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Bristol-Myers Squibb to Present Data That Advances Understanding of Effects of Immuno-Oncology Therapies on Cancer Biology and Patient Outcomes at AACR 2017

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Bristol-Myers
Squibb Company
(NYSE:BMY) today announced that new clinical data
will be presented at the American Association for Cancer Research (AACR)
Annual Meeting 2017 in Washington, D.C., from April 1-5. Research to be
presented represents the company's ongoing commitment to investigating
long-term survival and safety data in advanced cancers, and to exploring
the interaction between biomarkers and Immuno-Oncology (I-O) therapy
across multiple tumor types. Results will be disclosed for Opdivo (nivolumab),
as a single-agent and in combination with Yervoy (ipilimumab), as
well as an investigational, optimized, once-daily IDO1 inhibitor alone
or in combination with Opdivo. IDO is part of Bristol-Myers
Squibb's robust early clinical development pipeline and one of 21
oncology compounds in clinical study. Bristol-Myers Squibb will also
share data generated as part of the International Immuno-Oncology
Network (II-ON), a global peer-to-peer collaboration with academia
established in 2012 and focused on advancing the science of I-O through
a series of preclinical, translational and biology-focused research
objectives.

"At Bristol-Myers Squibb, we are committed to translational research as
we advance the development of next-generation Immuno-Oncology therapies
and conduct biomarker research that will help us determine which
patients are most likely to benefit from our treatments," said Fouad
Namouni, M.D., head of development, Oncology, Bristol-Myers Squibb. "In
all of our research efforts, we are driven by our overarching goal of
changing the way patients live with cancer."

The full set of data to be presented by Bristol-Myers Squibb includes:

Melanoma / Skin Cancer

  • Overall survival results from a phase III trial of nivolumab
    combined with ipilimumab in treatment-naïve patients with advanced
    melanoma (CheckMate -067)

    Author: James Larkin
    Abstract
    # CT075
    Minisymposium: Update, Novel Indication, and New
    Immuno-oncology Clinical Trials
    Monday, April 3, 2017, 3:35 –
    3:50 p.m., Ballroom C, Level 3
  • Non-comparative, open-label, multiple cohort, phase 1/2 study to
    evaluate nivolumab in patients with virus-associated tumors (CheckMate
    -358): Efficacy and safety in Merkel cell carcinoma

    Author:
    Suzanne Topalian
    Abstract # CT074
    Minisymposium: Update,
    Novel Indication, and New Immuno-oncology Clinical Trials
    Monday,
    April 3, 2017, 3:05 – 3:20 p.m. Ballroom C, Level 3
  • Overall survival and safety experience from an expanded access
    program of nivolumab for patients with advanced melanoma who
    progressed after prior ipilimumab treatment (CheckMate -168)

    Author:
    Milton Barros e Silva
    Abstract # LB-055
    Late-Breaking Poster
    Session: Clinical Research 1
    Monday, April 3, 2017, 8:00 a.m. –
    12:00 p.m., Poster Section 34; Poster Board #18

Lung

  • Impact of tumor mutation burden on the efficacy of first-line
    nivolumab in stage IV or recurrent non-small cell lung cancer: an
    exploratory analysis of CheckMate -026

    Author: Solange Peters
    Abstract
    # CT082
    Minisymposium: Update, Novel Indication, and New
    Immuno-oncology Clinical Trials
    Monday, April 3, 2017, 5:20 –
    5:30 p.m., Ballroom C, Level 3
  • Five-year follow-up from the CA209-003 study of nivolumab in
    previously treated advanced non-small cell lung cancer: Clinical
    characteristics of long-term survivors

    Author: Julie Renee
    Brahmer
    Abstract # CT077
    Minisymposium: Update, Novel
    Indication, and New Immuno-oncology Clinical Trials Monday, April 3,
    2017, 4:05 – 4:20 p.m., Ballroom C, Level 3
  • An Open-label Phase 3b/4 Safety Trial of Flat-Dose Nivolumab in
    Combination With Ipilimumab in Patients With Advanced Non-Small Cell
    Lung Cancer

    Author: Rathi N. Pillai
    Abstract #
    CT070
    Poster Session: Phase II/III Clinical Trials in Progress
    Monday,
    April 3, 2017, 1:00 – 5:00 p.m. ET, Halls A-C, Poster Section 33,
    Poster Board #20

