Kereos' targeted therapeutics and molecular imaging agents will enable clinicians to both deliver therapeutic agents to specific diseased tissues and to confirm the delivery of the therapeutic agents to the target. This unique combination of targeted delivery and MRI imaging verification allows for much greater control over patient dosing and monitoring response.
The Kereos nanodroplet technology is comprised of two main excipients (pharmacologically inert ingredients): a perfluorocarbon (PFC) core, and a lipid monolayer surrounding the core. These excipients have been previously studied in humans. The PFC core is highly visible on new fluorine MRI systems, enabling verification of delivery to the target sites. The lipid monolayer provides the anchor for therapeutic payloads and targeting molecules. Fusion of the lipid monolayer with the target cell membrane provides highly efficient delivery of the therapeutic payload to the diseased cells.
Added to the excipients are the active ingredients of targeting molecules (ligands) and the drug payload. Although targeted drug delivery has long been a goal of researchers and companies, Kereos is one of the first companies to develop a platform in which the drug remains stably confined to the nanodroplet when it enters the blood stream, but appears to release quickly and specifically when the target is reached.
The Kereos technology incorporates a ligand that targets the ανβ3 integrin associated with cancer and cardiovascular disease. This targeting ligand provides more direct targeting of the drug product to the disease site, allowing for more effective treatment and diagnosis.
The desired combination of stability and efficacious delivery is achieved by delivering the drug compound to the cells through the fusion of the lipid layer of the nanodroplet and lipid layer of the cell, rather than simple diffusion across the extracellular fluid. The drug payload appears to remain largely confined to the lipid layer as it passes from the nanodroplet to the cell membrane.
Once safely across the cell membrane, the therapeutic payload (usually a prodrug, which is a modified version of the active drug) is delivered to the diseased cells and enzymatically cleaved to produce the active drug. This results in efficient delivery to the target, minimal systemic toxicity due to aqueous diffusion of the drug to locations other than the target cells, and the ability to keep fragile protein-based therapeutics stable and active throughout the delivery process. This mechanism of action has been demonstrated in vitro and in vivo.
Kereos has an extensive intellectual property portfolio covering all aspects of its nanodroplet technology, as well as the targeting ligand
Kereos is addressing the targeted cancer therapeutics market, which is by far the fastest growing and the highest value portion of the oncology drug market. The targeted therapeutics market is expected to be around $19.14 billion by the end of 2013. Targeted therapeutics include a number of sub-categories, such as targeted monoclonal antibodies (mAb), small-molecule therapeutics that target specific molecules involved with cancer, and targeted payloads of anti-cancer drugs. The latter category of targeting cancer drugs to tumors is currently receiving significant attention, as it is hoped that selectively targeting large quantities of anti-cancer drugs to the disease may result in greater efficacy and lower systemic toxicity to the patient. As the Kereos nanodroplet technology is capable of delivering far more drug to the target than antibody-based methods, it may offer significant improvements in clinical performance as a targeted drug delivery technology.
The key advantages of the Kereos nanodroplet drug delivery platform include:
• Targeting: Increases amount of drug delivered to disease target, while reducing off-target distribution. This offers the potential of increased efficacy and reduced toxicity, as compared to existing cancer therapeutics.
• Much higher drug payload than antibody-based targeted delivery: 10-1000x more active drug compound per particle.
• Much lower cost of goods: $10-$100 per dose as compared to $10,000 per dose for many antibody therapies
• Confirmation of delivery by MRI imaging: Kereos nanodroplets are highly visible on MRI, so it may be possible to confirm that targets have been hit, and quantify how much drug has been delivered.
• Enables targeted delivery of peptide, small-molecule and natural product therapeutics: Many of these are either too toxic or too fragile to be delivered systemically, yet they are of enormous interest for their therapeutic potential.