Dr. Alexandra E GrahamVice President, LaGrayPresident, PhytoSearch International

DEVELOPMENT OF DRUGS FROM INDIGENOUS AFRICAN SOURCES

Partnerships Between North and South

LaGray, Inc. MissionWe 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.

LaGray, Inc. Vision

Our vision is to provide lasting solutions to Africa’s healthcare problems through sustainable technological growth that leads to self-sufficiency

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

Sponsor Funding

2000 2009 2013

The US Overseas Private Investment Corporation

Africinvest

History2005

Fidelity Capital Partners

??

VIDEOCourtesy of

Africa Report on December 31, 2010 in Success Stories

Recognition

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

“As Ghanaian and Nigerian Americans, you have a unique ability to help because of the power of your experience”

- William Jefferson Clinton

(April 2003)

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

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

Anti-malarial Drug Discovery: Conquests

• 1630: Discovery of infusion of bark of Cinchona sp. For treatment of malaria

• Production of Jesuit powder as wonder drug in aid of colonization

Spanish colonization

1

2

French colonization

• 1820: Isolation of quinine from Cinchona nitida . Availability of quinine as a drug in quest to colonize

N

HO

2

45

8

H3CO

N

H

Quinine

Anti-malarial Drug Discovery: World Wars

• 1917: German identification of quinacrine based on quinine pharmacophore

Lessons from WWI

3

N

N

OCH3

CH3

N

CH3

CH3

Cl

H

N

HO

2

45

8

H3CO

N

H

Quinine

Quinacrine

Anti-malarial Drug Discovery: World Wars

• 1939: German synthesis of chloroquine based on quinine pharmacophore

4N

HO

2

45

8

H3CO

N

H

N

NH

Cl

CH3

N

CH3

CH3

Quinine

Chloroquine

• 1942: American synthesis of amodiaquine based on quinine pharmacophore

5N

N

Cl

H

OH

N

CH3

CH3

Amodiaquinine

World War II

Anti-malarial Drug Discovery: Other Wars

N

HO

2

45

8

H3CO

N

H

N

HO

CF3

CF3

NH

HO

F3C

Cl

Cl

N

CH3

CH3

Mefloquine

Halofantrine

• 1963: American synthesis of mefloquine as prophylactic against malaria

6

7• 1970: American synthesis of halofantrine – one day treatment

Vietnam War

Anti-malarial Drug Discovery: Other Wars

Artemisia annua

Artemisinin

O

O

H

CH3H

O

OH3C

CH3

O

• 1971: Chinese isolation of artemisinin from Artemisia annua to help their Vietnam allies

8

Combination of artemisinin derivatives with aminoquinolines – now standard first line treatment

Vietnam War – The other side

Antimalarial Natural Resources

Cinsapelos mucrantaMaytenus senegalensisSalacia madagascariensisZanthoxylum chalybeumPicranila nitidaCassia abbreviataSenna petersianaAzerya garcheanaAjuga revertaChlorodendrum nyricoidesVangueria infansta

Triclisia patensCochlospermum tinctoriumCryptolepis sanguinolenta

Croton lobatusPhyllanthus niruri

Euphoria lintaAlbizia gummifera

Microglossa pyrifoliaAcanthospermum hispidum

Pavetta crassipesTerminalia microptera

Psidium girajava

Proven activity against Plasmodium falciparum comparable to extracts of Artemisia annua

Published in Refereed Scientific Journals

Cryptolepis sanguinolenta

• Wild creeping/climbing shrub• Root decoction for fevers

Cryptolepine

• In vitro activity vs. chloroquine sensitive and resistant

P. falciparum• MOA: inhibition of heme

detoxification in parasite

• Cytotoxicity• LD50 mousePoor therapeutic index

CryptolepinePlant extract – Decoction/tea bag

• Efficacy in malaria comparable to chloroquine

• 93.5% cure rate • Antipyretic and

antiinflammatory properties

• No overt toxicity observed

G.L. Boye, Proc. Int. Symp. On East-West Medicine, 1989, Oct. 10-11, Seoul, S. KoreaK.A. Bugyei, Ghana Med. J., 44, 3 (2010)

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

Development of standardized active plant material

Manufacture of clinical Samples under cGMP

Manufacturing process development and validation

Private Sector Partner: Drug Development

Development of standardized formulationsCapsules/Dispersible tablets

Private and Public Partners: Sustainability

• Cultivars developed from seeds• Seedlings can be given for farming• C. sanguinolenta has potential as a cash crop