Head and Neck Cancer

  • Treatment Beyond Progression With Nivolumab in Patients With
    Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
    in the Phase 3 Checkmate -141 Study

    Author: Robert Haddad
    Abstract
    # CT157
    Poster Session: Phase II/III Clinical Trials in Progress
    Monday,
    April 3, 2017, 1:00 – 5:00 p.m. ET, Halls A-C, Poster Section 33

Pipeline

  • BMS-986205, an optimized indoleamine 2,3-dioxygenase 1 (IDO1)
    inhibitor, is well tolerated with potent pharmacodynamic activity,
    alone and in combination with nivolumab in advanced cancers in a phase
    1/2a trial

    Author: Lillian L. Siu
    Abstract # CT116
    Plenary
    Session: Novel Immuno-oncology Agent Clinical Trials
    Tuesday,
    April 4, 2017, 11:13 – 11:28 a.m., Ballroom C, Level 3
  • Structure, in vitro biology and in vivo pharmacodynamic
    characterization of a novel clinical stage IDO1 inhibitor

    Author:
    John T. Hunt
    Abstract # 4964
    Minisymposium: Novel Approaches
    for Experimental Therapeutics
    Tuesday, April 4, 2017, 3:20 – 3:35
    p.m. ET, Room 144, Level 1

Biomarkers and Dosing

  • Evaluation of oral microbiome profiling as a response biomarker in
    squamous cell carcinoma of the head and neck: Analyses from CheckMate
    -141

    Author: Robert L. Ferris
    Abstract # CT022
    Clinical
    Trials Plenary Session: Immuno-oncology Biomarkers in Clinical Trials
    Sunday,
    April 2, 2017, 4:48 – 5:03 p.m., Hall D-E, Level 2
  • Tumor-associated immune cell PD-L1 expression and peripheral immune
    profiling: Analyses from CheckMate -141

    Author: Robert L.
    Ferris
    Abstract # CT021
    Clinical Trials Plenary Session:
    Immuno-oncology Biomarkers in Clinical Trials
    Sunday, April 2,
    2017, 4:33 – 4:48 p.m., Hall D-E, Level 2
  • Immunogenomic analyses of tumor cells and microenvironment in
    patients with advanced melanoma before and after treatment with
    nivolumab

    Author: Timothy A. Chan
    Abstract # 2988
    Minisymposium:
    Clinical Biomarkers
    Monday, April 3, 2017, 3:35 – 3:50 p.m. ET,
    Room 151, Level 1
  • Immunomodulatory effects of nivolumab and ipilimumab in combination
    or nivolumab monotherapy in advanced melanoma patients: CheckMate -038

    Author:
    Antoni Ribas
    Abstract # CT073
    Minisymposium: Update, Novel
    Indication, and New Immuno-oncology Clinical Trials
    Monday, April
    3, 2017, 3:20 – 3:35 p.m., Ballroom C, Level 3
  • A model-based exposure-response assessment of a nivolumab 4-weekly
    (Q4W) dosing schedule across multiple tumor types

    Author:
    Xiaochen Zhao
    Abstract # CT101
    Poster Session: Phase I
    Clinical Trials
    Tuesday, April 4, 2017, 8:00 a.m. – 12:00 p.m.
    ET, Halls A-C, Poster Section 33
  • A Comparative Study of PD-L1 IHC 22C3 and 28-8 FDA-Approved
    Diagnostic Assays in Cancer

    Author: Cory Batenchuk
    Abstract
    # 4015
    Poster Session: Assay Technology
    Tuesday, April 4,
    2017, 1:00 – 5:00 p.m. ET, Halls A-C, Poster section 1
  • Soluble HLA-G and -E (sHLA-G/E) as potential biomarkers of clinical
    outcomes in patients with advanced, refractory squamous (SQ) NSCLC
    treated with nivolumab: CheckMate -063

    Author: Vera Rebmann
    Abstract
    # CT126
    Poster Session: Phase I-III Clinical Trials and Pediatric
    Clinical Trials
    Tuesday, April 4, 2017, 1:00 – 5:00 p.m. ET,
    Halls A-C, Poster Section 33
  • Pooled analysis of PD-L1 expression across 6 tumor types in the
    nivolumab clinical program

