Research and Development

SQUALAMINE

Eye Drop Formulation for Ophthalmology Indications
Squalamine is a first-in-class small molecule anti-angiogenic drug with a novel intracellular mechanism of action. The drug acts against the development of aberrant neovascularization by inhibiting multiple protein growth factors of angiogenesis, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor growth factor (bFGF), with high potency at nanomolar concentrations.

OHR Pharmaceutical has developed a novel eye drop formulation of squalamine for the treatment of wet-AMD designed for self-administration which may provide several potential advantages over the FDA approved current standards of care (Lucentis, and Eylea Intravitreal Injections).

• Eye drops versus standard of care which is an intravitreal injection directly into the eye every 4-8 weeks on a chronic basis
• Reducing or eliminating intravitreal inections has the potential to provide the patient with improved safety by reducing or eliminating side effects associated with the intravitreal injection procedure
• Inhibition of multiple growth factors (VEGF, PDGF, bFGF) may achieve superior visual acuity outcomes. Clinical evidence has shown that inhibiting VEGF and PDGF increases the percentage of patients achieving significant gains in visual acuity
• Cost advantage of a small molecule when compared to the current standards of care which are large molecules and cost $1,850-$2,000 per intravitreal injection

Preclinical testing has demonstrated that the eye drop formulation is both safe to optical tissues and achieves in excess of target anti-angiogenic concentrations in the tissues of the back of the eye. The company expects to discuss these studies at scientific conferences in 2012, and commence a Phase II clinical trial for the treatment of Wet-AMD with this novel eye drop formulation in 2012.

Squalamine had previously been evaluated for the treatment of wet-AMD using an intravenous formulation in over 250 patients. The trials demonstrated that the molecule had biologic effect and maintained and improved visual acuity outcomes, with both early and advanced lesions responding. The program had been taken into to a phase III study with a special protocol assessment and fast track status from the US FDA, but had been discontinued due to the commercial challenges of a chronic weekly IV infusion for this patient population.

Intravenous Formulation for Oncology Indications
Because of its potent anti-angiogenic effects, squalamine also shows considerable promise in the treatment of solid tumors such as ovarian cancer. In addition to its anti-angiogenic mechanism, it also inhibits the sodium-proton antiporter pump system in the cell membrane, thus creating entry points in the cell membranes of resistant Cancer cells to allow for standard chemotherapeutic agents to enter and induce apoptosis. In a concluded Phase IIa study, patients with stage III & IV Refractory and Resistant Ovarian Cancer received Squalamine in conjunction with Carboplatin, and demonstrated impressive overall response rates. The drug has been awarded Orphan Drug Status from the US FDA for this indication, The company expects to make the progression free survival and overall survival data from this completed study available through publication in a scientific journal or meeting in 2013.