Tools and Strategies for Launching a Successful Generic in Today’s Ultra Competitive EnvironmentKATE KUHRT

BERLINSEPTEMBER 27, 2008

BEST OF TIMES…

• Population all over the world getting older

• Increase in the size of middle class in many countries

• Governments and employers promoting use of generic drugs in efforts to slow down increase in health care spending

• Increased acceptance of generic drugs by patients and physicians

• A number of blockbusters losing patent protection

…AND WORST OF TIMES

• Innovation drought

• ANDA backlog and authorized generics

• Pressure on prices and diminishing margins– Government regulation

– Consolidation among wholesalers and retailers

– Increased competition• Generic filings and approvals at all-time high

• A number of new entrants, many from India, often with access to low-cost APIs

• Overcapacity in manufacturing

• Focus on market share rather than bottom line

• Authorized generics in the U.S.

ANDA APPROVALS BY INDIAN GENERICS

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1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007*

# A

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Source: Newport Strategies’ Horizon Global system

*Through August 15, 2007

2007 YTD FINAL ANDA APPROVALS BY COUNTRY

USA; 116; 39%

India; 85; 28%

Germany; 25; 8%

Israel; 23; 8%

Other; 20; 7%Iceland; 6; 2%

Canada; 11; 4%

Switzerland; 13; 4%

Source: Newport Strategies’ Horizon Global system

*Through August 15, 2007

ARE THE GENERICS INDUSTRT’S GOLDEN YEARS OVER?

• Expectation that only the fittest will survive

• Coping strategies aimed at:– Reducing cost

– Reducing risk

– Improving speed to market

– Differentiation

– Achieving critical mass

COPING STRATEGIES: CONSOLIDATION

• Consolidation expected to continue in pursuit of

– Top-line growth

– Opportunities in new markets

– Synergies

• Example: Barr’s acquisition of Pliva

– Biogenerics

– New dose forms

– Presence in emerging markets

– Access to API

• Result: Industry will likely be dominated by a handful of global players plus many small, focused players

LEAGUE TABLES ARE CONSTANTLY SHIFTING

Source: TS Research

Global IsraelTeva 8400

Global AustriaSandoz 5960

Global GermanyMerck KGaA 2200

EU SloveniaKrka 600

Global USMylan 1260

EU Germanyratiopharm 2000

Global IndiaRanbaxy 1170

EU GermanyStada 1400

Global IndiaCipla 740

US USPerrigo 1024

Global CanadaApotex 770

US USWatson 2550

Global USBarr 3000

EU HungaryGedeon Richter 600

Focus HQSales $M

Global USHospira 3480

Global IndiaDr Reddy’s 550

US USActavis 1835

US USEndo 650

Purchase by Mylan expected to close H2 07

Sold US Business

Lost Bid for Pliva

Acquired Mayne

Acquired Pliva

Acquired Andrx

Acquired Betapharm

Majority stake in Matrix; Acquiring Merck KGaA

COPING STRATEGIES: GEOGRAPHIC DIVERSIFICATION: EUROPE• Recent Examples

– Barr-Pliva– Mylan-Merck Generics– Hospira-Mayne– DRL-Betapharm– Matrix-Docpharma– Ranbaxy-Terapia– Aurobindo-Milpharm– Alkem close to buying two firms in UK and Germany

• Pros– Counterweight to the U.S. market– Some markets still focused on branded generic– Rapid growth of pharma industry in E. Europe and Russia

• Cons– Some markets as competitive as U.S.– Generic uptake high at the expense of margins

COPING STRATEGIES: GEOGRAPHIC DIVERSIFACTION: JAPAN

• Pros– Japanese generics market seen as having a tremendous

growth potential• Currently 5% by value, 17% by volume

• Cons– Some still skeptical about actual market potential

• Difficult for foreign companies to do it alone– Acquisitions, JVs, and marketing agreements provide

ready access to:• Manufacturing

• Marketing

• Distribution relationships

• Acquisitions

– Zydus Cadila acquired a 100% stake in Nihon Universal Yakuhin in April 2007

• Joint Ventures

– In November 2005, Ranbaxy increased equity stake in Nippon Chemiphar from 10% to 50%

