1. Big Pharma?
Clotilde Bourdon Olivia Scaccia Pauline Fontaine Antoine Henninot

2. Teva’s id Headquarters : Petak Tikva, Israel Stock exchange : Nasdaq
SEAQ International London
Francfort
Tel-Aviv
Sector : Generics, Branded drugs, Brands
One of the 20-largest pharmaceutical companies in the world
Operating in ≥ 60 countries, employees

3. Teva and its concurrents

4. History of the company Teva: public on the Tel Aviv Stock Exchange
Imported medicines trough Jerusalem
Teva: public on the Tel Aviv Stock Exchange
only source of treatments for the local market
1901
1930
WW II
1948
1951
Teva: pharmaceutical
industry
Israel state

5. History of the company (2)
Teva Phcal Industries, Israel’s largest drugmaker
2nd innovative drug, ttt PD
July 2006
1996
2005
Acquisition of IVAX
QVAR®, ProAirHFA®
Acquisition of Ikapharm, and other companies

6. History of the company (3)
MHRA:
expanded label for
Copaxone +
Laquinimod: « fast track » designation (FDA)
Strategic R&D agreement with
Jexys Phctls
Dec
2008
Dec 2008
Jan 2009
Feb 2009
Aug
2009
Acquisition of Barr Phtcal
Joint venture with Lonza Group to market biosimilars
Launch its generic version of the birth control pill Yasmin

7. Strategy Increasing generic Market Share
Increase organic growth through R&D
Redefining Customer Service
Intellectual property
Biopharmaceuticals
Vertical integration
Horizontal integration 1.
2. Accelerating Investment in Product Portfolio:
3. Rapidly responding to customers’ needs
4. : niche therapeutic areas, products with differentiated clinical attributes
5. : acquisitions + partnership in the technologies, infrastructure and capabilities => develop + produce biopharmaceuticals, including biogenerics
7. : Strategic acquisitions => diverse products + local expertise

8. Strategy based on Diversification :
Products
Geographical
Therapeutic areas
Pharmaceutical technology
Management’s flexibility + ability to react to changing market conditions
Dynamism
: Generics + Branded generics + Branded drugs + Biosimilars + in development drugs (innovative drugs)
diversity : +60 nations)
:Analgesic, Anti-infective, Cardiovascular, Oncolytic dermatologic, Anti-inflammatory, Asthma, allergy, women health, neurological area,respiratory, oncology, autoinmune….
: tablets, capsules, liquids, creams, matrix systems, special coating systems for sustained release products, orally disintegrating systems, syringes, drug device combinations and nasal delivery systems…

9. UNBRANDED GENERICS

10. Context : growth in generics
Generic versions of biologic drugs
Managed healthcare expenses +
Expiration of patents on branded drugs
1984: Drug Price Competition and Patern Term Restoration Act,
in generic drug manufacturers
According to Pharmalot.com, in 2008 more than 60% of prescription market volume was dispensed as generic
As more brand name drugs go off patents in coming years, generic drug manufacturers’ profits are likely to increase
Generig drug companies have also branched out into generic versions of biologic drugs

11. Expanding generic market
Increasing demand in generics
With a number of blockbuster drugs expected to lose patent protection in the next few years, generic market would grow rapidly providing an opportunity to generic companies to expand their product portfolio
Hélène Casaert - Elodie Duvinage - Emilie Fovez

12. Teva: The king of generic drugs
Largest generic pharmaceutical manufacturer in the world
22% of all generic prescriptions in the U.S
=> Teva Pharmaceutical Industries
is swallowing Big Pharma's market share!
Teva ≥ 300 products within 40 factories, various areas therapeutics

13. Geographical Expansion
USA
Ivax: 2005, $7.4 billion
Barr Pharmaceutical: 2008, $7.46 billion
EUROPE
2008, US generic firm Bentley Pharmaceuticals, deal = $360 million
JAPAN
Kowa: 2008, ~ $ 100 million
Taisho: 2009, ~ $ 100 million
CANADA
Agreement with Novopharm

