2012 Annual Report A Robust Pipeline for Tomorrow 8 Bristol-Myers Squibb  Sustaining a robust pipeline of pos- sible new therapies is critical to our  company’s success. sive lung disease. For heart failure, we  entered into a discovery collaboration  with Ambrx Pharmaceuticals, focusing  on what may be an important biologi- cal target to treat the disease (also  see page 12). sparing patients the difficult-to-tolerate  therapies that are components of the  current standard of care. These agreements and others reflect a  broader strategy that recognizes that  scientific innovation can and should  come from both internal and external  sources. By selectively integrating  capabilities in research and develop- ment, we can better leverage new tech- nologies and therapeutic opportunities. Fortunately, strategies to sustain suc- cess have been in place for a number  of years – and are working. Today,  we rank among the pharmaceutical  industry’s leaders in success rates for  compounds getting through discovery  and development as well as for our  average R&D spend for each new  molecular entity approved.  We formalized that process in 2007  through a String of Pearls business  development strategy that has since  led to about 20 strategic alliances,  partnerships and acquisitions, includ- ing Amylin Pharmaceuticals, acquired  in 2012, along with its first-in-class  diabetes therapies, its pipeline and  its expertise in metabolic disorders. “Over the years, we have treated  external and internal innovation just the  same,” Cuss adds. “It has become a  core capability of ours.” Hepatitis C (HCV), which affects 170  million people worldwide, represents  another frontier area where Bristol- Myers Squibb does not yet have a  marketed product, but does have  multiple candidates based on a mul- tipronged strategy that offers the real  potential for cure. Efforts continue to recharge thera- peutic areas, with new HIV therapies  to overcome drug resistance as well  as new classes like HIV attachment  and maturation inhibitors; an ongo- ing focus on new target inhibition in  oncology with, for example, JAK inhibi- tors for certain blood cancers; and  programs for additional autoimmune  diseases, including lupus and inflam- matory bowel disease. We jump-started our efforts in fibrotic  diseases, caused by the buildup of  potentially deadly scar tissue in differ- ent tissues of the body, by acquiring  Amira Pharmaceuticals in 2011, which  already had a lead compound in early  clinical development. And we entered  into a translational R&D collaboration  with Duke University to further explore  biomarkers, assays and dosages for  the lead Amira program for idiopathic  pulmonary fibrosis, a chronic progres- “Our North Star remains significant  unmet medical need,” says Francis  Cuss, senior vice president, Research. “We guide ourselves and navigate by  it.” That approach allows us to define,  but not necessarily limit ourselves to, a  specific set of disease areas – adjust- ing based on changes in unmet medi- cal need, the competitive environment  and evolving science. As a result, we  have added new exploratory disease  areas, including fibrosis, heart failure,  neurodegenerative disorders such  as Parkinson’s disease, and diabetic  kidney disease. For instance, for  Parkinson’s, we entered into a licens- ing agreement and collaboration with  Vanderbilt University to develop novel  compounds to treat the disease. Leading the way are two internally  discovered oral antivirals - daclatasvir  and asunaprevir - which, in Phase II  trials, demonstrated a high cure rate in  patients infected with the genotype 1b  strain of HCV. A regulatory submis- sion is planned in Japan in 2013 seek- ing to benefit patients there (some  1.5 million) who share this genotype. Also, having presented Phase II data  in November 2012 on a triple regimen  that adds a third company-discovered  antiviral, expectations are to move that  all-oral triple regimen into Phase III  trials in 2014. Finally, for some patient  populations who might benefit, we  are continuing development of a novel  peginterferon lambda-1a for both  hepatitis B and hepatitis C. We believe that the global HCV patient  population is diverse and therefore  will require different treatment types,  including a variety of combinations.  In fact, our researchers were the first  to demonstrate the potential for cure  with an all-oral regimen, potentially  Also being studied is elotuzumab, a  monoclonal antibody in Phase III trials  for multiple myeloma, an incurable dis- ease with about 50,000 cases in the  U.S. and Europe each year and about  100,000 cases worldwide. While  elotuzumab does not work directly  on immune system targets (also see  pages 14-15), it instead binds to a  protein that is widely expressed on 