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ILSI Health and
Environmental Sciences
Institute
Syril D Pettit, MEMExecutive Director
February 25, 2015Member Meeting
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
Comprehensive In Vitro Proarrhythmia Assay: Three Core Pillars
Evaluation of Clinical
Drugs for Proarrhythmi
c TdP Liability
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Drug Effects on Multiple Human Cardiac Currents
In Silico Reconstruction
Human Ventricular
Cellular Electrophysiology
In Vitro Effects Human Stem-Cell Derived
Ventricular Myocytes
High Risk
Inter-mediate
Risk
Low Risk
Preclinical ECG & Phase 1 ECG Studies: Complementary Data
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
2015HESI Strategic Plan Renewal
Current plan expires in 2015
Process for renewal launched in fall 2014, Tecker & Associates hired
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PATH FORWARDJanuary 2015 – ‘Environmental Scan’ & Values Statement
First Quarter – Survey input from members, EIC, ORs & selected stakeholders June 10-12, 2015 – Extended strategic plan strategy session at June 2015 Annual Meeting (all invited)4Q 2015 – Finalization of the 2016-2020 Strategic PlanJanuary 2016 – Board Vote to Approval 2016+ Strategy
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Some topics identified in January 2015
• Shifts in resource availability • Greater emphasis on technology for evaluation and every day tasks• New opportunities for expertise (crowd sourcing, developing regions, etc.)• Globalization and global economy• Shifting health care priorities and concerns (epidemics, aging population, personalized
medicine, etc.)• Digital communication – speed and transfer of information and news• New approaches to how science research is conducted and communicated• New regulatory environments (animal welfare, environmental concerns, risk aversion,
harmonization, public involvement, etc.)
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Your Thoughts?
•
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NEW HESI PROJECTSNEW HESI PROJECTSEmerging Issues Committee Update – February 2015Emerging Issues Committee Update – February 2015
New Subcommittee: Framework for Intelligent Non-Animal Alternative Methods for Safety AssessmentSelection and Initiation:• Selected by EIC in fall 2014.• First meeting of Cmte in January 2015.
Leadership:Prof. Alan Boobis Imperial College LondonDr. Craig Rowlands Dow Chemical Company
Dr. Natalie Burden NC3Rs
Dr. Beatrize Silva Lima University of Lisbon
Dr. Matt Hurtt Pfizer
Dr. Norbert Kaminski Michigan State University
Dr. Suzanne Fitzpatrick US FDA
Staff:Dr. Stan Parish (HESI Scientific Program Manager)
Objective: Develop a set of consistent, internationally relevant criteria against which the reliability and fitness-for-purpose of new non-animal methods or approaches are assessed.
EI Proposal Solicitation:Timeline
TIMELINE: 15 December 2014: Proposals due to HESI. 10 February 2015: Submitted proposals undergo detailed
review by EIC. March 2015: Submitters are contacted by HESI staff with
decisions about each proposal. June 2015: Selected proposals are presented at the HESI
Annual Meeting. Summer 2015: Proposals presented at the HESI Annual
Meeting are distributed for prioritization and voting by the HESI constituency.
Fall 2015: The EIC selects one or two proposals for action.
Topics for Voting in June 2015
• Nonclinical efficacy and safety studies in support of neonatal pediatric therapeutic use and development
• Models/tests to assess stem cells as therapeutic agents – safety and mode of action and efficacy.
• Frameworks for assessing the protectiveness and predictability of human health risk assessments
• Transforming exposure science through emerging technologies and big data to improve predictive exposure capabilities.
ECO ASSESSMENT- Development of ecotoxicological TTC (ecoTTC)- Effluent testing for ecotoxicity
BIOMARKERS • Cardiac biomarkers after exposure to doxorubicin/diclofenac in the Zucker Diabetic
Fatty rat model• Biomarkers of prolactin (evaluating stress vs. chemical-induced responses)
IN VITRO APPROACHES• Testing developmental toxicants in alternative in vitro assays.
NEW TECHNOLOGIES• Workshop: Fetal imaging in regulatory toxicity testing
Other New projects
HESI ANNUAL MEETING
JUNE 9-12, 2015WASHINGTON, DC
SAVE THE DATE!!!!
ILSI Health and
Environmental Sciences
Institute
Syril D Pettit, MEMExecutive Director
Ayako Takei, MPHHESI Science Advisor in
HESI: Health and Environmental Sciences Institute
BACKUPS
HESI Staff
Syril Pettit, MEM, Executive Director
Nancy Doerrer, MS, Associate Director
Michelle Embry, PhDSenior Scientific Program Manager
Raegan O’Lone, PhDSenior Scientific Program Manager
Connie Chen, MPH, PhDScientific Program Manager
Jennifer Pierson, MPHScientific Program Manager
Jennifer Tanir, PhDScientific Program Manager
Cynthia Nobles, Branch Administrator
Oscar BermudezScience Program Associate
Brianna Farr,Science Program Associate
Stanley Parish, PhDScientific Program Manager
Science never appears so beautiful as when applied to the uses of human life. Thomas Jefferson, 1798. Charlottesville, Virginia.
• http://www.monticello.org/site/research-and-collections/historic-landscape-institute
