Japan Pharma Outlook 2015: 2015 –Year to Watch out for Authorized Generics (AGs), Biosimilars and Overseas Strategic Initiatives

Table of Contents

2015 -Year tWatch out for Authorized Generics (AGs), Biosimilars and Overseas Strategic Initiatives

Company Analysis:
Astellas - Xtandi uptake in Pre-chemPC, Isavuconazole US approval & Uptake will provide cushion tNext batch of innovation (Roxadustat, CMV vaccine, ASP8273)!
Xtandi- Xtandi's early stage clinical data in HER2 positive, HR+ve, AR +ve Breast cancer and Data from TERRAIN/STRIVE study in early PC will drive Xtandi momentum in 2015, while PhIII data read out of ARN-509 from SPARTAN study is the key near term threat
Isavuconazole: Our view on US approval and Uptake
Myrbetriq: Myrbetriq uptake in OAB market - a blockbuster potential likely- EB178 (FDC/combof Solifenacin+ Mirabegron) combination - Next Batch of Innovation
Roxadustat- Can change the current treatment paradigm mainly in CKD-NDPatients- AKB-6548 is the key competitor
Key advantage over current EPO
Biosimilar EPis not a threat
Pipeline HIF inhibitors and clinical data comparison
ASP-8273 (Ph 1, Irreversible mutant selective EGFR inhibitor)
Evolocumab
Table 1: Deals done by Astellas in 2013, 2014
Table 2: Pipeline Early stage Androgen Receptor antagonist
Table 3: Competitive landscape for Antifungals
Table 4: Competitive landscapes for OAB drugs
Table 5: Pipeline HIF alpha stabilizer- AKEBIA AKB-6548 is closest competitor
Table 6: Competitive landscape- Anti PCSK9 MAB- ALIROCUMAB vs. EVOLOCUMAB
Chart: 1, 2 - Current and Future use of anti androgens in treatment of Prostate Cancer Chugai - Alectinib, ACE910 Global Success - Next Growth Driver!

Chugai's - Breast Cancer Franchisee: Breast Cancer Franchise-
Perjeta will be the key growth driver for the franchisee-not Kadcyla -
In long term, Perjeta + Herceptin + Chemwill be the standard of care vs. currently Herceptin + chemo. Kadcyla will cater 2nd line market, while data from APHINITY trial in 2016 will decide Perjeta + Herceptin use for adjuvant setting in Breast cancer
Failure of MARIANNE Study further increases threat of Herceptin biosimilar
Chugai's NSCLC franchisee:
MPDL3280A (anti-PDL1 mAB, PhIII, NSCLC, Melanoma) - It is in PhIII in Japan and for NSCLC indication- Nivolumab is the closest competitor.
April 2014 price cut tLong listed products resulted in sales decline of Suvenyl, Sigmart and Alfarol ?.
MPDL3280A - Anti PD1 from Roche- competitive landscape and status in Japan
Table 1: Deals Done By Chugai Pharma in 2013-2014
Table 2: Ongoing Important Clinical Studies of Kadcyla in Late Stage Her 2 Positive Cancers
Table 3: Actemra - Ongoing Global Trials

Daiichi Sanky-Edoxaban uptake + Ranbaxy/Sun Closure will provide Momentum in 2015!
Ranbaxy +Sun= Sun = 9% equity stake in New Sun- Exit or hold???-
Vision 2017 Revision is expected around FY03/15 results:
Edoxaban: A blockbuster potential likely despite restricted US launch and will be 4th Entrant in NOAC market
Acquisition of Ambit bioscience
Quizaritinib
Other Assets from Ambit
Other Assets in Pipeline- CL 108 and Etanercept biosimilar
JP domestic market - Long listed products sales decline?..
Daiichi SankyEspha (DSE) - New pricing policy make difficult road ahead
Table 1: Edoxaban - Possible ScenariAnalysis and Peak Sales Estimate
Table 2: % Patients Crcl Table 3: Launched Noac- Efficacy And Safety Comparision - In Renally Imparied Patients
Table 4: Launched Noac- Ww Reported Sales
Table 5: Competitive Landscape - Select Late And Mid Stage Drug Targeting Aml
Table 6: Select Jak 2/1 Inhibitors: Mid- TLate-Stage Pipeline
Annexure 1: 5-Year Business Plan: Numerical Targets For Fy2017
Annexure 2: Core Strategies Of 5-Year Business Plan
Annexure-3: New Generation Oral Anticoagulants - Market Dynamics

