Core Technology

IC14 is a clinical stage recombinant chimeric monoclonal antibody which recognizes and blocks the function of human CD14, an essential component of the innate inflammatory response to bacterial infection.  CD14 triggers activation of the innate immune response to bacterial components including lipopolysaccharide via the Toll-like receptor (TLR) pathway. Lung inflammation in response to innate immune activation through the TLR pathway is a primary factor in the early pathogenesis of acute lung injury (ALI).

IC14 had earlier been in development for severe sepsis at Icos Corporation which was acquired by Lilly in 2007. It has been used in the treatment of more than 150 patients, and has well characterized safety and pharmacology profiles. Implicit intends to initiate Phase 2 clinical development in ALI during 2009.

ALI is a severe inflammatory disease which can rapidly progress to acute respiratory distress syndrome, multi-organ dysfunction and death. The incidence of this disorder is estimated at around 200,000 cases per annum in the US and it is responsible for over 75,000 deaths – more than breast cancer and HIV AIDS combined. It is diffuse heterogeneous lung injury characterized by hypoxemia, non-cardiogenic pulmonary edema, low lung compliance and widespread capillary leakage. ALI is caused by any stimulus of local or systemic inflammation and commonly occurs after acute insults to the body, such as trauma, severe pneumonia and sepsis.

Implicit is developing the small molecule dipeptide oglufanide disodium (ODS) for a range of community and hospital-acquired infections. The mechanism of action of ODS avoids the challenge which the rapid mutation of these pathogens pose to antimicrobial drugs. Likewise, this mechanism accounts for the exceptionally broad spectrum of infections against which ODS has demonstrated efficacy, including various biowarfare agents. It also means that ODS may complement or synergise with current drugs, offering the possibility of superior clinical outcomes in severe cases, and extending the useful life of older drugs which have become less effective over time due to pathogen mutation.