Synlogic Inc · OTC:SYBX
Synlogic — Investor Presentation (June 2019)
36 slides from Synlogic's investor presentation, Jun 12, 2019
Slide 1: Synlogic Corporate Presentation June 2019
Synlogic DESIGNED FOR LIFE June 2019 Corporate Presentation Exhibit 99.1
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
Slide 3: Harnessing nature and technology to create living medicines
Harnessing nature and technology to create LIVING medicines designed to significantly improve patients’ LIVES Synthetic BioticTM Medicines Designed For Life
Slide 4: Synthetic Biotic Medicines: A Novel Class of Engineered Living Medicines
v Synthetic BioticTM Medicines A Novel Class of Engineered Living Medicines Designed genetic circuits to execute biological functions Degradation of disease-causing metabolites Production of therapeutic molecules Bacterial chassis Non-pathogenic Amenable to genetic manipulation PATHWAYS, COMBINATION
Slide 5: Synthetic Biotic Portfolio: Breadth and Potential
Synthetic Biotic Portfolio: Breadth and Potential Initial Applications Designed to Target Different Sites of Action in Metabolic and Immunomodulatory Diseases Oral Administration IMMUNOMODULATION METABOLIC DISEASES Immuno-Oncology Inflammatory and Autoimmune Small or Large Intestine “Cold” Solid Tum
Slide 6: Platform Collaboration to Accelerate Development of Synthetic Biotic Medicines
Builds off validated pilot program initiated in 2017 Provides access to Ginkgo’s industrial scale, high-throughput strain optimization and screening Enables screening and identification of higher quality optimized candidates, increasing potential for success Delivers novel tools for increased candid
Slide 7: Platform Collaboration with Ginkgo
Platform Collaboration to Accelerate Development of Synlogic’s Synthetic Biotic Medicines Industry leader in the construction and editing of microbial strains and organisms Leaders in non-therapeutic commercial applications of synthetic biology Comprehensive database of microbial genome sequences an
Slide 8: Investing in Development of a Robust Pipeline for Range of Diseases
Investing in Development of a Robust Pipeline for Range of Diseases Hyperammonemia – Urea Cycle Disorder Research IND-Enabling Studies Phase 1 Phase 2 Phenylketonuria Additional Rare Metabolic Diseases Hyperammonemia – Hepatic Encephalopathy (HE) Inflammatory Bowel Disease Immuno-Oncology Solid Tumo
Slide 9: SYNB1020 for Hyperammonemia: UCD and Hepatic Encephalopathy
UREA CYCLE DISORDERS (UCD) SYNB1020 for Hyperammonemia Indications Characterized by Systemic Ammonia Accumulation Neuropsychiatric complication in patients with end-stage liver disease (cirrhosis) Liver dysfunction leads to ammonia accumulation Toxic to brain, leading to HE crisis & hospitalization
Slide 10: SYNB1020 Mechanism of Action
Arginine Urea SYNB1020 Mechanism of Action: Under normal conditions, the urea cycle metabolizes ammonia into urea In UCD and HE, ammonia is not efficiently metabolized via urea cycle. SYNB1020 provides an alternative mechanism Conversion of Toxic Ammonia into Beneficial Arginine for the Treatment of
Slide 11: In vivo data demonstrate mechanism of action
In vivo data in mouse models and healthy volunteers demonstrate mechanism of action SYNB1020 data recently published in Science Translational Medicine PLASMA NITRATE URINARY NITRATE MOUSE MODEL
Slide 12: SYNB1020 Clinical Data in Healthy Volunteers
SYNB1020 Clinical Data in Healthy Volunteers Dose-dependent Increase in SYNB1020 in Feces, Clearance on Cessation of Dosing DOSE-DEPENDENT INCREASE IN FECES CLEARANCE Dosing period = 14 days Dosing period = 14 days Samples collected daily
