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Strategic Outlook on Protein Kinase Inhibitors in Oncology

Published by: BioSeeker Group AB

Published: Feb. 20, 2006


Table of Contents



1 Executive Summary




2 Cancer Highlights




3 Methodology




4 Table of Contents

4.1 List of Boxes

4.2 List of Figures

4.3 List of Tables




5 Rationale for Development of Kinase Inhibitors in Oncology




6 Protein Kinase Targets - A Growing Family

6.1 Challenges in Protein Kinase Drug Discovery

6.1.1 Enabling Structure-Based Drug Design is the Key

6.1.2 Specific Kinase Inhibitors without Kinase Profiling?

6.2 Drugs according to Target

6.2.1 Cyclin-dependent Kinase Target Inhibitors

6.2.2 Aurora Kinase Target Inhibitors

6.2.3 Cell Cycle Checkpoint Target Controls Inhibitors

6.2.4 Tyrosine Kinase Receptor Inhibitors

6.2.5 Other Serine/Threonine Kinase Target Inhibitors

6.3 Dual or Multiple Kinase Inhibitor Analysis

6.3.1 Presentation of Drugs Targeting A to F Kinases

6.3.2 Presentation of Drugs Targeting G to T Kinases

6.4 Targets According to Indication

6.4.1 Breast Cancer

6.4.2 Prostate Cancer: What Cannot be Found in the ‘Groins’?

6.4.3 Lung Cancer: A Need for Improved Survival Rates

6.4.4 Colorectal Cancer: EGFR & VEGFR are Strong Targets but there are Others

6.4.5 Leukemia: Show Me the Power of PKI

6.4.6 Melanoma

6.4.7 Lymphoma: We Are In



7 Growing Competition in the Field

7.1 Big Pharma Outlook: The Race is On

7.1.1 Novartis Deals - Digs Deeper into Cell Cycle Inhibitors

7.1.2 AstraZeneca - Wheeling and Dealing

7.1.3 Pfizer’s Long Look at OSI Pharmaceuticals

7.1.4 GlaxoSmithKline Gains Momentum

7.2 Strategic Deals Creating Competitive Edge

7.2.1 Mergers

7.2.2 Astex - the PKI Switchboard

7.2.3 Big Pharma’s Darling



8 Current Protein Kinase Inhibitors in Therapy

8.1 Mechanism, Target and Developmental History

8.2 Approvals: Indications & Markets




9 Protein Kinase Inhibitors in Drug Development - A Progress Analysis

9.1 Progress Analysis - Breast Cancer

9.2 Progress Analysis - Prostate Cancer

9.3 Progress Analysis - Lung Cancer

9.4 Progress Analysis - Colorectal Cancer

9.5 Progress Analysis - Leukemia

9.6 Progress Analysis - Melanoma

9.7 Progress Analysis - Lymphoma




10 Selected Company profiles




11 Disclaimer




12 Drug Index




13 Company Index




List of Boxes

Box 1: The Power of Ambit’s Kinase Profiling

Box 2: Summary Terms of the Exelixis Transaction




List of Figures

Figure 1: Top 10 PKI Drug Developing Companies

Figure 2: Clinical Trial Distribution in Breast Cancer for PKI Drugs

Figure 3: Clinical Trial Distribution in Prostate Cancer for PKI Drugs

Figure 4: Clinical Trial Distribution in Lung Cancer for PKI Drugs

Figure 5: Clinical Trial Distribution in Colorectal Cancer for PKI Drugs

Figure 6: Clinical Trial Distribution in Leukemia for PKI Drugs

Figure 7: Clinical Trial Distribution in Melanoma for PKI Drugs

Figure 8: Clinical Trial Distribution in Lymphoma for PKI Drugs




List of Tables

Table 1: Overview of Targets in Commercial Development

Table 2: Cyclin-dependent Kinase Targets in Development

Table 3: Aurora Kinase Targets in Development

Table 4: Cell Cycle Checkpoint Targets in Development

Table 5: Epidermal Growth Factor Receptor Targets in Development

Table 6: FMS-like tyrosine kinases and their Synonyms

Table 7: Fms-related Tyrosine Kinase Targets in Development

Table 8: Platelet-derived Growth Factor Receptor Targets in Development

Table 9: Kinase Insert Domain Targets in Development

Table 10: Drugs in Development Targeting the PI3K/Akt/mTOR pathway

Table 11: Drugs in Development Targeting the Ras-Raf-MEK-ERK (ERK) pathway

Table 12: Serine/Threonine Kinase Inhibitors in Development

Table 13: Protein Kinase Targets in Clinical Trials for Breast Cancer

Table 14: Protein Kinase Targets in Clinical Trials for Prostate Cancer

Table 15: Protein Kinase Targets in Clinical Trials for Lung Cancer

Table 16: Protein Kinase Targets in Clinical Trials for Colorectal Cancer

Table 17: Protein Kinase Targets in Clinical Trials for Leukemia

Table 18: Protein Kinase Targets in Clinical Trials for Melanoma

Table 19: Protein Kinase Targets in Clinical Trials for Lymphoma

Table 20: Drugs in Therapy - Mechanism & Targets

Table 21: Current and Developmental History of PKI Drugs in Therapy

Table 22: Approvals: Indications & Markets

Table 23: Top 10 Drugs in Terms of Number of Clinical Trials

Table 24: List of Cancer Indications Targeted by Protein Kinase Inhibitors

Table 25: PKI Drugs in Development for Breast Cancer

Table 26: PKI Drugs in Development for Prostate Cancer

Table 27: PKI Drugs in Development for Lung Cancer

Table 28: PKI Drugs in Development for Colorectal Cancer

Table 29: PKI Drugs in Development for Leukemia

Table 30: PKI Drugs in Development for Melanoma

Table 31: PKI Drugs in Development for Lymphoma

Abstract


Introduction

Since the discovery that the v-Src oncogene encoded a protein kinase in 1978, kinases have become a targeted therapy strategy in oncology for the pharmaceutical industry. The perfect date between Gleevec and Chronic Myeloid Leukemia (CML) will be hard to achieve by other inhibitors currently in development, because of CMLïs strong link to a sole pathogenic event - the Philadelphia chromosome. Thus, it is expected that multiple inhibitors may have to be used together to effect higher cure rates in cancers with multiple genetic abnormalities.

Scope of this report

Drugs according to protein kinase target; Dual or multiple kinase inhibitor analysis
Targets according to indication
Competitive landscape assessment
Protein kinase inhibitors on market
Thorough review of the seven largest cancer indications in the field of protein kinase inhibitors

Research and analysis highlights

The number of protein kinase inhibitor (PKI) drugs has risen sharply, as the number of targets. The fiercest competition in PKI drug development is found in breast, lung, leukemia, prostate, and colorectal cancer. Several big pharma companies are out hunting for promising technology and drugs to complement their internal pipeline.

Key reasons to read this report

Understand the clinical and strategic challenges to the commercialization of protein kinase inhibitor treatments
Assess opportunities and risks for the continued development of innovative developmental treatments
Adopt knowledge from this analysis to drive strategic planning decisions in oncology drug development

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