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December 8, 2003
Volume 81, Number 49
CENEAR 81 49 pp. 17-26
ISSN 0009-2347

Small technology providers and major drug firms become allies to find the causes of disease, to validate targets, and to understand drug response


In April, U.S. researchers produced a final sequence of the human genome and announced that "the genome era is now a reality." By October, competing gene chip companies Affymetrix and Agilent Technologies were offering the entire genome on single microarrays as small as a glass laboratory slide.

DIAGNOSTIC Bayer's acquisition of Visible Genetics Inc. in 2002 expanded its capabilities in genotyping assays, used to assess the genetic make-up of viruses, such as HIV, and monitor and make therapy decisions to optimize patient outcomes.
In just over a decade, the race to sequence the genome generated data faster than expected and then put it in the palms of researchers' hands. These are notable technological milestones based on advances in gene sequencing and biochip capacity. But in some respects, such leaps did a disservice to the science of genomics, shaping unrealistic expectations around how quickly it would bear fruit.

Genomics hasn't yet fully proven its worth in drug R&D, many people in the field admit. Last year, for example, the Food & Drug Administration approved 18 new chemical entities, only one of which involved a new target identified from the human genome project, notes a leading genomics company executive.

In defense of genomics, most industry researchers say that with only about four or five years under their belts since genomics started to take off, it's simply too early to expect results. The biggest factors controlling the pace of applying genomics in drug R&D have been time and cost.

"The jury's still out," says Mitchell Martin, research leader for bioinformatics, genetics, and genomics at Roche. He points out that disease targets and potential drug candidates identified so far through genomics represent only the very first steps in a 12-year drug development process.

Meanwhile, genomics technologies--for sequencing, genotyping, and expression analysis--have become more routine, faster, and less expensive. "The technologies are moving toward being cost-effective," comments Melvyn Hollis, head of functional genomics at Aventis. "But it's still expensive to do many things, and so we tend to apply them in limited ways.

"We're currently taking snapshots, not making movies," Hollis explains. "It would be great to move to where we really are taking the right number of pictures and can string them together, but that would bring with it the need to handle all the data."

Indeed, an explosion of data is challenging researchers' abilities to handle and analyze information. Having a robust and integrated informatics infrastructure is becoming critical to making progress, drug R&D managers say.

"We've moved from knowing just a little bit about maybe 3,000 human genes five or six years ago to now knowing just a little bit about maybe 30,000 genes," Roche's Martin says. "We used to be casting a fly-fishing line into a creek, and now we're on the open ocean."

Genomics research is, however, starting to yield a better understanding of the molecular basis of disease, R&D managers believe, as many big drug companies attempt to make sense of what's been unearthed so far. Much of this work is being done through alliances with a new generation of genomics firms that have emerged since the late 1990s.

In the mid-1990s, most of the large drugmakers tapped into emerging gene-sequencing and genomics activities via alliances with a first generation of technology firms, such as CuraGen, Incyte, Genome Therapeutics, Human Genome Sciences, Myriad Genetics, and Millennium Pharmaceuticals. At the time, these deals were among the largest ever seen in biotechnology, each bringing hundreds of millions of dollars to the small companies.

But since the genomics boom of 2000, when a draft of the human genome was completed, investors have soured on technology companies and shifted their attention to product-based firms. Most of the small genomics companies no longer want to be considered technology providers and have made substantial cuts in staff, eliminated early discovery programs, and refocused on advancing their most promising drug products. And many of the mega-alliances have run their course.

In August, Millennium and Abbott Laboratories ended what was to have been a five-year collaboration focused on obesity and diabetes after just over two years and Abbott's investment of $250 million in Millennium. In line with a restructuring announced in June, Millennium had decided to exit this line of research.

The alliance was expected to deliver two drug candidates into the clinic by 2002 and two to three each year thereafter. Although the companies started Phase I trials in November 2001 on their first genomically derived obesity drug, they later dropped the drug.

Still, the alliance resulted in "many interesting compounds, targets, and technology," Terry Opgenorth, Abbott vice president for metabolics drug discovery, said in August. Abbott, having retained a license, will continue to develop targets and compounds that show the most promise.

In October, Millennium's five-year, $465 million collaboration with Bayer came to a scheduled end. The partners have amended the agreement to give Bayer continued access for up to seven years to a pool of 280 drug targets that the companies say have not yet been configured into screening assays for technical reasons.

