Market Overview

Synlogic Publishes Preclinical Data Supporting Development of SYNB1618, a Synthetic Biotic™ Medicine as a Potential Treatment for Phenylketonuria


– Preclinical studies published in Nature Biotechnology identify key
biomarkers of SYNB1618 activity in healthy animals and disease models –

– Clinical data expected in 2018 from healthy volunteer cohorts of
ongoing Phase 1/ 2a study of SYNB1618; data from patients with
phenylketonuria (PKU) in 2019 –

Synlogic, Inc., (NASDAQ:SYBX) a clinical stage company applying
synthetic biology to probiotics to develop novel, living
medicines, today announced the publication of data from preclinical
studies of SYNB1618, the Company's Synthetic Biotic development program
targeting PKU, in Nature Biotechnology. The data
demonstrate that oral administration of SYNB1618 significantly reduced
blood phenylalanine (Phe) levels, the key metabolite associated with
PKU, in mouse models of PKU and resulted in dose-dependent
pharmacodynamics in healthy non-human primates (NHPs).

The paper titled "A
translational pathway for the development of a synthetic organism for
the treatment of phenylketonuria
" appears as an Advance Online
Publication on Nature Biotechnology's website.

"These preclinical studies highlight the potential of our engineered
Synthetic Biotic medicines to act with potency within the gut to
normalize systemic levels of a toxic metabolite. In addition, in two
species, we demonstrate dose-dependent production of biomarkers of
activity for SYNB1618, which will be very useful in evaluating its
efficacy in our ongoing clinical study in healthy volunteers and
patients with PKU," said Paul Miller, Ph.D., Synlogic's chief scientific
officer. "These data provide compelling evidence to support the
continued development of our orally administered Synthetic Biotic
medicine, SYNB1618, for the potential treatment of PKU."

Synlogic's Synthetic Biotic platform leverages the tools and principles
of synthetic biology to engineer a strain of probiotic bacteria (E.
Nissle) to perform or deliver specific functions lost or
damaged due to disease. SYNB1618 is designed to metabolize Phe and was
engineered by inserting specific genetic circuits including a bacterial
gene that encodes phenylalanine ammonia lyase (PAL). PAL is an enzyme
that breaks down Phe to generate trans-cinnamic acid (TCA), which is
converted to hippuric acid (HA) in the liver and excreted in urine.
Thus, plasma TCA and urinary HA levels can serve as biomarkers of PAL
and, therefore, of SYNB1618 activity in vivo.

The publication describes the engineering and characterization of
SYNB1618, as well as preclinical studies of SYNB1618 in both a mouse
model of PKU (Pah enu2/enu2) and healthy NHPs
that have a metabolism and gastrointestinal (GI) physiology more similar
to humans. Synlogic scientists confirmed previously reported
observations in rodents that Phe is abundant in the small intestine and
derived from two sources, the diet and the blood. In both species, Phe
re-enters the GI tract in the form of enzymes and secretions via a
process known as enterorecirculation, supporting the feasibility of a
GI-based approach for Phe consumption.

To monitor SYNB1618 activity in vivo, Synlogic scientists
investigated the production of major SYNB1618-derived metabolites,
including TCA and HA. Studies demonstrated that orally administered
SYNB1618 resulted in a significant decrease in blood Phe levels
independent of dietary protein intake in the PKU mouse model, and
inhibited increases in serum Phe after an oral Phe challenge in healthy
NHPs. In both species, SYNB1618 exhibited dose-responsive
pharmacokinetics, as determined by production of urinary HA.

Synlogic is currently evaluating SYNB1618 in a Phase 1/2a clinical trial
for the management of PKU and expects to report interim data from
healthy volunteers in 2018 and full data, including cohorts of patients
with PKU, in 2019. More information about Synlogic's Phase 1/2a clinical
trial in healthy adult volunteers and patients with PKU can be found at
under the study ID NCT03516487.

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 and approved therapies of PKU involve strict dietary protein
restriction with the consumption of Phe-free protein supplements,
representing a significant need for additional treatments. 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 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

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. 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: inborn errors of
metabolism, liver disease, inflammatory and immune disorders, and
cancer; the future clinical development of Synthetic Biotic medicines;
the approach Synlogic is taking to discover and develop novel
therapeutics using synthetic biology; the potential of Synlogic's
technology to treat hyperammonemia and phenylketonuria; 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.

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