Experts in nutrition science have long fretted about the correlation between diets that are rich in certain foods—such as red meat and dairy products—with an increased risk of heart attacks, cancer, and other diseases associated with inflammation.
Ajit Varki, a UC San Diego professor of molecular and cellular medicine, has identified a potential explanation—from an inflammatory response to a type of sialic acid sugar molecule called N-glycolyneuraminic acid, or Neu5Gc. Varki, who has been working in the area for more than a decade, has shown that Neu5Gc provokes a strong immune response in some people, likely worsening conditions in which chronic inflammation is a major issue.
Varki also has moved to commericalize his research findings by co-founding Sialix, a bicoastal startup based Cambridge, MA, and San Diego. The company plans to develop nutritional supplements and drugs that are intended to moderate or inhibit the body’s inflammatory response to Neu5Gc. Sialix also has targeted cancers that accumulate Neu5Gc.
Sialic acid sugar molecules like Neu5Gc are found on many proteins, and normally coat the surface of animal cells. These sugar molecules serve a key role in interacting with other cells, and play an important role in bacterial and viral entry into cells. While Neu5Gc is found in most mammals, including primates, humans somehow lost the ability to make Neu5Gc. As a result, the cells of human beings are coated instead with Neu5Ac, the sialic acid precursor to Neu5Gc that differs from Neu5Gc by a single oxygen atom.
The difference has long been known, and the presence of Neu5Gc in our diet was not deemed significant because scientists believed that healthy human immune systems did not react to it.
But Varki argues that’s not the case after all. He started Sialix in 2006 in a bid to moderate the body’s immune response to Neu5Gc. In November, the early stage company entered Janssen Labs, the life sciences business accelerator in San Diego that Johnson & Johnson established as part of its Janssen Research & Development’s West Coast Research Center.
Sialix CEO Jeff Behrens said the Janssen Labs program offers a multitude of advantages, including premier lab facilities, shared technology and equipment, and the chance to interact with the scientists and entrepreneurs from other biotech start-ups in the program. The Janssen Labs facility, which has room for 20 startups, has admitted 15 companies so far, and Behrens says, “it is an exciting place to be.”
Diego Miralles, who leads Janssen Healthcare Innovation, led the effort to establish the life sciences accelerator in San Diego as part of a “no strings attached” approach to fostering innovation. Miralles, who also is a San Diego Xconomist, wrote recently that Janssen Labs is an example of a broader effort by big pharmaceutical companies to stimulate innovation in drug development.
So does Sialix nevertheless feel pressured to collaborate with J&J in the future? Behrens said, “It is truly no strings attached,” and that he feels free to initiate relationships with different pharmaceutical partners and to control the direction of Sialix products.
In fact, Behrens said he views the insider access to J&J as one of the draw cards of the Janssen accelerator program. By lessening the financial strains, the arrangement allows time for the Sialix team to prove the depth and value of their company.
Behrens describes Sialix as a “semi-virtual” company, with a core team of scientists and advisors who also rely on extensive outsourcing of lab services. With two scientists and one technician at Janssen Labs, Behrens runs the company headquarters in Cambridge and travels to San Diego every three or four weeks. He said the setup allows Sialix to access the centers of funding and expertise on both coasts.
Sialix is pursuing two branches of development—a nutritional supplement to reduce chronic inflammation and a monoclonal antibody for the treatment of localized cancers. At the center of both technologies is Neu5Gc, abundant in red meat and dairy products. Humans lack the enzyme to synthesize Neu5Gc, so the molecule attaches itself to the ends of the glycans, or sugar chains, on the surfaces of our cells. In this way, dietary Neu5Gc is incorporated into human tissue, and as Varki has shown, the presence of this foreign molecule can trigger an ongoing immune response.
With sensitive assays, nearly all people test positive for antibodies to Neu5Gc, Behrens said. An additional 10 to 15 percent have significantly elevated antibody levels, indicative of a strong immune response. Sialix is designing its nutritional supplement to prevent Neu5Gc from accumulating in the body as a way to prevent this inflammatory response.
Varki’s lab also discovered that Neu5Gc is more highly expressed on the cells of solid tumors than in normal tissue. This presents the possibility that Neu5Gc may contribute in some way to cancer growth and also could serve as a “cancer specific” target. In addition, other glycans are mutated in predictable ways in cancers, which present additional cancer targets. To tackle these targets, Sialix is developing monoclonal antibodies to aggressively bind and destroy cells that express these non-human sialic acids and other cancer-specific glycans.
A prescription drug of this complexity remains in the preclinical phase, but Behrens says the nutritional supplement is targeted for human trials in 12-18 months. The company recently signed an option agreement on this first cancer program with Momenta Pharmaceuticals. The company also recently announced the formation of its scientific and business advisory boards, and Behrens says Sialix also is considering raising more capital. He declined to say how much capital the company intends to raise, or how much Sialix has raised previously from angel investors in New England.
Meanwhile, moving into Janssen Labs provides a chance for Sialix and Janssen R&D to get to know each other without committing to a long-term partnership. Behrens wouldn’t comment on where Sialix would be without Janssen Labs, but he says the incubator is an “enormous help,” and that Sialix is “thrilled to be there.”