Presentations by Dr. Alexandra Graham, Phytosearch and BDA Foundation/PharmAfrican made at the Euro-Africa Health Investment Conference, March 26 - 27, 2013, London, United Kingdom.

1. DEVELOPMENT OF DRUGS FROM
INDIGENOUS AFRICAN SOURCES
Partnerships Between
North and South
Dr. Alexandra E Graham
Vice President, LaGray
President, PhytoSearch
International

2. LaGray, Inc. Mission
We establish state of the art
pharmaceutical manufacturing facilities
in Africa that are compliant with
international standards of GMP;
We develop African indigenous remedies
into quality-assured medicines;
We form partnerships to deliver
healthcare solutions in Africa.

3. LaGray, Inc. Vision
Our vision is to provide lasting
solutions to Africa’s healthcare
problems through sustainable
technological growth that leads
to self-sufficiency

4. LaGray Chemical Company, Ghana
Objective to establish fully vertically
integrated pharmaceutical manufacturing
company in Africa
• Fully GMP Compliant
• Vertically integrated
• Drug discovery and development
capabilities

5. History
2000
2005
2009
2013
Sponsor Funding
??
Africinvest
The US Overseas
Private Investment
Corporation
Fidelity Capital Partners

6. VIDEO
Courtesy of
Africa Report on December 31, 2010 in Success Stories

8. Recognition
“As Ghanaian and Nigerian Americans,
you have a unique ability to help because
of the power of your experience”
- William Jefferson Clinton
(April 2003)
2009 Frost & Sullivan African Excellence award for innovation in
the pharmaceuticals business
2nd Ghana Business & Finance Excellence award, Gold Category
2010
3rd Ghana Business & Finance Excellence Award, Gold Category
2011
ANDI Center of Excellence for Drug Manufacturing 2012

9. Set up for partnerships
Public private partnerships for custom
solutions to pharmaceutical needs in Africa
Custom manufacturing services to other
companies, distributors, NGOs
Partnering for drug discovery from
indigenous natural product resources

10. Phytosearch is a non-profit 501 c (3) corporation
Focused on development of indigenous African
medicinal plants into affordable standardized
medicines with proven:
• Efficacy in specified indications
• Good safety profile
• Assurance of consistent quality

11. Anti-malarial Drug Discovery: Conquests
Spanish colonization
•
1
H
•
1630: Discovery of infusion of bark of
Cinchona sp. For treatment of malaria
Production of Jesuit powder as
wonder drug in aid of colonization
N
French colonization
HO
H 3 CO
5
4
2
8
N
Quinine
•
2
1820: Isolation of quinine from
Cinchona nitida . Availability of
quinine as a drug in quest to colonize

12. Anti-malarial Drug Discovery: World Wars
H
N
Lessons from WWI
HO
H 3 CO
Quinine
5
•
3
4
2
8
N
CH 3
CH 3
H
N
N
OCH
CH 3
3
Quinacrine
Cl
N
1917: German identification of
quinacrine based on quinine
pharmacophore

13. Anti-malarial Drug Discovery: World Wars
H
World War II
N
HO
H 3 CO
5
4
N
CH 3
OH
N
H
•
4
1939: German synthesis of
chloroquine based on quinine
pharmacophore
•
5
Quinine
2
8
1942: American synthesis of
amodiaquine based on
quinine pharmacophore
CH 3
N
Amodiaquinine
Cl
N
CH 3
CH 3
N
H
CH 3
N
Chloroquine
Cl
N

14. Anti-malarial Drug Discovery: Other Wars
H
Vietnam War
HO
N
N
H
HO
5
•
6
4
N
2
8
N
1963: American
synthesis of
mefloquine as
prophylactic against
malaria
•
7
H 3 CO
1970: American
synthesis of
halofantrine – one
day treatment
CF 3
CF 3
Mefloquine
CH 3
CH 3
N
HO
Cl
F 3C
Halofantrine
Cl

15. Anti-malarial Drug Discovery: Other Wars
Artemisia annua
•
8
CH 3
H
O
H 3C
Vietnam War – The other side
O
1971: Chinese isolation of
artemisinin from Artemisia annua to
help their Vietnam allies
O
H
O
CH 3
O
Artemisinin
Combination of artemisinin
derivatives with aminoquinolines
– now standard first line
treatment

