West Coast Editor
Acceleron Pharma Inc.'s $31 million from a Series C financing fortifies the company to start Phase II trials with its lead product for bone growth in the first quarter of next year, as well as a Phase I study with its compound to increase muscle mass, with a third candidate due to enter the clinic in the second half of 2008.
Working with the biology of the growth and differentiation factor (GDF) protein superfamily, Acceleron earlier this month offered preclinical data during a scientific meeting that showed ACE-031 for muscle dystrophy, amyotrophic lateral sclerosis and cancer-related muscle loss built muscle in a mouse model despite treatment at the same time with glucocorticoids.
"We have a pretty dominant position in this [GDF] area of biology," said Steven Ertel, vice president of corporate development for Cambridge, Mass.-based Acceleron.
He acknowledged Phase II efforts by Wyeth, of Madison, N.J., and by Thousand Oaks, Calif.-based Amgen Inc. with compounds inhibiting one protein in the class, GDF-8, or myostatin, as a way to build muscle, but said Acceleron's "pan" approach could work better.
"There are published data showing that myostatin is important but by no means the only regulator of muscle," Ertel said. "In humans, it's not clear what role myostatin plays relative to other negative regulators of muscle mass."
The lead pipeline product is ACE-011, an inhibitor of activin, the negative regulator of bone loss. In September, Acceleron offered data from a study in cynomolgus monkeys that showed the compound improved bone microarchitecture and increased bone mineral density and bone mechanical strength. Effects on markers of bone formation and bone resorption proved similar to those reported in a Phase I trial.
Specifically, ACE-011 is based on the activin receptor type IIA (ActRIIA), which is the natural high-affinity receptor for activin. The compound combines the part of ActRIIA that binds tightly to activin with a component of an antibody molecule, allowing the drug to circulate freely in the body.
Acceleron is developing ACE-011 for bone loss caused by multiple myeloma (MM), metastases of solid tumors to bone and cancer treatments. The standard of care for skeletal morbidity in MM and other cancers is therapy with intravenous bisphosphonates, which decrease the rate of bone resorption but don't help build new bone or relieve bone pain, fractures and spinal compressions.
"We're the only player targeting activin," Ertel said.
Partly that's because in vitro experiments led to a division of opinion regarding whether activin is a positive or negative regulator of bone mass. Acceleron thus was able to accumulate a strong intellectual property portfolio from the Falk Institute, and gained first-mover advantage in the space.
For both compounds, the primary patient population will be cancer patients, Ertel told BioWorld Today. "The muscle program is clearly intriguing, just because of its novelty - a selective agent addressing only skeletal muscle mass and strength," he said, unlike anabolic steroids or human growth hormone.
Farther back in the lineup, preclinical ACE-041 binds a member of the GDF family necessary for angiogenesis. "Unlike the dozens of angiogenesis inhibitors out there, this does not target VEGF" specifically, but hits multiple mediators, Ertel said. The drug apparently blocks VEGF and FGF-induced angiogenesis, thus possibly proving useful in such diseases as age-related macular degeneration, rheumatoid arthritis and cancer.
The Series C round gives Acceleron enough cash to operate into early 2009, Ertel said. Although the firm is talking with potential partners, officials chose its lines of research because they can be pursued independently. "There's no urgency," he said.
Bessemer Venture Partners led the Series C round along with other new investors MPM BioEquities and QVT Financial. All existing institutional investors participated in the round including Advanced Technology Ventures (ATV), Flagship Ventures, OrbiMed Advisors, Polaris Ventures, Sutter Hill Ventures and Venrock.
In connection with the financing, Acceleron reorganized its expanding board, and elected Richard Pops, CEO of Cambridge, Mass.-based Alkermes Inc., was elected lead director.