1/CTLA4 reprograms tumor microenvironment to drive tumor necrosis and antigen release    SYN-STING activates innate cytokines and adaptive T-cell response to drive tumor regression    Combination of initiator & sustainer circuit in one strain to enhance activity  Production of cyclic-di-AMP  Consumption of L-kynurenine  KYN (mM)  C-di-AMP (mM)      200  400  600  0  Day 1  Day 9  Day 4  Control  SYN  SYN-STING  Days  Tumor volume (mm3)        Control: Responders 0%  SYN/aPD-1/aCTLA4  SYN-KYN/aPD-1/aCTLA4  Responders71%  Responders 25%  Tumor volume (mm3) 

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

 Synlogic:Significant Delivery in 2017 …. Primed to Deliver in 2018          2017 Accomplishments  2018 Goals  Significant pipeline progress: SYNB1020: UCD / HEPhase 1 completionFast track designationSYNB1618: PKUOrphan statusIND on track for Q1 ’18Corporate:Public listing on NASDAQ1st milestone in AbbVie collaboration in IBDStrategic collaboration with Gingko BioworksOrganization growth: hiring into key roles to support clinical and manufacturing functions  Programs:SYNB1020: UCD / HEPhase 1 results presentation at medical conferences: Q1 ’18Initiate Phase 1b / 2a in HE in Q1 ’18Initiate Phase 1b / 2a in UCD mid ’18SYNB 1618: PKUPhase 1 SAD / MAD study in HV and PKU patients in H1 ’18Early pipeline: new indications (including IO) data presentation at major meetingsCorporate:Advance existing collaborationsExpand platform reach through new partnerships 

       Synlogic Overview    NovelTherapeuticClass  Dominant Synthetic Biotic IP PortfolioAs of Jan 2018  Strong Balance Sheet  Leader of therapeutic synthetic biology, genetically reprogram probiotics for transformative impact on disease treatmentSimple, robust and rapid process for the discovery, development and manufacturing of drug candidatesKey differentiation: potency, pharmacology/dose responses, reproducible manufacturing      Robust Pipelinewith Orphan Drug Programs  SYNB1020 for Hyperammonemia including Urea Cycle Disorder (UCD) & Hepatic Encephalopathy (HE). Healthy volunteer study completed November 2017: Safe and well tolerated, positive Proof of Mechanism SYNB1618 for Phenylketonuria (PKU); Positive PoM in NHPs. 2018 IND and clinical study    $96.6M in cash as of 3Q 2017Investors include: Aju IB Investment, Ally Bridge Group, Atlas Venture, Deerfield Management, New Enterprise Associates (NEA), OrbiMed, Perceptive Advisors, Rock Springs Capital      Highly Experienced Management Team  JC Gutierrez-Ramos, CEOAoife Brennan, CMOTodd Shegog, CFOAndrew Gengos, COO  Paul Miller, CSODean Falb, CTORichard Schwartz, SVP ManufacturingCaroline Kurtz, VP Translational Science                 Broad Platform - Multiple Product Opportunities  Immuno Oncology: Non pathogenic bacterial chasis “armed” synthetically with effector functions that activate/expand immune response for tumor regression and memory response Inflammatory Bowel Disease (IBD) partnered with Abbvie Liver Diseases and CNS diseases: direct exposure to Liver/plasma of designed metabolites       20 Issued/Allowed Patents41 Patent Families122 Pending Patent Applications 

