Amalyte has been working on a class of known compounds represented by AM1101, which have modulatory activity for the enzyme lactosylceramide synthase (Gal T-2). Gal T-2 transfers galactose from UDP-galactose to GlcCer to generate lactosylceramide (LacCer). The compounds have been shown to function through a well-defined molecular pathway involving LDL, PDGF, EGF, and VEGF all of which converge on the enzyme Gal T-2 to produce lactosylceramide, which in turn, through a series of steps, stimulates cell proliferation. Bioprofiling studies on AM1101 indicate potentially broad utility in a wide variety of hyper-proliferative conditions/diseases, including restenosis, polycystic kidney disease (PKD), atherosclerosis, and inflammation.
The efficacy of AM1101 has been demonstrated in a variety of animal models, most notably (i) a rabbit model of restenosis, where AM1101, given 24 hrs before balloon angioplasty and daily thereafter for 7 days completely mitigates neo-intimal proliferation, and (ii) age-related macular degeneration, supported by in vitro data in a large number of other therapeutic settings. Amalyte is currently focused on developing small molecule inhibitors, including the lead compound AM1101.
Market Opportunity
Amalyte believes that inhibitors of Gal T-2 may be useful in restenosis, age-related macular degeneration, and polycystic kidney disease. All of these represent large market opportunities.
The use of coronary stents as a vehicle for localized drug delivery has proven to be widely effective in reducing restenosis after angioplasty. However, the safety and efficacy of the drugs currently used in drug-eluting stents are a significant medical concern. These drugs delay healing, with characteristics like tissue necrosis and persistent local fibrin deposits, increasing the risks of late thrombosis and hypersensitivity. In fact, recent reports on late thrombosis have dramatically reduced the use of stents in the first half of 2007. Based on the cell pathways involved and early cell based data, Amalyte believes that targeting Gal T-2 inhibitors will not induce late stage thrombosis. Amalyte believes there is a well-defined clinical need and significant market opportunity for a new family of drugs with a different mode-of-action, to minimize the problems described.
Age-related macular degeneration (AMD) is the leading cause of vision loss in people 60 and older. This is a multibillion dollar market which is expected to increase dramatically over the next decade due to the demographics of the aging population and the inadequacy of current therapies. Current treatments are estimated to be only around 40% effective at slowing the progression of the disease. Treatments that can improve this efficacy rate are expected to have blockbuster potential. Initial animal studies suggest that inhibitors of Gal T-2 may provide additional therapeutic benefit in AMD either alone or in conjunction with existing therapies.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common autosomal disease, affecting 500,000 Americans, and 7,000 new patients are identified each year, ranking first among inherited and congenital causes of end stage renal failure and death. PKD is a chronic disease involving cyst formation and cell growth due to the abnormal action of growth promoting factors and cyclic AMP that accelerates fluid secretion, accumulation and expansion of the cysts. There is currently no therapy available for the disease. Amalyte believes that Gal T-2 inhibitors may be useful in the treatment of PKD.