14. Opportunities for Teva
drugs will lose patent exclusivity (Atorvastatin Calcium – 12.4 billion in sales)
Hatch-Waxman Act -> + 6 months of sales exclusivity
lawyers looking for patent weaknesses
=> Lotrel (amlodipine) elements of the patent => public domain
=> $330 million in 6 months
FDA 218 applications of generics; Teva is challenging the patents of more than half of them
=> Most robust generic pipeline
=> Big Pharma isn't happy about the way Teva operates
135
next 3 years : $89 billion worth of

15. BRANDED GENERICS

16. Respiratory Products 2005 : acquisition of IVAX
QVAR® (beclomethasone dipropionate HFA): maintenance treatment of asthma
ProAirHFA® (albuteral sulfate): relieves the symptoms of bronchospasms
=> leading competitor in the field of respiratory therapy

17. Respiratory Products Asthma, COPD , Allergic rhinitis
Easi-Breathe®, breath-activated inhaler (BAI),
Spiromax™/Airmax™, a multi-dose dry powder inhaler,
Steri-Nebs™, the blow-fill-seal based nebulizers,
Cyclohaler®, a single dose dry powder device
Develop new medications not based on new molecules but based on new medical devices
Match patient’s needs : ease of use and effectiveness
+++ compliance

18. RESPHIR operation
TEVA and PHR: campaign for asthmatic patients in France
Brands+ Unbranded generics
Two main objectives: - role of the pharmacist in the therapeutic education of the patients
- enhance the proper use of medicines and improve patient compliance

19. Women’s Health Barr Pharmaceutical
Plan B™ OTC/Rx (levonorgestrel) emergency oral contraceptive,
Enjuvia™ (synthetic conjugated estrogens, B) hormone therapy to treat moderate-to-severe vulvar and vaginal atrophy associated with menopause,
Seasonique® : next generation extended-cycle oral contraceptive product continuous hormonal support
estradiol for 84 consecutive days, followed by seven days of low-dose estrogen (0.01 mg of ethinyl estradiol) SEASONIQUE

20. Women’s Health
2009 : generic version of the birth control pill Yasmin rather than licensing it from Bayer Schering
=> branded generic « Ocella »

21. TEVA + IVAX

22. BIOSIMILARS
Shlomo Yanaï,  PDG de Teva « Nous avons identifié les biosimilaires comme des relais de croissance majeurs dans notre stratégie à long terme, et nous sommes en train de consolider nos connaissances, nos capacités et nos infrastructures pour positionner Teva comme un leader de ce marché »

23. Biopharmaceuticals and Biogenerics
Biogenerics = important long-term growth opportunity
Cancer, Arthritis, Rare genetic disorders =
faster-growing segments of the global pharmaceutical market + major contributors to prescription drug costs
Primary biopharmaceutical products =
INF alpha 2b
GCSF (granulocyte colony-stimulating factor)
hGH (human growth hormone) in the U.S. (agreement with Savient)
TevaGrastim® = the 1st GCSF biosimilar marketed yesterday in UE
Microbial and mammalian cell culture products, with the most mature compounds in Phase II studies and launch targeted for 2013

25. Teva + Sicor 2003 : Acquisition
US manufacturer Sicor, for $3.4 billion
=>Teva: access to Sicor’s injectable products and biosimilar development capacity
expanded biopharmaceutical pipeline
=> take advantages of CoGenesys biological technology
develop, manufacture and market a portfolio of biosimilars
highly complementary companies => leading position in the emerging biosimilars market
Teva + CoGenesys 2008 : Acquisition
Teva + lonza January 2009 : Signed a joint venture
(=ne remplit pas toutes les conditions du médicament générique, différences entre les procédés de fabrication du médicament biologique et du médicament biologique de référence)

26. CoGenesys: albumin-fusion technology
division within Human Genome Sciences Inc. (HGSI), 2005
fusing the gene that expresses human albumin +
the gene that expresses a therapeutically active protein
=> long-acting protein drugs => long-acting treatment options
efficacy and safety similar to or better than that of existing protein drugs
more convenient dosage schedules

