When a big company like Amgen Inc. shows an interest in a particular pathway, many younger biotech companies follow suit.
But in the case of Auxeris Therapeutics Inc., Amgen's recent interest in the RANK ligand merely validates work already done at the two-year-old St. Louis-based company.
Auxeris is developing therapeutics for bone diseases, such as osteoporosis and bone metastasis. The company wants to prevent or reverse bone loss, as opposed to just stopping its progression.
Bone disease is an imbalance between osteoblasts and osteoclasts, bone-forming and bone-resorbing cells. That imbalance leads to osteoporosis in 50 percent of women older than 50.
Auxeris was founded in January 2002 by three men: Mark Mendel, of RiverVest Venture Partners in St. Louis, and Steven Teitelbaum and Patrick Ross, of Washington University School of Medicine.
The company was incubated based on science done at Washington University in which Teitelbaum crystallized RANK ligand.
"It's the primary cytokine, the factor responsible for the bone resorption you see in bone metastasis and, in fact, it's the primary factor that's responsible for all bone resorption," said Laurent Fischer, president and CEO of Auxeris.
Fischer joined the company in February 2003. Mendel said Fischer brought a wealth of management expertise to the young company. Fischer, who was a senior vice president at DuPont-Merck Inc. and Dupont Pharmaceuticals, of Wilmington, Del., helped bring two life-saving HIV drugs, one being Sustiva, to market. Fischer also started two other specialty pharmaceutical companies before moving to Auxeris.
"The things that are most exciting about this company to me are the quality of the senior management team, particularly Laurent," said Mendel, who serves as chairman of the company, "and what makes him outstanding is he has the rare attribute of great entrepreneurial success."
The company needed a leader like that to advance its two programs, both of which could enter the clinic by the third quarter of 2005. AUX 202, an injectable anti-resorptive, is a biological agent being developed to treat bone metastasis. Only one drug is approved for bone metastasis, Fischer said - Basel, Switzerland-based Novartis AG's Zometa, which had more than $1 billion in worldwide sales last year.
Auxeris' other product, AUX 102, is a bone-targeted beta-blocker discovered by a Baylor College of Medicine scientist, Gerard Karsenty. It is the first oral bone anabolic drug for the treatment of osteoporosis. Karsenty is a world expert on osteoblasts who found that bone formation could be accelerated by beta-blockers.
"[Karsenty] was able to demonstrate that by blocking the system with beta-blockers in animals, he could increase bone mass by 20 percent in adult mice," Fischer told BioWorld Today.
Auxeris has found that it can prevent bone resorption in a model of postmenopausal osteoporosis using that product.
Last month, Amgen, of Thousand Oaks, Calif., highlighted its programs, showing a strong interest in its AMG 162 monoclonal antibody that targets the receptor activator of nuclear factor kappa B ligand (RANKL) for osteoporosis, a key mediator of the body's natural pathway of the resorptive phase of bone remodeling. In a Phase II trial, AMG 162 showed an effect on bone endpoints and appeared to be well tolerated. Amgen expects to enter Phase III work with the drug this year.
"We've been working on the same target with a different approach," Fischer said. "We're gratified that this target has been validated."
While Auxeris identified the crystal structure, Amgen separately has conducted its own research and is further along than Auxeris. But Auxeris will focus mainly on bone metastasis with AUX 202, while Amgen is looking at osteoporosis, Fischer said.
As for protecting its intellectual property, Auxeris has filed 12 patents to cover both products. All of them are pending.
RiverVest Venture Partners loaned Auxeris its initial start-up money, then later RiverVest worked with Domain Associates, of Princeton, N.J., to provide $2.5 million in October 2002 for the company.
In January of this year, the company raised $1.6 million in an extension to a Series A financing round, bringing the total raised to date from both investors to $4.1 million.
At the same time, Auxeris acquired all technology assets from Houston-based Ceros Pharmaceuticals, which included AUX 102.
While drugs are available to stop the destruction of bone, there is little by way of therapies that reverse osteoporosis. Since beta-blockers have been used in millions of people, the company already has a safety profile for the drug candidate.
A study in more than 1,000 patients published in the January issue of The Journal of Bone and Mineral Research showed that patients who used beta-blockers had a 30 percent decrease in the risk of fracture, as well as an increased bone mineral density.