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GlaxoSmithKline and Mpex Pharmaceuticals form alliance to develop novel efflux pump inhibitors for use against serious gram-negative infections


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Potential to combine compounds with multiple new and existing antibiotics to create a broad offering of anti-infective medicines with activity against drug-resistant organisms

Issued – June 2008, London, UK & San Diego, California

GlaxoSmithKline (GSK) and Mpex Pharmaceuticals today announced that they have entered into a worldwide strategic alliance for the discovery, development and commercialisation of novel medicines for bacterial diseases. The collaboration provides GlaxoSmithKline access to Mpex’s novel efflux pump inhibitors (EPI) and related proprietary technology for use in combination with a variety of antibiotics. The collaboration will focus on the discovery and development of novel drug regimens comprising Mpex’s EPIs combined with GSK’s novel development stage compounds as well as existing commercial antibiotics to improve potency and broaden the spectrum of antibacterial activity.

Under the terms of the agreement, Mpex will grant GlaxoSmithKline rights to product candidates developed under the collaboration that are directed to three different target product profiles and with the potential to deliver up to seven treatment options. Mpex will be responsible for the discovery of EPI drug candidates and the development of combination product candidates through clinical proof of concept, at which point GlaxoSmithKline will have an option to exclusively license each product candidate for further development and commercialization on a worldwide basis. Mpex will retain the right to further develop and commercialize product candidates for which GlaxoSmithKline does not exercise its option. Mpex will receive an $8.5 million upfront payment and a $6.5 million equity financing commitment from GlaxoSmithKline. Contingent on achieving certain milestones, Mpex is eligible to receive development, regulatory and commercial milestones ranging up to $200 to $250 million for each product candidate. If GlaxoSmithKline exercises its option, Mpex will receive tiered royalties, which are dependent on sales achieved, for EPIs used in combination with commercially available antibiotics and with proprietary GSK antibiotics. GlaxoSmithKline will participate in the alliance through its Infectious Diseases Centre of Excellence for Drug Discovery (ID CEDD).

"We believe this collaboration has the potential to lead to a number of important new anti-infective products,” said Daniel Burgess, President and CEO of Mpex Pharmaceuticals. “The critical role of antibiotic efflux has been well recognized in bacterial resistance, but to date, safe and effective efflux pump inhibitors have not been developed. Given the progress Mpex has made in this program over the last several years, we are optimistic that combining our efforts with an industry leader such as GlaxoSmithKline will maximize our chances of success to develop a portfolio of products from this platform technology that is greater than we could hope to develop on our own. In addition, GlaxoSmithKline has an impressive array of novel new classes of antibiotics in development, and we believe that a number of these antibiotic opportunities could benefit from the addition of an Mpex efflux pump inhibitor.”

“Antibiotic discovery has faced tremendous challenges with the discovery of only two new classes of antibiotics over the last 3 decades,” stated Zhi Hong, Senior Vice President of the ID CEDD at GlaxoSmithKline. “Novel discovery-enabling and paradigm-shifting approaches are needed to address the ever increasing medical needs due to life-threatening bacterial infections and drug resistance. Efflux pump inhibitors have the potential to add value to existing antibiotics and also enable progressive development of GSK’s novel antibiotic pipeline. Mpex has a first rate entrepreneurial R&D team with deep experience in antibacterial research and has validated efflux pump inhibition for potentiation of antibacterial activity, as well as expanding the spectrum of bacterial susceptibility. I look forward to having a great synergy in this important and strategic collaboration.”

Bacterial efflux pumps are an intrinsic defense mechanism in gram-negative bacteria that expel toxins such as antibiotics that have permeated the outer cell membrane before they can reach their targets and kill the bacteria. Higher intracellular antibiotic concentrations achieved through efflux pump inhibition can increase the potency and pharmacological barrier against other drug resistance mechanisms (e.g., target-based mutations). There are currently no drugs approved to inhibit the activity of these efflux pumps and restore the potency of otherwise effective antibiotics. Mpex has been a leader in this field of research for a number of years and has identified several series of lead EPIs that are now being optimized for development. These compounds have been shown in both in vitro and in vivo pre-clinical studies to significantly improve the potency of a number of different antibiotic classes against drug-resistant gram-negative pathogens, including Pseudomonas aeruginosa and Klebsiella pneumoniae.

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Under the safe harbour provisions of the U.S. Private Securities Litigation Reform Act of 1995, the company cautions investors that any forward-looking statements or projections made by the company, including those made in this Announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Factors that may affect the Group’s operations are described under ’Risk Factors’ in the ’Business Review’ in the company’s Annual Report on Form 20-F for 2007.


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