2011 ANNUAL REPORT
`
`growth through
`
`Innovation
`Innovation
`
`Yervoy patient and
`flight paramedic Bobby Harsh
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`Mylan v. AstraZeneca
`IPR2015-01340
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`

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`Bristol-Myers Squibb relies on innovation to discover,
`develop and deliver therapies to patients around the
`world – medicines that fight serious diseases and
`address significant unmet medical needs.
`
`On the Cover:
`
`
`Yervoy (ipilimumab) patient and flight paramedic Yervoy (ipilimumab) patient and flight paramedic Yervoy Bobby Harsh first discovered
`
`
`a pimple on his face that wouldn’t go away. It turned out to be malignant mela-
`noma, the deadliest form of skin cancer. After 10 hours of facial reconstruction
`surgery and 90 stitches, the Maryland State Trooper’s battle for survival was
`just beginning.
`
`Even after an experimental vaccine and two rounds of an immunotherapy
`called interleukin-2, the cancer spread to his lungs. “Being told you have
`a cancer that could kill you was very difficult,” he says more than two years
`later. “Once it metastasized, the odds were very slim I was going to live.”
`
`So Bobby, his wife and his three children decided to go on a long-planned
`camping trip to as many national parks as possible. When he returned, he
`got the last slot in a clinical trial for an investigational drug called ipilimumab
`at the Blumenthal Cancer Center in Charlotte, North Carolina, five hours
`from his suburban Baltimore home. Still, he stopped making future plans:
`“I was preparing for the likelihood that I wasn’t going to be here in a year.”
`
`After just 12 weeks, his first scans showed major improvement. Today, still in
`the clinical trial and back to work, Bobby gets a checkup at Blumenthal every
`
`
`three months. Ipilimumab (now Yervoy) was approved for use in adults with Yervoy) was approved for use in adults with Yervoy
`unresectable or metastatic melanoma in the U.S. in March 2011 and cleared
`for marketing in Europe in July. It is the first immunotherapy to deliver a signifi-
`cant long-term survival benefit in metastatic melanoma in a Phase III study.
`
`“You start looking at life differently,” Bobby admits. “When I work a night shift,
`I get to watch the sunrise. Now that means something different; things you
`take for granted, you just don’t anymore.”
`
`Yervoy is one of a number of innovations that have helped the company grow Yervoy is one of a number of innovations that have helped the company grow Yervoy
`
`
`in 2011, offering great promise for patients. A Special Report on Growth
`through Innovation begins on page 5.
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`
`Lamberto Andreotti, Chief Executive Officer
`
`To our STockholderS
`
`Message from the Chief Executive Officer
`
`We have just completed a very important year for
`Bristol-Myers Squibb.
`
`Executing against our BioPharma strategy, we delivered
`positive results, while setting the stage for a solid future.
`We increased sales. We moved forward with business
`development. We made significant clinical advances.
`And we launched three new products.
`
`In fact, last year marked a turning point for our company.
`
`Having transformed our company over the preceding
`years, we were in a position to start delivering … and
`that is exactly what we did. New products. New indica-
`tions. New markets. New business opportunities. New
`clinical advances. New approaches to customers.
`
`At the heart of our BioPharma strategy has been a firm
`commitment to innovation – one that not only drives
`our growth; it also defines our company. And in 2011,
`it helped deliver our success.
`
`Our Strong Financial Performance
`Last year, shareholder value remained a top priority.
`Indeed, our 39.5 percent shareholder return was
`one of the industry’s best.
`
`We grew our sales by 9 percent to over $21 billion. This
`was made possible by double-digit growth in several mar-
`kets. It was also made possible by double-digit growth in
`some key products, namely, Baraclude, Sprycel, Onglyza
`and Orencia, as well as a strong start for Yervoy.
`
`We maintained our strong financial health through disci-
`plined financial allocation. This included another increase
`in our annual dividend, a continuation of our $3 billion
`share repurchase program and ending the year with
`over $11.6 billion in cash and marketable securities.