Bayer research executives have called the collaboration "extraordinarily successful." The goal was to identify 225 therapeutically relevant drug targets in a variety of disease areas; Bayer has moved 180 into various stages of assay configuration and drug discovery, and two projects have yielded preclinical candidates.

Another goal was to create a pipeline of 30 preclinical candidates. Jan-Anders Karlsson, head of international research for Bayer HealthCare's pharmaceuticals division, maintains that, with access to the 460 targets, the company is "in an excellent position to capitalize on our results to fuel our pipeline with candidates based on our understanding of the genome."

Back in late 2001, Bayer and Millennium said they expected to put their first genomics-derived small-molecule drug into Phase I trials, pending successful completion of preclinical studies. However, the trials never materialized.

"We used to be casting a fly-fishing line into a creek, and now we're on the open ocean."

MILLENNIUM IS FREQUENTLY asked why nearly all the molecules in its own pipeline have appeared there via acquisitions and what this says about the ability of genomics to deliver products. When the question was raised at an analyst and investor day in October, Robert Tepper, Millennium's president for R&D, emphasized that genomics targets will be working their way into the pipeline in the next several years.

"A part of that is the natural time course it takes to bring something through discovery and development, and part of it is the amount of resources we've been able to focus internally," Tepper explained. "And many of the genomics targets we've identified across multiple disease areas are not our molecules, but are molecules we've delivered to our partners."

Millennium has scaled back its genomics and informatics groups, which largely supported external alliances, and instead has integrated genomics approaches broadly across its R&D programs. Representative of its product-oriented shift, Millenium's most recent alliance--signed in June with Johnson & Johnson--focuses on marketing its acquired cancer drug, Velcade.

CuraGen, another pioneering genomics firm, also saw two major technology deals--one with Roche and another with GlaxoSmithKline--end in 2001. And through a restructuring unveiled in June, CuraGen, too, is focusing on products, having spent $100 million and several years to build a technology base. The company says its systematic approach has allowed it to identify 8,000 novel and known targets, of which it has qualified 500, through cellular and animal models, as playing roles in disease.

CuraGen says it was one of the first firms to discover, validate, and successfully advance a drug candidate from the human genome into clinical trials: It started Phase I trials of its drug for cancer-therapy-induced oral mucositis in March. The company's pipeline of candidates derived from novel genomic targets consists of 15 protein therapeutics that it is developing on its own; 15 monoclonal antibodies, including four licensed from its collaborator Abgenix; and six small molecules for obesity and diabetes developed in an alliance with Bayer.

Jonathan M. Rothberg, CuraGen president, chairman, and chief executive officer, describes the company's evolution as an "amazing journey" through the ups and downs of the genome era. "Some of those deals are producing a pipeline for us now," he recently told investors and analysts, "and others taught us things such as how to make and prioritize drugs."

OVER THE PAST DECADE, big pharmaceutical firms invested a significant amount of money in small genomics companies. Although executives from small companies still see interest from potential collaborators, the large firms tend to be more conservative. And many deals being signed today are smaller.

CONDENSED Affymetrix offers a gene chip that holds the protein-coding content of the human genome on a single microarray. IMAGE COURTESY OF AFFYMETRIX
"It's hard to dissect out what the real reasons are for a more cautious approach," one executive says. He cites the overall economy, more careful spending in the current business environment, and maybe some sense that the promise of genomics was hyped. There's clearly also an awareness that finding a gene or protein target does not equate with a new drug, and companies are adjusting deal valuations accordingly.

The first generation of genomics companies "saw themselves as being able to do everything, from soup to nuts, and wanted to become drug companies," Roche's Martin says. Many small companies today are realistic about what it takes to be successful, he adds. Realizing that they have relatively narrow expertise or key intellectual property, they decide instead to engage in more focused partnership interactions.

Big pharmaceutical companies acknowledge they've gained something from connecting with the small firms. For example, research managers generally say it doesn't make sense to develop technologies in-house that they can acquire or access externally. "We're much more inclined and likely to be adapting and implementing technologies developed on the outside," Aventis' Hollis comments.

Aventis' functional genomics group, which includes five centers around the world supporting the firm's disease groups and broader drug innovation and approval efforts, has participated in technology alliances with Affymetrix, Celera Genomics, and Incyte. With Millennium, it ran a five-year, $200 million technology transfer agreement--completed ahead of schedule in April after about three years--and maintains an ongoing R&D collaboration in inflammation.

The technology transfer agreement, Hollis says, "really made a very big impact on the way we generate our internal pipeline of target opportunities." Joint project teams helped bring a broad spectrum of technologies--such as high-throughput sequencing, high-throughput molecular pathology, and gene discovery--into Aventis, he notes.

