Bristol-Myers Squibb and MD Anderson Announce New Research Collaboration in Immuno-Oncology Focused on Lung Cancer

HOUSTON & NEW YORK–(BUSINESS WIRE)– Bristol-Myers
Squibb Company (NYSE:BMY) and The
University of Texas MD Anderson Cancer Center today announced a new
clinical research collaboration to evaluate innovative strategies for
the potential use of Bristol-Myers Squibb’s immuno-oncology (I-O) agents Opdivo
(nivolumab) and Yervoy
(ipilimumab) to treat early- and advanced-stage lung cancer patients.

The collaboration will help support multiple Phase 1 and 2 clinical
trials testing Opdivo as monotherapy, in combination with Yervoy,
or in regimens with other agents, radiation or surgery in a range of
clinical settings. These studies will also incorporate extensive
translational work including exploration of novel biomarkers to better
differentiate responders from non-responders in lung cancer as well as
preclinical studies of next generation immunotherapeutic agents that may
be used to expand the benefits to larger numbers of patients.

Opdivo is a PD-1 immune checkpoint inhibitor currently approved
in 50 countries globally for the treatment of patients with metastatic
non-small cell lung cancer (NSCLC) with progression on or after
platinum-based chemotherapy, and Yervoy is a CTLA-4
immune checkpoint inhibitor approved in 50 countries globally for
patients with unresectable or metastatic melanoma.

The collaboration will leverage MD Anderson’s existing immunotherapy
platform, which helps to link immunologic data with the genomic and
proteomic platforms across a range of cancer types, and broaden the
scientific understanding of I-O via preclinical and clinical studies in
lung cancer. Data generated will assist Bristol-Myers Squibb in
optimizing I-O combinations for future clinical trials while also
enhancing mechanistic understanding of immune system function in
mounting of anti-tumor responses.

“Immunotherapy agents, such as nivolumab, already have prolonged the
lives of many patients with metastatic NSCLC. Through our
multidisciplinary collaboration with Bristol-Myers Squibb, we look
forward to exploring innovative ways to integrate immunotherapy with
other treatments, including surgery and radiation, with the goal of
improving standard of care and expanding treatment options for all
patients, including those with early stage disease,” said John Heymach,
M.D., Ph.D., chair of Thoracic/Head and Neck Medical Oncology at MD
Anderson.

Heymach also is co-leader of MD Anderson’s Lung Cancer Moon Shot, part
of the institution’s Moon Shots Program to reduce cancer deaths by
accelerating the development of new therapies, prevention efforts and
early detection from scientific discoveries.

“Strategic collaborations with academia have been central to helping
Bristol-Myers Squibb develop and deliver new immuno-oncology treatment
options to patients,” said Jean Viallet, M.D., Global Clinical Research
Lead, Oncology, Bristol-Myers Squibb. “This collaboration will leverage
the considerable experience of MD Anderson to accelerate and expand our
scientific and clinical understanding of how the immune system and other
treatments might work together to fight cancer.”

MD Anderson’s immunotherapy platform, also part of the Moon Shots
Program, conducts immune monitoring of tumors and blood before, during
and after treatment to better understand how and when immunotherapy
works.

“Having approved PD-1 inhibitors for metastatic NSCLC gives us the
chance to explore what it is about the tumor microenvironment that
allows response to these agents,” said Padmanee Sharma, M.D.,
Ph.D., immunotherapy platform scientific director and professor of
Genitourinary Medical Oncology and Immunology at MD Anderson. “Immune
monitoring can generate data that will improve our understanding of the
mechanisms that lead to response or resistance to treatment and
facilitate the development of new biomarkers to personalize treatments
and match patients to the right therapies or combinations.”

I-O is an innovative approach to cancer research and treatment that is
designed to harness the body’s own immune system to fight cancer. Lung
cancer is the leading cause of cancer deaths globally, resulting in more
than 1.5 million deaths each year, according to the World Health
Organization.

In September of 2014, Bristol-Myers Squibb and MD Anderson entered into
an I-O clinical collaboration that is focused on the evaluation of
Bristol-Myers Squibb I-O assets for the treatment of hematologic
malignancies, such as acute and chronic leukemia. In December 2015,
Bristol-Myers Squibb and MD Anderson signed a collaboration agreement to
leverage MD Anderson’s immunotherapy platform to help to link
immunologic data with the genomic and proteomic platforms across a range
of cancer types.

