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): November 10, 2018
 
SYNLOGIC, INC.
 
(Exact name of registrant as specified in its charter)
 
Delaware
 
001-37566
 
26-1824804
(State or other jurisdiction
of incorporation)
 
 
(Commission
File Number)
 
 
(IRS Employer
Identification No.)
 
 
301 Binney St., Suite 402
Cambridge, MA
 
 
02142
(Address of principal executive offices)
 
(Zip Code)
 
Registrant’s telephone number, including area code: (617) 401-9975
 
 
 Not applicable
(Former Name or Former Address, if Changed Since Last Report)
 
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 (see General Instruction A.2. below):
 
□  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.

On November 10, 2018, Synlogic, Inc. (“Synlogic”) conducted an investor webcast and presentation summarizing preclinical data from its Synthetic Biotic medicine clinical candidate, SYNB1891, which Synlogic is developing for the treatment of cancer.  A copy of the presentation is furnished with this Current Report on Form 8-K as Exhibit 99.1.

The information in Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing.


Item 9.01. Financial Statements and Exhibits.
 
(d)            Exhibits

                         99.1 Investor presentation provided by Synlogic dated November 10, 2018
 
 


SIGNATURES
 
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.
 
 
 
SYNLOGIC, INC.
 
 
 
 
 
 
 
 
 
Date: November 12, 2018
By:
/s/ Todd Shegog
 
 
Name:
Todd Shegog
 
 
Title:
Chief Financial Officer
 
Exhibit 99.1

 Development of Synthetic Biotic™ Medicines in Oncology  Designed for life  © 2018 Synlogic, Inc. All rights reserved.  Aoife Brennan, M.B., B.Ch., President and CEOSITC 2018- Washington, DCNovember 10th, 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 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.  © 2018 Synlogic, Inc. All rights reserved.  2 
 

 12:30 pm - 12:40 pm Introductions and intro to Synlogic platform and approach Aoife Brennan, MB, ChB President & CEO, CMO, Synlogic Inc.12:40 pm - 12:55 pm Unmet medical need in solid tumor immunotherapy Filip Janku, MD, PhD MD Anderson Cancer Center12:55 pm - 1:10 pm Role of Type I IFN in tumor immune recognition and therapy Dmitriy Zamarin, MD, PhD Memorial Sloan Kettering Cancer Center1:10 pm 1:40 pm Review of SYNB1891 data and program Jose Lora, PhD VP, Research, Synlogic Inc.1:40 pm 2:00 pm Q&A and closing remarks Aoife Brennan  © 2018 Synlogic, Inc. All rights reserved.  3  Agenda 
 

         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  4  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 Breadth and Potential: Pipeline Focused on Three Therapeutic Areas  5  SYNB1891 
 

       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.  6  Bacteria Recognized as Earliest Immunotherapy  Engineer a Living Solution: Synthetic Biotic Medicines  Reimagining Early Immunotherapy for Combinatorial Effect  Synlogic Immuno-Oncology Approach  Rationally Designed for Combinatorial EffectLocally Inflame the TME Systemically Drive Tumor Antigen-Specific Immunity In Situ Vaccination: Neo-antigen Priming and Sustained Immune Response 
 

   © 2018 Synlogic, Inc. All rights reserved.  7  Expand the benefits of immunotherapy broadly across tumor types  Synlogic Vision for Immuno-Oncology  For indications where immune checkpoint inhibitors are indicated, only 13-45% of patients 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   
 

 Unmet medical need in solid tumor immunotherapy   Filip Janku, MD, PhDAssociate ProfessorClinical & Translational Research Center Medical Director  Investigational Cancer Therapeutics(Phase I Clinical Trials Program)MD Anderson Cancer CenterHouston, TX 
 

 