`
`This, in turn, allowed us to pursue a tailored but deter-
`mined business development initiative – one that is
`flexible in its approach and ranges from relatively simple
`technology agreements to outright company acquisi-
`tions. Known as String of Pearls, this initiative provided
`us with several exciting opportunities – all of which have
`added significantly to our long-term vision. From them,
`we acquired skilled people, great science and poten-
`tial products. Our most recent transaction involved the
`purchase of Inhibitex, a clinical-stage biopharmaceutical
`company best known for its work to develop a treatment
`for hepatitis C and other serious infectious diseases.
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`
`“At the heart of
`our BioPharma
`strategy has been
`a firm commitment
`to innovation –
`one that not only
`drives our growth;
`it also defines our
`company.”
`
`Our Increasingly Diversified Portfolio
`More than anything, 2011 will be remembered
`for our pipeline advances. Despite some recent
`setbacks, including having received a complete
`response letter for dapagliflozin, we had three
`new product approvals: Yervoy for metastatic
`melanoma, Eliquis for the prevention of venous
`thromboembolic events (VTE) and Nulojix for
`kidney transplant rejection.
`
`Yervoy
`Yervoy was a game-changer for patients. When it
`was launched last March, this innovative medicine
`for metastatic melanoma gave patients with this
`devastating unmet medical need something truly
`special: hope. For the first time in over a decade,
`they had a new treatment.
`
`Indeed, prior to Yervoy, no single standard of care
`existed, and no therapy had demonstrated an
`overall survival benefit. And while its launch was
`followed by another new melanoma product on
`the market, Yervoy’s reach has continued to grow.
`
`Eliquis
`Similarly, we hope that Eliquis can become a
`game-changer for patients, too.
`
`It was approved last year in Europe for VTE
`prevention in adult patients who have undergone
`elective hip or knee replacement surgery and
`was launched in a number of EU countries. More
`significantly, however, we announced last sum-
`mer the results of a major Phase III clinical study
`that demonstrated Eliquis’ superiority to warfarin
`with respect to both safety and efficacy for stroke
`prevention in patients with atrial fibrillation – a
`common heart arrhythmia that affects an estimated
`10 million patients worldwide. This is a condition
`that greatly increases the risk of stroke, the third
`leading cause of death in the U.S.
`
`This study was a triple win in that it demonstrated
`a significant reduction in the risk of stroke, major
`bleeding and mortality – making Eliquis the first
`potential anticoagulant to show a significant
`reduction in these three areas in patients with
`atrial fibrillation. This complements an earlier study
`that demonstrated that, for patients unsuitable for
`therapy such as warfarin, Eliquis was statistically
`
`superior to aspirin in reducing the risk of stroke
`without a significant increase in major bleeding,
`fatal bleeding or intracranial bleeding.
`
`We are expecting regulatory decisions in the U.S.
`and Europe on the indication for stroke prevention
`in patients with atrial fibrillation in 2012.
`
`Nulojix
`And Nulojix, the third new product launched last
`year, is a breakthrough medicine for the prevention
`of organ rejection in adult patients receiving
`a kidney transplant. This first-in-class biologic
`immuno-suppressive therapy addresses a signifi-
`cant previously unmet medical need.
`
`Nulojix was the first new mechanism to be
`approved for kidney transplants in more than a
`decade and now provides patients with a new
`therapeutic option – one that preserves the renal
`function of the transplanted kidney and one that
`also helps make long-term renal health more
`likely. Achieving sustained improvements in renal
`function has been a major challenge to overcome
`in the treatment of kidney transplant patients.
`
`Our Valued Customers
`To drive our BioPharma growth and to make sure
`that our medicines get to the patients who need
`them, we developed a completely new approach
`to customers.
`
`Called Customers@Center, our novel, more
`holistic approach focuses on all aspects of the
`patient’s journey and all of the customers and other
`stakeholders involved, including physicians, nurses,
`payers, hospitals and of course, patients. With a
`deeper understanding of this journey, we are now
`able to deliver a superior customer experience –
`one that increases the impact our products have
`on patient lives by speeding access and facilitating
`understanding of how to use the products.
`
`Our Valued People
`In 2011, we intensified our focus on the people
`at the center of our success: our employees.
`
`They are the ones who conduct the research, lead
`the clinical trials and manufacture the medicines.
