Athenagen Inc. raised $5.7 million in its first round of financing to advance into the clinic its first small-molecule products aimed at a recently discovered angiogenesis pathway.
The Series A investment includes $3.2 million that closed last week, along with an additional $2.5 million upon reaching certain milestones over the next 12 months. San Mateo, Calif.-based Sanderling Ventures led the financing, and Palo Alto, Calif.-based Life Science Angels also participated.
Athenagen was founded last year by two Stanford University scientists who discovered nicotinic acetylcholine receptors (nAChR) on endothelial cells.
That nAChR pathway helps regulate angiogenesis, and is related to the vascular endothelial growth factor (VEGF) that has served as the target for wet age-related macular degeneration drugs such as New York-based Eyetech Inc.'s Macugen, approved late last year, and South San Francisco-based Genentech's Lucentis, which is in late-stage development, said Scott Harkonen, president and CEO of Athenagen.
Harkonen told BioWorld Today that "for a number of years, companies have been developing drugs to target [nAChR] to treat certain neurological diseases. What the Stanford scientists found is that is also plays a role in angiogenesis."
The discovery itself came as somewhat of a surprise, said John Cooke, company co-founder and a professor of medicine in the department of cardiovascular medicine at Stanford. His team had received a grant from the state of California to conduct research in the prevention of tobacco-related diseases, specifically atherosclerosis. At the start, one of the group's hypotheses was that tobacco impaired blood vessel function.
"We though it would impair growth," Cooke said. "But when we used nicotine at low concentrations, we actually found quite the opposite."
Research went on to show that nicotine accelerated blood vessel formation and could stimulate tumor angiogenesis, as well as plaque vascularization. Then Cooke and other scientists discovered that acetylcholine, a well-known neurotransmitter, also is made by endothelial cells, meaning that nAChR pathway could be targeted to inhibit or provoke angiogenesis.
Though the nAChR pathway shares some similarities to VEGF, Cooke said, it's "really quite different."
The protein VEGF binds to a tyrosine kinase receptor, which causes dimerization of the receptor and leads to autophosphorylation and activation of downstream signaling. Acetylcholine, on the other hand, is a small molecule that binds to the nicotinic acetylcholine receptor, causing the pore in the receptor to open up.
"Basically, the receptor looks like a barrel," Cooke said, "and it opens a pore in the cell membrane so calcium and sodium can enter.
"Our contribution found that this receptor activation causes angiogenesis and suggests that we could manipulate it for therapeutic purposes," he added.
That's what Athenagen is attempting to do. After Cooke and co-founder Ken Kengatharan, a staff scientist at Stanford, formed the company and licensed necessary technology from the university, Harkonen was brought on board as CEO to help with the Series A round.
"So we're really just getting started," Harkonen said, describing Athenagen as a "classic biotech model." The company's work will focus on two parallel applications: One will investigate the potential of an existing nAChR blocker, an oral blood pressure drug called mecamylamine, as a treatment for wet AMD, while the other will focus on establishing a drug discovery program to "come up with more specific drugs to target the pathway."
Since several diseases potentially could be treated with anti-angiogenics, Athenagen eventually could look at developing drugs for cancers, rheumatoid arthritis, diabetic retinopathy and inflammatory diseases.
"The other side of the coin is to stimulate the pathway to promote blood vessel growth," Harkonen said, adding that the company is working on a topical gel agonist to treat diabetic foot ulcers.
That product and the mecamylamine drug for AMD both are expected to begin trials next year.
Athenagen is considering pursuing development and commercialization of its AMD drug on its own, but Harkonen said the company likely will look for partners for other indications, such as cancer.
"We expect to come up with receptor-specific drugs and new targets," he said, "and we think having new targets will be very attractive to pharmaceutical companies with big libraries of potential drugs to test against those targets."
Athenagen has five employees and expects that number to increase to 12 early next year. Though temporarily housed in Menlo Park, Calif., the company is preparing to lease a permanent facility in South San Francisco.