16. Antimalarial Natural Resources
Triclisia patens
Cochlospermum tinctorium
Cryptolepis sanguinolenta
Croton lobatus
Phyllanthus niruri
Euphoria linta
Albizia gummifera
Microglossa pyrifolia
Acanthospermum hispidum
Pavetta crassipes
Terminalia microptera
Psidium girajava
Cinsapelos mucranta
Maytenus senegalensis
Salacia madagascariensis
Zanthoxylum chalybeum
Picranila nitida
Cassia abbreviata
Senna petersiana
Azerya garcheana
Ajuga reverta
Chlorodendrum nyricoides
Vangueria infansta
Published in Refereed Scientific Journals
Proven activity against Plasmodium falciparum comparable
to extracts of Artemisia annua

17. Cryptolepis sanguinolenta
•
•
Wild creeping/climbing shrub
Root decoction for fevers

18. Cryptolepine
Plant extract – Decoction/tea bag
• Efficacy in malaria comparable
to chloroquine
• 93.5% cure rate
• Antipyretic and
antiinflammatory properties
• No overt toxicity observed
Cryptolepine
• In vitro activity vs. chloroquine
sensitive and resistant
P. falciparum
• MOA: inhibition of heme
detoxification in parasite
• Cytotoxicity
• LD50 mouse
Poor therapeutic index
G.L. Boye, Proc. Int. Symp. On East-West Medicine, 1989, Oct. 10-11, Seoul, S. Korea
K.A. Bugyei, Ghana Med. J., 44, 3 (2010)

19. Approach
• Identify required expertise in Africa and form
partnerships
− Public research institutions
− Private sector expertise
− Government commitment and support
• Seek funding to support public private partnership
• Lead milestone-driven process to develop clinically
proven product

20. Private Sector Partner: Drug Development
Development of standardized
active plant material
Development of standardized formulations
Capsules/Dispersible tablets
Manufacture of clinical
Samples under cGMP
Manufacturing process
development and validation

21. Private and Public Partners: Sustainability
• Cultivars developed from seeds
• Seedlings can be given for farming
• C. sanguinolenta has potential as a cash crop

22. Scalability: Cryptolepis sanguinolenta
• Demonstration farm established
• Good Agricultural Practices to be employed
for harvesting and rotation

23. Government of Ghana
Contribution
USD 1 Million for Clinical Trials of Cryptolepis
sanguinolenta capsules by Noguchi Memorial
Institute for Medical Research (NMIMR)

24. Partnerships for Drug Development
Herbal
Medicines
Validated
through
Science
Developed
through
partnership
Research
Institutions
Commercialized
by
Africa-based
Manufacturers
Private
Sector
Government
Support

25. Thank You
Dr. Alexandra E. Graham, MBA
alexandra.graham@lagray.org

26. The Medicines Patent Pool
advancing innovation, expanding access, promoting public health
Greg Perry
Executive Director
www.medicinespatentpool.org

27. MPP Created to Expand Access, Increase
Innovation, Promote Health in HIV
• MPP endorsed by the UN General Assembly, the World Health
Organization and the G8
WIN-WIN-WIN
SOLUTION
ONE-STOP
SHOP
• Global treatment gap: Only 54% PLHIV, 28% CLHIV on treatment
• Access to patented products is critical for the lives of millions in
Africa. MPP can make innovation accessible through IP sharing

28. African Context
• 34 million PLHIV. 69% live in Sub-Saharan Africa
• 3.4 million CLHIV. 90% live in Sub-Saharan Africa
• Since 2001, the number of people newly infected in the
Middle East and North Africa increased by more than 35%
• CHALLENGES:
Intellectual Property
Regulation
Price / Purchasing power

29. Three Main Objectives
•
Enable the development of fixed
dose combinations (FDCs) of
which the patents are held by
different entities
•
Enable the development of
adapted formulations for
children or for specific developing
country needs (e.g., heat stable)
•
Accelerate the availability of
generic versions of new ARVs in
developing countries
29

