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Plexxikon Partners with Genentech, Offering Target-Compound Crystallization En Masse

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Last week, protein structure-based drug discovery company Plexxikon announced a collaboration with Genentech, its “first significant deal,” according to CEO Peter Hirth.

Under the multi-year agreement, Genentech will provide the Berkeley, Calif.-based company with a protein kinase that is implicated in cancer. Plexxikon will develop a series of small molecule inhibitors against this target. In return, the company receives an upfront technology access fee, research funding, milestone payments, and royalties on sales of drugs that might result from the project. The company would not disclose the amount of the payment, but Kathleen Glaub, Plexxikon’s president and CFO, said that the company anticipates covering 40 percent of its expenses this year with revenues from partner deals, “and this first deal with Genentech goes a very long way to helping us accomplish that.” Besides financing, the deal provides “very strong validation” of the company’s platform, which relies on co-crystallizing targets and their compounds, according to Hirth.

Since last year (see PM 12-10-01), Plexxikon has been applying its technology to target proteins from three different families, all of which have produced drug targets in the past: kinases, nuclear receptors, and phosphodiesterases. The company starts out by screening targets against a special compound library in a biological assay, like a kinase assay. Members of this library, so-called scaffolds, only have an average molecular weight of 200 Da, much smaller than conventional libraries, according to Hirth. Scientists then co-crystallize active inhibitors along with their respective target and build them out into compounds with nanomolar affinity. “The advantage of starting with such a small molecule is that you have lots of room to design features into the molecule that address the issues of selectivity, solubility, and other characteristics,” said Hirth. Furthermore, since nobody else uses the same small scaffolds, patenting is easier, he added.

The approach, which only became feasible recently when technologies for high-throughput crystallizaton evolved, differs from that of Astex Technology, for instance, which starts with even smaller drug fragments. According to Hirth, these are too small to be tested in biochemical assays.

So far, Plexxikon has crystallized 10 protein kinases, six nuclear hormone receptors, and two phosphodiesterases and has generated about 150 co-crystals of kinases and compounds alone. Several compounds are in animal trials, and the company hopes to take leads in three therapeutic programs — which include oncology, sexual dysfunction, inflammation, and metabolic disorders — further next year. But Plexxikon is also looking for collaborations, said Hirth, “so we can spread the risk amongst different partners.”

Besides progressing in its research, the company has been able to boost its funding: Last year, it raised $27 million in a Series B round, and an additional $4 million in a second closing of that round in January. This will sustain Plexxikon well into 2004, even without any partnerships, said Glaub. However, with the Genentech deal, it will extend out farther, “and we are anticipating doing additional deals this year,” she added.

— JK