Synlogic Inc · OTC:SYBX
Synlogic — 2019 Wedbush PacGrow Healthcare Conference
29 slides from Synlogic's conference presentation, Aug 13, 2019
Slide 1: 2019 Wedbush PacGrow Healthcare Conference
Synlogic DESIGNED FOR LIFE 2019 Wedbush PacGrow Healthcare ConferenceScott Plevy, MD, Chief Scientific OfficerAugust 13, 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: 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 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 Tu
Slide 7: Metabolic Disease Pipeline
© 2019 SYNLOGIC. ALL RIGHTS RESERVED. | 7 Metabolic Disease Pipeline
Slide 8: SYNB1020 for Hyperammonemia Indications
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 9: SYNB1020 Mechanism of Action
Arginine Urea SYNB1020 Mechanism of Action: Dose-responsive ammonia lowering in multiple preclinical models Conversion of Toxic Ammonia into Beneficial Arginine for the Treatment of UCD and HE Ammonia/NH4Cl UreaCycle Converts ammonia to Arginine Can re-enter the Urea Cycle Ammonia metabolism blocked
Slide 10: SYNB1020 Clinical Data in Healthy Volunteers
SYNB1020 Clinical Data in Healthy Volunteers Dose-dependent Exposure, Clearance on Cessation of Dosing and Strain Activity DOSE-DEPENDENT INCREASE IN FECES PLASMA NITRATE URINARY NITRATE CLEARANCE
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 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 14: 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 SYNB1618 provides an alternative mechanismPAL3
Slide 15: 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 Part 2: PKU Patients PKU Clinical Trial DesignRando
Slide 16: SYNB1618 in the Clinic: Safety
SYNB1618 in the Clinic: Safety No treatment-related SAEs, no systemic toxicity or infections Mild or moderate severity treatment-related AEs. Most GI-relatedSingle dose MTD in healthy volunteers 2x1011 CFU Evaluated dose of 7x1010 CFU TID over seven days in PKU patients. Well tolerated - no disconti
Slide 17: 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 basel
Slide 18: 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 19: 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 20: SYNB1618 Milestones
SYNB1618 Milestones 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)Initiated bridging study with solid formulation Q3 2019
Slide 21: Immuno-Oncology Pipeline
© 2019 SYNLOGIC. ALL RIGHTS RESERVED. | 21 Immuno-Oncology Pipeline © 2019 SYNLOGIC. ALL RIGHTS RESERVED. CONFIDENTIAL | 21
Slide 22: 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 23: Dual Innate Immune Activator (SYNB1891)
Dual Innate Immune Activator: 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 into genome under the control of inducible promoter (Pfnr) to
Slide 24: SYNB1891 Designed to Locally Inflame the TME
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 25: 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 26: 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 27: 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.Complete ongoing study
Slide 28: 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 29: 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.
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