`They are the ones who work at our regulatory
`approvals and who market and promote our
`
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`
`Net Sales ($B)
`
`Diluted Earnings per Share ($)
`(from continuing operations attributable to Bristol-Myers Squibb)
`
`GAAP
`
`Non-GAAP
`
`Dividends per Share ($)
`
`For further detail on management’s use of non-GAAP financial information and reconciliation to
`non-GAAP to GAAP EPS, see “Management’s Discussion and Analysis of Financial Condition and
`Results of Operations – Non-GAAP Financial Measures” in the Financial Review and the “Quarterly
`Package of Financial Information” on the company’s web site at www.bms.com.
`
`company and brands. They are the ones who support all
`of the others on legal, compliance, finance, human resource
`and communication matters. In other words, they are the
`ones who make it all happen.
`
`For that reason, in 2011, we devoted a great deal of time
`and other resources to hire, train and develop our people.
`Through a series of employee-focused initiatives, we worked
`to strengthen our BioPharma culture by placing even greater
`emphasis on collaboration, innovation and excellence.
`
`We also made some important additions to our leadership
`team. Specifically, we welcomed three new members –
`Giovanni Caforio, Lou Schmukler and Paul von Autenried –
`to our Senior Management Team.
`
`Our Corporate Responsibility
`And finally, in 2011, we built upon our strong tradition
`of corporate responsibility through a range of important
`activities to better our world and the people living in it.
`
`Our Bristol-Myers Squibb Foundation philanthropic work
`continued in Africa (HIV/AIDS), Europe (cancer), Asia
`(hepatitis) and the U.S. (mental health and diabetes). We
`deepened our involvement with the United Nations Global
`Compact, a strategic policy initiative for businesses com-
`mitted to a series of social and environmental principles.
`We pursued our internal “Go Green” environmental
`sustainability initiatives at company sites throughout the
`world. And when an earthquake and tsunami devastated
`parts of Japan, our Foundation and many of our employees
`from around the globe rose to the challenge by providing
`support to co-workers and others affected by the crisis.
`
`Our Exciting Future
`Without question, this is a very good moment in the life
`of Bristol-Myers Squibb. We see it in the numbers. We
`see it in the products. We see it in the engagement of our
`employees. We see it in the lives of the patients we serve.
`And I have every reason to believe that we can continue
`to see it – this year and in years to come.
`
`To be sure, 2012 will pose challenges for us. Most notably,
`we will lose exclusivity for two of our biggest products –
`Plavix and Avapro – and we will face an increasingly
`uncertain global regulatory and economic environment.
`
`But I am firmly confident in our future. With a robust
`pipeline … a solid financial position … a strong manage-
`ment team … and a commitment to innovation that runs
`through every part of our organization … our long-term
`growth potential and ability to deliver are real.
`
`To that end, we will continue to seize opportunities and
`navigate challenges. We will continue to balance short-term
`results and long-term investments. We will continue striving
`to deliver success in everything we do.
`
`This is what it means to be the benchmark BioPharma
`company – the benchmark for helping people prevail over
`serious diseases. The benchmark for innovation that matters.
`
`Lamberto Andreotti
`Chief Executive Officer
`March 8, 2012
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`“Innovation is central
`to the cutting-edge
`work being done
`in our laboratories,
`the state-of-the-art
`operations at our
`manufacturing plants
`and our pioneering
`approach to com-
`mercialization and
`product promotion.”
`
`Message from the Chairman
`
`I am very proud of all that our company has accomplished.
`
`We read about it in the media. We hear about it from analysts. We see it in the lives of the
`patients we serve. Our company is driving results and delivering success.
`
`Financially, we are in a solid position. Our products are generating strong revenue, while
`our productivity is achieving real savings. Our shareholder return has been one of the best
`in the industry.
`
`Clinically, we have a late-stage pipeline that is robust and diversified – one that is a mix of
`both small molecules and biologics. Some were discovered internally. Some were sourced
`from external innovation. All have the potential to improve the standard of care for patients
`with high unmet medical need.
`
`The key to this success has been our steadfast focus on innovation.
`
`In fact, Bristol-Myers Squibb is a company rooted in innovation. It guides our work. It fuels
`our growth.
`
`This is true throughout our entire organization. Innovation is central to the cutting-edge
`work being done in our laboratories, the state-of-the-art operations at our manufacturing
`plants and our pioneering approach to commercialization and product promotion.
`
`In 2011, this focus on innovation paid off. It was one of our most successful years.