Dainippon SumitomPharma - Latuda growth is the Key tsupport Regenerative/Cell therapy Innovation!
BBI-608 - Post failure in PhIII CRC (Colorectal cancer) study, focus now shifts tPhIII clinical data
Pipeline CSC Inhibitors
BBI-503- Clinical data from PhI/II study in 2015 will decide its future potential-BBI-503
Regenerative medicine/Cell therapy medicine - A long way tgo!!!-SB623

Other Pipeline candidates:
EPI-743
AS-3201 (Ranirestat)
DSP-1747
Dasotraline
Table 1: Pipeline Of Drugs Targeting Cancer Stem Cell
Table 2: Pipeline Of Boston Biomedical
Table 3: Psychiatrists See High Unmet Need
Table 4: Latuda Swot Analysis
Table 5: Dainippon Sumitomo-Key Pipeline Candidates- Japan
Table 6: Dainippon Sumitomo-Key Pipeline Candidates- Us
Table 7: Deals Done By Dainippon In 2013-2014
Chart 1: Atypical antipsychotics market

Eisai - Success in R&D is the Only Hope!
LENVATINIB
Thyroid cancer
Hepatocellular carcinoma
Lung Cancer
Table 1: Sales outlook for major lung cancer drugs vs. Lenvatinib expectation
Halaven - Eisai's Flagship Product After Aricept and Aciphex
Table 2: Indications Prospects For Halaven
Fycompa tmaintain presences intCNS space
E2006 is another candidate strengthening base of CNS franchise
Annexure 1; EISAI R&D Pipeline (Ph II and III Only)

Kyowa HakkKirin - PoteligeCombination Trial With ITherapy Will Drive The Story
KHK's Potelligent technology
Biosimilar JV

Our view on its global late stage pipeline candidates
KW-0761
KW-6002
KRN-23
MEDI-563/Benralizumab/KHK4563
Archimedes acquisition Strengthen Prostakan Product portfoli+ EU presence
Newly launched products in Domestic Market (Japan) Poteligeo, Nouriast, Onglyza - Very slow
uptake does not allow KHK twithstand pricing pressure /biosimilar competition in domestic
market - G-Lasta may change the picture
Table 1: Competitive Landscape Of Biologics In Severe Asthma
Table 2: Parkinson's disease competitive landscape of recently launched PD Drugs in Japan
Table 3: Global Pipeline And Our Comments
Table 4: Deals Done By Khk In 2013-2014
Table 5: Potelligent Technology

Meiji Seika- : Strengthening CNS Foothold & Gx Fusion Strategy tDrive Growth
The core focus on antidepressant market is going tstrengthen further:
Medreich Acquisition - a bold step tventure intoverseas markets
Success in Generic business likely tcontinue
Table 1: Pharma contribution on sales
Table 2: High Profitability of Pharma Segment
Table 3: R & D pipeline
Table 4: Meiji Seika overseas R & D activity

Mitsubishi Tanabe - Overseas Efforts tbe intensified in Coming Years!
Growth drivers vs. long listed exposure
Our view on MT's acquisition strategy
Remicade: biosimilars are unlikely tgenerate massive loss in near term
Invokana- tplay important role in Japan SGLT-2 inhibitor market
Invokana US prescription vs. newly launched products in type 2 diabetes space
Gilenya: Gilenya sales well on track, nimpact of negative data from PPMS
Our view on Gilenya growth going forward & upcoming competition
Key reasons why Gilenya will continue tMaintain its market share in the new competitive landscape
Venture intVaccine Business tunfold soon
Table 1:Clinical data comparison of CT-P13 (Celtrion/NK Remicade biosimilar) vs. INX. In RA (54 week, PLANETRA study) in EU study
Table 2: Top Ten Most Expensive Drugs Procured By Tokyo
Medical Hospital
Table 3: SGLT -2 Inhibitors And Dppiv Players In Japan

