Hale & Tempest Generic Country Markets & Biosimilars Chesapeake Dr. Brian W Tempest UK March 2014

Hale & Tempest 7. Generic Country Markets

Hale & Tempest Europe source: EGA

Hale & Tempest Reference Pricing Globally Endemic Source : Istanbul September 2012  Pharma purchases reduced from 1.7% of GDP to 1.0% of GDP in Turkey  Russia, South Korea & Saudi Arabia health ministries requested Turkish prices  Everybody is referencing everybody else on Pharma prices in Europe  Bulgaria is referencing prices in 17 other countries

Hale & Tempest Europe – generics take half the volume but a fraction of value sales

Hale & Tempest EU Chemical Sales source: Chemistry World September 2013

Hale & Tempest Open letter to Barroso from the Chairman of INEOS on 7 March 2014

Hale & Tempest Generic Global Volume Share Source: Sandoz

Hale & Tempest 30 generic packs, >2 years treatment £ king size cigarettes £68 Source: Generics Bulletin 15 Feb 2013

Hale & Tempest European Generic Prices Source Ranbaxy

Hale & Tempest Indian Pharma penetration of the UK source: FT January

Hale & Tempest Security of Power Supplies in Europe source: Economist 15 April 2014

Hale & Tempest France Generic Market Source: Generics Bulletin 15 February 2013

Hale & Tempest US DMFs from India source: Citi Research 2013

Hale & Tempest Number of USA Para IVs source: Generics Bulletin 14 September 2012, quarter indian

Hale & Tempest USA Generic Market - Latest Challenges source: Jefferies 10 March 2014

Hale & Tempest Africa Management source Ranbaxy

Hale & Tempest Nigeria, South Africa & Angola source: Economist 12 April 2014

Hale & Tempest African Factories

Hale & Tempest Japan Generic Market source: Citi Research August 2013

Hale & Tempest Japan Generic Opportunity

Hale & Tempest Japanese Generic Market source: Mint 28 January 2014

Hale & Tempest Brazil Generic Packs

Hale & Tempest Brazil Top 10 Generic Cos

Hale & Tempest Russia 2020 Strategy for Public Health

Hale & Tempest Russian Market Evolution source: Frost & Sullivan 2011

Hale & Tempest Vaccine Plant to take 1/3 Russian Market source: St Petersburg Times, 16 April 2014

Hale & Tempest USA Generic Market - Latest Challenges source: Jefferies 10 March 2014

Hale & Tempest Russia VLS List

Hale & Tempest Russia 2020 Strategy 90% local manufacture of VLS list

Hale & Tempest Russia 2020 Strategy 50% local manufacture of all products

Hale & Tempest New Novartis Plant in St Petersburg source: Top Emerging Pharmaceutical Markets by Kathlyn Stone

Hale & Tempest Russia & India – Big Picture source: ET March

Hale & Tempest Russia & India – Big Picture source: ET March

Hale & Tempest Indian Pharma in Russia - DRL source: website, 20 years

Hale & Tempest Indian Pharma in Russia - Ranbaxy source: RUR, 20 years, 15% MS IMS May 2013, across 56 Regions

Hale & Tempest Chinese Debt 200% of GDP in 2013 source: FT 2 April 2014

Hale & Tempest Chinese NGOs source: Economist 12 April 2014

Hale & Tempest China Pharma Industry Capex Plans Source: Stravencom

Hale & Tempest China Price Cuts source: Jefferies

Hale & Tempest China API Exports decline by -9% source: Pharmatiimes February

Hale & Tempest Hisun Pfizer Pharmaceuticals Ltd source: Launch Announcement September

Hale & Tempest Hisun USA source: website

Hale & Tempest Hisun USA acquires FDA approved DPI source: Press Release January

Hale & Tempest Hisun USA acquires FDA approved DPI source: Press Release January

Hale & Tempest China: Optimistic view of Domestic Market source: Jefferies 17 March 2014

Hale & Tempest China Provincial Tenders source: Jefferies 17 March 2014

Hale & Tempest Sino Biopharm strongest domestic pipeline source: Jefferies March

Hale & Tempest Zhejiang Huahai (Novast also received an ANDA for an OC in 2010)

Hale & Tempest China - Actavis Withdraws source: Bloomberg January

Hale & Tempest South Africa Generics

Hale & Tempest Middle East & North Africa

Hale & Tempest Jordan punches above its Weight

Hale & Tempest Canada Generic Market Source: Generics Bulletin 15 Feb2013

Hale & Tempest Myanmar – a new market

Hale & Tempest 8. Biosimilars

Hale & Tempest Which Way?