 Response rates to checkpoint inhibitors in approved indications  Melanoma Pembrolizumab: RR ~ 30% Nivolumab/ipilimumab: RR ~ 50%Non-small lung cancer Pembrolizumab: RR ~ 20%-40%Nivolumab: RR ~ 20%SCC of head and neck Pembrolizumab: RR ~ 18%Nivolumab: RR ~ 13% Urothelial cancer Pembrolizumab: RR ~ 21%Nivolumab: RR ~ 28%Atezolizumab: RR ~ 15%-26%  Robert NEJM 2015Wolchok NEJM 2013Garon NEJM 2015Reck NEJM 2016Ferris NEJM 2016Chow J Clin Oncol 2016Bellmunt 2017Rosenberg 2016 
 

 Classification by tumor immune phenotype in urothelial cancers  Immune excluded (CD8 trichrome stain)    Mariathasan S. Nature 2018 
 

 Immunotherapy: unmet need        MSI-H: ~5% of mCRC                Siegel CA J Cancer Clin 2018  Ovarian cancerSoft tissue sarcomasGliomaMyeloma 
 

 Predictive factors for response to immune checkpoint inhibitors        PD-L1 expression  TMB  MSI-H/dMMR 
 

 Stimulatory and Inhibitory Factors in the Cancer-Immunity Cycle  Chen DS. Immunity 2013 
 

 Mechanisms of immunoresistance   Syn Lancet Oncol 2017Blank Science 2016 
 

 Converting Cold Tumors into Hot  Haanen Cell 2017 
 

 Patient with MPNST (sarcoma) with spontaneous remission after prolonged infection with coagulase negative staphylococcus and Klebsiella Pneumoniae  January 2013  May 2013  September 2013  Prolonged infection with bacteremia January to February 2013     
 

 Anticancer activity of single intratumor injection of Clostridium Novyi-NT  Janku CRI-CMIT-EATI-AACR 2018 
 

 Cytokine response after single intratumor injection of Clostridium Novyi-NT  Janku CRI-CMIT-EATI-AACR 2018 
 

   Antitumor Activity of STING  Barber Nat Rev Immunol 2015 
 

 Harrington ESMO 2018  Phase I: Intratumor STING agonist MK-1454 +/- pembrolizumab  Phase I: Accelerated Titration Design -> modified Toxicity Probability IntervalEndpointsPrimary: safety, doseSecondary: PK/PDExploratory: objective responseDLTs:Monotherapy (26 patients): G3 vomiting (1)Combination (25 patients): G2 erythema multiforme (1), G3 injection site pain (1), G3 skin/tumor necrosis (1) AEs: Pyrexia (65.2%/42.9%), chills (39.1%/25%), injection site pain (47.8%/10.7%), fatigue (34.8/25%) 
 

 Harrington ESMO 2018  Phase I: Intratumor STING agonist MK-1454 +/- pembrolizumab  EFFICACYMonotherapyMyoepitehlial carcinoma > - 30% (not confirmed as PR)2 patients with shrinkage of injected lesionsCombinationPartial response: 6 (TNBC, 1; HNSCC, 3; ATC, 2)Shrinkage of injected and noninjected lesions observed PRs were durable (>6 months)Median 83% reduction in size of target lesions for responders 
 

 SITC 2018: MIW815 STING agonist  41 pretreated patients with solid tumors or lymphomasNo DLTsThe most common AEs: pyrexia (7; 17.1%), injection site pain (6; 14.6%), headache (6; 14.6%). Grade 3/ 4 AEs: increased lipase (2; 4.9%), elevatedamylase, tumor pain, dyspnea, respiratory failure,and injection site reaction (1 each; 2.4%). On-treatment tumor biopsies showed increases in CD8 T cells infiltrating the injected tumors in a subset of patients. PR: Merkel cell (CPI naïve), Parotid gland (CPI pretreated), both response appear to be durable  Meric-Bernstam. SITC 2018 
 

