Bristol-Myers Squibb Reports Results for Phase 3 Trial of Yervoy® (Ipilimumab) in Previously-Treated Castration-Resistant

  Bristol-Myers Squibb Reports Results for Phase 3 Trial of Yervoy®
  (Ipilimumab) in Previously-Treated Castration-Resistant Prostate Cancer

  *Primary endpoint of overall survival did not reach statistical
    significance in this advanced patient population (p=0.053); however,
    anti-tumor activity was observed in other efficacy endpoints, including
    progression-free survival
  *Drug-related adverse events were mostly immune-related, consistent with
    those observed previously with Yervoy
  *Phase 3 trial (Study 095) assessing overall survival of Yervoy in patients
    with less advanced castration-resistant prostate cancer who have received
    no prior cytotoxic treatment is ongoing

Business Wire

PRINCETON, N.J. -- September 12, 2013

Bristol-Myers Squibb Company (NYSE:BMY) today reported results from the Phase
3 randomized, double-blind clinical trial (Study 043) comparing Yervoy 10
mg/kg (ipilimumab) (n=399) to placebo (n=400) following radiation in patients
with advanced metastatic castration-resistant prostate cancer (mCRPC) who have
received prior treatment with docetaxel. The study’s primary endpoint of
overall survival (OS) did not reach statistical significance (HR = 0.85; 95%
CI = 0.72-1.00; p = 0.053). However, anti-tumor activity was observed across
some efficacy endpoints, including progression free-survival. These data will
be presented at the 2013 European Cancer Congress in an oral session on
September 28 (Abstract # 2850).

Treatment-related adverse events were common, with most being immune-related
(irAEs), and were managed using standard Yervoy management protocols. Grade ≥3
irAEs in the Yervoy and placebo arms, respectively, were gastrointestinal (GI;
18% vs. 1%), liver (5% vs. 1%), endocrine (2% vs. 1%), and dermatologic (1%
vs. 0%). The incidence of drug-related death was 1%.

“While we are disappointed that the primary endpoint of overall survival was
not met, we remain encouraged that results in this advanced population support
the potential role of immunotherapies for prostate cancer. We are committed to
continuing our development of Yervoy in prostate cancer,” said Brian Daniels,
senior vice president, Global Development and Medical Affairs, Bristol-Myers
Squibb. “Immuno-oncology is a rapidly evolving treatment modality and findings
from this study provide important scientific insights that can be applied to
current and future studies of Yervoy as well as our broad pipeline of
immunotherapies in development.”

Yervoy 3 mg/kg monotherapy is currently approved in more than 40 countries for
the treatment of patients with unresectable or metastatic melanoma.

“Although the study did not meet its primary endpoint, clinical activity was
observed in this Phase 3 trial with a suggestion of greater activity in those
with less advanced castration-resistant prostate cancer,” said W.R. Gerritsen,
MD, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. “These
results offer important insights for ongoing and future studies of Yervoy in
prostate cancer, including a second large trial of Yervoy in patients with
less advanced disease.”

The Phase 3 program for Yervoy includes Study 095, an ongoing Phase 3
randomized double-blind trial comparing the efficacy of Yervoy 10 mg/kg versus
placebo in patients with mCRPC who have not received prior cytotoxic
treatment. Yervoy is also being studied in Phase 3 trials in adjuvant melanoma
and non-small cell lung cancer.

Study 043 Results

In the intent-to-treat population, the median OS was 11.2 months for Yervoy
and 10 months for placebo and the hazard ratio was 0.85 (95% CI = 0.72-1.00; p
= 0.053). The one- and two-year survival rates for Yervoy versus placebo were
47% versus 40%, and 26% versus 15%, respectively.

Median progression-free survival favored Yervoy over placebo (HR=0.70; 95% CI
= 0.61-0.82) as did prostate-specific antigen (PSA) response rates, as
evidenced by declines of ≥50% in evaluable patients (13.1% vs. 5.3%,
respectively). Pre-specified subset analyses suggest that Yervoy may be more
active in patients with indicators for less advanced disease.

