By Randall Osborne
West Coast Editor
Lining up its nucleic acids to attack drug discovery, new biotechnology company Archemix Inc. has licensed for $17.5 million Gilead Sciences Inc.¿s aptamer technology ¿ a small piece of which already has been the subject of Gilead¿s deal worth almost twice as much.
Last year, in an agreement valued at $32 million at least, Gilead granted an exclusive, worldwide license for NX 1838, its proprietary aptamer and inhibitor of vascular endothelial growth factor (VEGF), to New York-based EyeTech Pharmaceuticals Inc., which focuses on drugs to reduce and prevent vision loss caused by eye disease. (See BioWorld Today, April 7, 2000.)
¿What Gilead did with EyeTech was to license out a particular aptamer, as you would a particular antibody for a particular disease, primarily macular degeneration,¿ said Martin Stanton, president of Cambridge, Mass.-based Archemix. ¿This is just one therapeutic use of aptamers. We got essentially all of the unlicensed applications for therapeutic uses ¿ any target, any diseases.¿
Aptamers are 3-dimensional nucleic acids that bind to molecular targets in a manner ¿conceptually similar¿ to antibodies, Archemix said, and could be applicable to drug discovery, target validation and affinity capture reagents.
¿You can do with an aptamer essentially anything you can do with an antibody,¿ Stanton told BioWorld Today. ¿Antibodies work very well, and people understand them. I¿m not saying these will supplant antibodies today, but they¿re an incredibly powerful alternative.¿
The advantages are several, he said.
¿[Aptamers are] made entirely through a benchtop procedure that takes a couple of weeks, where you identify an aptamer that binds very specifically and tightly to a specific protein,¿ Stanton said, noting that antibody manufacture is much more time consuming.
Chemically synthesized, aptamers also are stable and easy to express in vivo, he added.
Archemix aims to combine the aptamer technology with its nucleic acid-based biosensors called RiboReporters to measure the level and state of molecules, developing platforms for in vitro and in vivo, making ¿snapshots¿ of cells before and after drugs, to examine differences.
¿That¿s where the fun starts, because we can say, Did this hit the target you wanted to hit? Did it elicit a toxic response?¿¿ Stanton said.
Like antibodies or aptamers, RiboReporters bind to molecular targets, but they also generate a signal when they bind.
¿We can make sensors to whatever you want, and have them reporting inside living cells inside animals,¿ Stanton said.
¿It¿s odd,¿ he added. ¿We¿re using nucleic acids to look at the proteins, and it¿s not even the proteins we¿re interested in studying. We¿re interested in the small-molecule drug leads that interact with the proteins.¿
Gilead acquired the aptamer technology in its $550 million stock buyout of Boulder, Colo.-based NeXstar Pharmaceuticals Inc. in 1999. (See BioWorld Today, March 2, 1999.)
¿Their primary interest is in small molecules, and so the use of aptamers wasn¿t really fitting into their core plan right now,¿ Stanton said.
NeXstar had an agreement dating back to 1993 with Schering AG, of Berlin, for aptamers with radiotherapeutics. ¿You attached some sort of radioisotope to an aptamer, and it binds to a cell, and you can kill that cell,¿ Stanton said.
Another deal, for in vitro diagnostics using aptamers, was made with SomaLogic, of Boulder, Colo.
¿Really, [the aptamer field] is wide open for therapeutics,¿ Stanton said.
Founded in May, Archemix, with 26 employees, has an alliance made that month with Ribozyme Pharmaceuticals Inc., of Boulder, Colo., for allosteric ribozyme technology. Archemix completed one round of financing at the same time, an $8.25 million funding through institutional investors that included Atlas Ventures, of Boston; Prospect Venture Partners LP, of Palo Alto, Calif.; and Rho Management Trust II, of New York.