Shionogi - Tivicay + Triumeq- Cushion for Shionogi's Next Batch of Innovation!
Tivicay- Tivicay (Dolutegravir) best in class profile has already set the stage for Triumeq use in first line setting, and helps Triumeq ttake the market share from Atripla/ Stribild, Post 2018, FDC with Truvada is a free call option
Pipeline HIV drugs competing with Triumeq- Nnear term threat- TAF- Stribild has its own disadvantage
Shionogi- Late stage pipeline analysis of the global candidates (Table 5)
S-297995
S-888711 (Lusutrombopag)
Shionogi- Early stage pipeline analysis
S-222611
S-010887
Shionogi- Japan- late stage pipeline analysis (Table 7)
S-556971
S-877489 9
Chart 1: Tivicay Prescription Trend vs. Isentress VS. Stribild
Chart 2: TIVICAY VS. ISENTRESS VS. STRIBILD- MARKET SHARE
Chart 3: Current HIV treatment paradigm
Table 1: Single Trial Data- Triumeq vs. Atripla
Table 2: Dolutegravir - Phiii Trials
Table 3: Treatment Of Thrombocytopenia - Recently Approved Drugs + Late Stage Pipeline
Table 4: Global Clinical Data Comparison Of Late Stage Oral TpMimetics For Treatment OF Thrombocytopenia Associated With Chronic Liver Disease
Table 5: Shionogi- Late Stage Pipeline Analysis Of Global Candidates
Table 6: Shionogi- Early Stage Pipeline Analysis - Out Licensing Opportunities
Table 7: Shionogi- Early Stage Pipeline Analysis - Out Licensing Opportunities
Table 8: Deals Done By Shionogi In 2013-2014

SymbiPharmaceuticals: All Eyes Are On Label Expansion Of Treakisym
Rigosertib - Catering Niche despite Negative ONTIME data- Ph II data read out by
YE2014/1H2015 will decide First line potential
In 2nd-line Higher Risk MDS patients (IV Rigosertib)
In 1st line lower risk MDS pts (Oral Rigosertib)
TREAKISYM
CLL
Front line NHL
RR aggressive NHL
Upcoming Milestones
Chart 1: Symbio- Pipeline
Table 1: RR/2nd line HR MDS- Select late-tmid stage pipeline

Takeda -Will the New Launches (Entyvio, Takecab, and Brintellix) Set The Stage For Next Growth Cycle???
Key milestones twatch for in 2015 are
EU portfolibecoming strong post ENTYVIand Natura alpha launch - Nycomed's strong GI market presence will boost this franchise
Entyvi(Vedolizumab/MLN0002, approved US/EU, vedolizumab, ?4?7 integrin inhibitor, Ulcerative colitis / Crohn's disease): Strong uptake confirms differentiated profile- blockbuster potential likely
Competition from Pipeline drugs:
Brintellix (Vortioxetine) - Cognition data will differentiate Brintellix in genericized depression market-
Vortioxetine vs. Currently Available Drugs
MLN-9708 (PhIII, Multiple Myeloma) interim PhIII data in RRMM in combination with Revlimid in 2015 will decide its potential in crowded Multiple Myeloma market:
Expected competition tVelcade in Second/third line setting and upcoming milestones before patent expiry (2017)
Table 1: Deals Done By Takeda In 2013-2014
Table 2: Key Late Stage Pipeline Global Candidates- Takeda
Table 3: Pipeline Leukocyte Traffic Inhibitor (Integrin Inhibitor)
Chart 1: Mln9708 -Trial Design Of Tourmaline-Mm1 - Rrmm
Table 4: competitive landscape -mln 0002/vedolizumab vs. marketed mab in ulcerative colitis
Table 5: Takeda Competitive Landscape mln 0002/vedolizumab vs. marketed mab in crohn's disease
Table 6: Takeda Mln 0002/Vedolizumab Clinical Trial Program
Table 7: Vortioxetine - Major Depressive Disorder
Table 8: Vortioxetine - Major Depressive Disorder - Drugs Discontinued In The Recent Past
Table 9: Vortioxetine - Major Depressive Disorder - Competitive Landscape
Table 10: Data Comparison - Newly Diagnosed Multiple Myeloma (Ndmm)
Chart 2: MLN-9708 Trial design
Chart 3: Reported adverse events in clinical trials- MLN9708
Table 11: Data Comparison - Relapsed And Refractory Multiple Myeloma (Rrmm)
Table 12: Data Comparison - Relapsed And Refractory Multiple Myeloma (Rrmm) -

