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FOR IMMEDIATE RELEASE

OneWorld Health, Amyris Biotechnologies and Sanofi-aventis Announce
Development Agreement for Semisynthetic Artemisinin
Partnership could help boost Artemisinin supply and treat up to 200 million malaria patients each year

San Francisco, CA, Emeryville, CA & Paris, France, March 3, 2008 – The Institute for OneWorld Health (iOWH), the US-based nonprofit pharmaceutical company, together with synthetic biology innovator Amyris Biotechnologies, and leading pharmaceutical company sanofi-aventis today announced they have entered into an agreement for the development of semisynthetic artemisinin, a key ingredient in first-line malaria treatments. This partnership will build on technology originated by Professor Jay Keasling at the University of California, Berkeley.

This collaboration aims to create a complementary source of non-seasonal, high-quality and affordable artemisinin to supplement the current botanical supply, thereby enabling millions of people infected with malaria to gain consistent access to lower-cost, life-saving artemisinin-based combination therapies (ACTs). Under the terms of the agreement, OneWorld Health, Amyris and sanofi-aventis will work jointly to develop and design pilot and commercial scale manufacturing processes, with the goal of introducing low-cost, semisynthetic artemisinin into the supply chain and ACTs in 2010.

“We are delighted to expand this partnership to build on the ground-breaking innovations of the University of California, Berkeley and Amyris Biotechnologies,” said Nina E. Grove, OneWorld Health’s Vice President for Commercial Planning & Strategy. “Sanofi-aventis’ historic commitment to the fight against malaria, its technical capabilities and the track record of its Access to Medicines program make them an ideal partner for this next phase of product development.”

OneWorld Health, UC Berkeley, and Amyris have been working together as the Artemisinin Project since late 2004 to develop a new, low-cost technology platform to produce artemisinin – a project funded by the Bill & Melinda Gates Foundation. UC Berkeley professor Jay Keasling, the originator of the technology, initially identified the genetic pathway and developed a microbial system that produces artemisinin via fermentation. After successfully completing its scientific responsibilities in the Artemesinin Project, U.C. Berkeley continues to license the technology to OneWorld Health and Amyris for further product development and ultimate use in ACTs for the treatment of malaria. Sanofi-aventis, which has extensive experience in the field of malaria drugs, will be the newest partner in this collaboration to increase global access to ACTs.

“Sanofi-aventis and Amyris are among the most advanced companies in synthetic biology,” said Paul Baduel, Director, Process Development Biotechnology of sanofi-aventis. “Sanofi-aventis Process Development teams in biotechnology and chemistry are proud to be involved in the design of an industrial process for the production of artemisinin.”

Amyris will provide strain engineering expertise using the novel tools of synthetic biology. Sanofi-aventis will provide fermentation and chemistry process development expertise, and OneWorld Health will focus on the achievement of public policy and global access goals. If technical benchmarks are achieved,
sanofi-aventis will commercialize the semisynthetic artemisinin.

“This collaboration enables us to reach a goal that some scientists only dream of,” said Jack Newman, founder and Senior Vice President of Amyris. “What started as breakthrough in the lab can now evolve into a real solution that will truly make a difference in the world.”

If it reaches commercial-scale, this alternative source of artemisinin would supplement the supply that is currently extracted from the botanical source Sweet Wormwood plant (Artemisia annua) and produce enough artemisinin for ACTs to treat up to 200 million of the more than 500 million estimated individuals who contract malaria each year. This complementary source of supply would improve the availability of high-quality artemisinin derivatives to drug manufacturers and contribute to stabilizing the price of artemisinin-containing antimalarials to benefit patients and payers.

The World Health Organization recommends using ACTs as a first-line treatment for malaria in regions where the usual first-line treatments for malaria are no longer effective because of increasing drug resistance. Malaria is responsible for more than one million deaths annually.

The Bill & Melinda Gates Foundation awarded OneWorld Health a five-year grant of $42.6 million in December 2004 to manage a research and development collaboration with Amyris and Dr. Jay Keasling of UC Berkeley to utilize the techniques of synthetic biology to develop a new technology platform for producing artemisinin and its derivatives.

