Acceleron Pharma Receives Grant for ACE-011 from MMRF

Acceleron Pharma, Inc., a biopharmaceutical company developing novel therapeutics that modulate the growth of tissues including bone and muscle, today announced that it was selected to receive a Biotech Investment Award from the Multiple Myeloma Research Foundation to support the research and development of ACE-011, a novel bone forming agent, for the treatment of multiple myeloma. In addition, Acceleron announced that it began a randomized, double-blind, placebo-controlled multiple ascending dose study of ACE-011.

"We are proud to receive this highly-regarded grant from the Multiple Myeloma Research Foundation," said John Knopf, Ph.D., Chief Executive Officer of Acceleron. "With this grant, we will continue to aggressively pursue the development of ACE-011, which has shown encouraging preclinical and clinical effects on bone formation, to treat the complications of bone loss associated with multiple myeloma."

The multiple dose study will be conducted in healthy, post-menopausal women. Subjects will receive four monthly subcutaneous doses of either ACE-011 or placebo. The primary objective of the study is to assess the safety, tolerability and pharmacokinetics of ACE-011. The pharmacodynamic effects of ACE-011 on bone will also be measured.

"We are excited to start this study with ACE-011 and expect to begin additional studies with this compound later this year for the treatment of cancer and cancer-related bone loss," said Matthew L. Sherman, M.D., Chief Medical Officer of Acceleron. "Our product pipeline continues to make great progress and we look forward to announcing additional clinical milestones throughout 2008."

About ACE-011

ACE-011, a protein therapeutic based on the activin receptor type IIA, is a novel bone forming agent. In numerous preclinical models of bone loss, ACE-011 increased bone mineral density, improved bone architecture, increased the mineral apposition and bone formation rates and improved bone mechanical strength. These effects have been demonstrated in therapeutic models of bone loss in which ACE-011 stimulated bone formation - a significant unmet medical need that is underserved by current treatments for bone loss. ACE-011 is currently in a phase 1b study and Acceleron expects to begin a phase 2a study in multiple myeloma in the middle of 2008.

About Acceleron Pharma

Acceleron is a privately held biopharmaceutical company committed to discover, develop, manufacture and commercialize novel biotherapeutics that modulate the growth of bone, muscle, fat and the vasculature to treat musculoskeletal, metabolic and cancer-related diseases. Acceleron's scientific approach takes advantage of its unique insight into the regenerative powers of two protein families: the Growth and Differentiation Factors (GDFs) and Bone Morphogenetic Proteins (BMPs). ACE-011, a novel bone forming agent, is the company's lead program, and is being developed to reverse bone loss in diseases such as cancer-related bone loss. In addition, the company is advancing through preclinical development product candidates that increase muscle mass, control angiogenesis and inhibit fat accumulation. Acceleron utilizes proven biotherapeutic technologies and capitalizes on the company's internal GMP manufacturing capability to rapidly and efficiently advance its therapeutic programs. The investors in Acceleron are Advanced Technology Ventures, Bessemer Ventures, Flagship Ventures, MPM BioEquities, OrbiMed Advisors, Polaris Ventures, QVT Financial, Sutter Hill Ventures and Venrock. For more information, visit www.acceleronpharma.com.

Vertebroplasty in Multiple Myeloma

McDonald RJ, Trout AT, Gray LA, Dispenzieri A, Thielen KR, Kallmes DF.

Medical Scientist Training Program, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minn; Department of Radiology, University of Michigan, Ann Arbor, Mich; Departments of Radiology and Hematology, Mayo Clinic, Rochester, Minn.

BACKGROUND AND PURPOSE: Despite the literature supporting the efficacy of vertebroplasty for treatment of osteoporotic vertebral compression fractures, few reports exist documenting its use in the treatment of compression fractures in multiple myeloma patients. Accordingly, we sought to characterize the imaging characteristics, clinical course, and outcomes in myeloma patients treated with vertebroplasty.

MATERIALS AND METHODS: We performed a retrospective review of clinical outcome data from 67 multiple myeloma patients treated with vertebroplasty since October 2000. Quantitative outcome data including the Roland Morris Disability Questionnaire (RDQ) and Visual Analog Scales for pain and qualitative outcome data (self-reported pain, mobility, and narcotic use) were collected preoperatively, immediately after vertebroplasty, and at 1 week, 1 month, 6 months, and 1 year after treatment.

RESULTS: Significant improvements in all of the outcome measures were observed postoperatively and throughout the duration of follow-up. Quantitative outcome measures (RDQ, analog pain scale 0-10, with rest and activity) improved by 11.0 (48%; P < .0001), 2.7 (25%; P < .001), and 5.3 (48%; P < .0001) points, respectively, with persistent improvement at 1 year (P < .01; P < .03; P < .001). Eighty-two percent and 89% of patients experienced a significant improvement in subjective rest pain and activity pain, respectively. Subjective scores achieved durable improvements, with 65% of patients requiring fewer narcotics after vertebroplasty and 70% having improved mobility.

CONCLUSION: Vertebroplasty provides significant and durable pain relief for patients with intractable spinal pain secondary to compression fractures resulting from multiple myeloma.

PMID: 18202234 [PubMed - as supplied by publisher]

Semafore and MMRC Phase I Study Of Targeted PI3 Kinase (PI3K) Inhibitor

Semafore Pharmaceuticals Inc. and the Multiple Myeloma Research Consortium (MMRC) announced the dosing of the first patient in a Phase I study of Semafore's lead product candidate, SF1126, a targeted PI3 kinase (PI3K) inhibitor.

The single-agent, dose-escalating, multiple-dose trial, which will enroll up to 30 multiple myeloma patients at three MMRC member institutions in the United States and Canada, is designed to evaluate the safety and tolerability of SF1126 in patients who have failed at least two prior treatments. The Winship Cancer Institute of Emory University in Atlanta is the lead site for the study.

Kathy Giusti, founder and chief executive officer of the MMRC, as well as a myeloma patient, said: "PI3 kinase is one of the premier targets for oncology overall, as well as for myeloma specifically. We are proud to have partnered with Semafore to rapidly move SF1126 into a clinical trial for multiple myeloma."

Semafore is currently evaluating SF1126 as a single agent in a multi-center Phase I trial involving patients with refractory or advanced solid tumors. The company expects to report data from this trial this year.

About SF1126

SF1126 is a small molecule conjugate containing a pan-PI3K inhibitor that selectively inhibits all PI3K class IA isoforms and other key members of the PI3K superfamily, including DNA-PK and mTOR. A major factor in tumor resistance to approved chemotherapy agents is thought to be the activation of the PI3K/PTEN pathway. As a result, it is thought that inhibiting this pathway, via SF1126, could cause the resetting of sensitivity to approved agents and exhibit synergistic anticancer effects.

Semafore is a clinical stage drug discovery and development company focused on small molecule modulators of the PI3 kinase and PTEN cell signaling pathway, a promising target pathway for multiple disorders, including the company's focus -- cancer. Semafore is one of the first biopharmaceutical companies to focus on both PI3K and PTEN and has successfully discovered and is developing a portfolio of drug candidates addressing these targets. For more information see the company's website at http://www.SemaforePharma.com.