Synlogic Presents New Preclinical Data from Synthetic Biotic™ Immuno-Oncology Program at FOCIS 2018

From Startup Synlogic Tx

Link to Full Article:

– Data highlight broad capabilities of Synlogic’s Synthetic Biotic
platform to generate candidates for the potential treatment of cancer –
– First program advancing into IND-enabling studies in 2H2018 –
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Jun. 25, 2018–
Synlogic, Inc. (Nasdaq:
SYBX), a clinical-stage drug discovery and development company
applying synthetic biology to probiotics to develop novel living
medicines, announced the presentation of new preclinical data from its
Synthetic Biotic medicine oncology program at the annual meeting of the
Federation of Clinical Immunology Societies (FOCIS 2018) held June
20-23, in San Francisco, CA. The data demonstrate the breadth of the
company’s platform to generate Synthetic Biotic medicines that secrete
or consume immunologically relevant compounds for the potential
treatment of cancer and inflammation.

“These data highlight the plasticity of our Synthetic Biotic platform
and its potential as a robust engine for the production and delivery of
a variety of immunological payloads, which can have a profound effect on
the tumor microenvironment and potential therapeutic use in
immune-related conditions,” said Jose Lora, Ph.D., Synlogic’s vice
president of research. “Our ability to control the expression of these
payloads using the tools of synthetic biology, and to combine multiple
effectors into a single Synthetic Biotic medicine has the potential to
provide potent stimulation of the immune response locally while limiting
systemic toxicity. We continue to explore the capability of this
platform in immunomodulation and look forward to advancing our first
immuno-oncology program into IND-enabling studies in the second half of

These preclinical data demonstrate that intra-tumorally injected E.
coli Nissle has the ability to colonize and persist in the tumor.
Synlogic uses a strain of probiotic bacteria, E. coli Nissle, as
the parent strain or “chassis” for its Synthetic Biotic medicines as it
is well-characterized, readily engineerable and non-pathogenic. In
addition, multiple functions can be engineered into a single bacterial
strain. These properties support the development of a Synthetic Biotic
immuno-oncology approach for the potential treatment of solid tumors,
particularly “cold” tumors that may be resistant to current
immunotherapies due to their lack of infiltrating immune cells or a
highly immunosuppressive tumor microenvironment.

In a presentation at FOCIS: A Synthetic Biology Approach for the
Treatment of Cancer and Inflammation, Synlogic described the
engineering of Synthetic Biotic strains to execute a range of functions
that are potentially useful for the treatment of cancer, including:

Consumption of immune-suppressive metabolites that accumulate in
tumors, such as adenosine and kynurenine. Synthetic Biotic strains
capable of consuming these metabolites have the potential to relieve
immunosuppression in the tumor microenvironment, enabling immune cells
to initiate an anti-tumor response;

Secretion of proteins, including immunomodulatory cytokines such as
IL-15, TNF-alpha and IFN-gamma, and production of small molecules,
such as STING agonists, that are able to trigger robust anti-tumor
immune responses as single agents; and

In situ conversion of pro-drugs, such as 5FC, to enable local
release of an active chemotherapy agent, 5FU, potentially reducing the
systemic toxicity of such drugs.

The data also demonstrate the use of “switches” to control the
engineered genetic circuits; Synthetic Biotic medicines can be
engineered to perform functions in response to environmental cues or
exogenously administered small molecules, such as tetracycline,
salicylate and cumate.

In a second presentation, Using Synthetic Biotic Medicines to
Activate Innate and Adaptive Immunity and Drive Antitumor Immune
Responses, data were presented from mouse tumor model studies of two
genetic circuits engineered into E. coli Nissle to generate two
bacterial strains, an immune “initiator” STING activating circuit
(SYN-STING) and an immune “sustainer” kynurenine consuming circuit
(SYN-Kyn). In contrast to other therapeutic approaches in development,
SYN-Kyn lowered levels of the kynurenine metabolite by degrading it, a
mechanism that is independent of the enzymes used by both immune and
tumor cells to produce kynurenine (IDO1/2 and/or TDO). The preclinical
data demonstrate:

SYN-STING treatment of either B16.F10 or A20 tumors resulted 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 checkpoint inhibitors led to significant
anti-tumor activity in multiple immunocompetent tumor models; 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.

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: 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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Source: Synlogic, Inc.
Synlogic, Inc.MEDIA CONTACT:Courtney Heath,
CONTACT:Elizabeth Wolffe, Ph.D.,

Please visit their site for more information: Synlogic

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2018-06-27 04:33:32