Acceleron Pharma

[Michael Scally MD]

Acceleron Pharma
http://www.acceleronpharma.com/ (Acceleron Pharma)

Since our initial financing in 2004, Acceleron’s goal has been to develop innovative therapies. Our company has built in-house drug development capabilities, allowing us to focus our creativity and innovation on the biology of the Growth and Differentiation Factor (GDF) protein family, while streamlining the development of novel therapies.

This strategy has already yielded a rich pipeline of compounds that have the potential to be therapeutic breakthroughs for a number of devastating diseases. Our approach has opened a completely new area of GDF-targeted therapies that can modulate the growth and repair of a variety of tissue systems, offering new hope and benefits to patients.

Focus on the GDF Family of Proteins

Acceleron is establishing itself as the premier company in GDF-targeted therapies. We have developed an unparalleled expertise in GDF biology, and our scientific advisory board consists of leaders and pioneers in the field. Our discoveries and technology have allowed us to unleash the therapeutic promise of this protein family, building a powerful and productive discovery platform.


ACE-031 (Soluble Activin Receptor Type IIB-IgG1) Increases Muscle Mass by Inhibiting Myostatin and Other Negative Regulators of Muscle: Non-Clinical and Clinical Studies. [See: OnLine First - Page 36 ]

 

[bigrobbie]

Impressive! :tiphat

Thank you for posting...

 

[Michael Scally MD]

Koncarevic A, Kajimura S, Cornwall-Brady M, et al. A Novel Therapeutic Approach to Treating Obesity through Modulation of TGF? Signaling. Endocrinology. http://endo.endojournals.org/content/early/2012/05/01/en.2012-1016.abstract (A Novel Therapeutic Approach to Treating Obesity through Modulation of TGF? Signaling)

Obesity results from disproportionately high energy intake relative to energy expenditure. Many therapeutic strategies have focused on the intake side of the equation, including pharmaceutical targeting of appetite and digestion. An alternative approach is to increase energy expenditure through physical activity or adaptive thermogenesis. A pharmacological way to increase muscle mass and hence exercise capacity is through inhibition of the activin receptor type IIB (ActRIIB). Muscle mass and strength is regulated, at least in part, by growth factors that signal via ActRIIB. Administration of a soluble ActRIIB protein comprised of a form of the extracellular domain of ActRIIB fused to a human Fc (ActRIIB-Fc) results in a substantial muscle mass increase in normal mice. However, ActRIIB is also present on and mediates the action of growth factors in adipose tissue, although the function of this system is poorly understood. In the current study, we report the effect of ActRIIB-Fc to suppress diet-induced obesity and linked metabolic dysfunctions in mice fed a high-fat diet. ActRIIB-Fc induced a brown fat-like thermogenic gene program in epididymal white fat, as shown by robustly increased expression of the thermogenic genes uncoupling protein 1 and peroxisomal proliferator-activated receptor-? coactivator 1?. Finally, we identified multiple ligands capable of reducing thermogenesis that represent likely target ligands for the ActRIIB-Fc effects on the white fat depots. These data demonstrate that novel therapeutic ActRIIB-Fc improves obesity and obesity-linked metabolic disease by both increasing skeletal muscle mass and by inducing a gene program of thermogenesis in the white adipose tissues.

 

[Michael Scally MD]

Attie KM, Borgstein NG, Yang Y, et al. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers. Muscle Nerve. A single ascending-dose study of muscle regulator ACE-031 in healthy volunteers - Attie - 2012 - Muscle & Nerve - Wiley Online Library

INTRODUCTION: ACE-031 is a soluble form of activin receptor type IIB (ActRIIB). ACE-031 promotes muscle growth by binding to myostatin and other negative regulators of muscle mass.

METHODS: This double-blind, placebo-controlled study evaluated the safety, pharmacokinetics, and pharmacodynamics of ACE-031 in 48 healthy, postmenopausal women randomized to receive 1 dose of ACE-031 (0.02-3 mg/kg SC) or placebo (3:1).

RESULTS: ACE-031 was generally well-tolerated. Adverse events included injection site erythema. Mean ACE-031 AUC(0-infinity) and C(max) increased linearly with dose; mean T((1/2)) was 10-15 days. Statistically significant increases in mean total body lean mass (3.3%; P = 0.03, by DXA) and thigh muscle volume (5.1%; P = 0.03, by MRI) were observed at day 29 in the 3 mg/kg group. Statistically significant changes in serum biomarkers suggest ACE-031 also improved bone and fat metabolism.

CONCLUSIONS: Single-dose ACE-031 treatment was generally well-tolerated and resulted in increases in muscle mass in healthy postmenopausal women.

 

[Michael Scally MD]

Acceleron
http://www.acceleronpharma.com/ (Acceleron Pharma)

Acceleron’s research focuses on the biology of the transforming growth factor beta (TGF-?) protein superfamily, a large and diverse group of molecules that that are key regulators in the growth and repair of tissues throughout the human body.


Acceleron Pharma, Inc. today announced that it has filed a registration statement on Form S-1 with the U.S. Securities and Exchange Commission (“SEC”) relating to the proposed initial public offering of its common stock. The number of shares to be offered and the price range for the offering have not been determined.
http://www.sec.gov/Archives/edgar/data/1280600/000104746913008540/a2216342zs-1a.htm

 

[Michael Scally MD]

Phase 1 Study of ACE-083 in Healthy Subjects -
https://clinicaltrials.gov/ct2/show/NCT02257489?term=Ace083&rank=1

This study is currently recruiting participants. This study will evaluate the the safety and tolerability of single and multiple doses of ACE-083 as a local injection into the thigh muscle of healthy subjects. The study will also determine the amount of ACE-083 that reaches the systemic circulation following local administration. Additionally, the study will assess whether local administration into the thigh muscle results in an increase in the size and/or strength of the injected muscle.

ACE-083 is a molecule that has been shown to increase skeletal muscle mass in animals and, therefore, has potential utility in certain diseases that affect skeletal muscle. This initial study in healthy human subjects will help determine the properties of ACE-083 (safety, tolerability, drug absorption and biologic activity), following local administration into skeletal muscle, in advance of clinical trials in patients.

The study will consist of up to 5 planned groups of 8 subjects each. Subjects in each cohort will be randomized to receive either ACE-083 or placebo. ACE-083 (or placebo) will be administered locally into the right quadriceps (thigh) muscle. Subjects will receive a total of either one dose (on Day 1) or two doses (on Day 1 and Day 22). Each dose administered could include up to 4 injections of study drug into pre-defined locations in the muscle.

A Safety Review Team (SRT) will review blinded, preliminary data from each treatment group to make recommendations regarding escalation to the next treatment grop. Subjects will be assessed for safety throughout the treatment and follow-up periods. Follow-up visits will occur over 12 weeks following the last dose of study drug.

 

[Drogan]

http://www.acceleronpharma.com/wp-content/uploads/2015/12/ACE-083-SCWD-Oral-Presentation-2Dec2015_FINAL.pdf