Full Press Release Details
Reports Positive Top-Line Phase 1 Data Demonstrating Safety and
Tolerability and Proof of Mechanism in Healthy Volunteers for SYNB1020,
a Synthetic BioticTM
Medicine for the Treatment of Hyperammonemia
SYNB1020 Oral Treatment Resulted in a Significant Dose-Dependent Effect
on a Plasma Nitrogen Endpoint Demonstrating Mechanistic Activity -
Support Initiation of Two Phase 1b/2a Studies in 2018 -
CAMBRIDGE, Mass.--(BUSINESS WIRE)--November 8, 2017--Synlogic,
Inc.,(Nasdaq:SYBX) a clinical-stage drug discovery and development
company applying synthetic biology to probiotics to develop novel
Synthetic Biotic medicines, today announced positive top-line clinical
data from its Phase 1 placebo-controlled single (SAD) and multiple
ascending dose (MAD) clinical trial of SYNB1020 in healthy volunteers.
The trial successfully met the primary objectives demonstrating safety
and tolerability in healthy volunteers and identifying the maximum
tolerated dose. Furthermore, proof of mechanism was demonstrated by a
clear signal in a plasma nitrogen endpoint.
SYNB1020, is a novel, first-in-class, Synthetic Biotic medicine that is
orally delivered and designed to treat elevated blood ammonia levels, or
hyperammonemia, in genetic urea cycle disorders (UCD) or in chronic
"The positive data from our Phase 1 study in healthy volunteers,
demonstrates that SYNB1020 was well-tolerated and had a statistically
significant dose-dependent effect on the level of a nitrogen endpoint,
providing evidence to support its mechanism of action," said Aoife
Brennan, M.B., B.Ch., Synlogic's chief medical officer. "These data
support the hypothesis that SYNB1020 treatment may provide clinical
benefit in patients with UCDs or liver disease, and will inform dose
selection in our planned Phase 1b/2a study of SYNB1020 in patients,
which we expect to begin in the first half of 2018."
"This first-in-human study represents a significant milestone for our
new class of Synthetic Biotic medicines and demonstrates that they can
operate from the gastrointestinal tract to metabolize systemic toxins,"
said JC Guti rrez-Ramos, Ph.D., Synlogic's president and chief executive
officer. "We look forward to evaluating SYNB1020 in patients, and to
moving our second program, SYNB1618 for the treatment of phenylketonuria
into clinical trials in 2018.
SYNB1020 was safe and well tolerated in subjects in multiple ascending
dose cohorts who received total daily doses of up to 1.5x1012
CFU for 14 days. There have been no serious adverse events (SAEs), and
no cases of infection with the bacteria in this study. While the study
is ongoing, there is no evidence of colonization by SYNB1020 as all
subjects who have completed follow-up have cleared the bacteria from
their systems within the expected timeframe.
In the MAD component of the Phase 1 study, daily dosing of SYNB1020 over
14 days in healthy volunteers enabled identification of a dose-response
relationship between SYNB1020 oral administration and changes in a
nitrogen endpoint in plasma which was found to be statistically
significant in the highest dose cohort compared to placebo. In addition,
viability and evidence of mechanistic activity of the Synthetic Biotic
was demonstrated in feces of subjects who received SYNB1020, but not in
control subjects. As expected, SYNB1020 did not lower blood ammonia
levels in these healthy individuals who had normal blood ammonia levels
at baseline. Collectively, the data support the hypothesis that SYNB1020
treatment may enable metabolism of potentially neurotoxic blood levels
of ammonia in patients with hyperammonemia stemming from UCDs or liver
About the SYNB1020 Phase 1 Study
The Phase 1 study was a randomized, double-blind, placebo-controlled
trial of orally administered SYNB1020 evaluating ascending doses each
administered on a single day and multiple ascending doses administered
over 14 days. The primary objective of the studies was to assess safety
and tolerability of SYNB1020 in healthy volunteers. Secondary objectives
were to characterize the microbial kinetics of SYNB1020 in feces as
measured by qPCR and gastrointestinal tolerability assessed by the
Gastrointestinal Symptom Rating Scale. Exploratory endpoints were
designed to evaluate the pharmacodynamic effects of SYNB1020, including
measurements of blood ammonia levels and other related biomarkers.
The results are from 52 healthy volunteers who were dosed orally with
either SYNB1020 or placebo (ratio three to one), which includes 28 from
7 cohorts of the SAD study and 24 subjects from 3 cohorts of the MAD
study. Complete safety results from the SAD and MAD Phase 1 study
demonstrate that SYNB1020 was well tolerated at total daily doses up to
1.5x1012 CFU for 14 days. Higher doses were associated with
mild to moderate gastrointestinal symptoms, mainly nausea and vomiting.
The observed dose-dependent changes in a plasma nitrogen end-point are
consistent with SYNB1020's mechanism of activity. SYNB1020 is
genetically programmed to convert ammonia, a product of protein
degradation, which can be toxic at high levels, into arginine, a
beneficial amino acid.
As expected, based on previous clinical observations with the
un-engineered probiotic and preclinical studies, subjects cleared
SYNB1020 within the expected timeframe. Eight subjects in the MAD
portion of the study continue to be followed for clearance of SYNB1020.
In the SAD study, seven cohorts treated with total daily doses of
SYNB1020 ranging from 2x109 to 6x1012 CFU were
tested against placebo in a three to one ratio in a total of 28 healthy
volunteers. Subjects received a single dose or three doses on a single
day. The maximum tolerated total daily dose was 1.5 x 1012CFU.
There were no SAEs reported, with all AEs being mild to moderate, the
most common being nausea and vomiting at the highest doses. Three
subjects at the highest dose cohorts discontinued dosing.
All three cohorts reported data from a total 24 healthy volunteers dosed
three times per day with SYNB1020 at total daily doses of up to 1.5x1012
CFU for 14 days or with placebo (three to one ratio). No SAEs were
reported, all AEs occurred during the first week of dosing, were mild,
and nausea and vomiting were most common. One subject at the highest
dose cohort discontinued dosing. A dose-responsive nitrogen endpoint was
identified in blood which was found to be statistically significant in
the highest dose cohort compared to placebo. While enrollment and
treatment have been completed, subjects enrolled in the highest dose
cohort continue to be monitored for clearance of SYNB1020.