HESI:
Health and Environmental Sciences Institute
Syril D Pettit, MEM
Executive Director
February 25, 2015
Member Meeting
HESI
Washington, DC USA
www.hesiglobal.org
ILSI Health and
Environmental Sciences
Institute
HESI Mission
Create science-based solutions for a
sustainable, healthier world.
Accurate
and Efficient
Chemical
Risk
Assessment
Safe and
Effective
Medicines
Environmental
Quality and
Sustainability
Food Safety
Protecting
sensitive
populations
Sustaining critical
environments
Supporting ecological
and human safety of
essential food
resources
Promoting Discovery
Predicting and
Protecting Against
Adverse Effects
from Chronic
Exposures
The HESI Model:
Bridging Research to Application
Academic
& basic
research
sector
SAFETY &
INNOVATION FOR
HUMAN &
ENVIRONMENTAL
HEALTH
Patient
Advocates,
Foundations
&
NGOs
Industry
R&D
Government
Research
&
Regulation
90
University
&
Research
Centers
From 14
Countries
47
Government
Agencies
66
Corporate
Sponsors
Across multiple
sectors
From 12
Countries
14
Scientific
Committees
>70
Distinct
Projects
Impact via
Quality
Science
HESI achieves its mission via…
Scientific
Research
Millions in in-kind
research annually
Publication
Communication
& Translation
Tools
Training
Novel programs
with
interdisciplinary
and cross-sector
focus
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
Integrating Alternatives
to Animal Testing for
Ecotox
Globally
recognized HESI
roadmaps to
guide
integration of data
and decisions.
Mode of Action
Risk / Safety
In vivo
In vitro
Toxicity
Innovating
Chemical Risk
Assessment
Matrix
QSAR/
TTC
Biomonitoring
Probabilistic
Deterministic
Minimal
Info
Assessing Adverse vs
Adaptive Transitions in
Toxicity Pathways
Exposure
Problem
Formulation
Conclude
Enhancing
AgChem
Safety
A spotlight
on one of
many…
US EPA Scientific and Technological
 Basis for OECD Guideline for
Achievement Award
Testing of Chemicals (443):
(Honorable Mention)
Extended One-Generation
Reproductive Toxicity Study
UK National Center for the
 Canine study requirement
Replacement, Refinement, and
dropped in EPA Pesticide
Reduction of Animals in Research
guidelines;
“Highly Commended Prize”
 Increased use of ADME to
enhance dose selection
Impact cited in 2 National Academy
reports
Enhancing
AgChem
Safety
Informing discovery
& decision-making
with new technologies
Toxicogenomics • First large scale TGx experimental
program, first public array/tox dbase
for Risk
• Led to adoption of data standards,
Assessment
genomic biomarkers
• Resource for strengths & limitations
of TgX use for safety
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
Translating from animal to human,
and back to improve predictive
safety
HESI Approach to Biomarkers
• Consensus on Safety or Translational Need
• Experimental Data
• Analysis & Publication
Nonclinical
cTn serum
assays
• Integration of Data & Context of Use
Nonclinical
Inhibin
Assays
Urinary
Renal
Protein
Biomarkers
MicroRNAs as
translation tox markers
2015:
PROGRAMS TO
IMPACT SCIENCE
AND HEALTH
Chemical Safety
Evaluation
Predictive models
Risk assessment methodologies
Sustainability
Capacity Building & Education
Predictive Models
Zebrafish &
multigenerational
epigenetics
Bioaccumulation:
In vitro method,
hepatic
clearance in trout
Utility of 2nd Species
for assessing
developmental
toxicity
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
Region of
Opportunity
Patient
Experience
Contemporary
Drivers
Enhance drug
discovery, don’t
compromise
safety
Support Cancer
Patient Survival &
Quality of Life
Prevent Another
TGN 1412
Ensure new therapeutic
modes are safe for sensitive
populations
Enhance drug
discovery, don’t
compromise
safety
What It Will Do:
-
Nature Review:
Drug Discovery.
Aug 2013
-
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
Drug Effects
on Multiple
Human Cardiac
Currents
In Silico
In Vitro Effects
Reconstruction Human StemHuman
Cell Derived
Ventricular
Ventricular
Cellular
Myocytes
Electrophysiology
Evaluation of
Clinical Drugs
for
Proarrhythmic
TdP Liability
High Risk
Intermediate
Risk
Low Risk
Preclinical ECG & Phase 1 ECG Studies: Complementary Data
Prevent Another
TGN 1412
HESI STUDY RESULTS:
 Significant variability
revealed (controls, assay
selection, design,
situational use,
interpretation)
 Identified opportunities to
improve forward prediction
with collaborative approach
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.
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
• 7 fold higher risk of
cardiac mortality
www.fredhutch.org
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!
The HESI Model:
Bridging Research to Application
Academic
& basic
research
sector
SAFETY &
INNOVATION FOR
HUMAN &
ENVIRONMENTAL
HEALTH
Patient
Advocates,
Foundations
&
NGOs
Industry
R&D
Government
Research
&
Regulation
CREATING NEW COMMUNITIES
OF PRACTICE TO ENHANCE
RELEVANCE & EFFICIENCY
IMPLEMENTING FIT FOR
PURPOSE SCIENCE TO MEET
PATIENT & ENVIRONMENTAL
NEEDS
POOLING RESOURCES TO
EXPEDITE EFFORTS, DIVERSIFY
EXPERTISE-BASE
Bridging Innovative
Research and
Application to
Enhance Safety
MOVING OUTCOMES INTO
PUBLIC DOMAIN TO BENEFIT
PUBLIC HEALTH AND
ENVIRONMENT COMMUNITY AT
LARGE
HESI Strategic Plan Renewal
2015
Current plan expires in 2015
Process for renewal launched in fall 2014, Tecker & Associates hired
PATH FORWARD
January 2015 – ‘Environmental Scan’ & Values Statement
N
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 Plan
January 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.)
Your Thoughts?
N
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NEW HESI PROJECTS
Emerging Issues Committee Update – February 2015
New Subcommittee: Framework for
Intelligent Non-Animal Alternative
Methods for Safety Assessment
Selection and Initiation:
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Selected by EIC in fall 2014.
First meeting of Cmte in January 2015.
Leadership:
Prof. Alan Boobis
Dr. Craig Rowlands
Imperial College London
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.
Other New projects
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
HESI ANNUAL
MEETING
JUNE 9-12, 2015
WASHINGTON, DC
SAVE THE DATE!!!!
HESI:
Health and Environmental Sciences Institute
Syril D Pettit, MEM
Executive Director
spettit@hesiglobal.org
Ayako Takei, MPH
HESI Science Advisor in Japan
atakei@hesiglobal.org
ILSI Health and
Environmental Sciences
Institute
BACKUPS
HESI Staff
Syril Pettit, MEM,
Executive Director
Nancy Doerrer, MS,
Associate Director
Cynthia Nobles,
Branch Administrator
Michelle Embry, PhD
Senior Scientific
Program Manager
Connie Chen, MPH, PhD
Scientific Program
Manager
Stanley Parish, PhD
Scientific Program Manager
Brianna Farr,
Science Program
Associate
Raegan O’Lone, PhD
Senior Scientific
Program Manager
Jennifer Tanir, PhD
Jennifer Pierson, MPH
Scientific Program Manager Scientific Program Manager
Oscar Bermudez
Science Program
Associate
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http://www.monticello.org/site/research-and-collections/historic-landscape-institute
Science never appears so beautiful as when applied to the uses
of human life. Thomas Jefferson, 1798. Charlottesville, Virginia.