The United States Department of Defense (DOD) completed its Travelan® shigellosis challenge studies in non-human primates.  It found that Travelan® prevented clinical shigellosis (bacillary dysentery) in 75% of Travelan® treated animals compared to placebo and demonstrated a significant clinical benefit. Moreover it learned that prophylactic administration of Travelan® may provide an effective prevention alternative to antibiotics of gastrointestinal infections in humans. 

The United States Army seeks a preventative treatment that protects against enteric diseases, specifically Shigella. The DOD research site-driven study sought to demonstrate that the Immuron technology platform would be effective at neutralizing pathogenic gastrointestinal bacterial infections and ultimately could potentially represent a safe and effective treatment for U.S. military personnel and civilians stationed or traveling in locations where the risk for such infections is high.

The Commercial Sponsor

The US Department of Defense (DOD) partnered with an Australian biotech venture called Immuron Limited (IMRN). IMRN focuses on developing and commercializing oral immunotherapeutics for the prevention and treatment of many gut mediated pathogens.

Immuron is a publicly traded Australian venture. It raised $6.1 million in an IPO April 18, 2017 at $10 per share. Its current share price is $3.08. A thinly capitalized venture, the partnership with the U.S. DOD undoubtedly is a valuable relationship that can support the ongoing early stage development of its investigational products.

Immuron has a novel and safe technology platform with one commercial asset Travelan® generating revenue. Immuron’s lead clinical candidate, IMM-124E, is presently in Phase II trials in Severe Alcoholic Hepatitis (SAH) and Pediatric Non-alcoholic Fatty Liver Disease (NAFLD). The company now has plans to develop a U.S. registration dossier for IMM-124E for Travelers’ Diarrhea. Immuron’s second clinical-stage asset, IMM-529, targets Clostridium difficile Infections (CDI), and is presently in a clinical trial in CDI patients. These products together with the Company’s other preclinical immunotherapy pipeline products currently under development targeting immune-related and infectious diseases are anticipated to meet pressing needs in the global immunotherapy market.

The Study

The Shigella challenge model was used to assess the therapeutic potential of Travelan as a prevention treatment for shigellosis or dysentery. The placebo-controlled study was carried out in 12 juvenile rhesus monkeys separated into 2 groups including 1) a Travelan treatment cohort of 8 and 2) a placebo cohort of 4, which were treated twice daily for a total of 12 doses over a 6-day period. The animals in this preclinical study were treated for 3 days prior to oral challenge with ~3 x 109 viable Shigellaorganisms.

The Results

As reported late last year, all (4 of 4 – 100%) placebo-treated animals displayed acute clinical signs of dysentery within 24 – 36 hours of Shigella challenge. Only two of the eight Travelan-treated group displayed any signs of dysentery. The remaining 6 of 8 (75%) of the Travelan-treated group remained healthy and without signs of dysentery post challenge. Recently completed histopathological analysis, which provides a comprehensive view of the clinical disease and its effect on tissues of gut, revealed that all animals in the placebo-treated group displayed severe inflammation in different parts of the gastrointestinal tract. These animals also had very high levels of inflammatory cytokines (IL-1b, IL-6 and IL-8) in fecal samples collected throughout the study. The inflammation seen in the gastrointestinal tract and the increase in inflammatory cytokines in the feces were closely associated with the observed clinical outcomes of dysentery. Only 3 of the 8 Travelan-treated animals had signs of inflammation in the gastrointestinal tract, and only 2 of those had high levels of inflammatory cytokines in fecal samples. All other animals in the Travelan-treated group were clinically healthy and did not excrete any inflammatory cytokines. Overall the results suggest that Travelan® is functionally cross-reactive and may have some prophylactic activity against Shigellosis.

U.S. Command Comments

Dr. Robert Kaminski, Chief, Subunit Enteric Vaccines and Immunology, Department of Enteric Infections, Bacterial Diseases Branch, WRAIR reported “The latest results reported by our colleagues at the US Armed Forces Research Institute of Medical Sciences (AFRIMS), an overseas laboratory of the Walter Reed Army Institute of Research (WRAIR), located in Bangkok Thailand are very impressive indeed. The study results clearly demonstrated that animals with severe inflammation in the gastrointestinal tract and high inflammatory cytokines in fecal samples were associated with severe dysentery and that prophylactic administration of Travelan significantly reduced the inflammatory response.”

Global Burden of Diarrheal Diseases

The global burden of these diseases outweighs any of the more complex diseases seen in gastroenterology clinics.  Each year an estimated 1.5 billion episodes of diarrhea occur worldwide. These episodes result in the deaths of approximately 2.2 million people—mostly children in developing countries according to research.

A high priority objective for the US Army is preventative treatment protecting against enteric diseases, specifically shigellosis. Shigella spp are estimated to cause 80-165 million cases of disease worldwide, resulting in 600,000 deaths annually. They are particularly prevalent in both sub-Saharan Africa and South Asia.

Source: Globe news wire

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