    Author: Gabriel Krigsfeld
    Abstract
    # CT143
    Poster Session: Phase I-III Clinical Trials and Pediatric
    Clinical Trials
    Tuesday, April 4, 2017, 1:00 – 5:00 p.m. ET,
    Halls A-C, Poster Section 33

II-ON

  • RNA-sequencing of tumor-educated platelets enables nivolumab
    immunotherapy response prediction

    Author: Mirte Muller
    Abstract
    # LB-248
    Poster Session: Lake-Breaking Clinical Research 2 /
    Endocrinology
    Tuesday, April 4, 2017,1:00 – 5:00 p.m. ET, Poster
    Section 34

Bristol-Myers Squibb & Immuno-Oncology:
Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do.
Our vision for the future of cancer care is focused on researching and
developing transformational Immuno-Oncology (I-O) medicines that will
raise survival expectations in hard-to-treat cancers and will change the
way patients live with cancer.

We are leading the scientific understanding of I-O through our extensive
portfolio of investigational and approved agents, including the first
combination of two I-O agents in metastatic melanoma, and our
differentiated clinical development program, which is studying broad
patient populations across more than 35 types of cancers with 13
clinical-stage molecules designed to target different immune system
pathways. Our deep expertise and innovative clinical trial designs
uniquely position us to advance the science of combinations across
multiple tumors and potentially deliver the next wave of I-O combination
regimens with a sense of urgency. We also continue to pioneer research
that will help facilitate a deeper understanding of the role of immune
biomarkers and inform which patients will benefit most from I-O
therapies.

We understand making the promise of I-O a reality for the many patients
who may benefit from these therapies requires not only innovation on our
part but also close collaboration with leading experts in the field. Our
partnerships with academia, government, advocacy and biotech companies
support our collective goal of providing new treatment options to
advance the standards of clinical practice.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor
that is designed to uniquely harness the body's own immune system to
help restore anti-tumor immune response. By harnessing the body's own
immune system to fight cancer, Opdivo has become an important
treatment option across multiple cancers.

Opdivo's leading global development program is based on
Bristol-Myers Squibb's scientific expertise in the field of
Immuno-Oncology and includes a broad range of clinical trials across all
phases, including Phase 3, in a variety of tumor types. To date, the Opdivo
clinical development program has enrolled more than 25,000 patients. The Opdivo
trials have contributed to gaining a deeper understanding of the
potential role of biomarkers in patient care, particularly regarding how
patients may benefit from Opdivo across the continuum of PD-L1
expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint
inhibitor to receive regulatory approval anywhere in the world. Opdivo
is currently approved in more than 60 countries, including the United
States, the European Union and Japan. In October 2015, the company's Opdivo
and Yervoy combination regimen was the first Immuno-Oncology
combination to receive regulatory approval for the treatment of
metastatic melanoma and is currently approved in more than 50 countries,
including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO®

OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 mutation-positive unresectable or
metastatic melanoma. This indication is approved under accelerated
approval based on progression-free survival. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) as a single agent is indicated for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY®
(ipilimumab), is indicated for the treatment of patients with
unresectable or metastatic melanoma. This indication is approved under
accelerated approval based on progression-free survival. Continued
approval for this indication may be contingent upon verification and
description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with metastatic non-small cell lung cancer (NSCLC) with
progression on or after platinum-based chemotherapy. Patients with EGFR
or ALK genomic tumor aberrations should have disease progression on
FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with advanced renal cell carcinoma (RCC) who have received
prior anti-angiogenic therapy.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with classical Hodgkin lymphoma (cHL) that has relapsed or
progressed after autologous hematopoietic stem cell transplantation
(HSCT) and post-transplantation brentuximab vedotin. This indication is
approved under accelerated approval based on overall response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with recurrent or metastatic squamous cell carcinoma of the
head and neck (SCCHN) with disease progression on or after
platinum-based therapy.

OPDIVO® (nivolumab) is indicated for the treatment of
patients with locally advanced or metastatic urothelial carcinoma who
have disease progression during or following platinum-containing
chemotherapy or have disease progression within 12 months of neoadjuvant
or adjuvant treatment with platinum-containing chemotherapy. This
indication is approved under accelerated approval based on tumor
response rate and duration of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in confirmatory trials.

IMPORTANT SAFETY INFORMATION

WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS

YERVOY can result in severe and fatal immune-mediated adverse
reactions. 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), adrenocorticotropic hormone
(ACTH) level, 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.