Hale & Tempest Biologics & Small Molecules source: Kozlowski et al., N England J Med, 365:5, 2011

Hale & Tempest Estimated 2016 sales of Top 20 products Source: Cowen

Hale & Tempest Biosimilar Share to 2018 source: EvaluatePharma 2012

Hale & Tempest Monoclonal antibodies $m Source: Synthon

Hale & Tempest New Biosimilar Company (with Merck)

Hale & Tempest Korean Pharma in Biosimilars source: Citi Research August 2013

Hale & Tempest Biosimilars from China/India Source: New York Times 20 Sep 2011

Hale & Tempest Biotech Drugs where India has no DMF Source: JGM Volume 6 p333 sep 2009

Hale & Tempest Biosimilars from India Source: Citi 25 September 2013 Market opportunity of $1.5b to $2b for US & EU More clarity now on regulatory pathways OECD -$100m for R&D development of a MAB, $300m- $400m to set up manufacturing capacity of 100,000L with annual R&D at $100m Developing Countries - $200m sales potential, $20m R&D per year, manufacturing capacity of 1,000L planned India companies will enter emerging markets but use partnerships and alliances for OECD eg DRL Developing Countries limited by affordability issues

Hale & Tempest Biosimilars Key Issue - Interchangeability source: GaBi Journal Biologics & Biosimilars 28 December 2013

Hale & Tempest Biosimilar Market Sizes Source: IMS, FT February Global Biologics including Big Pharma blockbusters in 2012 is $170 b Biosimilars market size in 2012 is $2.5b and in 2020 is estimated at $25b VERSUS cost of manufacturing plant, cost of clinical trials, lower hospital tender prices, no interchangeability, cost of reps, patient-innovator relationship, competition from South Korea, authorised generics

Hale & Tempest First Herceptin Trastuzumab Biosimilar source: ET January Rs 40,000 per 440mg vial, Roche halved price at Rs 55,000

Hale & Tempest Sandoz Biosimilars – an 12 years ROI source: Pharmacloud June 2012

Hale & Tempest India Pharma in Biosimilars source: Citi Research August 2013

Hale & Tempest BiosimiIar Challenges for CEOs Do I enter or keep out?  Rituximab >100 patient CT for Roche, >600 patient CT for Generic companies  Interchangeability (AB rating) unlikely  Cabilly patents may delay US mAbs  EU mAb in 2013 from Hospira/Celltrion  EPO biosimilar side effects in Thailand  Many biosimilar manufacturers in China but few will reach EU/USA  Scientifically challenging - Amgen  Biobetters need a full dossier with health economic data

Hale & Tempest Biosimilar Alliances – to share the risk  Cipla & Biomab, China $165m 12 products  Richter & Stada – mABs  Celltrion, Korea -Hospira, Egis, Hikma, BB, etc  Biocon & Mylan, USA, mABs: Xbiotech  Teva & Lonza, EU – dissolved July 2013  Biocon Idec & Samsung, Japan – now Merck  Watson & Amgen, USA  Fuji Film & Kyowa Hakko Kirin  DRL & Merck-Serono, Germany – mABs  Bionovis (Brazil) & Merck Serono - 6

Hale & Tempest NIBS (tyrosine kinase inhibitors) Will these small molecules replace mAbs?  Axitinib, Pfizer, cancer  Cediranib, AZ, cancer  Pazopanib, GSK, cancer  Regorafenib, Bayer, cancer  Semaxanib, Sugen, cancer  Sorafenib, Bayer(Nexavar),cancer  Sunitinib, Pfizer, cancer  Toceranib, Pfizer, cancer  Vandetanib, AZ, cancer  Tofactinib, Pfizer, RA

Hale & Tempest BTD : Breakthrough Therapy Designation source: Evaluate,FDA Jan products in ibs & 3 mabs J&J 4, GSK 3, Nov 3, smaller cos 12

Hale & Tempest Thank You