Synlogic Presents Preclinical Data from Synthetic Biotic Immuno-Oncology Program at the American Association for Cancer Research 2018 Annual Meeting
– Data highlight the application of Synthetic Biotic medicines for the potential treatment of a variety of solid tumors –
– Company is advancing the first candidate from this program into IND-enabling studies in 2018–
“Our IO program highlights the potential of our Synthetic Biotic platform for the design and engineering of novel living medicines with multiple mechanisms of action to treat a broad range of diseases, including cancer,” said J.C. Gutiérrez-Ramos, Ph.D., Synlogic’s president and chief executive officer. “Our approach enables us, in a single treatment, to locally deliver multiple, regulatable activities that stimulate an immune response and modulate the tumor environment in order to mobilize the immune system against the tumor and its metastases. We intend to advance our first IO program into IND enabling studies this year.”
In a presentation in the late-breaking research immunology session, Activation
of Innate and Adaptive Immunity via Combinatorial Immunotherapy using
Synthetic Biotic Medicines,
In preclinical studies,
- In vitro, SYN-STING produces biologically-relevant levels of ci-di-AMP, activating APCs, while SYN-Kyn consumes kynurenine at concentrations comparable to those found in patients’ tumors;
- SYN-STING treatment of either B16.F10 or A20 tumors results in robust tumor rejection or control, which correlates with an early rise in innate-immune cytokines and later results in T cell activation in tumors and tumor-draining lymph nodes;
- Combining SYN-Kyn with a checkpoint inhibitor led to profound anti-tumor activity in the CT26 immunocompetent tumor model; and
- A strain engineered to combine both genetic circuits (SYN-STING:Kyn) demonstrates equivalent production of ci-di-AMP and consumption of kynurenine in vitro compared to the individual strains SYN-STING and SYN-Kyn, respectively.
A second presentation entitled Metabolic Modulation of the Tumor Microenvironment using Synthetic Biotic Medicines demonstrated that engineered bacterial strains designed to consume either kynurenine (SYN-Kyn) or adenosine (SYN-Ade) effectively relieved TME immunosuppression and promoted anti-tumor activity.
- Invitro SYN-Kyn and SYN-Ade can deplete kynurenine and adenosine, respectively, at concentrations that are clinically relevant;
- SYN-Kyn demonstrated rapid and near-complete reductions in tumor kynurenine levels in vivo;
- A combination of either SYN-Kyn or SYN-Ade with checkpoint inhibition led to superior anti-tumor activity in the MC38 immunocompetent tumor model compared with checkpoint inhibitors alone.
About Synthetic Biotic Medicines
Synlogic’s innovative new class of Synthetic Biotic medicines 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 phenylketonuria, respectively. Patients with these diseases
are unable to break down commonly occurring by-products of digestion
that then accumulate to toxic levels and cause serious health
consequences. When delivered orally, these 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 patient.
Synlogic is pioneering the development of a novel class of living medicines, Synthetic Biotic medicines, based on its proprietary drug development platform. Synlogic’s initial pipeline includes Synthetic Biotic medicines for the treatment of rare genetic diseases, such as urea cycle disorders (UCD) and phenylketonuria (PKU). 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).
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