Lux Biosciences’ Proprietary Technologies for the Ocular Delivery of Drugs

Lux Biosciences has two distinct exclusive technology platforms at its disposal for the development of proprietary products tailored to ophthalmic use.

• The bio-erodible polymer technology can be applied broadly to hydrophobic molecules as validated with LX212, or with hydrophilic (water soluble) molecules including potentially certain biologics. This technology is suited for implants or injectable preparations for either anterior segment or back-of-the-eye applications.

• The mixed nanomicellar technology is specifically designed for topical ophthalmic use of hydrophobic (water insoluble) molecules, which are very common among pharmaceuticals, and which have been traditionally very challenging to formulate. This platform has been validated with LX214.

Lux Biosciences’ ocular drug delivery technologies are highly versatile and allow the company to expand its development pipeline with additional proprietary products. Lux Biosciences may also license the technologies for use in indications and with drug molecules not pursued internally.

bio-erodible PolyMER based Ocular DRUG DELIVERY Technology

Rutgers' polymer libraries are derived from the naturally occurring amino acid L-tyrosine and consist of both polyarylates (which contain hydrolytically labile "aryl" ester linkages) and polycarbonates (which contain hydrolytically labile carbonate bonds). The combinatorial library for polyarylates consists of 112 polymers, and that of the second-generation polycarbonates of some 10,000 polymers. The polymer matrix allows for hydrogen bonding and other stabilizing interactions with the embedded drug molecule and thus is very well suited for delivery of natural drug products such as peptides. These polymers are bioerodible; during the polymer degradation process, the embedded drug is released slowly, providing therapeutic drug levels for the required period of time, typically 3 to 12 months. Invented in the laboratory of Professor Joachim Kohn at Rutgers University, these proprietary polymers are among the most advanced biomaterials currently available.

These very large libraries of polymers allow Lux Biosciences to select the most appropriate polymer for a given drug; i.e. interactions between an active drug molecule and a polymer can be fine-tuned to achieve targeted release features. For example, for certain drugs, hydrogen-bonding interactions with the polymer can be used to retard the drug release rate. For heat sensitive drugs such as biological molecules, it is possible to select polymers that can be fabricated into drug-releasing implants at a low temperature. This approach offers greater flexibility than typical development programs where only a few polymers are available and the drug-polymer interactions cannot be effectively optimized for a given drug.

In addition, the polymer formulations can be fabricated into implants, by an extrusion process, or into drug-containing micro- or nanospheres, which can be suspended in a fluid and injected into the eye, including the vitreous for direct delivery to the retina.

Using the same polymer libraries licensed to Lux Biosciences, other Rutgers partners have received marketing approval from FDA for a polyarylate-based hernia repair device and are conducting clinical trials with a polycarbonate-based bioerodible coronary stent.

MIXED nANOMICELLAR tECHNOLOGY

In collaboration with Professor Ashim Mitra of the University of Missouri at Kansas City (UMKC), Lux has developed a novel technology for the topical delivery of hydrophobic drug molecules. These mixed nanomicelles are formed from the combination of specific surfactants in specific relative proportions. The micelles are of nanometer size, small enough that the resulting aqueous solution is homogeneous and perfectly clear on appearance. Relatively high concentrations of drug could be achieved, e.g. 0.2% for the highly hydrophobic and water-insoluble voclosporin. These nanomicelles are stable over prolonged periods of time, although high temperature can melt the nanomicelles and render the fluid cloudy. Interestingly, this process is reversible when the temperature is lowered. Two patents have been filed in which the use of the technology for a wide variety of active ingredients is claimed. Unique features include the lack of irritation when compared to the classic emulsions (a milky fluid), and the ability to establish high drug levels locally. Also of particular interest is that drug levels in retina and choroid have been found to be therapeutic for several drugs examined.