MELBOURNE, Australia—Immuron Ltd., a microbiome company specializing in developing and commercializing oral immunotherapeutics for the treatment of gut-mediated diseases, has seen promising results from recent preclinical studies. IMM-529, a first-in-class oral therapeutic, was shown to prevent Clostridium difficile infection recurrence in more than 77.8 percent of infected mice in preclinical studies.
The mouse models in question were developed by Associate Professor Dena Lyras of Monash University and her team to assess IMM-529’s effectiveness when combined with the antibiotic vancomycin. The studies found that combination therapy with IMM-529 and vancomycin led to a significant reduction in mortality: the combination dropped disease recurrence and mortality to 22.2 percent, compared to 88.9 percent mortality in the control group treated with vancomycin alone.
“We are delighted with these findings,” said Lyras. “This is a key proof-of-concept study which confirms the clinical potential for this class of drug in the treatment of C. difficile. We now have successfully demonstrated in three preclinical models that IMM-529 can be utilized as a therapeutic in all three aspects of the disease, including prevention, treatment of primary disease and recurrence, the latter representing a growing unmet need in the fight against C. difficile.”
IMM-529 is a biologic under development for the prevention and treatment of C. difficile infections. Unlike antibiotic treatments, this approach does not destroy the microbiome, allowing it to return to a healthy state. The antibodies in IMM-529 have been shown to be cross-reactive with a variety of human and animal C. difficile isolates as well as to their associated toxin B, vegetative cell and spore components. These antibodies have also been shown to neutralize toxin B from a historical C. difficile strain (630) and from a hypervirulent strain responsible for the recent worldwide outbreaks.
“Our IMM-529 is a first-in-class program and a potential paradigm-changing new anti-infective product. The successful completion of our preclinical studies has demonstrated that IMM-529 could be the first oral non-antibiotic therapeutic against C. difficile, and we look forward to progressing this asset to the clinic in 2016,” Thomas Liquard, CEO of Immuron, added in a press release.
A RedChip analyst upgraded Immuron in the wake of these results, noting in a report that “From a mechanism of action standpoint, we see a number of advantages of IMM-529 when compared to Merck’s recently approved drug for C. difficile, bezlotoxumab. Bezlotoxumab is a monoclonal antibody which neutralizes toxin B that has entered the blood stream. IMM-529 is a polyclonal antibody that targets toxin B, plus spores and vegetative cells. Also, IMM-529 targets toxin B in the human gut, which is the specific site of C. difficile infection, while bezlotoxumab targets toxin B in the blood stream, after it passes through the gut and colon. These advantages are promising, although it remains to be seen if these advantages will translate into improved results in humans.”
C. difficile infections are one of the leading serious health issues within hospitals and long-term care facilities. Antibiotics are the preferred method for treating C. difficile infections, but some have limited efficacy and/or cause an imbalance in the gut microbiome that can lead to recurrent infection. Recurrent C. difficile infection affects approximately 100,000 people in the United States every year, with an estimated 28,000 deaths recorded annually in the United States alone. Globally, the annual economic burden cause by these infections is estimated at more than $10 billion.
Research and consulting firm GlobalData reported in late 2015 that the global market for C. difficile infection (CDI) is expected to grow by a compound annual growth rate of 15.8 percent to reach more than $1.5 billion by 2024, “driven by the modest uptake of patent-protected, CDI-specific antibiotics and the arrival of novel non-antibiotic approaches to treat and prevent recurrent CDI.”
Given those growth prospects, it’s not surprising that Immuron and Merck are far from the only companies targeting this promising market space—Seres Therapeutics, Rebiotix, Sanofi Pasteur and Synthetic Biologics all have contenders in the ring as well. Seres is advancing SER-109 for CDI in adults who have had three or more episodes in the previous nine months, and has received a Breakthrough Therapy designation for the compound from the U.S. Food and Drug Administration. Rebiotix’s lead compound, RBX2660 for recurrent CDI, is approaching Phase 3, and the company is also advancing RBX7455 for oral C. difficile prevention. Sanofi Pasteur is going the preventive route, with a prophylactic vaccine ACAM-CDIFF. Synthetic Biologics is developing SYN-004, which is in Phase 2 development for the prevention of CDI and antibiotic-associated diarrhea.