Innovative Biotechnologies for Human Healthcare … · Innovative Biotechnologies for Human...

13.10.2012

Innovative Biotechnologies for Human Healthcare

Prof. Theo DingermannInstitut für Pharmazeutische Biologie

BiozentrumMax-von Laue-Str. 9

60438 Frankfurt am MainDingermann@em.uni-frankfurt.de

Setting the SceneFrom Copying Towards Designing

Prof. Dr. Theodor Dingermann – Personalized Medicine

Mortality 1889 and 1992

1900: ca. 7 % of the 9 % living were healthy, i.e. 2 % were ill2000: ca. 30 % of the 58 % living are healthy, i.e. 28 % are ill

Mortality and Morbidity 1889 and 1992

Available drugs at the beginning of the 20th century:

Times of Pharmaceutical Revolutions...

• Acetylsalicylic (Aspirin®)• Aminopyrine (Pyramidon®)• Arsphenamine (Salvarsan®)• Barbital (Veronal®)• A Diphtheria Serum• Morphine• Procaine (Novocain®)• Strophanthine (Kombetin®)• Several Plant preparations

Modern drug development started in the mid 50th of the 20th

century!

Discovery of DNA as a universal coding concept of all biological systems in 1953.

Bob Weinberg (MIT)„With the discovery of the DNA double helix by Watson and Crick, biology became an exact science “.

Times of Biological Revolutions...

Discovery of DNA as a universal coding concept of all biological systems in 1953.

Cracking the genetic code in 1961 and the realization that this code is a universal code.

Times of Biological Revolutions...

Rekombinant Proteins

Genetic information unit = universally

understood in allbiological organisms

”Target"-organism

”Source"-organism

Rekombinant Proteins

Genetic information unit = universally

understood in allbiological organisms

Control units = extremely specific

”Target"-organism

”Source"-organism

Rekombinant Proteins

”Source"-organism

”Target"-organism

"genetic engineering"Control units Information unit

Geneticallymodified organism

(GMO) Extraction undpurification

Rekombinant Proteins

197 Biopharmaceuticals in the market by the end of 2011

mABs

27

Insulins Epoetin

100

50

0

32

8

Hormones

21

Enzymes

11

Clotting-factors

12

Interferons

9

Other

12

Vaccines

56

114

Indications for Biologicals

• Anemia• Angiogenesis Inhibition /

Macular Degeneration (AMD)• Antithrombotic• Asthma• Bacterial/viral Infections• Cancer• Chronic Inflammation • Coagulation Disorders• Diabetes• Fertility Disorder• Fractures• Growth Disorders• Immune Prophylaxis

• Impaired Wound Healing• Infarction/Stroke• Lysosomal Storage Diseases• Metabolic Disorders• Mucosal Inflammation• Multiple Sclerosis• Osteoporosis• Paroxysmal Nocturnal

Hemoglobinuria• Psoriasis• Respiratory Infections• Rheumatism• Sepsis• Transplantation

Rekombinant Drugs

At first glance it seems obvious:•recombinant drugs correspond to a natural, human molecule!

The second view shows:•A significant number of approved recombinant drugs does not correspond to a natural, human molecule!

• Some modifications are concessions to the technical feasibility – sometimes gaining significant clinical improvement (product generation 1a).

• Some molecules are in fact identical to human biomolecules (product generation 1b).

• Some intended modifications improve the clinical performance compared to the natural counterparts, partly because they take into account the significant differences between the physiological and the therapeutic delivery (2nd generation products).

• Some molecules are simply “newly invented" (3rd generation products).

