New diabetes and metabolic disorders drugs waiting in pipeline for Plexxikon
East Bay Business Times - by Susan L. Thomas
Every quarter, Plexxikon Inc. CEO Peter Hirth and his top executives sit down to do a little triage. They determine which projects will continue and which ones will be shelved.
Sometimes the process is arduous, but Hirth considers it essential to determine where to invest the company's brain power.
Plexxikon's disciplined approach so far has produced the kind of results investors like. The nearly six-year-old Berkeley firm has landed a significant partnership, has one compound in midstage clinical trials and is preparing to start testing several other drug candidates in humans within a year. And it is going after some of the hottest markets in life sciences today - cancer, metabolic diseases such as diabetes and inflammation.
The firm garnered some attention in 2004 when it landed a $372 million deal with Wyeth Pharmaceuticals, yet Plexxikon has operated in an unusual stealth mode since its inception, rarely issuing press releases or calling much attention to itself.
The company's most advanced work is with Wyeth, and choosing metabolic diseases for its first project was no accident. Plexxikon wanted to accomplish its goals fast, says Hirth, who founded the company in 2000. Plexxikon considered where its technology would best marry with the market, and the company went to work.
In less than two years, it identified and, with Wyeth, began human tests of an experimental treatment that could give patients with Type 2 diabetes the ability to take one pill daily - rather than several - to help control their disease.
To explain the value of Plexxikon's technology, Hirth uses the analogy of a dark cave. Most drug discovery and development firms are working in a dark cave, he said, unable to see how the pieces in the room fit together. They build chemical structures in places that will never connect with the other pieces necessary for them to function.
Creating a different approach
Plexxikon has built a so-called platform technology that Hirth believes brings daylight to the cave, enabling researchers to see beforehand what connections might work and, just as importantly, those that will not. The goal is to speed the process of discovering and developing drugs, thereby reducing costs. Plexxikon aims to winnow the time it takes to identify new compounds from years to months. Its approach differs from traditional tools companies, which use high throughput screening that quickly analyzes millions of molecules but also may eliminate potentially useful molecules.
Here is how the technology works. Plexxikon starts by testing its collection of very tiny, low-weight molecules against several targets in a protein family as the foundation for developing an experimental drug. Traditional screens are more interested in finding molecules that bind strongly with the potential target and eliminate smaller molecules altogether. Instead, Plexxikon saves the heavy lifting for later. It is more concerned with how well the molecules and the targets bind rather than the strength of the bond. From there, co-cyrstallography is used to analyze the structure of these "scaffolds" allowing researchers to determine which compounds can be developed most easily and quickly.
Hirth's and Plexxikon's story is not one of a young struggling biotechnology firm and its founder. An industry veteran, Hirth started Plexxikon after a stint as president of Sugen Inc. before it was sold to Pharmacia Inc. in 1999, with a belief that there was a "shortage of good chemistry" going on and that drug discovery could be done differently. "Let's try to use crystallography as a filter," he remembers thinking.
Early on, the company secured financing from some of the top venture capitalists in the industry, including Alta Partners. A.M. Pappas and Advanced Technology Ventures. To date it has raised about $55 million.
Technology speeds process
Firms that focus on drug discovery are not new, and in fact investors were burned by many in this category after the mapping of the human genome. A backlash occurred in the industry, and some tools firms that succeeded also began focusing on drug development. So far, Plexxikon's technology has proved to speed the process, at least early on.
In the area of diabetes and metabolic disorders, for example, Plexxikon intends to file two applications this year and another next year to start clinical trials on potential drug candidates. Plexxikon hopes the science will pay off in an oncology program, as well, by honing in on genetic mutations that cause cancer.
The company has identified a potential small molecule drug candidate that could inhibit the cancer causing form of the B-Raf gene. The mutation occurs in about 70 percent of skin cancers, and in some colorectal, ovarian and thyroid cancers. Plexxikon also is collaborating with a diagnostic company to develop a test for the mutation. Hirth would not identify the company.
"Its an unbelievable opportunity," Hirth said, adding that Plexxikon's drug could potentially be the first in its class.
Focusing on the end game
Still, Hirth believes that what differentiates Plexxikon from similar companies that have developed platform technologies is a mindset that focuses on the end game.
"It's really about how to get to a product most quickly," he said.
Investors, too, may soon have their eyes more closely fixed on the end game for Plexxikon. Now that the company has notched some early successes, Hirth frequently hears the question, "So, Peter, what is it that you want to be when you grow up?"
The cost of shepherding drug candidates through clinical trials is cost prohibitive for such a small firm, as is building up those capabilities. Plexxikon has taken the strategy of finding partners earlier, at around the first clinical trials, rather than later. That strategy, he said, can work to retain value for investors and save money - if a company has a differentiated product.
"We are patient for growth," Hirth said, "not profit."
As with any young company, Plexxikon is considering its options, with an initial public offering or acquisition possibly taking center stage.
slthomas@bizjournals.com | 925-598-1432
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