8-K

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): September 4, 2018

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))

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 September 4, 2018, Synlogic, Inc. (“Synlogic”) will conduct an investor webcast summarizing clinical data from an interim analysis of the healthy volunteer part of its Phase 1/2a clinical trial to evaluate its product candidate SYNB1618, which is being developed for the management of phenylketonuria (PKU).  A copy of the presentation is furnished with this Current Report on Form 8-K as Exhibit 99.1.

The information in Item 7.01 of this Current Report on Form 8-K and Exhibit 99.1 attached hereto is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934 (the “Exchange Act”) or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933 or the Exchange Act, except as expressly set forth by specific reference in such filing.

Item 8.01. Other Events.

On September 4, 2018, Synlogic issued a press release announcing clinical data from an interim analysis of the healthy volunteer part of its Phase 1/2a clinical trial to evaluate its product candidate SYNB1618, which is being developed for the management of PKU.

The full text of Synlogic’s press release regarding the announcement is filed as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

Item 9.01  Financial Statements and Exhibits.

(d)	Exhibits
	99.1 Investor presentation provided by Synlogic dated September 4, 2018
	99.2 Press Release dated September 4, 2018

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.

	Company NameSYNLOGIC, INC.
Date: September 4, 2018	By:	/s/ Todd Shegog
	Name:	Todd Shegog
	Title:	Chief Financial Officer

EX-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 

EX-99.2

Exhibit 99.2

Synlogic Reports Positive Interim Phase 1/2a Data Demonstrating Safety, Tolerability and Proof-of-Mechanism in Healthy Volunteers for SYNB1618, in Development for the Management of Phenylketonuria (PKU)

– Data demonstrate statistically significant dose-dependent effects on SYNB1618 activity-associated biomarkers, supporting further development of SYNB1618 –

– SYNB1618 dose established for treatment arm of ongoing Phase 1/2a study in patients with PKU; top-line data expected in mid-2019 –

– Company to hold conference call and webcast today, September 4, at 8:00 a.m. ET–

CAMBRIDGE, Mass.--(BUSINESS WIRE)--September 4, 2018--Synlogic, Inc., (Nasdaq:SYBX) a clinical stage company applying synthetic biology to probiotics to develop novel, living medicines, today announced positive interim clinical data from the healthy volunteer (HV) arm of its ongoing Phase 1/2a study of SYNB1618 in HVs and patients with PKU. The first part of this trial, which evaluated SYNB1618 versus placebo (PBO) in single- (SAD) and multiple-ascending dose (MAD) cohorts of HVs, successfully met the study’s primary objectives, to demonstrate safety and tolerability of SYNB1618 in HVs and to identify a suitable dose to evaluate in patients with PKU. Consistent with preclinical studies, the Phase 1/2a clinical data demonstrated that oral administration of SYNB1618 resulted in significant dose-dependent production of biomarkers specifically associated with SYNB1618 activity, demonstrating proof-of-mechanism.

"The significant dose-dependent production of SYNB1618-specific biomarkers in healthy volunteers is an exciting first step towards delivering a potential therapy for patients with PKU,” said Aoife Brennan, M.B., B.Ch., Synlogic’s interim president and chief executive officer and chief medical officer. "We have identified a dose for the next phase of our ongoing trial in patients with PKU and we look forward to expanding on these interim results when we report top-line data from the patient treatment arm of this trial in mid-2019. Importantly, the data also demonstrate the potential for our Synthetic Biotic platform to address conditions in which an engineered living medicine can be designed to perform a specific metabolic function within the gastrointestinal tract."

Synlogic’s Synthetic Biotic platform leverages the tools and principles of synthetic biology to engineer a strain of probiotic bacteria (E. coli Nissle) to perform or deliver specific functions lost or damaged due to disease. SYNB1618, in development for the management of PKU, is designed to function in the gastrointestinal tract (GI) and has been engineered to consume phenylalanine (Phe), an essential amino acid that can accumulate to harmful levels in patients with PKU with severe consequences. SYNB1618 metabolizes Phe to harmless compounds including trans-cinnamic acid (TCA) in the blood which is further metabolized in the liver and excreted as hippurate (HA) in the urine. TCA and HA,therefore, represent specific biomarkers of SYNB1618 activity as demonstrated by Synlogic’s preclinical data that were recently published in Nature Biotechnology.

Phase 1/2a Trial Design

Synlogic’s Phase 1/2a trial is a randomized, double-blind, PBO-controlled study of orally administered SYNB1618, evaluating ascending doses administered on a single day and multiple ascending doses administered over seven days. The primary objective of the study was to assess safety and tolerability of SYNB1618 in HVs and to establish a suitable dose to evaluate in patients with PKU, with secondary objectives to characterize the microbial kinetics of SYNB1618 in feces, as measured by qPCR, and GI tolerability, assessed by GI-related adverse events. Exploratory endpoints were designed to evaluate the pharmacodynamic effects of SYNB1618, including previously identified biomarkers related to SYNB1618 activity, TCA in plasma and HA in urine.

