Synlogic Presents Data at the 2018 Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD)

From Startup Synlogic Tx

Link to Full Article: https://investor.synlogictx.com/news-releases/news-release-details/synlogic-presents-data-2018-liver-meeting-annual-meeting

– Data support ongoing evaluation of Synthetic BioticTM
SYNB1020 for the potential treatment of hyperammonemia –
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Nov. 12, 2018–
Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage drug discovery and
development company applying synthetic biology to beneficial microbes to
develop novel living medicines, today announced the presentation of data
from a cross-sectional study on ammonia levels in patients with
cirrhosis and healthy volunteers, and preclinical studies of its
Synthetic Biotic strains in rodent models of liver failure. The
presentations were made at The Liver Meeting, the annual meeting of the
American Association for the Study of Liver Disease (AASLD), which is
being held in San Francisco, November 9 to 13, 2018.

“Hepatic Encephalopathy is a major cause of morbidity and mortality in
patients with chronic liver disease. Elevated blood ammonia is an
important risk factor for HE, however, it is difficult to measure in the
setting of multicenter clinical trials,” said Aoife Brennan, M.B., Ch.
B., Synlogic’s president and chief executive officer “The confirmatory
preclinical data presented at this meeting support the ongoing
development of SYNB1020. In addition, the data provided by our
cross-sectional study have enabled us to maximize the quality of ammonia
measurement in our ongoing Phase 1b /2a clinical trial of SYNB1020.”

Two presentations were given at the Liver Meeting, both were selected as
posters of distinction. The data are summarized below:

Blood Ammonia Levels are Labile and Responsive to Protein Intake
in Patients with Compensated Cirrhosis Without Overt Hepatic
EncephalopathySynlogic conducted a study in
patients with cirrhosis who have not had an episode of overt hepatic
encephalopathy (HE) to determine the level and inter-individual
variability of fasting blood ammonia and the impact of a standard
protein meal on blood ammonia levels. In addition, blood ammonia
reference ranges of healthy volunteers at five clinical sites were
compared as well as the intra-sample variability between fresh samples
or fresh and frozen samples.The data demonstrated that:

Sample handling and processing have a major impact on ammonia levels
and are critical for data quality

Venous ammonia is elevated in a subset of patients with cirrhosis
without a history of overt HE and increases significantly after a meal
containing 20g of protein for at least two hours

Normal ranges determined using healthy volunteers and strict sample
processing and analysis procedures can differ significantly from the
normal range provided by the kit manufacturer

There is an excellent correlation between paired fresh samples,
however, freezing affects ammonia levels

Age and gender do not appear to influence ammonia levels, however, as
expected, higher MELD score is associated with higher baseline ammonia

The study provided key foundational data for the establishment of
optimal protocols for blood ammonia measurement in Synlogic’s ongoing
Phase 1b/2a clinical trial of its ammonia consuming Synthetic Biotic
strain, SYNB1020, in patients with cirrhosis and elevated ammonia.

Genetically Engineered E.coli Nissle Attenuates Hyperammonemia
in Two Experimental Models of Hepatic EncephalopathyThe
study was designed to explore the effect of Synthetic Biotic strains
engineered to consume ammonia on plasma ammonia levels and bio-markers
of liver damage in two rodent models of liver damage, the mouse
thioacetamide (TAA) model and the rat bile duct ligation (BDL) model.
The rat BDL model studies were conducted in the laboratory of
Synlogic’s collaborator, Christopher Rose, Ph.D., Professor at the
Department of Medicine at the Université de Montréal and a researcher
at the Centre de recherche du Centre hospitalier de Université de
Montréal (CRCHUM) where he heads the Hepato-Neuro Laboratory.The
study evaluated two engineered strains of E.coli Nissle: SYNARG,
designed to consume ammonia and convert it to arginine, and SYNARG+BUT
which was engineered to also synthesize the short chain fatty acid
butyrate in the gastrointestinal (GI) tract. Butyrate has been
reported to reduce inflammation and help maintain gut barrier
integrity.The data demonstrated that:

In vitro SYNARG and SYNARG+BUT both consume ammonia and produce
arginine and SYNARG+BUT also produces butyrate

Statistically significant reductions in serum ammonia were observed in
both the mouse TAA and rat BDL models

Markers of liver injury were reduced in TAA mice, suggesting
additional potential benefits of the engineered strains in liver
disease beyond the direct consumption of ammonia in the GI tract

Future studies will also explore the effect of Synthetic Biotic
medicines on measures of cognitive function in the rat BDL model.
Elevated levels of ammonia in the brain lead to neurological symptoms,
including impaired memory, shortened attention span, seizures, lack of
muscle coordination and coma. The study provided supportive evidence for
the potential beneficial effect of Synthetic Biotic medicines designed
to consume ammonia from the GI tract in attenuating chronic liver
disease.

About SynlogicSynlogic 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 beneficial
microbes to perform or deliver critical functions missing or damaged due
to disease. Synthetic Biotic medicines are designed to act locally and
have a systemic effect to address disease in patients. Synlogic’s two
lead programs, SYNB1020 and SYNB1618, are orally administered and target
hyperammonemia as a result of liver damage or genetic disease, and
phenylketonuria, respectively. Synlogic is also developing SYNB1891 as
an intratumorally administered Synthetic Biotic medicine for the
treatment of cancer. In addition, the company is leveraging the broad
potential of its platform to create additional Synthetic Biotic
medicines for the treatment of liver disease, as well as inflammatory
and immune disorders including Synlogic’s collaboration with AbbVie to
develop Synthetic Biotic-based treatments for inflammatory bowel disease
(IBD). For more information, please visit www.synlogictx.com.

Forward-Looking StatementsThis 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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20181112005766/en/
Source: Synlogic, Inc.

Synlogic, Inc.Media Contact:Courtney Heath,
617-872-2462courtney@scientpr.comorInvestor
Contact:Elizabeth Wolffe, Ph.D., 617-207-5509liz@synlogictx.com

Please visit their site for more information: Synlogic Therapeutics.com

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2018-11-13 05:46:39