Addressing the Challenge of Drug-Induced Kidney Injury (DIKI) within Preclinical Drug Development (S01)

Symposium Chair(s)

• Samantha Faber, PhD, DABT

  Principal Scientist
  Amgen Inc.
  Thousand Oaks, California, United States

• Lauren Lewis, PhD

  Senior Scientist
  Apellis Pharmaceuticals
  Sparta, New Jersey, United States

Symposium Speaker(s)

• Anna-Karin Sjögren, PhD, DABT, ERT

  Director
  CPSS CVRM Safety
  AstraZeneca
  Gothenburg, Vastra Gotaland, Sweden

• Adeyemi Adedeji, DVM, PhD, DACVP

  Distinguished Scientist-Pathologist
  Safety Assessment
  Genentech, Inc.
  South San Francisco, California, United States

• Lauren Aleksunes, PharmD, PhD, DABT

  Professor
  Pharmacology and Toxicology
  Rutgers University
  Bridgewater, New Jersey, United States

• Brandon Jeffy, PhD, DABT

  Senior Director
  Nonclinical Safety and Toxicology
  Crinetics Pharmaceuticals
  San Diego, California, United States

Educational Co-Support Provided by: Takeda and American College of Toxicology

Drug-induced kidney injury (DIKI) is among the most frequently reported adverse events across drug development and can result in dose-limiting toxicities and the discontinuation of treatment in patients. Further, with the advent of many new modality therapeutics, kidney-related adverse events continue to increase, warranting additional investment into translational models of DIKI and improved mechanistic understanding. Addressing various limitations including species-specific differences, biomarker sensitivity and specificity, as well as relevant in silico, in vitro, and in vivo models for nephrotoxicity can aid in advancing safety strategy surrounding DIKI outcomes throughout drug development and improve predictivity in the early drug discovery space. This symposium will present novel research pertaining to DIKI and highlight approaches to better evaluate safety liabilities. In addition, the utility of kidney injury biomarkers and in vitro models in the regulatory framework for pharmaceuticals will be explored. Our first speaker will explore the utility of advanced human in vitro models (e.g., microphysiological systems) for de-risking nephrotoxicity throughout drug development. Next, speaker two will discuss the implementation of translational biomarkers for DIKI to provide early detection and inform critical drug development decisions. Speaker three will detail the advancement of preclinical in vivo models for assessment of immune-mediated DIKI following exposure to immunotherapies. The final speaker will conclude the course by discussing safety-by-design strategies for prevention/mitigation of DIKI across modality agnostic programs and related regulatory aspects. As experts in their field, the speakers offer key insights into kidney physiology and toxicological parameters that are essential for successful implementation of kidney model platforms and safety strategy approaches, which will aid in accelerating drugs from bench to bedside to provide patient populations with effective treatment.

Presentations:

• 9:00 AM - 9:15 AM CT

  Introduction
  

  Symposium Speaker: Samantha Faber, PhD, DABT – Amgen Inc.
• 9:15 AM - 9:45 AM CT

  Utility of In Vitro Models for Predicting Drug-Induced Nephrotoxicity
  

  Symposium Speaker: Anna-Karin Sjögren, PhD, DABT, ERT – AstraZeneca
• 9:45 AM - 10:15 AM CT

  Utility of Kidney Biomarkers in Preclinical Toxicology Studies
  

  Symposium Speaker: Adeyemi O. Adedeji, DVM, PhD, DACVP – Genentech, Inc.
• 10:15 AM - 10:45 AM CT

  Break
• 10:45 AM - 11:15 AM CT

  Investigating Immune-Related Nephrotoxicity of Checkpoint Inhibitors in Humanized Mice
  

  Symposium Speaker: Lauren Aleksunes, PharmD, PhD, DABT – Rutgers University
• 11:15 AM - 11:45 AM CT

  Discovery Toxicology Approaches to Assessment of Drug-Induced Kidney Injury
  

  Symposium Speaker: Brandon D. Jeffy, PhD, DABT – Crinetics Pharmaceuticals
• 11:45 AM - 12:00 PM CT

  Panel Discussion