27. CoGenesys: Pipeline
growth hormone and interferon alpha (by HGS and Novartis)
Zablin, phase 3 ended
Submits FDA licencing for hepatite C chronic
Once every two weeks
GLP-1 (being developed by GlaxoSmithKline under license from HGS)
Albiglutid, Phase III, once a week or less
B-type natriuretic peptide (BNP). CoGenesys' lead clinical candidate, Cardeva, is a long-acting form of BNP (treatment of chronic heart failure)
advancing toward the clinic for outpatient.
Albugranin, a long-acting form of Granulocyte Colony Stimulating Factor (GCSF),
readied for clinical development,
treatment of febrile neutropenia associated with chemotherapy

28. Teva’s ideas for the coming years
difficult to copy
BUT Teva is eager to produce "biogeneric" versions of drugs
"The good news for us is that, because [biogenerics] require high- cost investments, we're only going to see a few competitors” (Teva's R&D chief)
US : No legal way to sell generic copies of biologics BUT Teva isn't waiting idly: sells them in Europe and is ramping up production capacities

29. BRANDS

30. Teva innovative R&D Central nervous system (CNS )
3 Therapeutic Fields
Central nervous system (CNS )
Autoimmune (AI) diseases
Oncology
Pipeline spécialisé : SNC pr sclérose en plaque et maladie d’alzeihmer
Onco stemex pr les personnes sans donneur compatible pr greffe de MO
is recently emerging as a potential new area
Hélène Casaert - Elodie Duvinage - Emilie Fovez

31. Copaxone
1997 : 1st major branded products : the multiple sclerosis treatment Copaxone
1st innovative drug developed in Israel that won FDA approval, Teva’s best seller

32. Multiple Sclerosis
myelin is lost scars= scleroses (“multiple sclerosis”)

33. Multiple Sclerosis (continued)
≥ 2 million patients
4 different forms of MS
++++ : Relapsing-Remitting form manifested by relapses followed by remission (incomplete at times : disability progression)

34. Copaxone®: action on rrms
limits the formation of new lesions in the CNS
brain atrophy
the average relapse rate in people with RRMS
regulates inflammation at the site of brain lesions + controls neurodegeneration + enhances repair
slows the in the NAA (N-acetyl aspartate), marker highly correlated with progression of disability in MS
daily sub-cutaneous injections of 20 mg.
well tolerated (common problems= itching and inflammation, flushing, weakness, nausea)

35. Azilect®: 2nd Teva’s innovative drug
DCI= Rasagiline
2nd generation MAO-B inhibitor
treatment of idiopathic Parkinson’s Disease as:
- monotherapy
- adjunct therapy (with levodopa) in patients with end-of dose motor fluctuations
Incidence: 1% people over 65
80-90% of patients with Parkinson’s disease are treated with levodopa (30% of them as
Monotherapy : patients receiving levodopa therapy alone)

36. BRANDS: PIPELINE

37. ≥ 11 innovative produts expected

38. StemEX Chemotherapy : medullar aplasia
Patients requiring bone marrow transplantation
Pb: Only 15% of patients requiring bone marrow transplantation: find matching donors
=> StemEx® : Treatment of leukemia and lymphoma
Stem/progenitor cells isolated from umbilical cord blood
StemEx® is composed of ex-vivo expanded cord blood stem/progenitor cells, which are transplanted in combination with non-expanded cells from the same cord blood unit
Stem cell cellules souches
Only 15% of patients requiring bone marrow transplantation, who do not have genetically matched relatives, are able to find matching donors
. As part of this strategy Teva led the Israeli cell therapy consortium "Genesis", and in addition to Gamida-Cell, invested in Proneuron, an Israeli company developing cell-based therapies for complete spinal cord injury
The execution of our
agreement with Teva places Gamida-Cell in the lead of the emerging, multi billion dollar Cell Therapy market."
However, there are a limited number of stem/progenitor cells in cord blood, enabling a quantity sufficient generally only for pediatric treatment. StemEx® employs a technology that expands this small number of cord blood stem/progenitor cells, increasing their therapeutic capacity for transplantation in adolescents and adults.
Du sang aux vertus thérapeutiques peut également être prélevé après la naissance d'un enfant. Il s'agit du sang prélevé sur le placenta (et non sur le nouveau-né) à partir du cordon. Le sang placentaire contient également des CSH. Ceux-ci ont l'avantage d'être jeunes et immatures et cela permet de réduire les risques de rejet immunologique et de réaction du greffon contre l'hôte. Un don même vers un malade avec lequel la compatibilité HLA n'est pas parfaite est alors possible.
Ce sang est souvent destiné à des enfants car la quantité limitée de cellules-souches s'y trouvant ne permet pas toujours de soigner un malade de plus de 50 kg. Certains travaux montrent qu'il est possible d'associer deux sangs de cordons (proches d'un point de vue de leur HLA) afin de soigner les adultes.
technique mise au point est d’augmenter significativement le volume de cellules produites à partir du sang du cordon ombilical, car jusque-là, les quantités produites étaient trop faibles pour servir à des patients adolescents ou adultes…
Transplantation to patient
Bone marrow regeneration after graft
Hélène Casaert - Elodie Duvinage - Emilie Fovez

