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Recommended Short Courses*

Monday, June 14
9:00 am – 12:00 pm
(SC3) Translating Safety Biomarkers from the Lab to the Clinic
(SC4) Use of Stem Cells for Safety Screening

2:00 pm – 5:00 pm
(SC6) Addressing Safety Concerns for Biological Drugs
(SC8) Mechanistic Insights into Cardiotoxicity 

Wednesday, June 16 (Dinner will be served.)
6:00 pm - 9:00 pm
(SC9) Mechanistic Insights into Hepatotoxicity

 *Separate Registration Required.

 

TUESDAY, JUNE, 15


7:15 am Registration and Morning Coffee


VALIDATING BIOMARKERS FOR RENAL INJURY

8:15 Chairperson's Opening Remarks

Stephen Furlong, Ph.D., Safety Science Lead, U.S. Patient Safety, AstraZeneca

8:25 The Damaged Nephron Defends the Urinary System by Delivering NGAL

Jonathan M. Barasch, M.D., Ph.D., Associate Professor, Medicine, Anatomy and Cell Biology, Columbia University Medical Center

NGAL (Siderocalin, lipocalin2) gene is rapidly expressed by epithelia in response to hypoxia, ischemia -reperfusion injury, bacterial sepsis and toxins. NGAL RNA rises 1000 fold and NGAL protein 10-500 fold in 3-6 hours after the insult. Using bioluminescent NGAL reporter mice and cross transplants between NGAL KO and WT mice we show that urine NGAL derives from specific cells in damaged nephrons. These tools allow us to screen for both nephrotoxins and conversely for inhibitors of the inflammatory and ischemic response.

8:55 NGAL as a Biomarker of Acute Kidney Injury and Nephrotoxicity

Prasad Devarajan, M.D., Professor, Pediatrics and Developmental Biology, University of Cincinnati College of Medicine

NGAL has emerged as an early diagnostic biomarker for acute kidney injury (AKI) after cardiac surgery, contrast administration, kidney transplantation, and even in heterogeneous subjects presenting to the emergency department or admitted to critical care units. NGAL is also emerging as an early biomarker in interventional AKI trials, and as a safety biomarker when using potentially nephrotoxic agents. A number of studies have also demonstrated the utility of early NGAL measurements for predicting the severity and clinical outcomes of AKI.

9:25 Approaches to Regulatory Qualification of Safety Biomarkers

Jonathan A. Phillips, Ph.D., Senior Scientist, Integrative Toxicology, Boehringer-Ingelheim Pharmaceuticals, Inc.

The scientific community is responding to the FDA’s Critical Path Initiative with innovative ways to improve the “drug development tool kit.”  The pharmaceutical industry, in partnership with government regulatory agencies and academic experts, is working to qualify next generation safety biomarkers.  A consortium approach allows for the collaborative nomination of potential biomarkers.  Experimental testing of biomarker performance leads to claims about the utility of the biomarkers.  The general process of regulatory qualification will also be discussed.  Once qualified, markers can then be used to streamline safety and efficacy decisions in drug development and use.

9:55 Networking Coffee Break

10:25 Practical Considerations for Introducing New Safety Biomarkers into Clinical Trials

Stephen Furlong, Ph.D., Safety Science Lead, U.S. Patient Safety, AstraZeneca

There is a growing expectation that new and better safety biomarkers, particularly for drug-induced kidney injury, will be used in clinical trials. This talk will review new biomarker assays, considerations for introducing these markers into clinical trials and considerations for using these biomarkers for decision making.

10:55 KEYNOTE ADDRESS: Biomarkers of Nephrotoxicity: Uses and Challenges in Pre-clinical and Clinical Studies

Joseph BonventreJoseph Bonventre, Ph.D., Professor of Medicine, Harvard Medical School, and Chief, Renal Division, Brigham and Women's Hospital

The kidney is an important target for toxicity of drugs. Hence, we need sensitive and specific biomarkers to signal nephrotoxicity earlier in pre-clinical and clinical studies, and also to better identify subjects who have clinically silent underlying abnormal kidney structure and function and might be at higher risk of drug toxicity. Over the years, a large number of biomarkers of kidney injury have been suggested, yet for various reasons, none have been routinely accepted in animal or clinical studies. In some cases, the biomarker was felt to be too sensitive, not sensitive enough, or too nonspecific. More recently, however, there have been a number of advances in the application of biomarkers to nephrotoxicity and we are now in an exciting time for kidney biomarker development. Many investigators and large consortia are testing these biomarkers in various clinical contexts with the promise that a subset of these biomarkers will be used to effectively diagnose and monitor nephrotoxicity in a sensitive and specific way to advance drug development and patient safety.