Scalability: Cryptolepis sanguinolenta

• Demonstration farm established• Good Agricultural Practices to be employed

for harvesting and rotation

Government of Ghana Contribution

USD 1 Million for Clinical Trials of Cryptolepis sanguinolenta capsules by Noguchi Memorial

Institute for Medical Research (NMIMR)

HerbalMedicines

Validated through Science

Developed through

partnership

Commercialized by

Africa-based Manufacturers

Partnerships for Drug Development

Research Institutions

Private Sector

GovernmentSupport

Thank YouDr. Alexandra E. Graham, MBAalexandra.graham@lagray.org

The Medicines Patent Pooladvancing innovation, expanding access, promoting public health

Greg PerryExecutive Director

www.medicinespatentpool.org

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

• 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

WIN-WIN-WIN SOLUTION

ONE-STOP SHOP

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 PropertyRegulationPrice / Purchasing power

• 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

Three Main Objectives

29

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

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

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 websitewww.medicinespatentpool.org

Thank You

“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 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

“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

“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

“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. 

“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

“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

FONDATION BDA PHARMAFRICAN

Going beyond manufacturing: the benefit of co-development and sustainable sourcing

Euro-Africa Health Investment ConferenceMarch 26-27, 2013London, UK

WORLD MARKETS & OPPORTUNITIES

FONDATION BDA PHARMAFRICAN

NU

TR

AWORLD MARKTOF NUTRACEUTICALS US$ 243 billions in 2015 (Global Industry Analysts, 2010)

WORLD MARKETOF BOTANICALS > US$ 60 milliards(CIC, Geneva)

SUB-SAHARIAN AFRICA 25% of natural world ressources, 0.01% OF WORLD MARKET.

WORLD MARKETOF BOTANICAL DRUGSUS$ 32.9 billion In 2013(BCC Research)

DR

UG

S

WORLD SALEOF HEALTH AND WELLNESS PRODCUTSUS$ 627.5 billions in 2010US$ 772 billions in 2016(Euromonitor international, 2011)

Annual sales growth5 years (BCC Research 2010) : Functional food 8.5 -10 % Cosmetic products 15 %

The cosmetics market is looking to diversify range. (BCC research 2010)

The antioxidants segment represents approximately $ 500 million of revenue for the component ingredients (Euromonitor 2011)

BDA-PHARMAFRICAN PLATFROM: AN ECOSYSTEM OF INNOVATION GENERATING A TRIPLE RETURN

ECONOMIC, SOCIAL AND ENVIRONMENTAL

BDA & THE PLANT ACTION PROGRAM

A new generation of agribusinessman

Responsible and sustainable sourcing of quality controlled botanicals

Entrepreneurship and

business mentorship

QA & QC

Botanicals production & processing

« ABS safe »

Plant Action Program

TRIPLE BOTTOM LINE IMPACTS

ECONOMIC SOCIALENVIRONMENTA

L

AFRICA BASED PROGRAM

PROCESSING CENTER QUALITY LABORATORY

MULTILATERAL DONNORS and GOVERNMENT together focussing on economic governance's improvement

FONDATION BDA PHARMAFRICAN

Ministry of AgricultureMinistry of EnvironnementMinistry of HealthMinistry of LabourMinistry of Plan

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

MULTIPLE INTERNATIONAL

AWARDS

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.

PHARMAFRICAN

WHAT IS A BOTANICAL DRUG ?

FDA published on 6/9/06

Identification of active compounds not essential Purification not required 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

A botanical drug is intended for use as drug; a drug that is prepared from a botanical substance.FDA definition

Regulatory context

Market

Pre-clinical

IND Phase I

Phase II Phase III DIN

Botanical drug

PharmAfrican Business Strategy

Deal with large pharmas looking for pipeline

Botanical drugs

Market accessible with large marketing investment

Natural Products –Supplements

Pre-clinical

Clinical studies

Health Canada NHPDFDA, Food supplement

FALLBACK POSITION

African universities ?

African governments ??

Early stage R&D in Africa

IMPACT INVESTNG

Investment in advanced R&D Clinical studies

Scale up

POCSpecialized investment funds

Venture Capital funds

Investment in Manufacturing

( + cGMP) infrastructures)

Commercialisation and marketing

Industries

OUR PLATFORM & INVESTMENT STRATEGY ?

We believe that companies that implement a Stakeholder Strategy will improve their returns to Shareholders

PARTNERING FOR IMPACT:  JOINING FORCES TOWARDECONOMIC RETURN, SOCIAL INNOVATION AND GLOBAL ISSUES

FONDATION BDA PHARMAFRICAN

Join the Team!We are interested in talking to

Partners, Donors, Investors Researchers and Innovators