`
`In 2012, we will certainly face our share of challenges. Most notably, we will have to work
`through the loss of exclusivity for two of our products, the volatility of foreign exchange
`rates and the impact of global economic uncertainty. I, however, remain confident in our
`ability to mitigate these challenges and to drive strong results.
`
`We have a first-rate Board of Directors, which recently welcomed our newest member,
`Gerald L. Storch, Chairman and Chief Executive Officer, Toys“R”Us, Inc., and a dynamic
`Senior Management Team, led by CEO Lamberto Andreotti. We have an outstanding
`organization of dedicated professionals whose record of achievement is matched only
`by its potential. And we have a companywide commitment to growth through innovation.
`
`Over the past few years, we have done much to transform our company into a BioPharma
`leader. We evolved our mission, strategy and overall approach. We developed a company
`culture better suited for our BioPharma future. We took the company in a new direction.
`
`Last year, we demonstrated the success of this transformation. This year, we plan to
`demonstrate its sustainability.
`
`As Chairman of the Board, I am very pleased with our recent success and very optimistic
`about our exciting future.
`
`James M. Cornelius
`Chairman
`March 8, 2012
`
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`Bristol-Myers squiBB special report
`
`growth through
`
`Innovation
`
`Generating new ideas and thinking differently are
`at the heart of everything we do at Bristol-Myers
`Squibb. That goes for discovering and developing
`new drugs, expanding our markets and harnessing
`technologies, keeping customers – especially our
`patients – at the center of everything we do, and
`acting responsibly to improve health outcomes
`around the world. It is this innovative spirit that
`has expanded opportunities for our company
`and for the people we serve.
`
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`Bristol-Myers Squibb Special Report
`
`Paradigm Shifts in Treating Disease
`
`Our focus on following the science,
`especially as it unfolds through
`clinical development, is leading
`to shifts in treatment paradigms.
`The result of these innovations
`often is new hope for patients.
`
`Eliquis: Seeking to
`Reduce Stroke Risk
`Patients suffering from atrial fibrillation
`(more than 5 million in the U.S. alone)
`are at increased risk for stroke. For
`decades, these patients have been
`prescribed warfarin, an effective oral
`anticoagulant, to prevent blood clots.
`But warfarin has challenges. “You
`have to dose very precisely for each
`patient. And there are unfavorable
`interactions with food and other medi-
`cines that, if not managed appropriately,
`can lead to serious bleeding complica-
`tions,” says Puneet Mohan, M.D.,
`medical lead for Eliquis (apixaban),
`an investigational compound.
`In developing a potential alterna-
`tive, Bristol-Myers Squibb focused
`on a compound to reduce the risk of
`stroke, systemic embolism and death
`in patients with nonvalvular atrial fibril-
`lation, potentially with a lower bleeding
`risk than warfarin and with no need for
`continuous monitoring.
`“Others were focused on developing
`a once-a-day formulation, the thought
`being that it would be more convenient
`for patients,” explains Jack Lawrence,
`M.D., Eliquis full development lead. “But
`when our early clinical data suggested
`that twice-daily administration was more
`likely to result in a more favorable trade-
`off between efficacy and bleeding, we
`followed the science and went against
`the grain. We believe it may make all
`the difference for this compound.”
`
`Eliquis has already been approved in
`Europe for preventing venous thrombo-
`embolic events (VTE) following elective
`hip and knee replacement surgeries
`and is under review in the U.S., the EU
`and Japan for patients with nonvalvular
`atrial fibrillation. “Major orthopedic
`surgery puts patients at high risk of
`developing VTEs, a painful condition
`that can lead to a pulmonary embolism,
`
`the potential to
`change how these
`patients are
`
`managedmanaged
`
`which may cause sudden death,” says
`Michael Rud Lassen, M.D., of Glostrup
`Hospital in Copenhagen, lead investi-
`gator for the VTE prevention trials. The
`studies supporting the EU approval
`demonstrated that Eliquis was more
`effective than the current standard of
`care, enoxaparin, without increasing
`bleeding. It also had an added benefit
`of not having to be used until after
`surgery, allowing time for surgeons
`to stabilize the patient.