 Synlogic Management Team: From Funding of Platform to Clinic in Less than Three Years    JC Gutierrez-Ramos, CEO Group SVP Biotherapeutics, PfizerSVP, Head Immunoinflammation Center for Drug Discovery, GSKCSO & Site Head, Amgen Mountain View  Dean Falb, CTOEntrepreneur in Residence, Atlas VentureVP, R&D, Stryker Regenerative Medicine   Aoife Brennan, CMOVP, Rare Disease Innovation Unit, BiogenMedical Director, Tolerx  Caroline Kurtz, SVP, Translational Science Vice President, GCC Platform Lead, Ironwood PharmaceuticalsDirector, Infectious Diseases, Genzyme   Todd Shegog, CFOSVP & CFO, Forum PharmaceuticalsSVP & CFO, Millennium Pharmaceuticals  Dick Schwartz, SVP, ManufacturingChief, Vaccine Production Program Lab, NIHSenior Director, Process & Manufacturing Sciences, MedImmune   Paul Miller, CSO VP, Infection iScience, AstraZenecaVP, Antibacterials Research Unit, Pfizer  Andrew Gengos, COO & Head of Corp. Dev.President and CEO ImmunoCellular TherapeuticsPresident & CEO Neuraltus PharmaceuticalsVP, Strategy & Corp. Development Amgen,VP, CFO & CBO Dynavax Technologies   Adam Thomas, CHROVP, Head of Human Resources for R&D, ShireHead of HR for Research, Development & Engineering, S.C. Johnson Co  Maiken Keson-Brooks, General CounselSVP, General Counsel, uniQureSVP, General Counsel, Forum Pharmaceuticals 

     SYNB1020 for Treatment of Liver Disease:Potential Mechanisms of Action  Engineered probiotic bacteria have the potential beyond ammonia control in hepatic encephalopathy  Hepatic EncephalopathyPathogenesis  800  400  0  1,200  HealthyControl  SYN1020  Vehicle  SYN1020  Heat inactivated SYN1020  Heat inactivated SYN1020  SYN1020  AST  ALT  OD  mg/dl  Toxin-induced liver disease model  Probiotic in disease model  Probiotic in disease model  Healthy  Healthy  Disease model  Disease model          Intestinal permeability  Hepatocyte Necrosis / Apoptosis  LiverFibrosis  HepaticInflammation  E. coli Nissle  Placebo  E. coli Nissle  Placebo  Graded Microbiological Findings in Human Stool Samples  p < 0.001  Serum endotoxin (UE/mL)  Naive  Cirrhosis 

           Animal Data  Human Data  Potency  In vitroAmmonia consumptionArginine production: nitrate precursor    Exposure  Survival past stomach and small intestine:In mouse models of disease In simulated human gut (Prodigest)  Dose exposure relationshipFunctional activity following transit through the gut  Biomarker  In vivoUnlabeled / wild-type mouse: increase in arginine and arginine metabolitesMouse and NHP: tracer data  Plasma and Urinary Nitrate (tracer data)  Efficacy  Efficacy in animal model of UCD and liver diseaseAmmonia lowering and survival in UCDAmmonia lowering in liver disease  Patient studies planned in 2018  SYNB1020 for Hyperammonemia:Strong Preclinical Package Informs Clinical Strategy 

                       Cohort 2: 2 x 1011 TID  Cohort 1: 2 x 109 TID  Cohort 3: 5 x 1011 TID                1x1012 CFU x 3 / day  Days   2x1010 CFU  5x1011 CFU x 3 / day  2x109 CFU / day  2x1011 CFU  2x1012 CFU x 3 / day  2x1012 CFU  A randomized, double-blind, placebo-controlled study to assess the safety, tolerability, and pharmacodynamics of SYNB1020 in healthy volunteers  SAD:Single dose / day  SAD:3 doses/ day  MAD:14 day dosing  1  30  57  MAD:6:2 active to placebo8 subjects per cohort (3 cohorts): 24 patients  SAD:3:1 active to placebo4 subjects per cohort (7 cohorts) - 28 patients  Met primary and secondary objectives Safe and well tolerated: no SAEs, AEs mild to moderate nausea and vomiting at highest doses testedWell tolerated in MAD up to 1.5x1012 CFU for 14 daysSYNB1020 cleared from system within 11 days  SYNB1020 Phase 1 SAD / MAD Study:Phase I Study - Safe and Well-Tolerated in Healthy Volunteers 

