1. www.visiongain.com Contents 1.1 Global Melanoma Drugs: Market Overview 1.2 Global Melanoma Drugs Market Segmentation 1.3 Why You Should Read This Report 1.4 How This Report Delivers 1.5 Key Questions Answered By This Analytical Report 1.6 Who Is This Report For? 1.7 Methodology 1.8 Frequently Asked Questions (FAQ) 1.9 Associated Reports 1.10 About Visiongain 2.1 Cancer: Physiology, Causes, And Effects 2.1.1 Uncontrolled Growth 2.1.2 Dedifferentiation 2.1.3 Invasiveness And Metastasis 2.1.4 Causes Of Cancer 2.2 Melanoma: A Brief Introduction 2.2.1 Causes Of Melanoma 2.2.2 Symptoms And Appearances Of Melanoma 2.3 Stages Of Melanoma 2.3.1 Early Stage Melanoma 2.3.2 Medium Stage Melanoma 2.3.3 Advanced Melanoma 2.4 The Incidence and Outlook for Melanoma Global Trends 2.5 Surgery As A Treatment For Melanoma 2.6 The Use Of Radiotherapy In Melanoma Treatment 1. Report Overview 2. An Introduction to Cancer, Melanoma, and Melanoma Treatments

2. www.visiongain.com Contents 2.7 Drug Treatments In Melanoma 2.7.1 Traditional Chemotherapy 2.7.2 Immunotherapy 2.7.2.1 Monoclonal Antibodies (mAbs) 2.7.2.2 Cancer Vaccines 2.7.2.3 Non-Specific Immunotherapies 2.8 Market Definition 3.1 Global Melanoma Drugs: Market Overview 3.1.1 Categorisation Of The Global Melanoma Drugs Market 3.2 The Global Melanoma Market In 2013 3.2.1 Market Dominance Of Immunotherapeutic Drugs And Targeted Therapies 3.3 Global Melanoma Drugs: Market Forecast 2014-2024 3.3.1 Market Sectors That Will Drive Growth 3.3.2 Global Melanoma Drugs Market - Changing Market Shares By Sector 2014-2024 4.1 The Global Market For Melanoma Kinase Inhibitors, 2013 4.1.1 Melanoma Kinase Inhibitors: Global Market Forecast 2014-2024 4.1.2 Melanoma Kinase Inhibitors - Changing Market Shares By Leading Drugs 2014-2024 4.2 Dabrafenib (Tafinlar) GlaxoSmithKline 4.2.1 Dabrafenib (Tafinlar) Sales Forecast, 2014-2024 4.3 Trametinib (Mekinist) GlaxoSmithKline 4.3.1 Trametinib (Mekinist) Sales Forecast 2014-2024 4.4 Vemurafenib (Zelboraf) Roche/ Genentech/ Chugai/ Daiichi Sankyo 4.4.1 Vemurafenib (Zelboraf) Historical Sales Analysis, 2011-2013 3. World Melanoma Drugs Market 2014-2024 4. Kinase Inhibitors For Melanoma: World Market Analysis and Forecast, 2014-2024 3. www.visiongain.com Contents 4.4.2 Vemurafenib (Zelboraf) Sales Forecast 2014-2024 4.5 The Market For Other Kinase Inhibitors In Melanoma 4.5.1 Other Kinase Inhibitors Sales Forecast 2014-2024 5.1 The Global Market For Immunotherapeutic Agents In Melanoma, 2013 5.1.1 Melanoma Immunotherapeutic Agents: Global Market Forecast 2014-2024 5.1.2 Melanoma Immunotherapeutic Agents - Changing Market Shares By Leading Drugs 2014-2024 5.2 Ipilimumab (Yervoy) Bristol Myers Squibb 5.2.1 Ipilimumab (Yervoy) Historical Sales Analysis, 2011-2013 5.2.2 Ipilimumab (Yervoy) Sales Forecast 2014-2024 5.3 PegIntron (Peginterferon Alpha-2b; Sylatron, IntronA) Merck 5.3.1 PegIntron Historical Sales Analysis, 2011-2013 5.3.2 PegIntron Sales Forecast 2014-2024 5.4 Proleukin (Aldesleukin) Prometheus Laboratories/ Novartis 5.4.1 Proleukin (Aldesleukin) Historical Sales Analysis, 2011-2013 5.4.2 Proleukin (Aldesleukin) Sales Forecast 2014-2024 5.5 Keytruda (Pembrolizumab) - Merck 5.5.1 Patent Disputes Over Keytruda 5.5.2 