Current Drug Development Market for Cytokines, Chemokines and Growth Factors

Table of Contents

CHAPTER 1: EXECUTIVE SUMMARY

CHAPTER 2: CYTOKINES

• Future Cytokine Modifications
  • Approved Therapeutic Biologics by CBER are Prerdominantly Cytokines or Growth Factor Related
  • The Biosimilar Debate
• Gene Therapy with Cytokines
  • Antisense and RNA Interference Technologies
• Interferons
  • Interferons (Avonex, Betaseron, Rebif) in the Multiple Sclerosis Multi-Billion Dollar Market
  • Interferon-based Drugs Being Developed for Immune Mediated Diseases
  • Interferons and Cancer
  • Interferons and Autoimmune Diseases such as Lupus, Asthma, and Crohn' s Disease
  • New Interferons and Interferon Inducers in Viral Hepatitis
  • Interferon Mimetics and Variants
• Interleukins
  • Interleukin 1 and Autoimmunity
  • IL-2 and Cancer
  • IL 6-Tocilizumab for Treatment of Castleman' s Disease
  • IL10, IL-11, IL-12, and IL-13 for Immune Cell Modulation
  • IL-21 and Its Receptor in Cancer Models of Mice
  • IL-1 and Autoimmune Disease (Rheumatoid Arthiritis, Psoriasis)
  • IL -4 Receptor and IL-5 in Asthma
  • IL-8' s Pathological Role in Psoriasis
  • IL-12, IL-13, IL-17, and IL-18 in TH1 Mediated Autoimmunity
  • Interleukins and Infection
• The Interferon and Interleukin Market

CHAPTER 3: TARGETING THE CYTOKINE TNF LIGAND AND RECEPTOR SUPERFAMILIES

• TNF-α Inhibitors: FDA-Approved and Follow-ons
  • Enbrel (Etanercept)
  • Remicade (Infliximab)
  • Golimumab (CNTO 148)
  • Humira (Adalimumab)
  • Cimzia (Certolizumab Pegol)
• Additional TNF-α Antibody Inhibitors in Autoimmunity and Inflammation
  • Nano- and Diabodies
  • TNF-α Vaccines
• TNF-α Antagonists and Modifiers
  • TNF-α Gene Therapy
• Tumor Necrosis Factor-α in Cancer and Infection
• TNF-β (Lymphotoxin-β) (Lymphotoxin-α) TNF Receptor/Ligand Superfamily Member1) and
• Lymphotoxin-β (TNF Receptor/Ligand Superfamily Member 3)
• TNF Receptor/Ligand Superfamily
  • OX40/OX40L
  • CD40/CD40L
  • Fas/FasL
  • CD27/CD70
  • CD30/CD30L
  • 4-1BB (CD137)/ 4-1BBL
  • TRAIL Receptors/Ligands
  • RANK Receptor/Ligand
  • TWEAK/DR3
  • BLyS and APRIL
• TNF Market Opportunities

CHAPTER 4: CHEMOKINES AND DRUG DEVELOPMENT

• Chemokines and Their Receptors
  • CC Chemokines
  • CXC Chemokines
  • C Chemokines
  • CX3C Chemokines
• Chemokines and Autoimmune Disease
  • CCR9 Chemokine Receptor
  • CCR2 Targeted as an Anti Inflammatory Drug
  • CCR2 and its Receptor MCP-1 Mediated Blockage
  • CCR1
  • CCR3 Blockade
  • Migration Inhibitory Factor (MIF)
• Chemokines and Cancer
  • CXCR4 Antagonist Mozobil
  • Other CXCR4 Antagonists
  • Chemokine (C-X-C motif) Ligand 9 (MIG)
  • CXCR4
  • Stromal Cell Derived Factor SDF-1
• Chemokines and HIV Infection
  • CXCR4 and CCR5 Chemokine Receptors to Target HIV
• Current Targets in the Chemokine Market

