Synlogic, Inc. (Nasdaq: SYBX) announced on 11/6/18 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 2018). 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 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.
“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 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 2018, Synlogic has demonstrated that: