Pipeline Insight: Small Molecule Targeted Cancer Therapies - New targets set to drive growth

Introduction

Small molecule targeted therapies represent a highly lucrative class of anticancer therapies with 12 drugs currently approved for various tumor types. This promise of high commercial rewards has driven considerable pipeline activity for small molecule targeted therapies within cancer.

Scope

• Examination of the small molecule targeted cancer therapies pipeline with in-depth clinical and commercial profiles of Phase III candidates
• Seven major pharmaceutical market sales forecasts for Phase III pipeline products through to 2019 with product-specific assumptions
• Segmentation and analysis of the current small molecule targeted cancer therapies pipeline by developmental phase, drug target and company
• Insight and analysis of market potential including commercial opportunity and discussion of unmet needs

Highlights

There are currently 288 small molecule targeted therapies in development for cancer. Single-target signal transduction inhibitors and multi-targeted inhibitors form the majority of the pipeline, accounting for 28% and 28% of the pipeline, respectively. These two classes each contain a number of agents with novel mechanisms of action.

Progress in understanding of how to target tyrosine kinases with small molecules has benefited oncology drug discovery. Efforts are continuing to develop small molecule inhibitors against other kinases that are more selective and capable of overcoming drug resistance. Around 30 distinct targets are currently being tested in Phase I clinical trials.

The late-phase small molecule therapies directed towards novel targets are forecast to generate sales of $3,635m by 2019 across the seven major markets. Abiraterone (Cougar Biotechnology/Johnson & Johnson) and BSI-201 (BiPar Sciences/Sanofi-Aventis) are forecast to achieve the highest sales by 2019.

Reasons to Purchase

• Identify key drugs and companies within the small molecule targeted cancer therapies pipeline based on sales forecasts and Datamonitor drug assessment
• Assess the shifting small molecule targeted cancer therapies market dynamic and how future treatment will incorporate pipeline products
• Identify licensing opportunities based on company portfolio and market needs

Overview 1
Catalyst 1
Summary 1
About Datamonitor Healthcare 2
About the Oncology pharmaceutical analysis team 2
Executive Summary 3
Strategic scoping and focus 3
Datamonitor insight into the small molecule molecular targeted therapy market 3
Related reports 5
Upcoming related reports 5
Table of Contents 6

1. Pipeline Overview and Dynamics 7
Key findings 7
Pipeline overview 7
Pipeline summary 7
There are 32 small molecule targeted therapies in late-phase development for cancer 7
Datamonitor forecasts 9
Single target signal transduction inhibitors and multi-targeted inhibitors dominate the current small molecule MTT pipeline 9
Comparative forecasts 10
Datamonitor drug assessment summary 12
Key companies involved in the biologic molecular targeted therapies pipeline 15
Pfizer 15
Novartis 17
Bristol-Myers Squibb 19
Key R&D company strategies 21
Developers of small molecule targeted therapies are maximizing their revenues through indication expansion across multiple tumor types 21
The development of companion diagnostics to improve chances of approval 21

2. Small molecule targeted cancer therapies - Market Potential 22
Key findings 22
Targeted therapies overview 22
Definition 22
Targeted therapies provide clues into the biology behind cancer 22
Conventional therapies are less cancer cell-specific 23
Increased specificity for targets could lead to the development of drugs with greater efficacy 23
Small molecules 23
Small molecules targeting tyrosine kinases have been a significant development in oncology drug discovery 23
Classification of pipeline products 24
Angiogenesis inhibitor/vascular disrupting agents 24
Angiogenesis is known to be aberrant in tumor cell proliferation 24
The process of angiogenesis 24
Angiogenesis inhibitors can target a number of pathways as viable antitumor agents 25
Three small molecule angiogenesis inhibitors exist on the market 26
Single-target signal transduction inhibitors 27
A plethora of potential targets exist along the signaling cascade 27
Three small molecule single target signal transduction have been approved in cancer 27
Multi-targeted inhibitors 28
Multi-targeted inhibitors have certain theoretical advantages over single targeted agents 28
The underlying mechanism of multi-targeted kinase inhibition is still unclear 28
Several multi-targeted inhibitors have been approved for cancer 29
Cell cycle and apoptosis targeted agents 30
Cell death can be induced via a number of different pathways 30
To date, only one apoptosis stimulator has reached the market 30
Immunomodulatory and immunoconjugated therapeutics 31
Research into immunomodulatory agents for cancer has been challenging owing to the complexities of the host-tumor relationship 31
There are two small molecule targeted immunomodulatory/immunoconjugated agents approved in oncology 31
Epigenetic modulators 32
Epigenetic dysregulation can contribute to tumor progression 32
There is one small molecule epigenetic modulator approved for oncology 33
Differences between biologic and small molecule targeted therapeutics 34

3. R&D Approach 35
Key findings 35
Clinical trial design for molecular targeted therapies 35
Patient selection 35
New generation compounds specific to tumor pathways are set to alter the traditional method of patient selection 35
More specific selection of patients in clinical trials may improve a drug's chances of commercial success and keep costs down 36
Sufficient follow-up is necessary to establish true clinical benefit 36
Clinical trial endpoints in oncology 36
Overall survival 37
Disease-free survival 37
Overall response rates 37
Progression-free survival 38
Disease control rate 38
Toxicity 38
Time to tumor progression 38

4. Pipeline Analysis & Forecasts: Angiogenesis Inhibitors and Vascular Disrupting Agents 39
Key findings 39
Overview of angiogenesis inhibitors 39
Pipeline summary 39
Late-phase pipeline of angiogenesis inhibitors and vascular-disrupting agents 39
Comparative forecasts 40
Definition of current comparator therapy 43
Sutent (sunitinib; Pfizer) 43
ASA404 (Antisoma/Novartis) 44
Drug overview 44
Drug profile 45
Key historical events 45
Clinical trial data 46
ASA404 is effective and well tolerated in NSCLC patients with both squamous and non-squamous histology 47
The addition of ASA404 to Taxotere does not have a significant impact on median survival in a Phase II study in castration-resistant prostate cancer 49
ASA404 fails its Phase III ATTRACT-1 trial in previously untreated NSCLC patients 50
SWOT analysis 51
Datamonitor drug assessment summary for ASA404 52
Clinical and commercial attractiveness 52
Failure of ATTRACT-1 trial comes as a serious blow to ASA404's chances of success in NSCLC patients with squamous cell histology 52
ASA404's combination with Taxotere will have to show very impressive results 53
Antisoma's partnership with Novartis will bolster ASA404's position in the cancer market 53
Forecasts to 2019 53
Cilengitide (Merck KGaA) 54
Drug overview 54
Drug profile 55
Key historical events 55
Clinical trial data 56
Cilengitide may offer added benefit to standard treatment for glioma 58
Cilengitide fails to confer a survival benefit over Taxotere in Stage IV NSCLC patients 59
SWOT analysis 60
Datamonitor drug assessment summary 61
Clinical and commercial attractiveness 62
Cilengitide is the only integrin antagonist in late-phase development for cancer 62
Selecting patients based on molecular markers could improve the chances of success 63
Fierce competition from Avastin could hamper uptake 63
Other targeted therapies could also pose a threat to cilengitide's commercial success 63
Intravenous formulation may be a disadvantage compared to Temodar 63
Merck KGaA's commercial expertise will assist in the commercialization of cilengitide 64
Forecasts to 2019 64

5. Pipeline Analysis & Forecasts: Cell cycle/ apoptosis targeted agents 65
Key findings 65
Overview of cell cycle/apoptosis targeted agents 65
Pipeline summary 65
Late-phase pipeline of cell cycle and apoptosis targeted agents 65
Comparative forecasts 66
Definition of current comparator therapy 72
Velcade (bortezomib; Takeda/Johnson & Johnson) 72
Alvocidib (flavopiridol; Sanofi-Aventis) 73
Drug overview 73
Drug profile 73
Key historical events 74
Clinical trial data 75
Optimization of alvocidib's dosing schedule has reawakened interest in the drug 75
Single-agent alvocidib induces responses in heavily pretreated CLL patients with unfavorable cytogenetics 76
Alvocidib has also shown promise in early stages studies in combination with fludarabine and Rituxan 77
SWOT analysis 77
Datamonitor drug assessment score card for alvocidib 78
Clinical and commercial attractiveness 79
Alvocidib has shown encouraging signs of activity in difficult-to-treat patients 79
Sanofi-Aventis will have to overturn negative perceptions of alvocidib's clinical development in CLL 80
Arzerra could prove to be a major competitor for alvocidib, given its more favorable toxicity profile 80
Forecasts to 2019 81
Abiraterone (CB-7630; Cougar Biotechnology/BTG/Johnson & Johnson) 81
Drug overview 82
Drug profile 82
Key historical events 82
Clinical trial data 83
Phase II results show abiraterone to confer encouraging efficacy in both chemotherapy-naïve and in heavily pretreated castration-resistant prostate cancer 84
SWOT analysis 87
Datamonitor drug assessment summary for abiraterone 88
Clinical and commercial attractiveness 89
Encouraging Phase II data have resulted in a media furor over abiraterone, starting with controversy over use of the term "hormone refractory" 89
Efficacy in a heavily pretreated patient population is striking in itself 90
Expansion into the first-line metastatic castration-resistant prostate cancer setting significantly increases abiraterone's commercial potential 91
Forecasts to 2019 91
BSI-201 (BiPar Sciences/Sanofi-Aventis) 92
Drug overview 92
Drug profile 93
Key historical events 94
Clinical trial data 95
BSI-201 has shown promising activity in its Phase II trial for triple-negative breast cancer 96
SWOT analysis 97
Datamonitor drug assessment summary for BSI-201 98
Clinical and commercial attractiveness 98
High potential to alter the treatment landscape for triple-negative breast cancer 98
BSI-201's mechanism of action could usher in a new generation of targeted PARP inhibitors in cancer 99
High unmet need in triple-negative breast cancer should assist in the commercial success of BSI-201 99
Fierce competition with several agents for a share of the triple-negative breast cancer market 99
Sanofi-Aventis's commercial expertise will bolster BSI-201's position in the market 99
Forecasts to 2019 99
Phenoxodiol (Marshall Edwards/Novogen) 100
Drug overview 100
Drug profile 101
Key historical events 101
Clinical trial data 102
The combination of phenoxodiol and cisplatin appears to be effective in ovarian cancer 103
SWOT analysis 104
Clinical and commercial attractiveness 105
Marshall Edwards's financial difficulties could affect the clinical development of phenoxodiol 105
Trabedersen (AP-12009; Antisense Pharma) 105
Drug overview 105
Drug profile 105
Key historical events 106
Clinical trial data 107
Trabedersen shows significant Phase II survival results in second-line glioma patients 107
SWOT analysis 109
Datamonitor drug assessment summary for trabedersen in 2010 109
Clinical and commercial attractiveness 110
Trabedersen's chances of approval are high if Phase III results are favorable 110
Trabedersen will be received with an air of skepticism due to past experiences with antisense oligonucleotides 111
Trabedersen will only realize its complete commercial potential with indication expansion 111
Competition from Avastin could restrict trabedersen's uptake for glioma 111
Securing a marketing partner will be crucial for trabedersen's success 112
Forecasts to 2019 112
Zibotentan (ZD-4054; AstraZeneca) 112
Drug overview 113
Drug profile 113
Key historical events 114
Clinical trial data 114
Phase II trial results show zibotentan to confer improved survival over placebo, with a possible effect on bone metastases 115
SWOT analysis 116
Datamonitor drug assessment summary for ZD-4054 117
Clinical and commercial attractiveness 118
Use of placebo as a comparator is controversial 118
Effect on bone metastases may result in lower overall cost of treatment 119
Xinlay has already failed where zibotentan is now being investigated 119
AstraZeneca has extensive experience in the prostate cancer market 119
Forecasts to 2019 119

