HDAC inhibitor

Histone deacetylases (HDACs) belong to a larger set of proteins collectively known as epigenetic regulators that can alter gene expression by chemically modifying DNA or its associated chromosomal proteins. Abnormal activity of these regulators is believed to play an important role in cancer and other diseases. There are currently two HDAC inhibitors, one oral and one injectable, approved by the FDA for the treatment of T-cell lymphoma.

lead candidate: Pracinostat

Pracinostat is a potential best-in-class, oral HDAC inhibitor that has been tested in more than 200 patients in multiple Phase I and pilot Phase II clinical trials in hematologic and solid tumor indications. Pracinostat has been tested in adult and pediatric patients and found to be generally well tolerated with readily manageable side effects often associated with drugs of this class. The results of these studies suggest that Pracinostat has potential best-in-class pharmacokinetic properties when compared to other oral HDAC inhibitors, including Panobinostat and Varinostat.

Pracinostat has demonstrated clinical evidence of single-agent activity, including two complete responses out of 14 patients (14%) with acute myeloid leukemia (AML) in a Phase I dose-escalation study. The results from this study were presented at the American Society of Hematology Annual Meeting in December 2010. In addition, data from a Phase II clinical trial of Pracinostat showed that eight out of 22 patients patients (36%) with intermediate or high-risk myelofibrosis experienced a clinical improvement, including two patients with anemia response and six patients with spleen size reduction. These results were published in the September 2012 issue of Leukemia Research.

In December 2012, data from a pilot Phase II clinical trial of Pracinostat in combination with Vidaza^® (azacitidine) in patients with advanced myelodysplastic syndrome (MDS) were presented at the American Society of Hematology Annual Meeting. Data from nine patients treated at the MD Anderson Cancer Center showed an overall response rate (CR+CRi+PR) of 89%, including seven complete responses. Combined with the results from an additional patient treated at the University of Wisconsin-Madison, another complete reponse, the trial showed an overall response rate of 90% (nine out of 10).

We plan to initiate a blinded, placebo-controlled Phase II trial of Pracinostat in combination with Vidaza^® in patients with intermediate and high-risk MDS in June 2013. In addition, we plan to initiate two open-label, single-armed Phase II trials of Pracinostat, both in combination with either Vidaza^® or Dacogen^®: 1) MDS patients non-responsive to front-line Vidaza^® or Dacogen^® and 2) elderly AML patients not suited for induction therapy. We expect to initiate both open-label trials during the third quarter of 2013.

We own exclusive worldwide rights to all of our drug candidates, including Pracinostat.