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Overview

Rucaparib is an oral, small molecule poly ADP-ribose polymerase (PARP) inhibitor that is a potent inhibitor of PARP-1 and PARP-2. We intend to develop rucaparib for the treatment of patients with cancers predisposed to PARP inhibitor sensitivity. Our initial focus is on tumors with defective DNA repair function in ovarian cancer.

Rucaparib is currently the subject of several clinical studies, including the ARIEL (Assessment of Rucaparib In Ovarian CancEr TriaL) program, which includes the Phase II ARIEL2 study and the Phase III ARIEL3 study, both in platinum-sensitive ovarian cancer patients. ARIEL2 is a single-arm, open label study designed to identify tumor characteristics that predict sensitivity to rucaparib using DNA sequencing to evaluate each patient's tumor. The ARIEL3 pivotal study is a randomized, double-blind study comparing the effects of rucaparib against placebo and evaluating whether rucaparib given as a maintenance therapy can extend the period of time for which the disease is controlled after a positive outcome with platinum-based chemotherapy. For more information on ARIEL2 and ARIEL3, please visit www.arielstudy.com.

In addition, a Phase II study is underway in the U.S. and U.K. to assess efficacy of rucaparib in patients with ovarian cancer, including in patients with hereditary, or germ-line, mutations in BRCA genes. During the first half of 2014 we plan to initiate a Phase II study of rucaparib in pancreatic cancer patients with BRCA mutations, given the reported presence of germ-line BRCA mutations in various pancreatic cancer patient populations and the clinical responses demonstrated in such patients in our Phase I study.

We own global development and commercialization rights to rucaparib.

DNA Repair and PARP

Cells in the human body are under constant attack from environmental factors that can cause damage to DNA, as well as DNA-binding chemicals that can cause changes in the composition of DNA. Since DNA is the vehicle by which fundamental information is passed on when a cell divides, it is critical that DNA damage be repaired. A fundamental principle of cancer therapy is to damage cells profoundly with radiation or DNA-binding drugs, for example, alkylating agents or platinums, and induce apoptosis in those cells, thus killing the cancer cells. DNA repair mechanisms may reduce the activity of these anti-cancer therapies, but, conversely, inhibition of DNA repair processes may enhance the effects of DNA-damaging anti-cancer therapies.

PARP initiates a process which quickly repairs DNA during the early stage of damage. In the absence of PARP, cells are unusually sensitive to DNA damage when exposed to radiation or DNA-alkylating agents. Additionally, tumors that are defective in BRCA are particularly prone to DNA damage, as BRCA is involved in DNA repair as well. There are two major forms of PARP that are involved in DNA repair in this way, PARP-1 and PARP-2. We believe that a drug that inhibits both PARP-1 and PARP-2 may have enhanced activity in preventing DNA repair in tumor cells, particularly those tumors that have defective BRCA.

Development of a Companion Diagnostic

Consistent with our strategy with CO-1686, we announced in August 2012 a collaboration with Foundation Medicine to develop a companion diagnostic to identify biomarkers to select patients most likely to respond to rucaparib.

rucaparib Scientific Presentations