Immune-Mediated Pneumonitis

OPDIVO can cause immune-mediated pneumonitis. Fatal cases have been
reported. Monitor patients for signs with radiographic imaging and for
symptoms of pneumonitis. Administer corticosteroids for Grade 2 or more
severe pneumonitis. Permanently discontinue for Grade 3 or 4 and
withhold until resolution for Grade 2. In patients receiving OPDIVO
monotherapy, fatal cases of immune-mediated pneumonitis have occurred.
Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients. In
patients receiving OPDIVO with YERVOY, immune-mediated pneumonitis
occurred in 6% (25/407) of patients.

In Checkmate 205 and 039, pneumonitis, including interstitial lung
disease, occurred in 4.9% (13/263) of patients receiving OPDIVO.
Immune-mediated pneumonitis occurred in 3.4% (9/263) of patients
receiving OPDIVO: Grade 3 (n=1) and Grade 2 (n=8).

Immune-Mediated Colitis

OPDIVO can cause immune-mediated colitis. Monitor patients for signs and
symptoms of colitis. Administer corticosteroids for Grade 2 (of more
than 5 days duration), 3, or 4 colitis. Withhold OPDIVO monotherapy for
Grade 2 or 3 and permanently discontinue for Grade 4 or recurrent
colitis upon re-initiation of OPDIVO. When administered with YERVOY,
withhold OPDIVO and YERVOY for Grade 2 and permanently discontinue for
Grade 3 or 4 or recurrent colitis. In patients receiving OPDIVO
monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of
patients. In patients receiving OPDIVO with YERVOY, immune-mediated
colitis occurred in 26% (107/407) of patients including three fatal
cases.

In a separate Phase 3 study of YERVOY 3 mg/kg, 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%)
patients. Across all YERVOY-treated patients in that study (n=511), 5
(1%) developed intestinal perforation, 4 (0.8%) died as a result of
complications, and 26 (5%) were hospitalized for severe enterocolitis.

Immune-Mediated Hepatitis

OPDIVO can cause immune-mediated hepatitis. Monitor patients for
abnormal liver tests prior to and periodically during treatment.
Administer corticosteroids for Grade 2 or greater transaminase
elevations. Withhold for Grade 2 and permanently discontinue for Grade 3
or 4 immune-mediated hepatitis. In patients receiving OPDIVO
monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of
patients. In patients receiving OPDIVO with YERVOY, immune-mediated
hepatitis occurred in 13% (51/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, 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%.

Immune-Mediated Neuropathies

In a separate Phase 3 study of YERVOY 3 mg/kg, 1 case of fatal
Guillain-Barré syndrome and 1 case of severe (Grade 3) peripheral motor
neuropathy were reported.

Immune-Mediated Endocrinopathies

OPDIVO can cause immune-mediated hypophysitis, immune-mediated adrenal
insufficiency, autoimmune thyroid disorders, and Type 1 diabetes
mellitus. Monitor patients for signs and symptoms of hypophysitis, signs
and symptoms of adrenal insufficiency, thyroid function prior to and
periodically during treatment, and hyperglycemia. Administer hormone
replacement as clinically indicated and corticosteroids for Grade 2 or
greater hypophysitis. Withhold for Grade 2 or 3 and permanently
discontinue for Grade 4 hypophysitis. Administer corticosteroids for
Grade 3 or 4 adrenal insufficiency. Withhold for Grade 2 and permanently
discontinue for Grade 3 or 4 adrenal insufficiency. Administer
hormone-replacement therapy for hypothyroidism. Initiate medical
management for control of hyperthyroidism. Withhold OPDIVO for Grade 3
and permanently discontinue for Grade 4 hyperglycemia.

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6%
(12/1994) of patients. In patients receiving OPDIVO with YERVOY,
hypophysitis occurred in 9% (36/407) of patients. In patients receiving
OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994) of
patients. In patients receiving OPDIVO with YERVOY, adrenal
insufficiency occurred in 5% (21/407) of patients. In patients receiving
OPDIVO monotherapy, hypothyroidism or thyroiditis resulting in
hypothyroidism occurred in 9% (171/1994) of patients. Hyperthyroidism
occurred in 2.7% (54/1994) of patients receiving OPDIVO monotherapy. In
patients receiving OPDIVO with YERVOY, hypothyroidism or thyroiditis
resulting in hypothyroidism occurred in 22% (89/407) of patients.
Hyperthyroidism occurred in 8% (34/407) of patients receiving OPDIVO
with YERVOY. In patients receiving OPDIVO monotherapy, diabetes occurred
in 0.9% (17/1994) of patients. In patients receiving OPDIVO with YERVOY,
diabetes occurred in 1.5% (6/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, 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 9 patients 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.

