When Boston-based biotech startup Acetylon Pharmaceuticals began operations in 2008, it grabbed attention for having attracted a big-named backer: the Kraft Group, the Foxborough, MA, holding company founded by New England Patriots owner Robert Kraft. Acetylon ultimately raised nearly $40 million from Kraft, a group of unnamed individuals, and, most recently, the Leukemia & Lymphoma Society. It’s enough to take Acetylon through the first two phases of human testing for its lead compound—a multiple myeloma drug that the company started dosing patients with last week.
Acetylon is one of many companies working on a class of drugs that inhibit histone deacetylases (HDACs), which are enzymes that regulate gene expression and that play a role in many cancers. The HDAC inhibitors that are on the market today are known as “pan-HDAC inhibitors,” because they target all 11 HDAC enzymes. Acetylon’s drug, called ACY-1215, only targets one: HDAC6.
Actylon CEO Walter Ogier believes that selectivity may give ACY-1215 an important edge. “HDAC inhibitors have a lot of activity,” he said during a mid-September interview at Acetylon’s brand-new Seaport Center office. That activity includes shutting down some normal cellular activities, which can result in side effects ranging from fatigue to nausea to anorexia. “Patients have a really lousy quality of life and find it hard to stay on drug regimens,” he says. “The opportunity we have is to maintain or improve on the anti-cancer effectiveness by being more selective.”
HDAC6 is involved in a process by which diseased cells destroy and dispose of damaged proteins. This enzyme is over-produced in some cancer cells, particularly in patients who become resistant to bortezomib (Velcade), a blockbuster multiple myeloma treatment from Millennium Pharmaceuticals. When HDAC6 is inhibited, the abnormal “misfolding proteins” pile up and prompt the sick cells to self-destruct. Acetylon’s scientists believe this could be useful in treating cancer, as well as other diseases ranging from rheumatoid arthritis to sickle cell anemia.
In Acetylon’s trial, patients will be treated with ACY-1215 alone, or with the drug in combination with bortezomib and another commonly used treatment.
Physicians who treat multiple myeloma are eager to try the new option from Acetylon. “There are a lot of HDACs in clinical development, but most are non-selective,” says Noopur Raje, director of the multiple myeloma program at Massachusetts General Hospital and an associate professor at Harvard University. Raje is one of the physicians participating in Acetylon’s clinical trials. “We would love to do away with that toxicity.” Raje says it’s too early to tell how effective the drug is, but the two patients she’s put on it so far “have not had any troubles in terms of tolerability. That’s the goal.”
Acetylon’s trial is being supported by the Leukemia & Lymphoma Society, which committed up to $4.85 million in milestone-based funding to Acetylon in a deal announced in May. The funding is part of a strategic initiative that the society calls the Therapy Accelerator Program (TAP), which is aimed at speeding new developments in blood cancers to market. For Acetylon, it’s a win-win, Ogier says. If the drug succeeds, the company will re-pay the money to the society. If not, Acetylon owes nothing. “It’s non-dilutive,” he adds. “There’s no royalty. And it’s conditionally repayable, so if we need to abandon the program, we don’t have a big overhang.”
The TAP grant is one element of a business-development model that Ogier describes as “being extremely judicious with resources.” In its first year as a company, Acetylon had no office. Meetings happened in Ogier’s family room, he says, or in the offices of the company’s scientific founders: Dana-Farber physician and researcher Kenneth Anderson, Dana-Farber and Harvard Medical School researcher James Bradner, and Harvard Medical School scientist Ralph Mazitschek, who is based at Mass General. A contract-research organization in Shanghai performs much of the chemistry work that goes into identifying potential compounds, Ogier says.
Ogier won’t name any of the other financiers who have poured money into Acetylon, except to say, “They’re mostly wealthy investors that have a philanthropic and financial interest in seeing us succeed.” Ogier says the company plans to raise more funding in the near future, which it needs not only to advance its lead compound, but also to expand its pipeline. The company is currently studying the potential of selective HDAC inhibitors in treating inflammatory diseases, malaria, and sickle cell disease, Ogier says.
Acetylon has only 11 employees, working in a neighborhood that isn’t exactly a biotech hotbed. But Ogier says that’s all part of the company’s judicious approach to developing a whole new way to attack tough diseases. “We’re paying half of what it would cost us to be in Cambridge,” he says of the company’s new Seaport Center office. “And we’re in close proximity to our founders.”