 STING agonists in the clinic  MK-1454: early data for monotherapy and combination with pembrolizumab presented at ESMO 2018MIW815: early data for monotherapy presented at SITC 2018MK-2118: clinical trial ongoing (monotherapy and combination with pembrolizumab) 
 

 Conclusions  Immunotherapy with immune checkpoint inhibitors can be effective in subsets of patients with melanoma, lung cancer and other tumor typesImmunotherapy with immune checkpoint inhibitors has not shown enough activity resulting in FDA approval in many common cancers including breast cancer, prostate cancer, ovarian cancer, MSS colorectal cancer and sarcomas, which creates unmet need for novel therapeutic approachesTurning cold tumors into hot with activators of innate immunity such as STING agonists (and others) offers a new promising approach to increase efficacy of cancer immunotherapy 
 

 Role of type I IFN in tumor immune recognition and therapy  Dmitriy Zamarin MD PhDAssistant Attending PhysicianTranslational Research DirectorGynecologic Medical Oncology ServiceImmunotherapeutics ServiceMemorial Sloan Kettering Cancer Center 
 

 Type I IFN: the first cytokine  Alick Isaacs  Jean Lindenmann  Isaacs, A., and Lindenmann, J., Proc. Roy. Soc., B, 147, 258 (1957) 
 

 Functions of type I IFN in infection  Ivashkiv et al. Nat Rev Immunol 2013 
 

 Cross-talk between type I IFN and adaptive immunity  Trinchieri G, JEM 2010. 
 

 Type I IFN- related transcripts correlate with T cell infiltration in tumors  Fuertes M.B. et al., JEM. 208:2005-16 (2011) 
 

 Type I IFN signature is associated with clinical benefit from ipilimumab in melanoma  Chiappinelli et al., Cell 2015 
 

 Type I IFN pathway is essential for the efficacy of cancer immunotherapy  a.  Zamarin D, Wolchok JD, Allison JP. Sci Transl Med. 2014 5:226ra  
 

 Mechanisms of activation of type I IFN pathway 
 

        
 

    
 

 STING pathway is required for immune recognition and elimination of tumors.   Woo …. Gajewski. Immunity 2015.  
 

 Therapeutic strategies to target type I IFN pathway in cancer  TLR agonistsSTING agonistsVirusesBacteriaEngineered viruses and bacteria 
 

 Development of a STING Agonist-producing Synthetic Biotic™ Medicine to Activate Innate and Adaptive Immunity and Drive Antitumor Immune Responses  Designed for life  © 2018 Synlogic, Inc. All rights reserved.  Jose M. Lora, PhDVice President, ResearchSITC 2018- Washington, DCNovember 10th, 2018 
 

   A Tumor Can Evade Multiple Critical Aspects of the Cancer-Immunity Cycle  .  39    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 
 

   40  Prime for Tumor Antigen-Specific VaccinationChassis effectProduce lytic factorsProduce agonists for immune cell activation  Promote TraffickingChassis effectProduce cytokines/chemokines  Promote and Sustain Immune Activation / ProliferationProduce Immunostimulatory MoleculesPromote Immune Cell Survival and Activity  Relieve ImmunosuppressionConsume immunosuppressive metabolitesProduce checkpoint inhibitors  Rational Design of Key Immunostimulatory Mechanisms in a Bacterial Chassis  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.  41  Synthetic Biotics Medicines Attributes  Platform Flexibility to Maximize Efficacy, Control, and Safety      EFFICACY DRIVERS  CONTROL  SAFETY  Sustained Payload Delivery: Persistence in TMEMultiple Mechanisms: Large gene insertion capacityCellular Bioreactors: Enzymatic activity  Large Engineering Toolkit: Design to sense / respond to inducerManufacturability: No mammalian cell culture  Low Systemic Risk: Initial programs intratumoralNon Pathogenic: Probiotic chassis, antibiotic deactivation 
 

