PRINCETON, NJ, Dec. 4 - While the pharmaceutical industry may agree that genomic technology will impact the drug discovery process, the jury is still out on what that impact may be, according to panelists at the Economist 's Pharmaceuticals 2001 conference, held December 3-4 in Princeton, NJ.
Speaking at the conference, Stephen Hoffman, senior vice president of biologics at Celera Genomics, said that the same focus on cutting-edge technology that enabled his company to sequence the human genome would not only make genomics indispensable to pharmaceutical companies, but would give Celera an edge over these companies as it moves forward with its own discovery efforts.
Hoffman laid out Celera's plans for transitioning from a data provider to a fully integrated biopharmaceutical company. Apparently, speed still matters for Celera, as Hoffman said the company is relying on "the right mixture of informatics, ideas, and hardware" to "make the process move faster." The key to speed at the new Celera, Hoffman said, will be its high-efficiency proteomics facility, high-throughput SNP identification, lead-based target identification and validation, and structure-based drug design.
The end result, Hoffman said, would be a "tremendous saving of time" between target identification and in vivo proof of concept.
Echoing Hoffman's comments, Trevor Trust, vice president of infection discovery at AstraZeneca R&D Boston, said anti-infective discovery process was essentially at a standstill until the sequencing of the Haemophilus influenza genome in 1995 ushered in "a new era in infection drug discovery."
Armed with fully sequenced microbial genomes, Trust said it is now possible to identify all possible targets within an organism rapidly and effectively. As an example, he said that AstraZeneca was able to identify over 100 genes essential for viability in the Helicobacter pylori genome in only six months using a combination of comparative genomics and knockout technology.
But, as Ted Torphy, vice president of research at Johnson & Johnson's Centocor division pointed out, the vast number of targets identified through genomics has yet to translate into new drugs. On the contrary, he noted, "having the human genome has done very little for us in terms of understanding the pathophysiology of disease."
Torphy said that genomics has only created a new rate-limiting step in drug discovery. "I used to lie awake at night thinking, ‘Where will our next target come from?', he said. "Now I lie awake at night thinking, ‘What am I going to do with those ten additional targets we discover tomorrow?'"
Torphy said that while "optimists" cite the average reduction of four years that genomics and other high-throughput approaches have brought to target identification, lead identification, and lead optimization, the overall cycle time has not gotten any shorter. Until high-throughput technology is developed for target validation and the pre-clinical and clinical stages as well, Torphy said, the process might actually take longer as more and more novel targets squeeze their way through the pipeline.
The target validation process is a particular sticking point, according to Torphy, who said the biological methods used to validate targets have not changed at all over the past decade. "No company has developed a paradigm-shifting process or technology in target validation," he said.
The only response is to "encourage the dog to wag the tail again," Torphy said. "Technology has been driving biology until now, but the needs of biologists should drive the development of new technology."