Alex Philippidis Senior News Editor Genetic Engineering & Biotechnology News

Successful models appear to focus on conducting discovery-stage work.

The software industry was a trailblazer in the field of open-source innovation. Savings to users were estimated at about $60 billion a year, according to a 2008 study by The Standish Group International. Open-source collaboration has now spread to the biopharma industry, among others.

For biotechnology and pharmaceutical businesses, the open-source model holds potential for advancing drug discovery faster and at lower cost than the model now in place. The current system emphasizes developing and protecting proprietary intellectual property, then spending years and additional dollars undergoing reviews with the aim of securing an FDA approval. The cost of developing a new drug has escalated to an all-time high of $1.3 billion, the Tufts Center for the Study of Drug Development said in January.

Hence pharma giants are trying to embrace not only more partnerships but more so-called open innovation efforts. These include less profitable disease indications that have struggled with attracting investment.

Merck’s Focus on In-House Drugs

Last year Merck & Co. launched Merck Oncology Collaborative Trials Network. The network was to consist of 15 academic and independent research institutes across North America, South America, Europe, and Asia. All 15 sites were to focus on development of Merck drug and vaccine candidates for cancer by leading the design and conduct of Phase 0 to IIa studies.

“Every year the network will enroll approximately 1,200 patients in 30 to 40 clinical trials,” Merck previously stated. “These studies will include investigator- and company-sponsored trials.” But after its $41 billion merger with Schering-Plough, Merck has spent the past nearly two years restructuring its operations to cut costs.

Earlier this year, Merck deactivated the network. “Given the changes in clinical strategy, Merck could no longer ensure that network enrollment requirements could be met, and therefore the difficult decision was made to discontinue,” Merck spokesman Ian R. McConnell told GEN.

GSK’s Open Lab for Neglected Diseases

A more successful example of a big pharma open-collaboration effort is GlaxoSmithKline’s (GSK) strategy, targeting diseases of the developing world. GSK launched its open innovation initiative early in 2010 by starting its first “Open Lab” based outside Madrid, Spain. Open Lab allows up to 60 scientists from around the globe to tap into GSK expertise while pursuing their own R&D in tropical diseases. GSK spent $8 million to seed-fund the research through a not-for-profit foundation.

“We decided to pursue this model of working in this disease area because we recognize the need to develop new medicines for malaria,” a GSK spokeswoman, Janet Morgan, told GEN. “There is a wealth of expertise in the malaria field area beyond GSK, and by sharing data and working collaboratively with the scientific community, we are increasing the likelihood of developing life-saving medicines.”

Open Lab has provided funding for three projects, totaling slightly over $425,000. Since the launch, six projects have begun in the Open Lab, including one with South Africa-based iThemba Pharmaceuticals in multidrug-resistant TB (MDR-TB) and co-infection with HIV/AIDS; GSK provided in-kind contribution and the support of its scientists. iThemba was the first company to take advantage of the Pool for Open Innovation against Neglected Tropical Diseases (POINT). GSK shares intellectual property and knowledge through POINT, which has made more than 2,300 patents available.

Open Lab scientists last year published a paper in Nature detailing more than 13,500 malaria compounds found when they carried out a whole-cell screen of the malaria parasite against GSK’s over two-million-compound library. Chemical structures and associated assay data of these compounds are now stored on leading public scientific websites including those of the European Bioinformatics Institute, the National Library of Medicine, and Collaborative Drug Discovery, according to Morgan.

When GSK launched its open innovation strategy last year, the company said that one of its goals was the development of a malaria vaccine at a profit of 5% above the cost of production.

Lilly’s Expanding Initiatives

The most recent example of big pharma’s interest comes from Eli Lilly. Late last month Lilly said it will expand its open-source effort beyond its two-year-old Phenotypic Drug Discovery (PD2) initiative, in which molecules can be submitted by scientists outside the company for screening. The new target discovery program called TargetD2 will screen molecules designed to interact with specific genomic targets believed to be involved in disease pathogenesis.