6. Pipeline Analysis & Forecasts: Multi-targeted inhibitors 121
Key findings 121
Overview of multi-targeted inhibitors 121
Pipeline summary 121
Late-phase pipeline of small molecule multi-targeted inhibitors 121
Comparative forecasts 123
Definition of current comparator therapy 127
Gleevec/Glivec (imatinib; Novartis) 127
Enzastaurin (LY-31761; Eli Lilly) 128
Drug overview 128
Drug profile 129
Key historical events 129
Clinical trial data 130
Enzastaurin shows marginal single-agent activity in relapsed/refractory DLBCL 132
SWOT analysis 133
Datamonitor drug assessment summary for enzastaurin 134
Clinical and commercial attractiveness 135
The response rates in the Phase II trial are not very impressive 135
Enzastaurin may have to compete with Afinitor and Revlimid if approved as a maintenance therapy for DLBCL 136
Forecasts to 2019 136
Linifanib (ABT-869; Abbott) 137
Drug overview 137
Drug profile 137
Key historical events 138
Clinical trial data 139
Phase II results show linifanib to confer clinical benefit in both the first- and second-line treatment settings for advanced hepatocellular carcinoma 139
SWOT analysis 140
Datamonitor drug assessment score card for linifanib 141
Clinical and commercial attractiveness 142
By excluding second-line patients from the ongoing Phase III trial, linifanib could show equivalent or superior survival results to standard-of-care Nexavar in hepatocellular carcinoma 142
Other pipeline agents in development for hepatocellular carcinoma pose a significant threat to linifanib... 143
...therefore Abbott could also target alternative treatment settings or patient subgroups within hepatocellular carcinoma to differentiate linifanib 143
Forecasts to 2019 143
Masitinib (AB-1010; AB Science) 144
Drug overview 144
Drug profile 144
Key historical events 145
Clinical trial data 146
Phase II trial shows a first-line combination of Gemzar and masitinib to confer similar efficacy to Gemzar monotherapy and other Gemzar-based combinations in pancreatic cancer 147
Encouraging Phase II results for masitinib in first-line Gleevec-naïve gastrointestinal stromal tumors 148
SWOT analysis 149
Datamonitor drug assessment summary for masitinib 150
Clinical and commercial attractiveness 150
If Phase II results can be replicated in the ongoing Phase III study, then approval will be likely in pancreatic cancer 150
Masitinib should in theory confer greater efficacy alongside Gemzar than Tarceva due to inhibition of multiple pathways in pancreatic cancer 151
There is room for a more effective therapy than Gleevec if the ongoing Phase III trial for first-line GIST proves to be favorable 151
Competition from several high profile drugs in clinical development for front-line gastrointestinal stromal tumors 151
AB Science will need to price masitinib competitively in order to enhance its uptake 151
In order to optimize masitinib's commercial potential, AB Science should seek a partner experienced in the human oncology market 152
Forecasts to 2019 152
Midostaurin (PKC412; Novartis) 153
Drug overview 153
Drug profile 153
Key historical events 154
Clinical trial data 155
Midostaurin shows promising evidence of efficacy in AML patients with wild-type and mutant Flt3 155
SWOT analysis 157
Datamonitor drug assessment summary for midostaurin 157
Clinical and commercial attractiveness 158
Patients with Flt3 mutations represent a good target population for midostaurin 158
Midostaurin would benefit from a more convenient commercially available companion diagnostic 159
Novartis's capabilities in niche hematological indications will boost midostaurin's commercial potential 159
Forecasts to 2019 159
Perifosine (KRX-040; AEterna Zentaris/Keryx Biopharmaceuticals) 160
Drug overview 160
Drug profile 161
Key historical events 161
Clinical trial data 162
Phase I/II trial finds perifosine to be well tolerated in patients with advanced multiple myeloma 164
Phase II study shows perifosine to have encouraging activity in heavily pretreated metastatic colorectal cancer 166
SWOT analysis 167
Datamonitor drug assessment summary for perifosine 168
Clinical and commercial attractiveness 169
Perifosine will have to demonstrate a highly favorable toxicity and efficacy profile in its Phase III trial for CRC 169
Keryx's strategy of targeting heavily pretreated patients may increase its prospect of approval in CRC 170
Perifosine could face barriers to uptake in cost-conservative healthcare markets 170
Perifosine will face fierce competition from several agents in the late-phase colorectal cancer pipeline 170
Absence of a Big Pharma partner will restrict perifosine's success 170
Forecasts to 2019 171
PF-2341066 (Pfizer) 171
Drug overview 172
Drug profile 172
Key historical events 173
Clinical trial data 173
PF-2341066 appears to demonstrate encouraging clinical activity in NSCLC patients harboring the EML4-ALK translocation 174
SWOT analysis 176
Datamonitor drug assessment summary for PF-2341066 176
Clinical and commercial attractiveness 177
PF-2341066 offers the opportunity to optimize treatment of NSCLC 177
PF-2341066 will need to demonstrate superior efficacy over Taxotere or Alimta to encourage uptake 178
Pfizer's strategy to progress PF-2341066 straight into Phase III trials may be risky 178
PF-2341066's label could restrict its commercial potential 178
Pfizer's growing position in the oncology market will assist in PF-2341066's success 178
Forecasts to 2019 179
Zactima (vandetanib; AstraZeneca) 179
Drug overview 180
Drug profile 180
Key historical events 180
Clinical trial data 181
Zactima shows promising results in the treatment of thyroid cancer 184
Multiple Phase III trials for NSCLC underway 186
The combination of Zactima with Taxotere and with Iressa appeared to be well-tolerated in the second-line setting 187
Zactima fails to demonstrate superior efficacy over Tarceva in the ZEST trial 189
AstraZeneca withdraws filing for Zactima in combination with chemotherapy in NSCLC over a lack of survival benefits 190
Zactima is being examined as a monotherapy in the third-line treatment of NSCLC in the ZEPHYR study 191
SWOT analysis 191
Clinical and commercial attractiveness 192
The head-to-head trial against Tarceva in NSCLC was a high-risk strategy 192
High unmet need in NSCLC could have been profitable for Zactima 192
It is unclear how AstraZeneca will recover the development costs of the NSCLC trials 192
Zactima is in Phase III development for medullary thyroid cancer 193
Forecasts to 2019 193
XL-184 (Exelixis/ Bristol-Myers Squibb) 193
Drug overview 193
Drug profile 193
Key historical events 194
Clinical trial data 195
Little information is available on XL-184's clinical activity in medullary thyroid cancer 196
XL-184 demonstrates encouraging activity in second-line or higher glioma 197
SWOT analysis 199
Datamonitor drug assessment summary for XL-184 200
Clinical and commercial attractiveness 201
XL-184 could satisfy an unmet need in the treatment of thyroid cancer 201
Uncertainty over XL-184's effectiveness in thyroid cancer 201
Tolerability will be critical to XL-184's success in second-line or higher thyroid cancer 202
Indication expansion will be needed to recover clinical development for XL-184 202
Activity in glioma could increase the commercial potential of XL-184 202
Fierce competition from other late-phase pipeline drugs 202
Bristol-Myers Squibb's partnership with Exelixis will be crucial to XL-184's success 203
Forecasts to 2019 203

