Cardioxyl Pharmaceuticals Initiates Phase I/IIa Study in Heart Failure

HUNT VALLEY, MD--(Marketwire - July 01, 2009) - Cardioxyl Pharmaceuticals, Inc., a clinical stage pharmaceutical company developing therapeutic agents for the treatment of cardiovascular disease, today announced the initiation of a Phase I/IIa dose-escalation study of lead drug candidate, CXL-1020, for the treatment of acute decompensated heart failure (ADHF). The study has already begun enrollment, and the first patient was dosed in June 2009.

The Phase I/IIa dose-escalation study will evaluate the safety and tolerability of CXL-1020 and specific effects on non-invasive hemodynamic parameters in patients with chronic stable heart failure. The study will also evaluate the pharmacokinetics of CXL-1020.

Chris Kroeger, MD, President and Chief Executive Officer of Cardioxyl Pharmaceuticals, commented, "There is significant clinical need for a safe and effective therapy to treat acute decompensated heart failure patients that would enhance both diastolic and systolic function, while concomitantly reducing vascular resistance." Kroeger continued, "CXL-1020 is a novel, first-in-class, small molecule nitroxyl (HNO) donor therapeutic drug candidate. Our initial studies in patients with stable heart failure are anticipated to provide a window through which we hope to better understand the potential utility of this novel agent in acute decompensated heart failure."

Wilson S. Colucci, MD of the Boston University Medical Center Cardiovascular Center and Steering Committee Chair commented, "In preclinical trials, CXL-1020 has exhibited a very attractive suite of physiologic effects in canine models of heart failure. We look forward to evaluating the safety and tolerability, as well as the hemodynamic effects of CXL-1020 in this dose-escalation study."

About CXL-1020 Phase I/IIa Study

The study is a multi-center trial that will be conducted in up to 6 sites in the U.S. with affiliated heart failure specialty centers or academic medical centers. The Phase I/IIa study will enroll up to 4 cohorts and 36 subjects with chronic stable heart failure, who will receive escalating doses of a sustained intravenous infusion. The primary endpoints for this study are the evaluation of the safety and tolerability of CXL-1020.

About Nitroxyl (HNO)

Cardioxyl has developed a nitroxyl chemistry platform technology that serves as the foundation for the company's drug discovery efforts. The work of Cardioxyl's scientific founders at Johns Hopkins University and colleagues elucidated the cardiovascular effects of nitroxyl in 2003, and Cardioxyl has since developed a formidable intellectual property portfolio and industry leading nitroxyl chemistry, pharmacology, manufacturing and formulation expertise. Cardioxyl's lead program is focused on the development of proprietary nitroxyl donors for the treatment of acute decompensated heart failure (ADHF).

About Congestive Heart Failure (CHF)

Congestive heart failure is the inability of the heart to pump enough blood to supply the metabolic demands of the body. Heart failure may result either from the heart's inability to effectively contract (systolic heart failure), or from the heart's inability to relax and fill with blood (diastolic heart failure). There are more than 5.7 million people in the U.S. and more than 22 million people world-wide with congestive heart failure (CHF), with over 650,000 new CHF diagnoses each year in the U.S. The prognosis for patients with CHF remains poor, with a 5-year mortality rate of 50 percent following diagnosis. The expected economic impact of the medical care for CHF is substantial, with over $37 billion spent in the U.S. in 2009 for the medical care of heart failure patients.

About Acute Decompensated Heart Failure (ADHF)

ADHF is an acute exacerbation of congestive heart failure and the leading diagnosis at the time of discharge from U.S. hospitals and the most common cause of hospitalization for patients over 65 years of age. ADHF is a deadly condition, with in-hospital mortality rates of 2-6 percent and six month readmission rates as high as 30-60 percent. Episodes of ADHF are marked by a severe diminution of cardiac function that typically result in fluid accumulation in the lungs (pulmonary edema) and consequent severe shortness of breath. There were 1.1 million hospitalizations for acute heart failure in the U.S. in 2006. Among patients hospitalized with ADHF, the thirty day mortality rate is approximately 11 percent and the one year mortality rate is 34 percent. These poor outcomes indicate the clear need for better therapies to treat this patient population.

Current Treatments for ADHF

Despite the severity of the condition, the treatment options available for patients with ADHF remain limited. Current first-line treatments target the removal of excess fluid (diuresis) and preload and afterload reduction (vasodilation). In order to improve the hemodynamic profile of the heart and increase cardiac contractility, a physician may also administer an intravenous inotropic agent such as dobutamine (beta-adrenergic agonist) or milrinone (PDE3-inhibitor). Administration of dobutamine or milrinone often requires very close monitoring in the hospital's cardiac or intensive care unit setting due to the life-threatening safety risks associated with these drugs, including ventricular/atrial arrhythmias, hypotension, sudden cardiac death, and other potential adverse long term outcomes.

About Cardioxyl Pharmaceuticals

Cardioxyl Pharmaceuticals is a clinical-stage pharmaceutical company focused on the discovery and development of new classes of safe and effective therapeutic agents for the treatment of cardiovascular disease. Cardioxyl has developed industry-leading expertise in the chemistry, biology and clinical applications of nitroxyl (HNO) technology. The company's core HNO platform has generated several preclinical and clinical candidates, including the company's lead compound, CXL-1020, currently in clinical development for ADHF. Cardioxyl is a privately held company financed by life science venture investors, including the Aurora Funds and New Enterprise Associates.

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