Similarly, Bayer decided in 1998 that the fastest way to build a competitive position in genomics was through a partnership with Millennium, explained Karl Ziegelbauer, director of research alliances and process management, at a recent pharmaceutical chemistry and drug discovery outsourcing meeting sponsored by Strategic Research Institute. Since then, Bayer has incorporated several related technologies into its own R&D and has gained an intellectual property position in novel genes.

Bayer has seen a rise in innovative research projects and the transfer of both know-how and R&D culture from having its scientists work on-site at Millennium, Ziegelbauer reported. The collaboration also showed that genomics enables "industrialized target identification and assay development," which needs to be followed by validating target relevance and generating pharmacological tools and lead compounds.

Although alliances are popular, many major pharmaceutical companies are working to create internal genomics capabilities. GlaxoSmithKline is frequently cited as among the most advanced in using genetics broadly across its drug discovery and development efforts under the leadership of Allen Roses, senior vice president for genetics research.

Roche also has been working for several years in both the pharmaceutical and diagnostics areas to be "well positioned for this new era of molecular medicine," Martin says. It operates the Roche Center for Medical Genomics in Basel and an oversight genetics organization to coordinate approaches and ideas as they apply to R&D and business.

"We've taken a couple of disease areas and intensively apply genetics, genomics, and proteomics technologies in a concerted effort to look for candidate diagnostic markers and therapeutics," Martin says. The initial focus was on colorectal cancer and type 2 diabetes, but the firm's work is now beginning to expand into other disease areas.

Similarly, Novartis operates its new Novartis Institutes for BioMedical Research (NIBR), headquartered in Cambridge, Mass., where it says "chemistry meets the genome." NIBR's mission includes understanding disease mechanisms, discovering new drugs reliably and predictably, and using new genomics and chemistry tools to shift attrition in the drug pipeline from the more expensive clinical testing stage back to drug discovery. Novartis' research foundation also funds the independent, for-profit Genomics Institute in San Diego.

ACCORDING TO MANY small technology providers, most major pharmaceutical firms at least have an internal functional genomics group to help them find drug targets. Others also have pharmacogenomics teams that either apply the technology or survey the field to keep up to date. From both internal efforts and the early collaborations, the drug industry has found itself with an abundance of potential targets that can be acted upon by small-molecule drugs.

Such targets are typically proteins expressed by human genes. Before the complete sequencing of the human genome, Millennium reports, pharmaceutical companies relied on only 500 drug targets for developing medical therapies. While the number of targets has multiplied, validating and prioritizing them has become a difficult bottleneck.

But some believe the flood of targets has helped improve target quality and selection. "We now have a higher number of target opportunities, but in general are still selecting a similar number as before to go on to the chemistry and preclinical work," Aventis' Hollis says. "But it's our belief that we've increased the hurdles, focused much more on validation, and are making better decisions."

For assistance in this target validation process, some companies are turning to a new generation of small firms offering fresh perspectives and new capabilities.

For example, much discovery work to date has employed gene expression to learn which genes are turned on and off and then used the genes as putative targets. "Gene expression is an extremely critical spoke in the wheel," says Michael J. Pellini, president and CEO of Genomics Collaborative Inc. (GCI). "But we never believed the discovery process would be that simple.

"In the future, the most successful drugs or drug targets probably will come from programs that integrate various aspects of genomics," Pellini explains, including RNA and protein expression, genetic variation analysis, and human genetic studies. "Each of these represents a piece of genomics," he adds, "and genomics represents just a piece of the overall drug discovery effort."

GCI has amassed a repository of tissue, DNA, RNA, and serum samples--about 550,000 specimens linked to disease and medical information from 120,000 participants--and offers partners access to these samples for genetic analysis. The company worked with a network of physicians to collect the samples through a standardized format mirroring a clinical trial. Besides its sample repository, GCI also has high-throughput genomic analysis capabilities.

Many major companies are not able to conduct large-scale genetic analysis, Pellini says, but are interested in the approach. GCI's genetics approach links human genes, proteins, and clinical outcomes to validate therapeutic and diagnostic targets. "We can actually use genetics to help prioritize the hundreds of targets sitting out there today and help the companies decide where they should place their bets," he adds.

GCI has signed more than 90 access agreements with more than 30 drug and biotech firms, including a collaboration established with NIBR in September that is GCI's largest to date. The two companies will look at up to 100 genetic targets in 1,000 to 2,000 clinical samples in at least two, and up to four, therapeutic areas, beginning with type 2 diabetes.