Lilly also added late last month a component to its TB Drug Discovery Initiative that will screen molecules for their ability to fight MDR-TB. Members including the Infectious Disease Research Institute (IDRI) and NIH contribute in-kind resources; IDRI handles in vitro work to test compounds, while NIH helps as needed with in vivo and development resources as well as researchers developing assays, for example.

“This entire program is one that provides unprecedented access to novel molecules around the globe,” Alan D. Palkowitz, Ph.D., vp of discovery chemistry research and technologies with Lilly, told GEN. “As we’re working in the TB initiative as part of a not-for-profit, and we know some of the challenges for TB drug discovery are really centered on identifying novel sources of compounds for screening, it seemed like an ideal way to leverage this platform that we’re using for some of our internally derived drug discovery efforts.”

He said the success of the TB initiative could serve as a model down the road for additional collaborations aimed at rare and neglected diseases, which are not usually a focus for Lilly and other pharma giants.

Under the new TargetD2, as with PD2, investigators retain intellectual property rights to their molecules until a promising compound emerges. “If we see something very interesting from the data, we will ask the investigator to share the structure with us,” Dr. Palkowitz said.

“And then if we are convinced that we are seeing something very promising, then only at that point would we approach the institution and the investigator to actually exercise our first right of access.” If the institution and researcher agree, they’ll negotiate a collaborative arrangement to further optimize the science as well as milestone and royalty fees. “If the institution is not interested, they’re free to use the data whatever way they like, whether it be to publish, to put in a grant application, or to actually pursue the science on their own,” Dr. Palkowitz explained.

Lilly’s open-collaboration effort includes more than 250 institutions in 27 countries. “By having both the phenotypic module and the target-based module, it allows us to add more assays, add more areas that are of interest to us over time as our area of disease focus evolves and changes. It’s something that now that it’s in place, can be easily scaled over time,” Dr. Palkowitz remarked.

PD2 has disclosed two open-innovation collaborations, one in cancer and the other in diabetes. PD2 has “probably about six or seven active collaborations” in all when partnerships that have been signed, those being negotiated, and those in early stages of exploration are all counted, he added.

Big pharma’s appetite for open-source collaboration has been evident in the past few years. The industry’s apparent focus has been on research and discovery work. Some academic-based groups have also formed, which seem to concentrate more on discovery through clinical development along with data-sharing initiatives. A few examples of those efforts will be examined in a separate story in this section.

The Six Projects Launched at GSK’s Open Lab Since January 2010

  • • Barcelona Centre for International Health Research will spend two years and €320,000 from GSK to create a continuous lab-based supply of the P. vivax malaria parasite in the blood stage.
  • • CIC bioGUNE will get €115,050 (about $153,000) from GSK for an 18-month program to characterize the ubiquitylation profiles of cells infected by multiple drug-resistant TB and the malaria parasite P. falciparum.
  • • Durham University will use £41,800 (about $65,000) from GSK over nine months to identify compounds that can inhibit a new target in kinetoplastid protozoan parasites.
  • • Weill Cornell Medical College will attempt to identify compounds that can affect both drug-sensitive, multidrug- and extensively drug-resistant TB in the nonreplicating phase. Over 24 months the team will be able to leverage GSK’s facilities and scientific support including the firm’s compound library, while The Bill & Melinda Gates Foundation is providing funding.
  • • iThemba Pharmaceuticals program covers multidrug-resistant TB and co-infection with HIV/AIDS. GSK provided in-kind contribution and the support of its scientists.
  • • Imperial College London, Drug Discovery Centre and The Wellcome Trust Sanger Institute are working to identify CDPK (calcium dependent protein kinase) inhibitors from the 13,500 compounds identified by GSK in 2010 as inhibiting P. falciparum growth. GSK scientists are contributing through their expertise in liquid handling and screening. While the project lasted two months starting in November 2010, analysis of data is ongoing.

Alex Philippidis is senior news editor at Genetic Engineering & Biotechnology News.

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