11:25 PANEL DISCUSSION

How Succesful Will Biomarkers be in Predicting Renal Injury?
Moderator: Stephen Furlong, Ph.D., Safety Science Lead, U.S. Patient Safety, AstraZeneca

11:55 Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own


Tools for Detecting and Imaging Renal Injury

1:25 Chairperson's Remarks

Bruce A. Molitoris, M.D., Director, Division of Nephrology and Professor of Medicine, Indiana University

1:35 Utilizing 2-Photon Fluorescent Microscopy to Understand Nephrotoxicity and Hepatotoxicity

Bruce A. Molitoris, M.D., Director, Division of Nephrology and Professor of Medicine, Indiana University

2-photon microscopy offer the opportunity to visualize and quantify multiple dynamic intra-vital processes simultaneously using up to 3 different fluorescent probes in 3D or 4-D(time) in multiple organ systems.Identification of specific cells where uptake occurs, intracellular compartmentation,and metabolism can all be determined in high resolution. Mechanistic data regarding the response to therapies is also possible.Therefore, 2-photon microscopy allows for high level evaluation of cellular drug handling and its effects in vivo with high translatability to human studies.

2:05 Kidney Biopsy Diagnosis of Diseases Caused by Nephrotoxic Drugs

Andrew M. Herzenberg, M.D., FRCPC, Assistant Professor, Pathology, Consultant Nephropathologist, University Health Network and University of Toronto

A number of therapeutic agents can adversely affect the kidney, resulting in tubulointerstitial, glomerular or vascular disease. Drug-induced tubulointerstitial nephritis and acute tubular necrosis are common, and are often due to antibiotics or NSAIDs. I will describe the morphologic patterns of drug-induced disease in the kidney. The pathologic changes of drug toxicity are often similar to those seen in other disease states, so that clinical correlation is usually necessary to confidently determine the etiology.

2:35 Renal Complications of Tyrosine Kinase Inhibitors

Ilya Glezerman, M.D., Assistant Attending Physician, Renal Service, Memorial Hospital for Cancer and Allied Diseases

Tyrosine kinase inhibitors affecting expression of vascular endothelial growth factor (VEGF) receptor have gained wide clinical use in oncology as potent anti-angiogenesis agents. The renal side-effects range from new or worsening hypertension and proteinuria to overt nephrotic syndrome, hypertensive crisis and thrombotic microangiopathy. Interstitial nephritis and electrolyte disturbances have also been described. While mechanism of the toxicity is not completely understood, experimental models have shown that reduction of VEGF in renal vasculature leads to significant thrombotic renal injury.

Sponsored by
SOLMEDX
3:05 ROX and BOX: New Tools for Detecting Patient Injury and Drug Toxicity    

Sam Sofer, Ph.D., PE, President, Solmedx 
ROXTM and BOXTM are tests that measure the immune system's ability to supply oxygen to defend against pathogens, signal and coordinate the immune response, and upkeep the level of homeostasis. ROX and BOX are an integral part of the mechanism that delivers large amounts of oxygen to tissues as required. ROX and BOX are tools for patient monitoring, drug screening, and biomarker evaluation

3:20 Sponsored Presentations (Opportunities Available)

3:35 Grand Opening Refreshment Break in the Exhibit Hall

PLENARY KEYNOTE PANEL

4:15 Shifting Sands of Pharmaceutical Discovery

Panelists:

Cris Waller Chris L. Waller, Ph.D., Senior Director, HealthCare Informatics, Medical Business Technology, Pfizer, Inc.







Gary PeltzGary Peltz, M.D., Ph.D., Professor, Anesthesia, Stanford University







Marvin BayneMarvin Bayne, Ph.D., Vice President, Head, Discovery Technologies, Merck Co.







Thomas BocanThomas Bocan, Ph.D., Senior Director, Head, Pre-clinical BioImaging Center, Pfizer Global RD,, Pfizer, Inc.







Peggy Guzzie-PeckPeggy Guzzie-Peck, Ph.D., DABT, Vice President, Head, Toxicology, Pathology LAM, Johnson Johnson, Pharma RD






Key questions to be addressed:

  • How does academic research impact pharma drug discovery?
  • How does the creation of cross-pharma pre-competitive collaborations impact drug discovery, spanning chemistry, biology, and knowledge management?
  • Adoption of new technologies, such as, molecular Imaging: Can it help drug discovery and how quickly?
  • How effectively and efficiently can we collaborate to develop safer drugs?

5:45 Happy Hour in the Exhibit Hall

6:45 End of Day


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