Bristol-Myers Squibb & immuno-oncology:
Advancing Oncology Research

At Bristol-Myers Squibb, we have a vision for the future of cancer care
that is focused on immuno-oncology, now considered a major treatment
choice alongside surgery, radiation, chemotherapy and targeted therapies
for certain types of cancer.

We have a comprehensive clinical portfolio of investigational and
approved immuno-oncology agents, many of which were discovered and
developed by our scientists. Our ongoing immuno-oncology clinical
program is looking at broad patient populations, across multiple solid
tumors and hematologic malignancies, and lines of therapy and
histologies, with the intent of powering our trials for overall survival
and other important measures like durability of response. We pioneered
the research leading to the first regulatory approval for the
combination of two immuno-oncology agents, and continue to study the
role of combinations in cancer.

We are also investigating other immune system pathways in the treatment
of cancer including CTLA-4, PD-1, SLAMF7, CD-137, KIR, LAG-3, CSF1R,
IDO, and a number of other targets. These pathways may lead to potential
new treatment options – most likely in combination – to help patients
fight different types of cancers.

Our collaboration with academia, as well as small and large biotech
companies, to research the potential immuno-oncology and
non-immuno-oncology combinations, helps achieve our goal of providing
new treatment options in clinical practice. At Bristol-Myers Squibb, we
are committed to changing survival expectations in hard-to-treat cancers
and the way patients live with cancer.

About Opdivo

Cancer cells may exploit “regulatory” pathways, such as checkpoint
pathways, to hide from the immune system and shield the tumor from
immune attack. Opdivo is a PD-1 immune checkpoint inhibitor that
binds to the checkpoint receptor PD-1 expressed on activated T-cells,
and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway’s
suppressive signaling on the immune system, including the interference
with an anti-tumor immune response.

Opdivo’s broad global development program is based on
Bristol-Myers Squibb’s understanding of the biology behind
immuno-oncology. Our company is at the forefront of researching the
potential of immuno-oncology to extend survival in hard-to-treat
cancers. This scientific expertise serves as the basis for the Opdivo
development program, which includes a broad range of Phase 3 clinical
trials evaluating overall survival as the primary endpoint across a
variety of tumor types. The Opdivo trials have also contributed
toward the clinical and scientific understanding of the role of
biomarkers and how patients may benefit from Opdivo across the
continuum of PD-L1 expression. To date, the Opdivo clinical
development program has enrolled more than 18,000 patients. Opdivo
was the first PD-1 immune checkpoint inhibitor to receive regulatory
approval anywhere in the world in July 2014, and currently has
regulatory approval in 50 countries including the United States, Japan,
and in the European Union.

U.S. FDA APPROVED INDICATIONS

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

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 demonstration of clinical benefit in confirmatory
trials.

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 demonstration of clinical benefit in 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.

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

Immune-mediated pneumonitis, including fatal cases, occurred with OPDIVO
treatment. Across the clinical trial experience with solid tumors, fatal
immune-mediated pneumonitis occurred with OPDIVO. In addition, in
Checkmate 069, there were six patients who died without resolution of
abnormal respiratory findings. Monitor patients for signs with
radiographic imaging and symptoms of pneumonitis. Administer
corticosteroids for Grade 2 or greater pneumonitis. Permanently
discontinue for Grade 3 or 4 and withhold until resolution for Grade 2.
In Checkmate 069 and 067, immune-mediated pneumonitis occurred in 6%
(25/407) of patients receiving OPDIVO with YERVOY: Fatal (n=1), Grade 3
(n=6), Grade 2 (n=17), and Grade 1 (n=1). In Checkmate 037, 066, and
067, immune-mediated pneumonitis occurred in 1.8% (14/787) of patients
receiving OPDIVO: Grade 3 (n=2) and Grade 2 (n=12). In Checkmate 057,
immune-mediated pneumonitis, including interstitial lung disease,
occurred in 3.4% (10/287) of patients: Grade 3 (n=5), Grade 2 (n=2), and
Grade 1 (n=3). In Checkmate 025, pneumonitis, including interstitial
lung disease, occurred in 5% (21/406) of patients receiving OPDIVO and
18% (73/397) of patients receiving everolimus. Immune-mediated
pneumonitis occurred in 4.4% (18/406) of patients receiving OPDIVO:
Grade 4 (n=1), Grade 3 (n=4), Grade 2 (n=12), and Grade 1 (n=1).

