Aspen Pharmacare: HIVAids Franchise

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• Aspen Pharmacare HIV/Aids Franchise
• Jackie Tau 2006.03.09

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Anti-retrovirals (ARVs)

• Voluntary Licenses and Access Arrangements
• Aspen successfully negotiated several
  arrangements which facilitate access to a variety
  of patented ARV molecules
• Aspen continues to identify key anti-retroviral
  molecules and negotiate with owners of
  intellectual property to secure affordable access
• Aspen is the ONLY company in the world to have
  all these valuable arrangements
• Boehringher Ingelheim
• Nevirapine
• Aspen secured a voluntary license
• Aspen developed a tablet and suspension dosage
  form

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ARVs

• Bristol Myers Squibb
• Stavudine and Didanosine
• Aspen has developed a range of Stavudine (15mg,
  20mg, 30mg and 40mg) capsules as well as a range
  of Didanosine (50mg, 100mg, 150mg, 200mg)
  dispersible tablets
• Atazanavir
• Technology transfer collaboration agreement for
  manufacture and distribution of a generic version
  of the product
• Gilead
• Tenofovir and Emtricitabine
• Technology transfer agreement for manufacture and
  distribution of Viread and Truvada

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ARVs

• GlaxoSmithKline
• Lamivudine and Zidovudine
• Voluntary license
• Aspen has developed forms containing both
  molecules individually
• Zidovudine 300mg tablets
• Zidovudine 100mg 200mg capsules
• Zidovudine 10mg/ml syrup, and
• Lamivudine 150mg tablet
• Lamivudine 10mg/ml syrup
• As well as the combination tablet Lamzid
• Lamivudine 150mg and Zidovudine 300mg
• Merck
• Efavirenz
• Voluntary license
• Aspen is developing tablet and capsule dosage
  forms for registration

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ARVsProducts registered at Medicines Control
Council (MCC)

• Stavudine 15mg, 20mg, 30mg and 40mg
• Didanosine buffered tablet 50mg, 100mg, 150mg and
  200mg
• Zidovudine 100mg and 200mg capsules, 300mg tablet
  and 10mg/ml syrup
• Lamivudine 150mg tablet and 10mg/ml syrup
• Lamivudine 150mg and Zidovudine 300mg tablet
• Nevirapine 200mg tablet and Nevirapine 50mg/5ml
  suspension
• Aspen Lamzid and Nevirapine Co-pack

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ARVs WHO Pre-Qualification

• The Aspen oral solid dosage (OSD) manufacturing
  site in Port Elizabeth has been approved by WHO
  for manufacture of the listed products
• Products already prequalified
• Aspen Stavudine 20mg, 30mg and 40mg capsules
• Aspen Lamivudine Tablets 150mg
• The following products are pending
  pre-qualification
• Aspen Lamzid Tablets (Lamivudine/Zidovudine
  combination)
• Aspen Nevirapine 200mg Tablets
• Aspen Zidovudine 300mg Tablets
• The following product is listed on the
  pre-qualification list by virtue of its FDA
  tentative approval
• Aspen Lamzid and Nevirapine Co-Pack
• Between 14 to 24 future developments will be
  submitted to WHO for pre-qualification within a
  year

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ARVsUnited States Food and Drug Administration
(FDA) (for access to PEPFAR funding)

• Products submitted either as New Drug
  Applications (NDA) or abbreviated New Drug
  Applications (ANDA) to the FDA
• Tentatively approved
• Aspen Lamzid and Nevirapine Co-Pack
• Awaiting tentative approval
• Aspen Lamzid
• To be submitted in the foreseeable future (/- 12
  months)
• At least 14 products as a combination of NDAs
  and ANDAs

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ARVsRegistration with African Regulatory
Authorities

• Products submitted or pending submission include
  the various presentations of
• Stavudine
• Didanosine
• Zidovudine
• Lamivudine
• Lamivudine/Zidovudine combination,
• Nevirapine
• Combination pack
• Gilead molecules and BMS Atazanavir handled
  separately

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ARVs

• Product registration status
• Dossiers submitted key registrations imminent
  in many territories
• Dossiers under compilation for submission into
  the following countries
• Cameroon, Benin, Burundi, Mali, Burkino Faso,
  Sudan, Cote DIvoire, Angola, Madagascar,
  Mauritius and Seychelles.
• Other countries to be added where required
• Products in Development
• A number of anti-retroviral products are in
  development
• Include fixed dose combinations, new molecules
  and new strengths of existing molecules
• There are 14 products currently in development
  which will all be submitted to MCC, WHO and FDA
  within the next 12 months

