Start-up Profiles

Published online: 25 April 2005, doi:10.1038/bioent856

Serenex

*Ken Howard Wilan is a contributing writer for Nature Biotechnology based in Boston. kenhoward@mindspring.com

Metamorphosis from tool company to drug discovery engine.

Founded in 2001, Durham, North Carolina-based Serenex quickly changed CEOs and business models. The company (see Serenex profile) was originally conceived of as a tools company, says Richard Kent, who became CEO in November 2002, taking over from founding chairman and CEO Robert Dishman. They were going to box up the technology and sell it to pharmaceutical companies, but it "quickly became evident that wasn't feasible, there was too much expertise needed for the technology. There's a lot of art to it," explains Kent. Instead, they decided to focus on bringing in revenue by selling their technique as a service to pharmaceutical companies as well as using it for their own in-house drug discovery and development program. And Dishman? He has a "history of starting new companies, he's more of an entrepreneurial start-a-company kind of guy than an operational guy," says Kent.

Kent, who had been chief medical officer at GlaxoSmithKline in Research Triangle Park, North Carolina, was brought in to steer the company's proteomic analysis technology towards pharmaceutical clients as well as the clinic. The science which got the company started—a high-throughput proteome screen meant to accelerate target identification and flag negative side effects of potential therapeutic agents early in the process—was licensed from the University of Virginia in Charlottesville, Virginia, where the company's scientific founder Tim Haystead had a lab before moving to Duke University in Durham. Haystead received $10 million in backing from Mediphase Venture Partners in Newton, Massachusetts, and Intersouth Partners of Durham.

Serenex's technology can screen for known targets of drugs while profiling against several thousand proteins¹, according to Steven Hall, senior vice president of R&D. "If there are any skeletons in the closet around a particular compound, we can find them very early," says Hall. The basic approach, he and others acknowledge, is similar to that of other companies, including San Diego-based Ambit Biosciences and Cellzome, based in Heidelberg, Germany, and Cambridge, UK.

Serenex's series of affinity media allows for the reversible capture of protein targets from multiple gene families (Fig. 1). The company is focusing initially on the super-family of proteins that possess binding sites for purines, which includes numerous enzyme classes such as kinases, helicases and phosphorylases. The first step involves binding the proteins present in a tissue, organ or cell line to the affinity medium. Next, the protein-bound medium is challenged with drug-like molecules that compete for the binding site on the proteins, causing them to elute them from the medium. The eluants are then analyzed to identify the protein binding partners for each compound. Serenex uses endogenous proteins from a variety of sources to profile compounds against multiple proteomes.

Fig. 1

		Functional protein fractionation and proteome mining.		Image Source: Serenex

Since shifting gears, the company has raised an additional $15 million in a Series B round and, according to Kent, is looking to raise an additional $40 million in Series C in 2005. They have collaborations with pharmaceutical companies, including GlaxoSmithKline and Indianapolis, Indiana's Lilly, which bring in over $1 million in revenue per year, says Kent, and are also using their high-throughput screen aimed at purine-binding proteins to analyze in-licensed compounds as well as drug candidates discovered in-house. The purine-binding protein super family encompasses up to 40% of drugable targets, according to Kent. He predicts that by the end of 2006 the company will have one or two compounds in phase 2 trials as well as two compounds ready for investigational new drug applications.

		"'Serenex is going through a metamorphosis. It has a good technology platform, it is trying to bring in product possibilities. Its story is still being told,' says Paul Pospisil, of Atlas Venture in Waltham, Massachusetts."

The company, launched at the tail-end of the genomics revolution, benefited from that excitement but also suffered for it, says Paul Pospisil, a partner in Atlas Venture in Waltham, Massachusetts. (Pospisil recently met with Serenex to consider an investment; he decided to hold off.) Pharmaceutical companies became supersaturated with new discovery tools, and the analytics and bioinformatics associated with the technology proved more complicated than people anticipated, says Pospisil. The service model for tool businesses took the hit.

"The reality is it will pay for some of your expenses but the company won't go anywhere," says Pospisil. Hence the move to drug discovery as the favored business model.

"Serenex is going through a metamorphosis," says Pospisil. "It has a good technology platform, it is trying to bring in product possibilities. Its story is still being told. If it brings in products it might not resemble its original business model. We should know in the next two years."

References

1. Graves, P.R. et al. Discovery of novel targets of quinoline drugs in the human purine binding proteome. Mol. Pharmacol. 62, 1364–1372 (2002).