Semi-synthetic Artemisinin: A New Source of Artemisinin to Reduce Barriers to ACT Access November 18, 2008 London, UK Presented By Philippe Desjeux, PhD

1 iOWH Mission The Institute for OneWorld Health Develops Safe, Effective, and Affordable New Medicines for People with Infectious Diseases in the Developing World

2 The Partnership

3 Project Vision: Semi-synthetic Artemisinin Increase Access to ACT Cures Global Health Challenges (Artemisinin Supply)  Synthetic Biology (Biotechnology )

4 Semi-Synthetic Artemisinin Project Goals  Create a complementary source of non-seasonal, high- quality and affordable artemisinin to supplement the current plant-derived supply  Contribute to stabilizing the price of artemisinin to benefit all stakeholders  Ensure semi-synthetic artemisinin is available to all high- quality derivatizers and ACT manufacturers  Enable millions of people infected with malaria to gain consistent access to affordable, high-quality, life-saving ACTs

5 A Second Source Supplements & Stabilizes the Artemisinin Supply Chain Chemistry Artemisinin Artemisini c Acid Yeast + Sugar Fermentation DERIVATIVES ACT Therapy Artemisinin Extraction Cultivation Months Days Controlled Process

6 Artemisinin As A Starting Material Artemisinin Dihydroartemisinin Artesunate Artemether Artelinate Arteether Artemisinic acid Raw material Defined specifications Starting material Defined specifications API Compendial specifications GMP manufacturing

7 Achievements & Goals Achievements Completed strain engineering to reach productivity targets at bench scale fermenter level Transferred technology (fermentation, purification, and chemistry) to manufacturing partner Reproduced laboratory data at pilot scale Goals Demonstrate chemical comparability between semi- synthetic and plant derived artemisinin  No need for bioequivalence studies Process optimization and development of industrial processes suitable for 100,000L scale

8 Artemisinin: A Starting Material for ACTs  In the production of ACTs, artemisinin is a starting material NOT an API  Derivatives manufactured from artemisinin are the active pharmaceutical ingredients (API) in ACTs  The WHO monograph, which currently lists artemisinin as an API, may need to be updated to reflect current manufacturing practices  The semi-synthetic process will consist of a well documented microbial fermentation to produce artemisinic acid (AA) followed by synthetic chemical steps to reach artemisinin.  The plan is to pursue chemical comparability as a regulatory approach for semi-synthetic artemisinin

9 Semi-synthetic Artemisinin Timeline Process Development and Scale up Industrialization Pre-Development 10,000L1000L100,000L Commercial Production 2 nd Source of Artemisinin for ACTs

10 Market Impact  Supplement botanical supply to support projected increased demand for ACTs  Semi-synthetic artemisinin cost is anticipated to be comparable to the current cost of high quality field production  Semi-synthetic artemisinin will be made broadly available to those derivative and ACT manufacturers who will apply the principle of “no profit, no loss”

11 Thank You