Oral optimism

CAMBRIDGE, Mass.—Clinical-stage biotechnology company Evelo Biosciences, Inc. shared preclinical data last week for for EDP1908 in a poster presentation at the Society for Immunotherapy of Cancer’s (SITC) 35th Anniversary Annual Meeting. The data show that orally administered EDP1908 demonstrated antitumor effects that surpassed those of both checkpoint inhibitors and orally delivered microbial strains in preclinical models.

EDP1908 is an extracellular vesicle product candidate being developed for the treatment of cancer. Extracellular vesicles are generated by some bacteria and share molecular content with their parent bacterium, though in particles that are approximately one-one thousandth the volume and that lack the ability to self-replicate. Between their smaller size and their innate abilities—facilitating bacterial communication and survival, host-immune modulation, material exchange and cell-cell interactions—they offer improved distribution and target engagement compared to microbes, as noted by Evelo.

“We are discovering and developing products that engage the small intestinal axis, SINTAX. They control systemic immune and inflammation responses by their action in the small intestine, which then sends potent immunomodulatory signals throughout the body. We have shown the potential of SINTAX medicines in the clinic and are exploring ways to optimize their effects using new forms and formulations,” stated Dr. Mark Bodmer, chief scientific officer of Evelo. “Today, we are unveiling new foundational data showing that an orally administered bacterial extracellular vesicle (EV) has striking preclinical anti-tumor effects without systemic distribution. These data suggest that EVs of appropriately selected microbes have the potential to drive an entirely new type of I/O therapy by engaging SINTAX.”

In the preclinical study, tumor-bearing mice received ascending doses of either oral EDP1908 or the parental microbial strain of EDP1908, or with anti-PD-1. Treatment with EDP1908 resulted in superior tumor growth control versus either the parent microbial strain or anti-PD-1 therapy, and demonstrated a dose-dependent reduction of tumor growth. The effects were also at least comparable to those reported in the literature for intra-tumoral immune stimulators.

Treatment with EDP1908 activated multiple parts of the immune system, including IFNγ-positive cytolytic and helper lymphocytes, dendritic cells, and interferon gamma-induced protein 10 (IP-10) in the tumor microenvironment. Fluorescent biodistribution analysis showed that EDP1908 was not detected outside the gastrointestinal tract. These data suggest that EDP1908 activates innate immunity by acting locally on host immune cells in the gut to trigger distal immune responses within the tumor microenvironment, with no apparent adverse safety or tolerability effects preclinically. Evelo reports that EDP1908 is in preclinical and manufacturing development.

According to Evelo, SINTAX “plays a central role in governing the immune, metabolic and neurological systems.” As noted on the company's website, “The small intestine is the largest part of the immune system and is a central hub of the body’s network of lymphatic vessels. Immune cells from around the body circulate via these lymphatic vessels through the tissues of the small intestine, where they are conditioned by exposure to the many antigens and immunomodulatory agents that continuously pass through. These conditioned immune cells can then impact disease and health at all sites of the body. Microbes, in particular, have the ability to condition immune cells in the small intestine.”