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2013 Archived Content

6th Annual Integrated Drug Safety Risk Assessments

Predicting Drug-Induced Organ Toxicities Using Functional Assays, Models and Marker


Predictive Drug Safety highlights innovative preclinical strategies that are underway, for predicting drug-induced organ toxicities early and accurately. The conference will bring together leading experts in drug safety to discuss the appropriate use of in silico, in vitro, and in vivo tools for early prediction and detection of drug-induced cardiotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity and more.

Day 1 | Day 2 | Day 3 | Download Brochure 

Recommended Short Courses*  

Monday, June 3

9:00am – 12:00pm

Addressing Safety Concerns for Biologics and Biosimilars

Utilization of Cardiac Contractility Assays for Preclinical Safety Testing 

Monday, June 3

2:00pm – 5:00pm

Use of Stem Cells for Safety Screening

Introduction to Drug Metabolism and Its Role in Drug Toxicity 

* Separate registration required

Tuesday, June 4

7:45 am Registration and Morning Coffee


8:30 Chairperson’s Opening Remarks

» 8:40 FEATURED PRESENTATION: Is Drug Safety Really a Problem in 2013? 

Paul Watkins Paul B. Watkins, M.D., Director, Hamner-UNC Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill

Data from 2008-2010 suggest that safety, including unfavorable risk to benefit ratio, account for only about 20% of clinical development failures. In addition, no drugs approved for marketing in the last 5 years have been permanently withdrawn from the market due to safety concerns. It is not correct to interpret these data as the result of great advances in preclinical safety testing or clinical safety signal detection. Concerns about safety have dramatically altered the drug development landscape such that important new drugs are never advanced into the clinic, doses used in clinical trials are too low to be efficacious, and the size, duration and costs of clinical drug development have ballooned. Concerns about drug safety remain the major bottleneck in the delivery of affordable new drugs to the patients who need them.

9:10 Endothelin-A Receptor Antagonists and Liver Toxicity: A Focus on Sitaxentan

John Erve, Ph.D., D.A.B.T., Former Principal Scientist, DMPK, Elan Pharmaceuticals, Inc.

Sitaxentan (Thelin™) an endothelin-A receptor antagonist (ERA) marketed for pulmonary arterial hypertension and considered to be less toxic than the ERA Bosentan (Tracleer™) was withdrawn in 2010 due to eight deaths from severe liver toxicity. Ambrisentan (Letaris™), the newest ERA, is a propanoic acid and has a lower risk of liver toxicity than either bosentan or sitaxentan which are sulfonamides. Studies to better understand the mechanisms of ERA hepatotoxicity are currently underway.

9:40 Opportunities for Integrated Safety Assessment - Early and Often

Sanjeev Thohan, Ph.D., Senior Research Fellow, Preclinical and Translational Sciences, Novartis Institute for Biomedical Research

As an industry, we have established comprehensive in vitro/in silico approaches for generating “on and off target” profiles for our drug candidates. An often overlooked opportunity to evaluate safety endpoints are the early pharmacology and efficacy studies. These studies often entail substantial dose escalations and can be effectively leveraged to understand the early changes with not only tissue histology but also biomarkers without compromise to study endpoints.

10:10 Coffee Break

10:40 A More Holistic Approach to Drug Design Concepts in Minimizing Cell-Based Target Organ Toxicity

Michael Aleo, Ph.D., Research Fellow, Investigative Toxicology, Pfizer Global Research & Development

Yvonne Will, Ph.D., Associate Research Fellow, Compound Safety Prediction, Pfizer Global Research & Development

Many mechanisms such as mitochondrial dysfunction, ER stress, inflammation, HERG have been identified as contributors to such toxicities. However, it has become evident that none of these mechanisms alone will accurately predict a particular organ toxicity or severity of toxicity and that only a risk matrix approach could potentially provide advancement to this dilemma. Here, we provide examples of such a risk matrix approach and how it can change upon exposure projection.

QUINTILES small logo11:40 Quintiles CardioCheck: Multi-Parameter Preclinical Profiling for Potential Cardiotoxicity of Drug Compounds

Kimberly Doherty, Principal Research Associate, Quintiles

High drug attrition rates are often due to toxic effects on the heart. Earlier preclinical assessment can reduce costly drug withdrawals and improve patient safety. Current methods of assessing cardiotoxicity are limited since they only assess a single mechanism or are done in less predictive animal models. Quintiles’ CardioCheck provides a comprehensive means of estimating cardiotoxic potential by assessing multiple parameters that are important in cardiac health and function in a human cardiomyocyte model.

Hepregen12:10 pm Luncheon Presentation I: Use of Micropatterned Cocultures (MPCC) to Detect Compounds That Cause Drug-Induced Liver Injury in Humans

Yvonne Will, Ph.D., Associate Research Fellow, Compound Safety Prediction, Pfizer Global Research & Development

Clinical DILI can be predicted with a sensitivity of ~50% and a false positive (FP) rate of ~5% using 24-h cultures of sandwich-cultured primary human hepatocytes and imaging of four cell injury endpoints (Xu et al., 2008). We hypothesized that long-term drug dosing in a functionally stable model of primary hepatocytes could provide for increased predictivity over short-term dosing paradigms.

12:40 Luncheon Presentation II (Sponsorship Opportunity Available) or Lunch on Your Own

» 1:30 Plenary Keynote Panel Discussion: Advancing Pharma R&D through Communication & Collaborations: Bio-Connectivity at Work 

Karim Dabbagh, Ph.D., Executive Director and Head, External R&D and Innovation Research Units, Pfizer Worldwide R&D

Glen N. Gaulton, Ph.D., Professor, Pathology and Laboratory Medicine; Executive Vice Dean and Chief Scientific Officer, Perelman School of Medicine, University of Pennsylvania

Peter Pitts, President and Co-Founder, Center for Medicine in the Public Interest

3:00 Grand Opening of the Exhibit Hall with Poster Viewing


3:55 Chairperson’s Opening Remarks

Yvonne Will, Ph.D., Associate Research Fellow, Compound Safety Prediction, Pfizer Global Research & Development

4:00 Systematic Approaches to Organ Specific Toxicities Using Zebrafish

Calum MacRae, M.D., Ph.D., Physician-Scientist, Department of Medicine, Cardiovascular Research Center, Brigham and Women’s Hospital; Associate Professor, Harvard Medical School

Many drug effects are a result of complex phenomena; using the larval zebrafish it is possible to model much of drug efficacy and toxicity in a native context and at throughputs compatible with discovery phase screening. We have exploited a range of assay approaches to move towards a ‘TOX’ reporter zebrafish line capable of the interrogation of core organ specific toxicities in a manner that ultimately may allow balancing of efficacy and toxicity during the early phases of drug discovery.

4:30 Organs-on-Chips for Predicting Drug Toxicity and Efficacy

Danilo Tagle, Ph.D., Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of Health

Organs-on-chips are bio-engineered microdevices that represent functional units of human organs such as, the lung, liver and heart, modeling both cell architecture and physiology. This unique platform could ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. To accomplish this goal, the NIH has partnered with DARPA and FDA to improve the process for predicting whether drugs will be safe in humans.

Chantest5:00 Janus Faces of Safety & Efficancy

Arthur M. Brown, Ph.D., President & CEO, ChanTest Corporation

5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

6:30 Close of Day

Day 1 | Day 2 | Day 3 | Download Brochure 

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