A Novel MOA in Ophthalmology
Iconic Therapeutics developed ICON-1, an immunoconjugate fusion protein, to address TF overexpression in wet age-related macular degeneration (AMD). With its novel mechanism of action (MOA), ICON-1 binds to cells in the choroidal neovasculature (CNV) that aberrantly overexpress TF and interfered with TF’s ability to drive angiogenesis and inflammation. In addition, the ability of ICON-1 to bind to and reduce or eliminate existing pathologic vessels makes it an attractive candidate for the treatment of pathological neovascularization, a defining characteristic of wet AMD. As such, it represents a novel and potentially disease-modifying approach. This property of ICON-1 distinguishes it from other drugs currently used in the treatment of wet AMD.

ICON-1 is in Phase 2 clinical development. Administered directly into the eye (intravitreally), ICON-1 selectively binds to TF present in the CNV, suppressing the abnormal blood vessel growth that lies at the root of the disease as well as reducing the production and release of factors such as VEGF that contribute to the pathophysiology of the disease.

We have completed Phase 1 and Phase 2a clinical trials of ICON-1 in wet AMD to assess its safety, biologic activity and pharmacodynamic effect in newly diagnosed patients. The randomized, double-masked, multicenter, active-controlled Phase 2a EMERGE study was conducted in 88 patients to evaluate the safety and biological activity of repeated intravitreal administration of ICON-1 in patients with choroidal neovascularization (CNV) secondary to AMD. Results showed that ICON-1 was well tolerated and that in combination with anti-VEGF therapy treated both the symptoms and the underlying process driving inflammation and CNV. The combination effectively reduced CNV lesion size, increased the durability of effect and improved removal of pathologic fluid from the retina.

Based on these positive Phase 2a results, we plan to initiate a Phase 2b study of ICON-1 in combination with anti-VEGF treatment in 2018. This trial will be larger than the Phase 2a study and will explore a higher dose of ICON-1 for a longer period of time.