2012 Annual Report
`
`AstraZeneca Exhibit 2114
`Mylan v. AstraZeneca
`IPR2015-01340
`
`Page 1 of 104
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`

`

`On the COver – Eliquis – the SCientifiC JOurney
`
`The scientific journey that resulted in Eliquis (apixaban), Bristol-Myers Squibb’s
`new anticoagulation therapy that works by directly inhibiting Factor Xa, dates
`back to 1994 and a group of dedicated researchers at DuPont Pharmaceuticals,
`a company Bristol-Myers Squibb acquired in 2001. At that time, Ruth Wexler,
`Ph.D., led DuPont’s Cardiovascular Chemistry group. “We strongly believed,
`based on preclinical data, that a high quality Factor Xa inhibitor could be a highly
`effective anticoagulant with the potential for an improved safety profile,” she
`says. By 1996, a cross-functional team helped identify the first inhibitors and
`by early 1998, the first of these entered human trials. Still, the team continued
`to develop additional Factor Xa inhibitors. Apixaban was synthesized by Michael
`Orwat (right), then an associate working in the laboratory of Donald Pinto, Ph.D.
`(left). Today, all three are still working in cardiovascular research at Bristol-Myers
`Squibb: Pinto, a research fellow in Medicinal Chemistry, and Orwat, a senior
`research scientist in Pinto’s lab, are helping develop a next generation of medi-
`cines for thrombosis. And Wexler is executive director in Medicinal Chemistry,
`leading the group as it develops a new wave of cardiovascular drugs. See a Spe-
`cial Report beginning on page 5 to learn more about how our company’s efforts
`in cardiovascular research and on other frontiers of drug development may help
`patients around the world.
`
`The patient stories shared in this Annual Report depict individual patient responses to our medicines or investigational compounds and are not representative
`of all patient responses. In addition, there is no guarantee that potential drugs or indications still in development will receive regulatory approval.
`
`We remain committed to a single overriding mission:
`to help more patients prevail in their fight against serious diseases.
`
`Page 2 of 104
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`

`Bristol-Myers Squibb 2012 Annual Report
`
`tO Our StOCkhOlderS
`
`Message from the Chief Executive Officer
`
`2012 was a year of strategic transition – one that allowed us to deliver meaningful results, while
`laying the groundwork for 2013 and beyond – one that further established Bristol-Myers Squibb
`as a benchmark BioPharma company.
`
`During the year, we evolved our portfolio. We reaffirmed our leadership in a range of therapeutic
`areas. We set the stage for sustained, long-term growth.
`
`Our revenues and earnings declined – due to the expected losses of exclusivity of Plavix and
`Avapro/Avalide – but we closed the year in a very good position. Our financials were solid. Our
`pipeline robust. Our portfolio strengthened by the addition of new, innovative medicines.
`
`Specifically, our new and in-line product sales grew by 15% in 2012. Among the strongest drivers
`with double-digit growth were Yervoy (metastatic melanoma), Onglyza (type 2 diabetes), Orencia
`(rheumatoid arthritis), Sprycel (myeloid leukemia) and Baraclude (hepatitis B). We had several key
`regulatory successes, including the European approval of Forxiga (type 2 diabetes) and multiple
`approvals of Eliquis (atrial fibrillation). And we made some significant clinical advances, particularly
`with respect to our immuno-oncology and hepatitis C assets.
`
`Taken together, it was an important year that ended strong.
`
`Our Solid Foundation
`
`Clearly, we did not get to our good position overnight.
`
`Beginning in 2007, our BioPharma Transformation has been comprehensive, impacting all parts of
`our organization in all parts of the world. It has been a journey. It has taken vision. And it has taken
`a lot of hard work.
`
`
`
`
`
`
`
`
`
`• It has also taken a new Mission – one based on helping patients prevail over serious diseases
`exclusively through innovative pharmaceutical products.
`
`• It has taken a new strategy – one premised on the three pillars of innovation, continuous
`improvement and selective integration.
`
`• It has taken a new approach to the way we do business – one guided and fueled by a more
`agile, entrepreneurial and accountable culture.
`
`• And it has taken an unwavering commitment to compliance, business ethics and personal integ-
`rity – a commitment that has become central to who we are, what we do and how we do it.
`
`Simply stated, our BioPharma Transformation has been built on a solid foundation of realistic expecta-
`tions, high aspirations and a commitment to excellence that runs throughout our entire company.
`
`
`
`Page 3 of 104
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`