Japan Generics:

Nippon Chemiphar - Less Vulnerability tNew Pricing System is Advantageous!
Relatively Modest Margins Profile Compared tPeers
Impact of April 14 NHI price revision
A balanced portfoliprovides flexibility in adopting favorable market strategies:
Table 1: Nippon Chemiphar Sales break up
Annexure 1- Key Features of New NHI Pricing System

Sawai - Poised Well TSail Through Tough Times!
Gradually improving wholesaler base is advantageous
Table 1: Gradually Improving Wholesaler Base
Primary Care Focused Product Mix- Not Highly Profitable yet less Risky
Table 2: Balanced Primary Care Products-Mix
Table 3: Better Performance by New products
Table 4: Value To/Of Products Going Off Patent In Next 5 Years
Table 5: Newly Listed Products In 2014
Figure 1: Sawai- Medium tlong term vision

Towa - Tough Time In Adapting TNew Pricing Regulations!
Need of decreasing dependence on direct sales channel under changed scenarios:
A solid foundation of organic growth is in place through years of constant Capex and R&D investments
GP Market Focus is Moving tDP Markets; HP Needs Improvement
Japan Generic Industry Outlook
Table 1: Direct Sales On Rise
Chart 1: Constantly Increasing Capex
Table 2: Key Launches Of 2014
Table 3: Steady Performance Of Key Products
Table 4: GP Market Focus Switching TDP Market

