Dyax, Genzyme Team On Anti-Inflammatory Protein

Dyax Corp. and Genzyme General (both of Cambridge, MA) have joined forces on an anti-inflammatory project that could bring Dyax $31 million in payments and royalties. The deal centers on a new protein, EPI-KAL2, which Dyax discovered using its proprietary phage display technology. Under the partnership arrangement, Dyax is responsible for clinical development while Genzyme assumes sales and marketing functions. The initial therapeutic indication for EPI-KAL2 will be hereditary angioedema (HAE), a condition that causes inflammation and severe pain in respiratory and abdominal tissues.

As part of the agreement, Genzyme has made a $3 million equity investment in Dyax's recent private placement, extended a $3 million line of credit to the company, and committed an additional $25 million in potential milestone payments.

"This alliance represents our second major development partnership with a leading biopharmaceutical firm," said Henry E. Blair, chairman and chief executive officer of Dyax. "Genzyme's experience in protein therapeutics will complement our internal scientific expertise as we advance EPI-KAL2 into the clinic. Selection of this protein for clinical development highlights the potential of Dyax's phage display technology to generate promising therapeutic candidates."

HAE, a genetic disorder affecting between 1 in 10,000 and 1 in 50,000 people worldwide, is caused by a deficiency in a natural inhibitor of C1- esterase and kallikrein. In HAE patients, the unregulated activity of kallikrein produces painful and potentially fatal inflammation of various tissues, including those of the gastrointestinal tract, bronchi and laryngeal structures. These attacks typically last from 1 to 4 days, with most patients experiencing one or more episodes per month. No satisfactory treatment for HAE exists. Many patients receive steroids as general immunosuppressive agents, but these individuals still remain susceptible to acute and potentially life-threatening attacks. In addition, a number of patients are resistant or intolerant to steroids.

EPI-KAL2, a recombinant protein, mimics the effect of the natural inhibitor by binding with high affinity and specificity to human plasma kallikrein, thereby potentially benefiting those with HAE. Dyax has obtained U.S. patent protection for the compound.

Dyax's patented phage display is a versatile, high-throughput technique with broad applications to drug discovery. According to Dyax phage display's advantages over combinatorial chemistry and antibody-based approaches include increased speed and reduced costs for discovery of lead compounds.

Phage display is used to select proteins that bind to a target of interest. The selection is made from a diverse set of up to hundreds of millions of proteins displayed on the surface of a bacteriophage (bacterial virus), known commonly as "phage."

The phage display process consists of:

• Generating a large collection of phage, known as a "library," that contains genes encoding up to hundreds of millions of related proteins, or potential binding compounds
• Screening the library by exposing it to a specified target and isolating those phage whose displayed proteins bind to the target
• Analyzing the selected binding compounds by sequencing their genes and by producing and characterizing small quantities for relative specificity and affinity to the target.

Screening a phage display library also entails three basic steps:

• Expose phage in the phage display library to a fixed target

• Wash away unbound phage and leave selected phage bound to target

• Release and amplify the selected phage for further binding evaluation

For more information: Henry E. Blair, CEO, Dyax Corp. One Kendall Square, Building 600 Cambridge, MA 02139. Telephone: 617-225-2500. Fax: 617-225-2501.