Dyax employs protein discovery to find new radiopharmaceuticals

Company intends to license targeted radiotracers

A Cambridge, MA, company is using a novel compound-screening processto discover proteins that may form the basis for targeted radiopharmaceuticalimaging agents. Dyax believes that its phage display technologycan speed up drug development by allowing the screening of hundredsof millions of proteins to find those that are most suited forimaging applications.

Dyax was formed last year through a merger of two companies,Biotage and Protein Engineering. The two firms had been workingtogether on using phage display to discover affinity ligands thatcould be used to help purify drugs and biotherapeutic compounds.

In the course of their research, they found that phage displaycould also be used to identify proteins that bind to specificsites in the body, according to Edward Cannon, president of thecompany's research division. By tagging them with radioisotopes,the proteins could form the basis for targeted radiopharmaceuticalssimilar to peptide- or monoclonal antibody-based agents.

Dyax's phage display technology is a type of molecular diversitytechnology in which large numbers of compounds are created andthen screened to discover those that contain the desired properties,such as binding to a specific site. Phage display is unique inthe number of compounds it can create, according to Cannon.

"What distinguishes phage display from other moleculardiversity technologies is the ability to create a larger numberof compounds, which means you have a higher likelihood of gettinga hit," Cannon said. "If you can screen enough differentcompounds, you have a very high likelihood of finding one thatbinds to your target with very high affinity."

Dyax has used phage display to discover a protein that bindsto human neutrophil elastase (HNE), a protein produced by whiteblood cells in response to an infection or inflammation. The HNEprotein therefore can be used to develop an imaging agent thattargets pathologies such as inflammatory bowel disorders, pulmonarydiseases, fevers of unknown origin, and osteomyelitis.

Ideally, an agent based on Dyax's HNE protein would be easierto use than white cell scanning, the current method for imaginginfection. In that process, a patient's blood is drawn, labeledwith a radiotracer, and then reinjected to target the infectioussites. Competition to Dyax's protein could come from peptide developerDiatide, which is developing a technetium-labeled peptide agentfor imaging infectious sites (SCAN 4/26/95).

Both proteins and peptides are strings of amino acids, butproteins differ from peptides in that proteins have definite structures,while peptides do not, Cannon said. Like peptides, Dyax's proteinsare far smaller than monoclonal antibodies. This confers advantagesin imaging applications because proteins bind to the sites theyare targeted for and wash out of the sites to which they are nottargeted.

"For an equivalent mass of our kind of protein versusan antibody, we will have 30 times the potency of the antibody,"Cannon said.

Dyax is preparing to begin animal efficacy studies of its HNEwhite blood cell protein, and in September received a $100,000phase I Small Business Innovation Research grant to fund the studies.The company is about six months away from demonstrating efficacyand lack of toxicity.

Dyax's proteins could become promising new products, but thecompany has chosen to seek licensing agreements for its compoundsbefore they enter human clinical trials rather than deal withthe expense and hassles of bringing the agents to market. Thecompany has held preliminary discussions with some radiopharmaceuticalcompanies but does not have any agreements in place, accordingto Cannon.

One imaging company with whom Dyax has a licensing agreementis monoclonal antibody developer Cytogen of Princeton, NJ. Cytogenhas licensed phage display for use in identifying compounds forthe human therapeutics and in vitro diagnostics fields. Dyax plansto retain rights to phage display for the medical imaging marketand several other industries, according to Cannon.

Although privately held Dyax is in the development stage inthe medical imaging market, the company is well established inthe drug purification market and is recognizing revenue from itsoperations in that industry, Cannon said.