Slide 13: SYNB1020 Clinical Development: Hepatic Encephalopathy Phase 1b/2a
SYNB1020 Clinical Development Hepatic Encephalopathy Phase 1b/2a in Patients with Cirrhosis and Elevated Ammonia Hepatic Encephalopathy Clinical Trial Randomized, double-blind placebo-controlled study ongoing at multiple sites in the US Primary outcome: establish safety/tolerability in patients with
Slide 14: SYNB1618 for Phenylketonuria (PKU)
PKU is a rare inherited amino acid metabolism disorder Causes build up of amino acid phenylalanine (Phe) in the body Today, less than half of adults are at or below target Phe levels of 120-360 mmol / L If left untreated, symptoms include cognitive impairment, convulsions, behavioral problems, skin
Slide 15: SYNB1618 Mechanism of Action
SYNB1618 Mechanism of Action Amino acids from dietary proteins (absorption and recirculation) Phe PKU Healthy Phenylalanine Hydroxylase (PAH) converts Phe into Tyrosine Tyrosine Accumulation of Phe to toxic levels Impaired PAH SYNB1618 Manage Phe levels When Phe is not efficiently metabolized (PKU)
Slide 16: SYNB1618 Preclinical Characterization
SYNB1618 Preclinical Characterization Biomarkers Demonstrate Activity of SYNB1618 in Mouse Model of PKU and Healthy NHPs IN VIVO EFFICACY IN (PKU) PAHenu2/enu2 MOUSE DOSE RESPONSE IN HEALTHY NHPs Nat. Biotechnol. 2018 Oct;36(9):857-864 Development of synthetic live bacterial therapeutic for the huma
Slide 17: SYNB1618 in the Clinic: Safety
SYNB1618 in the Clinic: Safety There 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 adverse events were GI-related Single dose MTD was defined as 2x1011 CFU. Doses a
Slide 18: SYNB1618 in the Clinic: Activity
SYNB1618 in the Clinic: Activity Statistically Significant Dose-dependent Activity of SYNB1618 in Healthy Volunteers SYNB1618 or placebo Protein shake / meal D5-Phe Measure over 6hrs: Plasma: Phe/D5-Phe TCA/D5-TCA Urine: HA/D5-HA TCA AUC SINGLE DOSE RESPONSE MAD URINARY HA AND D5-HA Key: HA: Hippura
Slide 19: SYNB1618 Clinical Development Phase 1/2a
SYNB1618 Clinical Development Phase 1/2a in Healthy Volunteers with Patient Cohort Phase 1 / 2a Phase 1 / 2a SAD / MAD Healthy Volunteers SD / MD PKU Patients PROGRAM PKU Clinical Trial Design Randomized, double-blind placebo-controlled study ongoing at multiple sites in the US Primary outcome: esta
Slide 20: Immuno-Oncology
© 2019 SYNLOGIC. ALL RIGHTS RESERVED. | Immuno-Oncology
Slide 21: Synlogic Vision for Immuno-Oncology
CHECKPOINT INHIBITORS HAVE TREATMENT FAILURES Synlogic Vision for Immuno-Oncology Expand the Benefits of Immunotherapy Broadly Across Tumor Types Other tumors, where CPIs are not indicated, show little-to-no response to checkpoint inhibitors Failure Rates for Select FDA Approved CPI Monotherapy 55%
Slide 22: Dual Innate Immune Activator: SYNB1891 Producing STING Agonist
Dual Innate Immune Activator: Synthetic Biotic Medicine Producing STING Agonist (SYNB1891) Synthetic biology applied to confer activities for efficacy and control for safety Designed as a dual innate immune activator: combined benefit of bacterial chassis and STING agonist The dacA gene is integrate
Slide 23: SYNB1891 In Vitro Characterization
SYNB1891 In Vitro Characterization Interferon Production Across Multiple Human STING Alleles – Activity Greater than Naked STING Agonist HUMAN PRIMARY DENDRITIC CELLS REPORTER HUMAN MONOCYTIC LINE Human STING Alleles STING Knockout
Slide 24: SYNB1891 In Vivo Characterization
