For Bite of Science (October 9, 2012)

Dr. Robert Kernstock

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 Current thought• Academic Science

Nobel Aspirations• Pharmaceutical

Science Money-Generating

Current Thinking• Working Together!• Applied Science• Using Each Other’s Strengths• Sharing the Real Rewards

Improving Quality of Life

So Who is Astellas?

At Astellas, our mission is to identify safe and effective medicines for people all over the world

Dermatology

Cardiovascular

Infectious Disease

Urology Immunology

Oncology Central Nervous System

U.S. Therapeutic Franchises

Urology

Immunology

Dermatology

Cardiovascular

Infectious Disease

Oncology

Our Lab Stuff

Ligand BindingGenotyping

Flow Cytometry

CyclesFlu

ore

scen

ce

Industry

Academic Drug DiscoveryMedical Science Liaison

Product Development

Genetic Engineering

Clinical Trial Research

Histology

PharmacodynamicsBiology

Chemistry

Physical Science

Physics

Anatomy

Astronomy

BioPharma: It’s Real World Science!

Science Career Opportunities in Pharma

ScienceDegree

Regulatory&

QA

R&D

Gov’t Affairs

Science Liaison

Business Dev’t

Sales & Marketing

PK Modeling

Pharmaco-vigilance

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 Y

EA

RS

DiscoveryGoal: 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.

PreclinicalGoal: 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

Phase I Phase II Phase III

Number of Subjects

Preclinical Phase IV

(1 year) (2 years) (4 years)(3-6 years)

Drug Discovery then Development

NUMBER OF SUBJECTS

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 MedicineEML4-ALK fusions in Lung Cancer

Tyr Kinase

1 1620TM

1 981

Basic WDEML4

Basic

1 1059496

Tyr Kinase

ALK（ Anaplastic Lymphoma Kinase ）

（ Echinoderm microtubule-associated protein like protein 4 ）

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.orgwww.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

Our FocusIn the U.S., we are intensely focused on five key therapeutic areas sowe can develop a deep understanding of the disease, our customersand patient needs.

Our ValuesAt Astellas we are committed to providing patients, customers, community and employees with a bright future by changing tomorrow.

Our ApproachAstellas is different, not only because of what we do but because of howwe do it.

What Sets Astellas Apart

A Commitment to Changing Tomorrow

COMMUNITY

Encourage employee involvement and

volunteerism

SCIENCE AND EDUCATION

Building a strong foundation in science to

ignite passion and interest in science

among today’s youth

SUSTAINABILITY

Helping to improve the environment through internal and external

practices

Our efforts align with our strong scientific orientation and a focus on the community we work

and live in

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)

Phase 1 - Pharmacokinetics

Time (day)

0 20 40 60 80 100 120 140

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Day 1, 14, 28, 42, 56

Time (day)

0 20 40 60 80 100 120 140

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Day 1, 28, 56

Time (day)

0 20 40 60 80 100 120 140

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Day 1, 14, 28, 56

Time (day)

0 20 40 60 80 100 120 140

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1.0

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Day 1, 7, 14, 28, 56

ASKP1240: PK in 7163-CL-0101 < multiple dose simulation > / model= 720

80 mg (1.0 mg/kg)

Time (day)

0 20 40 60 80 100 120 140

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1.0

10

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Day 1, 14, 28, 42, 56

Time (day)

0 20 40 60 80 100 120 140

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1.0

10

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Day 1, 28, 56

Time (day)

0 20 40 60 80 100 120 140

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1.0

10

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Day 1, 14, 28, 56

Time (day)

0 20 40 60 80 100 120 140

0.1

1.0

10

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Day 1, 7, 14, 28, 56

ASKP1240: PK in 7163-CL-0101 < multiple dose simulation > / model= 720

240 mg (3.0 mg/kg)

Establish Dose and Frequency

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.

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7 Y

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– 2

YR

S