A New Statin Drug: A Brief History of My Career Bonny Ortolano, Ph.D. Genome Pharmaceuticals Cambridge, Massachusetts

My Educational Background B.S. in Chemistry from Temple University, 1982 Ph.D. in Biochemistry from Bryn Mawr College, 1987 Postdoctoral Research, Cornell University, Ithaca, NY,

My Professional Background Joined Genome Pharmaceuticals, 1989, as Research Scientist Promoted to Research Team Leader, 1994 Promoted to Senior Scientist in 2001 Supervised development of a new statin drug

Research and Development Organization at Genome

Statin Drugs Class of cholesterol- lowering drugs Inhibitors of HMG- CoA reductase, an enzyme Enzyme catalyzes rate-limiting step in sterol biosynthesis Cholesterol is a sterol Example statins –Lovastatin –Pravastatin –Simvastatin –Atorvastatin –Fluvastatin –Cerivastatin

HMG-CoA Reductase Target enzyme of statin drugs Enzyme is key catalyst in synthesizing cholesterol Catalyzes conversion of HMG-Co to mevalonate Statin drugs block enzyme, inhibits production of cholesterol Acetyl CoA HMG-CoA Mevalonate Cholesterol 2 steps HMG-CoA Reductase 10 steps

Example Statin: Lipitor Generic name: atorvastatin Our drug is similar, but more effective in diabetics Patent pending

Effectiveness of Lipitor

Getting a Drug to Market Scientists design and synthesize drug Test drug in vitro (in test tube) Get pre-approval of FDA for clinical trials Perform placebo-controlled dose-response study on hypercholesterolemia patients Submit results to FDA Get preliminary approval Test on wider group Get final approval from FDA Design delivery system, packaging, etc. Market drug through physicians

Reality of Drug Development Initial development and testing –6 years –$1.5 million Clinical testing and FDA approval –6 years and –$6 million Development and marketing –1 year –$2 million

My Career Exciting and challenging Meet lots of bright people Financial rewards Satisfaction in developing new pharmaceuticals