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Gilead

• Aspen to manufacture innovator product
• Viread which contains Tenofovir 300mg
• Truvada which contains Tenofovir 300mg and
  Emtricitabine 200mg
• License agreement makes provision for Aspen to
  manufacture and distribute in the following
  countries
• Algeria, Angola, Benin, Botswana, Burkina Faso,
  Burundi, Cameroon, Cape Verde, Central African
  Republic, Chad, Comoros, Congo, Congo, Dem. Rep.
  of the Côte d'Ivoire, Djibouti, Egypt, Equatorial
  Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana,
  Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia,
  Libya, Madagascar, Malawi, Mali, Mauritania,
  Mauritius, Morocco, Mozambique, Namibia, Niger,
  Nigeria, Rwanda, Sao Tome and Principe, Senegal,
  Seychelles, Sierra Leone, Somalia, South Africa,
  Sudan, Swaziland, United Republic of Tanzania,
  Togo, Tunisia, Uganda, Zambia, Zimbabwe

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Gilead

• Aspen manufacture for Gilead distribution in the
  following territories
• Afghanistan, Antigua and Barbuda, Bahamas,
  Bangladesh, Barbados, Bhutan, Bolivia, Cambodia,
  Dominica, Dominican Republic, Grenada, Guatemala,
  Guyana, Haiti , Honduras, Indonesia, Jamaica,
  Kiribati, Kyrgyzstan, Lao People's Dem. Rep.
  (Laos), Maldives, Moldova, Rep. of Mongolia,
  Myanmar, Nepal, Nicaragua, Pakistan, Papua New
  Guinea, Saint Kitts and Nevis, Saint Lucia, Saint
  Vincent the Grenadines, Samoa, Solomon Islands,
  Syria, Tajikistan, Timor-Leste, Trinidad and
  Tobago, Tuvalu, Uzbekistan, Vanuatu, Vietnam,
  Yemen

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Gilead

• Viread Registration Status

• Truvada Registration Status

• Gilead Products
• Submission of files into all countries to be
  completed within a year
• Aspen manufacturing cutover for supply due in May
  2006 for Viread and July 2006 for Truvada
• Validation batches completed

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BMS

• Atazanavir
• 3 strengths 20mg, 100mg and 200mg capsules
• License agreement offered to only two
  manufacturers
• Aspen Emcure (India)
• License agreement makes provision for Aspen to
  manufacture and distribute in the following
  countries
• Angola, Benin, Botswana, Burkina Faso, Burundi,
  Cameroon, Cape Verde, Central African Republic,
  Chad, Comoros, Congo, Democratic Republic of
  Congo, Côte d'Ivoire, Djibouti, Equatorial
  Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana,
  Guinea, Guinea-Bissau, Kenya, Lesotho, Liberia,
  Madagascar, Malawi, Mali, Mauritania, Mauritius,
  Mozambique, Namibia, Niger, Nigeria, Reunion,
  Rwanda, Sao Tome and Principe, Senegal,
  Seychelles, Sierra Leone, Somalia, South Africa,
  Sudan, Swaziland, Tanzania, Togo, Uganda, Zambia,
  Zimbabwe
• Products to be submitted for registration
  following successful generation of data required
• Critical product as WHO estimate because of
  resistances 500 000 patients will need 2nd line
  regimens in the next 2 years

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ARVsWHO ART guidelines for Adults and
Adolescents (revised 2005)

• 1st Line Regimen
• 2nd Line Regimen

Zidovudine or Stavudine
Nevirapine
Lamivudine or Emtricitabine
Tenofovir or Abacavir
Efavirenz
Didanosine or Tenofovir
Abacavir
Atazanavir/Ritonavir or Lopinavir/r or
Sequinavir/r
Efavirenz or Nevirapine
Zidovudine (/- Lamivudine)
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ARV Statistics

• 96 of Africa on 1st line time ARVs
• Projections
• WHO/UNAIDS tableting treatment in
• 2008 5.2m lives
• 2020 10.0m lives
• 50 of these lives will be in Africa
• We believe these to be too ambitious
• Clinton projection for 2008 is
• High 5.2m patients
• Low 2.3m patients
• Currently 400 000 treated in Africa (excluding
  SA)
• Aspen has a meaningful share
• Africa volume demand is for fixed dose
  combination
• Development of fixed dosage combination will
  increase volume opportunities
• Developed individual molecules first