Immune-Mediated Nephritis and Renal Dysfunction

OPDIVO can cause immune-mediated nephritis. Monitor patients for
elevated serum creatinine prior to and periodically during treatment.
Administer corticosteroids for Grades 2-4 increased serum creatinine.
Withhold OPDIVO for Grade 2 or 3 and permanently discontinue for Grade 4
increased serum creatinine. In patients receiving OPDIVO monotherapy,
immune-mediated nephritis and renal dysfunction occurred in 1.2%
(23/1994) of patients. In patients receiving OPDIVO with YERVOY,
immune-mediated nephritis and renal dysfunction occurred in 2.2% (9/407)
of patients.

Immune-Mediated Skin Adverse Reactions and Dermatitis

OPDIVO can cause immune-mediated rash, including Stevens-Johnson
syndrome (SJS) and toxic epidermal necrolysis (TEN), some cases with
fatal outcome. Administer corticosteroids for Grade 3 or 4 rash.
Withhold for Grade 3 and permanently discontinue for Grade 4 rash. For
symptoms or signs of SJS or TEN, withhold OPDIVO and refer the patient
for specialized care for assessment and treatment; if confirmed,
permanently discontinue. In patients receiving OPDIVO monotherapy,
immune-mediated rash occurred in 9% (171/1994) of patients. In patients
receiving OPDIVO with YERVOY, immune-mediated rash occurred in 22.6%
(92/407) of patients.

In a separate Phase 3 study of YERVOY 3 mg/kg, severe, life-threatening,
or fatal immune-mediated dermatitis (eg, 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.

Immune-Mediated Encephalitis

OPDIVO can cause immune-mediated encephalitis. Evaluation of patients
with neurologic symptoms may include, but not be limited to,
consultation with a neurologist, brain MRI, and lumbar puncture.
Withhold OPDIVO in patients with new-onset moderate to severe neurologic
signs or symptoms and evaluate to rule out other causes. If other
etiologies are ruled out, administer corticosteroids and permanently
discontinue OPDIVO for immune-mediated encephalitis. In patients
receiving OPDIVO monotherapy, encephalitis occurred in 0.2% (3/1994) of
patients. Fatal limbic encephalitis occurred in one patient after 7.2
months of exposure despite discontinuation of OPDIVO and administration
of corticosteroids. Encephalitis occurred in one patient receiving
OPDIVO with YERVOY (0.2%) after 1.7 months of exposure.

Other Immune-Mediated Adverse Reactions

Based on the severity of adverse reaction, permanently discontinue or
withhold treatment, administer high-dose corticosteroids, and, if
appropriate, initiate hormone-replacement therapy. Across clinical
trials of OPDIVO the following clinically significant immune-mediated
adverse reactions occurred in <1.0% of patients receiving OPDIVO:
uveitis, iritis, pancreatitis, facial and abducens nerve paresis,
demyelination, polymyalgia rheumatica, autoimmune neuropathy,
Guillain-Barré syndrome, hypopituitarism, systemic inflammatory response
syndrome, gastritis, duodenitis, sarcoidosis, histiocytic necrotizing
lymphadenitis (Kikuchi lymphadenitis), myositis, myocarditis,
rhabdomyolysis, motor dysfunction, vasculitis, and myasthenic syndrome.

Infusion Reactions

OPDIVO can cause severe infusion reactions, which have been reported in
<1.0% of patients in clinical trials. Discontinue OPDIVO in patients
with Grade 3 or 4 infusion reactions. Interrupt or slow the rate of
infusion in patients with Grade 1 or 2. In patients receiving OPDIVO
monotherapy, infusion-related reactions occurred in 6.4% (127/1994) of
patients. In patients receiving OPDIVO with YERVOY, infusion-related
reactions occurred in 2.5% (10/407) of patients.

