Irish firm adds diversity to chiral catalyst sector

Related tags Catalysis Enantiomer

Irish start-up Celtic Catalysts believes it can tackle two of the
major obstacles holding back the use of catalysts to make chiral
drugs - the strong patent positions of existing players and
difficulties in scale-up - with its platform technology, reports
Phil Taylor.

Drug compounds often exist as asymmetric (right- and left-handed) mirror images (enantiomers), but usually only one of the structures exhibits the desired pharmacological activity. If a drug can be made one-handed, or chiral, it generally means that smaller doses are needed and potential side effects from the other form can be avoided.

In an interview with​, one of the company's founders, Brian Kelly, said that despite widespread recognition that catalysis is often the best way to make a chiral molecule, the most common method is still the resolution method. In essence, this means that you make both versions of the molecule, and throw away or recycle the unwanted one.

At present, there are still only a few chiral catalysis processes used by the pharmaceutical industry, although the number is growing all the time, said Kelly, citing a study conducted a couple of years ago that found less than 20 processes in use, but another 30 or so in the research pipeline.

The reasons are two-fold.

"Firstly, there are not a lot of industrially applicable catalysts. Many work well on the bench scale, but technical and cost issues often preclude scaling up to the level needed for production,"​ he said.

Secondly, the intellectual property position centred around those catalysts that are in use tends to be so strong, that the developers can charge a lot for licenses. And that raises costs, which can mean that resolution is the preferred method, despite the wastage or recycling requirement.

Giving an example, Kelly cited Takasago Corp of Japan's BINAP, which he described as very useful catalyst that ran into problems as a result of the strong IP position. "They priced themselves out of the market,"​ said Kelly, noting that today chiral technology suppliers need to be more realistic in their pricing strategies to succeed in the marketplace.

Diversity is the key

Celtic Catalysts hopes to overcome these problems by tapping into a technology platform developed by Kelly and the company's other founder, Declan Gilheaney at University College Dublin. This relies on a set of chemistries that allow the creation of vast numbers of catalyst compounds - hundreds of thousands of molecules - that greatly adds to the diversity of catalysts available and makes Celtic Catalysts unique in the marketplace, he said.

At present, companies focusing on chiral catalysts - such as Chiral Quest and Solvias - offer toolboxes of up to around 30 ligands (catalyst precursors) targeting specific applications. Meanwhile, the larger chemical players (Avecia, Degussa, Johnson Matthey etc) tend to have just a handful of catalysts that complement the other parts of their businesses, spanning early-stage development to full-scale manufacturing.

Celtic Catalysts plans to put together pallets of catalysts - for specific applications - that can be screened from its wider catalyst library. Once a promising candidate to catalyse a reaction is found, the company can then generate a series of others - based on similarities in structure and activity models - that can be tested for activity by customers or by Celtic Catalysts itself.

Seeking partners

At present, the Irish company is looking for a co-development partner to help take the business forward, while simultaneously optimising the process to make the targeted catalyst pallets.

To date, Celtic Catalysts has operated with a total of around €1.6 million in start-up funding, including €650,000 from a venture capital round last month. The company is based at NovaUCD, University College Dublin's technology park, and has five staff at present.

Last year, a report published by Frost & Sullivan predicted that the market for chiral compounds destined for the drug industry will rise from $7.0 billion (€6bn) in 2002 to $14.9 billion in 2009. In 2002, 55 per cent of chiral compounds were generated by traditional resolution technologies, 35 per cent by chemocatalysis and 10 per cent by biocatalysis.

Meanwhile, F&S also predicts that global sales of single-enantiomer compounds will reach $8.57 billion by the end of 2004 and $14.94 billion by the end of 2009, an 11.4 per cent annual growth rate.

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