Histone Deacetylase Inhibitor Program

Histone deacetylases (HDACs) are a family of enzymes which have attracted a great deal of interest as therapeutic targets in cancer. However, the potential of these HDAC inhibitors goes well beyond this relatively rare malignancy due to the activity of these compounds, both as single agents and in combination with other therapeutics, in many blood and solid cancers.

HDACs catalyze the removal of acetyl groups from lysine residues on histones, but also from other acetylated proteins such as transcription factors and heat shock proteins, thus resulting in widespread transcriptional changes and other cellular effects. The HDAC family consists of 11 different isoforms and Pharmacyclics is developing both pan- and isoform-selective HDAC inhibitors.

Abexinostat hydrochloride (PCI-24781) is an oral pan-HDAC inhibitor that has an optimized combination of potency and pharmacokinetics for use in oncology indications. In vitro abexinostat HCl has been shown to have potent anti-tumor activity in many preclinical tumor models (Buggy et al 2006), and it also potentiates many of the commonly used chemotherapies when used in combination. Currently, abexinostat HCl is being tested in clinical trials in the US and in Europe; please refer to ClinicalTrials.gov for more information on abexinostat clinical trials.

Partnering

Ex-US Partnership with Les Laboratoires Servier

In April 2009, the company entered into a collaboration agreement with Les Laboratoires Servier, the largest independent pharmaceutical company in France, pursuant to which Pharmacyclics granted to Servier an exclusive license for its Pan-HDAC inhibitors, including abexinostat HCl, for territories throughout the world excluding the United States. Pharmacyclics will continue to own all rights within the United States.