BMS has agreed to buy Cardioxyl Pharma in a transaction valued at up to $2bn that would give it rights to a heart failure drug in phase II trials.
The deal – which includes $300m in upfront and near-term milestones – revolves around CXL-1427, a nitroxyl donor that is being tested as an intravenous therapy for acute, decompensated heart failure. Another $1.78bn could come if development, regulatory and sales objectives are met.
After administration, CXL-1427 acts as a prodrug, releasing the active nitroxyl (HNO) component – a form of nitric oxide (NO) with one less electron – within the body.
Nitroxyl is thought to have beneficial effects on heart muscle, specifically by reversing the loss of contractility in the heart associated with heart failure, without altering heart rate or oxygen consumption as occurs with currently-available drugs.
It also has positive effects on the circulatory system such as dilating blood vessels to cause a drop in vascular resistance, reducing the workload on the failing heart.
HNO has been tested as a possible alternative to NO-donating therapy with drugs such as nitroglycerin in heart failure for years, but the field has been hampered because HNO itself has a vanishingly short half-life in the body.
Much of the work involving the molecule has been devoted to the development of donor compounds that release HNO in a steady, controlled fashion that is more likely to have a lasting beneficial effect on the heart.
BMS’ agreement with privately-held Cardioxyl reflects an increased focus on heart failure, which has relied on treatment with established drugs for many years. That changed recently with the approval of Novartis‘ first-in-class, neprilysin inhibitor-based Entresto (sacubitril and valsartan), which has been predicted to become a $5bn-a-year brand.
CXL-1427 “has the potential to change the course of the disease rather than simply treating the symptoms”, according to BMS‘ chief scientific officer Francis Cuss. The company also has a portfolio of in-house drugs with potential in heart failure patients, including an Ikur inhibitor with potential to treat atrial fibrillation in phase I.
US-based Cardioxyl also has an orally-active HNO-donator called CXL-1036 in early development for chronic heart failure, as well as candidates for pulmonary arterial hypertension.