Kinase Therapeutics: Pipeline Assessment and Commercial Prospects - Overview

The number of kinase inhibitors entering clinical development has increased significantly in recent years. In addition to major pharmaceutical and biotech companies, an increasing number of emerging companies are focusing on their development. By 2020, small-molecule kinase inhibitors could generate annual revenues > $25 billion. This report assesses:R&D considerations specific to targeting kinases Current kinase inhibitor ...

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The number of kinase inhibitors entering clinical development has increased significantly in recent years. In addition to major pharmaceutical and biotech companies, an increasing number of emerging companies are focusing on their development. By 2020, small-molecule kinase inhibitors could generate annual revenues > $25 billion. This report assesses:

• R&D considerations specific to targeting kinases
• Current kinase inhibitor pipelines
• Commercial successes to date
• Near- and longer-term market outlook
• Corporate activities of firms involved with kinases

Kinases are now firmly established as a major class of drug targets. It was previously thought that kinases would be intractable drug targets due to the presumed need to compete with ATP and the assumption that sufficient selectivity would be unattainable. However, considerable progress has been made in understanding kinases and their function, and the past few years have seen a number of kinase inhibitors reach the market. Imatinib (Novartis’ Gleevec) is currently the most commercially successful, with sales reaching $3.7 billion in 2008. Erlotinib (OSI/Roche’s Tarceva) generated revenues of $1.1 billion the same year.

In recent years, there has been an explosion in the number of kinase inhibitors entering the clinic, and many more are in preclinical development. Kinase Therapeutics: Pipeline Assessment and Commercial Prospects identifies which kinase families and their respective members have attracted the greatest interest for therapeutic development and in which indications these kinases play a physiological or pathophysiological role and thus are most relevant for kinase inhibitor development. 
 

Biotechnology Industry

CHAPTER 1
KINASES
1.1. The Function of Kinases
1.2. The Human Kinome
1.3. Kinase Classification
AGC Family
CAMK Family
CMGC Family
CK1 Family
STE Family
TK Family
TKL Family
Atypical Protein Kinases
1.4. Kinase Structure
1.5. Kinases as Drug Targets

CHAPTER 2
INDICATIONS
2.1. Introduction
2.2. Cancer
2.3. Angiogenic Conditions
2.4. Inflammatory Diseases
2.5. Metabolic Disorders
2.6. CNS Conditions
2.7. Cardiovascular Disease

CHAPTER 3
R&D CONSIDERATIONS
3.1. Introduction
3.2. Kinase Selectivity
Profiling
Selectivity Profiles of Selected Inhibitors
How Selective?
3.3. Structural Features
X-Ray Structures and Multiple Conformations
3.4. Kinase Mutations
Bcr-Abl
Pharmacogenomics
3.5. Intellectual Property Issues

CHAPTER 4
CURRENT COMMERCIAL SUCCESSES
4.1. Introduction
4.2. Small Molecules
Overview
Abl Inhibitors
Gleevec (imatinib)
Tasigna (nilotinib) and Sprycel (dasatinib)
EGF Family Inhibitors
Tarceva (erlotinib) and Iressa (gefitinib)
Tykerb (lapatinib)
Multi-Kinase Inhibitors
Nexavar (sorafenib)
Sutent (sunitinib)
Palladia (toceranib) and Masivet (mastinib)
mTOR Inhibitors
Rapamune (sirolimus)
Torisel (temsirolimus), Afinitor/Certican (everolimus), Endeavor (zotarolimus)
Rho Inhibitor
Eril (fasudil)
4.3. Biological Agents

CHAPTER 5
CURRENT KINASE INHIBITOR PIPELINES
5.1. Introduction
5.2. Overview
5.3. Kinase Inhibitors in Phase III
Enzastaurin and Ruboxistaurin
Midostaurin
Pan-VEGFR Inhibitors
Votrient (pazopanib)
Cediranib
Motesanib
Axitinib
Aflibercept
Vandetanib
BIBW-2992
Neratinib
Pertuzumab
FGFR Inhibitors
BIBF-1120
Brivanib
Alvocidib
Bosutinib
Lestaurtinib
Ridaforolimus
Masitinib
BMS-907351
CP-690550
INCB-18424
5.4. Kinase Inhibitors in Phase II Development
5.5. Kinase Inhibitors in Phase I Development
5.6. Growth Factor Receptor Kinases
ErbB Family Kinases
ErbB2 and ErbB3
ErbB2 and EGFR
Pan-ErbB
Antibodies
FGF
IGF
VEGF
Multi-Kinase Inhibitors
Flt3
5.7. Popular Kinase Cascades
PI3K, Akt, mTOR, S6K
Perifosine
Triciribine
Archexin
Ras, Raf, MEK, ERK
Roche
Ardea Biosciences and Bayer
Array and AstraZeneca
JAK Family
5.8. Cell Cycle Inhibitors
Cyclic-Dependent Kinase (CDK)
Checkpoint Kinase (Chk)
Polo-Like Kinase (PLK)
BI-2536 and BI-6727
5.9. Popular Kinase Targets
Abl
p38
GSK-3
Protein Kinase C
Aurora
Broad Spectrum
Pan-Aurora
Aurora 1
Aurora 2
c-Met
Rho
JNK
Src Family
Kinases in Inflammatory Diseases
5.10. Other Kinases
Serine/Threonine Kinases
Tyrosine Kinases
Tyrosine-Like, CAMK, and Atypical Kinases
5.11. Outlook

CHAPTER 6
CORPORATE ACTIVITIES
6.1. Introduction
6.2. Major Companies
Abbott
Amgen
Astellas
AstraZeneca
Bayer
Boehringer Ingelheim
Bristol-Myers Squibb
Daiichi Sankyo
Eisai
Eli Lilly
GlaxoSmithKline
Johnson & Johnson
Merck & Co.
Merck Serono
Novartis
Pfizer
Roche
sanofi-aventis
Takeda
6.3. Specialist Companies
ACT Biotech
Advenchen
Array BioPharma
Avila Therapeutics
Calistoga Pharmaceuticals
Cellzome
Cyclacel Pharmaceuticals
Cylene Pharmaceuticals
Deciphera Pharmaceuticals
Emiliem
Exelixis
Intellikine
Kai Pharmaceuticals
Nerviano Medical Sciences
Oncalis
OSI Pharmaceuticals
Rigel Pharmaceuticals
S*Bio
Semafore Pharmaceuticals
SuperGen
TargeGen
Vertex Pharmaceuticals
6.4. Service Companies
Ambit Biosciences
Galapágos
Invitrogen
KINAXO Biotechnologies
ProQinase
SignalChem
Upstate (Millipore)

CHAPTER 7
MARKET OUTLOOK
7.1. Introduction
7.2. Near-Term Developments
7.3. Longer-Term Outlook

CHAPTER 8
EXPERT INTERVIEWS

REFERENCES

COMPANY INDEX WITH WEB ADDRESSES