Special Company Pipeline

• Isis Pharmaceuticals’s Antisense Pipeline

• Top 20 Blockbuster Biologics (excl. vaccines)
• Top Selling Classes of Biologicals Products (excl. vaccines)

• Two in-house lead clinical phase II projects with 2 nd generation antisense technology in diabetes and hypercholesterolemia;
• 1 st generation antisense product Alicaforsen enema available for partnering before phase III;
• IL-4 receptor targeting antisense and aerosol delivery for asthma and rhinitis in preclinical stage;
• Licensed antisense projects in clinical stages I and II mainly in oncology at OncoGenex, Lilly and Antisense Therapeutics;
• Phase I planned with c-raf kinase antisense for ocular disease at iCo Therapeutics

Top 20 Blockbuster Biologics

• 19 of the TOP 20 recombinant biologics with 2005 sales of more than US$ 1 bln;
• 2 chimeric, 3 humanized and one fully human antibody among TOP 20;
• One fusion protein, 2 pegylated, 1 glyco-engineered, native and analog proteins among TOP 20 biologics;
• Strongest growth rates over previous year achieved with Avastin (+ 141 %), Humira (+ 64 %) and Herceptin (+ 48 %)

Top Selling Classes of Biological Products

• Total 2005 sales of TOP 12 Classes of Biological Products = US$ 50 bln.;
• Erythropoietins continue to be strongest selling class of biologics, but with modest growth and conversion from native to longer acting EPO;
• Strong double digit growth of TNF-targeting antibodies with total sales of US$ 7.64 bln in 2005;
• Novo Nordisk with 51 % volume share of insulin market (TOP 3 selling class);
• Four cancer antibodies with 2005 sales of US$ 6.77 bln (TOP 4);
• Inteferon alfa market nearly completely converted to pegylated products (TOP 9);
• Antiviral antibody Synagis with first time sales of more than US$ 1 bln