By Jennifer Van Brunt


Even as the massive scientific undertaking to sequence the entire human genome starts into the home stretch, biotechnology companies with genomics-based drug discovery programs are busy forging partnerships with leading universities to gain exclusive rights to newly discovered genes with promising potential as therapeutics for mankind's most devastating diseases. The number of research-based collaborations and straight licensing deals that center on newly discovered genes has skyrocketed in parallel with the sophisticated technologies that allow scientists to unravel the mysteries of the genetic code. Biotech firms — both private and public — are latching on to new genetic data almost as quickly as research scientists at universities and nonprofit institutions are generating them.

And companies that have mounted programs in pharmacogenomics are taking the effort one step further. Integral to pharmacogenomics is the ability to identify patient populations that might benefit from a drug candidate. Even before the clinical trials start, it behooves the sponsoring company to pinpoint just that patient population that is most apt to benefit from the drug therapy. So it's not surprising that many a biotechnology company with an eye to the future has taken to aligning partnerships with research institutions and hospitals that have amassed tissue samples and pathology data from the many patients that have passed through their portals over the years.

One of these is Millennium Pharmaceuticals Inc. (NASDAQ:MLNM), which formed a predictive medicine spin-off in early December 1997. The company, Millennium Predictive Medicine Inc., was formed to harness the combined power of pharmacogenomics — the prescribing of a drug based on a genetic analysis of which patients will (and will not) benefit from that drug — and diagnomics — disease-state analysis using genomic and/or proteomic techniques — to bring new drug therapies to market.

As part of this initiative, Cambridge, Mass.-based Millennium has begun to forge a network of clinical research alliances to broaden its capabilities in the large-scale identification of gene targets and markers important for the prognosis, diagnosis and treatment of disease. In August, the company announced the first two of these — with the University of Texas M.D. Anderson Cancer Center and with the University of Pittsburgh. Both alliances allow Millennium to tap into valuable clinical samples and tissue collections — the databases that form one important aspect of any pharmacogenomics effort. For its part, Millennium will provide financial support as well as access to its integrated genomics technologies. It's also in the position to form specific, basic research collaborations with institutional researchers along the way.

Millennium's Clinical Network

Through its three-year alliance with M.D. Anderson, based in Houston, Millennium has been afforded access to vast source material in the field of oncology. In particular, the company is focusing its efforts on breast, ovarian and lung cancers. Once it collects data from M.D. Anderson's existing clinical samples and tissue collections, Millennium will use its repertoire of genomics technologies to identify gene targets, disease markers and specific DNA sequences closely associated with disease genes. In parallel, the company will study patterns of gene expression that correlate with chemotherapy resistance or sensitivity. Ultimately, the information will be used to diagnose disease and customize therapies for individual patients. But, importantly, it also will allow the company to design its clinical trials for a hand-picked group of patients, thus tipping the scales in favor of a positive outcome for the experimental drug.

In its arrangement with the University of Pittsburgh Medical Center Health System, Millennium has signed a three-year research collaboration to create a clinically annotated tissue bank, which will build on the Western Pennsylvania Genitourinary Tissue Bank that was established in 1992. The medical center will provide diseased tissues and pathological and clinical information on patients' tissue specimens. Here again, the goal is to identify molecular targets for the development of new drugs and diagnostics, especially in the fields of oncology and cardiovascular and pulmonary diseases.

Just about the time that Millennium was spinning out its predictive medicine company, Incyte Pharmaceuticals Inc., of Palo Alto, Calif., was forming a new venture in diagnomics with British pharmaceutical heavyweight SmithKline Beecham plc. Created with an eye to exploiting the diagnostics applications of both partners' genomics programs, diaDexus LLC gained immediate access to two of the world's largest commercial libraries of genetic information. It can tap into SmithKline's genomics and bioinformatics capabilities — including discoveries made by London and Philadelphia-based SmithKline using the SmithKline/Human Genome Sciences Inc. database — as well as Incyte's (NASDAQ:INCY) leading-edge databases, including its human and microbial databases (for diagnostic applications) and its bioinformatics capabilities. DiaDexus' initial efforts will be to develop tests for disease detection, as well as for diagnosis, staging and patient stratification, in the areas of oncology and infectious diseases. As well, the company plans to develop pharmacogenomic tests to tailor drugs to patients.

DiaDexus was born in September 1997; one year later, the Santa Clara, Calif., firm had signed an exclusive licensing deal with London-based Cancer Research Campaign Technology Ltd. for technology related to cervical cancer screening, in particular a cervical cancer marker discovered by scientists at the University of Cambridge. The company intends to offer the assay initially as part of a conventional Pap test, to improve the sensitivity and specificity of cervical cancer screening. This is a huge market, with close to 110 million tests performed on a worldwide basis every year.

Incyte Pharmaceuticals has covered the other side of the pharmacogenomics/diagnomics equation, too. In August of this year, it announced the formation of a pharmacogenetics business unit, Incyte Genetics. The lofty goal of the new unit is to complete a map of the human genome in one year, produce a large-scale genome sequence database and generate single nucleotide polymorphism (SNP) data for every human gene. To implement its plans, Incyte bought Cambridge, U.K.-based Hexagen plc, which has built a technology platform for SNP discovery. The technology will enable the genetic profiling of patients, and correlating genetic variation with disease severity and drug response leads to individually tailored drugs.

Beyond The Year 2000

Incyte's president and chief scientific officer, Randy Scott, claimed at the time that the company would not only have a map of the human genome completed in one year but also a commercial genetic sequence available in 12 to 24 months. In late October, Scott repeated that claim while speaking at the National Conference on Biotechnology Ventures, co-sponsored by Ernst & Young LLP and Oxford Bioscience Partners. Scott predicted that through efforts mounted by Incyte as well as the other major players in the field — including the new company Celera Genomics Corp. (formed by Perkin-Elmer Corp. and The Institute for Genomic Research in May 1998) — the entire human genome will be sequenced within three years. Of course, that's only the beginning. "It's not how many sequences you have, but how you use the information," Scott said. "The real contribution of biotechnology is not in developing new drugs, but in understanding the molecular basis for virtually every human disease."

And that goal — seemingly unapproachable even 10 years ago — now seems well within reach. Pharmacogenomics, diagnomics, proteomics, chemistry-based genomics and bioinformatics all provide the keys to unlock the final mysteries. According to Scott's vision, we could hold the answers to all human ailments by the year 2005. *