On November 6, 2018 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage drug discovery and development company applying synthetic biology to beneficial microbes to develop novel living medicines, reported the presentation of preclinical data from its first immuno-oncology (IO) program at the 33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2018) (Press release, Synlogic, NOV 6, 2018, View Source [SID1234530844]). Synlogic’s first Synthetic Biotic clinical candidate (SYNB1891) is designed to induce the production of type I interferon (IFN) through dual activation of innate immune pathways. Data that will be presented at SITC (Free SITC Whitepaper) 2018 demonstrate that SYNB1891 generated significant anti-tumor activity, systemic immunity and long-term immunological memory in mouse tumor models. The data highlight the advantages of SYNB1891 for the potential treatment of cancers that are resistant to current immunotherapy approaches.

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"Our goal is to design Synthetic Biotic medicines that enable us to expand the benefits of immunotherapy broadly across tumor types," said Aoife Brennan, M.B., Ch. B., Synlogic’s president and chief executive officer. "Tumors have multiple mechanisms to evade the immune system and our Synthetic Biotic platform is uniquely suited to address this area of unmet medical need given our ability to engineer multiple mechanisms in a single biotic. We are excited to move this first program into the clinic."

"Our Synthetic Biotic drug candidate, SYNB1891, enabled dual activation of the innate immune system via both the bacterial chassis and its STING agonist payload in mouse tumor models," said Jose Lora, Ph.D., Synlogic’s vice president of research. "We have engineered a non-pathogenic bacterial strain to deliver immunostimulatory molecules directly into the tumor microenvironment, which has the potential to induce a local immune response and establish systemic immunity while minimizing systemic toxicity."

In a presentation, Development of a STING Agonist-producing Synthetic Biotic Medicine to Activate Innate and Adaptive Immunity and Drive Antitumor Immune Responses, to be given at the SITC (Free SITC Whitepaper) 33rd Annual Meeting on Friday, November 9, 2018, Synlogic scientists will describe an engineered strain of E. coli Nissle, (SYNB1891) that produces cyclic di-AMP (CDA) which stimulates the STING pathway. Recent studies have demonstrated that activation of the STimulator of INterferon Genes (STING) pathway can play a critical role in the initiation of an anti-tumor immune response via activation of antigen presenting cells (APCs) and presentation of tumor antigens. SYNB1891 can be delivered directly into the tumor where it remains active for several days to stimulate a local immune response. When the bacteria are engulfed by APCs within the tumor, the STING pathway is activated within the cell resulting in a type I IFN response. In addition, the bacterial chassis used in Synlogic’s Synthetic Biotic approach is believed to be able to stimulate the innate immune system by several other mechanisms, including via Toll-like receptors (TLRs), potentially adding to the magnitude of the overall immune response.

In preclinical studies that will be presented at SITC (Free SITC Whitepaper) 2018, Synlogic has demonstrated that:

In vitro, SYNB1891 produces biologically-relevant levels of CDA, activating both mouse and human APCs
In a reporter assay, SYNB1891 induced production of higher levels of type I IFN protein compared to naked CDA, and in human primary APCs SYNB1891 treatment resulted in significantly higher expression of genes encoding type I IFN-beta and IL-6, when compared to naked STING-agonist treatment
Treatment with the un-engineered E. coli Nissle (SYNB) alone resulted in increased tumoral innate cytokine levels and anti-tumor activity, demonstrating that the bacterial chassis itself triggers complementary innate immunity pathways which are further potentiated by arming the bacteria with STING agonist
SYNB1891 prototype-treated tumors demonstrate upregulation of an inflammation-related gene signature
SYNB1891 prototype treatment of B16.F10 melanoma tumors resulted in an early rise in innate-immune cytokines and at later times resulted in T cell activation in tumors and tumor-draining lymph nodes
These pharmacodynamic changes correlated with robust anti-tumor responses and complete tumor regressions
Mice that exhibited complete regression of tumors in response to SYNB1891 prototype treatment demonstrated long-term immunological memory when re-challenged with tumor cells >40 days post tumor eradication
Investor and Analyst Event Details
On Saturday, November 10, 2018, at the SITC (Free SITC Whitepaper) 33rd Annual meeting in Washington D.C., Synlogic will also host an Investor and Analyst Event. The program will feature commentary from experts Filip Janku, M.D., Ph.D., Associate Professor in the Department of Investigational Cancer Therapeutics and Center Medical Director for the Clinical and Translational Research Center at MD Anderson Cancer Center, and Dmitriy Zamarin, M.D., Ph.D., Assistant Attending Physician in Gynecologic Medical Oncology and Immunotherapeutics Services at the Memorial Sloan Kettering Cancer Center who will discuss the unmet medical need and current landscape in immuno-oncology, as well as company representatives who will outline Synlogic’s plans for clinical development of its clinical candidate, SYNB1891.

Presentations will begin at 12:30 pm, until 2:00 pm. ET, on Saturday, November 10, 2018.

The event will be webcast live and available via a link on the company’s website in the Events Calendar in the Investors and Media section.