39. 16 Feb 05 : joint venture Teva Pharmaceutical Industries Ltd - Gamida-Cell Ltd => $25 million
Gamida Cell: world leader in stem cell expansion technologies and therapeutic products
Israel, 2009: Gamida Cell-Teva Joint Venture announced :
orphan designation for StemEx® for the treatment of acute lymphoblastic leukemia and acute myeloid leukemia
StemEx: currently Phase II/III, reaching of the market in 2011

40. Laquinimod
oral medication major therapeutic advantage compared to Copaxone, SC administration
multiple sclerosis (MS)
Kynurenine pathway inhibitor : TRP metabolism : neuroactive intermediate NMDA, key role in the communication between SNC and immune system => inflammation
Confirm the position as world leader Teva for the treatment of MS
Terfluonamide (Sanofi)
Hélène Casaert - Elodie Duvinage - Emilie Fovez

41. Teva + MediWound, 2009
Debrase® Gel Dressing (DGD)= Bromelain based enzymatic debriding agent (mixture of proteolytic enzymes extracted from pineapple plant stem)
Dissolution (high specificity and selectivity) of eschar in burns
Alternative to surgery and/or lengthy non-surgical procedures
Superior and more cost effective treatment option for burns BUT painful
phase III study, Marketing authorization in Europe during 2010
In accordance with EMEA
. Teva Innovative Ventures currently has about 20 portfolio companies.
DGD dissolves the burn eschar within four hours of application, providing an effective, selective, fast and safe alternative to current debriding means, such as surgery and non-surgical methods.

42. teva + oncogenex : 2009 OGX-011 = custirsen sodium ;
=> adjunct therapy to enhance the effectiveness of chemotherapy
Blocks clusterin production(cell survival protein) overproduced in several cancers
Multiple Oncology Indications:
2010: global Phase III :Metastatic Castrate Resistant Prostate Cancer (CRPC)
Phase III :1st-Line, in association, treatment of Advanced, Unresectable Non-Small Cell Lung Cancer (NSCLC) : initiated by early 2011.
key component of Teva branded oncology medicines franchise.

43. Treatment of Type I Diabetes modulates immune response
Diapep 227
Treatment of Type I Diabetes
modulates immune response
Synthetic analog of diabetes epitope HSP 60 in beta cells (Diapep 24AA ( HSP 60))
Phase 3 on going, 300 patients
1st criteria : beta cell function preservation

44. TEVA in 2010

45. FINANCIAL PART

46. sales worth a record US $13,9 billion in 2009

47. Major sales in the Neurological area

48. Copaxone is TEVA’s blockbuster drug
Teva is the only generics maker with its own blockbuster drug
While the bulk of Teva’s revenues are derived from generics, the company has one major innovative product, Copaxone

49. "One of the biggest concerns on Wall Street is, When does Teva become the Pfizer of generics?" asks Ken Cacciatore, an analyst at Cowen & Co. "When does it become too big to grow?"