Immune-Mediated Colitis

Immune-mediated colitis can occur with OPDIVO treatment. Monitor
patients for signs and symptoms of colitis. Administer corticosteroids
for Grade 2 (of more than 5 days duration), 3, or 4 colitis. As a single
agent, withhold OPDIVO for Grade 2 or 3 and permanently discontinue for
Grade 4 or recurrent colitis upon restarting OPDIVO. When administered
with YERVOY, withhold OPDIVO for Grade 2 and permanently discontinue for
Grade 3 or 4 or recurrent colitis upon restarting OPDIVO. In Checkmate
069 and 067, diarrhea or colitis occurred in 56% (228/407) of patients
receiving OPDIVO with YERVOY. Immune-mediated colitis occurred in 26%
(107/407) of patients: Grade 4 (n=2), Grade 3 (n=60), Grade 2 (n=32),
and Grade 1 (n=13). In Checkmate 037, 066, and 067, diarrhea or colitis
occurred in 31% (242/787) of patients receiving OPDIVO. Immune-mediated
colitis occurred in 4.1% (32/787) of patients: Grade 3 (n=20), Grade 2
(n=10), and Grade 1 (n=2). In Checkmate 057, diarrhea or colitis
occurred in 17% (50/287) of patients receiving OPDIVO. Immune-mediated
colitis occurred in 2.4% (7/287) of patients: Grade 3 (n=3), Grade 2
(n=2), and Grade 1 (n=2). In Checkmate 025, diarrhea or colitis occurred
in 25% (100/406) of patients receiving OPDIVO and 32% (126/397) of
patients receiving everolimus. Immune-mediated diarrhea or colitis
occurred in 3.2% (13/406) of patients receiving OPDIVO: Grade 3 (n=5),
Grade 2 (n=7), and Grade 1 (n=1).

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

Immune-mediated hepatitis can occur with OPDIVO treatment. 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 Checkmate 069
and 067, immune-mediated hepatitis occurred in 13% (51/407) of patients
receiving OPDIVO with YERVOY: Grade 4 (n=8), Grade 3 (n=37), Grade 2
(n=5), and Grade 1 (n=1). In Checkmate 037, 066, and 067,
immune-mediated hepatitis occurred in 2.3% (18/787) of patients
receiving OPDIVO: Grade 4 (n=3), Grade 3 (n=11), and Grade 2 (n=4). In
Checkmate 057, one patient (0.3%) developed immune-mediated hepatitis.
In Checkmate 025, there was an increased incidence of liver test
abnormalities compared to baseline in AST (33% vs 39%), alkaline
phosphatase (32% vs 32%), ALT (22% vs 31%), and total bilirubin (9% vs
3.5%) in the OPDIVO and everolimus arms, respectively. Immune-mediated
hepatitis requiring systemic immunosuppression occurred in 1.5% (6/406)
of patients receiving OPDIVO: Grade 3 (n=5) and Grade 2 (n=1).

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 Dermatitis

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

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

Hypophysitis, adrenal insufficiency, thyroid disorders, and type 1
diabetes mellitus can occur with OPDIVO treatment. Monitor patients for
signs and symptoms of hypophysitis, signs and symptoms of adrenal
insufficiency during and after treatment, thyroid function prior to and
periodically during treatment, and hyperglycemia. Administer
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. Administer insulin for type 1 diabetes. Withhold OPDIVO
for Grade 3 and permanently discontinue for Grade 4 hyperglycemia.

