Synlogic Inc · OTC:SYBX
Synlogic — Investor Presentation (March 2019)
34 slides from Synlogic's investor presentation, Mar 20, 2019
Slide 1: Synlogic Corporate Presentation March 2019
Synlogic DESIGNED FOR LIFE Corporate PresentationMarch 2019
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: Synthetic Biotic Medicines: Designing for LIFE
Synthetic BioticTM Medicines Designing for LIFE Patient NeedThere remain many indications for which conventional medicines do not provide effective solutions for all patients Conventional Approaches LimitedSingle mechanism agents do not address complex biology, often lead to systemic exposure withou
Slide 4: A Novel Class of Engineered Living Medicines
v Synthetic BioticTM Medicines A Novel Class of Engineered Living Medicines Designed genetic circuits to execute biological functionsDegradation of disease-causing metabolitesProduction of therapeutic molecules Bacterial chassisNon-pathogenicAmenable to genetic manipulation PATHWAYS, COMBINATIONS, B
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: Synthetic Biotic Portfolio
Synthetic Biotic Portfolio 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 Tumors Additional Oncology Applications SYNB1
Slide 7: SYNB1020 for Hyperammonemia
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 accumulationToxic to brain, leading to HE crisis & hospitalizationPat
Slide 8: SYNB1020 Mechanism of Action
Arginine Urea SYNB1020 Mechanism of Action: Under normal conditions, the urea cycle metabolizes ammonia into ureaIn 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 9: 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 10: 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 daysSamples collected daily
Slide 11: SYNB1020 Clinical Development: Hepatic Encephalopathy
SYNB1020 Clinical Development Hepatic Encephalopathy Phase 1b/2a in Patients with Cirrhosis and Elevated Ammonia Hepatic Encephalopathy Clinical TrialRandomized, double-blind placebo-controlled study ongoing at multiple sites in the US Primary outcome: establish safety/tolerability in patients with
Slide 12: SYNB1618 for Phenylketonuria (PKU)
PKU is a rare inherited amino acid metabolism disorder Causes build up of amino acid phenylalanine (Phe) in the bodyToday, less than half of adults are at or below target Phe levels of 120-360 mmol / LIf left untreated, symptoms include cognitive impairment, convulsions, behavioral problems, skin ra
Slide 13: 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 14: Iteration Potential Advantage of Synthetic Biotic Design
Iteration Potential Advantage of Synthetic Biotic Design Build Test Cycle 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+ SYNB1618 LEAD OPTIMIZATION
Slide 15: 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 NHP’s Nat. Biotechnol. 2018 Oct;36(9):857-864 Development of synthetic live bacterial therapeutic for the hum
Slide 16: 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-relatedSingle dose MTD was defined as 2x1011 CFU. Doses ab
Slide 17: 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-PheTCA/D5-TCAUrine: HA/D5-HA TCA AUC SINGLE DOSE RESPONSE MAD URINARY HA AND D5-HA Key: HA: Hippurate, D
Slide 18: SYNB1618 Clinical Development
SYNB1618 Clinical Development Phase 1/2a in Healthy Volunteers with Patient Cohort 2018 2019 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Phase 1 / 2a Phase 1 / 2a SAD / MAD Healthy Volunteers SD / MDPKU Patients PROGRAM PKU Clinical Trial DesignRandomized, double-blind placebo-controlled study ongoing at multiple sites
Slide 19: Immuno-Oncology
© 2019 SYNLOGIC. ALL RIGHTS RESERVED. | 19 Immuno-Oncology
Slide 20: 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 21: 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 Insufficientactivity/proliferation Immuno-suppression Insufficient trafficking Insufficient priming Recognized Need to Comb
Slide 22: Intra-tumoral Injection of Synthetic Biotic Chassis
BEHAVIOR WITHIN TUMOR CHASSIS DISTRIBUTION Intra-tumoral Injection of Synthetic Biotic Chassis: Tumor Colonization Without Leakage; Local Innate Immunity Robust proliferation in tumor.No significant leakage in B16.F10 Mice Survival/proliferation in tumors 10-15 days post-single dose. Potential for l
Slide 23: Dual Innate Immune Activator: SYNB1891
Dual Innate Immune Activator:Synthetic Biotic Medicine Producing STING Agonist (SYNB1891) Synthetic biology applied to confer activities for efficacy and control for safetyDesigned as a dual innate immune activator: combined benefit of bacterial chassis and STING agonistThe dacA gene is integrated i
Slide 24: Innate Immune Activation through Multiple Pathways
Innate Immune Activation through Multiple Pathways Uniquely Signals Through CDN-STING and Bacterial Chassis in Target Cells to Drive Efficacy CDN-STINGActivation SYN-STING Naked STING Agonist Gram-negative BacteriaE. coli Nissle TLR4 IFN-b1 Type 1 IFN P IRF3 Phagosome CDNsC-di-AMP STING BACTERIALT
Slide 25: SYNB1891 In Vitro Characterization
SYNB1891 In Vitro Characterization Interferon Production Across Multiple Human STING Alleles Greater than Naked STING Agonist Additional Proinflammatory Pathways Engaged HUMAN PRIMARY DENDRITIC CELLS REPORTER HUMAN MONOCYTIC LINE Human STING Alleles STING Knockout
Slide 26: 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 27: 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 28: Dual Innate Immune Activator SYNB1891
Dual Innate Immune Activator SYNB1891 A STING Agonist-producing Synthetic Biotic Designed to Locally Inflame the TME and Systemically Drive Tumor Antigen-Specific Immunity Tumor Colonization without LeakageEnhanced Activity vs. Naked STING AgonistIntracellular Activation of STING and Bacterial-Induc
Slide 29: Additional Synthetic Biotic Effectors
Additional Synthetic Biotic Effectors VISION: Rational Design to Locally Inflame the TME AND Systemically Drive Tumor-Antigen Specific Immunity Chassis effectCXCL10Hyaluronidase Kyn ConsumptionAde ConsumptionαPD-1 scFv Chassis effect5FC5FUSTINGαCD40 scFv/CD40L TNFαIFNγαCD47 ScFv / SirpαGM-CSF TUMOR
Slide 30: 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 31: 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 OptimizedProcess Scale-up Process development and la
Slide 32: Progress and 2019 Milestones
Progress and 2019 Milestones 2019 Milestones SYNB1618 in PKUComplete ongoing study in patientsData expected mid-2019 (safety, tolerability and biomarkers)SYNB1020 in HyperammonemiaPreclin. and HV clin. data published in Sci. Transl. Med.Complete ongoing study in patients with cirrhosisData expected
Slide 33: Synlogic summary statements
© 2019 SYNLOGIC. ALL RIGHTS RESERVED. | 33 Synlogic is designing microbes that are engineered to compensate for missing functions in a variety of diseases The Company has demonstrated that Synthetic Biotic medicines function as designed in humans Synlogic is building a path to a broad portfolio of p
Slide 34: Contact information
301 BINNEY ST., #402, CAMBRIDGE, MA 02142TEL: 617-401-9975WEB: WWW.SYNLOGICTX.COM | EMAIL: INFO@SYNLOGICTX.COM© SYNLOGIC. CONFIDENTIAL. ALL RIGHTS RESERVED.