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• Tarceva is a tyrosine kinase inhibitor and its target is EGFR (Epidermal Growth Factor Receptor), a receptor that plays a key role in development and progression of several different kinds of malignant tumors.

• Targeting EGFR represents a promising molecular approach in treating a wide range of cancer patients.

• Several EGFR inhibitors from competitors are in clinical development or were just launched. However, most of them are biologics such as Erbitux – costly to manufacture. Tarceva™ is a small molecule – relatively easy to produce.

Kinases

• Kinases are enzymes that catalyze the transfer of phosphate group from  ATP to protein substrates (tyrosine or serine/threonine residues)

• 
  Located inside the cell, the compounds have to cross cell membranes to go to the site of actions
   
• There are about 500 known kinases that play roles in signal transduction. Most of the known inhibitors bind in the ATP region, thus selectivity could be potential problem. Toxicity profile of inhibiting kinases in human was not known.

Discovery

• Tarceva™ was jointly discovered as part of a long-standing cancer alliance between Pfizer and OSI pharmaceuticals which was completed in 2001.
   
• In June 2000, OSI pharmaceuticals gained full development and marketing rights to Tarceva™ in order to allow Pfizer to meet certain requirements of the U.S. Federal Trade Commission arising from the FTC’s review of Pfizer’s merger with Warner-Lambert Company.
   
• OSI received a royalty-free license to all rights for the further development and commercialization of Tarceva™ and were not required to make any payments to Pfizer for the license
   
• A competitive position against other EGFR inhibitors.
   
• Bring Tarceva™ to market in as timely a manner as possible
   
• Over 100 clinical trial on Tarceva™, approximately thirty-two of these studies are being conducted in collaboration with the National Cancer Institute – significantly increase the product’s visibility.
   
• Focus on treatment of non-small cell lung cancer – a common type of lung cancers with a market share of $1.49 billion in 2002.
   
• In the face of two already entrenched rivals, AstraZeneca's Iressa and ImClone's Erbitux, OSI leadership team plans to do one-on-one marketing to doctors instead of full-page ads and slick TV commercials.
   
• Looking beyond, OSI plans to market Tarceva for many different cancers, including pancreatic and glioblastoma, a severe form of brain cancer.

The beginning of personalized medicine

• Compared to popular “Copycat”, “Me-Too” approaches, Tarceva works through a novel mechanism to satisfy a severe unmet medical need.
   
• People who respond to these drugs have common mutations in their tumors (The mutations aren't inherited, but seem more frequent among Japanese patients, women, and people who had a subtype called bronchoalveolar cancer nonsmokers for yet unknown reasons).
   
• The beginning of personalized medicine: Genetic test is being developed to screen for these mutations to identify the 10-13 percent of patients likely to to benefit most. Early preventative prescription and first-line treatment rather than standard chemotherapy should save lives and lower cost.
   
• The drug is the first of its kind to show in a major study of more than 700 patients that the approach can extend the life of patients with non-small cell lung cancer (NSCLC), the most common form of lung cancer, compared to a placebo. Actual results from the study will be announced in June, 2004.
   
• Tarceva is the fifth cancer medicine with a proven survival benefit, joining breast cancer drugs Herceptin and Xeloda, blood cancer treatment Mabthera, and colorectal cancer drug Avastin.
   
• Lung cancer is one of the most common and lethal types of cancer, killing 85 percent of its sufferers.
   
• 2004 statistics: 173,770 new cases annually; 160,440 deaths annually; More deaths from lung cancer than prostate, breast and colorectal cancers combined.
   
• Helping even a subset of patients is highly desired.

Summary

• Tarceva™ is a small molecule kinase (EGFR) inhibitor being developed by OSI, Genentech, and Roche.
   
• In very recent data from Phase III studies with NSCL cancer  patients, Tarceva is shown to be effective and extends lives.
   
• It’s most likely to work best with cancer patients having particular mutations, thus it could be among few drugs that will be used in personalized medicine.
   
• It is another good example of biotech and big pharma’s successful collaboration.
   
• These type of drugs developed based on mechanistic understanding of tumerogenesis at the molecular level are future of the cancer treatments.