Synlogic Reports Positive Interim Phase 1/2a Data Demonstrating Safety, Tolerability and Proof-of-Mechanism in Healthy Volunteers for SYNB1618, in Development for the Management of Phenylketonuria (PKU)

From Startup Synlogic Tx

Link to Full Article:

– Data demonstrate statistically significant dose-dependent effects
on SYNB1618 activity-associated biomarkers, supporting further
development of SYNB1618 –
– SYNB1618 dose established for treatment arm of ongoing Phase 1/2a
study in patients with PKU; top-line data expected in mid-2019 –
– Company to hold conference call and webcast today, September 4, at
8:00 a.m. ET–
CAMBRIDGE, Mass.–(BUSINESS WIRE)–Sep. 4, 2018–
Synlogic, Inc., (Nasdaq:SYBX)
a clinical stage company applying synthetic biology to probiotics to
develop novel, living medicines, today announced positive interim
clinical data from the healthy volunteer (HV) arm of its ongoing Phase
1/2a study of SYNB1618 in HVs and patients with PKU. The first part of
this trial, which evaluated SYNB1618 versus placebo (PBO) in single-
(SAD) and multiple-ascending dose (MAD) cohorts of HVs, successfully met
the study’s primary objectives, to demonstrate safety and tolerability
of SYNB1618 in HVs and to identify a suitable dose to evaluate in
patients with PKU. Consistent with preclinical studies, the Phase 1/2a
clinical data demonstrated that oral administration of SYNB1618 resulted
in significant dose-dependent production of biomarkers specifically
associated with SYNB1618 activity, demonstrating proof-of-mechanism.

“The significant dose-dependent production of SYNB1618-specific
biomarkers in healthy volunteers is an exciting first step towards
delivering a potential therapy for patients with PKU,” said Aoife
Brennan, M.B., B.Ch., Synlogic’s interim president and chief executive
officer and chief medical officer. “We have identified a dose for the
next phase of our ongoing trial in patients with PKU and we look forward
to expanding on these interim results when we report top-line data from
the patient treatment arm of this trial in mid-2019. Importantly, the
data also demonstrate the potential for our Synthetic Biotic platform to
address conditions in which an engineered living medicine can be
designed to perform a specific metabolic function within the
gastrointestinal tract.”

Synlogic’s Synthetic Biotic platform leverages the tools and principles
of synthetic biology to engineer a strain of probiotic bacteria (E.
coli Nissle) to perform or deliver specific functions lost or
damaged due to disease. SYNB1618, in development for the management of
PKU, is designed to function in the gastrointestinal tract (GI) and has
been engineered to consume phenylalanine (Phe), an essential amino acid
that can accumulate to harmful levels in patients with PKU with severe
consequences. SYNB1618 metabolizes Phe to harmless compounds including
trans-cinnamic acid (TCA) in the blood which is further metabolized in
the liver and excreted as hippurate (HA) in the urine. TCA and
HA,therefore, represent specific biomarkers of SYNB1618 activity as
demonstrated by Synlogic’s preclinical data that were recently published
in Nature
Phase 1/2a Trial Design

Synlogic’s Phase 1/2a trial is a randomized, double-blind,
PBO-controlled study of orally administered SYNB1618, evaluating
ascending doses administered on a single day and multiple ascending
doses administered over seven days. The primary objective of the study
was to assess safety and tolerability of SYNB1618 in HVs and to
establish a suitable dose to evaluate in patients with PKU, with
secondary objectives to characterize the microbial kinetics of SYNB1618
in feces, as measured by qPCR, and GI tolerability, assessed by
GI-related adverse events. Exploratory endpoints were designed to
evaluate the pharmacodynamic effects of SYNB1618, including previously
identified biomarkers related to SYNB1618 activity, TCA in plasma and HA
in urine.

In the SAD portion of this study, six cohorts of four HVs received a
single dose of SYNB1618 ranging from 1×1010 to 5×1011
CFU or PBO (3 treated:1 PBO). In the MAD portion of this study, four
cohorts of eight HVs received either SYNB1618 at doses of up to 1×1011
CFU TID or PBO (6 treated:2 PBO), for seven days. During the treatment
part of the study, subjects were housed in a clinical unit and provided
a defined diet. The activity of SYNB1618 was evaluated in fasted
subjects in both the SAD and MAD cohorts after administration of a
standardized breakfast drink containing a defined amount of protein. At
one dose level in the SAD portion of the study, solid food containing an
equivalent amount of protein was substituted for the liquid meal. In
addition, a labeled Phe tracer (D5-Phe) was orally administered. Blood
and urine were collected over a subsequent six-hour period and several
metabolites were measured including Phe and SYNB1618-specific biomarkers
of Phe metabolism, TCA in blood and HA in urine. This was conducted in
the SAD cohorts on the day of dosing and in the MAD cohorts on Day -1
(baseline) and Day 7 (the last day of dosing).