Different „Product Generations"

Met-Somatropin (Protropin®)

H H

G

I E K D KR

M

Growth hormone

Somatropin

H H

G

I E K D KR

Growth hormone

Pegylated Somatropin

H H

G

I E K D KR

longer half-lifeModified growth hormone

Pegvisomant (Somavert®)

H H

G

I E K D KR

D D

NARST

KS

Growth hormone GH Receptor Antagonist

Anchor Innovation: „Genetically Modified Antibodies“

Anchor Innovation: „Genetically Modified Antibodies“

Anchor Innovation: „Genetically Modified Antibodies“

Anchor Innovation: „Genetically Modified Antibodies“

TNF Antagonists

Remicade®

(Infliximab)

TNF Antagonists

Remicade®

(Infliximab)

Humira®

(Adalimumab)

TNF Antagonists

Enbrel®(Etanercept)

Remicade®

(Infliximab)

Humira®

(Adalimumab)

TNF Antagonists

Enbrel®(Etanercept)

Remicade®

(Infliximab)

Humira®

(Adalimumab)Cimzia®

(Certolizumab)

TNF Antagonists

Enbrel®(Etanercept)

Remicade®

(Infliximab)

Humira®

(Adalimumab)Cimzia®

(Certolizumab)

Pegsunercept

Medical Progress is Expensive – Very Expensive ..

Medical Progress is Expensive – Very Expensive ..

INN Therapy costs Therapy costs

Human-Insuline per year ca. 420 €

Modified Insuline per year ca. 600 €

Cetuximab (Erbitux®) per month ca. 5.000 € initially,there after ca. 4.500 €

Trastuzumab (Herceptin®)(metastatic Mamma-CA)

per month ca. 3.400 € initially,thereafter ca. 2.800 €

Bevacizumab (Avastin®)(Mamma-CA)

per month 2 x 10 mg/kg ca. 6.600 €

Bevacizumab (Avastin®)(Colon-CA)

per month 2 x 5 mg/kg ca. 3.300 €2 x 10 mg/kg ca. 6.600 €

… Because Medical Progress Ignores Moore‘s Law!

Moore‘s Law

The number of transistors that can be placed inexpensively on anintegrated circuit doubles approximately every two years

Is the Medical Progress the “Quiet Killer” of the System?

medicalstandard

Additional costs

healthimprovement

worse and more expensive

better and cheaper

better and more expensive

cheaper and worse

What Makes a Medical Intervention Cost Effective?

economically determined cost effectiveness

MedizinischerStandard

Additional costs

worse and more expensive

better and cheaper

better and more expensive

cheaper and worse

rational prioritization on the basis of individual benefit

We Need a New Paradigm

Times of Biological Revolutions...

Decoding of the human genome in 2001: 3,2 x 109 genetic letters, ca. 25.000 genes

These properties result from genomic variations.They are inherited and are therefore stored in all cells of

an individual.

These properties result from genomic variations.They are inherited and are therefore stored in all cells of

an individual.

Some 7 Billion Genomes exist on Earth

inheritedfactors

acquired factors

The Sick Patient

The Sick Patient

Disease results from a combination of inherited factors and acquired factors (mutations)

The Sick Patient

any timefrom any cell

in case of a diseasefrom an affected cell

Medical progress has failed to be scalable so far, but moleculardiagnostics will change that.

Molecular Diagnostics Will Become a Key Technology

healthy

healthy

at risk

sick

healthy

at risk

efficacious

efficacious

partially efficacious

ineffective

efficacious

partially efficacious

tolerable

tolerable

problematic

toxic

tolerable

problematic

Classical diagnostics:• Detection of diseases

Molecular diagnostics:• Detection of diseases• Detection of disease risks• Prediction of

drug efficacydrug tolerability

Prof. Dr. Theodor Dingermann – Personalized Medicine

Diagnostics

Molecular diagnostics will provide the rationale for a personalized therapy and could help to make medical progress scalable.

Stratified Medicine = Efficacy & Effectiveness

Stratified Medicine = Efficacy & Effectiveness

Responder vs. Non-Responder

Antibodies Directed Against EGFR

Prof. Dr. Theodor Dingermann – Personalized Medicine

Antibodies Directed Against EGFR

ADRADR--ResponderResponder

ResponderResponder

NonNon--ResponderResponder

Optimal therapy for every individual patient

Solutions Through Innovative Technologies

From Copying Towards Designing

THANK YOU VERY MUCH