Other companies, such as Ardais and First Genetic Trust, are also in the sample repository and genetic analysis business, filling a niche for aggregating the biomaterials needed for research programs. First Genetic Trust largely provides genetic banking, data handling, and bioinformatics services in support of drug company clinical trials and postmarketing studies. It has an alliance with GlaxoSmithKline.

ARDAIS OFFERS biospecimen management systems and has worked with four medical centers to create its collection of 180,000 tissue samples from 14,000 donors. It has commercial agreements with more than 25 companies--including AstraZeneca, Aventis, Bristol-Myers Squibb, and CuraGen--for access to what it calls its biomaterials and information for genomic research, or BIGR, repository and to other "clinical genomics" resources.

"The first examples of clinical genomics really emerged three or four years ago when human disease was directly analyzed using genomics technologies," says Alan J. Buckler, Ardais founder and chief scientific officer. "Although the technologies are still maturing, it's become clear we can start to use them in ways more directly relevant to the drug discovery process."

In simple terms, he says, scientists realized that cancers that looked the same under a microscope actually looked different on a molecular level. Changes in genes, proteins, and their activities could be linked with differences in patients' disease progression and outcome and suggested biological targets for therapeutic intervention.

Thus, diseases can be both identified and classified based on molecular events, and therapies can target these events. "Disease is becoming redefined by molecular profiling studies," Buckler asserts. "Not all diseases with the same name are really the same disease, and because of that they require different treatments.

"It's pretty exciting because for the first time you can find molecular entry points into human disease as opposed to using traditional animal- or cell-based models," he says. "And since you are actually looking at the disease, there's higher confidence that what you observe is directly relevant, the results are going to be much more compelling, and more robust diagnostics and therapeutic approaches should emerge."

Based on a similar desire to explore the underlying biology of disease, deCode Genetics applies human genetics specifically to drug discovery. The seven-year-old company has unique access to genetic and medical information from the Icelandic population, a group whose geographic separation has resulted in a well-characterized genetic pool.

From this pool, the company has isolated more than 15 specific disease genes--about 75% of which are "druggable"--meaning the genes, gene products, or associated pathways can be manipulated by small-molecule drugs--and has located genes involved in more than 25 common diseases. DeCode's success, compared with attempts made by others a decade ago, depends on linkage studies using a statistical population-based approach, according to CEO Kári Stefánsson.

"People were trying to apply genetics to drug development before it was at a stage of maturity where it had anything to contribute," Stefánsson says. "There were a significant number of deals on gene discovery in common diseases, but the companies were not in a position to isolate genes because at that time it was simply too technologically difficult.

"They could not deliver reliably enough on the gene discovery end," he continues, "and probably didn't give the world as much return as people had hoped." Meanwhile, the alternative approach of expression profiling "left you with the question of whether the target you pull out has anything to do with the disease or not," since probably 99% of changes in gene expression are a reaction to the disease process rather than the cause.

"We are not selecting the target based on a hypothesis; we are isolating the major genes that cause the disease," Stefánsson emphasizes. "And when you are starting drug discovery and development and going down a path that's going to lead to enormous expenditures, it gives you real comfort to begin that process with something solid under your feet."

"We are not selecting the target on the basis of a hypothesis, we are isolating the major genes that cause the disease."

Within about 18 months of being formed, deCode signed a five-year, $200 million gene discovery agreement with Roche. In 2001, deCode signed another deal, worth a potential $300 million, to develop products and services with Roche's diagnostics division. When the first agreement was completed in early 2002, the two companies set up a new three-year alliance to turn their gene work into drugs.

In late 2002, Merck agreed to pay deCode a potential $90 million under a three-year alliance targeting obesity. DeCode also has pharmacogenomics collaborations with Pfizer and Wyeth.

DeCode expects to send its first drug, from its own internal peripheral arterial occlusive disease project, to Phase I clinical trials by the end of 2004. In January, it announced the identification of specific variations, or markers, within a single gene that confers significant increased risk of osteoporosis. Having duplicated the results in other patient populations, the company expects to launch a new diagnostic test with Roche in early 2004.

Linkage studies, like deCode's, often yield disease susceptibility genes, Roche's Martin explains, that in turn are often connected to a loss of gene or protein function. "That's an important fact because pharmaceutical companies tend to find it easier to make inhibitors to proteins rather than activators," he points out.