`

`diseases, and with it, three mar-
`keted products, including Byetta
`and Bydureon, and a state-of-the-art
`manufacturing plant in Ohio. And
`very importantly, we also expanded
`our 5-year-old diabetes partnership
`with AstraZeneca.
`
`Toward the end of the year, we gained
`European Commission approval for
`Forxiga, a once-daily oral medication
`that provides a completely new option
`to improve glycemic control in adult
`patients with type 2 diabetes.
`
`In light of all of these developments,
`we are now able to offer three innova-
`tive classes of medicines to help
`address the diverse needs of patients
`with type 2 diabetes. This is good
`news for our company and for the
`patients we serve. Type 2 diabetes
`is a chronic, progressive disease
`that is growing in prevalence across
`the globe. According to the World
`Health Organization (WHO), there
`are an estimated 346 million people
`with diabetes worldwide. By 2030,
`that number is projected to double.
`Consequently, there is a real need
`for new treatment options.
`Immuno-Oncology
`Yervoy continued to get established
`in markets throughout the world.
`Global sales increased 96% over the
`previous year, and this breakthrough
`product demonstrated an unprec-
`edented 5-year survival curve for
`melanoma patients.
`
`Our Research and Development team
`also made progress with two potential
`products – nivolumab, which is in
`Phase III trials for lung, renal and skin
`cancers, and elotuzumab, for multiple
`myeloma.
`
`These developments reaffirmed
`Bristol-Myers Squibb’s position as
`
`Lamberto Andreotti, Chief Executive Officer
`
`“Simply stated, our
`BioPharma Transformation
`has been built on
`a solid foundation of
`realistic expectations,
`high aspirations and a
`commitment to excellence
`that runs throughout our
`entire company.”
`
`has been the standard of care for this
`patient population.
`
`Finally, this was a very positive
`development for our company and
`for our alliance with Pfizer, because it
`further underscored the value of our
`partnership and the leadership role
`both companies continue to play in
`providing innovative medicines for the
`treatment of cardiovascular disease.
`
`Diabetes
`In 2012, we continued to expand our
`Onglyza franchise and delivered a
`50% increase in year-over-year sales.
`
`We also acquired Amylin, a biophar-
`maceutical company specializing
`in diabetes and other metabolic
`
`2012 Annual Report
`
`Our Diversified Portfolio and
`Pipeline
`
`This foundation, in turn, made it
`possible for us to work through
`challenges and seize opportunities
`in 2012, while positioning ourselves
`for a successful future.
`
`Most notably, it helped us to manage
`the losses of exclusivity of Plavix and
`Avapro/Avalide. Having long known
`that two of our biggest products were
`going off patent in 2012 and that the
`financial impact would be consider-
`able, we planned accordingly and
`executed successfully. We strength-
`ened our diversified portfolio with new
`products and new indications. We
`achieved significant clinical advances.
`And we renewed our commitment to
`productivity.
`
`Cardiovascular Disease
`In the last weeks of the year, we
`gained several approvals for Eliquis,
`a new medication for the prevention
`of stroke and systemic embolism for
`adult patients with nonvalvular atrial
`fibrillation, or NVAF. Specifically,
`Eliquis was approved in Europe,
`Canada, Japan and the United States.
`
`This was an important development
`for patients. Atrial fibrillation is a
`common heart arrhythmia that affects
`millions of people worldwide. It is a
`condition that significantly increases
`the risk of stroke as well as the bur-
`den to patients who suffer a stroke.
`
`This was also an important devel-
`opment for physicians. Eliquis is
`the only anticoagulant with proven
`superior risk reduction versus war-
`farin in the three critical outcomes
`of stroke prevention, major bleeding
`and all-cause death in patients with
`NVAF. For nearly 60 years, warfarin
`
`2
`
` Bristol-Myers Squibb
`
`
`
`Page 4 of 104
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`