Keytruda (Pembrolizumab) Sales Forecast 2014-2024 5.6 The Market For Other Immunotherapeutic Agents In Melanoma 5.6.1 Other Immunotherapeutic Agents Sales Forecast 2014-2024 6.1 The Global Market For Melanoma Chemotherapeutic Agents, 2013 5. Immunotherapeutic Agents For Melanoma: World Market Analysis and Forecast, 2014-2024 6. Chemotherapeutic Agents For Melanoma: World Market Analysis and Forecast, 2014-2024 4. www.visiongain.com Contents 6.1.1 Melanoma Chemotherapeutic Agents: Global Market Forecast 2014-2024 6.2 Dacarbazine (DTIC-Dome) - Bayer 6.2.1 Possible Combination Therapies Involving Dacarbazine 6.3 Temodar/Temodal (Temozolomide) Merck 6.3.1 Temodar/Temodal (Temozolomide) Historical Sales Analysis, 2011-2013 6.3.2 Temodar/Temodal (Temozolomide) Sales Forecast 2014-2024 6.4 Other Chemotherapeutic Agents In Melanoma Treatment 6.4.1 Cisplatin (Platinol) 6.4.1.1 Cisplatin (Platinol) Historical Sales Analysis, 2010-2012 6.4.2 Fotemustine 6.4.3 Bleomycin (Blenoxane) 6.4.4 Other Chemotherapeutic Agents Sales Forecast 2014-2024 7.1 The Melanoma Drugs Market By Region 7.1.1 The Global Distribution of Melanoma Drugs In 2013 7.2 Leading National Markets: Forecast 2014-2024 7.2.1 Changing Market Shares By Region, 2014-2024 7.3 Regional Melanoma Drugs Markets: Analysis And Forecasts, 2014-2024 7.4 United States: The Largest Melanoma Drug Market 7.4.1 US Melanoma Drugs Market: Market Forecast 2014-2024 7.5 The EU5 Markets: Growth Expected In Each Country 7.5.1 EU5 Melanoma Drugs Market: Market Forecast 2014-2024 7.5.1.1 EU5 Markets: Changing Market Shares By Country, 2014-2024 7.5.2 Germany: New Reforms To Medicinal Pricing May Impact Market Entry 7.5.2.1 German Melanoma Drugs Market: Market Forecast 2014-2024 7.5.3 France: Changing Drug Approval Process May Delay Regulatory Submissions 7.5.3.1 French Melanoma Drugs Market: Market Forecast 2014-2024 7.5.4 UK: Cost-Effectiveness Measures Impacting Growth 7. Leading National Markets for Melanoma Drugs, 2014-2024 5. www.visiongain.com Contents 7.5.4.1 UK Melanoma Drugs Market: Market Forecast 2014-2024 7.5.5 Italy: Economic Recovery To Boost Future Of Oncology 7.5.5.1 Italian Melanoma Drugs Market: Market Forecast 2014-2024 7.5.6 Spain: High Level Of Patient Needs Will Counter Healthcare Rationalisation Measures 7.5.6.1 Spain Melanoma Drugs Market: Market Forecast 2014-2024 7.6 Australia: Highest Melanoma Incidence Rate Globally 7.6.1 Australian Melanoma Drugs Market: Market Forecast 2014-2024 7.7 Japan: Openness To Innovation Will Drive Revenue Increase 7.7.1 Japanese Melanoma Drugs Market: Market Forecast 2014-2024 7.8 China: Heavy Reliance On Traditional Herbal Remedies 7.8.1 Chinese Melanoma Drugs Market: Market Forecast 2014-2024 7.9 India: Contrasting Effects Of A Growing Population And Weak IP Protection 7.9.1 Indian Melanoma Drugs Market: Market Forecast 2014-2024 7.10 Brazil: Political Mandates And Economic Development Will Stimulate Growth 7.10.1 Brazilian Melanoma Drugs Market: Market Forecast 2014-2024 7.11 Turkey: Population Growth And Migration Will Be Tools For Growth 7.11.1 Turkish Melanoma Drugs Market: Market Forecast 2014-2024 7.12 Russia: High Income Nation With Low Per-Capita Healthcare Spending 7.12.1 Russian Melanoma