• Marketing Agreements

– In August 2005, Lupin entered into a long-term marketing agreement with Kyowa Pharmaceutical

– In March 2006, Hospira-Taiyo agreement to sell each other’s injection agents

• Additional companies to watch

– Continued speculation that Teva will eventually acquire a Japanese firm

– Rumors that one of the three large generics (Nichi-iko, Sawai, Towa) will come under part ownership by a large multinational

– Torrent Pharma opened a fully-owned subsidiary in Yokohama in April 2006

– Dr. Reddy's considering setting up an office in Tokyo or Osaka

COPING STRATEGIES: GEOGRAPHIC DIVERSIFACTION: JAPAN

COPING STRATEGIES: BACKWARD INTEGRATION INTO API• Recent examples

– Mylan-Matrix

– Barr-Pliva

• Pros

– More control over cost and access to API• Decreasing number of established API manufacturers still

independent due to M&A

– Different parts of the value chain may make money in different products

– Faster response times

• Cons

– No one plant can make all APIs required by a typical generic

– Making just enough for captive use often not economical

– Other dose companies wary of buying API from a competitor

COPING STRATEGIES: MOVING MANUFACTURING AND R&D TO LOWER-COST COUNTRIES• Applies to both API and dose

• Examples– Sandoz – multiple units in India– Teva – scientists in Faridabad, acquired Regent Drugs (JK)– Apotex – manufacturing and R&D facilities in Bangalore– Ratiopharm – R&D center in Goa– Stada – production sites in Russia, Vietnam (50:50 JV) and China– Perrigo – JV in China for ibuprofen– Actavis – API development facility and CRO in India

• Pros– Abundance of scientists– Cost savings

• Cons– Language barriers– Potential for intellectual property theft– Quality control

COPING STRATEGIES: ALLIANCES WITH COMPANIES IN LOWER-COST COUNTRIES• Applies to both API and dose Manufacturing

• Examples– Alpharma-Shasun

• 2005 agreement for 10 finished dose products and undisclosed number of APIs– Actavis-Orchid

• 2007 agreement involving 9 cephs in Europe• Development, manufacturing, and distribution agreement for 10 non-cephs in

the U.S.

• Pros– Cost savings– Access to a diverse talent pool

• Cons– Longer response time to changes in market dynamics– Potential delays due to regulatory issues– Potential loss of IP– Challenges with managing long-distance relationships

COPING STRATEGIES: SOURCING API FROM LOWER-COST COUNTRIES• Examples

– Teva, Apotex, Watson has been sourcing from India for years

– Indian companies increasingly sourcing out of China

• Pros

– Cost savings

– Many qualified API sources to choose from

• Cons

– Many API sources with limited track record

– FDA inspections more lax overseas?

– Language barrier

– QA costs

– Potential shortages due to stricter enforcement of local environmental laws

COPING STRATEGIES: SOURCING API FROM LOWER-COST COUNTRIES (cont)

Source: Newport Strategies Horizon Global ™

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COPING STRATEGIES: FOCUS ON NICHE PRODUCTS

• Examples– Ranbaxy, DRL eyeing Bradley Pharmaceuticals

(dermatology)

• Pros– Less competition

– Margins in difficult formulations likely to remain higher• Inhaled products, certain injectables, controlled release

• Cons– Even $20M products attracting interest

– If multiple generics get involved, may not recoup investment

– Costly barriers to entry for certain products

COPING STRATEGIES: INNOVATION• New formulations

– Andrx – Altoprev (controlled-release lovastatin)

– Ranbaxy – Riomet (metformin oral solution)

• New molecules– Best known examples: Pliva – Zithromax (azithromycin), Teva –

Copaxone (glatiramer)

– Ranbaxy expects to be the first Indian pharma co to launch a new NCE (exp. 2011)

• Pros– Potential for big returns during patent and exclusivity period

• Cons– Original R&D very expensive and risky: It may take 1000s of failures

before a successful NCE

– Possible reimbursement issues and higher marketing costs for “generic plus” products

