Graybug is developing injectable controlled-release technologies to allow dosing once every four to six months for the treatment of neovascular age-related macular degeneration (AMD), thereby reducing patient burden from 20+ injections yearly to two to three injections. The company is planning to file an Investigational New Drug application before year-end.
Graybug licensed the simple, particle suspension technology from Wilmer Eye Institute (Baltimore), and the broad platform will allow for multiple indications, including glaucoma, Interim CEO Jeffrey Cleland, PhD, said. The company has developed “novel chemical entities” to allow for intraocular pressure (IOP) lowering and neuroprotection from a single agent over a six-month period. The technology encapsulates a drug inside microparticles to then be injected into the vitreous. Particles come out as continuous gel in a viscous vehicle. Over a very short period of time, they aggregate together and form a solid implant-like structure. Even out now to three months, images show an intact implant structure with no free-floating individual particles in the visual axis that can be observed by fundus photography or slit lamp exams.
Wilmer physicians (Justin Hanes, Peter Campochiaro, and Peter McDonnell) found that adding a hydrophilic coating to the polymer would “significantly” reduce inflammation and subsequent analysis has shown the particles to aggregate upon injection, minimizing interference with the visual axis.
Details from a rabbit study are expected in early May 2016. However, at three months post-injection, 1,000 full KI of the molecule is sustained in the retinal pigment of the choroid, and the company is seeing “very therapeutic effects” after three months, Dr. Cleland added. These initial results suggest the formulation may be viable for an every-four-month dosing. To date, no inflammation, histology, or toxic effects have been noted.
Initial mouse studies indicated duration of treatment with no diminuation through nine weeks; the company is now evaluating rabbit choroidal neovascularization (CNV) models up to six months to demonstrate the relationship between the pharmacokinetic profile that has been seen in the ocular tissues and the inhibition of laser-induced CNV.
The company has begun collaborating with Aerie Pharmaceuticals to develop Aerie’s compounds in Graybug’s delivery systems. In other glaucoma programs, Graybug is developing novel chemical entities to create prodrugs delivered on its platforms, and believes it might be successful in combining prostaglandins with carbonic anhydrase inhibitors as a single agent. That program is slated to begin in 2017.
Jeffrey Cleland, PhD
Jeff has 20 years of industry experience in research and development, including more than a decade at Genentech, Inc.