Cardioxyl Pharmaceuticals Announces Positive Results from First Clinical Study of its Lead Therapy, CXL-1020, in Heart Failure Patients

CHAPEL HILL, N.C., Aug. 2 /PRNewswire/ -- Cardioxyl Pharmaceuticals, Inc., a clinical-stage pharmaceutical company developing novel therapeutic agents for the treatment of cardiovascular disease, today announced that it has achieved positive safety and tolerability results in the first clinical study of its lead drug candidate, CXL-1020, for the treatment of patients with acute decompensated heart failure (ADHF).  Each year in the United States, more than one million patients are hospitalized with acute heart failure.

Cardioxyl's Phase I/IIa placebo-controlled, double-blind, dose-escalation study was conducted at seven sites in the United States with affiliated heart failure specialty centers or academic medical centers. The Phase I/IIa study enrolled 28 subjects with chronic stable heart failure and involved 67 exposures of a sustained intravenous infusion across four cohorts. In the trial, CXL-1020 demonstrated an acceptable safety profile, an attractive pharmacokinetic profile, and was well tolerated by patients. The drug led to no serious adverse events, with patients tolerating doses up to 10 ug/kg/min. In addition, CXL-1020 clearly demonstrated statistically significant hemodynamic activity in patients with relevant underlying disease. More information on the trial results will be presented at upcoming scientific meetings.

"Cardioxyl is making significant clinical progress in the development of CXL-1020, an important treatment for patients with ADHF," said Chris Kroeger, M.D., President and Chief Executive Officer. "Results from our recently completed Phase I/IIa dose escalation study demonstrate that the drug has a very attractive safety profile and an important impact on cardiac and vascular function. We also believe that CXL-1020 is the only product in development that provides the ideal balance of blood vessel dilation combined with direct enhancement of cardiac diastolic and systolic function."

Dr. Garrie J. Haas, M.D., FACC, Section Director of Heart Failure/Transplant, and Medical Director of the Cardiovascular Clinical Research Organization, Professor of Medicine in the Division of Cardiovascular Medicine at The Ohio State University Medical Center and an investigator in the Cardioxyl Phase I/IIa trial stated, "There is currently a significant clinical need in the United States for a safe and effective therapy to treat the large population of hospitalized patients with heart failure. With its unique mechanism of action as compared to the limited options available on the market today, CXL-1020, if successful, will provide a novel and very useful new therapy for the treatment of these often severely ill patients."  

Cardioxyl Raises an Additional $15 Million in Funding

Cardioxyl also announced today that it has raised $15 million in funding from existing investors Aurora Funds and New Enterprise Associates (NEA).

Said Dr. Kroeger, "With this additional funding, Cardioxyl is well capitalized to execute on a Phase IIa trial for CXL-1020 and to continue development of our promising research portfolio. We are pleased to have the continued enthusiastic support of Aurora and NEA."

About CXL-1020

Cardioxyl has developed a nitroxyl chemistry platform technology that serves as the foundation for the company's drug discovery efforts. In research published by Cardioxyl's scientific founders from Johns Hopkins University, nitroxyl was shown to have positive vasodilatory and direct myocardial effects.  CXL-1020, a proprietary nitroxyl donor, is Cardioxyl's lead compound for the intravenous treatment of acute decompensated heart failure (ADHF).  In pre-clinical models of heart failure, CXL-1020 improves cardiovascular performance by enhancing the contractility (inotropy) and relaxation (lusitropy) of the failing heart and dilating the peripheral vasculature (vasodilation), without increasing heart rate or myocardial oxygen consumption.  Cardioxyl completed a Phase I/IIa safety and dose-escalation study of CXL-1020 in stable chronic heart failure subjects and will soon initiate a Phase IIa trial. Based on all pre-clinical studies to date, CXL-1020 is anticipated to improve the symptoms, hemodynamics and clinical status of patients with ADHF.  

About Acute Decompensated Heart Failure (ADHF) & Current Treatment Options

ADHF is 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. (1)  Well over $39 billion was spent in the U.S. in 2009 for the medical care of heart failure patients.  ADHF is a deadly condition, with in-hospital mortality rates of two to six percent and six-month readmission rates as high as 30 to 60 percent.  Episodes of ADHF are marked by a severe reduction of cardiac function that typically results 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 30-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. (2,3)

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 HNO (nitroxyl) 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 Aurora Funds and New Enterprise Associates.

(1) Heart Disease and Stroke Statistics 2009 Update. A Report From the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2009; 119:e1-e161

(2) Gheorghiade, M. Reassessing treatment of acute heart failure syndromes: the ADHERE Registry. Eur Heart J Suppl.  2005  7: B13-B19

(3) Jong, P et al. Prognosis and Determinants of Survival in Patients Newly Hospitalized for Heart Failure. Arch Int Med, 2002; 162:1689-1694

SOURCE Cardioxyl Pharmaceuticals, Inc.