`

`2012 Annual Report
`
`3
`
`
`
` Bristol-Myers Squibb
`
`a leader in the field of oncology and
`a pioneer in the new, increasingly
`promising field of immuno-oncology.
`
`Hepatitis C
`With respect to hepatitis C, we
`were disappointed about the need to
`discontinue the BMS-986094 clinical
`program, but in the interest of patient
`safety, we acted swiftly to end it.
`
`Despite this situation, our hepatitis
`C portfolio remains significant. We
`made important progress on an
`oral dual-regimen in development in
`Japan, where we plan to file a regula-
`tory submission in 2013, and we
`intensified our focus on the Phase II
`development of an all-oral triple regi-
`men, preparing the way for Phase III
`trials in 2014.
`
`Our Improved Organization
`
`Central to our transformation and
`a key to our ongoing success has
`been an active focus on continuous
`improvement, particularly through
`enhanced productivity and forward-
`looking changes to our organization.
`
`In 2012, we began implementing a
`new global structure – one better
`suited for our increasingly diversified
`portfolio and geographical emphasis.
`This included a restructuring of our
`U.S. and European operations as well
`as our approach to global markets.
`We also launched the Enterprise
`Services organization, an effort to
`streamline internal operations, and we
`unveiled a new, cutting-edge Plant
`Network Strategy in our manufactur-
`ing organization.
`
`To my Senior Management Team
`I welcomed three new executives in
`2012 and one more early in 2013.
`Promoted from within our company
`were John Elicker (Public Affairs and
`
`Investor Relations) and Samuel Moed
`(Strategic Planning and Analysis).
`Recruited to our company were
`Frances Heller (Business Develop-
`ment) and Ann Powell Judge (Human
`Resources).
`
`Individually and collectively, these
`organizational changes are all
`designed to help us to do our work
`faster, smarter and better – to deliver
`the promise of our portfolio more
`effectively and efficiently – and to
`impact positively the lives of people
`around the world.
`
`Our Steadfast Commitment
`
`After all, people are at the center
`of everything we do. People who
`depend on our innovative medicines.
`People who live in our communities.
`People who work for our company.
`Our commitment is to them and their
`families, and in 2012, this was dem-
`onstrated in compelling ways.
`
`For patients, our commitment includes
`our work in the laboratory to discover
`and develop innovative new medicines
`as well as our work in the field to
`promote access to them. We there-
`fore focus a great deal of time and
`resources also making access a reality
`for people living in the most challeng-
`ing circumstances. In 2012, that meant
`expanding our U.S.-based Together
`on Diabetes program – which began
`in 2010 with a $100 million grant – to
`China and India, two countries with
`the largest populations of diabetic
`patients. It also meant completing
`the first successful phase of our
`five-country collaboration with the
`WHO concerning the HIV/tuberculo-
`sis epidemic in sub-Saharan Africa,
`an initiative that represents an exten-
`sion of our landmark SECurE THE
`FuTurE program.
`
`For communities, our commitment
`expressed itself through our contin-
`
`ued work with the United Nations
`Global Compact and with our own
`Go Green and Earth Day initiatives.
`These efforts – combined with the
`progress made on our Sustainability
`2015 Goals – contributed to our top
`designation on the 2012 Corporate
`Responsibility magazine’s 100 Best
`Corporate Citizens list.
`
`For employees, our commitment was
`clear in the work we did to develop,
`enrich and recognize our people.
`We reaffirmed our longstanding
`adherence to equal opportunity prin-
`ciples and rededicated ourselves to
`maintaining a work environment that
`values diversity and that embodies
`fairness, equity and respect. Once
`again, we placed an emphasis on
`maintaining an atmosphere designed
`to promote a good work product and
`a good work experience.
`
`Clearly, we are in a strong position.
`Our BioPharma Transformation has
`been a journey during which we have
`worked through many challenges and
`seized many opportunities. We have
`been finding our way through the
`losses of exclusivity. We have been
`adapting to the “new normal” of
`global economic uncertainty. And we
`have just completed an important year
`of transition – one that underscored
`the potential of our increasingly
`diversified portfolio and pipeline of
`innovative medicines.
`
`All of this enables us to bring new
`possibilities to patients.
`
`Lamberto Andreotti
`Chief Executive Officer
`March 11, 2013
`
`Page 5 of 104
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`

