Scientific Rationale

Oral Immune Therapy 

  1. Oral immune therapy is a method for alteration of the systemic immune system via an effect on the gut immune system.
  2. Oral immune therapy is based on an inherit mechanism in which the GI immune system inhibits or promotes its reaction towards an orally administered antigens, adjuvants, and/or antibodies.
  3. The gut immune system has a unique ability to differentiate between harmful antigens which induce inflammatory response, and non-harmful epitopes which can induce tolerance. Dendritic cells as well as other innate cells are involved in this process.
  4. Oral immune therapy is a platform for a wide range of diseases, and has limited side effects or toxicity, as it is not associated with general immune suppression, and therefore has no risks of severe infection or malignancy, and is easily tolerated by patients.
  5. Oral immune therapy targets the innate immune system of the gut, including NKT cells and dendritic cells to send a signal to the systemic immune system and promote regulatory T cells (Tregs) that suppresses inflammation at the site of disease. The specificity of the effect is therefore dependent on the site of inflammation
  6. In addition, oral immune therapy targets the gut microbiome, thereby affecting NASH and the metabolic syndrome via alteration of the balance between pro and anti-inflammatory-inducing cells.

Inflammation and disease: Metabolic syndrome and NASH

Click here for our phase 1/2 NASH results

  1. Disruption of the interface between inflammatory and metabolic pathways is central to the pathogenesis of NASH.
  2. Obesity and NASH are characterized by chronic activation of inflammatory pathways in peripheral tissues.
  3. The balance between mediators derived from the immune system or adipose tissue plays a role in hepatic and systemic insulin action and in the development of the metabolic syndrome and NASH.
  4. Inflammation is part of the cascade (the "two hits" hypothesis) leading to NASH.
  5. The gut microbiome plays a role in the pathogenesis of NASH. Both the microbiome diversity as well as specific bacterial strains were described to be associated with the development of NASH.

The innate immune system in the gut serves as a bridge delivering signals from the gastrointestinal tract to the systemic immune system

  1. The gut mucosal immune system is the largest lymphoid organ in the body. It differentiates the antigenic signals against the high “background noise” of food and bacterial antigens. Despite constant antigenic stimulation, suppression of inflammation is the rule.
  2. Several components of the gut immune system, including dendritic cells, epithelial cells, natural killer cells, intraepithelial lymphocytes, M cells, and others serve as a target for signals from the lumen.
  3. These components of the gut immune system can deliver the signals to the systemic immune system, thereby affecting the immune response of the host. Both the secretion of cytokines and chemokines, as well as the promotion of subsets of innate and adaptive cells are involved in the transmission of signals from the gut to the systemic immune system.

Sphingolipids in NASH and diabetes

  1. NASH signatures can be made based on lipidomics data:  Circulating phospholipid profiling identifies NASH signature.
  2. The insulin receptor is localized at the cell surface in a glycosphingolipid-containing lipid micro-domain.
  3. Modulation of glycosphingolipids metabolism improves insulin sensitivity and reverses hepatic steatosis. Glycosphingolipids may interact with upstream and downstream elements of the insulin receptor.
  4. Data in animal models supports the effects of orally administered glycolipids on intracellular cell signaling, cell membranes, and on alteration of the immune cellular balance.

Immuron Clinical and Pre Clinical Trial products: IMM-124E & IMM-529

Immuron has several products in trial including:

  •   IMM-124E: anti LPS+ adjuvants
  •   IMM-529:  anti Toxin B Clostridium Difficile

Click here to view our C. Diff Scientific Presentation

Bovine antibodies targeting primary and recurrent clostridium difficile disease are a potent antibiotic alternative

 Mode of action

  1. IMM-124E is composed of anti-LPS antibodies and adjuvants, many of which are glycosphingolipids, targeting the gut microbiome and the innate immune system of the gut.
  2. The dual-effect of IMM-124E was shown synergistic in animal model of diabetes and fatty liver disease, demonstrating an enhanced effect of oral administration of the anti-LPS antibodies with the adjuvants as compared to each of them alone.
  3. The dual mechanism of action is based on the promotion of regulatory T cells by the specific adjuvants, which can suppress inflammation as the site of disease without inducing generalized immune suppression, along with an anti-LPS effect of the antibodies altering the gut microbiome.
  4. Immune modulation via promotion of regulatory T cells and alteration of NKT cells.
  5. Improve signals between the gut and the systemic immune system for induction of a balanced immune homoesotatis.
  6. Target cells: Alteration of the innate immune cells including: dendritic cells; NKT cells; tight junction; epithelial cells.
  7. Effectors: Microbiome derived products; Adjuvants; Anti-LPS.

Data in animal models

     IMM-124E was also shown effective in animal models of :

  • Fibrosis (CCL4 fibrosis model)

  • NASH (ob/ob)

  • Type 2 diabetes (ob/ob)

  • Colitis (mouse-TNBS colitis)

  • Immune mediated hepatitis 

  1. In the ob/ob model of diabetes and NASH, oral administration of IMM124E decreased serum TNF-a levels, and increased the number of splenic CD4+CD25+, CD4+CD25+Foxp3+ Tregs, and NKT cells. The effects on the systemic immune system were associated with a decrease in ALT serum levels and hepatic triglycerides, and improved glucose intolerance.

  2. In the mouse-TNBS colitis model, oral administration of IMM-124E increased serum levels of the anti-inflammatory cytokine IL10, and promoted both CD4+CD25+ and CD4+Foxp3+ Tregs. These effects were associated with amelioration of body weight loss and improved bowel histology. Both extent of disease, inflammation score, and colitis damage and regeneration scores decreased in treated mice.

  3. In the CCL4 fibrosis model, oral administration of IMM-124E was effective in alleviation of liver injury as was determined by the following measures: A decrease in liver enzymes and bilirubin levels. Liver pathology staining with trichrom blue and Masson red showed improvement in periportal necro-inflammatory score, bridging and confluent necrosis and hepatocellular apoptosis. The fibrosis score – Metavir improved in treated mice. These effects were associated with decrease number of F4/80 in the liver and a decrease is alpha SMA measure of fibrosis.

  4. In immune mediated hepatitis model, oral administration of IMM-124E suppressed the inflammation and alleviated the immune mediated liver damage along with suppression of the pro inflammatory cytokines.