6. Pipeline Analysis & Forecasts: Single-target signal transduction inhibitors 204
Key findings 204
Overview of single-target signal transduction inhibitors 204
Pipeline summary 204
Late-phase pipeline of small molecule single-target signal transduction inhibitors 204
Comparative forecasts 204
Definition of current comparator therapy 207
Tarceva (erlotinib; OSI Pharmaceuticals/Genentech/Roche/Chugai) 207
OSI-906 (OSI Pharmaceuticals) 208
Drug overview 208
Drug profile 209
Key historical events 209
Clinical trial data 210
Phase I continuous dosing trial shows OSI-906 to be tolerable in advanced solid tumors 210
SWOT analysis 211
Clinical and commercial attractiveness 211
Lack of clinical trial data makes it difficult to assess OSI-906 211
PLX-4032 (Plexxikon/Roche) 212
Drug overview 212
Drug profile 212
Key historical events 213
Clinical trial data 214
Phase I trial shows early signs of efficacy in second-line metastatic melanoma 214
SWOT analysis 216
Datamonitor drug assessment summary for PLX-4032 217
Clinical and commercial attractiveness 217
PLX-4032 has the potential to treat a highly underserved population should its early signs of efficacy be reproduced in Phase III studies 217
Phase I results should be greeted with caution 218
Step towards more individualized therapies 218
PLX-4032 will be profitable for Plexxikon and Roche should Phase III trials be successful 218
Roche's marketing power will provide the necessary platform for PLX-4032's success 218
Forecasts to 2019 219

7. Innovative Early-Stage Approaches 220
Key findings 220
Overview of early-stage innovative projects 220
Aurora protein kinase 222
Kinesin-spindle protein (KIF11) 223
Mitogen activated protein kinase/ extracellular signal-regulated kinase (MEK) 224
The future of treatment with small molecule targeted therapies 224
Improvements in diagnostics and prognostic analysis will enhance cost-effectiveness of treatment 224
Enhanced preventative strategies will ease the disease burden 224
Increased understanding of cancer evolution should result in a large range of potential drug targets 224
Bibliography 226
Journals 226
Websites 234
Datamonitor reports 237
APPENDIX 239
Epidemiology forecasts 239
Product forecasts 239
About Datamonitor 242
About Datamonitor Healthcare 242
About the Disease analysis team 242
Datamonitor consulting 243
Disclaimer 243