`

`careful planning and smart execution,
`we ended 2012 in a solid position.
`
`Going forward, the foundation estab-
`lished in recent years – coupled with
`our proven ability to deliver under
`difficult circumstances – should help
`guarantee our continued success.
`
`Since joining our company in 2006,
`I have had the opportunity to work
`with some extraordinary people during
`some extraordinary times. As CEO,
`I was able to launch our BioPharma
`Transformation and help guide the
`organization through the early years
`of this important process. As Chair-
`man, I have been able to work closely
`with CEO Lamberto Andreotti and
`his team as they take the company
`to the next level. In addition, I want
`to thank Louis Freeh, who recently
`retired from the Board, and R. Sanders
`Williams, who will retire on May 7,
`for their dedicated and outstanding
`service to the company.
`
`We have literally transformed Bristol-
`Myers Squibb into a BioPharma
`leader and are making an important
`difference in the lives of our patients
`and in the communities in which we
`live and work. And as we transition
`to the portfolio of the future with an
`organization well positioned to own
`that future, I feel extremely confident
`and genuinely proud.
`
`James M. Cornelius
`Chairman
`March 11, 2013
`
`James M. Cornelius, Chairman
`
`“Going forward, the
`foundation established in
`recent years – coupled
`with our proven ability
`to deliver under difficult
`circumstances – should
`help guarantee our
`continued success.”
`
`franchise through a major acquisi-
`tion, a new product approval and the
`strengthening of our alliance with
`AstraZeneca. The further develop-
`ment of our exciting work in immuno-
`oncology. The much-anticipated
`approval in several countries of Eliquis
`for atrial fibrillation.
`
`All of this has made it possible to
`mitigate the impact of the patent
`losses and find our way through an
`increasingly complex, increasingly
`challenging global economic environ-
`ment. Granted, we will continue to
`feel the effect of those losses, but
`there is no mistaking it: Through
`
`2012 Annual Report
`
`Message from the Chairman
`of the Board
`For years, we had been talking about
`a “patent cliff” – an enormous drop in
`sales and earnings that would occur
`when two of our biggest products,
`Plavix and Avapro/Avalide, lost their
`exclusivity in the United States. We
`discussed its likely impact on our
`organization. We debated its effect
`on our portfolio. Some even wondered
`whether we could recover.
`
`Over time, however, that conversation
`took a different turn.
`
`In fact, when both products lost their
`exclusivity in 2012, we did not fall
`off a cliff. We remained strong and
`just continued doing what we do best:
`driving sales, launching products,
`building our future. In the end, the
`“cliff” turned into more of a “slope,”
`and the conversation refocused on
`our bright future.
`
`This is an important story, because it
`speaks to the strength, the resiliency
`and the capacity of Bristol-Myers
`Squibb.
`
`Over the past several years, our
`company has changed in significant
`ways. We have evolved our mission
`and strategy. We have diversified
`our portfolio and geographical focus.
`We have repurposed and redirected
`our organization. All in all, we have
`done a great deal to transform
`Bristol-Myers Squibb into a bench-
`mark BioPharma company.
`
`And last year, the results were impres-
`sive. Strong double-digit growth in
`sales of our new and in-line products.
`The augmentation of our diabetes
`
`4
`
` Bristol-Myers Squibb
`
`
`
`Page 6 of 104
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`

`

`Bristol-Myers Squibb 2012 Annual Report
`
`Frontiers oF science
`
`the
`
`Developing New Possibilities for Patients
`
`5
`
`
`
` Bristol-Myers Squibb
`
`Today we stand on the frontiers of extraordinary new possibilities
`for addressing significant unmet medical need. And while we have
`come a great distance in the past several years to successfully
`transform ourselves into a benchmark BioPharma company, there
`are great opportunities to do even more. Most importantly, we have
`and will continue to attract and retain the best people around the
`world. And each day they come to work, they remain committed to
`a single overriding mission: to help more patients prevail in their
`fight against serious diseases.
`As we look to the future, we will need to focus our efforts across
`a number of essential areas:
`
`• Extending the Reach of Our Medi-
`cines – Ensuring that more patients
`around the world gain access to
`our leading medicines will help
`them prevail over their illnesses,
`create value for our shareholders
`and develop the resources required
`to invest in our future.
`• Ensuring a Robust R&D Pipeline – In
`addition to the diseases for which we
`have medicines already available, we
`continue to diversify and expand our
`horizons in areas like hepatitis C, neu-
`rodegenerative disorders and fibrosis.
`• Creating a Culture of Continuous
`Improvement – Working smarter,
`better and faster will help us drive
`
`our competitive advantage to deliver
`the promise of new medicines.
`• Developing Innovations on the
`Frontiers of Medicine – Cardiovas-
`cular disease, immuno-oncology
`and diabetes are three leading areas
`where we have recently introduced
`new medicines and where we are
`developing a pipeline of innovative
`therapies that expand the frontiers
`of biomedical research.
`• Committing to Responsible Citizen-
`ship – Acting in a socially respon-
`sible, ethical and sustainable manner
`is a commitment we must make and
`act upon every day.
`
`In this Special Report, we examine each area and introduce you to exam-
`ples of how our people continue to transform Bristol-Myers Squibb and
`in so doing, help develop new possibilities for patients everywhere.
`
`Page 7 of 104
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`