About the Institute for OneWorld Health
The Institute for OneWorld Health, the first US nonprofit pharmaceutical company, develops safe, effective and affordable new medicines for people with infectious diseases in the developing world. The Institute for OneWorld Health, headquartered in San Francisco, California, USA, is a tax-exempt 501 (c) (3) US corporation. Media resources are available at http://www.oneworldhealth.org/media/index.php/

About Amyris Biotechnologies
Amyris (www.amyris.com) is applying its proprietary, breakthrough technology to address major global health and energy challenges. Amyris’ technology is used to produce high-value compounds to enable the production of lower cost artemisinin-based anti-malarial drugs and a slate of renewable hydrocarbon biofuels which are expected to be cost-effective and compatible with existing engines and distribution infrastructure. Based in Emeryville, CA, Amyris is a privately-held venture backed company whose investors include DAG Ventures, Khosla Ventures, Kleiner Perkins Caufield & Byers and TPG Ventures.

About the University of California, Berkeley
The University of California, Berkeley, is the nation's number one public university and is home to more top-ranked departments than any academic institution, public or private. The flagship of the 10-campus University of California system, UC Berkeley enrolls more nearly 25,000 undergraduates and more than 10,000 graduate students each year. The university's research budget exceeds half a billion dollars annually, one of the highest of any university without a medical school. Currently on the faculty are seven Nobel Prize winners, 131 members of the National Academy of Sciences and 84 members of the National Academy of Engineering.

About sanofi-aventis
Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT PARIS: SAN) and in New York (NYSE: SNY).

Forward-looking statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include product development, product potential projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans” and similar expressions. Although sanofi-aventis’ management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMEA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labeling and other matters that could affect the availability or commercial potential of such products candidates, the absence of guarantee that the products candidates if approved will be commercially successful, the future approval and commercial success of therapeutic alternatives as well as those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in sanofi-aventis’ annual report on Form 20-F for the year ended December 31, 2006. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.

Contacts:

Institute for OneWorld Health
James Hickman +1-415-403-6317
jhickman@oneworldhealth.org

Amyris
Annika Jensen +1-510-740-7482
jensen@amyris.com

UC Berkeley
Robert Sanders +1-510-643-6998
rsanders@berkeley.edu

Sanofi-aventis
Dr François Bompart
Tel: +33 1 41 24 53 45
Mobile: +33 6 08 25 61 67
francois.bompart@sanofi-aventis.com

FOR IMMEDIATE RELEASE

Research Milestone Brings Goal Closer of Inexpensive Antimalarial Drug for Developing World

Berkeley, Calif. - April 12, 2006 - Researchers striving to create a less expensive version of a life-saving antimalarial drug, artemisinin, have cleared a major hurdle, according to a new report in the journal Nature.

Two and a half years ago, a University of California, Berkeley, team led by Jay D. Keasling, UC Berkeley professor of chemical engineering and bioengineering, succeeded in engineering bacteria to make a chemical precursor of artemisinin – the best drug available today to cure malaria.

The team's ultimate goal was to retool the microbe's metabolism to perform as much of the drug synthesis as possible in order to sidestep the expensive laboratory synthesis needed to make artemisinin. That synthesis would have increased the drug's cost beyond the researchers' ambitious target of 25 cents per dose.

They now have nearly achieved that goal by engineering the production of artemisinic acid, one chemical alteration away from artemisinin. The fact that the researchers have not yet been able to produce artemisinin itself is not a disadvantage, they said, since drugs currently on the market – all made from extracts of the wormwood plant, Artemisia annua – are synthetic derivatives of both artemisinic acid and artemisinin.

"This is probably as close to artemisinin as we are going to get in microbes. The rest is going to be done by chemistry," said Keasling, His lab partnered with the San Francisco-based Institute for OneWorld Health, a nonprofit pharmaceutical company, and Emeryville, Calif.,-based Amyris Biotechnologies in late 2004 on a $43 million grant from the Bill and Melinda Gates Foundation to develop low-cost artemisinin drugs using Keasling's genetically engineered microbes.