Complications of Allogeneic HSCT after OPDIVO

Complications, including fatal events, occurred in patients who received
allogeneic HSCT after OPDIVO. Outcomes were evaluated in 17 patients
from Checkmate 205 and 039, who underwent allogeneic HSCT after
discontinuing OPDIVO (15 with reduced-intensity conditioning, 2 with
myeloablative conditioning). Thirty-five percent (6/17) of patients died
from complications of allogeneic HSCT after OPDIVO. Five deaths occurred
in the setting of severe or refractory GVHD. Grade 3 or higher acute
GVHD was reported in 29% (5/17) of patients. Hyperacute GVHD was
reported in 20% (n=2) of patients. A steroid-requiring febrile syndrome,
without an identified infectious cause, was reported in 35% (n=6) of
patients. Two cases of encephalitis were reported: Grade 3 (n=1)
lymphocytic encephalitis without an identified infectious cause, and
Grade 3 (n=1) suspected viral encephalitis. Hepatic veno-occlusive
disease (VOD) occurred in one patient, who received reduced-intensity
conditioned allogeneic HSCT and died of GVHD and multi-organ failure.
Other cases of hepatic VOD after reduced-intensity conditioned
allogeneic HSCT have also been reported in patients with lymphoma who
received a PD-1 receptor blocking antibody before transplantation. Cases
of fatal hyperacute GVHD have also been reported. These complications
may occur despite intervening therapy between PD-1 blockade and
allogeneic HSCT.

Follow patients closely for early evidence of transplant-related
complications such as hyperacute GVHD, severe (Grade 3 to 4) acute GVHD,
steroid-requiring febrile syndrome, hepatic VOD, and other
immune-mediated adverse reactions, and intervene promptly.

Embryo-Fetal Toxicity

Based on their mechanisms of action, OPDIVO and YERVOY can cause fetal
harm when administered to a pregnant woman. Advise pregnant women of the
potential risk to a fetus. Advise females of reproductive potential to
use effective contraception during treatment with an OPDIVO- or YERVOY-
containing regimen and for at least 5 months after the last dose of
OPDIVO.