TABLES

• Table: Late-phase pipeline of small molecule molecular targeted therapies (MTTs) for cancer, 2009
• Table: Sales forecasts for late-phase small molecule MTTs in the seven major markets ($m), 2010–19
• Table: Pfizer’s marketed and pipeline small molecule targeted therapy oncology portfolio, 2010
• Table: Novartis’s marketed and pipeline small molecule targeted therapy oncology portfolio 2010
• Table: Bristol-Myers Squibb’s marketed and pipeline small molecule targeted therapy oncology portfolio, 2010
• Table: Approved small molecule angiogenesis inhibitors, 2010
• Table: Approved small molecule single target signal transduction inhibitors, 2010
• Table: Approved small molecule multi-targeted inhibitors, 2010
• Table: Approved small molecule cell cycle/apoptosis targeted agents, 2010
• Table: Approved small molecule targeted immunomodulatory/immunoconjugated therapeutic, 2010
• Table: Approved small molecule targeted epigenetic modulator, 2010
• Table: Differences between biologic and small molecule molecular targeted therapies (MTTs) for cancer
• Table: Late-phase small molecule angiogenesis inhibitors/vascular-disrupting agents pipeline, 2010
• Table: Forecast assumptions for angiogenesis inhibitors and vascular disrupting agents in late phase development across the seven major markets, 2010 (1 of 2)
• Table: Sales forecasts small molecule angiogenesis inhibitors and vascular disrupting agents in late phase development for cancer in the seven major markets ($m), 2010–2019
• Table: Sutent – drug profile, 2010
• Table: ASA404 – drug profile, 2010
• Table: ASA404: key historical events, 2005–09
• Table: Clinical development of ASA404 in cancer, 2010
• Table: Sales forecast for ASA404 in cancer across the seven major markets ($m), 2010–2019
• Table: Cilengitide – drug profile, 2010
• Table: Cilengitide: key historical events, 1999–2009
• Table: Clinical development of cilengitide, 2010
• Table: Sales forecast for cilengitide in cancer across the seven major markets ($m), 2010–2019
• Table: Late-phase small molecule cell cycle/apoptosis targeted agents pipeline in cancer, 2010
• Table: Forecast assumptions for cell cycle/apoptosis targeted agents in late phase development across the seven major markets, 2010 (1 of 4)
• Table: Forecast assumptions for cell cycle/apoptosis targeted agents in late phase development across the seven major markets, 2010 (2 of 4)
• Table: Forecast assumptions for cell cycle/apoptosis targeted agents in late phase development across the seven major markets, 2010 (3 of 4)
• Table: Forecast assumptions for cell cycle/apoptosis targeted agents in late phase development across the seven major markets, 2010 (4 of 4)
• Table: Sales forecasts for cell cycle/apoptosis targeted agents in late-phase development for cancer in the seven major markets ($m), 2010–2019
• Table: Velcade – drug profile, 2010
• Table: Alvocidib – drug profile, 2010
• Table: Alvocidib: key historical events, 2004–2010
• Table: Clinical development of alvocidib in chronic lymphocytic leukemia (CLL), 2010
• Table: Phase I dose-escalating study of alvocidib in combination with chemotherapy in patients with indolent B-cell non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL) and mantle cell lymphoma
• Table: Sales forecast for alvocidib in cancer across the seven major markets ($m), 2010–2019
• Table: Abiraterone – drug profile, 2010
• Table: Abiraterone: key historical events, 2004–2010
• Table: Clinical development of abiraterone in cancer, 2010
• Table: Sales forecast for abiraterone in cancer across the seven major markets ($m), 2010–2019
• Table: BSI-201 – drug profile, 2010
• Table: BSI-201: key historical events, 2006–09
• Table: Clinical development of BSI-201 in cancer, 2010
• Table: Sales forecast for BSI-201 in cancer across the seven major markets ($m), 2010–2019
• Table: Phenoxodiol – drug profile, 2010
• Table: Phenoxodiol: key historical events, 1999–2010
• Table: Clinical development of phenoxodiol in cancer, 2010
• Table: Trabedersen – drug profile, 2010
• Table: Trabedersen: key historical events, 2002–09
• Table: Clinical development of trabedersen in cancer, 2010
• Table: Sales forecast for trabedersen in cancer across the seven major markets ($m), 2010–2019