A detailed description of the researchers' work appears in the April 13 issue of Nature.

Keasling noted that his team achieved its recent feat in yeast, not E. coli bacteria. Bacteria breed faster and are often the microbes of choice, but the ability to get the drug out of both bacteria and yeast provides flexibility in achieving the goal of complete synthesis of artemisinin within another four years, he said.

Despite its achievement, the team cautioned that a microbe-produced version of artemisinin will not be on the market soon. It added that the current method of production – extraction from the wormwood plant grown by farmers in Asia – will be essential in the next five to 10 years until production and widespread distribution of the less costly alternative becomes possible.

"While we have made a lot of progress in the past two years, there still are a lot of unknowns," Keasling said. Keasling is director of the UC Berkeley Synthetic Biology Center and of the Lawrence Berkeley National Laboratory's Synthetic Biology Department, and a UC Berkeley member of the California Institute of Quantitative Biomedical Research (QB3).

Artemisinin derivatives, in combination with other drugs, have proven nearly 100 percent effective against malaria, and thus represent a major hope for the 300-500 million people each year who become infected with malaria, and the more than 1.5 million people – largely children in Africa and Asia – who die. Even at $2.40 per person for a cure, however, the cost is too great for most developing countries.

In 2003, Keasling and his team pieced together bacterial genes, yeast genes and genes from the wormwood plant to create a chemical pathway – essentially a miniature factory – in bacteria to make amorphadiene, an artemisinin precursor that can be converted chemically into artemisinin.

Supported by funding from the Gates Foundation, Keasling and his team will work with Amyris to push the research towards a final goal: a microbe that can make sufficient amounts of artemisinic acid to allow scientists to produce the antimalarial drug inexpensively enough for widespread use in Africa and Asia, where malaria is endemic.

To ensure affordability, UC Berkeley has issued a royalty-free license to both OneWorld Health and Amyris to develop the technology to treat malaria. Amyris will transform the Keasling lab's research into a robust fermentation process and perform the chemistry and scale-up necessary to bring the drug to market. OneWorld Health will conduct pre-clinical studies and implement a global access strategy for the drug.

"The work coming out of the Keasling lab is world-class. We are very confident that the UC Berkeley-Amyris collaboration team will be able to build on this work to finish the development of an artemisinin production process," said Kinkead Reiling, president of Amyris.

"The team at UC Berkeley has done a great job moving this important project forward," said Victoria Hale, founder and CEO of OneWorld Health. "We still have a long way to go, but this puts us one step closer to a low-cost treatment for malaria."

The team's work accelerated after first author Dae-Kyun Ro, the UC Berkeley artemisinin project manager, identified last July the enzyme in wormwood that chemically changes amorphadiene into artemisinic acid. He plucked the gene out of wormwood after searching for candidate genes in the published genomes of A. annua's relatives – lettuce and the sunflower.

The enzyme, a member of a large family of cytochrome P450 enzymes, attaches itself to internal cell structures not present in bacteria, so Keasling's team tried first to make it work in yeast, which has the required internal membranes.

Led by UC Berkeley graduate student Eric Paradise, co-first author of the Nature article, a large team of plant biologists, chemical engineers, organic chemists, biochemists, bacteriologists, bioengineers, bioinformatics and fermentation specialists worked together to construct in yeast a mirror of the pathway engineered earlier in bacteria. The researchers used some of the yeast's own genes, plus bacterial genes and wormwood genes inserted into the yeast genome. With the added wormwood gene for the P450 enzyme, the yeast manufactured the desired chemical, artemisinic acid.

"We reached our goal early, thanks to a number of miracles: The first gene Dae-Kyun isolated was the right one, the gene was functional in yeast, the gene's enzyme did in one step what we thought took three enzymes, and the artemisinic acid it produced didn't interfere much with the cell," Keasling said.

The yeast produces perhaps one-tenth the amount of amorphadiene as the current version of the engineered bacteria, he noted, so its output of artemisinic acid is still relatively low. But Keasling is optimistic.