`A significant development for Eliquis
`was the communication of the results of
`ARISTOTLE, a Phase III study evaluat-
`ing Eliquis for stroke prevention in atrial
`fibrillation. The data, presented at the
`European Society of Cardiology and
`published in the New England Journal
`of Medicine, showed Eliquis was
`superior to warfarin in reducing strokes,
`systemic embolism and mortality, as
`well as the incidence of major bleeding.
`
`In the landmark ARISTOTLE trial,
`when compared to warfarin, apixaban
`reduced the risk of stroke and systemic
`embolism by 21 percent, the risk of
`major bleeding by 31 percent, and
`mortality by 11 percent. Lars Wallen-
`tin, M.D., Ph.D., of Sweden’s Uppsala
`University, one of the trial’s principal
`co-investigators, says, “When we saw
`the results for the first time, reducing
`complications like stroke, reducing mor-
`tality and seeing an improvement for
`the risk of bleeding, it was amazing.”
`Stuart Connolly, M.D., at Canada’s
`McMaster University, was lead
`investigator on another large Phase
`III trial focused on reducing the risk of
`stroke in patients with atrial fibrilla-
`tion. The AVERROES trial compared
`apixaban with aspirin in patients who
`were expected or demonstrated to be
`unsuitable for a vitamin K antagonist
`such as warfarin. “In the past, only
`about half of patients with atrial fibrilla-
`tion at risk for stroke actually received
`warfarin,” he says. “Those patients
`may receive aspirin instead. Apixaban
`showed a substantial reduction in
`stroke risk and no increased risk of
`major bleeding or intracranial hemor-
`rhage when compared to aspirin in
`those patients.”
`Based on the results of ARISTOTLE
`and the previously reported AVERROES
`data, the company, with its alliance
`partner Pfizer, received priority review by
`the U.S. Food and Drug Administration
`(FDA) for Eliquis for reduction of stroke
`and systemic embolism in patients with
`nonvalvular atrial fibrillation.
`“If Eliquis is approved for nonvalvular
`atrial fibrillation, we have the potential
`to change how these patients are
`
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`hopeful
`
`Before his heart troubles surfaced, Larry Narkiewicz,
`77, (pictured with son Robert) would spend his time
`helping his family, working at his son’s construction
`business and playing nickel slot machines in casinos
`not far from his suburban Philadelphia home. Once,
`he even won $10,000. Then, in 2007, he discovered
`he had atrial fibrillation, an abnormal heart rhythm that
`puts patients at a higher risk of stroke. To help prevent
`dangerous blood clots, he was put on what was then
`the standard of care. “There was no consistency in
`the levels of the drug in my system,” he says. His
`daughter, Rita Ann, says he was always “concerned,
`frustrated and upset.” His cardiologist suggested that
`Larry enter a clinical trial studying a treatment alterna-
`tive – apixaban, a potential new therapy to reduce the
`risk of strokes in patients with atrial fibrillation, now
`awaiting regulatory approval. Today, Larry’s looking
`forward to being able to help his family again and
`maybe even hitting another jackpot.
`
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`Bristol-Myers Squibb Special Report
`
`managed and to deliver to physicians
`a product with demonstrated superior
`outcomes in risk reduction for stroke,
`systemic embolism and mortality, as
`well as reductions in major bleeding
`versus warfarin,” says Lynn Stagon,
`Eliquis global commercial lead.
`
`Yervoy: Improving Survival
`In March 2011, Yervoy (ipilimumab)
`was approved in the U.S. for the treat-
`ment of melanoma that has spread or
`cannot be cured with surgery. It also
`became the first drug to demonstrate
`long-term survival for people with this
`most deadly form of skin cancer by sup-
`porting the body’s own natural defense
`mechanisms to attack melanoma cells.
`Says Ronald Peck, M.D., Yervoy full
`development lead, “We have known
`for years that the body’s immune
`system could potentially be harnessed
`to treat patients with cancer. There
`is now no question that real benefit
`can be achieved with Yervoy for many
`patients with advanced melanoma.
`We are excited to be studying this
`approach more broadly.” The company
`continues to invest in exploring new
`regimens, combinations and other
`possible uses, such as in earlier
`stages of melanoma and other tumors
`like prostate cancer and lung cancer.
