Xention Siphons Off OAB Therapy Into New Spin Out, Provesica

Atrial fibrillation will be Xention's focus following the spin-out of its overactive bladder assets into a new company, Provesica

U.K. ion channel modulator company Xention Ltd. announced the spin-out of its overactive bladder (OAB) program and its associated lead product, XEN-D0501, into a separate company, Provesica Ltd., on Dec. 16.

"We took the view that OAB and our other research focus, atrial fibrillation, are totally different things, and it makes sense to split them up and finance them separately," Xention's chief executive Tim Brears said in an interview.

"They are likely to have different partnership requirements and different time frames for financing," he added.

The decision to run the companies separately reflects a broader trend toward asset-focused financing, a phenomenon that can lead toward more efficient drug development and tighter managerial focus. It also allows investors to make narrower and more specific bets on assets they think have the best chance of success (Also see "PanGenetics' NGF Antibody Sale Illustrates Index's Asset-Focused Strategy" - Scrip, 1 Dec, 2009.).

Provesica is for now owned by Xention's shareholders, and two of them, Forbion Capital Partners and Seroba Kernal Life Sciences Ltd, have also provided £4 million ($6.2 million) in new funding to progress XEN-D0501 through to the completion of a Phase II clinical trial during 2011. That trial is expected to start in January.

Seroba-Kernal Life Sciences was a new investor when it led Xention's £8 million Series D financing last month; that cash is earmarked specifically for the development of Xention's atrial fibrillation products. Existing investors also took part in that financing, including Forbion Capital Partners, Credit Agricole Private Equity, MVM and BTG International.

Initially, Brears will also be managing director of Provesica, and the company's development requirements will outsourced to Xention. Ultimately, Provesica might develop other OAB products, Brears commented. As part of this approach, Xention has been restructured, with a holding company, Xention Pharma Ltd., and a wholly-owned R&D subsidiary, Xention Ltd.

Brears explained that XEN-D0501 has a new mechanism of action for a potential OAB therapy. It is an antagonist of the vanilloid TRP (transient receptor potential) receptor, TRPV1, which is expressed on the detrusor muscle in the bladder. It has shown promise in OAB in animal studies and in three Phase I trials.

The aim is to develop an OAB therapy that is not an antimuscarinic agent, virtually all of which have dry mouth as a side-effect to some extent, Brears said.

TRPV1 is also a target various pain indications and has been the subject of multiple deals in that space - Eli Lilly & Co. paid Glenmark Pharmaceuticals Ltd. $45 million up-front for rights to its anti-TRPV1 compound in November 2007, for example - and it has not escaped the notice of internal R&D teams at large pharmas either.

More Selective Anti-Arrhythmics Needed

Xention's continued focus on atrial fibrillation is driven by a need for new agents that inhibit single ion channels in the atria but not in the ventricles, Brears said.

"The heart is full of ion channels, and if you start affecting ion channels that are expressed in the ventricles there is a danger of inducing long QT interval syndrome, which is what you want to avoid."

Xention has identified two specific atrial ion channels, Kv1.5 and IKACh, and one Kv1.5 antagonist, XEN-D0101, is currently in Phase I studies. A more potent and selective Kv1.5 antagonist, XEN-D0103, is expected to enter Phase I trials in the first half of 2011.

Big pharma has expressed an interest in the research, but Xention thinks it has a leading position with the two atrial fibrillation targets, Brears said.

An atrial fibrillation agent would compete against Sanofi-Aventis's new therapy, Multaq (dronadarone), and Merck & Co/Cardiome's mixed ion channel antagonist, vernakalant (Also see "Merck And Cardiome Obtain EU Approval For Vernakalant In Atrial Fibrillation" - Pink Sheet, 2 Sep, 2010.)).

- John Davis ([email protected])