ilsi health and environmental sciences institute updated april 2015 hesi washington, dc usa hesi:...

ILSI Health and

Environmental Sciences

Institute

Updated April 2015

HESIWashington, DC USAwww.hesiglobal.org

HESI: Health and Environmental Sciences Institute

HESI Mission Create science-based solutions for a

sustainable, healthier world.

Accurate and Efficient Chemical Risk Assessment

Food SafetySafe and Effective Medicines

Environmental Quality and Sustainability

Protecting sensitive

populations

Supporting ecological and human safety of essential food resources

Predicting and Protecting Against Adverse Effects from Chronic Exposures

Sustaining critical environments

Promoting Discovery

SAFETY & INNOVATION FOR

HUMAN & ENVIRONMENTAL

HEALTH

Academic & basic

research sector

Industry R&D

Patient Advocates, Foundation

s & NGOs

Government

Research &

Regulation

The HESI Model: Bridging Research to Application

From 14 Countries

90 University

& Research Centers

47 Government

Agencies

66 Corporate Sponsors

14 Scientific

Committees

Impact via Quality Science

>70Distinct Projects

From 12 Countries

Across multiple sectors

HESI achieves its mission via…

Scientific Research

Millions in in-kind research annually

Novel programs with interdisciplinary and cross-sector focus

Publication

Communication & Translation

Tools

Training

Platforms for Interaction

Active public-private partnership

HESI: A Key Contributor to Global Safety Research

In 2014/2015….

Two OECD supportive research projects

Pig-A genotoxicity mutation assay

Fish hepatic biotransformation assay – bioaccumulation

HESI research part of active guideline discussions with ICH

Cardiac paradigms (CIPA project)

Developmental toxicity (2nd Species Project)

We know the model works…

HESI’s scientific programs and publications have..

Influenced their approach to safety or risk assessment decision-making; 70%

Influenced their level of confidence in the use of particular technologies, markers, endpoints, or analysis approaches; 80%

Directly and positively impacted safety of patients and the

environment

Organization Strong & Growing

Increasing public and private sector involvement

65

History of Success

Creating frameworks to integrate data and

decision-making

Prioritize risks, Protect

ecosystems and their inhabitants

Problem Formulation Conclude

Mode of Action

In vivo

In vitro

QSAR/ TTC

Biomonitoring

Probabilistic

Deterministic

MinimalInfo

Toxicity

Exposure

Risk / Safety

Matrix

Globally recognized HESI

roadmaps to guide

integration of data and decisions.

Integrating Alternatives to Animal Testing for

Ecotox

Assessing Adverse vs Adaptive Transitions in

Toxicity Pathways

Innovating Chemical Risk

Assessment

Enhancing AgChem

Safety

Enhancing AgChem

Safety

US EPA Scientific and Technological Achievement Award (Honorable Mention)

UK National Center for the Replacement, Refinement, and Reduction of Animals in Research “Highly Commended Prize”

Impact cited in 2 National Academy reports

Basis for OECD Guideline for Testing of Chemicals (443): Extended One-Generation Reproductive Toxicity Study

Canine study requirement dropped in EPA Pesticide guidelines;

