Acceleron Pharma (CAMBRIDGE, Massachussetts) and Celgene Corp (SUMMIT, New Jersey) announced a worldwide strategic collaboration for the development and commercialization of ACE-011, a first-in-class, novel bone-forming compound for the treatment of cancer-related bone loss. Acceleron is a privately-held biopharmaceutical company developing novel biotherapeutics that modulate the growth of tissues including bone and muscle to treat musculoskeletal, metabolic, and cancer-related diseases; Celgene is an integrated global pharmaceutical company engaged primarily in the discovery, development, and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases. ACE-011, a protein therapeutic based on the activin receptor type IIA (ActRIIA), has demonstrated positive results in key biomarkers of bone formation in preclinical and early clinical studies.

The companies signed an option agreement for certain discovery stage programs, under which they also will jointly develop, manufacture, and commercialize Acceleron’s products for bone loss. Celgene will make an upfront payment to Acceleron of $50 million, which comprises a $5 million equity investment in Acceleron. Furthermore, in the event Acceleron files for IPO, Celgene will purchase a minimum of $7 million of Acceleron’s common stock.

Acceleron will retain responsibility for initial study activities, including research and development, through the end of phase IIa clinical trials, as well as for manufacturing the trial’s clinical supplies. Acceleron will pay a share of the development expenses and is eligible to receive development, regulatory, and commercial milestones of up to $510 million for the ACE-011 program, and up to an additional $437 million for each of 3 discovery stage programs. Celgene will conduct the phase IIb and phase III clinical studies, and will oversee the manufacture of phase III and commercial supplies. The companies will copromote the products in North America. Acceleron will receive tiered royalties on worldwide net sales.

ACE-011 works by inhibiting activin, a member of the Growth and Differentiation Factor protein family, which prevents new bone formation by having both stimulatory effects on osteoclasts and inhibitory effects on osteoblasts. ACE-011 acts as a decoy receptor and binds to activin before it is able to bind to ActRIIA on the surface of bone tissue cells. ACE-011’s prevention of activin signaling allows normal bone formation to occur and increase in bone mineral density (BMD) and bone strength.

In preclinical models of bone loss, ACE-011 demonstrated beneficial effects on both trabecular and cortical bone, increased BMD, improved bone architecture, increased mineral apposition and bone formation rates, and improved bone strength. In a sinlge-dose, phase I clinical study in healthy postmenopausal women, the agent showed an encouraging safety profile, and increased bone formation biomarkers and decreased bone resorption biomarkers. ACE-011 is currently in a phase Ib study, and Acceleron expects to begin a phase IIa study in multiple myeloma by mid-2008.

Skeletal morbidity in multiple myeloma and other cancers causes significant loss of physical function and quality of life. The current standard of care is antiresorptive therapy with intravenously administered bisphosphonates. These antiresorptive agents decrease the rate of bone resorption, but do not lead to the formation of new, high-quality bone. Furthermore, despite treatment, many patients continue to experience severe bone pain, fractures, and spinal compressions. The use of ACE-011 has the potential to significantly improve the bone health of these patients.