In the SAD portion of this study, six cohorts of four HVs received a single dose of SYNB1618 ranging from 1x10¹⁰ to 5x10¹¹ CFU or PBO (3 treated:1 PBO). In the MAD portion of this study, four cohorts of eight HVs received either SYNB1618 at doses of up to 1x10¹¹ CFU TID or PBO (6 treated:2 PBO), for seven days. During the treatment part of the study, subjects were housed in a clinical unit and provided a defined diet. The activity of SYNB1618 was evaluated in fasted subjects in both the SAD and MAD cohorts after administration of a standardized breakfast drink containing a defined amount of protein. At one dose level in the SAD portion of the study, solid food containing an equivalent amount of protein was substituted for the liquid meal. In addition, a labeled Phe tracer (D5-Phe) was orally administered. Blood and urine were collected over a subsequent six-hour period and several metabolites were measured including Phe and SYNB1618-specific biomarkers of Phe metabolism, TCA in blood and HA in urine. This was conducted in the SAD cohorts on the day of dosing and in the MAD cohorts on Day -1 (baseline) and Day 7 (the last day of dosing).

SAD Phase 1 Results:

In the SAD portion of this study, which included a total of 24 subjects, the maximum tolerated dose (MTD) was 2 x 10¹¹ CFU. There were no drug-related significant adverse events (SAEs) reported. All AEs were mild-to-moderate in severity; of the moderately severe AEs, nausea and vomiting were the most common. A statistically significant dose-dependent increase in both plasma TCA and urinary HA was observed in SYNB1618 treated subjects but not in those treated with PBO. Production of metabolites from Phe administered as a free amino acid was similar to Phe administered as whole protein. In addition, production of metabolites was similar whether the protein was administered as a liquid or as a solid meal.

MAD Phase 1 Results:

In the MAD portion of this study, which included a total of 32 subjects, HV were administered PBO or SYNB1618 at doses of up to 1x10¹¹ CFU TID for seven days. No drug-related SAEs were reported. All AEs were mild to moderate and observed in both the SYNB1618-treated and PBO groups. Of the moderately severe AEs, nausea and vomiting were the most common; only one subject in the highest dose cohort discontinued dosing. As observed in the SAD portion of the study, a statistically significant dose-dependent increase in plasma TCA and urinary HA was observed in SYNB1618-treated subjects but not in those treated with PBO. In HVs, who all have normal Phe metabolism, there was no impact on blood Phe levels. All HVs enrolled in the study have cleared SYNB1618 from their GI tracts.

SYNB1618 Clinical Development Plans and Upcoming Milestones

Synlogic’s ongoing Phase 1/2a trial of SYNB1618 will advance in patients with PKU, who will be administered 7x10¹⁰ CFU of SYNB1618. Synlogic expects to report top-line data from the patient treatment arm of this study in mid-2019 and plans to present final data from this clinical trial, including data from both HVs and patients, at an appropriate medical meeting. More information about Synlogic’s Phase 1/2a clinical trial in healthy adult volunteers and patients with PKU can be found at https://clinicaltrials.gov under the study ID NCT03516487. In addition, Synlogic will continue to optimize manufacturing process development and formulation of SYNB1618 in preparation for later stage clinical studies.

Conference Call & Webcast Information

Synlogic will host a conference call and live webcast at 8:00 a.m. ET on Tuesday, September 4, 2018. To access the live webcast, please visit the “Event Calendar” page within the Investors and Media section of the Synlogic website at https://investor.synlogictx.com/. Alternatively, investors may listen to the call by dialing +1 (844) 815-2882 from locations in the United States or +1 (213) 660-0926 from outside the United States. The conference ID number is 1584778. A replay of the call will be available for seven days post the event, investors may listen to the call by dialing +1 (855) 859-2056 from locations in the United States or +1 (404) 537-3406 from outside the United States. A replay of the webcast will be available on the Synlogic website for 90 days following the call.

About Phenylketonuria (PKU)

PKU is caused by a defect in the gene encoding phenylalanine hydroxylase (PAH), a liver enzyme that metabolizes Phe. Phe is an essential amino acid that enters the body as a component of dietary protein and can be toxic if it accumulates in the blood and brain. Current disease management of PKU involves strict dietary protein restriction with the consumption of Phe-free protein supplements. Life-long Phe control is challenging due to the highly restrictive nature of the diet and patients typically experience worsening neurological function depending on the severity of their genetic mutation and their treatment compliance. PKU is diagnosed at birth, and the National PKU Alliance estimates that there are currently approximately 16,500 people living with the disorder in the U.S.

About Synlogic

Synlogic is pioneering the development of a novel class of living medicines, Synthetic Biotic medicines, based on its proprietary drug development platform. Synlogic leverages the tools and principles of synthetic biology to genetically engineer probiotic microbes to perform or deliver critical functions missing or damaged due to disease. The company’s two lead programs, SYNB1020 and SYNB1618, target hyperammonemia as a result of liver damage or genetic disease, and PKU, respectively. When delivered orally, Synthetic Biotic medicines can act from the gut to compensate for the dysfunctional metabolic pathway and have a systemic effect, with the potential to significantly improve symptoms of disease for affected patients. In addition, the company is leveraging the broad potential of its platform to create Synthetic Biotic medicines for the treatment of more common diseases, including liver disease, inflammatory and immune disorders, and cancer. Synlogic is collaborating with AbbVie to develop Synthetic Biotic-based treatments for inflammatory bowel disease (IBD). For more information, please visit www.synlogictx.com.

Forward-Looking Statements

This press release 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, including statements regarding Synlogic’s plans and expectations for the development of SYNB1618. All statements, other than statements of historical facts, included in this press release 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 press release, 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 contained in this press release 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.

CONTACT:
For Synlogic, Inc.
MEDIA:
Lisa M Guiterman, 301-217-9353
lisa.guiterman@gmail.com
or
INVESTORS:
Elizabeth Wolffe, Ph.D., 617-207-5509
liz@synlogictx.com