In another sure sign of Big Pharma's recent embrace of specialist diseases, GlaxoSmithKline on Oct. 13 announced a deal for four compounds with Holland's Prosensa, which is focused on RNA-modulating therapeutics for Duchenne Muscular Dystrophy.

The deal hinges on a straightforward license component--Glaxo takes an exclusive worldwide license to lead compound PRO051, in exchange for a £16 million up-front payment. And far more typical for Glaxo, the drug maker also gets exclusive options to license three further RNA-based compounds. The total development and commercial milestones across all four candidates could reach £412 million, and Prosensa may also receive double-digit royalties.

Duchenne Muscular Dystrophy (DMD) is a rare, genetic disorder which affects one in 3,500 newborn boys. It's characterized by a progressive loss of muscle strength and early death. The disorder results from mutations in the gene for dystrophin, a protein that's necessary for normal muscle cell function. PRO051--which is due to start a Phase III trial early in 2010--works by skipping a particular exon, or protein-coding DNA sequence, known as exon 51, on the gene for dystrophin.

Treating Sub-Populations of an Already Rare Disease

But skipping that particular exon will only be suitable for approximately 13 percent f all DMD patients--a small proportion of an already highly niche disease. That's why the deal was broadened to include three further compounds targeting other DMD exons, and thus further sub-populations.

PRO044, for instance, works by skipping exon 44. This compound may enter a Phase I/II study by the end of 2009 and Glaxo's option to license it --for which terms have been pre-agreed, according to Prosensa chief executive Hans Schikan--will be triggered if this study is successful. The two further exon-skipping compounds in the deal have yet to be identified.

Still, "I didn't, in the beginning, honestly expect GSK to be interested" in the programs, admits Schikan, given the small size of the DMD market. In the event, Glaxo wasn't the only Big Pharma attracted to Prosensa's RNA-based platform technology and its Duchenne's candidates.

"There was a range of companies interested, and thus we had the luxury of picking the best partner," Schikan said, describing the tie-up as "one of the first real marriages between 'big' and 'niche' in a rare disease area."

Discussions began with Glaxo's Center of Excellence for External Drug Discovery (CEEDD), which focuses on collaborations with leading platform technology groups in particular, and which has driven much of Glaxo's option-based deal making activity.

Prosensa will work with this unit on the three follow-up compounds, whereas development of PRO051 will be pursued in collaboration with Glaxo's Neurosciences Medicines Development Center, which is responsible for development post-proof-of-concept. Glaxo will fund all further studies of PRO051.

Prosensa Free to Exploit Broader Platform Opportunities

That funding--plus the up-front payment--gives Prosensa the freedom to focus additionally on other compounds it has identified and to leverage the potential of its platform beyond DMD into further neuromuscular diseases such as myotonic dystrophy and spinal muscular atrophy, and possibly into oncology and infectious diseases too.

Prosensa's platform--which was jointly developed with Leiden University Medical Center--uses splice modulators to modify RNA processing and correct translation, allowing, in the case of DMD, the synthesis of a functional, if truncated, protein.

The biotech has also hung onto certain commercial participatory rights associated with programs in which Glaxo is a partner and has an option to expand those in certain European countries.

"Eventually, we aim to become a fully-integrated company," Schikan explains, confident in the number of exon-skipping agents that the company has identified to date and will continue to uncover.

Prosensa's existing contacts with numerous not-for-profit DMD-focused organizations - which offers access to their networks of patients, doctors and families - and the small number of patients makes its go-it-alone strategy perfectly plausible even for a small company.

Adding Glaxo's resource and infrastructure, however, should speed up development and eventual patient access. "The combination of our knowledge and their strength and power means a lot of patients can be helped," sums up Schikan.

And since DMD is a new field for GSK, Prosensa expects to retain a key role in the collaboration. "I'm not afraid that one day I'll feel they (Glaxo) have taken everything over," Schikan says.

Prosensa had raised a total of €31.5 million ($47 million) in two private funding rounds since 2007, including LifeScience Partners, Abingworth, GIMV and AGF. Since the most recent round was in December 2008, Prosensa was in a fairly comfortable position financially, even before this deal. Now it's luxuriating.

As for Glaxo, this deal adds, at relatively low cost, a late-stage pipeline candidate plus the potential for a related franchise in DMD, for which there's currently no cure. It also chalks up another partner in the still-hot RNA modulation field, where most Big Pharma have already spent significant dealmaking dollars.

Glaxo, itself, in 2006 signed up with Sirna (which is now part of Merck & Co.) in small-interfering RNA for respiratory diseases, and a year later collaborated with Santaris for RNA antagonists to treat viral diseases. Last year, the Big Pharma tied-up with Regulus (a joint venture between Alnylam and Isis) for anti-inflammatory microRNA antagonists. The latter two deals were both option-based.

- Melanie Senior (m.senior @elsevier.com)

GlaxoSmithKline in a Rare-Disease Pact with Prosensa for RNA-modulation Drugs

More from Archive

More from Pink Sheet