30. Our Licences
Components of our licences:
Transparent
Broad developing country reach
economies of scale
Technology transfer (Gilead)
Data exclusivity waivers
Right of manufacturing globally (ViiV)
Voluntary

31. Impact
•
Five priority ARVs including one paediatric ARV licence in MPP
•
Six ARV manufacturers licensed from MPP, more affordable ARVs
already being purchased in at least 10 developing countries
•
Technology transfer to generic manufacturers carried out in relation to
four ARVs
•
On track to accelerate availability of new ARVs in developing countries
•
Awarded a Deal of Distinction Award by the Licensing Executives
Society
•
Patent Status Database is "an invaluable step towards furthering
access to treatment of HIV/AIDS" by UN agencies and major
organizations procuring ARVs

32. Viiv Licence – Call For Generics
Just announced invitations to sub-licencees for paediatric abacavir.
The two key criteria are:
Demonstrated capability and willingness to develop, manufacture and
distribute ARV paediatric formulations in developing countries
Quality requirements: WHO Prequalification, USFDA, EMA or other
stringent regulatory authority
More information is available on our website
www.medicinespatentpool.org

33. Thank You
“Encouraging the voluntary use, where appropriate, of new mechanisms such as partnerships, tiered
pricing, open-source sharing of patents and patent pools benefiting all developing countries, including
through entities such as the Medicines Patent Pool, to help reduce treatment costs and encourage
development of new HIV treatment formulations, including HIV medicines and point-of-care diagnostics, in
particular for children” – UN General Assembly Political Declaration on HIV/AIDS, June 2011
“The Medicines Patent Pool is a means to enhance availability and facilitate the
development of new fixed-dose combinations and adapted formulations, such as
paediatric formulations, through voluntary licence agreements.” - HIV Strategy
2011-2015
“We welcome the Patent Pool Initiative launched by UNITAID…and we invite the voluntary participation of
patent owners, private and public, in the project.” – G8 Summit, Deauville, France, May 2011
“Encourage the use of new mechanisms such as the UNITAID Medicines Patent Pool to help
reduce treatment costs and promote the development of new treatment
formulations, including paediatric formulations and fixed-dose combinations.” – Sao Paulo
Parliamentary Declaration on Access to Medicines and Other Pharmaceutical
Products, Global Fund Partnership Forum, June 2011
“The Medicines Patent Pool has potential to support access to more appropriate and affordable ARVs in
developing countries by setting incentives for product adaptation and generic production. We will
encourage the pharmaceutical sector to engage actively with the Medicines Patent Pool to support the
availability of more appropriate and affordable ARVs.” – UK Position Paper on HIV, May 2011
"One promising initiative that can help decrease the cost of patents for the Index Countries is
the patent pool initiative of UNITAID.“ - ATM Index 2010
“We urge all public institutions and pharmaceutical companies to follow the measures taken
by the NIH, and to share without delay their patents on this and other antiretrovirals with the
Medicines Patent Pool, in order to facilitate access to these treatments at the lowest possible
price for countries in need.” - Prof. Michel Kazatchkine, Former Executive Director
“This licence underlines the U.S. Government’s commitment to the Medicines Patent Pool and its goal to
increase the availability of HIV medicines in developing countries. We are now discussing licensing to the
Medicines Patent Pool other patents that could have a positive impact on the treatment of HIV/AIDS.”
- NIH Director Francis S. Collins, M.D., Ph.D.

35. Objectives for this session
▪
Medical products in Africa
Present a perspective on the opportunities in the
Continent and the implications for local/global players
▪
Innovation and tech transfer
Discuss what is needed in terms of innovation and
the positioning of local players
▪
Open questions
Openly discuss how access and innovation can be
enhanced
McKinsey & Company
|1