`How did science lead the way in
`its clinical development? Generally,
`the traditional way to determine the
`efficacy of a new cancer therapy has
`been to use classic chemotherapy
`guidelines. That includes, with che-
`motherapy agents that target tumor
`cells directly, determining if the tumor
`is progressing – or growing. That
`therapeutic effect usually comes
`early or not at all. But with Yervoy, an
`immuno-oncology agent that targets
`the immune system instead of the
`tumor itself, the result was different.
`
`Page 8 | Bristol-Myers Squibb 2011 Annual Report
`
`Yervoy (ipilimumab) patient Bobby Harsh (center), here with
`his wife, Donna, and three children (from left, Lindsey, Julie and
`Dan), enrolled in an ipilimumab clinical trial in August 2009.
`You can read his story on the inside front cover of this report.
`
`Jon Richards, M.D., an oncologist
`in a Chicago suburb who treats only
`melanoma patients and participated in
`the clinical trials, explains: “In the past,
`we considered it a failure when we saw
`things growing. But with ipilimumab,
`when we saw that happening for many
`patients, the investigators and the com-
`pany decided to wait and see, instead
`of pulling the plug on the trial. We
`readjusted our expectations and began
`to recognize that the drug was going to
`take some time to work, unlike standard
`chemotherapy. The initial response – a
`swelling – looked like growth or tumor
`progression. What they actually were
`witnessing was the immune system
`kicking in, doing battle with the tumor.
`“With ipilimumab, for many patients,
`we saw things getting worse and then
`dramatically getting better. They had
`reached the tipping point when the
`immune system was suddenly empow-
`ered to recognize the melanoma,” he
`continues. “I wasn’t surprised by what
`I saw. ‘Ecstatic’ is the right word.”
`“Ultimately,” says Jedd Wolchok,
`
`M.D., Ph.D., an oncologist also
`specializing in melanoma and a
`clinical investigator at Memorial
`Sloan-Kettering Cancer Center,
`“ipilimumab has validated the entire
`notion of using immune checkpoint
`manipulation to treat cancer. We
`treat the patient, and the patient’s
`immune system sculpts itself to form
`a very specific immune reaction to the
`tumors. The result has been unprec-
`edented improvement in survival for
`many patients with metastatic mela-
`noma. That in itself is a landmark.”
`
`Nulojix: Focusing on
`Transplant Outcomes
`Nulojix (belatacept) received approval
`in June 2011 in the U.S. and Europe
`to prevent organ rejection in adults
`who have received a kidney transplant
`when used in combination with cortico-
`steroids and certain other medicines.
`Nulojix represents a first-in-class
`biologic that works by blocking certain
`signals in the body’s own immune
`system that can lead to rejection of
`the kidney transplant.
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`“It represents the first T-cell
`co-stimulation blocker to maintain
`immunosuppression after a kidney
`transplant,” says Mary Beth Harler,
`M.D., Nulojix full development lead.
`“More than 15 years in development,
`our scientists used rational drug
`design to engineer a molecule that
`would inhibit two different sites on
`the antigen-presenting cells that
`activate the immune system’s T-cells
`to attack a transplanted organ.”
`Using rational drug design in
`biologics to create a co-stimulation
`blocker was in itself an innovation.
`Bristol-Myers Squibb scientists also
`allowed science to lead the way in its
`clinical trial design to provide evidence
`of belatacept’s efficacy and to address
`significant unmet medical needs in
`renal organ transplantation.
`Traditionally, the prevention of acute
`rejection, an immune response to the
`implanted organ leading to graft dys-
`function or failure, has been viewed as
`a measure of a transplant drug’s suc-
`cess. More than 90 percent of kidney
`transplant patients receiving cyclospo-
`rine, a well-established therapy, have a
`functional graft one year after trans-
`plantation. But patients on cyclosporine
`may experience declining kidney func-
`tion, diabetes and high blood pressure.
`It was clear to Bristol-Myers Squibb
`that a significant unmet medical need
`remained. Some measures of success
`of kidney transplantation, in the eyes
`of patients and physicians, would be
`improved graft function and patient
`and graft survival.
`A Phase III clinical program consisted
`of two large three-year trials evaluat-
`ing Nulojix head-to-head against
`cyclosporine, each in combination with
`certain other medications and together
`enrolling more than 1,200 patients.