"This was our highest hurdle, what kept me up at night," he said. "Now that we've got all the parts, I feel it's just a matter of time before we have a microbe ready for scale-up to production."

The team's next goal, he said, is to try for the same result in bacteria, which grow faster and thus are preferable if the goal is to produce lots of the drug quickly and inexpensively. Ro admitted, however, that large scale production of the drug by yeast could turn out to be a superior strategy.

"Yeast is an easier host in which to express the P450 enzyme that transforms amorphadiene to artemisinic acid," he said. "However, we plan to push forward with engineering the P450 and expressing it in the amorphadiene-producing E. coli strain. For now, we are delighted to have one attractive host strain for artemisinic acid production in our hands, and we now are considering yeast as an alternative fermentation organism for the production of artemisinic acid."

UC Berkeley coauthors with Ro, Paradise and Keasling are co-project manager Karyn L. Newman and post-doc Michelle C. Y. Chang and research assistants Mario Ouellet, Rachel A. Eachus and Kimberly A. Ho of QB3; post-docs James Kirby and Sydnor T. Withers and visiting scholar Yoichiro Shiba of the Department of Chemical Engineering; post-doc John M. Ndungu and assistant professor Richmond Sarpong of the Department of Chemistry; and graduate student Timothy S. Ham of the Department of Bioengineering. Karl J. Fisher of Amyris also coauthored the paper.

The work was supported by the Gates Foundation as well as by the Akibene Foundation, U.S. Department of Agriculture, UC Discovery Grant Program, National Science Foundation and Diversa Corp.

More information on the collaboration between the Institute for OneWorld Health, UC Berkeley and Amyris Biotechnologies to develop a low-cost malaria drug, can be found at www.artemisininproject.org.

FOR IMMEDIATE RELEASE

$42.6 Million Five-Year Grant From Gates Foundation for Antimalarial Drug Brings Together Unique Collaboration of Biotech, Academia and Nonprofit Pharma Effort Could Significantly Reduce Cost, Boost Supplies of Artemisinin

San Francisco, Calif. - Dec. 13, 2004   - A $42.6 million grant from the Bill & Melinda Gates Foundation to the Institute for OneWorld Health, the first nonprofit pharmaceutical company in the United States, will create a powerful new approach to developing a more affordable, accessible cure for malaria, which kills more than a million children each year.

OneWorld Health, which announced the grant today, will work in partnership with the University of California, Berkeley, and Amyris Biotechnologies. UC Berkeley will conduct research to perfect a microbial factory for the compound artemisinin, currently the most effective treatment for malaria, and Amyris, a new biotech company founded on the breakthroughs in synthetic biology pioneered at UC Berkeley, will develop the process for industrial fermentation and commercialization. OneWorld Health will perform the drug development and regulatory work to demonstrate the bio equivalence of microbially-produced artemisinin derivative to the drug's natural form.

Malaria has become increasingly resistant to front-line medications, but combination drugs containing artemisinin show nearly 100 percent effectiveness after a short three-day regimen. Yet, at a price of $2.40 per adult course for artemisinin combination therapies provided through the World Health Organization, these drugs are still beyond the reach of millions of the world's poorest people. Artemisinin is in short supply, and producing it currently is labor-intensive and relatively expensive.

The partnership will utilize a high-technology solution to bring down the cost of treatment to well under a dollar, a price more affordable for patients in developing countries.

"This is an extraordinary partnership between public and private institutions that combines cutting-edge science with a commitment to affordability and accessibility for those people in need," said Regina Rabinovich, M.D., M.P.H., director of infectious diseases at the Bill & Melinda Gates Foundation. "I hope that UC Berkeley's participation will serve as a model for other academic institutions to apply their scientific knowledge and resources to critical global health problems."

Each year, between 300 and 500 million people, most of them poor, become infected with malaria, and at least 1.5 million die, primarily children in Africa and Asia.  