36. Emerging markets become an ever more important focus
%, $ billions
Global Medical Device Market1
Growth drivers in emerging markets
Developed markets
Emerging markets2
100% = 313
81
322
80
355
CAGR
2010-16
%
397
445
77
73
69
~3
31
~13
1 Households spending proportionally more
on healthcare as income rises
▪ Increasing wealth, average age, changing
lifestyle and prevalence of chronic diseases
▪ Increasing middle class, substantially
increasing discretionary income
2016
19
20
23
27
2008
10
12
14
2 Government HC spend increasing fast,
steadily rising as percent of spend
▪ Expanding insurance coverage
▪ Investment in delivery and medical
infrastructure
3 Physician education and training on the rise
Key to market penetration and development,
especially for medical products
What is happening in Africa?
1 Excludes surgical & injectable aesthetic devices & traditional wound care products; includes imaging service revenues
2 Includes Latin America, Africa, Carribean, Middle East, Asia (excluding Japan, New Zealand & Australia) & CEE
SOURCE: Health Research International 2010; Business Monitor International; McKinsey analysis
McKinsey & Company
|2

37. From the turn of the century Africa has started to generate
superior growth
Africa
Real GDP, CAGR, percent based on 2000 constant USD
Broad independence
and first military
coups
4.8
Communism, oil
shocks, and selfenrichment
The lost decade
4.5
3.8
3.1
1970 - 80
1980 - 90
▪
▪
▪
▪
▪
Most African
countries (32) gain
independence (e.g.,
Algeria, Nigeria)
Several military
coups (DRC, Ghana)
1964 – Mandela
sentenced
1967 – Egypt six-day
war
SOURCE: World Bank. McKinsey
▪
▪
▪
Last decade
+96%
4.9
1960 - 70
▪
AIDS, drought,
genocide, terrorism,
and Mandela
5.3
2.6
▪
World
5 more countries
gain independence
(e.g., Angola)
Oil price increases
from USD 3 to 38
1971 - 79 – military
coup by Amin in
Uganda
1974 – Rumble in
the Jungle
▪
▪
▪
▪
Oil price crashes
Reagan supporting
anti-communist
1983 – Islamic
revolution in Sudan
1984 – Ethiopia
famine
1985 – Military coup
in Nigeria
Carter push sanctions
on SA
2.6
2.8
2.5
1990 - 2000
▪
▪
▪
▪
▪
2000 - 10
AIDS epidemic
1993 – Battle of
Mogadishu in Somalia
1994 – Rwanda
genocide
1994 – Mandela wins
SA elections
1997 – U.S. firms
barred from doing
business with Sudan
(terrorism)
McKinsey & Company
|3

39. Example – South Africa’s medical product market growth
expected to accelerate to 11% p.a.
South African medical product sales
R1 bn, 2008-11



Upgrade of hospitals nationally
($2-3bn over 3 years)
+11% p.a.
Phased introduction of national
health insurance (additional $2030bn into the system over next
15 yrs)
Rapidly growing middle income
segment / consuming class (1520% growth of middle income
groups by some estimates)
2.1
1.9
+3% p.a.
1.8
1.6
1.2 1.2
1.3
1.4 1.4
08 09 10 11
12 13 14 15 16
1 Nominal
SOURCE: BMI Pharmaceuticals & Healthcare Report, Q2 2012; McKinsey analysis
McKinsey & Company
| 5

43. There are important access barriers
Limited
infrastructure/
capacity
Countries with poor
health-care
infrastructure (e.g.,
number of
physicians and
hospital beds)
Poor quality
Markets with
physicians lacking
awareness or skills
(e.g., to perform
advanced
procedures)
Restricted
funding and
reimbursement
Markets with
infrastructure and
quality, but restrictions on funding or
pricing (e.g.,
medical device
spending/ healthcare spending)
Broad access
Markets with good
infrastructure,
capacity/quality,
and favorable
funding or pricing
situation
Most Africa today
CEE today
Short-term
Rest of Europe today
Long-term
McKinsey & Company
|9