Although researchers must still figure out how to make these genes druggable, "you can get a much greater understanding of disease ideology," Martin says. "Many genes deCode has identified for us have revealed entirely new biology that we knew nothing about, including tissues and pathways we wouldn't have considered targeting, and that gives us a great advantage.

"Genetics research is highly dependent on the input," Martin points out, requiring well-characterized, appropriately collected samples and supporting information. But drug companies often have their own clinical samples and may seek partners with the technology to analyze them. To this end, Roche also has an alliance with ParAllele BioScience.

ParAllele has technology for high-throughput discovery and genotyping of single-nucleotide polymorphisms. SNPs are the variable sites across the genome, occurring about once in every 1,000 base pairs, that confer heterogeneity among people, including in disease susceptibility and drug response. SNP discovery--trying to sort out millions of changes from within vast amounts of human genetic material--is widespread among private and public efforts.

To avoid costly and time-consuming resequencing, ParAllele uses oligonucleotide-based molecular inversion probes to interrogate up to 10,000 SNPs at a time--orders of magnitude more than earlier approaches--in a single well of a microtiter plate, ParAllele President Nick Naclerio explains. The company calls its approach "lab-in-a-tube."

"The power is all in novel biochemistry, not automation, to give us very large scale," Naclerio says. "In our lab, you wouldn't see any robots or any big capital equipment.

"Its comprehensiveness means we can afford to look across the whole genome, across all different types of variation, whether it's common SNPs, rare SNPs, or private mutations," he continues. Whereas linkage studies may find one or a few major disease genes, proponents of whole-genome scanning note that many diseases or drug responses may involve multiple genes or factors spread across the entire genome.

"And because our technology is cost-effective, we can afford to look across thousands of individuals with very high accuracy," Naclerio tells C&EN. In fact, large numbers of samples are necessary to yield statistically meaningful results.

Roche will provide clinical samples and fund testing to find genetic variations in a group of genes associated with type 2 diabetes. "Ultimately, we see these case-controlled gene association studies becoming a large part of how we assess targets and markers," Martin suggests. Such pharmacogenomic information may also be used to select patients for clinical trials and perhaps identify those most likely to have safe and efficacious responses to drugs.

ParAllele has another SNP genotyping collaboration with Merck, but the partners are offering no details. "Companies come to us with an interesting problem they want solved, and we work with them to solve it," Naclerio comments. "Our business is to help enable drug companies, not to be a drug company."

ParAllele's business plan includes providing its technology to third parties, such as Baylor College of Medicine. "There's a market of several thousand labs in academia, clinical medicine, and the pharmaceutical and biotech industries that could be performing these kinds of experiments," Naclerio explains.

"We certainly have no problem engaging pharmaceutical companies on a collaborative basis," he continues. "But ultimately, with the number of labs out there, we can't possibly scale up our service business to address all of them, and so our intention is to make the technology very widely available and turn it into kits that can be run on standard instrumentation."

Like ParAllele's lab-in-a-tube, other approaches have emerged to analyze large amounts of genomic information. In 2000, CuraGen created its 454 Life Sciences subsidiary to "break through the high-throughput sequencing bottleneck." It has developed methodologies for rapidly sequencing whole genomes in "days instead of years," using a massively parallel platform based on solid-phase sequencing in picotiter plates.

Similarly, Perlegen Sciences, a 2000 spin-off of Affymetrix, uses whole-genome scanning based on gene-chip technology to make SNP discovery faster and more affordable. In its first 18 months of operation, the company sequenced and compared 50 haploid human genomes, the equivalent of one genome every 10 days, in contrast to the years it took to complete the original human genome sequence. It also discovered and confirmed more than 1.5 million SNPs.

Since doing this, Perlegen has formed pharmacogenomic partnerships with Eli Lilly, GlaxoSmithKline, Bristol-Myers Squibb, and Pfizer to find genetic variations associated with disease or drug response. Bristol-Myers, for example, hopes that genome scans of clinical trial participants will identify markers for patient response to drugs already in its portfolio.

"Not all diseases with the same name are really the same disease."

THE RISING NUMBER of pharmacogenomics alliances is evidence that this emerging field is increasingly attractive to major drug producers. The hope is to improve success in clinical trials and the overall productivity of the drug development process by better understanding what drugs will work in which patients and when side effects might occur.

"A 10% or 20% change in the attrition rate for development candidates could really have a significant impact on the business," Aventis' Hollis comments. Using targeted patient populations, late-stage clinical trials could possibly be smaller and less expensive to run. Overall, R&D managers expect better predictability in R&D to yield better returns on investments.

