CAMBRIDGE, Mass., Dec. 14, 2020 /PRNewswire/ -- Synlogic, Inc.
(Nasdaq: SYBX), a clinical stage company bringing the
transformative potential of synthetic biology to medicine, today
announced SYNB1891 has advanced into the combination therapy stage
of the ongoing Phase 1 trial. SYNB1891 is an investigational
drug for the intra-tumoral treatment of solid tumors and lymphoma,
composed of an engineered Synthetic Biotic designed to
activate the STING pathway in the tumor microenvironment in order
to upregulate the patient's immune response.
SYNB1891 is being advanced due to acceptable safety at doses
evaluated to date, intratumoral injection feasibility, successful
escalation to clinically relevant dose levels, and evidence of
target engagement and immune system upregulation.
"Our goal is to bring the benefits of immunotherapy to patients
fighting cancer who do not have the option of immunotherapies
today," said Aoife Brennan, M.B.
Ch.B., Synlogic's President and Chief Executive Officer. "Synlogic
is designing Synthetic Biotic medicines that work uniquely inside
the tumor microenvironment, boosting the patient's immune response
and promoting the body's ability to detect and destroy cancer
cells. The interim results of our monotherapy cohorts suggest
SYNB1891 is working as designed, upregulating the immune system in
the tumor microenvironment via the STING pathway. We are excited to
move this study forward."
"The body of data validating our unique approach to
immunomodulation with Synthetic Biotic medicines continues to
grow," said Dr. Richard Riese,
M.D., Synlogic's Chief Medical Officer. "The
investigation of SYNB1891 combined with the PD-L1 checkpoint
inhibitor atezolizumab (Tecentriq®) is warranted by the
encouraging and consistent results we have seen thus far across
preclinical models, tumor response, and biomarkers of target
engagement. We would like to thank the investigators, patients, and
their families who continue to work closely with us as we advance
this novel therapy."
- SYNB1891 is being evaluated in a Phase 1, open-label,
multicenter study administered by intratumoral injection to
patients with advanced, metastatic solid tumors or lymphomas
- The monotherapy arm of the study has enrolled four dose cohorts
to date. A maximum tolerated dose has not been reached. Enrollment
of additional monotherapy dose escalation cohorts will
- Study results to date across four dose cohorts of SYNB1891
- SYNB1891 is safe and well-tolerated at currently evaluated dose
levels, as an intratumoral injection in a heterogenous patient
population with no dose limiting toxicities or infections to
- Treatment with SYNB1891 demonstrates activation of the STING
pathway and target engagement as assessed by:
- Upregulation of IFN-stimulated genes, chemokines, cytokines,
and T-cell response
- Pharmacodynamic effects including increases in serum
- Evidence of durable stable disease was observed in two patients
being treated for metastatic melanoma and metastatic small cell
lung cancer. Both patients experienced disease progression on
immunotherapy with anti- PD-1/PDL-1 antibodies prior to enrollment
in the study.
- The combination arm of the study will combine escalating dose
levels of SYNB1891 with a fixed dose of the PD-L1 checkpoint
inhibitor atezolizumab, to establish a recommended Phase 2 dose for
the combination regimen.
- The study protocol has been amended to allow for the injection
of visceral lesions in addition to cutaneous and subcutaneous
lesions in both monotherapy and combination therapy cohorts.
- Results of the SYNB1891 Phase 1 study will be presented at a
future medical meeting.
The clinical development plan for SYNB1891 is based on
compelling research from preclinical studies that demonstrate
anti-tumor activity and generation of immunological memory by
SYNB1891 in mouse models of cancer, as well as its robust
activation of human antigen presenting cells (APCs) that are key to
the generation of an anti-tumoral immune response. The Nature
Communications publication titled, "Immunotherapy with an
engineered bacteria by targeting the STING pathway for
anti-tumor immunity," details the engineering and
characterization of SYNB1891 (Leventhal, D.S., Sokolovska, A., Li,
N. et al. Nature Communications 11, 2739 (2020)).
Learn more about Synlogic's programs and pipeline by visiting
SYNB1891 is an investigational drug for
the intra-tumoral treatment of solid tumors and lymphoma, composed
of an engineered Synthetic Biotic strain of E. coli Nissle that
produces cyclic di-AMP (CDA), a stimulator of
the STING (STimulator of INterferon Genes)
pathway. This mechanism can play a critical role in the
initiation of an anti-tumor immune response via activation of APCs
and presentation of tumor antigens. The bacterial chassis of
SYNB1891 also stimulates the innate immune system by several other
mechanisms, including via Toll-like receptors (TLRs), potentially
adding to the magnitude of the overall immune response. While
SYNB1891 has been engineered with safety features that are designed
to prevent its replication unless supplemented with specific
nutrients, the bacteria remain active for several days within the
injected tumor to stimulate a local immune response. SYNB1891 is
being evaluated in a Phase 1 clinical trial.
Synlogic™ is bringing the
transformative potential of synthetic biology to medicine. With a
premiere synthetic biology platform that leverages a reproducible,
modular approach to microbial engineering, Synlogic designs
Synthetic Biotic medicines that target validated underlying biology
to treat disease in new ways. Synlogic's proprietary pipeline
includes Synthetic Biotics for the treatment of metabolic disorders
including Phenylketonuria (PKU) and Enteric Hyperoxaluria (HOX).
The company is also building a portfolio of partner-able assets in
immunology and oncology.
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, clinical development
plans, 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, 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 including the Phase 1
study for SYNB1891, and availability of clinical trial data from
that study and other studies.
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 clinical and
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.
Tecentriq® (atezolizumab) is a registered trademark of
Genentech, a member of the Roche Group.
SOURCE Synlogic, Inc.