Treatment-related adverse events were common and most were immune-related.
Grade ≥3 irAEs in the Yervoy and placebo arms, respectively, were
gastrointestinal (GI; 18% vs. 1%), liver (5% vs. 1%), endocrine (2% vs. 1%),
and dermatologic (1% vs. 0%). Most were managed using standard Yervoy
management protocols, including the administration of systemic
corticosteroids, dose interruption/discontinuation and/or other
immunosuppressants. Incidences of drug-related death and GI perforation, per
investigator assessment, were 1% and 0.5%, respectively.

About Study 043

CA-184-043 is a randomized, double-blind, Phase 3 study comparing Yervoy to
placebo following radiotherapy in patients with CRPC who have received prior
treatment with docetaxel. Patients received bone-directed radiation therapy
after being randomly assigned 1:1 to receive Yervoy 10 mg/kg (n=399) or
placebo (n=400) every three weeks for a total of four doses. Eligible patients
received maintenance treatment every three months.

Patient baseline characteristics were indicative of advanced disease.
Forty-eight percent had baseline pain of ≥4, based on the Brief Pain Inventory
(BPI), a questionnaire used by clinicians to assess and measure pain.

About Prostate Cancer

Prostate cancer is the second most frequently diagnosed cancer and the sixth
most deadly cancer in men.In the United States, it is estimated that more
than 238,000 men will be diagnosed with prostate cancer and more than 29,700
will die from the disease in 2013. Most of these deaths will be caused by
metastatic castration-resistant prostate cancer, which occurs when the cancer
becomes resistant to standard hormonal treatment and spreads from the prostate
to other organs in the body.New treatment options have recently become
available for patients with mCPRC, yet the disease remains largely incurable.

About Yervoy

Yervoy, which is a recombinant, human monoclonal antibody, blocks the
cytotoxic T- lymphocyte antigen-4 (CTLA-4). CTLA-4 is a negative regulator of
T-cell activation. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4
with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment
T-cell activation and proliferation. The mechanism of action of Yervoy’s
effect in patients with melanoma is indirect through T-cell mediated
anti-tumor immune responses. On March 25, 2011, the FDA approved Yervoy 3
mg/kg monotherapy for patients with unresectable or metastatic melanoma.
Yervoy is now approved in more than 40 countries.

YERVOY^® (ipilimumab) INDICATIONS & IMPORTANT SAFETY INFORMATION

YERVOY is indicated for the treatment of unresectable or metastatic melanoma.

Important Safety Information

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse reactions due to
T-cell activation and proliferation. These immune-mediated reactions may
involve any organ system; however, the most common severe immune-mediated
adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic
epidermal necrolysis), neuropathy, and endocrinopathy. The majority of these
immune-mediated reactions initially manifested during treatment; however, a
minority occurred weeks to months after discontinuation of YERVOY.

Assess patients for signs and symptoms of enterocolitis, dermatitis,
neuropathy, and endocrinopathy and evaluate clinical chemistries including
liver function tests (LFTs) and thyroid function tests at baseline and before
each dose.

Permanently discontinue YERVOY and initiate systemic high-dose corticosteroid
therapy for severe immune-mediated reactions.

Recommended Dose Modifications

Withhold dose for any moderate immune-mediated adverse reactions or for
symptomatic endocrinopathy until return to baseline, improvement to mild
severity, or complete resolution, and patient is receiving <7.5 mg prednisone
or equivalent per day.

