LONDON – A phoenix has arisen from the ashes of Provesica Ltd., raising £1.9 million (US$3.1 million) to repurpose the failed company’s only asset, XEN-D0501, as a treatment for chronic cough.

Provesica Ltd. was spun out of ion channel specialist Xention Ltd. three years ago, raising £4 million to develop XEN-D0501, an antagonist of the ion channel TRPV1 (transient receptor potential), also known as the capsaicin receptor, as a treatment for overactive bladder. The product subsequently failed in Phase II.

“We didn’t meet the endpoint in overactive bladder, but the data in cough are amazing,” said John Ford, CEO of Provesica’s successor, Ario Pharma Ltd.

“The human tissue data and preclinical package for cough were enough to persuade the venture capital investors in Provesica to invest in Ario,” he told BioWorld Today.

In addition to the existing investors, Forbion Capital Partners and Seroba Kernel Life Sciences, Ario has attracted New Science Ventures as a new investor.

In preclinical studies, XEN-D0501 suppresses ex vivo vagal nerve firing in response to tussive agents and completely abolishes cough counts in animal models. Along with the compelling preclinical cough data, XEN-D0501 has the fat safety file that comes from the 200-patient study in overactive bladder.

Ario has worked for a year with Maria Belvisa of the National Heart and Lung Institute at Imperial College London, who is one of the leading experts of the role of TRPV1 in respiratory diseases, to build on the growing body of evidence implicating TRP channels in driving cough reflex hypersensitivity and inflammatory responses, and to shape up XEN-D0501 for its new indication.

The company also is collaborating with Jacky Smith, of Manchester University, who has developed the only ambulatory cough monitoring technology to have approval from the FDA.

Chronic cough – defined as a cough that lasts for longer than eight weeks – can have different causes ranging from upper respiratory tract infections to gastroesophageal reflux. “There are a lot of distinct patient groups, but we think they have the TRP pathway in common,” Ford said. Ario will test XEN-D0501 in the two specific subsets of chronic idiopathic cough and cough associated with chronic obstructive pulmonary disorder.

Ford explained that this will make it possible to power the placebo-controlled trials with as few as 20 patients. “That’s one of the great things about cough; if you go into distinct patient groups, it’s easy to power,” Ford said. “We can get proof of mechanism for a low cost compared to other disease areas.”

In the UK, patients with chronic cough are referred to specialist cough clinics, and the trials will take place at one such clinic at the University Hospital South Manchester. The FDA-approved device Smith has developed for capturing cough is worn around the neck, picking up movement in the chest and sound from the wearer’s mouth.

Ford said he believes that makes it possible to run more robust trials than is generally the case in cough, which typically must rely on patient questionnaires. “This will be objective, and we will only need to dose for a couple of weeks, meaning we should get the readout in mid-2014,” he said.

With the device doing the counting, the primary endpoint of percentage reduction in cough is clear cut. Assuming positive results, Ford said he intends to ramp up partnering in May or June 2014, with the aim of seeing the VC investors to an exit. He also hopes to open the door to setting up other programs, establishing Cambridge, UK-based Ario as a respiratory diseases specialist. “We plan to build on the emerging role of TRPV1 in other respiratory diseases and to initiate discovery projects against other TRP channels,” he said.

The parent company of both Ario and Provesica is Xention, which spun out Provesica in December 2010 in a move intended to allow Xention to concentrate on developing ion channel modulators as treatments for atrial defibrillation. Ford noted that ion channels are relevant to multiple indications. “Experience showed that these are different business fields for pharma, so it makes sense for us to specialize by therapeutic areas, too,” he said.