BioWorld International Correspondent

LONDON - Three university scientists frustrated at waiting for grant applications to be processed have opted instead to start a company to advance their research in second-generation histone deacetylase (HDAC) inhibitors.

Karus Therapeutics Ltd. has been spun out of Southampton University with £750,000 (US$1.4 million) from SULIS, the university's seedcorn fund and IP2IPO Group plc, a quoted technology management company.

Co-founder Paul Townsend told BioWorld International: "We are three young scientists and wanted to see if we could do it. Submitting grant [applications] is long-winded, and the HDAC inhibitor market is getting very competitive; we wanted to see if we could go faster." The other founders are chemist A. Ganesan and Graham Packham, an oncologist.

Karus' second-generation inhibitors offer improved specificity over those being developed because they target particular enzyme subtypes. That is expected to mean they will cause fewer side effects than first-generation HDAC inhibitors, such as Cambridge, Mass.-based Gloucester Pharmaceuticals Inc.'s product in pivotal trials for cutaneous T-cell lymphoma, which are pan specific.

"We are building on the basic principles of what is known," Townsend said. "The target is validated so we don't have to mess around with that. We are starting from templates and optimizing them. We are confident we will avoid the toxicity issues associated with other compounds in development."

Karus has discovered a number of small-molecule inhibitors, the most advanced of which are ready to move into animal testing.

Townsend is a cardiac specialist, and while to date the majority of HDAC inhibitors in development are for treating cancer, Karus intends to target cardiovascular diseases, including cardiac hypertrophy, also. Earlier this year, Myogen Inc., of Denver, concluded a deal for HDAC inhibitors in the treatment of cardiovascular disease with Novartis AG, of Basel, Switzerland, after demonstrating that HDAC inhibitors can block cardiomyocyte hypertrophy and increase expression of the alpha myosin chain.

HDAC biology plays a role in neurological and bone diseases also and Townsend said Karus will explore those areas, too.

Within the scope of the initial funding Karus expects to advance at least one compound to Phase I.

"We are also close to appointing a CEO, and have irons in the fire for a second funding round," Townsend said.

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