Dr. Dean Bottino, Roche, to Discuss Multi-Scale Modeling in Development of Cancer Drugs in Rosa’s Impact Webinar Series
Dr. Bottino will present the Webinar “Multi-scale modeling to optimize the antitumor effect of antibody-dependent cell-mediated cytotoxicity (ADCC) enhanced therapies” on June 19, 2013.
San Carlos, CA, May 28, 2013 --(PR.com)-- Rosa & Co. LLC today announced that Dr. Dean Bottino, Head Modeling & Simulation Oncology, Roche Pharmaceuticals, will present a webinar entitled “Multi-scale modeling to optimize the antitumor effect of antibody-dependent cell-mediated cytotoxicity (ADCC) enhanced therapies” on Wednesday, June 19, 2013 at 1:00 - 2:00 pm EDT. This webinar is 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 current applications and the advantages of using M&S in product discovery, development, and marketing programs.
According to Dr. Bottino, “Antibody-dependent cell-mediated cytotoxicity (ADCC) is thought to augment the efficacy of IgG1 mAb therapeutics (eg. cetuximab) via the recruitment and activation of CD16+ cells, which in turn will mediate tumor cell killing. This observation has led to drug design efforts to intentionally exploit ADCC for enhanced anti-tumor efficacy. For example, GA201 (Roche pRED Oncology) is a humanized and glycoengineered IgG2 anti-EGFR monoclonal antibody (mAb) with enhanced ADCC currently undergoing investigation in phase 2 trials.
The dual mechanisms of action of ADCC-enhanced mAbs such as GA201 result in new and challenging drug development questions, for example:
1. Can the relative contributions of ADCC and target inhibition toward tumor shrinkage be quantified?
2. In light of (1), what markers (eg. KRAS mutation status, NK cell function) are predicted to confer sensitivity or resistance to the mAb?
3. Given observed kinetics of CD16+ cell depletion and recovery following administration of the mAb, what is the optimal schedule to optimize ADCC?
4. In the case of combination therapy with an immune-enhancing treatment, what dose and schedule would provide optimal synergy with the mAb’s ADCC effect?
A mathematical modeling framework for ADCC is proposed with the intention of addressing the questions posed above across several ADCC-relevant therapies. The proposed model would integrate clinically obtainable data sources, for example: FACS counts of (CD16+/56+) cells, NK cell function (CD107a, K562), tumor size (CT scan), mAb concentration in blood, and downstream target inhibition (eg pERK).”
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 (M&S) 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.
More information can be found online at http://www.rosaandco.com.
Rosa and the Rosa logo are registered trademarks of Rosa & Co. LLC.
According to Dr. Bottino, “Antibody-dependent cell-mediated cytotoxicity (ADCC) is thought to augment the efficacy of IgG1 mAb therapeutics (eg. cetuximab) via the recruitment and activation of CD16+ cells, which in turn will mediate tumor cell killing. This observation has led to drug design efforts to intentionally exploit ADCC for enhanced anti-tumor efficacy. For example, GA201 (Roche pRED Oncology) is a humanized and glycoengineered IgG2 anti-EGFR monoclonal antibody (mAb) with enhanced ADCC currently undergoing investigation in phase 2 trials.
The dual mechanisms of action of ADCC-enhanced mAbs such as GA201 result in new and challenging drug development questions, for example:
1. Can the relative contributions of ADCC and target inhibition toward tumor shrinkage be quantified?
2. In light of (1), what markers (eg. KRAS mutation status, NK cell function) are predicted to confer sensitivity or resistance to the mAb?
3. Given observed kinetics of CD16+ cell depletion and recovery following administration of the mAb, what is the optimal schedule to optimize ADCC?
4. In the case of combination therapy with an immune-enhancing treatment, what dose and schedule would provide optimal synergy with the mAb’s ADCC effect?
A mathematical modeling framework for ADCC is proposed with the intention of addressing the questions posed above across several ADCC-relevant therapies. The proposed model would integrate clinically obtainable data sources, for example: FACS counts of (CD16+/56+) cells, NK cell function (CD107a, K562), tumor size (CT scan), mAb concentration in blood, and downstream target inhibition (eg pERK).”
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 (M&S) 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.
More information can be found online at http://www.rosaandco.com.
Rosa and the Rosa logo are registered trademarks of Rosa & Co. LLC.
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Rosa & Co LLC
Rebecca Baillie
(610) 636-2332
http://www.rosaandco.com
Rebecca Baillie
(610) 636-2332
http://www.rosaandco.com
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