`

`2012 Annual Report
`
`Medicines That Fuel Our Growth
`
`At Bristol-Myers Squibb, we rely on a
`strong lineup of products to acceler-
`ate our growth and help fuel research
`for promising future possibilities. Key
`brands today include Orencia (abata-
`cept) for rheumatoid arthritis (RA);
`Sprycel (dasatinib) and Erbitux (cetux-
`imab) for cancer; reyataz (atazanavir),
`Atripla (efavirenz with emtricitabine
`and tenofovir) and Sustiva (efavirenz)
`for HIV/AIDS; Baraclude (enteca-
`vir) for hepatitis B; and Onglyza
`(saxagliptin), and Kombiglyze XR and
`Komboglyze (saxagliptin and metfor-
`min HCl fixed-dose combinations) for
`diabetes (also see pages 16-17). Not
`only is use of many of these therapies
`on the rise for approved indications,
`but in many cases, new research is
`seeking to examine their ability to
`benefit more patients.
`
`Orencia
`
`Orencia crossed $1 billion in annual
`sales in 2012. Additional growth has
`
`come with the approval of subcutane-
`ous (SC) administration in the U.S.,
`Europe and Australia, allowing patients
`who wish to do so to self-administer the
`medication. Worldwide, SC formula-
`tions currently represent about 70 per-
`cent of the total RA biologics market,
`80 percent in Europe alone. With its
`unique mechanism of action, differ-
`ing from standard anti-tumor necrosis
`factor (TNF) agents, and a balance of
`efficacy and safety, Orencia provides
`an important biologic alternative to stan-
`dard anti-TNF treatments. Also, Orencia
`is the only biologic agent currently avail-
`able in both intravenous (IV) and SC
`formulations for the treatment of RA.
`
`New clinical data from the AMPLE
`study, presented last year, further
`
`supports the efficacy of Orencia. The
`first large head-to-head trial of its kind
`in RA, AMPLE found that Orencia
`showed comparable efficacy to a com-
`monly prescribed TNF inhibitor. Further
`exploring additional uses, Phase III
`trials are beginning in lupus nephritis,
`a complex disease with a high unmet
`need, and in psoriatic arthritis.
`
`Sprycel and Erbitux
`
`Sprycel became a billion-dollar prod-
`uct globally for the first time in 2012,
`having established itself as an impor-
`tant medicine to treat chronic myeloid
`leukemia (CML) in both treatment-
`naïve and refractory patients. Physi-
`cians appreciate the fast and deep
`responses to the disease that Sprycel
`offers and its ability to achieve early
`response milestones. The approval
`of Sprycel as a first-line therapy has
`helped provide additional benefits
`for patients newly diagnosed with
`CML. Also, patients and physicians
`
`increasingly value the demonstrated
`long-term benefit and the simplicity of
`Sprycel’s once-daily dosing regimen.
`Sprycel was successfully launched
`in China in mid-2012 for second-line
`CML treatment, becoming our compa-
`ny’s first oncology therapy launched in
`China in 17 years. To further address
`areas of unmet medical need, ongo-
`ing studies are examining whether
`CML patients who have significant
`responses to Sprycel can eventually
`come off therapy and maintain their
`responses. Early studies also are
`assessing Sprycel in mutation-defined
`lung cancer and in pancreatic cancer.
`
`In 2012, Erbitux was approved for
`use as a first-line treatment option for
`patients with KRAS-mutation-negative
`
`(wild type) metastatic colorectal
`cancer (mCRC) (about 60 percent of
`the total mCRC population). Erbitux
`was initially approved in 2004 as a
`second-line or later treatment option
`for mCRC. In 2011, Erbitux also
`received approval as a first-line treat-
`ment option in recurrent metastatic
`squamous cell carcinoma of the head
`and neck. The new indications are
`important advances in the treatment
`of these two prevalent tumor types,
`offering both prolonged survival and
`increased response rates.
`
`Reyataz, Atripla and Sustiva
`
`A long-time leader in HIV treatments,
`Bristol-Myers Squibb was the first
`(partnering with Gilead) to bring a
`single-tablet regimen to the market
`with Atripla. Despite an increasingly
`competitive environment, Atripla
`remains the number-one-prescribed
`single tablet HIV regimen in the U.S., a
`position built on a foundation of proven
`
`efficacy and long-term virologic sup-
`pression. reyataz, launched in 2003,
`exhibits durable viral control and a
`strong resistance profile. It is used in
`both treatment-naïve and drug-resistant
`patients and plays an important role
`in the treatment of women, with data
`supporting its efficacy and safety in this
`population and with a unique label for
`use in pregnant women with HIV/AIDS.
`
`Indeed, we have placed a special
`focus on women living with HIV, a
`vulnerable and growing population.
`In Europe, for example, where women
`represent one-third of new HIV
`diagnoses, the company, in partner-
`ship with an independent faculty that
`includes health care providers and
`patient groups, has launched SHE, an
`
`6
`
` Bristol-Myers Squibb
`
`
`
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`

