## A Robust Pipeline for Tomorrow 

Sustaining a robust pipeline of pos- sible new therapies is critical to our company’s success. 

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. 

“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. 

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- 

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). 

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. 

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. 

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 

sparing patients the difficult-to-tolerate therapies that are components of the current standard of care. 

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. 

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. 

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 