In Checkmate 069 and 067, hypophysitis occurred in 9% (36/407) of
patients receiving OPDIVO with YERVOY: Grade 3 (n=8), Grade 2 (n=25),
and Grade 1 (n=3). In Checkmate 037, 066, and 067, hypophysitis occurred
in 0.9% (7/787) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2
(n=3), and Grade 1 (n=2). In Checkmate 025, hypophysitis occurred in
0.5% (2/406) of patients receiving OPDIVO: Grade 3 (n=1) and Grade 1
(n=1). In Checkmate 069 and 067, adrenal insufficiency occurred in 5%
(21/407) of patients receiving OPDIVO with YERVOY: Grade 4 (n=1), Grade
3 (n=7), Grade 2 (n=11), and Grade 1 (n=2). In Checkmate 037, 066, and
067, adrenal insufficiency occurred in 1% (8/787) of patients receiving
OPDIVO: Grade 3 (n=2), Grade 2 (n=5), and Grade 1 (n=1). In Checkmate
057, 0.3% (1/287) of OPDIVO-treated patients developed adrenal
insufficiency. In Checkmate 025, adrenal insufficiency occurred in 2.0%
(8/406) of patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=4), and
Grade 1 (n=1). In Checkmate 069 and 067, hypothyroidism or thyroiditis
occurred in 22% (89/407) of patients receiving OPDIVO with YERVOY: Grade
3 (n=6), Grade 2 (n=47), and Grade 1 (n=36). Hyperthyroidism occurred in
8% (34/407) of patients: Grade 3 (n=4), Grade 2 (n=17), and Grade 1
(n=13). In Checkmate 037, 066, and 067, hypothyroidism or thyroiditis
occurred in 9% (73/787) of patients receiving OPDIVO: Grade 3 (n=1),
Grade 2 (n=37), Grade 1 (n=35). Hyperthyroidism occurred in 4.4%
(35/787) of patients receiving OPDIVO: Grade 3 (n=1), Grade 2 (n=12),
and Grade 1 (n=22). In Checkmate 057, Grade 1 or 2 hypothyroidism,
including thyroiditis, occurred in 7% (20/287) and elevated thyroid
stimulating hormone occurred in 17% of patients receiving OPDIVO. Grade
1 or 2 hyperthyroidism occurred in 1.4% (4/287) of patients. In
Checkmate 025, thyroid disease occurred in 11% (43/406) of patients
receiving OPDIVO, including one Grade 3 event, and in 3.0% (12/397) of
patients receiving everolimus. Hypothyroidism/thyroiditis occurred in 8%
(33/406) of patients receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=17),
and Grade 1 (n=14). Hyperthyroidism occurred in 2.5% (10/406) of
patients receiving OPDIVO: Grade 2 (n=5) and Grade 1 (n=5). In Checkmate
069 and 067, diabetes mellitus or diabetic ketoacidosis occurred in 1.5%
(6/407) of patients: Grade 4 (n=3), Grade 3 (n=1), Grade 2 (n=1), and
Grade 1 (n=1). In Checkmate 037, 066, and 067, diabetes mellitus or
diabetic ketoacidosis occurred in 0.8% (6/787) of patients receiving
OPDIVO: Grade 3 (n=2), Grade 2 (n=3), and Grade 1 (n=1). In Checkmate
025, hyperglycemic adverse events occurred in 9% (37/406) of patients.
Diabetes mellitus or diabetic ketoacidosis occurred in 1.5% (6/406) of
patients receiving OPDIVO: Grade 3 (n=3), Grade 2 (n=2), and Grade 1
(n=1).

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

Immune-mediated nephritis can occur with OPDIVO treatment. Monitor
patients for elevated serum creatinine prior to and periodically during
treatment. For Grade 2 or 3 increased serum creatinine, withhold and
administer corticosteroids; if worsening or no improvement occurs,
permanently discontinue. Administer corticosteroids for Grade 4 serum
creatinine elevation and permanently discontinue. In Checkmate 069 and
067, immune-mediated nephritis and renal dysfunction occurred in 2.2%
(9/407) of patients: Grade 4 (n=4), Grade 3 (n=3), and Grade 2 (n=2). In
Checkmate 037, 066, and 067, nephritis and renal dysfunction of any
grade occurred in 5% (40/787) of patients receiving OPDIVO.
Immune-mediated nephritis and renal dysfunction occurred in 0.8% (6/787)
of patients: Grade 3 (n=4) and Grade 2 (n=2). In Checkmate 057, Grade 2
immune-mediated renal dysfunction occurred in 0.3% (1/287) of patients
receiving OPDIVO. In Checkmate 025, renal injury occurred in 7% (27/406)
of patients receiving OPDIVO and 3.0% (12/397) of patients receiving
everolimus. Immune-mediated nephritis and renal dysfunction occurred in
3.2% (13/406) of patients receiving OPDIVO: Grade 5 (n=1), Grade 4
(n=1), Grade 3 (n=5), and Grade 2 (n=6).

Immune-Mediated Rash

Immune-mediated rash can occur with OPDIVO treatment. Severe rash
(including rare cases of fatal toxic epidermal necrolysis) occurred in
the clinical program of OPDIVO. Monitor patients for rash. Administer
corticosteroids for Grade 3 or 4 rash. Withhold for Grade 3 and
permanently discontinue for Grade 4. In Checkmate 069 and 067,
immune-mediated rash occurred in 22.6% (92/407) of patients receiving
OPDIVO with YERVOY: Grade 3 (n=15), Grade 2 (n=31), and Grade 1 (n=46).
In Checkmate 037, 066, and 067, immune-mediated rash occurred in 9%
(72/787) of patients receiving OPDIVO: Grade 3 (n=7), Grade 2 (n=15),
and Grade 1 (n=50). In Checkmate 057, immune-mediated rash occurred in
6% (17/287) of patients receiving OPDIVO including four Grade 3 cases.
In Checkmate 025, rash occurred in 28% (112/406) of patients receiving
OPDIVO and 36% (143/397) of patients receiving everolimus.
Immune-mediated rash, defined as a rash treated with systemic or topical
corticosteroids, occurred in 7% (30/406) of patients receiving OPDIVO:
Grade 3 (n=4), Grade 2 (n=7), and Grade 1 (n=19).