   Elicits innate responses (e.g., IL-6, TNFα) in the tumor, not in circulation  Intra-tumoral Injection of Synthetic Biotic Chassis: Tumor Colonization Without Leakage; Local Innate Immunity  © 2018 Synlogic, Inc. All rights reserved.  42  Robust proliferation in tumor.No significant leakage to tissues  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 
 

 Synthetic biology applied to IO programs to confer activities for efficacy and control for safetySYNB1891 designed as a dual innate immune activator: Combined benefit of bacterial chassis and STING agonistdacA gene: Integrated into the genome under the control of inducible promoter (Pfnr) to produce c-di-AMP (CDA)Dual biosafety feature via auxotrophiesLearnings inform future combinations    Dual Innate Immune ActivatorSynthetic Biotic Medicine Producing STING Agonist: SYNB1891  © 2018 Synlogic, Inc. All rights reserved.  13 
 

 Dual Innate Immune Activator  © 2018 Synlogic, Inc. All rights reserved.  44  TUMOR  CDA-STINGActivation  1  SYN-STING  Naked STING Agonist    Gram-negative BacteriaE.Coli Nissle SYNB1891   TLR4              IFN-b1  Type 1 IFN  P    IRF3  Phagosome  CDAC-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)         
 

   SYNB1891 Leverages Natural Phagocytic Activity of Antigen Presenting Cells  © 2018 Synlogic, Inc. All rights reserved.  45      CDA    Agonizes STING in Natural Context 
 

   In Vitro Characterization of SYNB1891  SYNB1891  SYN  STING Agonist Not Released to Extracellular Space  Dose-dependent Activity in Mouse APCs  © 2018 Synlogic, Inc. All rights reserved.  46  EC: ExtracellularIC: Intracellular  SYNB1891-PT1 IC  SYNB1891-PT1 EC  SYN EC  SYN IC     
 

   © 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  47    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 Vivo Bacterial Kinetics of SYNB1891  Restricted to Tumor and Cleared Quickly  1x107 Dose  1x108 Dose  1x109 Dose  48  © 2018 Synlogic, Inc. All rights reserved.    Tumor Homogenate (CFU, CDA, IFNb)  BF16-F10 tumors ~200mm3,Randomize groups  Tumor  Blood 
 

   Pharmacodynamic Characterization of SYNB1891  Dose-dependent Increases in Tumoral IFNβ and Other Innate Immune Markers      Saline  SYNB1891 (1e7 CFU)  SYNB1891 (1e8 CFU)  SYNB1891 (1e9 CFU)    49  © 2018 Synlogic, Inc. All rights reserved.  Administration of SYNB1891 Results in Dose-dependent Increase in Tumoral CDA along with Innate Cytokines  Prototype Elicits Inflammation-related Gene Signature in Injected Tumors  Additional Innate Immune Markers  Dose Dependent IFNβ Following 1 Injection 
 

   d1  108 or 109 cfu, i.t. (SYNB1891)  B16-F10 tumors ~100 mm3, randomize groups  d7  d4  d18  In Vivo Characterization of SYNB1891  d1  109 cfu, i.t. (SYNB or SYNB1891)  B16-F10 tumors ~100 mm3, randomize groups  d7  d4  d21  SalineSYNBSYNB1891   Study Day  Dose    Dose  Delivers Anti-tumor Activity as a Single Agent  50  © 2018 Synlogic, Inc. All rights reserved.    Saline  SYNB1891 (1e8 CFU)  SYNB1891 (1e9 CFU)  Dose  Dose    Saline  SYNB (1e9 CFU)  SYNB1891 (1e9 CFU)  Dose               
 

