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PGx to Play Role in Pfizer Drug Repositioning Partnership with Wash U

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By Turna Ray

Touting "a first-of-a-kind collaboration between academia and industry" to discover new uses for existing drug candidates, Pfizer announced this week that it would move its Indications Discovery Unit laboratory from its current location in Chesterfield, Mo., to be near the Washington University School of Medicine's campus in St. Louis.

The five-year partnership between the drug giant and the academic center builds upon a 20-year relationship between the two parties and will provide Wash U $22.5 million and "unprecedented access" to clinical data on more than 500 pharmaceuticals candidates that were previously or are currently in clinical testing. Wash U researchers will investigate the molecular-level mechanisms of these compounds and will seek to identify genetic variations linked to patient response.

"The new agreement differs from other relationships in which pharmaceutical companies, even in collaborations with academic scientists, have not disclosed propriety information about drug compounds," Pfizer said in a statement.

Don Frail, chief scientific officer of Pfizer's Indications Discovery Unit, told Pharmacogenomics Reporter this week that under the terms of the agreement, "each party owns the inventions that it makes." Joint inventions will be jointly owned, and both parties will have opportunities to negotiate commercialization terms to the inventions, Frail added.

Jeffrey Gordon, director of the Center for Genome Sciences at Wash U's School of Medicine in St. Louis described the university's work with Pfizer as a computational biology effort intended to "deepen knowledge of human biology around key molecular targets and disease areas." According to Gordon, Pfizer and Wash U researchers will evaluate drug targets and pathways involved in key disease areas of strategic interest to both entities.

"Analyses will result from comprehensive collection and interpretation of all public data combined with the internal collection, profiling, analysis, and interpretation of disease-relevant human samples," Gordon said. "Genetic, functional genomic, proteomic, metabolomic, and histopathological data are all compiled to provide a detailed understanding of disease processes and patient subpopulations."

Wash U and Pfizer are each bringing certain expertise to the partnership. For instance, Pfizer's Indications Discovery Unit has internal computational biology expertise and will work with the university's preclinical and clinical departments to analyze data.

The university's Genome Sequencing Center and department of genetics will also work on identifying genomic subpopulations of interest associated with particular drugs. In addition, the Wash U medical school's Institute of Clinical and Translational Sciences will help researchers interpret the downstream clinical value of early-stage research.

For the partnership, not only is Pfizer moving its Indications Discovery Unit to the Center of Research Technology and Entrepreneurial Exchange biosciences district in St. Louis, but has also developed an online portal through which university investigators will be able to access "extensive clinical and preclinical data" on Pfizer's proprietary drug candidates. An advisory committee, involving both Pfizer and Wash U researchers, will put forth proposals about which drug candidates to advance into research.

"All research conducted under this agreement will be collaborative, a central premise being co-authored proposals," Frail said. "The specific details around project execution will differ from case to case. Early-stage proof-of-concept clinical trials could be conducted at Washington University or Pfizer, whereas in general, it is anticipated that later-stage development activities would be led by Pfizer."

When it comes to validating the biomarker discoveries that are expected to result from this joint effort, Wash U said it intends to conduct "small, 'smart' proof-of-concept clinical trials that leverage well-characterized patient populations."

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According to Pfizer, the drug candidates involved in the collaboration have already been "extensively studied and their mechanisms of action are well understood." As such, Wash U researchers looking at the repositioning potential of these drug candidates will not have to replicate preclinical studies, which Pifzer is hoping will "shave years off the time it takes to evaluate new uses for existing drugs."

With $110 billion in global sales expected to go off patent for the top 50 drug companies by 2014, time is of the essence for the drug industry to employ cost-cutting measures and more efficient drug development strategies. In particular, Pfizer, whose $50 billion mega-blockbuster Lipitor is going off patent in November 2011, has made aggressive changes in anticipation of the "patent-cliff," including merging with Wyeth, reducing its staff, consolidating facilities, and re-prioritizing its pipeline. In addition, the pharma giant has been among the first in the drug industry to invest in genomic strategies to find the best responders to its drugs or to reposition drug candidates in its pipeline.

"There are two realities in drug discovery," Frail said in a statement. "The majority of candidates tested in development do not give the desired result, yet those drugs that do succeed typically have multiple uses. By harnessing the scientific expertise at this leading academic medical center, the collaboration seeks to discover entirely new uses for these compounds in areas of high patient need that might otherwise be left undiscovered."

Industry observers estimate that the attrition rate for investigational drugs going into human studies for the first time is around 90 percent. The attrition rate is particularly deplorable in oncology, where 82 percent of drug candidates fail during clinical trials.

However, according to a report publish in Nature Reviews last year by Ian Walker, licensing manager at Cancer Research Technology, and Herbie Newell, director of translational research at Cancer Research UK, the development of molecularly targeted cancer agents has shown an improved success rate in drug development, as kinase inhibitors have an attrition rate of 53 percent in Phase I and have even better chances of success in later development stages.

The molecular targets involved in cancer treatments make them popular targets for personalization and resuscitation as big pharma become more comfortable incorporating genomic strategies into its drug development strategies. For example, in addition to inking drug/diagnostic partnerships to develop genomically targeted drugs for brain cancer and non-small cell lung cancer, Pfizer is also attempting to use protein markers to revive the melanoma drug tremelimumab, which it stopped developing two years ago due to low efficacy (PGx Reporter 04/28/10).

The dissolution of the one-size-fits-all blockbuster model has also brought about more collaboration among drugmakers. In addition to sharing data with academics at Wash U, Pfizer is also working with its peers in industry to advance genomic knowledge industry-wide.

Earlier this year, Lilly, Merck, and Pfizer together formed the Asian Cancer Research Group, and agreed to compile precompetitive pharmacogenomic data in the hopes of accelerating the discovery of targeted treatments for gastric and lung cancer (PGx Reporter 02/24/10).

Pfizer's partnership with Wash U will involve drugs for diseases other than oncology, but the disease areas have yet to be decided.

"Given the pace of scientific discovery globally, Pfizer recognizes that there are opportunities for many good collaborations outside our walls," Frail said. "The breadth of expertise in both basic and clinical sciences afforded by the Wash U School of Medicine complements Pfizer’s internal development capabilities and our longstanding relationship provides the ideal opportunity for us to pioneer this new way of working between academia and pharma."

Big pharma's reputation for closely guarding its pipeline has often made it difficult for academia and smaller firms to ink mutually beneficial collaborations with drugmakers. Undoubtedly, a key factor in Pfizer's decision to share proprietary data with Wash U was their existing collaboration on early-stage drug research for immune-inflammatory disorders.

"We believe that together we can advance important understanding of disease mechanisms to proof-of-concept clinical studies," Gordon said. "We remain optimistic that our 20-plus year collaboration will continue to prosper and evolve."

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