CHAPTER 5: GROWTH AND COLONY STIMULATING FACTOR DRUGS IN DEVELOPMENT

• Epidermal Growth Factor Receptors
  • EGF Receptor Inhibitors
  • Other EGFR/HER-2 Targeting Drugs
• Vascular Endothelial Growth Factor VEGF in Angiogenesis
  • Angiogenesis Antibodies-Avastin and Lucentis
  • VEGF Antagonists Macugen, Multi-kinase Inhibitor Sutent, and Nexavar
  • VEGF Monoclonals and Inhibitors
  • VEGF Gene Therapy
• Hepatocyte Growth Factor
  • Antibodies, rHGF, Gene Therapy, and the MET Pathway
• Platelet-derived Growth Factor
  • Gleevec and other Protein Tyrosine Kinase Inhibitors
  • The Tyrosine Kinase Market
• Fibroblast Growth Factor
  • Recombinant FGF -1, Basic rFGF, r bFGF-2, FGF-20, and Monoclonals
• Transforming Growth Factor
  • TGF Binding Proteins, and Inhibitors of TGF Beta Signaling
• Insulin-like Growth Factor
  • Increlex and Iplex-rhIGF-1 and rhIGF-3
• Nerve Growth Factor
  • Monoclonals and Synthetic Neurotropin Like Agonist
• Keratinocyte Growth Factor
  • rhKGF for Oral Mucositis
• Connective Tissue Growth Factor (CTGF)
  • Monoclonal Against CTGF
• Colony Stimulating Factors (CSF)
  • Recombinant Human rhG-CSF
  • Antibodies Targeting the G -CSF Receptor and Gene Therapy
  • Non Immunological Cytokine-"Poietins" are a $10 Billion US Market
  • Erythropoietin
  • Thrombopoietin
  • Angiopoietin
• Bone Morphogenetic Proteins and Growth Differentiation Factors
  • rhBMP-2, rhBMP-7, and OPG
• Growth and Differentiation Factors GDF
  • rhGDF-5, rhBMP, Inhibition of Myostatin
• Neurotrophic Factors in Development
  • Neurturin, GDNF Gene Delivery, BDNF, CNTF
• Survival Factors as Drug Development Targets
  • Antisense to eIF-4E, Survivin
• Current Growth Factor Pipeline and Market
• The Cytokine/Growth Factor Market Revenues
• Nine Out of the Top Ten Blockbuster Drugs in 2006 were Cytokine and Growth Factor Related

CHAPTER 6: COMPANY PROFILES

• Anacor Pharmaceuticals
• Angiogenix
• Antisense Pharma
• BioMimetic
• Biopharm GmbH
• BioVex
• Cantabria
• Domantis
• ESBATech
• Nautilus Biotech
• Neovacs
• Pivotal BioSciences
• Renovo
• Scil Technology
• Uriach
• Vaccinex
• Xencor
• Yes Biotech

TABLE OF EXHIBITS

• Exhibit 2.1 Approved Immunotherapeutic Drugs Transferred to CDER
• Exhibit 2.2 Cytokine and Growth Factor Drug Revenues in 2006
• Exhibit 2.3 Worldwide Sales of FDA Approved Interferons in the US Market
• Exhibit 2.4 Mechanisms of Action for Interferon-β in MS
• Exhibit 2.5 Approved MS Interferon-β Drugs
• Exhibit 2.6 Interferon Drugs in Current Clinical Testing
• Exhibit 2.7 Combination Therapies Clinical Trials for RCC (2005)
• Exhibit 2.8 Molecular Model of Albuferon
• Exhibit 2.9 Structure of Human Interferon-ƒÁ
• Exhibit 2.10 Interleukin Drugs in Current Clinical Testing
• Exhibit 2.11 Pleiotropic Action of IL-6
• Exhibit 2.12 Antitumor Activity of Interleukin-21
• Exhibit 3.1 Status of UCB' s Cimzia Anti-TNF Monoclonal
• Exhibit 3.2 Neovacs' Pipeline
• Exhibit 3.3 Ligation of TRAIL-R2 Receptors by Monoclonal Antibody
• Exhibit 3.4 Configuration of Atacicept
• Exhibit 3.5 Sales of Selected FDA-Approved TNF Inhibitors
• Exhibit 3.6 Other TNF Family Drugs in Current Clinical Testing
• Exhibit 3.7 TNF-α Drugs in Current Clinical Testing
• Exhibit 4.1 A Schematic Diagram of a Chemokine
• Exhibit 4.2 Structure of Chemokine Receptors
• Exhibit 4.3 ChemoCentryx' s Chemokine Pipeline
• Exhibit 4.4 Biokine' s BKT-RP3 Modeling
• Exhibit 4.5 Chemokine Drugs in Clinical Testing
• Exhibit 5.1 Structural Formula of Tarceva (erlotinib)
• Exhibit 5.2 Structural Formula of Tyrphostin (AG1478)
• Exhibit 5.3 Structural Formula of Iressa (gefitinib)
• Exhibit 5.4 Structural Formula of Sutinib Malate
• Exhibit 5.5 Structural Formula of Gleevec (imatinib mesylate)
• Exhibit 5.6 TGF-β in Fibrotic Disease
• Exhibit 5.7 Combination Immunogene Therapy
• Exhibit 5.8 Trophic and Colony Stimulating Factors in Clinical Testing
• Exhibit 5.9 Ceregene' s Neurotrophic Factor Pipeline
• Exhibit 5.10 Growth Factor Drugs in Clinical Testing
• Exhibit 5.11 Forecast for 2010 Market Sector
• Exhibit 5.12 Nine out of the top ten drugs in 2005/2006 targeted Cytokines/ Growth Factors