Shigatoxin-producing E. coli (STEC) is primarily a foodborne bacterial infection affecting approximately 314,000 people annually in the industrialized world. Most STEC secrete two toxins, Shigatoxin 1 (Stx1) and Shigatoxin 2 (Stx2) which can cause serious health complications, particularly in young children and the elderly. There are no approved products available for the treatment of STEC infections. STEC infection is characterized by acute diarrhoea with severe abdominal cramps. Bloody diarrhoea is observed in about 70% of all STEC cases. In 10-15% of STEC cases patients progress to Hemolytic Uremic Syndrome (HUS) a life-threatening condition that results in a combination of red blood cell destruction, acute renal failure and a low platelet count. HUS is the most important cause of acute renal failure in children which can lead to end-stage renal disease requiring dialysis and possibly kidney transplantation.
Thallion’s Shigamabs product consists of two monoclonal antibodies designed to bind specifically and exclusively to the Stx1 and Stx2 toxins secreted by STEC. The antibodies bind to their respective toxin and neutralize them by forming a complex that is absorbed and destroyed by the liver and spleen. The dual antibody approach enables Shigamabs to address cases in which both Shigatoxins are present and also overcomes the inability of existing diagnostic technology to distinguish between cases caused by only one of the two toxins.
Thallion has completed multiple preclinical studies and four Phase I clinical trials evaluating the efficacy and safety of Shigamabs. The clinical trials demonstrated that Shigamabs are safe and well tolerated when administered both individually and in combination at various dose levels. No serious adverse events were experienced in any of the 50 healthy volunteers that have received Shigamabs. In preclinical studies Shigmabs demonstrated a significant protective effect at relatively low doses, and animal rescue was possible even when Shigamabs were administered 72 hours post-infection.
Thallion has met with the U.S. Food and Drug Administration in preparation for its next clinical trial. Thallion intends to conduct a pivotal Phase II/III trial pending further discussions with the FDA. Upon approval to proceed from the FDA, Thallion anticipates that filing for regulatory approval after the successful completion of a pivotal trial could occur as early as 2010. Shigamabs have been granted Orphan Drug Status in the U.S. and EU which provides for seven and ten years, respectively, of market exclusivity for the approved indication following regulatory approval. Thallion is pursuing a global development and commercialization strategy targeting industrialized nations, which represent approximately 80% of STEC cases in the world.