• THE COMPANY
  • Executive Summary
  • The Team
• TECHNOLOGY
  • hI-con1™
  • hI-con1™ and Wet AMD
  • hI-con1™ and Cancer
• PLANS FOR CLINICAL STUDIES
• OPERATIONAL OVERVIEW
  • Manufacturing
  • GLP Safety Studies
  • Analytics
  • Regulatory Affairs
  • Intellectual Property
• REFERENCES
• CONTACT

hI-con1™

hI-con1 is a chimeric, IgG-like homodimeric protein composed of a targeting domain (mutated, inactive factor VIIa) fused to an effector domain (IgG Fc) with an intact hinge region.  hI-con1 targets Tissue Factor (TF) which is expressed on the luminal surface of many pathologic cells. Such cells include choroidal neovascularization associated with wet age-related macular degeneration (Bora, et. al, 2003), TF-expressing cancer cells (Cocco, et. al. 2010; Kasthuri, et. al. 2009) and tumor-associated pathologic blood vessels (Hu, et. al 1999).  TF is not present on the surface of normal cells (Drake et al., 1989; Contrino et al., 1996).

The effector domain of hI-con1 (IgG Fc) triggers immune destruction of hI-con1 targeted cells.  The two functional domains of hI-con1 are connected by the hinge region of IgG1 containing two disulfide bonds (See Figure 1).

FIGURE 1: hI-con1™ MOLECULAR STRUCTURE

Factor VII is an initiator of the clotting cascade and it begins the clotting process by binding very tightly to TF.  Consequently, hI-con1 has a very high affinity for TF, an affinity which is much higher than can be achieved by an antibody.  In order to prevent unscheduled clotting, the FVIIa domain in hI-con1 has been mutated such that it is defective as a trigger of clotting.  Some have raised the concern that bleeding may occur if hI-con1 leaks into the blood stream (Kasthuri, et al, 2009).  In the GLP safety studies (intravenous and intravitreal) Iconic conducted in support of its wet AMD clinical plan, hI-con1 was not observed to cause unscheduled bleeding (data on file at company).

Once hI-con1 is bound to TF on the surface of these pathologic cells, the immune system is triggered to selectively destroy those cells by dispatching natural killer cells, leaving normal cells unaffected.  The antibody domain of hI-con1 that signals the immune system of the patient to dispatch natural killer cells to destroy the target cells is the effector region of hI-con1, an Fc portion of IgG1 (See Figure 2). 

FIGURE 2:  hI-con1™ MeECHANISM OF ACTION

While the drug product is stored a < -60°C, hI-con1 is stable at room temperature for 8 hours.