46. Collaboration for knowledge and technical transfer from large
global players is key– China example
Partnership
examples
Deal structure
Deal rationale
▪ Established joint
▪ GE: Leverage Shinva’s product portfolio and strengths
venture (GE 49% stake)
▪ Total JV investment
$25mn
▪ Philips acquired
Goldway in a deal worth
$46mn
in local manufacturing and procurement to develop and
promote mid-/low-end X-ray systems for the lower-end
healthcare market, which is a focus of the healthcare
reform
▪ Shinva: Obtain technology and quality support from
GE, and improve its brand image
▪ Philips: Leverage Goldway’s complementary patient
monitor portfolio, not only for the Chinese market, but
for export to other value-conscious, high-growth
markets
▪ Goldway: Take both brand and technology advantages
of Philips to improve marketing competitiveness and
provide more reliable and affordable products
▪ Medtronic acquired
▪ Medtronic: Expand beyond the high-end ortho market
15% stake of Weigao
with $221mn
▪ Established a JV for
orthopedic product line
(Medtronic 51% stake)
by leveraging Weigao’s mid- to low-end product
portfolio and sales network
▪ Weigao: Broaden business and improve R&D capability
to become a leading medical device company in Asia
SOURCE: Literature search; McKinsey analysis
McKinsey & Company
| 12

47. We see broader efforts in Africa emerging, but still lots of room to build
Recent partnerships in Africa

Philips and local partner PPC Ltd are
collaborating with the Federal Ministry of Health
with new Brilliance CT 16-slice scanner.

Phillips Healthcare partnered with the non-profit
organization Imaging the World (ITW) to
introduce the Philips CX50 Compact Xtreme
portable ultrasound system in local hospitals
▪ Siemens in partnered with Meditec Systems Ltd to
provide a complete solution to the Cancer Care
Centre in Nairobi, Kenya, which serves the
community of East and Central Africa
▪ Siemens and TOGA (ZA) have partnered on the
innovative TOGAtainer – a turnkey lab that can be
placed anywhere for decentralized lab services
SOURCE: McKinsey
McKinsey & Company
| 13

48. Support to establish local R&D hubs is another way
to transfer tech and improve access
Strategic initiatives
▪ Significant investments in R&D infrastructure
– Opened first global technology center in Gurgaon
– Conducts product development on all categories of
▪ Entered the Indian market through
$1.65bn acquisition of Howmedica, a
Pfizer subsidiary and leading producer of
orthopedic implants and instruments in 99
▪ Headquartered in Gurgaon, Haryana
▪ Has a 20% share in the joint replacements
market in India, but also sells surgical
equipment and hospital beds
SOURCE: Web search, press searches
operation
– Functions as a global talent hub for Stryker
operations throughout the world
– Plans to set up state-of-the-art operation theater at
the Gurgaon facility for interactive visual learning
with partners around the world
▪ Phase-wise product launch approach
– Went national after one year of launch in a region
(e.g., autologous blood transfusion product,
CONSTAVAC CBC II, the first such product in India)
▪ Market expansion through technology use
– Setting up telemedicine centers in India for
educational purposes through alliances with reputed
research institutes
McKinsey & Company
| 14

50. The markets are very different and still shaping and growing
South Africa
45
Share of
total business
from small
player incl. locals
Global players
have 2-3%
shares
▪ Most products are still imported (e.g.,
▪
▪
Nigeria
▪
51
6 global players
including (incl. Mindray)
90% in Kenya), and global link through
local distributors
Some local production in South Africa but
focus mostly on distribution
The market still looking for broader
quality/price balance and service/tech.
support
Players like Toshiba and Mindray now
making strong in-roads
Local players should
▪ Start investing in selected
Kenya
▪
25
5 Global players
SOURCE: McKinsey analysis
▪
granular opportunities
Look for similar opportunities
already implemented ex-Africa
Early ventures/entrepreneurs
should actively seek investment
to capture selected growth
McKinsey & Company
| 16

52. Euro-Africa Health Investment Conference
March 26-27, 2013
London, UK
Going beyond manufacturing:
the benefit of co-development and sustainable sourcing
FONDATION BDA
PHARMAFRICAN

53. WORLD MARKETS & OPPORTUNITIES
Annual sales growth
5 years (BCC Research 2010) :
 Functional food
8.5 -10 %
 Cosmetic products 15 %
WORLD SALE
OF HEALTH AND WELLNESS PRODCUTS
US$ 627.5 billions in 2010
US$ 772 billions in 2016
(Euromonitor international, 2011)
The cosmetics market is looking
diversify range. (BCC research 2010)
WORLD MARKT
OF NUTRACEUTICALS
US$ 243 billions in 2015
The antioxidants segment represents
approximately $ 500 million of revenue for
the component ingredients (Euromonitor 2011)
(Global Industry Analysts, 2010)
WORLD MARKET
OF BOTANICALS
> US$ 60 milliards
(CIC, Geneva)
WORLD MARKET
OF BOTANICAL DRUGS
US$ 32.9 billion In 2013
(BCC Research)
SUB-SAHARIAN AFRICA
25% of natural world
ressources, 0.01% OF WORLD
MARKET.
FONDATION BDA
to
PHARMAFRICAN

