Synlogic Inc · OTC:SYBX
Synlogic — H. C. Wainwright 20th Annual Global Investment Conference (September 2018)
28 slides from Synlogic's conference presentation, Sep 5, 2018
Slide 1: H. C. Wainwright 20th Annual Global Investment Conference
H. C. Wainwright 20th Annual Global Investment ConferenceAoife Brennan, M.B., B.Ch., Interim President and CEO, & CMO September 5, 2018 A Novel Class of Living Medicines Synthetic BioticTM medicines to perform and deliver critical therapeutic functions to treat diseases throughout the body
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: A Novel Class of Living Medicines
Synthetic BioticTM 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 substan
Slide 4: Advantages of a Synthetic Biotic Approach
Advantages of a Synthetic Biotic Approach: Unique Mechanisms to Treat Systemic Metabolic and Immune Dysfunction Can program bacteria to execute an entire metabolic pathway multiple therapeutic functions with potencyand generate biomarkers of activitySwitches provide ability to control or “tune” func
Slide 5: Synthetic Biotic Platform Breadth and Potential
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 Diseas
Slide 6: Synthetic Biotic Platform Breadth and Potential: Current Pipeline
Synthetic Biotic Platform Breadth and Potential:Current Pipeline 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 Acidemi
Slide 7: Initial Synthetic Biotic Programs: Different Sites of Action
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 Intra-tumoral Administration IO program: Site o
Slide 8: SYNB1020 for Hyperammonemia
SYNB1020 for Hyperammonemia Indications: Urea Cycle Disorders (UCD) and Hepatic Encephalopathy (HE) Both diseases are characterized by systemic ammonia accumulation Diminished/absent urea cycle activity Ammonia Ammoniabuild up (toxic levels) Urea cycle ! Liver Disease or UCD Urea Cycle DisordersGene
Slide 9: SYNB1020 Mechanism of Action
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 alternat
Slide 10: SYNB1020 Preclinical Characterization
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 1x
Slide 11: SYNB1020 in Healthy Volunteers
Dose dependent steady-state SYNB1020 qPCR Clinical Data SYNB1020 in Healthy Volunteers: Dose-Dependent Increase in SYNB1020 in Feces, Clearance on Cessation of Dosing Steady-state qPCR copy number increases with increasing SYNB1020 dose SYNB1020 clearance within 2 weeks following completion of dosin
Slide 12: Nitrate as a Biomarker for SYNB1020 Activity
Nitrate as a Biomarker for SYNB1020 Activity
Slide 13: SYNB1020 Clinical Development: Next Steps
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 – HE study initiated Urea Cycle DisordersDemonstrate safety/tolerability in adults with late onset UCDInitiate Phase
Slide 14: SYNB1618 for Phenylketonuria (PKU)
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 in all proteinsDiagnosed: 16,500 in US, similar
Slide 15: SYNB1618 Mechanism of Action
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 (HA) Manage Phe l
Slide 16: Preclinical data: Biomarkers demonstrate activity of SYNB1618
Preclinical data: Biomarkers demonstrate activity of SYNB1618 in mouse model of PKU and healthy NHPs In vivo activity and efficacy of SYNB1618 in mouse model of (PKU) Pahenu2/enu2 Dose response and PD of SYNB1618 in healthy NHPs
Slide 17: SYNB1618 in the Clinic: Safety
SYNB1618 in the Clinic: SafetyInterim Analysis of Phase 1/2a SAD/MAD Study Healthy Volunteer Cohorts The study enrolled 56 healthy volunteers, all of whom received at least one dose of SYNB1618 or placebo. The subjects were predominantly male Caucasians and the age range of enrolled subjects was 18-
Slide 18: SYNB1618 in the Clinic: Dose-dependent activity in healthy volunteers
SYNB1618 in the Clinic: Statistically significant dose-dependent activity of SYNB1618 in healthy volunteers
Slide 19: SYNB1618 in the Clinic: Phase 1/2a SAD/MAD
SYNB1618 in the Clinic:Phase 1/2a SAD/MAD in Healthy Volunteers with Patient Cohort 2017 2018 2019 Q1 Q2 Q3 Q4 Q1 Q2 IND enabling studies SD/MD Patient cohorts SAD / MAD HV Goal: assess safety, tolerability and kinetics in healthy volunteers across a range of dosesIncludes cohorts of SD/MD PKU patie
Slide 20: Synthetic Biotic Medicines: Applicability Beyond Rare Disease
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, Serotoni
Slide 21: Synlogic Vision for Immuno-Oncology: Turn a Cold Tumor Hot
Synlogic Vision for Immuno-Oncology: Living Medicines to Turn a “Cold” Tumor “Hot” Dendritic Cells T Cells Tumor antigen-specific, systemic T cell immunity Synthetic Biotic therapyImmune Initiator (innate) + Immune Sustainer (adaptive) Non-inflamed “cold” tumor Inflamed “hot” tumor
Slide 22: Synlogic Vision for Immuno-Oncology: High Response Rates
Synlogic Vision for Immuno-Oncology: Living Medicines with High Response Rates and Abscopal Effect as Single Agents Immune Initiator Immune Sustainer Concept: 1 Single Drug Antigen Release, Immune Activation & Priming Immune Augmentation & T Cell Expansion 2 mechanistic modules
Slide 23: Design of Initiator SYN-STING and Sustainer SYN-Kyn
Design of Initiator SYN-STING and Sustainer SYN-Kyn
Slide 24: Initiator (STING) Module Characterization
Initiator (STING) Module Characterization: STING Agonist Producer with Anti-tumor Activity as Single Agent (B16F10) Dose-dependent inhibition of tumor growth (A20)
Slide 25: Sustainer (Kyn) Module Characterization
Sustainer (Kyn) Module Characterization : Consumes Kynurenine - Arrests Tumor Growth in Combination; Increased Response Rates as Triple Combo Kyn-consuming strain reprograms the tumor microenvironment by depleting kynurenine Time (hr) Kyn (mM) Tumor PD Naive SYN SYN-KYN 0 2 4 7 2 1 6 8 0.0 0.2 0.4 0
Slide 26: Synlogic Development Pipeline: Programs' Timelines Summary
Synlogic Development Pipeline:Programs’ Timelines Summary 2018 2019 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 SD/MD Patient Cohort HE Ph 1b / 2a IND enabling studies UCD Ph 1b / 2a PKU Program IO UCD HE SAD/MAD HV
Slide 27: Synlogic Synthetic Biotic Platform: Bringing Rational Drug Development to the Microbiome
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
Slide 28: Synlogic
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