Synlogic™ Doses First Subject in Phase 1 Trial of Novel Class of Synthetic Biotic™ Medicines

– Healthy volunteers study initiated for SYNB1020, a Synthetic
Biotic™ medicine for the treatment of hyperammonemia –

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Synlogic™ has dosed the first subject in a Phase 1 healthy volunteers
study designed to assess the safety and tolerability of its lead
compound, SYNB1020. SYNB1020 is an investigational Synthetic Biotic™
medicine intended as an oral treatment for hyperammonemia in diseases
such as urea cycle disorders (UCD) and hepatic encephalopathy (HE),
which are both associated with serious health consequences. SYNB1020 is
the first in a novel class of living medicines under development by
Synlogic. Synthetic Biotic medicines are generated using the company’s
proprietary technology platform, leveraging synthetic biology to
genetically reprogram probiotic bacteria to perform critical functions
or deliver therapeutic factors that compensate for those missing or
damaged due to disease.

“The dosing of our first subject with our lead Synthetic Biotic
medicine, SYNB1020, represents a significant milestone, not only for the
program, but for the advancement of an entirely new class of living
medicines,” said Jose Carlos Gutierrez-Ramos, Ph.D., president and chief
executive officer of Synlogic. “SYNB1020 has been designed to deliver a
complementary metabolic pathway in the gut with the intended consequence
of removing excess ammonia in the blood, essentially ‘replacing’ what a
patient cannot do with his or her liver. We believe this novel approach
could change the treatment paradigm for patients suffering from these
devastating conditions.”

SYNB1020 is the first Synthetic Biotic candidate, developed using
Synlogic’s technology platform, to enter the clinic. The data obtained
from the Phase 1 study will inform future clinical trials of SYNB1020 as
well as other investigational candidates in the company’s portfolio
generated by the platform. Pending the success of this first study in
healthy volunteers with SYNB1020, Synlogic plans to initiate two
additional clinical trials with the investigational candidate, by
mid-2018, in symptomatic patients with urea cycle disorders (UCD) and
hepatic encephalopathy (HE), both diseases where patients experience
elevated and toxic ammonia levels. In the first half of 2018, the
company also plans to initiate a clinical trial with SYNB1618, a
Synthetic Biotic medicine designed to treat phenylketonuria (PKU), which
is caused by defective metabolism of the amino acid phenylalanine.

About the Phase 1 Healthy Volunteers Study:

This Phase 1, dose-escalating, randomized, double-blinded study will
evaluate SYNB1020 in placebo-controlled cohorts, enrolling approximately
50 subjects across two study parts. The first part will investigate a
single-ascending dose (SAD) in healthy volunteer male and female
subjects evaluated in several dose cohorts to identify the maximum
tolerated dose (MTD) within the single dose-range studied. Subsequently,
multiple-ascending doses (MAD) will be studied in an inpatient setting
in healthy volunteer male and female subjects evaluated in several dose
cohorts at doses that were proven tolerable in the SAD part of the study.

The primary outcome measures will evaluate the safety and tolerability
of SYNB1020 by assessing nature and frequency of adverse events (AEs),
laboratory assessments, and electrocardiogram (ECG). Secondary measures
will investigate the gastrointestinal (GI) tolerability and the kinetics
of SYNB1020.

More information about this study including inclusion and exclusion
criteria can be found on clinicaltrials.gov
(Study ID number: NCT03179878).

About Hyperammonemia:

Hyperammonemia is a metabolic condition characterized by an excess of
ammonia in the blood. In healthy individuals, ammonia is primarily
produced in the intestine as a by-product of the body’s metabolism of
dietary protein. Ammonia is then converted to urea in the liver and is
excreted in urine. However, in urea cycle disorders (UCDs) and hepatic
encephalopathy (HE) patients, the liver’s ability to convert ammonia is
reduced, either due to a genetic defect or acquired liver cirrhosis,
respectively. As a result, ammonia begins to accumulate to toxic levels
and eventually reaches the brain, where it acts as a neurotoxin. This
toxicity can cause a number of severe consequences including neurologic
crises requiring hospitalization, irreversible cognitive damage, and
death.

About Synthetic Biotic™ Medicines:

Synlogic’s innovative new class of Synthetic Biotic™ medicines leverages
the tools and principles of synthetic biology to genetically reengineer
beneficial, probiotic microbes to perform or deliver critical functions
missing or damaged due to disease. The company’s two lead programs
target a group of rare metabolic diseases – inborn errors of metabolism
(IEM). Patients with these diseases are born with a faulty gene,
inhibiting the body’s ability to break down commonly occurring
by-products of digestion that then accumulate to toxic levels and cause
serious health consequences. When delivered orally, these medicines can
act from the gut to compensate for the dysfunctional metabolic pathway
and have a systemic effect. Synthetic Biotic medicines are designed to
clear toxic metabolites associated with specific metabolic diseases and
promise to significantly improve the quality of life for affected
patients.

About Synlogic™

Synlogic™ is pioneering the development of a novel class of living
Synthetic Biotic™ medicines based on its proprietary drug discovery and
development platform. Synlogic’s initial pipeline includes Synthetic
Biotic medicines for the treatment of rare genetic diseases, such as
Urea Cycle Disorder (UCD) and Phenylketonuria (PKU). In addition, the
company is leveraging the broad potential of its platform to create
Synthetic Biotic medicines for the treatment of other diseases, such as
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 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. 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, the future clinical development of
SYNB1020 and its prospects as a potential treatment for hyperammonemia
and the future development of other product candidates, such as
SYNB1618. 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.

Contacts

MEDIA:
Synlogic
Courtney Heath, 617-872-2462
courtney@scientpr.com
or
INVESTORS:
Synlogic
Elizabeth
Wolffe, Ph.D., 510-710-8767
liz@synlogictx.com
or
Stern
IR, Inc.
Christina Tartaglia, 212-362-1200
christina@sternir.com