54. BDA-PHARMAFRICAN PLATFROM:
AN ECOSYSTEM OF INNOVATION GENERATING A TRIPLE RETURN
ECONOMIC, SOCIAL AND ENVIRONMENTAL

55. BDA & THE PLANT ACTION PROGRAM
AFRICA BASED PROGRAM
Plant Action Program
Entrepreneurship
and business
mentorship
PROCESSING CENTER
QA & QC
Botanicals
production &
processing
« ABS safe »
QUALITY LABORATORY
A new generation of agribusinessman
Responsible and sustainable sourcing of quality
controlled botanicals
TRIPLE BOTTOM LINE IMPACTS
ECONOMIC
SOCIAL
ENVIRONMENTAL

56. and GOVERNMENT together
focussing on economic governance's improvement
MULTILATERAL DONNORS
Ministry of Agriculture
Ministry of Environnement
Ministry of Health
Ministry of Labour
Ministry of Plan
MULTIPLE INTERNATIONAL
AW A R D S
Terre de Femmes Canada
International Biodiversity
Sustainable development Leader
Carole Robert Women of the Year
Canada-Africa Partnership
ABS model program | COP10
Model of Green Ecomony | Rio+20
FONDATION BDA
PHARMAFRICAN

57. PHARMAFRICAN
PharmAfrican is a young biopharma start-up, with a mission
to provide 3BL to shareholders (economic, social and
environmental) by developing and commercializing
inovative health ingredients » derived from highly value
added African plants, « botanicals », and responding to
the requirements and needs of B2B market:
 of
the
natural
health
products
(Superfoods, cosmetics, nutraceuticals and functional
foods): PHARMAFRICAN INC. DIVISION
 of the biopharmaceutic products («botanical drug»):
PHARMAFRICAN PHARMA DIVISION
PharmAfrican
works
in
partnership
with
Government, academic, industrial and social innovation
actors as part of a sustainable development hybrid
platform, to meet 3 levels of needs namely
economic, social and environmental, by promoting the
sharing of profits with a vision of development and
sustainable commitment.

58. Regulatory context
WHAT IS A
BOTANICAL DRUG ?
A botanical drug is intended for use as drug; a
drug that is prepared from a botanical substance.
FDA definition
 Identification of active compounds not essential
 Purification not required
FDA published on 6/9/06
 Chemistry/Manufacturing and Control (CMC) is extended to raw material
 Pre-clinical evaluations may be reduced
 Same level of clinical efficacy/safety requirements as standard drugs
 Utilization of the “historical” safety information to expedite early stage
testing and evaluation of botanical products

59. PharmAfrican Business Strategy
Botanical drugs
Pre-clinical
IND
Phase I
Phase II
Phase III
DIN
Market
Botanical drug
Deal with large pharmas looking for pipeline
FALLBACK POSITION
Pre-clinical
Clinical studies
Natural Products –
Supplements
Health Canada NHPD
FDA, Food supplement
Market accessible with large
marketing investment

60. OUR PLATFORM & INVESTMENT STRATEGY ?
Early stage R&D
in Africa
IMPACT
INVESTNG
?
Investment in
advanced R&D
Clinical studies
Scale up
Investment in
Manufacturing
( + cGMP) infrastructures)
Commercialisation and
marketing
African
universities ?
African
governments ?
POC
Specialized investment funds
Venture Capital funds
Industries

61. PARTNERING FOR IMPACT: JOINING FORCES TOWARD
ECONOMIC RETURN, SOCIAL INNOVATION AND GLOBAL ISSUES
Join the Team!
We are interested in talking to
Partners, Donors, Investors
Researchers and Innovators
We believe that companies that
implement a Stakeholder Strategy will
improve their returns to Shareholders
FONDATION BDA
PHARMAFRICAN