Drug development & biotechnology

Drug Development & Biotechnology

Case Study for PCR901

November 16, 2011

Karen, Nichole & Zinia

Outline

• Introduction• Departmental / Team Structure

– Organogram• Business Model• Research Interests• Services Offered• Project Team Composition• The Legendary Case Study• Challenges & Rewards

Introduction: Biologics and Biopharmaceuticals

• Biotechnology– The use of living organisms and bioprocesses in

engineering, technology, medicine and other fields requiring bioproducts.

• Biopharmaceutical– A medical drug derived from biological sources and

produced by biotechnology.

BIOTECH

THERAPEUTIC PROTEINS

MONOCLONAL ANTIBODIES

VACCINES

IMMUNO- THERAPY

BLOOD COMPONENTS

TISSUES AND CELLS

BUSINESS MODEL

“One of the biggest challenges for the biotechnology and pharmaceutical companies in the 21st century will be to develop and deliver drugs that fit the individual patient’s biology and pathophysiology”

Jan Trost Jorgensen principal scientist at Dako

Traditional Business Model

• Searching for the “Blockbusters”• Closed Innovation model• a.k.a. the FIPCOs (Fully Integrated

Pharmaceutical Companies)– Majority of research is conducted internally– Firms conduct basic research, confident that

they have downstream manufacturing and commercialization capabilities

– Accidental (serendipitous) discoveries that did not fit with corporate therapeutic interests were most often cancelled

Traditional Business Model

• Open Innovation model– Expectation is that knowledge is acquired from

external sources– Licence out knowledge that does not fit the

business model

Contemporary Business Model

• Large pharma:– In house development, manufacturing, marketing and

sales; – Some with generic/biosimilar subdivisions

• Medium pharma:– Outsource one or more components, retain in house

marketing and sales• Small pharma:

– Bring in products researched, developed and manufactured elsewhere

– Simply register, import / acquire, store and distribute

• Company size by number of employees (%)

Biotechnology Industry

Size Percentage

1 – 20 28.1%

21 – 50 19.8%

51 – 100 11.9%

101 – 200 9.9%

201 – 400 4.1%

401+ 6.2%

SERVICES OFFERED

• Pre-Clinical & Clinical Development

• Registration Submissions & Support

• GxP (GMP, GCP, CLP) & Regulatory Consultancy

• CRO Qualification• Preparatory regulatory

audits• Due Diligence Audits

Typical Areas of Product Development

• Vaccines• Peptides and Proteins• Follow On Biologics• Natural Products• Transdermals• Radionucleotides• Osteopathic Devices• In-vitro Diagnostic Reagents

RESEARCH INTERESTS

Growing Importance of Biotech Medicine

• Proven to be safe and effective• Biotechnology has produced more than 125

medicines• Treatment for some of the most serious and

intractable diseases• In 2008:

– 633 biotech medicines in development– 254 for cancer and related conditions– 162 for infectious diseases

• Full therapeutic potential can take time to be realized; new treatment advances are often realized after product has been on the market for some time

Drug Discovery Research

On going Research Topics

Specific Research

Erythropoeteins:• The hormone responsible for producing red blood

cells in bonemarrow• Most common use in people with anemia related

to kidney disfunction• Drugs Epoitin alpha ( Epogen, Procrit)• Darbepoetin alpha (Aranesp)

Specific Research

Monoclonal antibodies• The newest one approved is Rituximab (Rituxan)• Several monoclonal anibodies are being

researched for treating rheumatoid arthritis (RA) and other conditions

• Anticancer and immunological therapies using monoclonal antibodies are being a focus of reseach

Current Research Focus

Biotechnology current

Long Term conditions

Oncology

Infectious diseasesGene therapy

Genetic Engineering

PROJECT TEAM COMPOSITION

Project Team Composition

• Clinicians• Pharmaceutical

Scientists• Regulatory Strategists• Business

Development Experts• Market Analysts

DEPARTMENTAL / TEAM STRUCTURE

R&D Organizational StructureChairman of

the Board and CEO

EVP Research & Development

SVP Discovery Research

VP Research (Chemistry)

VP Research (TA)

VP Research (TA)

VP Research (TA)

SVP Translational

Sciences

VP Comparative Biology & Safety

(Preclinical)

VP PK & Drug Metabolism (Preclnical)

VP Process & Product

Development

VP Medical Sciences

SVP Clinical Development

VP Scientific Affairs

VP Development (TA)

VP Development (TA)

VP Development (TA)

SVP Regulatory Affairs and

Safety

VP Regulatory Affairs

VP Safety

VP Intl RA & Safety

Exec Dir RA & Safety

Operations

SVP International

R&D

Exec Medical Dir (EU)

Exec Medical Dir (North America)

Exec Medical Dir (Asia/Pacific)

Exec Medical Dir (Emerging Countries)

VP Program Mgt & Strategic Ops

Exec Dir Strategic

Operations

Exec Dir Program Mgt

(TA)


(TA)


(TA)

Executive Director

Compliance

Director Quality Compliance

Director Compliance

Auditing

Director Systems

Compliance

Director Training & Development

R&D Organization Structure

Level 3

Level 4

Level 5

Level 6

Level 7

Level 8

Level 9 Vice President

Executive Director

Director

Principal/Senior Manager

Specialist/Manager

Senior Associate

Associate

CASE STUDY

Drug Discovery Drug Development Commercialization

New Product Development



• Project Procurement– Identify unmet medical need– What is known about the disease?– What are the current treatment options, if any?– Does the company have the expertise, technology

and financial resources?– Potential competitors and regulatory constraints?