Immune-Mediated Encephalitis

Immune-mediated encephalitis can occur with OPDIVO treatment. 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 Checkmate 067, encephalitis was
identified in one patient (0.2%) receiving OPDIVO with YERVOY. In
Checkmate 057, fatal limbic encephalitis occurred in one patient (0.3%)
receiving OPDIVO.

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. In < 1.0% of patients
receiving OPDIVO, the following clinically significant, immune-mediated
adverse reactions occurred: uveitis, pancreatitis, facial and abducens
nerve paresis, demyelination, polymyalgia rheumatica, autoimmune
neuropathy, Guillain-Barré syndrome, hypopituitarism, systemic
inflammatory response syndrome, gastritis, duodenitis, and sarcoidosis.
Across clinical trials of OPDIVO as a single agent administered at doses
of 3 mg/kg and 10 mg/kg, additional clinically significant,
immune-mediated adverse reactions were identified: motor dysfunction,
vasculitis, and myasthenic syndrome.

Infusion Reactions

Severe infusion reactions have been reported in <1.0% of patients in
clinical trials of OPDIVO. 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 Checkmate 069 and 067, infusion- related
reactions occurred in 2.5% (10/407) of patients receiving OPDIVO with
YERVOY: Grade 2 (n=6) and Grade 1 (n=4). In Checkmate 037, 066, and 067,
Grade 2 infusion related reactions occurred in 2.7% (21/787) of patients
receiving OPDIVO: Grade 3 (n=2), Grade 2 (n=8), and Grade 1 (n=11). In
Checkmate 057, Grade 2 infusion reactions requiring corticosteroids
occurred in 1.0% (3/287) of patients receiving OPDIVO. In Checkmate 025,
hypersensitivity/infusion-related reactions occurred in 6% (25/406) of
patients receiving OPDIVO and 1.0% (4/397) of patients receiving
everolimus.

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 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 relative
to the OPDIVO arm. 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 037, serious adverse reactions occurred in 41% of
patients receiving OPDIVO. 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. 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 057, serious adverse reactions
occurred in 47% of patients receiving OPDIVO. The most frequent serious
adverse reactions reported in ≥2% of patients were pneumonia, pulmonary
embolism, dyspnea, pleural effusion, and respiratory failure. In
Checkmate 025, serious adverse reactions occurred in 47% of patients
receiving OPDIVO. The most frequent serious adverse reactions reported
in ≥2% of patients were acute kidney injury, pleural effusion,
pneumonia, diarrhea, and hypercalcemia.

Common Adverse Reactions

In Checkmate 067, the most common (≥20%) adverse reactions in the OPDIVO
plus YERVOY arm 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 arm were fatigue (53%), rash
(40%), diarrhea (31%), and nausea (28%). In Checkmate 037, the most
common adverse reaction (≥20%) reported with OPDIVO was rash (21%). In
Checkmate 066, the most common adverse reactions (≥20%) reported with
OPDIVO vs dacarbazine were fatigue (49% vs 39%), musculoskeletal pain
(32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate
057, the most common adverse reactions (≥20%) reported with OPDIVO were
fatigue (49%), musculoskeletal pain (36%), cough (30%), decreased
appetite (29%), and constipation (23%). In Checkmate 025, the most
common adverse reactions (≥20%) reported in patients receiving OPDIVO vs
everolimus 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 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%).

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.

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as
one of the world’s most respected centers focused on cancer patient
care, research, education and prevention. MD Anderson is one of only 41
comprehensive cancer centers designated by the National Cancer Institute
(NCI). For the past 25 years, MD Anderson has ranked as one of the
nation’s top two cancer centers in U.S.
News & World Report’s annual « Best Hospitals » survey.
MD Anderson receives a cancer center support grant from the NCI of the
National Institutes of Health (P30 CA016672). Get
MD Anderson News Via RSS Follow
MDAnderson News on Twitter.

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 as a single
agent or in combination with Yervoy will receive regulatory approval for
additional indications in lung cancer. 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, 2015
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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