List of Tables

Astellas : Table 2: Pipeline Early stage Androgen Receptor antagonist
Table 3: Competitive landscape for Antifungals
Table 4: Competitive landscapes for OAB drugs
Table 5: Pipeline HIF alpha stabilizer- AKEBIA AKB-6548 is closest competitor
Table 6: Competitive landscape- Anti PCSK9 MAB- ALIROCUMAB vs. EVOLOCUMAB
Chugai: Table 1: Deals Done By Chugai Pharma in 2013-2014
Table 2: Ongoing Important Clinical Studies of Kadcyla in Late Stage Her 2 Positive Cancers
Table 3: Actemra - Ongoing Global Trials
Daiichi Sanky: Table 1: Edoxaban - Possible ScenariAnalysis and Peak Sales Estimate
Table 2: % Patients Crcl Table 3: Launched Noac- Efficacy And Safety Comparision - In Renally Imparied Patients
Table 4: Launched Noac- Ww Reported Sales
Table 5: Competitive Landscape - Select Late And Mid Stage Drug Targeting Aml
Table 6: Select Jak 2/1 Inhibitors: Mid- TLate-Stage Pipeline
Annexure 1: 5-Year Business Plan: Numerical Targets For Fy2017
Annexure 2: Core Strategies Of 5-Year Business Plan
Annexure-3: New Generation Oral Anticoagulants - Market Dynamics
Dainippon Sumitom: Table 1: Pipeline Of Drugs Targeting Cancer Stem Cell
Table 2: Pipeline Of Boston Biomedical
Table 3: Psychiatrists See High Unmet Need
Table 4: Latuda Swot Analysis
Table 5: Dainippon Sumitomo-Key Pipeline Candidates- Japan
Table 6: Dainippon Sumitomo-Key Pipeline Candidates- Us
Table 7: Deals Done By Dainippon In 2013-2014
Eaisai: Table 1: Sales outlook for major lung cancer drugs vs. Lenvatinib expectation
Table 2: Indications Prospects For Halaven
Annexure 1; EISAI R&D Pipeline (Ph II and III Only)
Kyowa HakkKirin : Table 1: Competitive Landscape Of Biologics In Severe Asthma
Table 2: Parkinson's disease competitive landscape of recently launched PD Drugs in Japan
Table 3: Global Pipeline And Our Comments
Table 4: Deals Done By Khk In 2013-2014
Table 5: Potelligent Technology
~Meiji Seika : Table 1: Pharma contribution on sales
Table 2: High Profitability of Pharma Segment
Table 3: R & D pipeline
Table 4: Meiji Seika overseas R & D activity
Mitsubishi Tanabe : Table 1:Clinical data comparison of CT-P13 (Celtrion/NK Remicade biosimilar) vs. INX. In RA (54 week, PLANETRA study) in EU study
Table 2: Top Ten Most Expensive Drugs Procured By Tokyo
Medical Hospital
Table 3: SGLT -2 Inhibitors And Dppiv Players In Japan
Shionogi: Table 1: Single Trial Data- Triumeq vs. Atripla
Table 2: Dolutegravir - Phiii Trials
Table 3: Treatment Of Thrombocytopenia - Recently Approved Drugs + Late Stage Pipeline
Table 4: Global Clinical Data Comparison Of Late Stage Oral TpMimetics For Treatment OF Thrombocytopenia Associated With Chronic Liver Disease
Table 5: Shionogi- Late Stage Pipeline Analysis Of Global Candidates
Table 6: Shionogi- Early Stage Pipeline Analysis - Out Licensing Opportunities
Table 7: Shionogi- Early Stage Pipeline Analysis - Out Licensing Opportunities
Table 8: Deals Done By Shionogi In 2013-2014
SymBiPharma : Table 1: RR/2nd line HR MDS- Select late-tmid stag e pipeline
Takeda : Table 2: Key Late Stage Pipeline Global Candidates- Takeda
Table 3: Pipeline Leukocyte Traffic Inhibitor (Integrin Inhibitor)
Chart 1: Mln9708 -Trial Design Of Tourmaline-Mm1 - Rrmm
Table 4: competitive landscape -mln 0002/vedolizumab vs. marketed mab in ulcerative colitis
Table 5: Takeda Competitive Landscape mln 0002/vedolizumab vs. marketed mab in crohn's disease
Table 6: Takeda Mln 0002/Vedolizumab Clinical Trial Program
Table 7: Vortioxetine - Major Depressive Disorder
Table 8: Vortioxetine - Major Depressive Disorder - Drugs Discontinued In The Recent Past
Table 9: Vortioxetine - Major Depressive Disorder - Competitive Landscape
Table 10: Data Comparison - Newly Diagnosed Multiple Myeloma (Ndmm)
Chart 2: MLN-9708 Trial design
Chart 3: Reported adverse events in clinical trials- MLN9708
Table 11: Data Comparison - Relapsed And Refractory Multiple Myeloma (Rrmm)
Table 12: Data Comparison - Relapsed And Refractory Multiple Myeloma (Rrmm) -
Nippon chemiphar : Table 1: Nippon Chemiphar Sales break up
Annexure 1- Key Features of New NHI Pricing System
Sawai : Table 1: Gradually Improving Wholesaler Base

List of Figures

Astellas : Chart: 1, 2 - Current and Future use of anti androgens in treatment of Prostate Cancer Chugai - Alectinib, ACE910 Global Success - Next Growth Driver!
Dainippon Sumitom: Chart 1: Atypical antipsychotics market
Shionogi: Chart 1: Tivicay Prescription Trend vs. Isentress VS. Stribild
Chart 2: TIVICAY VS. ISENTRESS VS. STRIBILD- MARKET SHARE
Chart 3: Current HIV treatment paradigm
SymBi: Chart 1: Symbio- Pipeline
Takeda :Chart 1: Mln9708 -Trial Design Of Tourmaline-Mm1 - Rrmm
Chart 2: MLN-9708 Trial design
Chart 3: Reported adverse events in clinical trials- MLN9708