By Jennifer Boggs
Assistant Managing Editor
A discovery in a Johns Hopkins University lab that a nitroxyl donor appears to have an effect on cardiac physiology
is being put to the test by Cardioxyl Pharmaceuticals Inc., which recently moved into the clinic with its lead product,
CXL-1020, in heart failure patients.
"We've taken benchtop science to the clinic in about 27 months," said Chris Kroeger, who took the helm as
president and CEO last fall, coming from Aurora Funds, one of the two investors in Cardioxyl's $14.5 million Series
A round in 2006.
Kroeger was heading up biopharma and medical device investing at the North Carolina VC firm when he met David
Kass, Nazareno Paolloci and John Toscano, who had developed a nitroxyl donor chemistry platform at Johns Hopkins.
The work was based on the discovery that Angeli's salt, a known nitroxyl donor, appeared to have an effect in a
heart failure model.
Since Angeli's salt itself can't be given as a drug, the researchers designed a platform for developing a smallmolecule
nitroxyl prodrug. But, back in 2005, "it was raw technology out of the university," Kroeger told BioWorld Today.
Cardioxyl, of Hunt Valley, Md., was set up with a specific three-step process in mind: The first year would focus on
medicinal chemistry to develop the platform and create a lead molecule, the second year would entail investigational
new drug application-enabling work and the third year "we would get into the clinic, and that's where we are now," he said.
A few weeks ago, the company initiated a Phase I/IIa study of CXL-1020. The dose-escalation trial is set to enroll
patients with chronic stable heart failure - instead of the usual healthy volunteers - to test safety and tolerability, as
well as specific effects on noninvasive hemodynamic parameters. Up to four cohorts and 36 subjects will be recruited.
Kroeger said data are anticipated by the first quarter of next year.
Pending successful results, Cardioxyl plans to move intravenous CXL-1020 into the desired patient population:
acute decompensated heart failure. Though not as large as the chronic heart failure market, that indication is still
substantial - estimated at $500 million to $1 billion, Kroeger said - and "something that's much more tractable for a
small, venture-backed firm."
The firm does have plans to develop an oral formulation of CXL-1020, but that's "more of a wheelhouse of a big
pharma partner," he added.
Right now, patients rushed to the hospital with acute decompensated heart failure have limited treatment options,
such as I.V. diuretics, which might improve the peripheral vasculature by reducing fluid buildup, or inotropic drugs,
which improve the heart's contractility but carry long-term mortality risks.
CXL-1020 is designed to "help the heart squeeze, help it relax better and helps in the peripheral vasculature,"
Kroeger said. "We want to pull all three of those levers to get the heart back to equilibrium."
Cardioxyl, with five employees, is operating on a "very virtual" basis, and "we'll continue to use that model," Kroeger
said, though the firm will be adding staff as it goes forward. Most recently, it added John Reardon as chief scientific
officer and is at the "tail end" of looking for a chief medical officer.
The Series A financing, which also included investments by New Enterprise Associates, has funded the firm's
progress to date, Kroeger said, and "we hope to close an additional financing soon."
BioWorld Today July 14, 2009