Permanently discontinue YERVOY for any of the following:

  *Persistent moderate adverse reactions or inability to reduce
    corticosteroid dose to 7.5 mg prednisone or equivalent per day
  *Failure to complete full treatment course within 16 weeks from
    administration of first dose
  *Severe or life-threatening adverse reactions, including any of the
    following

       *Colitis with abdominal pain, fever, ileus, or peritoneal signs;
         increase in stool frequency (≥7 over baseline), stool incontinence,
         need for intravenous hydration for >24 hours, gastrointestinal
         hemorrhage, and gastrointestinal perforation
       *AST or ALT >5 × the upper limit of normal (ULN) or total bilirubin >3
         × the ULN
       *Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash
         complicated by full-thickness dermal ulceration or necrotic, bullous,
         or hemorrhagic manifestations
       *Severe motor or sensory neuropathy, Guillain-Barré syndrome, or
         myasthenia gravis
       *Severe immune-mediated reactions involving any organ system
       *Immune-mediated ocular disease which is unresponsive to topical
         immunosuppressive therapy

Immune-mediated Enterocolitis:

  *In the pivotal Phase 3 study in YERVOY-treated patients, severe,
    life-threatening or fatal (diarrhea of ≥7 stools above baseline, fever,
    ileus, peritoneal signs; Grade 3-5) immune-mediated enterocolitis occurred
    in 34 (7%) and moderate (diarrhea with up to 6 stools above baseline,
    abdominal pain, mucus or blood in stool; Grade 2) enterocolitis occurred
    in 28 (5%) patients
  *Across all YERVOY-treated patients (n=511), 5 (1%) developed intestinal
    perforation, 4 (0.8%) died as a result of complications, and 26 (5%) were
    hospitalized for severe enterocolitis
  *Infliximab was administered to 5 of 62 (8%) patients with moderate,
    severe, or life-threatening immune-mediated enterocolitis following
    inadequate response to corticosteroids
  *Monitor patients for signs and symptoms of enterocolitis (such as
    diarrhea, abdominal pain, mucus or blood in stool, with or without fever)
    and of bowel perforation (such as peritoneal signs and ileus). In
    symptomatic patients, rule out infectious etiologies and consider
    endoscopic evaluation for persistent or severe symptoms
  *Permanently discontinue YERVOY in patients with severe enterocolitis and
    initiate systemic corticosteroids (1-2 mg/kg/day of prednisone or
    equivalent). Upon improvement to ≤Grade 1, initiate corticosteroid taper
    and continue over at least 1 month. In clinical trials, rapid
    corticosteroid tapering resulted in recurrence or worsening symptoms of
    enterocolitis in some patients
  *Withhold YERVOY for moderate enterocolitis; administer anti-diarrheal
    treatment and, if persistent for >1 week, initiate systemic
    corticosteroids (0.5 mg/kg/day prednisone or equivalent)

Immune-mediated Hepatitis:

  *In the pivotal Phase 3 study in YERVOY-treated patients, severe,
    life-threatening, or fatal hepatotoxicity (AST or ALT elevations >5x the
    ULN or total bilirubin elevations >3x the ULN; Grade 3–5) occurred in 8
    (2%) patients, with fatal hepatic failure in 0.2% and hospitalization in
    0.4%
  *13 (2.5%) additional YERVOY-treated patients experienced moderate
    hepatotoxicity manifested by LFT abnormalities (AST or ALT elevations
    >2.5x but ≤5x the ULN or total bilirubin elevation >1.5x but ≤3x the ULN;
    Grade 2)
  *Monitor LFTs (hepatic transaminase and bilirubin levels) and assess
    patients for signs and symptoms of hepatotoxicity before each dose of
    YERVOY. In patients with hepatotoxicity, rule out infectious or malignant
    causes and increase frequency of LFT monitoring until resolution
  *Permanently discontinue YERVOY in patients with Grade 3-5 hepatotoxicity
    and administer systemic corticosteroids (1-2 mg/kg/day of prednisone or
    equivalent). When LFTs show sustained improvement or return to baseline,
    initiate corticosteroid tapering and continue over 1 month. Across the
    clinical development program for YERVOY, mycophenolate treatment has been
    administered in patients with persistent severe hepatitis despite
    high-dose corticosteroids
  *Withhold YERVOY in patients with Grade 2 hepatotoxicity

