Functional genomics company Sagres Discovery, which last week signed a multi-year collaboration with Boehringer Ingelheim to identify oncology drug targets, exemplifies a “newer wave” of bioinformatics methodology, according to CEO and co-founder David Ferrick.
“We’ve gone from a predictive to more of a deductive type of bioinformatics,” said Ferrick of the Davis, Calif.-based startup.
Sagres relies very heavily on bioinformatics as part of its discovery process, Ferrick said, but has shifted the traditional emphasis a bit. Using a high-throughput retroviral approach, company scientists first experimentally identify genes that are likely to cause tumors in vivo in mice, deriving a subset of several thousand that they have dubbed the “Oncogenome.” The bioinformatics comes in after this step, with all the advantages of a smaller data set that has been functionally verified experimentally.
“By doing this Oncogenome screen, instead of having to look through the genome, which is where a lot of people’s starting point is, we’re actually starting at the point of where cancer is caused in vivo,” Ferrick said.
The Boehringer Ingelheim deal, the company’s first pharmaceutical collaboration, is significant, Ferrick added, because it will “prove that our starting point in discovery is maybe better than how people have traditionally been starting their discovery efforts.”
Under the agreement, Boehringer Ingelheim will have exclusive rights to certain targets to develop and market antibody and small-molecule products worldwide, while Sagres will retain rights to certain targets and will also receive a “significant” up-front payment, additional research funding, milestone payments, and royalty payments from product sales. Financial details were not disclosed.
Kerstin Felix, a Boehringer Ingelheim spokeswoman, declined to comment on the selection of Sagres as the company’s research partner, noting only that the deal is part of Boehringer Ingelheim’s oncology strategy.
Novel Genes, Next- Generation Database
Sagres claims to have the largest single repository of oncogenes in the industry, and is pursuing an aggressive patenting strategy to protect genes it has identified through its unique combination of experimentation and bioinformatics. Ferrick estimates that up to 30 percent of the thousand or so genes it has found so far are entirely novel.
The company has built a suite of software tools to help it map cancer-causing mouse genes in the Celera database to their orthologs in the human genome. While mouse-human synteny maps are now appearing in the public domain with the recent publication of the mouse genome, Ferrick said that when Sagres began its work two years ago, it had to develop all of its mouse-human mapping programs from scratch.
Sagres is also building statistical and graphical tools to help it analyze the various combinatorial possibilities of mutations within cellular pathways — combinations of co-mutations that are likely, or not likely, to cause cancer. Public and in-house data are integrated into a relational database that Sagres researchers can query.
Although Sagres has identified drug discovery as its primary goal, Ferrick hasn’t ruled out the possibility of delving into the data-provider business in the future. The company is currently developing a portal that will initially allow its collaborators to access and view the fully annotated Oncogenome. Eventually, however, “We would hope to become the purveyor of a lot of that information to the public as well.”
Once Sagres has mined the information it needs from its database, it hopes to become “the centralized clearing house” for the information. Ferrick has no doubt that there’s plenty of information in the resource for others once Sagres has skimmed its share off the top: “We can’t exploit it all, not even close.”
Sagres seems to have learned a valuable lesson from Celera, which started life with the intention of selling data, and later realized the limited revenue potential of that model and turned to discovery as plan B. Ferrick explained that Sagres plans to work out a fair balance between its own discovery priorities and those of its academic and commercial collaborators. “We want to hopefully do a little better job than Celera did with the public in terms of working out a consortium so that it can get to investigators without necessarily compromising our ability to grow as a company,” he said.
Ferrick noted that the company has the advantage of following in Celera’s footsteps: “They went for the structural genome first, while we went for the functional cancer genome first. So obviously the structural genome has limited value. It just tells you the playing field, it doesn’t tell you what anyone’s doing in that field.”
He was quick to note, however, “if we didn’t have Celera, we couldn’t do what we did. Because we have a genome that’s structurally defined, it allows us to pinpoint where the biology is occurring, so that’s a very important component.”
Yet despite his admiration for Celera’s contribution to genomics, Ferrick took the opportunity to gloat a bit. “They’re going to regret the day they gave [the genome data] to us or companies like us. We’re going to derive way more value than they’re ever going to see from it.”