SEC Filing - Synlogic

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

_________________________________________________________________________________

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): August 13, 2019

SYNLOGIC, INC.

(Exact name of registrant as specified in its charter)

Delaware		001-37566		26-1824804
(State or other jurisdiction of incorporation)		(Commission File Number)		(IRS Employer Identification No.)

301 Binney St., Suite 402 Cambridge, MA		02142
(Address of principal executive offices)		(Zip Code)

Registrant’s telephone number, including area code: (617) 401-9975

Not applicable
(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock	SYBX	The Nasdaq Capital Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).

Emerging Growth Company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☒

Item 7.01. Regulation FD Disclosure.

On August 13, 2019, Synlogic, Inc. (the “Company”) updated its investor presentation (the “Investor Presentation”), which the Company expects to use in connection with general corporate presentations and will be made available on the Company’s website or distributed by the Company in hardcopy or electronic form.

A copy of the Company’s updated Investor Presentation is attached as Exhibit 99.1 to this Current Report on Form 8-K. The Investor Presentation is current as of August 13, 2019, and the Company disclaims any obligation to update the Investor Presentation after such date.

In accordance with General Instruction B.2 on Form 8-K, the information set forth in this Item 7.01 and the Investor Presentation attached to this report as Exhibit 99.1 is “furnished” and shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section, nor shall such information be deemed incorporated by reference in any filing under the Securities Exchange Act of 1934, as amended, or the Securities Act of 1933, as amended.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits

99.1 Investor Presentation of Synlogic, Inc., dated August 13, 2019

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	SYNLOGIC, INC.


Date: August 13, 2019	By:	/s/ Todd Shegog
	Name:	Todd Shegog
	Title:	Chief Financial Officer

Exhibit 99.1

Synlogic DESIGNED FOR LIFE 2019 Wedbush PacGrow Healthcare ConferenceScott Plevy, MD, Chief Scientific OfficerAugust 13, 2019

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 this presentation 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, the words “may,” “could,” “should,” “anticipate,” “believe,” “estimate,” “expect,” “intend,” “plan,” “predict” and similar expressions and their variants may identify forward-looking statements. Examples of forward-looking statements include, but are not limited to, the approach we are taking to discover and develop novel therapeutics using synthetic biology; statements regarding the potential of our platform to develop therapeutics to address a wide range of diseases, including: inborn errors of metabolism, liver disease, inflammatory and immune disorders, and cancer; the future clinical development of Synthetic Biotic medicines; the potential of our technology to treat hyperammonemia and phenylketonuria; the expected timing of our anticipated clinical trial initiations; the benefit of orphan drug and fast track status; the adequacy of our capital to support our future operations and our ability to successfully initiate and complete clinical trials; the results of our collaborations; and the difficulty in predicting the time and cost of development of our product candidates. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the uncertainties inherent in the preclinical development process; our ability to protect our intellectual property rights; and legislative, regulatory, political and economic developments, as well as those risks identified under the heading “Risk Factors” in our filings with the SEC. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in our Annual Report on Form 10-Q filed with the SEC on August 8, 2019. The forward-looking statements contained in this presentation reflect our current views with respect to future events. We anticipate that subsequent events and developments will cause our views to change. However, while we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so. These forward-looking statements should not be relied upon as representing our view as of any date subsequent to the date hereof.

Harnessing nature and technology to create LIVING medicines designed to significantly improve patients’ LIVES Synthetic BioticTM Medicines Designed For Life

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, BIOMARKERS PROGRAMMABLE POTENCY AND CONTROL LOCAL ACTIVITY, REDUCED SYSTEMIC TOXICITY BIOTIC SYNTHETIC

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 Tumors Small or Large Intestine Rare MetabolicDisease BroadMetabolicDisease

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 Tumors Additional Oncology Applications SYNB1020 SYNB1618 SYNB1020 SYNB1891 Rare Metabolic DiseasesBroad Metabolic DiseaseImmunomodulation

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 & hospitalizationPatients: 165,000 diagnosed overt patients in USUp to 70% of patients with cirrhosis characterized as covert (subclinical)Treatment: Lactulose: laxative with significant side effectsRifaximin: reduction in overt HE recurrence Genetic defects in Urea CycleDeficiency in one of the six enzymes Nitrogen accumulates as toxic ammonia leading to metabolic crisisPatients: ~2,000 diagnosed in US; similar in EUTreatment: Ammonia scavengers: Buphenyl® (sodium phenylbutyrate), Ravicti® (glycerol phenylbuterate)Low protein diet with amino acid supplements Target Profile to Address Unmet Need:Reduce episodes of hospitalizationImprove cognitive outcomes, Quality of Life HEPATIC ENCEPHALOPATHY (HE) Target Profile to Address Unmet Need:Maintain blood ammonia in normal range, avoid crisisProtein liberalization: 50-100% more per dayOral administration

