New study provides molecular-level understanding of common anti-malarial drugs

November 12, 2002

Transform & Weizmann Institute study uncovers mechanism of action of common anti-malaria drugs

Published data provides molecular-level understanding of common anti-malarial drugs

Lexington, MA, November 12, 2002 - TransForm Pharmaceuticals Inc. today announced a new understanding of the connection between the physical chemistry and mechanism of action of quinoline-based drugs used to treat Malaria. These findings can be applied to further discovery and design of research that may overcome the problem of drug resistance that has developed to the Malaria parasite. The study, conducted in collaboration with The Weizmann Institute in Israel, and published in the November/December 2002 issue of Crystal Growth and Design, provides new insights on how a better understanding of the physical chemistry, associated with some diseases, can be used to develop new and improved drugs. The paper entitled "Quinoline Binding Site on Malaria Pigment Crystal: A Rational Pathway for Anti-Malaria Drug Design" is also available through http://pubs.acs.org/journals/cgdefu/index.html.

The paper describes a new understanding of the molecular-level of action of common anti-malarial drugs. The malaria parasite develops unique crystals that protect it from toxins it forms during the digestion of hemoglobin--its main food source. TransForm researchers were able to leverage their crystal chemistry expertise to uncover the mechanism of action by developing a detailed understanding of the interaction between quinoline-based drugs and these crystals. The data showed that drugs like chloroquine slow the growth of crystals. Slowing the crystal growth enables heme to accumulate to toxic levels and ultimately kill the parasite. TransForm utilized the recently reported crystal structure of synthetic beta-hematin combined with computational technologies to test the novel-binding site for the quinoline drugs.

"This discovery illustrates the value of understanding physical chemistry and crystalline surface structure to explain the mechanism of a drug's action," stated Colin Gardner, Ph.D., Chief Scientific Officer at TransForm. "This is a very exciting development, and demonstrates the importance of examining biophysical crystals as drug targets."

The World Health Organization estimates that between 300 and 500 million new cases of Malaria arise each year, and that more than one million people die from the disease annually. Although eradicated in many countries including the U.S, the growing drug resistance to the malaria parasite of current drug therapies combined with a lack of new compounds to treat Malaria makes the disease a significant global health concern.

"Over the last decade, Malaria has reemerged as one of the most widespread infectious diseases due to its resistance to the quinoline drug family," stated Robert Rubin, M.D., Osborne Professor of Health Sciences and Technology and Professor of Medicine at Massachusetts Institute of Technology and Harvard Medical School. "These findings are critical in providing us with better information on current drugs that are subject to emerging resistance as well as offering help in the development of new drugs to treat Malaria."
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About TransForm

TransForm Pharmaceuticals is reinventing the pharmaceutical industry's approach to form and formulation, with a novel set of high-throughput, automated platform technologies, powered by state-of-the-art informatics and a scientific and managerial team with deep experience in pharmaceuticals. It uses these capabilities to optimize drug form and/or formulations, and increase the clinical and commercial value of pharmaceutical products, across the entire pharmaceutical value chain.

In R&D, TransForm is working with partners such as Alza Corporation and Lilly, to help them make better candidate selection decisions, and reduces attrition and development time and cost. For later stage and marketed products, TransForm can help partners enhance product life cycle management by rapidly discovering novel forms and/or formulations to potentially improve bioavailability, broaden intellectual property protection and enable new dosage forms and/or combination products.

TransForm is also using these capabilities to develop its own proprietary product portfolio. TransForm, founded in late 1999 with initial technology from Millennium Pharmaceuticals (NASDAQ:MLNM), is a privately held company located in Lexington, MA. For more information visit our website at www.transformpharma.com.

For more information, please contact:
TransForm Pharmaceuticals, Inc.
Colin Gardner, Ph.D.
781/926-8587

Noonan Russo
Robert Stanislaro
212/845-4268

Noonan/Russo Communications

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