"With UC Berkeley's innovative technology, Amyris' advancement of this new process, and our drug development and regulatory expertise, we'll provide a new, scalable and stable supply of affordable antimalarial's for the developing world," said Victoria Hale, Ph.D., founder and CEO of OneWorld Health.

To ensure affordability, UC Berkeley has issued a royalty-free license to both OneWorld Health and Amyris, of Albany, Calif., to develop the technology for malaria treatments. In exchange, Amyris will produce the drugs at cost, and OneWorld Health will perform the detailed non-clinical regulatory work that will be required by United States and other global agencies to allow the low-cost, microbially-based product to be substituted for plant-based product by manufacturers of combination drugs containing artemisinin.

The nonprofit nature of this partnership could be a model for attacking neglected diseases in the developing world, said Jay Keasling, Ph.D., professor of chemical engineering at UC Berkeley, who created the genetically engineered microbial drug factories. Keasling also is director of the synthetic biology department at Lawrence Berkeley National Laboratory and a California Institute for Quantitative Biomedical Research (QB3) faculty affiliate.

"This project will use some of the latest advances in molecular biology to engineer a microbial chemical factory and reduce the cost of a much-needed drug tenfold," he said. "In many ways, this project is a dream project: interesting science, high technology, rapid transition from the bench to the bedside, and most important, critical need."

To produce the artemisinin, Keasling and his team have genetically modified microbes. This approach, one of the first triumphs of a field called synthetic biology, also produces a reliably pure compound.   While synthetic biology can be used to create any number of useful chemicals called isoprenoids that form the basis for products such as perfumes and flavorings, Keasling has chosen to focus on the creation of much-needed pharmaceuticals, such as artemisinin, for the developing world.

Extraction of artemisinin from the wormwood plant is labor intensive and, in some developing countries, it is produced by a diesel fuel purification process that may retain toxic impurities in the final drug product.   UC Berkeley will complete development of the synthetic process and maximize production of artemisinic acid, a precursor to artemisinin. The breakthrough technology that makes all this possible was developed by Keasling and his UC Berkeley team over the past 10 years.

Amyris will develop processes to produce large quantities of microbial artemisinic acid and chemically convert it to artemisinin and other effective medicines.   These new processes can be easily scaled to meet the enormous demand for low-cost pharmaceuticals in developing countries.

"We're focusing our groundbreaking technology on producing a known pharmaceutical -- the most effective antimalarial out there -- so that it reaches the people who need it most.   This is just the beginning of drug production using synthetic biology," said Jack D. Newman, Ph.D., a founding scientist at Amyris.  

The Institute for OneWorld Health, the first U.S. nonprofit pharmaceutical company, develops new, affordable medicines for infectious diseases that disproportionately affect people in the developing world. OneWorld Health applies its entrepreneurial business model with a staff of experienced pharmaceutical scientists that identifies promising leads and drives development from pre-clinical studies to clinical trials through regulatory approval. The Institute for OneWorld Health, headquartered in San Francisco, Calif., is a tax-exempt 501(c) (3) U.S. corporation (http://www.oneworldhealth.org). Media resources are available here.

At UC Berkeley, the Keasling laboratory has pioneered the use of synthetic biology to engineer bacteria to produce useful drugs and to degrade toxic environmental contaminants. Jay Keasling can be reached at (510) 642-4862 or keasling@socrates.berkeley.edu. The Keasling lab's web site is http://www.cchem.berkeley.edu/~jdkgrp/. Video of Keasling, Hale and Newman is available from UC Berkeley Media Relations. (Contact Julie Huang at (510) 642-6051 or jch@pa.urel.berkeley.edu). Still images are available here. The QB3 web site is http://www.qb3.org.

Amyris Biotechnologies, Inc. uses synthetic biology to produce complex natural chemicals important to the pharmaceutical and fine chemical industries.   Using engineered microbes and high-throughput gene discovery, Amyris gains access to promising new drugs that have not been developed because of supply limitations.   Amyris employs a variety of new biosynthetic pathways engineered in microbes to produce a range of high-value molecules in large scale at low cost. Amyris' web site is http://www.amyrisbiotech.com.

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