Innovative Science
Karus's research and development strategy is focused on the design and development of new small molecule anti-cancer and anti-inflammatory therapeutics that function through the regulation of epigenetic mechanisms and lipid kinase signaling pathways.
Epigenetics
One of our main focus areas is the discovery of novel histone deacetylase (HDAC) inhibitors. HDACs have emerged as important molecular targets, playing an essential role in chromatin remodelling and regulating the expression of oncogenes, tumor suppressor genes and inflammatory genes. There is a strong scientific and clinical rationale for the development of HDAC inhibitors (HDIs) to treat chronic diseases including cancer, rheumatoid arthritis (RA), psoriasis, organ transplant rejection, multiple sclerosis (MS), systemic lupus erythematosus (SLE), and inflammatory bowel and respiratory disorders.
Our approaches to HDAC inhibition are unique: our most advanced programs are focused on the development of novel, re-engineered HDIs that display best-in-class in vitro potency and in vivo efficacy, but which importantly lack the off-target and toxicity limitations presented by competitor compounds. We have also developed a structurally-novel series of highly potent HDAC6-selective inhibitors that have therapeutic potential in the treatment of immune-inflammatory disorders, cancer and neurogeneration. Development candidates from these three programs are being advanced for the treatment of solid tumors, RA, psoriasis and organ transplant rejection. First clinical trials are scheduled to commence in early 2011.
Lipid Kinase Signaling
At Karus, we have extensive experience gained over many years in the field of lipid kinase signaling, and have successfully designed and developed several novel series of class I PI3K inhibitors for the treatment of PTEN-null and haematological tumors, and autoimmune diseases including RA, inflammatory skin disorders and organ transplantation. These series comprise a class of dual p110β/δ-specific inhibitors, and distinct classes of inhibitors that selectively target p110δ and p110β. We have established important academic collaborations for these programs, notably with Professor Bart Vanhaesebroeck and the cell-signaling laboratory at Queen Mary, University of London to develop inhibitors targeting class II and III PI3Ks. Preclinical development in our lipid-kinase signaling programs is currently underway.
Potency and selectivity are key challenges for the next generation of HDAC inhibitors. Karus's inhibitors exhibit best-in-class biochemical and cellular activity - significantly greater than the approved drug, Vorinostat - and have an exquisite specificity profile for the HDAC superfamily.
Stephen Shuttleworth PhD FRSC, Chief Scientific Officer
Karus Therapeutics Ltd
2 Venture Road
Southampton Science Park
Chilworth
Hampshire
SO16 7NP
United Kingdom