Drugs Market: Market Forecast 2014-2024 7.13 Rest of the World 7.13.1 Rest of the World Melanoma Drugs Market: Market Forecast 2014-2024 8.1 Melanoma Drugs Market: A Highly Dynamic Market Space 8.2 Bayer AG 8.2.1 Bayer Oncology Drug Portfolio, 2014 8.2.2 Bayer Oncology Drug Pipeline, 2014 8.3 Bristol Myers Squibb 8.3.1 Bristol Myers Squibb: Oncology Drug Portfolio, 2014 8. Leading Companies In The Melanoma Drugs Market, 2014 6. www.visiongain.com Contents 8.3.2 Bristol Myers Squibb: Oncology Development Pipeline, 2014 8.4 GlaxoSmithKline (GSK) 8.4.1 GSK: Oncology Drug Portfolio, 2014 8.4.2 GSK: Oncology Development Pipeline, 2014 8.4.3 GSK Asset Swap with Novartis to Restructure Consumer Health 8.5 Merck 8.5.1 Merck: Oncology Drugs Portfolio, 2014 8.5.2 Merck: Oncology Development Pipeline, 2014 8.6 Prometheus Laboratories 8.6.1 Prometheus Laboratories: Oncology Portfolio, 2014 8.7 Roche 8.7.1 Roche: Oncology Portfolio, 2014 8.7.2 Roche: Oncology Development Pipeline, 2014 9.1 Innovative Products Currently In Development Will Drive Growth 9.1.1 Co-Developments And Collaborations Are Crucial For Market Growth 9.2 Developmental Pipeline - Kinase Inhibitors For Melanoma, 2014 9.2.1 Binimetinib (MEK162) Novartis 9.2.1.1 Binimetinib (MEK162) Sales Forecast 2014-2024 9.2.2 Cobimetinib - Exelixis /Genentech/ Roche 9.2.2.1 Co-Development And Licensing Agreements For Cobimetinib 9.2.2.2 Clinical Trials And Development Efforts For Cobimetinib 9.2.2.3 Cobimetinib Sales Forecast 2014-2024 9.2.3 Encorafenib (LGX818) - Novartis 9.2.4 Tasigna (Nilotinib) - Novartis 9.2.4.1 Tasigna - Indications And Market Exclusivity 9.2.4.2 Tasigna In Melanoma 9.2.4.3 Tasigna (Nilotinib) Sales Forecast 2014-2024 9. Melanoma Drugs: R&D Pipeline, 2014-2024 7. www.visiongain.com Contents 9.3 Developmental Pipeline - Immunotherapeutic Agents In Melanoma, 2014 9.3.1 Genasense (Oblimersen Sodium) - Genta Incorporated 9.3.2 INCB024360 Incyte Corporation 9.3.3 MEDI4736 AstraZeneca/ MedImmune 9.3.4 MPDL3280A Roche/Genentech 9.3.5 Nivolumab (Opdivo) Bristol Myers Squibb/ Ono Pharmaceutical 9.3.5.1 Nivolumab (Opdivo) Sales Forecast 2014-2024 9.4 Developmental Pipeline - Vaccine Therapies In Melanoma, 2014 9.4.1 Astuprotimut-R (MAGE-A3 ASCI) - GlaxoSmithKline 9.4.1.1 Clinical Trials And Development Efforts For Astuprotimut 9.4.2 CDX-1401 Celldex Therapeutics 9.4.3 Talimogene Laherparepvec (T-Vec) - Amgen 9.4.3.1 Clinical Trials And Development Efforts For T-Vec 9.4.3.2 Talimogene Laherparepvec (T-Vec) Sales Forecast 2014-2024 9.5 Developmental Pipeline - Genetic Therapies In Melanoma, 2014 9.5.1 Allovectin-7 (Velimogene Aliplasmid) - Vical Incorporated 9.5.1.1 Allovectin-7 Trial Setbacks And Efficacy Issues 9.5.2 Dorgenmeltucel-L NewLink Genetics Corporation 9.5.2.1 Clinical Trials And Development Efforts For Dorgenmeltucel-L 9.6 Developmental Pipeline - Other Therapies In Melanoma, 2014 9.6.1 Abraxane - Celgene Corporation 9.6.1.1 Clinical Trials And Development Efforts For Abraxane 9.6.1.2 Abraxane Sales Forecast 2014-2024 9.6.2 Autologous Dendritic Cell-Tumour Cell Immunotherapy NeoStem 10.1 Market Factors Influencing The Melanoma Drugs Market 10.2 SWOT Analysis Of The Melanoma Drugs Market, 2014-2024 10. Qualitative