Most SNP discovery and genomics firms are involved in pharmacogenomics as well. But Genaissance Pharmaceuticals has focused on pharmacogenomics alone for creating diagnostic and therapeutic products, says Gerald F. Vovis, the company's executive vice president and chief technology officer. The company has collaborations with Pfizer and Johnson & Johnson to identify markers in the companies' clinical samples.

Rather than using whole-genome scanning, Genaissance makes the problem more tractable by using the candidate gene approach. "Generally you have enough biological knowledge that you can draw up a list of between 50 and 100 genes that are most likely involved and look for variations within those," Vovis explains. He says this leads to less data to sort through and fewer false positives.

Although critics say the downside is having to pick genes from the outset or possibly missing genes, Vovis says the approach has worked well in several company studies looking for drug efficacy. He acknowledges that finding markers for side effects, as in Genaissance's newest study to find markers for the schizophrenia drug clozapine, does present challenges in knowing which candidate genes to pick.

On its own, Genaissance conducted a 16-week clinical study of statins, the class of anticholesterol drugs that leads the pharmaceutical industry in sales. Although the drugs are closely related chemically, patients are known to respond to them differently. The company looked for genetic markers of clinical effectiveness in more than 400 patients and says data related to two genes support the idea of DNA-based diagnostic tests to improve treatment and dosing decisions.

The recently publicized results have attracted both AstraZeneca, which just launched a new statin called Crestor, and Bayer, which withdrew its drug Baycol from the market in 2001 because of life-threatening side effects. AstraZeneca has taken a nonexclusive license to access the study data for research purposes. Bayer Diagnostics has exclusive rights to develop and market diagnostics tests for safety and efficacy and intends to launch one by 2005.

Diagnostics based on disease-susceptibility genes or pharmacogenomic markers likely will offer the nearest term product opportunities. Through its May purchase of DNA Sciences, Genaissance acquired intellectual property related to a genetic defect that can be inherited or acquired and that can lead to a life-threatening prolongation of the QT interval, or timing between heart beats.

"About half the drugs withdrawn from the U.S. market since 1998 have caused cardiac side effects" Vovis says. "We are going to be offering a diagnostic test that cardiologists can use starting early in the second quarter of next year for the familial form of long QT syndrome and then hope to develop the technology around the drug-induced form."

Pharmacogenomics is expected to play an increasingly larger role in clinical trials of new drugs and in improving the use of existing drugs. "While most of our activity has been focused on target identification and validation, we're moving to where we're starting to apply genomics technologies throughout the pipeline to help support decisions," Aventis' Hollis says.

Roche's Martin concurs and points to the company's broad program for identifying markers to help select patients and monitor efficacy. "We are taking a close look at both marketed drugs as well as the ones that are now in clinical trials," he says. "This is just going to be a part of the landscape here, not a 'one off' here and there."

"In the future, most successful drugs or drug targets probably will come from programs that integrate various aspects of genomics."

BIG COMPANIES also see the opportunity to use pharmacogenomics to salvage drugs that may be failing or have failed--due to side effects or lack of efficacy--by finding appropriate patient groups. Although narrower patient populations might mean smaller markets for individual drugs, drug developers hope more of them will make it to the market. Small firms, meanwhile, see a chance to pick up drugs the major firms have dropped.

For example, last month deCode in-licensed a developmental compound from Bayer. The compound is active against a target within an inflammatory pathway related to a gene discovered by deCode that predisposes individuals to heart attacks.

Although Bayer had unsuccessfully used the same compound and target in another disease indication, deCode can start in with Phase II trials since Bayer had already taken the drug through Phase I safety trials. Bayer will receive milestones as the compound advances and royalties on any sales as a marketed drug.

"This is a transforming event for deCode," Stefánsson says. "We will be able to leapfrog several stages in the drug development process." He says the company can advance by a matter of years the time it takes to turn one of its genetic discoveries into a new drug.

In coming years, executives from both the large pharmaceutical and the small technology firms expect genomics to generate many more results across the drug R&D process from discovery through postmarketing studies. "There are already clues that there's value here, and that it isn't just a fishing expedition," GCI's Pellini says.

Cover Story
Small technology providers and major drug firms become allies to find the causes of disease, to validate targets, and to understand drug response

Brush Up On Your 'Omics'

Proteomics Emerges As The Next Frontier

FDA Offers Guidelines On Pharmacogenomic Data


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