SYNB1891 In Vivo Characterization d1 107, 5x107 or 108 CFU, i.t. (SYNB1891-PT1) A20 tumors ~100 mm3, randomize groups d7 d4 d18 Dose-dependent Anti-tumor Activity of SYNB1891 Prototype Strain (PT1) as a Single Agent Control Control SYNB1891-PT1 (1 x 107) SYNB1891-PT1 (5 x 107) SYNB1891-PT1 (1 x 108)
Slide 25: SYNB1891 In Vivo Characterization: Systemic Anti-tumor Immunity
SYNB1891 In Vivo Characterization SYNB1891 Prototype Strain (PT1) Leads to Systemic Anti-tumor Immunity SYNB1891-PT1 dose Re-challenge d1 108 CFU, i.t. (Bacteria) A20 tumors ~80-100 mm3, randomize groups d7 d4 d35 d63 Rechallenge (2e5 A20 cells) d1
Slide 26: Dual Innate Immune Activator SYNB1891
Dual Innate Immune Activator SYNB1891 Designed to Locally Inflame the TME and Systemically Drive Tumor Antigen-Specific Immunity Tumor Colonization without Leakage Enhanced Activity vs. Naked STING Agonist Intracellular Activation of STING and Bacterial-Induced Immune Pathways Within APCs Dose-depen
Slide 27: A Tumor Can Evade Multiple Aspects of the Cancer-Immunity Cycle
A Tumor Can Evade Multiple Critical Aspects of the Cancer-Immunity Cycle Killing Recognition Infiltration Antigen release Presentation Priming and activation T cell trafficking Insufficient activity/proliferation Immuno-suppression Insufficient trafficking Insufficient priming Recognized Need to Com
Slide 28: Additional Synthetic Biotic Effectors
Additional Synthetic Biotic Effectors VISION: Rational Design to Locally Inflame the TME AND Systemically Drive Tumor-Antigen Specific Immunity Chassis effect CXCL10 Hyaluronidase Kyn Consumption Ade Consumption αPD-1 scFv Chassis effect 5FCà5FU STING αCD40 scFv/CD40L TNFα IFNγ αCD47 ScFv / Sirpα GM
Slide 29: Broad Ambitions in Immuno-Oncology
Broad Ambitions in Immuno-Oncology SYNB1891 DISCOVERY PORTFOLIO INTRATUMORAL Vision: Expand and Exceed the Effect of Cancer Immunotherapies COMBINATIONS HARNESS THE MICROBIOME ORAL
Slide 30: Synlogic Internal GMP Manufacturing Capabilities
Synlogic Internal GMP Manufacturing Capabilities In-house Process Development and Clinical Manufacturing for Early & Mid-Stage Trials Biotherapeutic Manufacturing Candidate Selection & Process Dev. Testing (in vitro and in vivo) Strain Engineering Optimized Process Scale-up Process development and l
Slide 31: Progress in Development of Lyophilized SYNB1618
Demonstrated Progress in Development of Lyophilized SYNB1618 Improved fermentation process enables production of a solid formulation of SYNB1618 with minimal impact on cell viability or activity Lyophilized SYNB1618 is similarly active to frozen liquid in terms of consumption of Phe or production of
Slide 32: Batch to Batch Consistency of SYNB1618 Solid Formulation
Batch to Batch Consistency of SYNB1618 Solid Formulation Viability Activity in WT mice
Slide 33: Stability of SYNB1618 Solid Formulation
Stability of SYNB1618 Solid Formulation
Slide 34: 2019 Progress and Milestones
2019 Progress and Milestones SYNB1618 in PKU Complete ongoing study in patients Data expected 3Q2019 (safety, tolerability and biomarkers) SYNB1020 in Hyperammonemia Preclin. and HV clin. data published in Sci. Transl. Med. Complete ongoing study in patients with cirrhosis Data expected 3Q2019 (safe
Slide 35: Harnessing nature and technology to create living medicines
Harnessing nature and technology to create LIVING medicines designed to significantly improve patients’ LIVES Synthetic BioticTM Medicines Designed For Life
Slide 36: Synlogic contact details
301 BINNEY ST., #402, CAMBRIDGE, MA 02142 TEL: 617-401-9975 WEB: WWW.SYNLOGICTX.COM | EMAIL: INFO@SYNLOGICTX.COM © SYNLOGIC. CONFIDENTIAL. ALL RIGHTS RESERVED.