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 in disease

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

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 cirrhosis and elevated ammoniaSecondary outcome: reduction of ammonia 2018 2019 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Phase 1b / 2a PROGRAM Hepatic Encephalopathy Mild Cirrhosis Patients, MELD1<12, Open label, TID for 6 days Sentinel cohort for safetyN = 6 Cirrhosis Patients: MELD < 20 & Elevated Ammonia; RCT, TID for 6 days Proof of MechanismN up to 40 Safety Evaluation Part 1 Part 2 1. MELD score: scoring system model for end-stage liver disease Urea Cycle Disorders(Plans to continue development in UCD dependent on data from Ph 1b/2a HE study)

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 rashPatients:16,500 diagnosed in US, similar in EU5Treatment: Phenylalanine is found in all proteins therefore low protein diet is followed (no meat, dairy, nuts, eggs)KUVAN® (sapropterin dihydrochloride): PAH cofactor. 20-40% of patients are respondersPalynziqTM (pegvaliase-pqpz): injectable, pegylated, bacterial enzyme (phenylalanine ammonia-lyase or PAL) for treatment of adult patients SYNB1618 for Phenylketonuria (PKU) Target Profile to Address Unmet Need:Manage Phe below target levels to prevent irreversible cognitive damageIncrease natural protein intake: classic PKU patients’ natural protein intake is typically less than 10g Oral dosing without systemic toxicity Goal: Managing Plasma Phe Levels

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 Focus

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: produces TCA which is converted to HA in the liver and is excreted in urineLAAD: produces phenylpyruvate (PP) IN VIVO EFFICACY IN (PKU) PAHenu2/enu2 MOUSE Nat. Biotechnol. 2018 Oct;36(9):857-864

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 DesignRandomized, double-blind placebo-controlled study at multiple sites in the US Primary outcome: establish safety/tolerability following single and multiple doses in HV and PKU patients Secondary outcome: SYNB1618 kinetics in fecesExploratory: change from baseline in plasma and urinary biomarkers of Phe metabolism Presented in September 2018 New Data

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 discontinuations.All subjects cleared SYNB1618 (one PKU patient in follow-up). No evidence of colonization Phase 1/2a SAD/MAD Study Demonstrates Safety and Clearance in Healthy Volunteers and PKU Patients 56 healthy volunteers, 14 PKU patients Received at least one dose of SYNB1618 or placebo AdultsAge range: 18-62 yrs old

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 baseline, CFP: change from placebo MD URINARY HA AND D5-HA

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)

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 commercialization-friendly presentationStability profile at 2-8 ◦C and room temperatureProcess is robust and reproducible at 30 L production scaleGMP cleanroom build-out has been completed, and lyophilized SYNB1618 material has been manufactured and released for clinical use

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 2019Initiate efficacy study in PKU patients to assess Phe lowering 1H 2020

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% NSCL 1st line 60% Melanoma 1st line 71% Bladder 1st line 87% Cervical / Gastric 2nd line Non-responders For indications where immune checkpoint inhibitors are indicated, 55-87% of patients fail to respond Nature often gives us hints to her profoundest secrets, and it is possible that she has given us a hint in which, if we will but follow, may lead us on to the solution of this difficult problem. “ ” Bacteria Recognized as Earliest Immunotherapy DR. WILLIAM B. COLEYIMMUNO-ONCOLOGY PIONEER Enable broad response and remission through engagement of multiple immunomodulatory pathways to enhance tumor inflammation and promote robust T cell responses

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 produce c-di-AMP (CDA)Dual biosafety feature via auxotrophies – no proliferation in tumor, systemic circulation or environmentLearnings inform future combinations ANAEROBIC ENVIRONMENT dacA Pfnr ATP +ATP Cyclic-di-AMP(STING Agonist) 02 AuxotrophiesDiaminopimelic acid (DAP)Thymidine Synthetic Biotic Medicine Producing STING Agonist (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-dependent Anti-tumor ActivityImmunological MemoryAtezolizumab supply agreement in placeIND Cleared by FDAPhase 1 monotherapy data expected in 2020 STING Agonism in Target Cells that Drive EfficacySparing Cells Where STING Agonism is DetrimentalActivation of Multiple Innate Immune PathwaysLow Systemic Risk PROMISE OVER OTHER APPROACHES PROGRESS TOWARDS THE CLINIC

Broad Ambitions in Immuno-Oncology SYNB1891 DISCOVERY PORTFOLIO INTRATUMORAL Vision: Expand and Exceed the Effect of Cancer Immunotherapies COMBINATIONS HARNESS THE MICROBIOME ORAL

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 candidate potencyIncluded equity investment at a premium, extending runway through multiple milestones Platform Collaboration to Accelerate Development of Synlogic’s Synthetic Biotic Medicines

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 in patients with cirrhosisData expected 3Q2019 (safety, tolerability and ammonia-lowering)With ammonia-lowering data define development planSYNB1891 in Immuno-OncologyIND Cleared by FDAClinical trial material manufactured and CPI agreement in placeAdvance AbbVie collaboration establish Ginkgo collaborationAdvance preclinical pipeline

Harnessing nature and technology to create LIVING medicines designed to significantly improve patients’ LIVES Synthetic BioticTM Medicines Designed For Life