AVX-470 for inflammatory bowel disease (IBD) is our lead program. IBD comprises two types of chronic inflammatory disease of the intestines. Ulcerative colitis affects only the colon while Crohn´s disease can be more wide spread but primarily affects the small intestine. There are more than 2.5 million people with IBD worldwide. The primary symptoms of both conditions are abdominal pain and diarrhea. These symptoms result in a significant reduction in quality of life and the risk of life-threatening complications and diseases, including cancer.

TNF is an inflammatory cytokine that has been implicated in IBD. Indeed, some of the most effective treatments for IBD are injectable anti-TNF antibodies. These antibodies bind to and neutralize TNF, which reduces inflammation. Although existing anti-TNF antibodies are efficacious, they distribute throughout the body rather than staying in the intestines where the inflammation occurs. As a result, they may cause serious side effects due to untargeted immunosuppression, such as lymphoma and reactivation of tuberculosis. Because of these side effects, anti-TNF antibodies are most often used only as a second- or third-line therapy despite evidence that earlier use could improve patient outcomes.

AVX-470 is an orally administered anti-TNF antibody that accesses and neutralizes TNF from within the intestine, rather than from outside like injected anti-TNFs. Because the drug acts locally within the intestine instead of systemically across the body, AVX-470 has the potential to achieve the efficacy of current anti-TNF drugs but with fewer (or no) systemic side effects.

The preclinical studies that Avaxia has conducted on AVX-470 look promising. We demonstrated that the TNF specific antibodies in AVX-470 were comparable to the marketed anti-TNF drug Remicade® (infliximab) in terms of binding, functional activity, and certain other characteristics. Initial preclinical work has been completed with statistically significant data generated in multiple models of IBD efficacy. Avaxia has also shown that AVX-470 remains in the intestine, with only low, sporadic levels in the blood of preclinical subjects. A 28 day GLP toxicology study showed no drug related adverse effects up to the highest levels tested.

Avaxia initiated a clinical trial of AVX-470 in ulcerative colitis patients in February 2013. The US FDA cleared an Investigational New Drug Application (IND) for this trial in late November 2012. The clinical trial is a randomized, double-blind, placebo-controlled trial in 24 patients with active ulcerative colitis. Three dose levels of AVX-470 will be administered to patients over 28 days in an ascending-dose design. The endpoints of the trial include safety, pharmacokinetics (measurement of AVX-470 in blood, stool and colon tissue), and immunogenicity. In addition, clinical symptoms and endoscopic disease severity will be measured, and levels of biomarkers of disease and inflammation will be measured in blood, stool and tissue before and after treatment.

Avaxia believes that AVX-470 has the potential to be a transformative first-line therapy for IBD, which would provide patients with a valuable new therapeutic option and could expand the anti-TNF market well beyond its current size of $2.5 billion annually.