Lactation

It is not known whether OPDIVO or YERVOY is present in human milk.
Because many drugs, including antibodies, are excreted in human milk and
because of the potential for serious adverse reactions in nursing
infants from an OPDIVO-containing regimen, advise women to discontinue
breastfeeding during treatment. Advise women to discontinue nursing
during treatment with YERVOY and for 3 months following the final dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients
receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in
42% of patients receiving OPDIVO . The most frequent Grade 3 and 4
adverse drug reactions reported in 2% to <5% of patients receiving
OPDIVO were abdominal pain, hyponatremia, increased aspartate
aminotransferase, and increased lipase. In Checkmate 066, serious
adverse reactions occurred in 36% of patients receiving OPDIVO (n=206).
Grade 3 and 4 adverse reactions occurred in 41% of patients receiving
OPDIVO. The most frequent Grade 3 and 4 adverse reactions reported in
≥2% of patients receiving OPDIVO were gamma-glutamyltransferase increase
(3.9%) and diarrhea (3.4%). In Checkmate 067, serious adverse reactions
(73% and 37%), adverse reactions leading to permanent discontinuation
(43% and 14%) or to dosing delays (55% and 28%), and Grade 3 or 4
adverse reactions (72% and 44%) all occurred more frequently in the
OPDIVO plus YERVOY arm (n=313) relative to the OPDIVO arm (n=313). The
most frequent (≥10%) serious adverse reactions in the OPDIVO plus YERVOY
arm and the OPDIVO arm, respectively, were diarrhea (13% and 2.6%),
colitis (10% and 1.6%), and pyrexia (10% and 0.6%). In Checkmate 017 and
057, serious adverse reactions occurred in 46% of patients receiving
OPDIVO (n=418). The most frequent serious adverse reactions reported in
at least 2% of patients receiving OPDIVO were pneumonia, pulmonary
embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and
respiratory failure. In Checkmate 025, serious adverse reactions
occurred in 47% of patients receiving OPDIVO (n=406). The most frequent
serious adverse reactions reported in ≥2% of patients were acute kidney
injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In
Checkmate 205 and 039, among all patients (safety population [n=263]),
adverse reactions leading to discontinuation (4.2%) or to dosing delays
(23%) occurred. The most frequent serious adverse reactions reported in
≥1% of patients were infusion-related reaction, pneumonia, pleural
effusion, pyrexia, rash and pneumonitis. Ten patients died from causes
other than disease progression, including 6 who died from complications
of allogeneic HSCT. Serious adverse reactions occurred in 21% of
patients in the safety population (n=263) and 27% of patients in the
subset of patients evaluated for efficacy (efficacy population [n=95]).
In Checkmate 141, serious adverse reactions occurred in 49% of patients
receiving OPDIVO. The most frequent serious adverse reactions reported
in at least 2% of patients receiving OPDIVO were pneumonia, dyspnea,
respiratory failure, respiratory tract infections, and sepsis. In
Checkmate 275, serious adverse reactions occurred in 54% of patients
receiving OPDIVO (n=270). The most frequent serious adverse reactions
reported in at least 2% of patients receiving OPDIVO were urinary tract
infection, sepsis, diarrhea, small intestine obstruction, and general
physical health deterioration.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (≥20%) reported with
OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse
reactions (≥20%) reported with OPDIVO (n=206) vs dacarbazine (n=205)
were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28%
vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common
(≥20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were
fatigue (59%), rash (53%), diarrhea (52%), nausea (40%), pyrexia (37%),
vomiting (28%), and dyspnea (20%). The most common (≥20%) adverse
reactions in the OPDIVO (n=313) arm were fatigue (53%), rash (40%),
diarrhea (31%), and nausea (28%). In Checkmate 017 and 057, the most
common adverse reactions (≥20%) in patients receiving OPDIVO (n=418)
were fatigue, musculoskeletal pain, cough, dyspnea, and decreased
appetite. In Checkmate 025, the most common adverse reactions (≥20%)
reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were
asthenic conditions (56% vs 57%), cough (34% vs 38%), nausea (28% vs
29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%),
constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain
(21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039,
among all patients (safety population [n=263]) and the subset of
patients in the efficacy population (n=95), respectively, the most
common adverse reactions (≥20%) were fatigue (32% and 43%), upper
respiratory tract infection (28% and 48%), pyrexia (24% and 35%),
diarrhea (23% and 30%), and cough (22% and 35%). In the subset of
patients in the efficacy population (n=95), the most common adverse
reactions also included rash (31%), musculoskeletal pain (27%), pruritus
(25%), nausea (23%), arthralgia (21%), and peripheral neuropathy (21%).
In Checkmate 141, the most common adverse reactions (≥10%) in patients
receiving OPDIVO were cough and dyspnea at a higher incidence than
investigator's choice. In Checkmate 275, the most common adverse
reactions (≥ 20%) reported in patients receiving OPDIVO (n=270) were
fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased
appetite (22%).

In a separate Phase 3 study of YERVOY 3 mg/kg, the most common adverse
reactions (≥5%) in patients who received YERVOY at 3 mg/kg were fatigue
(41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Checkmate Trials and Patient Populations

Checkmate 067 - advanced melanoma alone or in combination with
YERVOY; Checkmate 037 and 066 - advanced melanoma; Checkmate
017
- squamous non-small cell lung cancer (NSCLC); Checkmate 057
- non-squamous NSCLC; Checkmate 025 - renal cell carcinoma; Checkmate
205/039
- classical Hodgkin lymphoma; Checkmate 141 -
squamous cell carcinoma of the head and neck; Checkmate 275 -
urothelial carcinoma.

Please see U.S. Full Prescribing Information for OPDIVO
and YERVOY,
including Boxed WARNING regarding immune-mediated adverse reactions
for YERVOY.

About the Bristol-Myers Squibb and Ono
Pharmaceutical Co., Ltd. Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co.,
Ltd (Ono), Bristol-Myers Squibb expanded its territorial rights to
develop and commercialize Opdivo globally except in Japan, South Korea
and Taiwan, where Ono had retained all rights to the compound at the
time. On July 23, 2014, Bristol-Myers Squibb and Ono further expanded
the companies' strategic collaboration agreement to jointly develop and
commercialize multiple immunotherapies – as single agents and
combination regimens – for patients with cancer in Japan, South Korea
and Taiwan.

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 us at BMS.com
or follow us on LinkedIn,
Twitter,
YouTube
and Facebook.

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 Opdivo, Yervoy or any
of the compounds mentioned in this release will receive regulatory
approval for an additional indication. 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, 2016
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.

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