 © 2018 Synlogic, Inc. All rights reserved.  In Vivo Characterization of SYNB1891  Control  SYN-STING 1e7  SYN-STING 5e7  SYN-STING 1e8  21  d1  107, 5x107 or 108 cfu, i.t. (SYNB1891-PT1)  A20 tumors ~100 mm3, randomize groups  d7  d4  d18    ControlSYNB1891-PT1 (1 x 107)  SYNB1891-PT1 (5 x 107)SYNB1891-PT1 (1 x 108)  SYNB1891-PT1 (1 x 107)  SYNB1891-PT1 (5 x 107)  SYNB1891-PT1 (1 x 108)  Control  Dose-dependent Anti-tumor Activity of SYNB1891 Prototype Strain as a Single Agent               
 

   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.  54  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.  55  NEXT STEPSIND-Enabling Studies On-goingIND Submission 2H19  Dual Innate Immune Activator SYNB1891      TUMOR  LYMPH NODE  Systemic Tumor Antigen Specific Immunity           Locally Inflame the TME  
 

   © 2018 Synlogic, Inc. All rights reserved.  56  Prime for Tumor Antigen-Specific Vaccination  Promote TraffickingChassis effectCXCL10Hyaluronidase  Promote and Sustain Immune Activation / ProliferationIL-15; IL-12Arg Production4-1BBLOX40L  Relieve ImmunosuppressionKyn ConsumptionAde ConsumptionαPD-1 scFv  Pipeline of Synthetic Biotic Effectors Poised to Deliver  Chassis effect5FC5FUSTINGαCD40 scFv/CD40L  TNFαIFNγαCD47 ScFv / SirpαGM-CSF      TUMOR  LYMPH NODE  Systemic Tumor Antigen Specific Immunity           Locally Inflame the TME  
 

 Designed for life  © 2018 Synlogic, Inc. All rights reserved.  Aoife Brennan, M.B., B.Ch., President and CEOJose M. Lora, PhDVice President, ResearchSITC 2018- Washington, DCNovember 10th, 2018  Q&A  Development of Synthetic Biotic™ Medicines in Oncology 
 

   © 2018 Synlogic, Inc. All rights reserved.  58  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.  59  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. 
 

 © 2018 Synlogic, Inc. All rights reserved.  61  Table of Synthetic Biotic Strains  Strain   Genetic Content  SYN  Un-engineered E. coli Nissle:Abx+  SYNB  DAP/Thy dln EcN (no dacA insert):Abx+  SYNB1891-PT1  DAP dln EcN:dacAplasmid:FnR-inducible:Abx+  SYNB1891-PT2  DAP/Thy dln EcN:dacAintegrated:FnR-inducible:Abx+  SYNB1891  DAP/Thy dln EcN:dacAintegrated:FnR-inducible:Abx- 
 

   Pharmacodynamic Characterization of SYNB1891  IL-6  GM-CSF  C-di-AMP  IFNb  Administration of SYNB1891 Results in Dose-dependent Increases in Tumoral CDA, Cytokines        Saline  SYNB1891 (1e7 CFU)  SYNB1891 (1e8 CFU)  SYNB1891 (1e9 CFU)  Production in Tumor Tissue    pg / g    mg / g    pg / g    pg / g  62  © 2018 Synlogic, Inc. All rights reserved.   
 

 © 2018 Synlogic, Inc. All rights reserved.  63  Pharmacodynamic Characterization of SYNB1891  d1  B16-F10 or CT-26 tumors ~100 mm3, randomize groups  d4  Harvest Tumor TissueIsolate Tumor Infiltrating LymphocytesPerform RNAseq on Purified T cells  Saline or 109 cfu SYNB1891-PT2, i.t.  SALINE  SYNB1891-PT2  SALINE  SYNB1891-PT2  CT26  B16          cytokine receptor  cytokine  cytokine  Immune response  cytokine  inflammation  inflammation  inflammation  inflammation  inflammation  inflammation  Immune response  cytokine  cytokine receptor  cytokine  cytokine receptor  cytokine  cytokine  Immune response  cytokine  cytokine  Immune response  Immune response  Immune response  inflammation  Immune response  Prototype Elicits Inflammation-related Gene Signature in Injected Tumors