COPING STRATEGIES: PARAGRAPH IV PATENT CHALLENGES

• Pros– Generic companies can make a considerable amount of

money during the 180-day exclusivity period

– First-to-market generic company often maintains a big market share even after the end of the exclusivity

• Cons– Expensive and risky

– Authorized generics and shared exclusivity reduce the potential payoff from the initial 180 days

PARAGRAPH IV PATENT CHALLENGES

• As of September 7, 2007, challenges on products encompassing– 341 unique brand names

– 282 unique molecules or molecule combinations

– 48 unique dose forms

• In 2006, 27 molecules (or new combinations) first were exposed to patent challenges

• So far in 2007, 17 molecules (or combinations) have seen their first patent challenges

Source: FDA, Newport Strategies Horizon Global ™

TOP 10 COMPANIES BY NUMBER OF PATENT CHALLENGES

Group Country NumberTeva Pharmaceutical Industries Ltd Israel 70Mylan Laboratories Inc USA 29Apotex Inc Canada 29Novartis AG Switzerland 27Dr Reddy's Group India 27Barr Laboratories Inc USA 25Ranbaxy Laboratories Ltd India 23Watson Pharmaceuticals Inc USA 18Sun Pharmaceutical Industries Ltd India 15Par Pharmaceutical Companies Inc USA 15

Source: Newport Strategies Horizon Global ™

IMPORTANCE OF API IN PATENT CHALLENGES• Risk of supplier failure is high for companies involved with patent

challenges

– Even one day of delay can cost the company FTF status

• Risk is also high for API manufacturers

– Generics may settle with innovators or do deals with other generics who use other API sources

– If dose company is backward integrated into API, may switch to internal API source when convenient

– If development starts too early, product may be withdrawn from market

• Backward integration into API may provide crucial advantages

– Coordinated API and dose development

– Coordinated regulatory submissions

– Speedy addressing of any issues

– Improved knowledge of polymorphs

INDIAN COMPANIES (*) ARE CLEARLY BASING THEIR PARAGRPH IV STRATEGY ON BACKWARD INTEGRATION

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DMF Held by PIV Filer No DMF Held by PIV FilerSource: Newport Strategies Horizon Global ™

COPING STRATEGIES: SOPHISTICATED PRODUCT SELECTION

• Companies need to pick products for development very carefully

– It is not enough to look at sales data!

• Pharmacodynamics• Toxicity• Country Regulations• Pack Pricing• Reimbursement

Data Needs during Product Selection

• Approvals• API Sources• Company Data• Manufacturing Capabilities• Bioequivalence• Stability

• Sales• Dose Form and Strength• Patents, Patent Challenges• Labeling• Chemistry, Synthesis• Data Exclusivity• Market Exclusivity

Targeting EvaluationDeal Making

Formulation Dev’t

Registration & Review

Launch

LaunchL – 18 monthsL – 8 years L – 7 years L – 6 years

COPING STRATEGIES: SOPHISTICATED PARTNER SELECTION

• Companies need to pick partners and acquisition targets carefully

Data Needs during Partner Selection

• Patent portfolio• Patent challenge experience• Approvals• Backward/forward integration• Current alliances• Location

• Product portfolio• Product pipeline• Geographic reach• Financials• Regulatory experience• Manufacturing capabilities

TOOLS TO TH RESCUE!

• Access global market, intellectual property and product info

• Predict key data in advance (e.g. competitiveness, generic launch date)

• Flexible, fast searching across multiple, exacting criteria

• Identify early, viable source of API supply and backup sources

• Spot in- and out-licensing capabilities

• Identify potential partner companies with multiple, exacting criteria

• Keep a watchful eye on potential acquisition targets and track competitors

THANK YOU!

Kate Kuhrt

Newport Strategies

Thomson Reuters

215 Commercial Street

Portland, Maine 04101

USA

+ 1 (207) 871-9700 x26

kaire.kuhrt@thomsonreuters.com