Celtic Catalysts, a spinoff from University College Dublin, has a simple mission. "We come up with ways of making chiral drugs more cost-effectively," says CEO Brian Kelly.

The goal may be straightforward, but achieving it is quite complicated. Resolving racemic mixtures of D- and L-isomers of a molecule - mirror images of one another with often quite distinct biological activities - can be a costly exercise. Effectively, half of the product has to be discarded. Asymmetric catalysis, which involves the production of single enantiomers, can offer a more streamlined alternative.

Celtic Catalysts' sales manager Kevin Dalton (left) and CEO Brian Kelly

Courtesy of Celtic Catalysts

There are good incentives to make the process more efficient. "Around 40% of all drugs on the market are chiral, and [they occupy] about 80% of the pipeline," says Kelly.

Since the company was set up in 2000, Celtic Catalysts has raised around €3 million ($4.6 million US) in equity and grants and is now "nearly profitable," says Kelly. Its business is based on two main pillars: the production of chiral ligands for driving asymmetric reactions in pharmaceutical manufacturing, and the production of high-value synthetic intermediates or drug building blocks. The company's main competitors are the in-house process-development teams within pharmaceutical manufacturers, although these are also its customers.

The company's client base is primarily but not exclusively found overseas. It has also completed research assignments with large players such as Pfizer, Wyeth, and DSM.

Celtic is particularly focused on phosphorus chirality, which has major relevance to drugs based on nucleoside analogs, widely used in cancer and antiviral therapy. Adding a phosphorus moiety to a nucleoside drug increases potency by several orders of magnitude, Kelly says. Why this happens is not fully understood, but it may be due to improved membrane transport.

It's a technically demanding area, says Kelly. "There's no one else doing that." Apart from a couple of notable exceptions, P-chiral ligands are difficult to synthesize on an industrial scale, and their use is mainly confined to laboratory settings.

Asymmetric synthesis is a cutting-edge discipline within chemistry, and Celtic can call on some of the key players in the field, among them Barry Sharpless of the Scripps Research Institute in San Diego. Sharpless was awarded the 2001 Nobel Prize in Chemistry for developing chiral catalysts for oxidation reactions. Celtic cofounder Declan Gilheany, who was Kelly's PhD supervisor, completed a stint as a Fulbright Scholar in Sharpless' lab at the Massachusetts Institute of Technology during 1988-1990.