Synlogic Presents New Preclinical Data from Synthetic Biotic™ Immuno-Oncology Program at FOCIS 2018
June 25 2018 - 7:10AM
Business Wire
- 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 –
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 2018.”
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
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. 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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Synlogic, Inc.MEDIA CONTACT:Courtney Heath,
617-872-2462courtney@scientpr.comorINVESTOR
CONTACT:Elizabeth Wolffe, Ph.D.,
617-207-5509liz@synlogictx.com
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