Synlogic Inc · OTC:SYBX
Synlogic — Investor Presentation (August 2019)
34 slides from Synlogic's investor presentation, Aug 20, 2019
Slide 1: Synlogic Corporate Presentation August 2019
Synlogic DESIGNED FOR LIFE August 2019Corporate Presentation
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 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: Investing in Development of a Robust Pipeline for a Range of Diseases
Investing in Development of a Robust Pipeline for a Range of Diseases Research IND-Enabling Studies Phase 1 Phase 2 Phenylketonuria Additional Rare Metabolic Diseases Inflammatory Bowel Disease Immuno-Oncology Solid Tumors Additional Oncology Applications SYNB1618 SYNB1891 Rare Metabolic DiseasesImm
Slide 7: Metabolic Disease Pipeline
© 2019 SYNLOGIC. ALL RIGHTS RESERVED. | 7 Metabolic Disease Pipeline
Slide 8: 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 9: 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 10: 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 11: SYNB1618 Phase 1/2a Study Design
SYNB1618 Phase 1/2a Study Design Single Ascending Dose (SAD)6 cohorts, N = 24 Multiple Ascending Dose (MAD)- TID x 7 days4 cohorts, N = 32 Dose ID Single Dose (SD)N = 4 Multiple Dose (MD)TID x 7 daysN =10 Dose Confirm MTD Part 1: Healthy Volunteers (HV) Part 2: PKU Patients PKU Clinical Trial Design
Slide 12: 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 in healthy volunteers was defined a
Slide 13: SYNB1618 in the Clinic: Activity
SYNB1618 in the Clinic: Activity Statistically Significant and Equivalent Activity of SYNB1618 in Healthy Volunteers and Patients SYNB1618 or placebo Protein shake /meal D5-Phe Measure over 6hrs:Plasma:Phe/D5-PheTCA/D5-TCAUrine: HA/D5-HA Key: HA: Hippurate, D5-HA: labeled HA, CFB: change from baseli
Slide 14: Modeling: Potential For Phe Reduction in PKU Patients
Modeling: Potential For Phe Reduction in PKU Patients % Blood Phe lowering 7x1010 1x1011 3x1011 5x1011 125100755025 TPP >30% SYNB1618 Dose (CFU) 8-18% 11-26% 34-79% 57-131% Ranges representLow: PAL mechanism only (conservative) High: PAL + LAAD activity (estimates maximum with both pathways)
Slide 15: SYNB1618 Potential to Address Unmet Need Across Patient Groups
SYNB1618 Potential to Address Unmet Need Across Patient Groups 360 mmol /L Uncontrolled Adults Partially Controlled Adults(Adults on Kuvanand/or low-Phe Diet) Pediatric Patients (controlled / partially controlled) (Pediatric patients on Kuvan and / or low-Phe diet Phe Natural protein Phe Phe Initial
Slide 16: Development of Lyophilized SYNB1618
Development of Lyophilized SYNB1618 Improved fermentation process enables production of a solid formulation of SYNB1618 with: Minimal impact on cell viability and activitySimilar activity to frozen liquid as measured by Phe consumption and biomarker productionImproved quality attributesPatient and c
Slide 17: Batch to Batch Consistency of SYNB1618 Solid Formulation
Batch to Batch Consistency of SYNB1618 Solid Formulation Viability Activity in WT mice
Slide 18: Stability of SYNB1618 Solid Formulation
Stability of SYNB1618 Solid Formulation
Slide 19: Upcoming Milestones and Path Forward
Upcoming Milestones and Path Forward Established new solid formulation and manufacturing process Completed EPO1 interactions with FDA to align on program plans (clinical, manufacturing, toxicology) Completed Phase 1/2a study (healthy volunteers and PKU patients)Initiate bridging study with solid for
Slide 20: Immuno-Oncology Pipeline
© 2019 SYNLOGIC. ALL RIGHTS RESERVED. | 20 Immuno-Oncology Pipeline © 2019 SYNLOGIC. ALL RIGHTS RESERVED. CONFIDENTIAL | 20
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: Synthetic Biotic Producing STING Agonist (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 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 LeakageEnhanced Activity vs. Naked STING AgonistIntracellular Activation of STING and Bacterial-Induced Immune Pathways Within APCsDose-dependen
Slide 27: A Tumor Can Evade Multiple Critical 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 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 effectCXCL10Hyaluronidase Kyn ConsumptionAde ConsumptionαPD-1 scFv Chassis effect5FC5FUSTINGαCD40 scFv/CD40L TNFαIFNγαCD47 ScFv / SirpαGM-CSF TUMOR
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 OptimizedProcess Scale-up Process development and la
Slide 31: Platform Collaboration with Ginkgo
Builds off validated pilot program initiated in 2017 Provides access to Ginkgo’s industrial scale, high-throughput strain optimization and screeningEnables screening and identification of higher quality optimized candidates, increasing potential for success Delivers novel tools for increased candida
Slide 32: 2019 Progress and Milestones
2019 Progress and Milestones SYNB1618 in PKUCompleted Phase 1/2a study in healthy volunteers and patients, top-line data presentedFull data presentation Sept. 2019 (SSIEM)Bridging study initiatedSYNB1020 in HyperammonemiaPreclin. and HV clin. data published in Sci. Transl. Med.Completed Phase 1b/2a
Slide 33: 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 34: BINNEY ST., #402, CAMBRIDGE, MA 02142TEL: 617-401-9975WEB: WWW.SYNLOGICTX.COM | EMAIL: INFO@SYNLOGICTX.COM© SYNLOGIC.…
301 BINNEY ST., #402, CAMBRIDGE, MA 02142TEL: 617-401-9975WEB: WWW.SYNLOGICTX.COM | EMAIL: INFO@SYNLOGICTX.COM© SYNLOGIC. CONFIDENTIAL. ALL RIGHTS RESERVED.