`

`2012 Annual Report
`
`Lucja Blesi
`
`7
`
`
`
` Bristol-Myers Squibb
`
`A Change for the Better
`
`For the past six years, Lucja Blesi, a 42-year-old
`mother of two and book dealer in St. Gallen, Swit-
`zerland, has been battling rheumatoid arthritis.
`
`It started as a mysterious joint swelling of a finger,
`and then worsened until her hands, feet and other
`joints were affected. The pain was constant and
`impaired her ability to walk. “I was unable to get up
`in the morning,” Blesi recalls. And while a standard
`therapy subsequently relieved much of the pain, “It
`was difficult to go on vacation. Many acute flareups
`still caused severe bouts of pain,” she admits.
`
`In 2011, her rheumatologist, Rüdiger Müller, M.D.,
`at the Cantonal Hospital of St. Gallen, prescribed
`Orencia IV. Her acute episodes have decreased and
`now she is back to taking walks and even skiing.
`Recently, Müller switched her to the newly approved
`subcutaneous formulation of Orencia so that she can
`administer the medication herself. He is enthusiastic
`about the broadened options for using Orencia. “This
`way,” he says, “we can treat patients with Orencia
`according to their preferred mode of administration.”
`
`“When I used to have these terrible episodes,” Blesi
`says, “I would think, ‘Why me? Why now?’ But now
`I am getting back to doing the things I used to do.”
`
`initiative to improve the quality of life
`for women living with HIV. The program
`seeks to educate health care provid-
`ers about the special needs of women
`while also empowering women to get
`the most out of health care services.
`SHE “units,” multidisciplinary teams
`based in clinics and hospitals, have
`been established at 16 health facilities
`in Europe, with 32 more planned for
`2013. The teams draw on SHE pro-
`gram medical and peer support mate-
`rials and faculty expertise to improve
`
`care and encourage best practices.
`
`Baraclude
`
`Baraclude sales were $1.4 billion in
`2012, with over 80 percent of sales
`coming from outside the U.S., including
`35 percent growth in China, its largest
`market. About three-quarters of the
`350 million people worldwide infected
`with hepatitis B virus are in Asia,
`including more than 90 million in China.
`The growth of Baraclude as first-line
`therapy for chronic hepatitis B infection
`
`is supported by data demonstrating
`sustained viral load reduction, minimal
`resistance and a favorable long-term
`safety profile, along with disease
`awareness efforts about understanding
`how the disease affects the liver.
`
`Looking to the future, studies are
`underway of a novel interferon, pegin-
`terferon lambda-1a, both as a poten-
`tial stand-alone hepatitis B treatment
`and as part of combination treatment
`r
`with Baraclude.
`
`Page 9 of 104
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`

`

`2012 Annual Report
`
`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
`
`8
`
` Bristol-Myers Squibb
`
`
`
`Page 10 of 104
`
`

`

`2012 Annual Report
`
`Nisha Gupta,M.D.
`
`9
`
`
`
` Bristol-Myers Squibb
`
`After a Long Struggle…Forever Grateful
`
`Too many times, it looked like Nisha Gupta’s battle
`against hepatitis C would end badly. The Detroit-area
`rheumatologist first contracted the chronic infection in
`May 1990 when, as a medical resident, she drew blood
`from an infected patient. Although she wore gloves, the
`needle pricked her skin. Soon she experienced her first
`symptoms and eventually was diagnosed with hepatitis C.
`
`Dr. Gupta received treatments on and off ever since,
`first to slow the infection’s advance and then mostly to
`control symptoms like severe itching, fatigue and mental
`confusion. “I worked until September 2009, when I found
`out I had liver cancer,” Gupta recalls. “By then I was
`prepared to die.”
`
`By her first liver transplant, she was suffering from hepatic
`encephalopathy, a worsening of brain function when the
`liver is no longer able to remove toxic substances in the
`blood. Her remissions after two liver transplants were
`short-lived, but her family and physician never lost hop