Biotechnology…A Promise Come True

Max SaráchagaMedical DirectorAmgen

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Treating DiseaseTreating People,

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People are part of an astonishing variety of life.

We’re all made of the same material.

Typical Cell

Protein

Sugar

Fat

Chronic Kidney Disease

People with kidney disease do not make enough of the EPO protein, produced by the kidneys to stimulate production of red blood cells.

Erythropoietin (EPO) Protein

When complex processes are all working precisely, we are healthy…

But for many people, something goes wrong. Disease is the result.

Different Treatments ______ ________

____________ ________

Different Causes of Disease,

Biotech Medicines: Live, & ComplexLarge

Biologics Differ From Traditional Drugs in Both Complexity and Sensitivity

ManufacturingUnique bank of living cells;Unlikely to achieve identical copy

Predictable chemical & reagent reaction;Identical copy can be made

CharacterizationMany products well-characterized;Correlation of structure-function elusive

Easy to fully characterize

StabilitySensitive to storage and handling conditions

More stable

Immunogenicity Higher potential Lower potential

Structure Complex Simple

Stability Complex Degradation Stable

Variability Heterogeneous ‘product’ Single defined structure

Biologics(Protein-based medicines)

Pharmaceuticals(Chemically-based drugs)

Size Large Small

Pro

per

ties

Typical Protein Production ProcessTypical Protein Production ProcessTypical Protein Production ProcessTypical Protein Production Process

Fermentation units. Host cells thrive in these vats (also called bioreactors) filled with a life-sustaining bath of nutrients.

Fermentation is the science of growing host cells in large quantities, so that the gene inside them produces the protein that we want in large quantities.

Typical Protein Production Process

Put gene intoDNA vector

Identify and isolate gene that will produce a medically useful protein

Transfer into Host Cell ExpressionScreening/Selection

DNA vectors are used to move genes into new organisms. They are generally plasmids (pieces of bacterial DNA that can live and replicate outside the chromosome).

Chinese hamster ovary (CHO) cells were introduced in the early 1960s as an ideal cell line for genetic studies.

Genes won’t produce proteins outside of a living cell, so we have to insert our gene into a living cell (a “host cell”).

Biotech Medicine: The final protein must have precisely the right amino acid sequence, folded into precisely the right three-dimensional shape. Downstream

Extraction/Purification/Dilution

We must validate that downstream processing continues to remove viruses, DNA and toxins from the protein product stream.

Validation testing may be defined as “the act of proving that any procedure, process, equipment, material, activity or system leads to the expected results.”

Biocomparables:Similar, not Identical to Original Products

Different cell lines

Different manufacturing processes

....but not identicalBiocomparables are similar...

Impact of small differences in either biological or manufacturing process could lead to different clinical efficacy and safety for patients

No therapeutic substitution

Immunogenicity differences

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We must always keep patients in mind.

Amgen: A Biotechnology Pioneer

• Founded in 1980, Amgen was one of the first biotechnology companies to successfully discover, develop, and make protein-based medicines

• Today, we’re leaders in the next wave of innovation:– Developing therapies in

multiple modalities

– Driving cutting-edge research and development

– Continuing to advance the science of biotechnological manufacturing

Our Worldwide Presence and a Leader In Biotechnology Manufacturing

The Netherlands

Belgium

Ireland

Spain

Switzerland

Juncos, Puerto Rico

Washington, DC

Louisville, KY

West Greenwich, RI

Cambridge, MA

Toronto, ON

Thousand Oaks, CA

Seattle, WA

Bothell, WA

Hungary

United Kingdom

Denmark

Portugal

Italy

Germany

Norway

FranceCzech Republic

Sweden

Austria

Poland

Australia

Boulder, CO

Longmont, CO

Finland

South San Francisco, CA

Slovenia

Slovakia

LithuaniaLatvia

Estonia

Luxembourg

Burnaby, BC

United Arab Emirates

Mexico City, Mexico

Hong Kong

India

Russia

Greece

Brazil

Japan

BulgariaRomaniaTurkey

Woburn, MA

54 Countries by 2011

75 Countries by 2015

35% of worldwide manufacturing capacity

Our ProductsOncology, Nephrology, Bone, Metabolism, Inflammation…

For additional information about Amgen products, including important safety information, please visit www.amgen.com

Research and Development at Amgen

Guiding Principles

• Focus on serious illness

• Be modality independent

• Assess efficacy in patients

• Seamless integration from research through commercialization

Pioneering ScienceDelivers Vital Medicines

For more information, visit www.amgen.com

Our Mission : To serve Patients