UniQure deal confirms red-hot interest in advanced therapies

If there is any sign that pharma is beating the bushes to flush out promising advanced therapies, it is that Bristol-Myers Squibb has shelled out $50m to license a preclinical gene therapy project that UniQure had acquired for just €1.5m ($1.6m) cash eight months ago.

For a near-term outlay of nearly $100m, Bristol-Myers gets the heart failure candidate AAV-S100A1 and three other targets. Along with Bluebird Bio, Celladon and Voyager Therapeutics, UniQure shows that gene therapy has begun a modest but noteworthy renaissance.

Bristol-Myers is spending $50m up front and is making an initial investment worth about $32m in UniQure equity to sew up the license for AAV-S100A1. In addition, it will pay $15m within three months for the identification of three more gene therapy targets in cardiovascular, liver or central nervous system disorders.

Up to 10 agents could be delivered under the deal, with Bristol-Myers having exclusive rights to all cardiovascular projects and exclusive rights to each target in the other disease areas. Bristol-Myers will provide R&D funding and lead clinical and regulatory work. Counting all milestones and royalties, the potential deal value is more than $2bn, UniQure said.

UniQure's shareholders gave an emphatic endorsement to the deal, driving shares up 47% yesterday.

Value added

The tie-up shows the acumen in UniQure’s takeout of the private University of Heidelberg spinout InoCard in August, which brought to the Amsterdam-based company the S100A1 target. This calcium-binding protein is downregulated in congestive heart failure patients, and targeting it aims to improve contractile force, heart muscle cell growth and rhythm stability.

UniQure has applied its adeno-associated virus delivery platform to a therapy that encodes for increased production of S100A1. InoCard was secured for €1.5m in cash and another €1.5m in shares, plus milestones and royalties, so its shareholders will most likely be seeing another round of cheques once the Bristol-Myers deal closes.

Uniqure’s life is surely a reflection of how gene therapy has lost and then regained favour. As Amsterdam Molecular Therapeutics the group essentially ran out of money just as its lead product, Glybera, a treatment for familial lipoprotein lipase deficiency, was about to achieve the first-ever approval for a gene therapy in western nations, from European regulators.

AMT’s assets were taken private as UniQure and then floated publicly again last year, this time on Nasdaq, in the midst of a new explosion of interest in immuno-oncology and gene therapy. This influx of capital has allowed it to progress other pipeline projects, such as candidates for haemophilia and sanfilippo syndrome.

It could be essential to UniQure’s survival to see other assets make progress. Glybera so far has only been made available in Germany, and Novartis might soon offer a small-molecule alternative in the form of LCQ908.

Bristol-Myers returns

Bristol-Myers, meanwhile, is re-entering a cardiovascular space it had largely vacated with Plavix’s patent expiry three years ago – and it has had little presence in heart failure since it lost Capoten and Monopril to generics.

Congestive heart failure has shown itself to be difficult to treat, and the therapeutic approaches that work have done so largely by making it easier for weakened hearts to pump blood. Gene and cell therapies have been proposed in congestive heart failure to repair damaged tissue or improve the function of remaining heart muscle cells – and as a one-time treatment they remove the risk of non-adherence with medication schedules.

A red-letter day should come later this month, when Celladon’s Cupid-2 trial of Mydicar reads out (Upcoming events: Data for Athersys in stroke, Celladon in heart failure, Heron in emesis, April 3, 2015). Celladon is at the leading edge of gene therapies for heart failure, but is by no means alone: the Cleveland Clinic spinout Juventas Therapeutics has initiated a phase II trial of JVS-100 in heart failure.

While Celladon’s candidate targets a different protein, UniQure and Bristol-Myers will no doubt be watching that result with great interest. It should show how well an AAV-based therapy works in delivering a gene therapy payload into heart tissue, providing the new partners with a big signal on how to proceed with the S100A1 approach.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @ByJonGardner on Twitter

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