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Synlogic Presents Preclinical Data from Synthetic Biotic Immuno-Oncology Program at the American Association for Cancer Research 2018 Annual Meeting

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Data highlight the application of Synthetic Biotic medicines for
the potential treatment of a variety of solid tumors

Company is advancing the first candidate from this program into
IND-enabling studies in 2018

Synlogic, Inc. (NASDAQ:SYBX), a clinical-stage drug discovery and
development company applying synthetic biology to probiotics to develop
novel living medicines, today announced that preclinical data from its
immuno-oncology (IO) program were featured in two presentations at the
annual meeting of the American Association for Cancer Research (AACR).
The data demonstrate that, in mouse models, Synlogic's Synthetic Biotic
medicines were shown to stimulate an antitumor response and robustly
reprogram the tumor microenvironment potentially enabling the treatment
of a variety of cancers.

"Our IO program highlights the potential of our Synthetic Biotic
platform for the design and engineering of novel living medicines with
multiple mechanisms of action to treat a broad range of diseases,
including cancer," said J.C. Gutiérrez-Ramos, Ph.D., Synlogic's
president and chief executive officer. "Our approach enables us, in a
single treatment, to locally deliver multiple, regulatable activities
that stimulate an immune response and modulate the tumor environment in
order to mobilize the immune system against the tumor and its
metastases. We intend to advance our first IO program into IND enabling
studies this year."

Synlogic is focused initially on developing Synthetic Biotic medicines
to treat so-called "cold tumors," which lack infiltrating anti-tumor
T-cells by first stimulating an innate anti-tumor response to make the
tumor "hot" and then modifying the tumor microenvironment (TME) to
enable T cell expansion and the development of memory, using a single
agent to both prime T-cells to mount an immune response and sustain the
response. Recent studies have demonstrated that activation of the
stimulator of interferon genes (STING) pathway can play a critical role
in the initiation of an anti-tumor immune response via activation of
antigen presenting cells (APCs) and presentation of tumor antigens. The
TME has long been understood to have a role in preventing or
interrupting this process. Certain metabolites produced within the tumor
such as kynurenine or adenosine can lead to T cell dysfunction and
exhaustion, significantly blunting anti-tumor immune responses. Data
presented at AACR demonstrate the potential of Synlogic's Synthetic
Biotic medicines to manipulate both pathways to enable efficient
anti-tumor activity in mouse models.

In a presentation in the late-breaking research immunology session, Activation
of Innate and Adaptive Immunity via Combinatorial Immunotherapy using
Synthetic Biotic Medicines,
Synlogic described two new genetic
circuits engineered into E. coli Nissle, an immune "initiator"
STING activating circuit (SYN-STING) and an immune "sustainer"
kynurenine consuming circuit (SYN-Kyn). SYN-STING can be delivered
directly into the tumor enabling its localized site of action. The
approach of using intra-tumoral injection elicits innate responses in
the tumor but not in the circulation, potentially decreasing the risk of
adverse events that may arise from the production of systemic type I
interferon. In contrast to other therapeutic approaches in development,
SYN-Kyn lowers levels of the kynurenine metabolite by degrading it, a
mechanism that is independent of the enzyme(s) used by both immune and
tumor cells to produce kynurenine (IDO1/2 and/or TDO).

In preclinical studies, Synlogic has demonstrated that:

  • In vitro, SYN-STING produces biologically-relevant levels of
    ci-di-AMP, activating APCs, while SYN-Kyn consumes kynurenine at
    concentrations comparable to those found in patients' tumors;
  • SYN-STING treatment of either B16.F10 or A20 tumors results in robust
    tumor rejection or control, which correlates with an early rise in
    innate-immune cytokines and later results in T cell activation in
    tumors and tumor-draining lymph nodes;
  • Combining SYN-Kyn with a checkpoint inhibitor led to profound
    anti-tumor activity in the CT26 immunocompetent tumor model; and
  • A strain engineered to combine both genetic circuits (SYN-STING:Kyn)
    demonstrates equivalent production of ci-di-AMP and consumption of
    kynurenine in vitro compared to the individual strains
    SYN-STING and SYN-Kyn, respectively.

A second presentation entitled Metabolic Modulation of the Tumor
Microenvironment using Synthetic Biotic Medicines
demonstrated that
engineered bacterial strains designed to consume either kynurenine
(SYN-Kyn) or adenosine (SYN-Ade) effectively relieved TME
immunosuppression and promoted anti-tumor activity.

In summary:

  • In vitro SYN-Kyn and SYN-Ade can deplete kynurenine and
    adenosine, respectively, at concentrations that are clinically
    relevant;
  • SYN-Kyn demonstrated rapid and near-complete reductions in tumor
    kynurenine levels in vivo;
  • A combination of either SYN-Kyn or SYN-Ade with checkpoint inhibition
    led to superior anti-tumor activity in the MC38 immunocompetent tumor
    model compared with checkpoint inhibitors alone.

About Synthetic Biotic Medicines

Synlogic's innovative new class of Synthetic Biotic medicines 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 phenylketonuria, respectively. Patients with these diseases
are unable 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, with the potential to significantly improve symptoms of
disease for affected patient. Synlogic has earlier-stage programs that
apply the broad potential of its Synthetic Biotic platform in other
disease areas, from inflammatory and immune disorders to cancer.

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's initial pipeline includes Synthetic
Biotic medicines for the treatment of rare genetic diseases, such as
urea cycle disorders (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 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).

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: 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; the potential of Synlogic's technology to treat
cancer, hyperammonemia, and phenylketonuria. 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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