KERYX Biopharmaceuticals

Protein Kinase Overview

Kinases are a large class of protein enzymes that regulate the transmission of signals between and within cells through a process called signal transduction. Consequently, kinases play a key role in the way cells function and communicate. If this communication is compromised, various diseases, such as cancer, diabetes, obesity, and immunological disorders, may result. Kinases represent exciting new targets for drug discovery, with a broad range of opportunities. Recent scientific developments have validated the potential utility of kinases as specific and important pharmaceutical leads. In addition, the genomics efforts of the biomedical community have identified and continue to identify an abundance of additional kinase targets that are available for drug discovery.

KinAce

Scientific validations are continuously driving intense interest in kinases as drug targets. However, as kinases share very similar structures, it is difficult to identify compounds that target specific kinases, without interfering with the activity of other kinases. KinAce, a rational signal transduction modulation platform, represents the first practical use of the human genomics database to systematically generate drug candidates that target specific protein kinases.

"Know the sequence (of a kinase), know the drug"

Using KinAce proprietary bioinformatics-based approach, Keryx requires only the amino acid sequence of the target kinase in order to generate a drug lead. Keryx does not require the 3-D structure of the kinase in its drug discovery process. Consequently, KinAce allows Keryx to significantly shorten the drug discovery and development process.

The KinAce algorithm identifies unique regulatory regions within each kinase. Using these unique regions as a basis, the Company can quickly design novel drug candidates to inhibit or stimulate specific kinases associated with particular disease states. In addition, the high level of specificity inherent in the drug leads derived from the KinAce platform offers the potential for significantly reduced toxicity.

Moreover, the KinAce platform's ability to rapidly generate these specific kinase modulators provides a powerful tool for discovering new kinase functions-this process is called kinase functional genomics. These newly discovered kinase functions can then become targets for the Company's KinAce drug discovery program.

Keryx has licensed exclusive worldwide rights to its KinAce technology from Children's Hospital of Boston and Yissum Research and Development the technology transfer arm of the Hebrew University in Jerusalem Israel. These rights include a recently issued fundamental U.S. patent, as well as several additional patent applications pending in various jurisdictions throughout the world. These patents applications cover regions within multiple kinase families as well as the algorithm for finding suitable drug candidates, individual compounds and specific indications.

KinAce

Drug Candidates

For additional information on the KinAce

drug candidates, please click on:

KRX-123

Emerging KinAce candidates

Small Integrated Building-blocks ("SIB") Technology

In January 2002, Keryx obtained the exclusive worldwide license to a novel technology known as Small Integrated Building-blocks ("SIB''), for the conversion of peptides and other existing drugs into small molecules that have the potential for oral delivery.

Keryx believes that the SIB technology is a breakthrough in rational small molecule drug design and is a natural complement to the Company's
KinAce platform. KinAce excels in generating therapeutic small peptide drugs for life threatening indications, such as KRX-123, which is currently in advanced preclinical development for the treatment of hormone resistant prostate cancer. However, for diseases which are not life-threatening and for which the treatment is longer-term, small molecules offer an advantage over peptides because of their potential for oral delivery and their improved pharmacokinetic properties.

Keryx believes that SIB will significantly increase the value of KinAce by allowing the rapid conversion of KinAce's peptide drug leads for non-life threatening indications into small molecules.

In addition, SIB provides Keryx with the opportunity to offer pharmaceutical companies with existing peptide and rigid small molecule drugs an opportunity to convert those compounds into more valuable small molecule drugs.

The technology utilizes modular building blocks (scaffolds) in order to mimic a targeted peptide or rigid small molecule. The SIB scaffolds are then used as a template to generate highly focused libraries of small molecule drug candidates that retain flexibility and are expected to possess superior pharmacokinetic properties compared to peptide and rigid small molecule drugs. The SIB technology has already demonstrated in-vitro efficacy.