• Table: ZD-4054 – drug profile, 2010
• Table: ZD-4054: key historical events, 2005–08
• Table: Clinical development of ZD-4054 in cancer, 2010
• Table: Sales forecast for ZD-4054 in cancer across the seven major markets ($m), 2010–2019
• Table: Late-phase small molecule multi- targeted pipeline, 2010
• Table: Forecast assumptions for multi-targeted inhibitors in late phase development across the seven major markets, 2010 (1 of 2)
• Table: Forecast assumptions for multi-targeted inhibitors in late phase development across the seven major markets, 2010 (2 of 3)
• Table: Forecast assumptions for multi-targeted inhibitors in late phase development across the seven major markets, 2010 (3 of 3)
• Table: Sales forecasts for multi-targeted inhibitors in late-phase development for cancer in the seven major markets ($m), 2010–19
• Table: Gleevec– drug profile, 2010
• Table: Enzastaurin – drug profile, 2010
• Table: Enzastaurin: key historical events, 2010
• Table: Clinical development of enzastaurin in cancer, 2010
• Table: Sales forecast for enzastaurin in cancer across the seven major markets ($m), 2010–2019
• Table: Linifanib – drug profile, 2010
• Table: Linifanib: key historical events
• Table: Clinical development of linifanib in cancer, 2010
• Table: Sales forecast for linifanib in cancer across the seven major markets ($m), 2010–2019
• Table: Masitinib – drug profile, 2010
• Table: Masitinib: key historical events, 2004–09
• Table: Clinical development of masitinib in cancer, 2010
• Table: Sales forecast for masitinib in cancer across the seven major markets ($m), 2010–2019
• Table: Midostaurin – drug profile, 2010
• Table: Midostaurin: key historical events, 2002–2010
• Table: Clinical development of midostaurin in acute myeloid leukemia, 2010
• Table: Sales forecast for midostaurin in cancer across the seven major markets ($m), 2010–2019
• Table: Perifosine– drug profile, 2010
• Table: Perifosine: key historical events, 1999-2010
• Table: Clinical development of perifosine in cancer, 2010
• Table: Phase I/II trial investigating the combination of perifosine and Velcade in heavily pretreated Hodgkin’s lymphoma patients; results for Velcade (bortezomib) relapsed or refractory patients
• Table: Updated results from a Phase I/II trial investigating the combination of perifosine and Velcade in heavily pretreated Hodgkin’s lymphoma patients
• Table: Sales forecast for perifosine in cancer across the seven major markets ($m), 2010–2019
• Table: PF-2341066 – drug profile, 2010
• Table: PF-2341066: key historical events, 2005–09
• Table: Clinical development of PF-2341066 in cancer, 2010
• Table: Sales forecast for PF-2341066 in cancer across the seven major markets ($m), 2010–2019
• Table: Zactima– drug profile, 2010
• Table: Zactima: key historical events, 2004–09
• Table: Clinical development of perifosine in cancer, 2009
• Table: Phase II results for Zactima monotherapy in metastatic hereditary medullary thyroid cancer
• Table: XL-184– drug profile, 2010
• Table: XL-184: key historical events, 2002-2010
• Table: Clinical development of XL-184 in cancer, 2010
• Table: Phase I study results for XL-184 in patients with medullary thyroid cancer
• Table: Sales forecast for XL-184 in cancer across the seven major markets ($m), 2010–2019
• Table: Late-phase small molecule single-target signal transduction inhibitors, 2010
• Table: Forecast assumptions for small molecule single target signal transduction inhibitors in late-phase development for cancer across the seven major markets, 2010
• Table: Sales forecasts small molecule single target signal transduction inhibitors in late phase development for cancer in the seven major markets ($m), 2010–19
• Table: Tarceva – drug profile, 2010
• Table: OSI-906 – drug profile, 2010
• Table: OSI-906: key historical events, 2006–09
• Table: Clinical development of OSI-906 in cancer, 2010
• Table: PLX-4032 – drug profile, 2010
• Table: PLX-4032: key historical events, 2006–2010
• Table: Clinical development of PLX-4032 in cancer, 2010
• Table: Sales forecast for PLX-4032 in cancer across the seven major markets ($m), 2010–2019
• Table: Top 10 Phase I/ II small molecule molecular targeted therapies drug targets, 2010
• Table: Datamonitor drug assessment parameters