Immune-mediated Dermatitis:

  *In the pivotal Phase 3 study in YERVOY-treated patients, severe,
    life-threatening or fatal immune-mediated dermatitis (e.g.,
    Stevens-Johnson syndrome, toxic epidermal necrolysis, or rash complicated
    by full thickness dermal ulceration, or necrotic, bullous, or hemorrhagic
    manifestations; Grade 3–5) occurred in 13 (2.5%) patients

       *1 (0.2%) patient died as a result of toxic epidermal necrolysis
       *1 additional patient required hospitalization for severe dermatitis

  *There were 63 (12%) YERVOY-treated patients with moderate (Grade 2)
    dermatitis
  *Monitor patients for signs and symptoms of dermatitis such as rash and
    pruritus. Unless an alternate etiology has been identified, signs or
    symptoms of dermatitis should be considered immune-mediated
  *Permanently discontinue YERVOY in patients with severe, life-threatening,
    or fatal immune-mediated dermatitis (Grade 3-5). Administer systemic
    corticosteroids (1-2 mg/kg/day of prednisone or equivalent). When
    dermatitis is controlled, corticosteroid tapering should occur over a
    period of at least 1 month. Withhold YERVOY in patients with moderate to
    severe signs and symptoms
  *Treat mild to moderate dermatitis (e.g., localized rash and pruritus)
    symptomatically. Administer topical or systemic corticosteroids if there
    is no improvement within 1 week

Immune-mediated Neuropathies:

  *In the pivotal Phase 3 study in YERVOY-treated patients, 1 case of fatal
    Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor
    neuropathy were reported
  *Across the clinical development program of YERVOY, myasthenia gravis and
    additional cases of Guillain-Barré syndrome have been reported
  *Monitor for symptoms of motor or sensory neuropathy such as unilateral or
    bilateral weakness, sensory alterations, or paresthesia. Permanently
    discontinue YERVOY in patients with severe neuropathy (interfering with
    daily activities) such as Guillain-Barré–like syndromes
  *Institute medical intervention as appropriate for management of severe
    neuropathy. Consider initiation of systemic corticosteroids (1-2 mg/kg/day
    of prednisone or equivalent) for severe neuropathies. Withhold YERVOY in
    patients with moderate neuropathy (not interfering with daily activities)

Immune-mediated Endocrinopathies:

  *In the pivotal Phase 3 study in YERVOY- treated patients, severe to
    life-threatening immune-mediated endocrinopathies (requiring
    hospitalization, urgent medical intervention, or interfering with
    activities of daily living; Grade 3-4) occurred in 9 (1.8%) patients

       *All 9patients had hypopituitarism, and some had additional
         concomitant endocrinopathies such as adrenal insufficiency,
         hypogonadism, and hypothyroidism.
       *6 of the 9 patients were hospitalized for severe endocrinopathies

  *Moderate endocrinopathy (requiring hormone replacement or medical
    intervention; Grade 2) occurred in 12 (2.3%) YERVOY-treated patients and
    consisted of hypothyroidism, adrenal insufficiency, hypopituitarism, and 1
    case each of hyperthyroidism and Cushing’s syndrome
  *Median time to onset of moderate to severe immune-mediated endocrinopathy
    was 11 weeks and ranged up to 19.3 weeks after the initiation of YERVOY
  *Monitor patients for clinical signs and symptoms of hypophysitis, adrenal
    insufficiency (including adrenal crisis), and hyper- or hypothyroidism

       *Patients may present with fatigue, headache, mental status changes,
         abdominal pain, unusual bowel habits, and hypotension, or nonspecific
         symptoms which may resemble other causes such as brain metastasis or
         underlying disease. Unless an alternate etiology has been identified,
         signs or symptoms should be considered immune-mediated
       *Monitor thyroid function tests and clinical chemistries at the start
         of treatment, before each dose, and as clinically indicated based on
         symptoms. In a limited number of patients, hypophysitis was diagnosed
         by imaging studies through enlargement of the pituitary gland

