Download Why Science? - Center for Excellence in Education

Dr. Robert Kernstock
For Bite of Science (October 9, 2012)
You May Be Wondering
Why I Am Here?...
•
•
•
•
•
Why Science?
How Did I Get Here?
What is Astellas?
My Job Now?
How are Drugs
made?
Why science, and ‘how did I
get here’?
Pharma: From ‘Bad Rap’
to Sought After Field
“Old-School” Thought
•Academic Science
Nobel Aspirations
•Pharmaceutical Science
Money-Generating
Current
Thinking
Current
thought
•Working Together!
•Applied Science
•Using Each Other’s Strengths
•Sharing the Real Rewards
Improving Quality of Life
So Who is Astellas?

Cardiovascular
Infectious Disease
Dermatology
Urology
Immunology
Oncology
Central Nervous System
At Astellas, our mission is
to identify safe and
effective medicines for
people all over the world
U.S. Therapeutic Franchises
Immunology
Dermatology
Cardiovascular
Infectious Disease
Urology
Oncology
Our Lab Stuff
Flow Cytometry
Ligand Binding
Fluorescence
Genotyping
Cycles
BioPharma: It’s
Real World Science!
Biology
Pharmacodynamics
Product Development
Physical Science
Industry
Anatomy
Physics
Histology
Genetic Engineering
Academic
Astronomy
Drug Discovery
Medical Science Liaison
Chemistry
Clinical Trial Research
Science Career Opportunities
in Pharma
Regulatory
&
QA
Pharmacovigilance
PK
Modeling
R&D
Science
Gov’t
Affairs
Degree
Science
Liaison
Sales &
Marketing
Business
Dev’t
So How Do Drugs Work?

Cells in our bodies carry out molecular reactions
to perform every function, for example:
– Digesting your lunch
– Moving your finger
– Transmitting thoughts in your brain

One molecule interacts with another, which
interacts with another, and so on.
– These cascades are called chemical pathways


A mistake in one of the steps in a pathway can
lead to disease.
Drug molecules interact with a molecule in the
pathway, changing their activity.
How Do We Fulfill
this Mission?
Drug Discovery then Development
Example
Discovered
The Discovery Process
Pre-Discovery:
Goal: Understand the disease and choose a target molecule.
How: Scientists in pharmaceutical research companies, government, academics
and for-profit research institutions contribute to basic research.
3 – 6 YEARS
Discovery
Goal: Find a drug candidate.
How: Create a new molecule or select an existing molecule
as the starting point. Perform tests on that molecule and
then optimize it (change its structure) to make it work better.
Preclinical
Goal: Test extensively to determine if the drug is safe
enough for human testing.
How: Researchers test the safety and
effectiveness in the lab and in animal
models.
The Development Process
Drug Discovery then Development
NUMBER OF SUBJECTS
(1 year)
(3-6 years)
Preclinical
Phase I
(2 years)
Phase II
Number of Subjects
(4 years)
Phase III
Phase IV
NDA
(2 yrs)
Personalized Medicine
• “The Dream”
– Plug and play medicine based on
individual’s gene signature
– We are all unique and a ‘conglomerate’ of
our biological relatives
Personalized Medicine
EML4-ALK fusions in Lung Cancer
1
ALK
Tyr Kinase
（Anaplastic Lymphoma Kinase）
1
EML4
1620
TM
Basic
981
WD
（Echinoderm microtubule-associated protein like protein 4）
1
Basic
496
1059
Tyr Kinase
A fused gene EML4 is connected to ALK (in DNA)
ALK fusions exist in 5% of lung cancer. A simple
PCR test to detect fusion.
Over 70% of ALK fusion + cancers are cured!
Question & Answer
Special thanks to Astellas and
Center of Excellence in Education
www.ibioinstitute.org
www.finding-your-future.org
(SCI: Science Career
Investigation)
www.scienceworx.org
Mission of a Pharmaceutical
Research Company

Take the path from understanding a disease to bringing a safe and
effective new therapy to patients.
–
–
–
–
–
–
Select a molecule in a pathway => target
Validate the target
Discover the right molecule to interact with the target
Test the compound in the lab for efficacy and safety
Test the compound in the clinic for efficacy and safety
Gain approval to get the drug to doctors and patients
What Sets Astellas Apart
Our Values
At Astellas we are committed to providing patients, customers, community
and employees with a bright future by changing tomorrow.
Our Approach
Astellas is different, not only because of what we do but because of how
we do it.
Our Focus
In the U.S., we are intensely focused on five key therapeutic areas so
we can develop a deep understanding of the disease, our customers
and patient needs.
A Commitment to
Changing Tomorrow
Our efforts align with our strong scientific
orientation and a focus on the community we work
and live in
COMMUNITY
SCIENCE AND
EDUCATION
SUSTAINABILITY
Encourage employee
involvement and
volunteerism
Building a strong
foundation in science to
ignite passion and
interest in science
among today’s youth
Helping to improve the
environment through
internal and external
practices
State-of-the-Art R&D Facilities
Astellas Research Institute of America (ARIA)
•
Based in Illinois, ARIA is committed to strengthening
research in transplantation through:
– Drug targeting research
– Clinical biomarker translation research
– Absorption, Distribution, Metabolism and Excretion
(ADME) prediction research
– Collaborations with delegate researchers (KOLs)
ASKP1240: PK in 7163-CL-0101 < multiple dose simulation > / model= 720
80 mg (1.0 mg/kg)
Phase 1 - Pharmacokinetics
1.0
0.1
ASKP1240: PK in 7163-CL-0101 < multiple dose simulation > / model= 720
0
20
40
60
80
100
120
140
20
20
20
40
60
80
100
Time (day)
Time (day)
Day 1, 14, 28, 42, 56
Day 1, 14, 28, 56
Day 1, 28, 56
Day 1, 7, 14, 28, 56
Establish Dose
and Frequency
0
0
0
240 mg (3.0 mg/kg)
40
40
60
80
60
80
Time (day)
Time (day)
100
100
Day 1, 14, 28, 56
120
120
140
140
0.10.1 1.01.010.0
10.0
0.10.1 1.01.010.0
10.0
0.1
1.0
10.0
Day 1, 28, 56
10.0
Day 1, 14, 28, 42, 56
0
0
20
20
40
40
60
80
60
80
Time (day)
Time (day)
100
100
Day 1, 7, 14, 28, 56
120
140
120
120
140
140
0.5 – 2 YRS
5 – 7 YEARS
The Approval Process
Investigational New Drug (IND):
Goal: Obtain FDA approval to test the drug in humans.
How: FDA reviews all preclinical testing and plans for clinical testing to
determine if the drug is safe enough to move to human trials.
Clinical Trials:
Goal: Test in human to determine if the drug is safe and effective.
How: Candidate drug is tested in clinical setting in three phases of
trials, beginning with tests in a small group of healthy volunteers and
moving into larger groups of patients.
Review:
Goal: FDA reviews results of all testing to determine if the drug can be
approved for patients to use.
How: The FDA reviews hundreds of thousands of pages of information,
including all clinical and preclinical findings, proposed labeling and
manufacturing plans. They may solicit the opinion of an independent
advisory committee.