SAD Phase 1 Results:

In the SAD portion of this study, which included a total of 24 subjects,
the maximum tolerated dose (MTD) was 2 x 1011 CFU. There were
no drug-related significant adverse events (SAEs) reported. All AEs were
mild-to-moderate in severity; of the moderately severe AEs, nausea and
vomiting were the most common. A statistically significant
dose-dependent increase in both plasma TCA and urinary HA was observed
in SYNB1618 treated subjects but not in those treated with PBO.
Production of metabolites from Phe administered as a free amino acid was
similar to Phe administered as whole protein. In addition, production of
metabolites was similar whether the protein was administered as a liquid
or as a solid meal.

MAD Phase 1 Results:

In the MAD portion of this study, which included a total of 32 subjects,
HV were administered PBO or SYNB1618 at doses of up to 1×1011
CFU TID for seven days. No drug-related SAEs were reported. All AEs were
mild to moderate and observed in both the SYNB1618-treated and PBO
groups. Of the moderately severe AEs, nausea and vomiting were the most
common; only one subject in the highest dose cohort discontinued dosing.
As observed in the SAD portion of the study, a statistically significant
dose-dependent increase in plasma TCA and urinary HA was observed in
SYNB1618-treated subjects but not in those treated with PBO. In HVs, who
all have normal Phe metabolism, there was no impact on blood Phe levels.
All HVs enrolled in the study have cleared SYNB1618 from their GI tracts.

SYNB1618 Clinical Development Plans and Upcoming Milestones

Synlogic’s ongoing Phase 1/2a trial of SYNB1618 will advance in patients
with PKU, who will be administered 7×1010 CFU of SYNB1618.
Synlogic expects to report top-line data from the patient treatment arm
of this study in mid-2019 and plans to present final data from this
clinical trial, including data from both HVs and patients, at an
appropriate medical meeting. More information about Synlogic’s Phase
1/2a clinical trial in healthy adult volunteers and patients with PKU
can be found at
under the study ID NCT03516487.
In addition, Synlogic will continue to optimize manufacturing process
development and formulation of SYNB1618 in preparation for later stage
clinical studies.

Conference Call & Webcast Information
Synlogic will host a conference call and live webcast at 8:00 a.m. ET on
Tuesday, September 4, 2018. To access the live webcast, please visit the
Calendar” page within the Investors and Media section of the
Synlogic website at
Alternatively, investors may listen to the call by dialing +1 (844)
815-2882 from locations in the United States or +1 (213) 660-0926 from
outside the United States. The conference ID number is 1584778. A replay
of the call will be available for seven days post the event, investors
may listen to the call by dialing +1 (855) 859-2056 from locations in
the United States or +1 (404) 537-3406 from outside the United States. A
replay of the webcast will be available on the Synlogic website for 90
days following the call.

About Phenylketonuria (PKU)

PKU is caused by a defect in the gene encoding phenylalanine hydroxylase
(PAH), a liver enzyme that metabolizes Phe. Phe is an essential amino
acid that enters the body as a component of dietary protein and can be
toxic if it accumulates in the blood and brain. Current disease
management of PKU involves strict dietary protein restriction with the
consumption of Phe-free protein supplements. Life-long Phe control is
challenging due to the highly restrictive nature of the diet and
patients typically experience worsening neurological function depending
on the severity of their genetic mutation and their treatment
compliance. PKU is diagnosed at birth, and the National PKU Alliance
estimates that there are currently approximately 16,500 people living
with the disorder in the U.S.

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,
including statements regarding Synlogic’s plans and expectations for the
development of SYNB1618. 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; and the
expected timing of Synlogic’s clinical trials and availability of
clinical trial data. 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

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Source: Synlogic, Inc.
For Synlogic, Inc.MEDIA:Lisa M Guiterman,
Wolffe, Ph.D.,

Please visit their site for more information: Synlogic

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2018-09-05 04:58:06