Learning through time

Gene therapy was supposed to be easy: find a disease caused by a single gene defect and replace the gene. After the NIH showed proof-of-principle with severe combined immune deficiency (SCID) in 1990, the diseases of choice were those caused by single gene mutations: hemophilia, sickle cell anemia and cystic fibrosis.

Targeted Genetics Corp. was one of the early players in CF. It was spun out of Immunex Corp. in 1992 with an exclusive license to a gene therapy technology portfolio and rights to related gene identification and cloning, cell lines, immunological assays and certain recombinant cytokines.

TGEN's evolution from targeting the classic single gene therapy to a focus on multigenic diseases conventionally treated with small molecules or biologics illustrates how early ideas about how to use a new technology evolve over time.

Along the way, the company has learned about how its vector works - including that it gets into certain tissues preferentially - and thus what disease areas to focus on.

As with any company, TGEN's progress through the years can be mapped as a series of decision points where it elected to follow one route rather than another.

There have been a number of key inflection points: First was an early decision to do in vivo rather than ex vivo gene therapy. Next was a decision to focus on adeno-associated virus (AAV) as the company's primary vector. Third was the decision to focus on CF as its initial disease area, which it believed would have a shorter and less expensive regulatory path than the other option at the time, which was cancer. Fourth was a decision to pursue some work in HIV, but only with other people's money.

Finally was the choice to move into inflammatory arthritis with a validated target (see "Targeted Genetics Evolves").

The company's decisions, and their consequences, are instructive for those managing corporate development. Thus one will find parallels between TGEN and the cancer vaccine developers who may be just now reaching proof-of-principle with their technologies(see "Informed Optimism," BioCentury, May 29).

Other take-home messages also are not so novel. For example, as has often been seen, the value of an asset may only become apparent years after its inception (see "Asset Accumulation," BioCentury, Sept. 6, 2004).Or treatment of a disease leapfrongs clinical trials.

Along the way, TGEN has raised about $200 million - not much by biotech standards - and has leveraged its AAV expertise and manufacturing infrastructure through partnerships to stay above water.

Now, the company hopes that AAV delivery of TNF alpha to arthritic joints will provide the first commercial success and

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