  *Withhold YERVOY in symptomatic patients. Initiate systemic corticosteroids
    (1-2 mg/kg/day of prednisone or equivalent) and initiate appropriate
    hormone replacement therapy. Long-term hormone replacement therapy may be
    necessary

Other Immune-mediated Adverse Reactions, Including Ocular Manifestations:

  *In the pivotal Phase 3 study in YERVOY-treated patients, clinically
    significant immune-mediated adverse reactions seen in <1% were: nephritis,
    pneumonitis, meningitis, pericarditis, uveitis, iritis, and hemolytic
    anemia
  *Across the clinical development program for YERVOY, immune-mediated
    adverse reactions also reported with <1% incidence were: myocarditis,
    angiopathy, temporal arteritis, vasculitis, polymyalgia rheumatica,
    conjunctivitis, blepharitis, episcleritis, scleritis, leukocytoclastic
    vasculitis, erythema multiforme, psoriasis, pancreatitis, arthritis, and
    autoimmune thyroiditis
  *Permanently discontinue YERVOY for clinically significant or severe
    immune-mediated adverse reactions. Initiate systemic corticosteroids (1-2
    mg/kg/day of prednisone or equivalent) for severe immune-mediated adverse
    reactions
  *Administer corticosteroid eye drops for uveitis, iritis, or episcleritis.
    Permanently discontinue YERVOY for immune-mediated ocular disease
    unresponsive to local immunosuppressive therapy

Pregnancy & Nursing:

  *YERVOY is classified as pregnancy category C. There are no adequate and
    well-controlled studies of YERVOY in pregnant women. Use YERVOY during
    pregnancy only if the potential benefit justifies the potential risk to
    the fetus
  *Human IgG1 is known to cross the placental barrier and YERVOY is an IgG1;
    therefore, YERVOY has the potential to be transmitted from the mother to
    the developing fetus
  *It is not known whether YERVOY is secreted in human milk. Because many
    drugs are secreted in human milk and because of the potential for serious
    adverse reactions in nursing infants from YERVOY, a decision should be
    made whether to discontinue nursing or to discontinue YERVOY

Common Adverse Reactions:

  *The most common adverse reactions (≥5%) in patients who received YERVOY at
    3mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%),
    and colitis (8%)

Please see full Prescribing Information, including Boxed WARNING regarding
immune-mediated adverse reactions available at www.bms.com.

YERVOY is a registered trademark of Bristol-Myers Squibb Company.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to
discover, develop and deliver innovative medicines that help patients prevail
over serious diseases. For more information about Bristol-Myers Squibb, visit
www.bms.com, or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward-Looking Statement

This press release contains "forward-looking statements" as that term is
defined in the Private Securities Litigation Reform Act of 1995 regarding the
research, development and commercialization of pharmaceutical products. Such
forward-looking statements are based on current expectations and involve
inherent risks and uncertainties, including factors that could delay, divert
or change any of them, and could cause actual outcomes and results to differ
materially from current expectations. No forward-looking statement can be
guaranteed. Among other risks, there can be no guarantee that the
investigational uses of Yervoy described in this release will lead to
additional approved indications. Forward-looking statements in this press
release should be evaluated together with the many uncertainties that affect
Bristol-Myers Squibb's business, particularly those identified in the
cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form
10-K for the year ended December 31, 2012, in our Quarterly Reports on Form
10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no
obligation to publicly update any forward-looking statement, whether as a
result of new information, future events or otherwise.

Contact:

Bristol-Myers Squibb Company
Media:
Melanie Brunner, 609-252-6338, melanie.brunner@bms.com
Sarah Koenig, 609-252-4145, sarah.koenig@bms.com
or
Investors:
Ranya Dajani, 609-252-5330, ranya.dajani@bms.com
Ryan Asay, 609-252-5020, ryan.asay@bms.com