Analysis for the Global Melanoma Drugs Market, 2014-2024 8. www.visiongain.com Contents 10.2.1 Strengths 10.2.1.1 Promising Pipeline Candidates Expected To Boost Product Choice And Competitiveness 10.2.1.2 Stratifying Patients Offers Clinical and Commercial Benefits 10.2.1.3 Improved Patient Compliance Offer Added Incentive For Growth 10.2.2 Weaknesses 10.2.2.1 Disease Recurrence And Low Disease Free Survival May Hinder Investments 10.2.2.2 High Development Costs Making Break-Even A Bigger Challenge For Marketed Drugs 10.2.2.3 The Complexity Of Melanomas Aetiology 10.2.3 Opportunities 10.2.3.1 Rising Melanoma Incidence Amidst A Rising Global Population Will Stimulate Growth 10.2.3.2 A Shift Towards Personalisation 10.2.3.3 Combination Therapies Bring Additive Benefits 10.2.3.4 Commercial Success Leveraged By Clinical Benefit 10.2.4 Threats 10.2.4.1 Inadequate Reimbursement Levels: Drug Pricing Creating Constraints On Market Growth 10.2.4.2 Melanoma Drugs Face The Prospect Of Generic Erosion Over Time 10.3 Porters Five Force Analysis Of The Melanoma Drugs Market, 2014-2024 10.3.1 Threat Of New Entrants: Medium 10.3.2 Threat Of Substitutes: Low 10.3.3 Power Of Suppliers: Medium 10.3.4 Power Of Buyers: Low 10.3.5 Rivalry Among Competitors: Medium 9. www.visiongain.com Contents 11.1 Interview With Dr Jean-Pierre Bizzari, Global Head Of Oncology, Celgene Corporation 11.1.1 Targeted Therapies And Immune Checkpoints Are Areas For Accelerated Development 11.1.2 The Economic Implications Of Patient Segmentation And Targeted Therapies 11.1.3 On The Possible Combination Between Celgenes Abraxane And Bristol Myers Squibbs Nivolumab 11.1.4 On Celgenes Strategy For Success In Oncology 11.1.5 On The Current Challenges In Oncology And The Possible Solutions To Be Implemented 11.1.6 On Work Being Done to Map Signalling Pathways And Exploit Cellular Mechanisms For Drug Development 11.1.7 The Future Impact Of Regulatory Hurdles and Trial Design On Survival Advantage 11.2 Interview With Dr Rosalie M. Luiten PhD, Head of the Laboratory of Experimental Dermatology, Dept of Dermatology, Academic Medical Center, University of Amsterdam 11.2.1 Stages Of Melanoma And The Currently Available Treatment Options 11.2.2 Recent Developments In Targeted Therapies For Melanoma 11.2.3 Combination Therapies And The Challenge To Increase Durable Response Rate 11.2.4 On The Current Treatment Options For Early Stage Melanoma 11.2.5 On The Rising Popularity Of Immune Checkpoint Blockade In Oncology 11.2.6 Monobenzone Therapy And Its Potential Use As A Melanoma Therapy 11.2.7 On The Interactions Between Monobenzone And Immune Activating Compounds 11.2.8 Future Plans For Monobenzone Therapy As A Melanoma Treatment 11.2.9 On The Link Between Vitiligo And Melanoma 11.2.10 On The Future Trend Of Per-Patient Treatment Approaches To Melanoma 11. Expert Opinions from Our Primary Research 10. www.visiongain.com Contents 12.1 Overview Of Current Market Conditions And Market Forecast, 2013-2024 12.2 The US To Remain As The Largest Market 12.3 Australia And Evolving Markets In Countries Such As Brazil And Turkey Will Stimulate Growth 12.4 Personalisation And Targeted Treatments Will Dominate 12.5 Strong Development Pipeline Will Be