Synlogic Inc · OTC:SYBX

Synlogic — Investor Presentation (November 2018)

35 slides from Synlogic's investor presentation, Nov 19, 2018

  1. Slide 1: Corporate Presentation

    Corporate Presentation Designed for life November 2018

  2. Slide 2: Forward Looking Statements

    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

  3. Slide 3: Synthetic Biotic Medicines: A Novel Class of Living Medicines

    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 Programm

  4. Slide 4: Pipeline Focused on Three Therapeutic Areas

    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 O

  5. Slide 5: Initial Synthetic Biotic Programs: Different Sites of Action

    © 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 Int

  6. Slide 6: SYNB1020 for Hyperammonemia

    © 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 Neu

  7. Slide 7: SYNB1020 Mechanism of Action

    © 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 provi

  8. Slide 8: SYNB1020 Preclinical Characterization

    © 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 Per

  9. Slide 9: SYNB1020 Clinical Data in Healthy Volunteers

    © 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

  10. Slide 10: Nitrate as a Biomarker for SYNB1020 Activity

    © 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

  11. Slide 11: SYNB1020 Clinical Development

    © 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: establi

  12. Slide 12: SYNB1618 for Phenylketonuria (PKU)

    © 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

  13. Slide 13: SYNB1618 Mechanism of Action

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

  14. Slide 14: Preclinical Characterization of SYNB1618

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

  15. Slide 15: SYNB1618 in the Clinic: Safety

    © 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 subjec

  16. Slide 16: SYNB1618 in the Clinic: Activity

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

  17. Slide 17: SYNB1618 Clinical Development

    © 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

  18. Slide 18: Synlogic Vision for Immuno-Oncology

    © 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 check

  19. Slide 19: A Tumor Can Evade Multiple Aspects of the Cancer-Immunity Cycle

    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

  20. Slide 20: Engineer a Living Solution: Synthetic Biotic Medicines

    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 Rec

  21. Slide 21: Intra-tumoral Injection of Synthetic Biotic Chassis

    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/proliferat

  22. Slide 22: Synthetic Biotic Medicines Engineered for Efficacy

    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 Activ

  23. Slide 23: Synthetic Biotic Medicines Attributes

    © 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

  24. Slide 24: Dual Innate Immune Activator: SYN-STING

    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-d

  25. Slide 25: Dual Innate Immune Activator

    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 CYTOSO

  26. Slide 26: In Vitro Characterization of SYNB1891

    © 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 Sol

  27. Slide 27: In Vitro: STING Agonist Induction by SYN-STING

    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

  28. Slide 28: In Vivo: SYN-STING Anti-tumor Activity in B16.F10 Model

    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 activa

  29. Slide 29: SYN-STING Dose-Dependent Tumor Control in A20 Lymphoma Model

    © 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

  30. Slide 30: In Vivo Characterization of SYNB1891

    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

  31. Slide 31: In Vivo Characterization of SYNB1891

    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

  32. Slide 32: Dual Innate Immune Activator SYNB1891

    © 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 o

  33. Slide 33: Additional Synthetic Biotic Effectors

    © 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 Synt

  34. Slide 34: Broad Ambitions in Immuno-Oncology

    © 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

  35. Slide 35: © 2018 Synlogic, Inc. All rights reserved.

    © 2018 Synlogic, Inc. All rights reserved.

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