Drug Discovery

Top 5 Death Causing Diseases in 2005 (NCHS)

Drug Discovery

Therapeutic Areas (TA)

• Oncology• Inflammation• Hematology/Nephrology• Metabolic Disorders• Neuroscience• Cardiovascular

Research Interest

Target Discovery

Target Validation

Screening

Drug Design

Drug Discovery



Clinical Study: Phase I

Clinical Study: Phase II

Clinical Study: Phase

III

Post-Market Surveillance:

Phase IV

Drug Development

Preclinical studies

Product Pipeline: Phase I

Product Name Product Modality Therapeutic Area

1 AMG139 Antibody Inflammatory Diseases

2 AMG145 Antibody Hypercholesterolemia

3 AMG151 Oral/Small Molecule Type II Diabetes

4 AMG157 Antibody Asthma

5 AMG167 Antibody Bone-Related Conditions

6 AMG181 Antibody Ulcerative Colitis


8 AMG208 Oral/Small Molecule Various Cancer Types

9 AMG319 Oral/Small Molecule Hematologic Malignancies



11 AMG557 Antibody Lupus

12 AMG745

Protein Muscle-Wasting Disorder

13 AMG747 Oral/Small Molecule Neuroscience

14 AMG761 Antibody Asthma

15 AMG780 Antibody Various Cancer Types

16 AMG811 Antibody Lupus




20 Dulanermin Protein Various Cancer Types

Product Pipeline: Phase I (cont'd..)


1 AMG386

Protein Various Cancer Types

2 AMG785 Antibody Bone-Related Conditions


4 AMG853 Oral/Small Molecule Asthma

5 Conatumumab Antibody Various Cancer Types

6 Denosumab Antibody Rheumatoid Arthritis

7 Ganitumab Antibody Various Cancer Types

8 Motesanib Oral/Small Molecule Breast Cancer

9 Nplate® Protein Thrombocytopenia

10 Nplate® Protein Myelodysplastic Syndromes

Product Pipeline: Phase II


11 Omecamtiv mercarbil Oral/Small Molecule Heart Failure

12 Rilotumumab Antibody Various Cancer Types

13 Sensipar® Oral/Small Molecule Post Renal Transplant

14 Vectibix® Antibody Head and Neck Cancer

Product Pipeline: Phase II (cont'd..)

Product Pipeline: Phase III Product Name Product Modality Therapeutic Area

1 AMG386 Protein Ovarian Cancer

2 Anaresp® Protein Anemia in Heart Failure

3 Ganitumab Antibody Pancreatic Cancer

4 Motesanib Oral/Small Molecules Lung Cancer

5 Prolia® Antibody Male Osteoporosis

6 Sensipar® Oral/Small Molecules Cardiovascular Disease and Chronic Kidney Disease

7 Vectibix® Antibody Colorectal Cancer

8 XGEVA™ Antbody Bone Metastases in Breast Cancer

9 XGEVA™ Antibody Bone Metastases in Prostate Canacer

Marketed Products: Phase IV

Product Name

1 Anaresp® (darbepoetin alfa)

2 Enbrel® (etanercept)

3 EPOGEN® (Epoetin alfa)

4 Neulasta® (pegfilgrastin)

5 NEUPOGEN® (Filgrastim)

6 Nplate® (romiplostim)

7 Prolia™ (denosumab)

8 Sensipar® (cinacalcet)

9 Vectibix® (denosumab)

10 XGEVA™ (denosumab)

CHALLENGES & REWARDS

Challenges and Resolutions

• More Expensive• Biosimilar Verification• Small molecule vs Large molecule therapies• Required comprehensive immunogenecity testing • Extended post market surveillance• Sterile Environment requirement• Batch-to-batch release – Section 12 of the ACT

Manufacturing techniques for cost reduction

• Portable clean room technology• The use of cell culture perfusion for production of

antibodies• Sequential micro column chromatography• Extensive use of inline dilution of buffer

concentrates

Advantages

• Stem cell therapies have the ability to eliminate concerns over viral or prion contamination prior to organ replacement

• Biopharmaceuticals have fewer side effects and more potent effects on target cells

• Pharmaceutical biotechnology is being further developed to fight cancer, viral infections, diabetes and hepatitis

• Safer and more effective antibiotics, insulins, interferons, estrogen and human growth hormones are being developed

Conclusions

• Globally, Canada ranks 2nd in number of biotech companies and spends the most on R&D per employee1

• Some slowdown in venture capital since decline of Harvard oncomouse patent

• Significant growth in Quebec, Ontario and BC; biotechnology is the place to be for up-and-coming innovators

1Statistics Canada; http://www.nature.com/bioent/2004/040501/full/bioent810.html

http://www.nature.com/bioent/2004/040501/full/bioent810.html

Questions & Comments?

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