`
`Significantly, Bristol-Myers Squibb
`researchers decided to measure renal
`function and use it as an important
`endpoint in these trials to compare the
`two therapies. In both studies, overall
`efficacy was comparable between
`
`significant unmet significant unmet
`
`medical needs
`in renal organ
`
`transplantationtransplantation
`
`Nulojix and cyclosporine. Yet Nulojix
`demonstrated superior renal function at
`one year, which was sustained through
`three years, compared to cyclosporine.
`In addition, at one year, a lower inci-
`dence of new onset diabetes and lower
`blood pressure were observed. The
`lower blood pressure persisted through
`three years of follow-up in patients
`treated with Nulojix compared with
`patients treated with cyclosporine.
`Patients treated with Nulojix are at
`increased risk of two potentially fatal
`
`diseases – post-transplant lympho-
`proliferative disorder (PTLD), predomi-
`nantly in the central nervous system,
`and progressive multifocal leukoen-
`cephalopathy. Nulojix also should not
`be used in patients if they have never
`been exposed to Epstein-Barr Virus
`because they are at higher risk for
`PTLD. The company has collaborated
`with the FDA to develop a risk mitiga-
`tion strategy to inform physicians and
`patients of the serious risks associ-
`ated with Nulojix and to ensure that
`physicians carefully weigh benefits
`versus risks for individual patients.
`The company also has established
`a patient registry to further evaluate
`the safety profile.
`“Not only was the discovery and
`development of the molecule that would
`ultimately become Nulojix innovative,
`but so was a clinical trial program that
`sought to elucidate the importance
`of renal function in these transplant
`patients,” Harler adds. “As a result,
`Nulojix offers physicians and patients a
`first-in-class molecule with a selective
`and targeted approach to maintenance
`of immunosuppression.” Y
`
`Onglyza: Further Exploring Safety and Benefit
`
`While the U.S. Food and Drug Administration has mandated that all compa-
`nies conduct post-approval studies on all new diabetes medicines to ensure
`they do not pose an unacceptable cardiovascular risk, Bristol-Myers Squibb
`and partner AstraZeneca are going a step further. In the SAVOR-TIMI 53
`clinical trial, 16,500 patients will be studied to also test whether Onglyza
`(saxagliptin) may prevent cardiovascular events like heart attack or stroke.
`“No type 2 diabetes drug has yet been shown to clearly impact the rate
`of cardiovascular events,” says Deepak L. Bhatt, M.D., M.P.H., a principal
`investigator and associate professor of medicine at Harvard Medical School.
`“However, we know Onglyza improves the ability of the tissue lining blood
`vessels to recover from injury, which may translate into cardiovascular ben-
`efit,” notes Itamar Raz, M.D., a principal investigator who heads the diabetes
`unit at Hadassah University Hospital in Jerusalem.
`
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`
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`
` Bristol-Myers Squibb 2011 Annual Report | Page 9
`
`Page 11 of 110
`
`

`
`Bristol-Myers Squibb Special Report
`
`A Pipeline of Possibilities
`
`“The key innovation was in being
`prepared to respond to the information
`that such patients provide.”
`As in other cancers and leukemias,
`it is necessary to identify among lung
`cancer patients those subpopulations
`who can truly benefit from individual
`targeted therapies. Patient tumors
`are screened for genetic mutations,
`with therapies selected based on the
`molecular abnormalities observed.
`
`potential new
`therapies rich
`with innovative
`
`possibilitiespossibilities
`
`Bristol-Myers Squibb’s pipeline of
`potential new therapies is rich with
`innovative possibilities. Here are a
`few examples in cancer, hepatitis C
`and immunotherapies.
`
`New Possibilities for Dasatinib
`By looking closely at the emerging
`science, Bristol-Myers Squibb is
`exploring additional uses for approved
`
`
`medicines such as Sprycel (dasatinib), Sprycel (dasatinib), Sprycel
`a Bristol-Myers Squibb drug currently
`approved for chronic myeloid leuke-
`mia. For example, two patients with
`advanced lung cancer and a very
`poor prognosis who were enrolled in
`separate small investigator-initiated
`trials where they received dasatinib
`did much better than others in those
`trials, who succumbed to their
`disease. One stayed on dasatinib for
`14 months; her tumor was found to
`have a specific mutation. T