Science Translational Medicine Publishes First-in-Human Clinical Data and Supporting Preclinical Data for SYNB1020, Synlogic’s Synthetic Biotic™ Medicine in Development as a Potential Treatment for Hyperammonemia

From Startup Synlogic Tx

Link to Full Article: https://investor.synlogictx.com/news-releases/news-release-details/science-translational-medicine-publishes-first-human-clinical

–Phase 1 clinical trial to evaluate safety and tolerability of
SYNB1020 in healthy volunteers demonstrated safety, clearance and proof
of mechanism–
– Data from ongoing Phase 1b/2a clinical trial in patients with
cirrhosis and elevated ammonia expected mid-2019 –
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Jan. 16, 2019–
Synlogic,
Inc., (Nasdaq: SYBX) a clinical stage company applying synthetic
biology to beneficial microbes to develop novel, living medicines, today
announced the publication in Science
Translational Medicine of clinical data from its Phase 1
clinical study in healthy volunteers and supporting preclinical data
from its investigational Synthetic Biotic candidate, SYNB1020. The data
support the continued development of SYNB1020 which is currently being
evaluated in a Phase 1b/2a clinical trial in patients with cirrhosis and
elevated blood ammonia.

“These data demonstrate that we can engineer bacteria to carry out a
specific function, deliver them to humans and that they perform as
designed,” said Paul Miller, Ph.D., Synlogic’s chief scientific officer.
“Ongoing manufacturing and formulation development work at Synlogic
gives us confidence we will be able to scale and formulate our Synthetic
biotic medicines to meet multiple needs in the marketplace for living
medicines. The compelling data in this publication encouraged us to
advance SYNB1020 into additional clinical studies and we look forward to
presenting data from our trial, designed to evaluate the potential of
SYNB1020 to lower ammonia in patients with cirrhosis, in mid-2019.”

Long-standing evidence supports the importance of the gastro-intestinal
(GI) tract as the major source of ammonia in the systemic circulation.
The current standard-of-care for conditions that result in
hyperammonemia, including hepatic encephalopathy stemming from liver
damage and urea cycle disorders (UCDs), which are genetic diseases,
employ orally administered approaches such as antibiotics, laxatives and
ammonia scavengers. However, each of these agents has limitations
resulting in a need for additional therapies to manage hyperammonemia.

The publication titled, “An
Engineered E. coli Nissle Improves Hyperammonemia and Survival in
Mice and Shows Dose-dependent Exposure in Healthy Humans,” describes
the engineering and characterization of SYNB1020, preclinical studies of
SYNB1020 in mouse models of hyperammonemia (OTC spfash
and the TAA model), safety in healthy mice and non-human primates (NHPs)
as well as clinical data from Synlogic’s Phase 1 study of SYNB1020 in
healthy volunteers.

Synlogic’s Synthetic Biotic platform leverages the tools and principles
of synthetic biology to engineer a strain of non-pathogenic bacteria (E.
coli Nissle) to perform or deliver specific functions lost or
damaged due to disease. Orally administered SYNB1020 has been designed
to respond to the low oxygen environment of the large intestine to
convert ammonia into arginine, an amino acid. In addition, Synthetic
Biotic medicines are engineered to limit their replication after
manufacturing so that they do not grow or colonize the GI tract.

The preclinical data demonstrate that orally administered SYNB1020 is
well tolerated in mice and NHPs, clears rapidly from the GI tract
following completion of dosing and is not found in tissues outside the
GI tract. When OTC spfash mice, a model of a
urea cycle disorder (UCD), were fed a high protein diet to increase
their blood ammonia levels, those that were orally dosed with SYNB1020
demonstrated lower blood ammonia and increased survival compared to mice
that received heat-killed, inactive SYNB1020. Similar data were obtained
in a mouse model of liver damage (TAA model).

The clinical data from Synlogic’s Phase 1 clinical study demonstrate
that in healthy volunteers, orally administered SYNB1020 was safe, well
tolerated, at daily doses up to 1.5 x1012 colony forming
units, and cleared from the gastrointestinal tract within two weeks. In
addition, dose-dependent elevation in plasma and urine of nitrate, a
biomarker of SYNB1020 activity, was observed in healthy volunteers
treated with SYNB1020 but not in those treated with placebo,
demonstrating proof of mechanism.

Synlogic is currently evaluating SYNB1020 in a Phase 1b/2a clinical
trial in patients with cirrhosis and elevated blood ammonia for the
management of systemic ammonia levels and expects to report data in
mid-2019. More information about Synlogic’s Phase 1b/2a clinical trial
can be found at https://clinicaltrials.gov
under the study ID NCT03447730.

About HyperammonemiaHyperammonemia 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
byproduct of protein metabolism. Ammonia is then converted to urea in
the liver and is excreted in urine. However, if the liver’s ability to
convert ammonia to urea is compromised, either due to a genetic defect
such as a urea cycle disorder (UCD) or acquired liver disease that leads
to cirrhosis, ammonia accumulates in the blood. Elevated blood ammonia
levels are toxic to the brain and can have severe consequences,
including neurologic crises requiring hospitalization, irreversible
cognitive damage and death.

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, rare metabolic diseases, 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/20190116005738/en/
Source: Synlogic, Inc.
MEDIA CONTACT:Courtney HeathPhone: 617-872-2462Email:
courtney@scientpr.com
INVESTOR CONTACT:Elizabeth Wolffe, Ph.D.Phone:
617-207-5509Email: liz@synlogictx.com

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

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2019-01-17 04:53:13