FIGURES

• Figure: Small molecule MTTs pipeline split by development phase and drug class, 2010
• Figure: Datamonitor drug assessment summary for small molecule angiogenesis inhibitors and vascular-disrupting agents in late-phase development for cancer, 2010
• Figure: Datamonitor drug assessment summary for small molecule cell cycle/apoptosis targeted agents in late-phase development for cancer, 2010
• Figure: Datamonitor drug assessment summary for small molecule multi-targeted inhibitors in late-phase development for cancer, 2010
• Figure: Datamonitor drug assessment summary for small molecule single target signal transduction inhibitors in late-phase development for cancer, 2010
• Figure: The process of tumor angiogenesis
• Figure: Datamonitor drug assessment summary for angiogenesis inhibitors/vascular disrupting agents in late phase development for cancer, 2010
• Figure: Phase II results for ASA404 with chemotherapy in first-line NSCLC
• Figure: Phase Ib/II results for ASA404 with chemotherapy in first-line non-small cell lung cancer (NSCLC)
• Figure: Phase II study results for ASA404 in castration-resistant prostate cancer
• Figure: ASA404 – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for ASA404 in cancer, 2010
• Figure: Phase II study of cilengitide in recurrent glioma
• Figure: Phase II study examining cilengitide’s effects in combination with Temodar and radiation therapy in newly diagnosed glioma
• Figure: Phase II randomized study comparing cilengitide to Taxotere in NSCLC
• Figure: Cilengitide – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for cilengitide in cancer, 2010
• Figure: Datamonitor drug assessment summary for cell cycle/apoptosis targeted agents in development for cancer, 2010
• Figure: Summary of data from Phase II clinical trial of alvocidib in relapsed/refractory CLL
• Figure: Alvocidib – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for alvocidib in cancer, 2010
• Figure: Phase II COU-AA-002 results for first -line abiraterone plus prednisone in castration-resistant prostate cancer
• Figure: Phase II COU-AA-003 results for second -line abiraterone in castration-resistant prostate cancer
• Figure: Phase II COU-AA-004 results for second/third-line abiraterone and prednisone in metastatic castration-resistant prostate cancer
• Figure: Abiraterone – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for abiraterone in cancer, 2010
• Figure: Phase II randomized study evaluating BSI-201 in combination with Gemzar and carboplatin in first-line or higher triple-negative breast cancer
• Figure: BSI-201 – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for BSI-201 in cancer, 2010
• Figure: Phase II results for phenoxodiol plus chemotherapy in resistant/refractory ovarian cancer
• Figure: Phase IIb randomized study evaluating trabedersen monotherapy in second-line high-grade gliomas
• Figure: Trabedersen – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment for trabedersen in cancer, 2010
• Figure: Phase II study investigating first-line zibotentan in castration-resistant prostate cancer (CRPC) with bone metastases
• Figure: Zibotentan – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for ZD-4054 in cancer, 2010
• Figure: Datamonitor drug assessment summary for multi-targeted inhibitors in development for cancer, 2010
• Figure: Phase II results for Enzastaurin in relapsed/refractory diffuse large B-cell lymphoma (DLBCL)
• Figure: Enzastaurin – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for enzastaurin in cancer, 2010
• Figure: Phase II M06-879 results for first/second-line linifanib in unresectable or metastatic hepatocellular carcinoma
• Figure: Linifanib – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for linifanib in cancer, 2010
• Figure: Phase II results for first-line Gemzar and masitinib in locally advanced and metastatic pancreatic cancer
• Figure: Phase II results of first-line masitinib in Gleevec-naïve metastatic GIST
• Figure: Masitinib – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for masitinib in cancer, 2010
• Figure: Summary of data from Phase Ib study of midostaurin in newly-diagnosed acute myeloid leukemia
• Figure: Midostaurin – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for midostaurin in cancer, 2010
• Figure: Phase I/II results for perifosine and Velcade (bortezomib) with or without dexamethasone in relapsed/refractory multiple myeloma patients
• Figure: Phase II randomized study evaluating perifosine in combination with chemotherapy in second-or third-line metastatic colorectal cancer
• Figure: Perifosine – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for perifosine in cancer, 2010
• Figure: Phase II trial examining PF-2341066 in second-line or higher NSCLC patients with the EMl4-Alk translocation
• Figure: SWOT analysis for PF-2341066, 2010
• Figure: Datamonitor drug assessment summary for PF-2341066 in cancer, 2010
• Figure: Phase II results for Zactima in medullary thyroid cancer
• Figure: Phase II results for Zactima with carboplatin and paclitaxel in first-line non-small cell lung cancer (NSCLC)
• Figure: Phase II results for Zactima with Taxotere in second-line non-small cell lung cancer (NSCLC)
• Figure: Phase II results for Zactima versus Iressa in advanced non-small cell lung cancer (NSCLC)
• Figure: Phase III ZEST study examining second/third-line Zactima in advanced non-small cell lung cancer (NSCLC)
• Figure: Zactima – SWOT analysis in cancer, 2010
• Figure: Phase II study of XL-184 monotherapy in second-line or higher glioma
• Figure: XL-184 –SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for XL-184 in cancer, 2010
• Figure: Datamonitor drug assessment summary for single target signal transduction inhibitors in development for cancer, 2010
• Figure: Phase I trial examining OSI-906 in second-line or higher advanced solid tumors
• Figure: Phase I trial examining PLX-4032 in second-line or higher BRAF mutation-containing tumors
• Figure: PLX-4032 – SWOT analysis in cancer, 2010
• Figure: Datamonitor drug assessment summary for PLX-4032 in cancer, 2010
• Figure: Early-stage pipeline for small molecule molecular targeted therapies split by drug class, 2010
• Figure: Datamonitor drug assessment summary for cell cycle/apoptosis targeted agents in late-phase development for cancer, 2010