50. Stock increase Key figures 1.6% since yesterday
7.17% since 1st January 2010
39% for 1 year
413% for 10 years

51. January 11 2010, 28th annual J.P Morgan Healthcare Conference :
Date
06/01/10
07/01/10
08/01/10
11/01/10
12/01/10
Dernier
(c)
(c)
(c)
(c)
(c) USD
Variation
+0.25%
-0.63%
+4.40%
-0.62%
-0.54%
Volume

52. THREATS ?

53. Dark sides
generic drug market => price = main differentiating factor -> competition -> profit margins
Teva enjoys : ++ competitive advantages => continue earnings excess returns + able to purchase competitors at a low price
The first company to introduce a new generic drug often captures market share that persists even when more generic drugs are introduced
. Even under very severe competition, Teva would be “the last man standing”

54. A generic of Copaxone – a hazard for Teva?
patent end : 2012
BUT
Continued growth: RRMS gold standard therapy
Pure generic of Copaxone unlikely + significant studies
Proprietary injection device
Limited competition: slow penetration of competitors
2009 : MHRA : expanded label => treatment of patients with clinical isolated syndrome suggestive of multiple sclerosis
(=medicines and healthcare products regulatory agency)

55. 2009: FDA blocks approval of a generic version of its Copaxone
Momenta Pharmaceuticals Inc. and Mylan Inc.
Petition : to slow the approval process + prolong market exclusivity
FDA -> no generic version of Copaxone in U.S. market until 2011

56. Competitors?
Novartis: biogeneric version of Pfizer's Genotropin (a human growth hormone), Japan
Merck: plans to develop biogenerics BioVentures
=> "Teva is going to be competing with the big boys,“
says Sanford Bernstein analyst Ronny Gal
Big Pharma : join the generic market:
- Pfizer would expand its portfolio of generics
- GSK: partnership with Indian generic company

57. Israel: threat? Inaccessible market such as Iran….
Political, military conflict

58. PERSPECTIVES

59. What about the futur ? $31 billion in 2015
net income of $6.8 billion in 2015
generics: $135 to $150 billion by 2015
government reforms: cost savings + $150 billion worth of brand name drugs losing patent protection in the next 5 years
boost profits by 14% annually for the next 5 years, compared with flat earnings at the five biggest pharmaceutical companies
So far the drugmaker is on target to reach that goal!

60. International expansion

61. Growth in biosimilars

62. Mix of generics and branded remains constant

63. SWOT Strengths Weaknesses Opportunities Threats
Teva-Barr is the largest global generics company
Growing position in CNS with branded products
Expertise in patent challenges
Acquisition of Barr limits scope for further large M&A in the near term
Opportunities
Threats
Make use of economic woes to generate support for favorable biosimilar legislation in the US
Further expansion into ex-US markets
Use of financial strength to launch at risk
Shift manufacturing to lower cost countries
Early arrival of generic Copaxone
Increasing strength of competing generics companies
Maturation of US and other key markets
Declining number of branded drugs to target

64. What about joining TEVA ?

67. End of phase III, 2012 Talampanel CT 011
Glutamat receptor antagonist, orphan drug
Monoclonal antibody against Pd1 protein=> inhib celular apoptosis
CT 011

68. Pipeline products in development
Project
Indication
Clinical phase
Partner
Formulation
Laquinimod MS
III
Active biotech
Oral
TV-1102
IIa completed
Antisense therapeutics Inc
Inj
Pagoclone
Persistent developmental stuttering
IIb
Endo pharmaceuticals
Talampanel
Amyotrophic lateral sclerosis II
Glioblastoma
II completed
Adenovirus vaccines
Respiratory diseases
US department of defense
inj
Cf Barr acquisition : prevent epidemics of an acute respiratory disease to armed forces personnel/market it to immunosuppressed patients

69. Projects in which they have an interest
Indication
Clinical phase
Partner
Investment Million $
StemEx
Hematological malignancies
III
Gamida cell 25
CT-011
Solid tumors and hematologicl malignancies II
Curetech
10.5
Debrase
Removal of burn-ijured tissue
III in Europe
MediWound 15
Diapep-277
Type I diabetes
Andromeda biotech 10