"Whereas advances in pharmacologic and mechanical reperfusion therapy have improved the outcomes of patients with STEMI, reperfusion injury, which is associated with severe damage to the cardiac tissue, is a significant complication that has no current safe and effective treatment options," commented Dr. Andrew Salzman, Inotek's President and CEO. "These Phase 2 data provide further support for our PARP inhibitor program in cardiovascular disease. These results combined with existing preclinical data suggest that INO-1001 produces significant PARP inhibition and has the potential to protect cardiac tissue from damage."
Researchers from the Brigham and Women's TIMI Study Group and Inotek Pharmaceuticals reported that plasma from patients treated with INO-1001 suppressed ex vivo PARP activation. This effect was observed up to 24 hours following drug admi nistration. Furthermore, INO-1001 treatment was associated with a trend towards reduced levels of select inflammatory proteins, including C-reactive protein and interleukin-6. No-drug related serious adverse events were observed in the 30 patients receiving drug during the study period.
The Phase 2 trial was a prospective, single-blind, multi-center, dose-escalation study of a single dose of intravenous INO-1001 (200 mg, 400 mg, or 800 mg) administered in adults presenting with acute STEMI who were to be treated with primary PCI. The study enrolled 40 patients between the ages of 48 and 63. The primary endpoint of the study was to evaluate the safety, tolerability and pharmacokinetic profile of INO-1001. The secondary objectives of the study were to characterize the pharmacodynamic profile of INO-1001 and to evaluate various biomarkers of necrosis and inflammation.
About PARP Inhibitors
Poly (ADP-ribose) polymerase (PARP) is an abundant nuclear enzyme that mediates the repair of DNA single strand breaks through the activation and recruitment of DNA repair enzymes. PARP's role in the inflammatory response may result from its ability to potentiate the activity of key inflammatory transcription factors (NF-kappaB and AP-1). PARP inhibitors have shown promise in a variety of inflammatory and ischemia/reperfusion diseases, including those related to acute cardiovascular conditions. PARP inhibitors may also have potential application in cancer, and are being studied to ascertain their ability to block one of the key defense mechanisms that cancer cells rely upon to resist standard chemotherapy. By blocking tumor defenses, PARP therapy may increase the susceptibility of tumors to standard chemotherapy or even reverse tumor resistance.
INO-1001 represents Inotek's lead candidate in a series of novel PARP inhibitors discovered by Inotek. In July 2006, Inotek and Genentech, Inc. entered into an exclusive global collaboration t o discover, develop, manufacture and commercialize PARP inhibitors, including INO-1001, for the potential treatment of cancer. Additionally, Genentech has retained an option to develop and commercialize Inotek's PARP inhibitors to prevent cell death and complications associated with various acute cardiovascular conditions and procedures. Inotek has retained all rights to develop and commercialize PARP inhibitors outside of cancer and the specific acute cardiovascular diseases included in Genentech's option. A number of oral and intravenous next generation PARP inhibitors are in development for various disease states, including cancer.
About Inotek Pharmaceuticals
Inotek Pharmaceuticals Corporation (www.inotekcorp.com) is a Phase 2, drug-development company with a deep pipeline of small molecule compounds targeting the key biological processes involved in cell survival and tissue injury. Inotek's three platform programs have resulted in six novel molecules in various stages of preclinical and clinical development that target: 1) PARP, a nuclear enzyme that is fundamental to DNA repair and inflammation; 2) peroxynitrite, a highly toxic oxidative and nitrosative species produced by cells in response to injury; and 3) the purinergic receptor family, with a specific focus on adenosine receptors.
Inotek was founded in 1996 and currently has 140 employees, located in its corporate headquarters and main research laboratories in Beverly, Massachusetts and its clinical operations and GMP production facilities in Israel. Inotek has developed integrated capabilities from early discovery through Phase 2 clinical development.
Inotek Pharmaceuticals Corporation
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