Increased use of ADME to enhance dose selection

A spotlight on one of

many…

Informing discovery & decision-making

with new technologies • First large scale TGx experimental

program, first public array/tox dbase • Led to adoption of data standards,

genomic biomarkers• Resource for strengths & limitations

of TgX use for safety

Toxicogenomics for Risk Assessment

Transgenic Models for Cancer Risk Assessment

• $33M collaborative effort• Critical data on predictivity of

available transgenic models• Data underpins current

guidelines on alternatives to 2 year mouse bioassay

• Improved prediction of safety

HESI Approach to Biomarkers

• Consensus on Safety or Translational Need

• Experimental Data

• Analysis & Publication

• Integration of Data & Context of Use

Translating from animal to human, and back to improve predictive

safety

Non-clinical Inhibin Assays MicroRNAs as

translation tox markers

Urinary Renal Protein Biomarkers

Nonclinical cTn serum assays

2015: PROGRAMS TO IMPACT SCIENCE AND HEALTH

Chemical Safety Evaluation

Predictive models

Risk assessment methodologies

Sustainability

Capacity Building & Education

Predictive Models

Zebrafish & multi-generational epigenetics

Utility of 2nd Species for assessing

developmental toxicity

Bioaccumulation: In vitro method, hepatic clearance in trout

Pig-A assay for genotoxicity

Risk Assessment Methodologies

RISK21

AOP and Ecotox

Sustainability

Capacity Building & Education

Scientist from the following organization’s collaborate with HESI on Chemical Risk Assessment research….

and many more!

SAFE AND EFFECTIVE MEDICINES

‘Crossing over the valley of death’ FasterCures. 2010. http://www.fastercures.org/reports/view/3

Underfunded? Or inefficient?FasterCures. 2010. http://www.fastercures.org/reports/view/3

Patient Experience

Region of Opportunit

y

Contemporary Drivers

Enhance drug discovery, don’t

compromise safety

Prevent Another TGN 1412

Support Cancer Patient Survival & Quality of Life

Ensure new therapeutic modes are safe for sensitive populations

Enhance drug discovery, don’t

compromise safety

Nature Review: Drug Discovery.

Aug 2013

What It Will Do: - Prevent early attrition due to hERG

liabilities- Provide a more complete assessment of

proarrhythmic risk - Obviate need for a TQT study and improve

efficiency- Potential to re-label drugs with risk

warnings- Standardize in vitro & in silico assays;

establish best practices for stem-cell derived cardiomyocytes

- Likely lead to revision of S7B, E14 guidelines

Prevent Another TGN 1412

HESI MOVING FORWARD

Centralized repository for positive/ negative controls for CRA

Prospective study across labs w consistent protocols, controls: outcome to help ID sources of variability, build best practices, guide interpretation.

HESI STUDY RESULTS: Significant variability

revealed (controls, assay selection, design, situational use, interpretation)

Identified opportunities to improve forward prediction with collaborative approach

Ensure new therapeutic modes are safe for sensitive populations

FC-Fusion Proteins (Biopharmaceuticals) a significant new area of therapeutic development- FC domain enhances half-life- Biopharmaceuticals with Fc region from IgG are known to cross

placenta - How to assess safety for women of childbearing age?

Support Cancer Patient Survival & Quality of Life

Simple numbers…terrible cost

www.fredhutch.org

• 7 fold higher risk of cardiac mortality

HESI’s is innovating the field with support for:- modeling-translational safety signals or monitoring-interdisciplinary platforms

Scientist from the following organizations collaborate with HESI on Drug Safety research….

and many more!

SAFETY & INNOVATION FOR

HUMAN & ENVIRONMENTAL

HEALTH

Academic & basic

research sector

Industry R&D

Patient Advocates, Foundation

s & NGOs

Government

Research &

Regulation

The HESI Model: Bridging Research to Application

POOLING RESOURCES TO EXPEDITE EFFORTS, DIVERSIFY EXPERTISE-BASE

Bridging Innovative Research and Application to Enhance Safety

CREATING NEW COMMUNITIES OF PRACTICE TO ENHANCE RELEVANCE & EFFICIENCY

IMPLEMENTING FIT FOR PURPOSE SCIENCE TO MEET PATIENT & ENVIRONMENTAL NEEDS

MOVING OUTCOMES INTO PUBLIC DOMAIN TO BENEFIT PUBLIC HEALTH AND ENVIRONMENT COMMUNITY AT LARGE

ILSI Health and

Environmental Sciences

Institute

Syril D Pettit, MEMExecutive Director

spettit@hesiglobal.org

HESI: Health and Environmental Sciences Institute