Dr. Pratap Singh, to Discuss PK/PD Modeling Analysis of a Compound Targeting Muscle Growth in Rosa's Impact Webinar Series

SAN CARLOS, CA, October 10, 2012 (Press-News.org) Rosa & Co. LLC today announced that Dr. Pratap Singh, Senior Principal Scientist at Pfizer, will present a webinar "Role of Myostatin in Muscle Growth: Key Learnings From PK/PD Modeling Analysis" on Wednesday, October 17, 2012 at 1:00 - 2:00 pm EDT as part of Rosa's ongoing monthly public webinar series. The purpose of the series, "Impact of Modeling & Simulation in Drug Development," is to foster the use of Modeling and Simulation (M&S) activities in biotechnology, pharmaceutics, and other life science industries. This series is geared to illustrate the advantages and applicability of M&S in product discovery, development, and marketing programs.

According to Dr. Singh, "Suppression of the myostatin (GDF-8) pathway is considered an important therapeutic strategy for the treatment of muscle-wasting disorders, including muscular dystrophy, cachexia and sarcopenia. Myostatin is a member of TGF-β superfamily and negatively regulates skeletal muscle mass, muscle fiber size, and fiber count. Clinical trials targeting the myostatin pathways have produced mixed results. ACE-031, a Fc fusion of ActRIIB, is a decoy receptor for GDF-8. ACE-O31 was reported to increase muscle mass in Phase I/II trials with healthy post-menopausal women and in patients with Duchenne muscular dystrophy (DMD). In contrast, an antibody against myostatin, MYO-029, failed to achieve clinical efficacy in DMD patients. Given these contrasting results, it is critical to understand whether the clinical and preclinical data support GDF-8 as a novel paradigm for the treatment of muscular dystrophy disease. We performed a detailed pharmacokinetic-pharmacodynamic (PK/PD) analysis of preclinical and clinical data on MYO-029 to address animal model translation and predict the level of target inhibition at the clinical doses. A combination of mouse, non-human primates, and clinical data were analyzed, and exposure-response relationships were established for various pharmacodynamic endpoints. These included muscle weight increase in SCID mice efficacy studies, muscle circumference changes in a 39-week toxicology study in monkeys, and total myostatin levels observed in multiple-ascending dose (MAD) studies in Phase I/II trials. Our modeling analysis revealed a significant, in-vivo potency shift between mice and monkeys species. Further, our results showed that the exposures of Myo-029 in humans had low probability of success in modulating the target or in providing robust efficacy. The PK/PD analysis presented in this report supported the rationale for therapeutic strategies targeting the myostatin pathway."

Register for this free webinar at http://www.rosaandco.com/webinar. After registering, a confirmation email will be sent with directions for joining the webinar. More information about the webinar series, an archive of past webinars, and a list of future webinar speakers may be found at http://www.rosaandco.com/webinar.

About Rosa
Rosa informs our customer's most critical decisions - from preclinical through clinical development - with the creation and use of mathematical models that simulate disease physiology, drug action, patient variability, and trial outcomes. To address the full spectrum of related issues, Rosa offers two customized approaches: classic pharmacokinetic/ pharmacodynamic (PK/PD) models and Rosa's innovative PhysioPD models. With these approaches, Rosa's clients collaborate in model creation and testing, retain the final model, and acquire the ability to use it and understand its implications for their drug development programs. Rosa's staff have unparalleled professional experience in using drug-disease modeling and simulation to accelerate drug development and have completed hundreds of engagements with dozens of clients in multiple therapeutic areas. The Rosa team is unique in their breadth and depth of disease area experience, which includes metabolic and cardiovascular diseases, oncology, gastro-intestinal disease, inflammatory diseases, immune dysfunction (including rheumatoid arthritis), pain, skin conditions, respiratory disorders, and antibacterials/antivirals.

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