EX-99.1 2 a51860948ex99_1.htm EXHIBIT 99.1

Exhibit 99.1
     Discussion of Interim Analysis of Data from Phase 1/2a Clinical Trial of SYNB1618  September 4, 2018  A Novel Class of Living Medicines  Synthetic BioticTM medicines to perform and deliver critical therapeutic functions to treat diseases throughout the body 

 Forward-Looking Statements   This presentation and various remarks which may be made during this presentation contain “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, including statements regarding Synlogic’s plans and expectations for the development of SYNB1618. All statements, other than statements of historical facts, regarding strategy, future operations, future financial position, future revenue, projected expenses, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this presentation and various remarks which may be made during this presentation, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants, as they relate to Synlogic may identify forward-looking statements. Examples of forward-looking statements, include, but are not limited to, statements regarding the potential of Synlogic’s platform to develop therapeutics to address a wide range of diseases including: cancer, inborn errors of metabolism, liver disease, and inflammatory and immune disorders; the future clinical development of Synthetic Biotic medicines; the approach Synlogic is taking to discover and develop novel therapeutics using synthetic biology; and the expected timing of Synlogic’s clinical trials and availability of clinical trial data. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including: the uncertainties inherent in the preclinical development process; the ability of Synlogic to protect its intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading “Risk Factors” in Synlogic’s filings with the SEC. The forward-looking statements reflect Synlogic’s current views with respect to future events. Synlogic anticipates that subsequent events and developments will cause its views to change. However, while Synlogic may elect to update these forward-looking statements in the future, Synlogic specifically disclaims any obligation to do so. These forward-looking statements should not be relied upon as representing Synlogic’s view as of any date subsequent to the date hereof.  

 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 Acidemias    Maple Syrup Urine Disease    Inflammatory Bowel Disease    Immuno Oncology 2    Hyperammonemia -Hepatic Encephalopathy  Immuno Oncology 3    SYNB1020 

 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 in EU5If left untreated, symptoms include cognitive impairment, convulsions, behavior problems, skin rashTreatment: Low protein diet (no meat, dairy, nuts, eggs)Kuvan: PAH cofactor. 20-40% of patientsPalynziq: injectable, pegylated, bacterial enzyme (PAL) (Adults)  Target Profile to Address Unmet Need:Manage Phe: Currently < half adults at target (120 - 360 mmol / L, source: NPKUA)Increase natural protein intake (less than 10g typically)Oral dosing without systemic toxicity 

   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 levels      Phenylalanine  t-CinnamicAcid      Metabolic Conversions  PheP: High-Affinity Uptake  FNR  FNR  PAL3  FNR  FNR  pheP  LAAD  AraC  AraC  t-Cinnamic Acid (TCA)  SYNB1618  When Phe is not efficiently metabolized (PKU) SYNB1618 provides an alternative mechanismPAL3 - Produces TCA which is converted to HA in the liver and is excreted in urineLAAD – Produces (PP)  Accumulation of Phe to toxic levels  Phenylalanine  Probiotic bacteria: E. Coli NissleComponents of Synthetic Genetic Circuit  Phenylpyruvate (PP)         

                           5x1010 CFU   7x1010 CFU   1x1010 CFU     1x1011 CFU                 5x1011 CFU  5x1010 CFU     1x1010 CFU  1x1011 CFU  2x1011 CFU  Timeline   Interim Analysis: TCA, HA production in HVs  1x1011 CFU / solid food  A randomized, double-blind, placebo-controlled study to assess the safety, tolerability of SYNB1618 in healthy volunteers across a range of doses; includes cohort of SAD / MAD PKU patients  Healthy Volunteer SAD:Single dose / day  PKU Single dose N=4  Healthy Volunteer MAD:7 day Dosing   SYNB1618 in the Clinic: Study DesignPhase 1/2a SAD/MAD in Healthy Volunteers with Patient Cohort  PKU Multi dose N=up to 20  H1 2018  H2 2018  2019  HV MAD:6:2 active to placebo (8 subjects per cohort)4 cohorts: 32 HVs  HV SAD:3:1 active to placebo (4 subjects per cohort) 6 cohorts: 24 HVs     

 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 18-62 yearsThere 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 AEs were GI-relatedAll subjects cleared the bacteria. There was no evidence of colonization, and no subject required antibioticsSingle dose MTD was defined as 2x1011 CFU. Doses above this level were associated with dose-limiting GI adverse eventsBased on pharmacodynamic data and tolerability profile a dose was identified for the second part of the study in PKU patients 

 Statistically significant dose-dependent activity of SYNB1618 in healthy volunteers 

   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 patientsInterim read: trans-Cinnamic acid and Hippuric acid production in healthy volunteersStudy duration: ~12 months      Q4    Q3