Bristol-Myers Squibb  the coming years. We also face significant challenges with an increasingly complex global and regulatory environment and global  economic uncertainty, particularly in the European Union (EU). We believe our strategy to grow our newer marketed products and  our robust research and development (R&D) pipeline, particularly within the therapeutic areas of immuno-oncology, cardiovascular/metabolic disease and virology, position us well for the future.  $^{ }$We continue to expand our biologics capabilities. We still rely significantly on small molecules as our strongest, most reliable starting  point for discovering potential new medicines, but large molecules or biologics, derived from recombinant DNA technologies are  becoming increasingly important. Currently, more than 40% of our pipeline compounds are biologics, as are four of our key marketed  products, including  Yervoy  (ipilimumab).  $^{ }$We also continue to support our pipeline with our licensing and acquisitions strategy, referred to as our “string of pearls.” During the  third quarter of 2012, we acquired Amylin, a biopharmaceutical company dedicated to the discovery, development and  commercialization of innovative medicines for patients with diabetes and other metabolic diseases. Following the completion of our  acquisition of Amylin, we entered into a collaboration with AstraZeneca Pharmaceuticals LP, a wholly-owned subsidiary of  AstraZeneca, which builds upon our existing alliance, further expanding our collaboration strategy. We are currently integrating the  Amylin business into our development, manufacturing and commercial operations. We are also seeking to build relationships with  academic organizations that have innovative programs and capabilities that complement our own internal efforts.  We manage our research and development (R&D) programs on a portfolio basis, investing resources in each stage of research and  development from early discovery through late-stage development. We continually evaluate our portfolio of R&D assets to ensure  that there is an appropriate balance of early-stage and late-stage programs to support future growth. We consider our R&D programs  that have entered into Phase III development to be significant, as these programs constitute our late-stage development pipeline. These Phase III development programs include both investigational compounds in Phase III development for initial indications and  marketed products that are in Phase III development for additional indications or formulations. Spending on these programs  represents approximately 30-40% of our annual R&D expenses. No individual investigational compound or marketed product  represented 10% or more of our R&D expenses in any of the last three years. While we do not expect all of our late-stage  development programs to make it to market, our late-stage development programs are the R&D programs that could potentially have  an impact on our revenue and earnings within the next few years. The following are the recent significant developments in our  marketed products and our late-stage pipeline:  Eliquis  – an oral Factor Xa inhibitor, targeted at stroke prevention in NVAF and the prevention and treatment of venous  thromboembolic (VTE) disorders. Eliquis  is part of our strategic alliance with Pfizer, Inc. (Pfizer)  $^{ }$Product and Pipeline Developments  $^{ }$• In December 2012, the U.S. Food and Drug Administration (FDA) approved  Eliquis  to reduce the risk of stroke and systemic  embolism in patients with NVAF. Eliquis  also received regulatory approval for this indication in Japan and Canada in December  2012, in the EU in November 2012, and in South Korea in January 2013. • In December 2012, the Company announced the results of the Phase III AMPLIFY-EXT trial, which evaluated treatment with  Eliquis  compared to placebo over a one year period for the prevention of recurrent VTE in 2,486 patients who had already  completed six to 12 months of anticoagulation treatment for VTE, including deep vein thrombosis or pulmonary embolism. In the  trial, extended treatment with  Eliquis 2.5 mg and 5 mg twice daily, demonstrated superiority versus placebo in the reduction of  the composite endpoint of symptomatic, recurrent VTE and death from any cause. Eliquis  also was superior to placebo for the  predefined secondary efficacy outcome of recurrent VTE and VTE-related death. The rate of the primary safety outcome of major  bleeding was comparable across treatment groups.  • In October 2012, the Company announced in a publication in  The Lancet  that the reductions in stroke or systemic embolism,  major bleeding and mortality demonstrated with  Eliquis  compared to warfarin in the ARISTOTLE trial were consistent across a  wide range of stroke and bleeding risk scores in patients with NVAF.  • In March 2012, additional analyses from the ARISTOTLE and AVERROES clinical trials were presented at the American  College of Cardiology’s 61st Annual Scientific Session.  $^{ }$• In November 2012, the EC approved  Forxiga  for the treatment of type 2 diabetes in the EU.  • In June 2012, at the 72$^{nd}$ American Diabetes Association Scientific Sessions, the Company and AstraZeneca announced results  from a Phase III clinical study that showed  Forxiga 10 mg demonstrated significant reductions in blood sugar levels (glycosylated  hemoglobin levels, or HbA1c) compared with placebo at 24 weeks when either agent was added to existing sitagliptin therapy  (with or without metformin) in adult patients with type 2 diabetes. The results were maintained over a 24-week extension and  similar results were observed when the data were stratified by background therapy. The study also demonstrated significant  reductions in total body weight and fasting plasma glucose levels in patients taking  Forxiga  added to sitigliptin (with or without  metformin), with results maintained throughout the duration of the study.  4 Forxiga  – an oral sodium-glucose cotransporter 2 (SGLT2) inhibitor for the treatment of diabetes that is part of our alliance with  AstraZeneca 