Crucial To Future Growth 12. Conclusions 11. Page 81www.visiongain.com Melanoma Drugs Market Forecast 2014-2024: Opportunities For Leading Companies 5.3.2 PegIntron Sales Forecast 2014-2024 Visiongain forecasts PegIntron sales for Merck to improve over the coming years. We estimate that ~20% of the sales revenue from PegIntron in 2013 was derived from its use as a treatment for melanoma. Over the coming years, we predict that the sales of the drug will increase steadily as healthcare providers increasingly favour biological drugs. These healthcare bodies will continue to use PegIntron for patients diagnosed with melanoma over the next few years. Merck expects the US patent for its conjugate PegIntron to expire in 2015 while the mature IFN-alphas US patent expires in 2020. Despite US patent expiration, Visiongain expects biosimilar competition not to massively impact on the sales of the drug over the forecast period. However, we expect more efficacious therapies to cannibalise the market share for PegIntron in the melanoma market. We forecast sales of PegIntron/Sylatron for use in the treatment of melanoma patients to increase from $99m in 2013 to $114m in 2015 at high single digit AGRs. However, lost of patent expiry for conjugate PegIntron will affect the growth rate slightly from 2015. Nonetheless, sales of the drug will continue to grow to 2018 when it will reach $128m (Table 5.8 and Figure 5.9), at a CAGR of 5.3% between 2013 and 2018. Sales growth will continue onwards to 2024, albeit at low AGRs, when sales of the drug will reach $139m. The introduction of alternative therapies into the market will contribute to the declining AGR in the second half of the forecast period, visiongain notes. Table 5.8 PegIntron (Sylatron): Sales Forecast ($m, AGR%, CAGR%), 2013-2024 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 PegIntron ($m) 99 106 114 119 124 128 132 135 136 138 138 139 AGR (%) 6.5 8.0 4.5 4.0 3.5 2.5 2.5 1.0 1.0 0.5 0.5 CAGR (%) 2013-18 CAGR (%) 2013-24 5.3 2018-24 1.3 3.1 Source: Visiongain 2014 Note that forecast accounts only for the sales of the drug for use in melanoma 12. Page 123www.visiongain.com Melanoma Drugs Market Forecast 2014-2024: Opportunities For Leading Companies Figure 7.18 The UK Melanoma Drugs Market: Market Forecast ($m, AGR%), 2013-2024 We forecast the market for melanoma drugs in the UK to rise from $83m in 2013 to $113m in 2018, with a CAGR of 6.2% between 2013 and 2018 (Table 7.16 and Figure 7.18). As the stringent cost- effectiveness measures are gradually relaxed, we expect the melanoma market in the UK to continue its growth to 2024 when it will reach $203m, rising with a CAGR of 10.3% in the second half of the forecast period (Table 7.16 and Figure 7.18). 7.5.5 Italy: Economic Recovery To Boost Future Of Oncology The market for melanoma drugs in Italy was valued at $51m in 2013, accounting for 13.4% of the total EU5 market (Table 7.17). The Italian climate changes dramatically from the cold alpine regions in the North, to the subtropical areas in the south. This leads to varying ultraviolet irradiation, with a North to South increasing trend. The incidence of malignant melanoma in the Caucasian population is reported to generally increase as the latitude decreases. 