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ARVs

• Our ARV volumes and values are increasing monthly
• Our three key markets are
• SA private market
• SA public market
• African Export market
• SA private market is increasing and should
  increase further
• ARVs included in prescribed minimum benefits
• Increased patient acceptance of Aspen generics
• SA public market
• Aspen has the lions share of the three year SA
  tender market
• patients have increased from /-20 000 a year ago
  to our estimate of 80 000 today
• this will increase substantially over the next
  twelve months

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ARVs

• Exports are the largest growth area
• In recent months have now exceeded the SA market
  sales
• Have been limited by individual countrys
  registration requirements
• Registrations now trickling through giving
  increased growth opportunities
• Key registrations and approvals expected within 8
  weeks
• Exports focus has absorbed human
  resources/production etc. but starting to show
  off-take

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Tuberculosis (TB)

• Why TB?
• Aspens social commitment is to provide quality
  care at affordable pricing for infectious
  diseases with a focus on
• HIV/AIDS
• TB including Multi-drug resistant TB (MDR-TB)
• Malaria
• In 2004 there were 529 000 new TB cases
• 66 of all TB cases in SA were also infected with
  HIV
• 83 of TB cases in KZN were also HIV positive

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TB

• The Medical Research Council (MRC) stated that
  SA faces one of the most devastating TB epidemics
  in the world. There are several reasons for
  this
• Large proportion of population are
• very poor
• immune-compromised
• 44 of population estimated to be in rural areas
  in 2005
• 67 of people experience problems with transport
• Therefore its not surprising multi-drug
  resistant TB (MDR-TB) is becoming more
  prevalent in SA
• MDR-sufferer transmits MDR-TB
• The WHO defines an MDR-TB hotspot as one in which
  the prevalence level is 3. In SA the current
  level of MDR-TB is 2.7

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TB

• Global TB
• 8.6m fresh TB cases diagnosed every year
• Proposed global joint venture with Lupin which
  gives us access to their API capabilities
  costings. MoU signed
• Key customers could include
• Multi-lateral TB agencies e.g.
• Global Development Fund (GDF)
• Green Light Committee (GLC)
• Procurement agencies in individual countries
• Donor agencies
• Other agencies many of which overlap as current
  ARV funders
• Through this global joint venture Aspen will
  with Lupin become the world leader by volume in
  supplying finished dosage form TB products with
  backward integration of APIs

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TB

• TB in South Africa
• Through Lupin Aspen has acquired the rights to
  key molecules required by State Tender
• Have local manufacturing rights
• Aspen owns all intellectual property
• Aspen has access to Lupins development pipeline
• For three of the four actives in first line TB
  treatment
• Lupin make
• 45 of worldwide Rifampicin
• 85 of worldwide Ethambutol
• 30 of worldwide Pyrazinamide
• Rifampicin and Ethambutol the key cost drivers

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MDR-TB

• Aspens OSD facility now manufacturing
  Cycloserine
• Aspens new sterile facility together with tech
  transfer for Lilly to provide a cost effective
  solution to MDR-TB product Capreomycin
• Aspen seeking registration from the WHO for the
  above products
• All TB including MDR-TB is curable
• Aspen and Lupin will provide a cost-effective
  solution

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Production

• A second IGS line is being installed
• Facing production challenges
• Particularly blister packaging
• Private market switch to small packs and ARVs
  impacted heavily on this area
• New product launches also mainly blister packed
• Impacting negatively on service delivery
• Cannot take advantage of opportunistic business
  in either Public or Private sectors
• New product start up were well managed
• Capacity is sufficient
• Challenge bringing it on line timeously
• As there are Regulatory, Tech transfer,
  time-consuming start-up validation requirements
  and numerous new products
• Given current forecasts and no further changes in
  the private market demand for small packs,
  production issues largely resolved by calendar
  year end

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Production

• Pain will be short term
• Our investment in capacity will put us at the
  forefront of meeting the expected increase in
  future volumes in SA, Africa and the developed
  world.
• Receiving management focus
• Aspen currently manufactures more than 100
  tablets per annum for each and every South
  African, our challenge is to extend our reach

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Summary

• Aspen is not one dimensional
• Affordable basket of chronic medication
• Offshore presence continues to grow
• Already have over 100 ARV registrations in Africa
• SAs best pipeline
• World class manufacturer

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Summary

• Aspen positioned to be global generic leader in
  infectious diseases
• Eagerly await finalisation of legislative changes
• Production delays negatively affecting our
  ability to make opportunistic sales in SA market
• Quality affordable medicines synonymous with
  Aspen product