 SYNB1020: Toxicology Package and Regulatory Path  Orphan Drug Designation (UCD, PKU)Fast Track Designation (UCD)Feedback from FDA Office of Vaccines Research and Review (CBER)No Recombinant DNA Advisory Committee (RAC) requiredLowering of blood ammonia level is an approvable end-point (UCD)  Preclinical:No toxicity at highest feasible dose in two speciesNo evidence of distribution outside the GI tractClinical:Well tolerated in MAD up to 1.5 x 1012 CFU for 14 daysMild nausea and vomiting at higher dose52 healthy volunteers dosed orally with either SYNB1020 or placeboSAD-28 subjects in 7 cohortsMAD-24 subjects in 3 cohortsSYNB1020 cleared from system within expected timeframe  Regulatory   Preclinical and Clinical Safety & Toxicology 

 CMO Manufacture - From Flask to Industrial Fermenter: Well-Controlled Process at 150L   Successful Scale-up to Biomass for Clinical Scale    Number of doses at 1e12 CFU  10000  1000  100    10  Shake flask – 250 mL  Shake flask – 500 mL  Shake flask – 1 L  Bench fermenter – 5 L  Pilot fermenter – 25 L  Pilot fermenter – 150 L  Engineering Run N=2 – 150 L  Pilot fermenter – 15 L                  6  12  24  100  300  500  3000  3000    Increasing Time Post Induction  Run 1 0hr-PI  Run 1 1hr-PI  Run 1 2hr-PI  Run 1 3hr-PI  Ref Std.  1.25  1.00  0.75  0.50  0.25  Arginine (umol/hr/1e9 cells)          Control of Activity During Manufacturing  Hours Post Induction    Clinical Trial Run – 150 L    3000 

  SYNB1618  PKU Design and Preclinical Characterization:Efficient Phe Degradation In Vitro and In Vivo                                            With pheP Transporter  Without pheP Transporter  20  10  10  0                                                                  5                        Phe Degradation Rate(μmoles/h/10e9cells)  IntegrationSite  PAL copyNumber  IntegrationSite  PAL copyNumber  pheP copyNumber  LAAD +3XPAL + pheP+  Lead Optimization in vitro  Greater Consumption  Less Consumption  Dose response for Blood Phe in vivo 

 SYN1618 Preclinical Characterization:Casein Study in NHPs  NHP challenge studies:Oral D5-PheSQ D5-PheOral dipeptides and tripeptides with D5-PheCasein containing D5-Phe   Plasma D5-Phe   Plasma D5-TCA   Plasma D5-HA    Phenylalanine  Probiotic bacteria: E. Coli Nissle    Synthetic Genetic Circuit  Phenylalanine  t-CinnamicAcid      Metabolic Conversions  High-Affinity Uptake  LAAD  FNR  FNR  PAL3  FNR  FNR  pheP  AraC  AraC  t-Cinnamic Acid (TCA) 

 Synthetic Biotic Medicines: Designed for Clinical Performance              BUILT TO TRANSLATE ACTIVITY & DOSE   In silico design, pathway modelingEnzyme selection, optimization10+ Switches for GI sensingPromoters for signal optimizationSystems profiling of cell metabolism  PROGRAMMED TO SENSE AND RESPOND  ENGINEERED FOR EFFICACY AND SAFETY  Biomarkers by designEx vivo GI modelAuxotrophiesIntegrated manuf. feasibilityPlatform formulation strategyLocal delivery  100sproteins/peptides that affect metabolic or immunomodulatory diseases from the gut  100s-1000sGI metabolites and conversions  Over 15progressed to in vivo activity  2 with dose dependent effect on systemic biomarker in primates  Over 40strains engineered with in vitro activity  9 landing pads for combinations15 Proteins secreted10 Secretion strategiesRibosome binding sites                                              0                                                                                               

   Synthetic Biotic Platform: Rational Drug Discovery and Development  Rapid Lead Generation    Predictable and Controlled Scale Up for Drug Substance    Rational and Efficient Lead Optimization    Drug Product Feasibility    PK/PD Based on Unique Biomarkers  Regulatory Path    Dose Response    Safety and ToxicologyResemble Probiotics                                                    Butyrate  Ammonia  Adenosine                                                                                                            PKU                  Orphan Drug DesignationFast Track Designation              Butyrate