0 2 4 6 8 10 12 0 50 100 150 200 250 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 AGR(%) MarketSize($m) Year Market Size ($m) AGR (%) Source: Visiongain 2014 13. Page 155www.visiongain.com Melanoma Drugs Market Forecast 2014-2024: Opportunities For Leading Companies Table 8.11 Merck: Oncology Portfolio, 2014 Product Description Indication Temodar (Temozolomide) Alkylating agent Treatment for certain types of brain tumours Emend (Aprepitant) Substance P antagonist Prevention of chemotherapy-induced and post-operative nausea and vomiting PegIntron (Peginterferon alpha-2b) Interferon Melanoma with microcopic or gross nodal involvement Pembrolizumab (Keytruda) PD-1 pathway inhibitor Melanoma Temozolomide is an alkylation agent for the treatment of glioblastoma multiforme an aggressive brain tumour. Temozolomide has also been used for treating melanoma as well as being used for the treatment of oligodendroglioma brain tumours in some countries. 8.5.2 Merck: Oncology Development Pipeline, 2014 Merck currently has a number of drugs under investigation for oncology indications. One of these is MK-8109 (Vintafolide), an investigational cancer candidate that is under review by the EMA. As part of an exclusive license agreement with Endocyte Inc, Merck is responsible for the development and worldwide commercialisation of Vintafolide in oncology. The EMA was reported to have accepted the MAA filings for vintafolide and Endocytes investigational companion diagnostic imaging agent, etarfolatide, for the targeted treatment of patients with folate-receptor positive platinum-resistant ovarian cancer in combination with pegylated liposomal doxorubicin. Both etarfolatide and vintafolide are said to have been granted orphan drug status by the EC; with vintafolide reported to have entered Phase 3 development in the US. Other drugs being investigated by Merck for cancer indications include MK-0646 (dalotuzumab) and MK-2206 (Table 8.12). Source: Merck 2014; Visiongain 2014 14. Page 167www.visiongain.com Melanoma Drugs Market Forecast 2014-2024: Opportunities For Leading Companies demonstrated excellent efficacy in early stage melanoma trials. Once on the market, cobimetinib will cannibalise market share of some of the already-launch kinase inhibitors to reach sales of $538m in 2024, with CAGR of 28.6% between 2015 and 2024 (Table 9.4 and Figure 9.2). Table 9.4 Cobimetinib: Sales Forecast ($m, AGR%, CAGR%), 2013-2024 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 Cobimetinib ($m) 0 0 56 130 221 318 385 435 483 510 527 538 AGR (%) 133.0 69.2 43.9 21.1 13.0 11.0 5.6 3.5 2.0 CAGR (%) 2015-24 28.6 Figure 9.2 Cobimetinib: Sales Forecast ($m, AGR%), 2013-2024 9.2.3 Encorafenib (LGX818) - Novartis Encorafenib (LGX818) is a BRAF inhibitor being developed by Novartis for treating melanoma and other cancers. Novartis describe LGX818 as a more efficacious option to Roches Zelboraf, with a better therapeutic window. Phase 1 trial data was reported to have demonstrated 100% disease 0 20 40 60 80 100 120 140 0 100 200 300 400 500 600 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 AGR(%) Revenue($m) Year Revenue ($m) AGR (%) Source: Visiongain 2014 Source: Visiongain 2014