Strategic immuno-oncology collaboration focused on development of CSF1R antibody (FPA008) in combination with Opdivo (nivolumab) and other therapies with the goal of bringing new treatment options to patients
Five Prime to receive up to $1.74 billion for FPA008, inclusive of $350 million upfront and potential development and regulatory milestone payments; additional double-digit royalties on future sales and option to co-promote in the U.S.
Five Prime to continue development of FPA008 in pigmented villonodular synovitis (PVNS) and in potential combinations with its own immuno-oncology candidates
Bristol-Myers
Squibb Company (NYSE:BMY) and Five
Prime Therapeutics, Inc. (Nasdaq:FPRX) today announced that they
have entered into an exclusive worldwide license and collaboration
agreement for the development and commercialization of Five Prime’s
colony stimulating factor 1 receptor (CSF1R) antibody program, including
FPA008 which is in Phase 1 development for immunology and oncology
indications. This agreement replaces the companies’ existing clinical
collaboration agreement to evaluate the safety, tolerability and
preliminary efficacy of combining Opdivo (nivolumab),
Bristol-Myers Squibb’s programmed-death 1 (PD-1) immune checkpoint
inhibitor, with FPA008 in six tumor types.
“By blocking a key mediator of immunosuppression in the tumor
microenvironment, CSF1R inhibition with FPA008 represents a potentially
important complementary immuno-oncology mechanism of action to the
T-cell directed antibodies and co-stimulatory molecules in our
pipeline,” said Francis
Cuss, MB BChir, FRCP, executive vice president and chief scientific
officer of Bristol-Myers Squibb. “This agreement, which builds upon our
existing relationship with Five Prime in immuno-oncology, is another
important example of our commitment to expanding our presence in this
space and to researching novel combination regimens.”
“We believe this transformational collaboration with Bristol-Myers
Squibb for our CSF1R antibody program represents the best of both worlds
in terms of maximizing the potential of FPA008,” said Lewis T. “Rusty”
Williams, M.D., Ph.D., president and chief executive officer of Five
Prime Therapeutics. “Bristol-Myers Squibb has undisputed leadership in
the immuno-oncology landscape, deep clinical development and regulatory
expertise, and an established commercial infrastructure to deliver
important new therapies to patients. Bristol-Myers Squibb also has a
rich pipeline of clinical candidates and approved products, a number of
which may have therapeutic synergy when coupled with FPA008, given the
potential of CSF1R inhibition to suppress the activity and survival of
tumor associated macrophages. At the same time, Five Prime will continue
to conduct trials in pigmented villonodular synovitis (PVNS) and
immuno-oncology with FPA008, which is a product of our proprietary
protein platform and our discovery of IL-34, one of the two ligands for
CSF1R that FPA008 blocks.”
Under the terms of the license and collaboration agreement,
Bristol-Myers Squibb will make an upfront payment of $350 million to
Five Prime. Bristol-Myers Squibb will be responsible for development and
manufacturing of FPA008 for all indications, subject to Five Prime’s
option to conduct, at its own cost, certain future studies including
registrational studies to support approval of FPA008 in PVNS and FPA008
in combination with Five Prime’s internal pipeline assets in
immuno-oncology. Five Prime will continue to conduct the current Phase
1a/1b trial evaluating the combination of Opdivo and FPA008 in
six tumor settings, which was announced as part of the companies’
initial clinical collaboration in November 2014, through to completion.
Bristol-Myers Squibb will be responsible for global commercialization,
and Five Prime will retain rights to a U.S. co-promotion option. In
addition to the upfront payment, Five Prime will be eligible to receive
up to $1.05 billion in development and regulatory milestone payments per
anti-CSF1R product for oncology indications (including combinations with Opdivo
and any other agent), and up to $340 million in development and
regulatory milestone payments per anti-CSF1R product for non-oncology
indications, as well as double digit royalties, such royalties to be
enhanced in the U.S. in the event that Five Prime exercises its
co-promotion option.
The effectiveness of the agreement is subject to clearance under the
Hart-Scott-Rodino Antitrust Improvements Act.
About FPA008
FPA008 is an investigational antibody that inhibits CSF1R and has been
shown in preclinical models to block the activation and survival of
monocytes and macrophages. Early data have shown that inhibition of
CSF1R in inflamed RA joints blocks the production of inflammatory
cytokines by macrophages and inhibits osteoclasts, monocyte-lineage
cells that can cause bone erosions and joint destruction. Inhibition of
CSF1R in preclinical models of several cancers reduces the number of
immunosuppressive tumor-associated macrophages (TAMs) in the tumor
microenvironment, thereby facilitating an immune response
against tumors. FPA008 is currently in phase 1 clinical trials in
several immunology and oncology indications.
About Opdivo
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 more than 37 countries including the United
States, Japan, and in the European Union.
In the U.S., Opdivo is indicated for patients with unresectable
or metastatic melanoma and disease progression following Yervoy (ipilimumab)
and, if BRAF V600 mutation positive, a BRAF inhibitor. Opdivo is
also approved for use in combination with Yervoy, for the
treatment of patients with BRAF V600 wild-type unresectable or
metastatic melanoma. These indications are approved under accelerated
approval based on tumor response rate and durability of
response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory trials. Opdivo
is also indicated in the U.S. for the treatment of patients with
metastatic non-small cell lung cancer (NSCLC) with progression on or
after platinum-based chemotherapy.
Bristol-Myers Squibb has a broad, global development program to study Opdivo in
multiple tumor types consisting of more than 50 trials – as a
monotherapy or in combination with other therapies – in which more than
8,000 patients have been enrolled worldwide.
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.
Immune-Mediated Pneumonitis
Immune-mediated pneumonitis or interstitial lung disease, including
fatal cases, occurred with OPDIVO treatment. Across the clinical trial
experience with solid tumors, fatal immune-mediated pneumonitis occurred
in 0.5% (5/978) of patients receiving OPDIVO as a single agent. In
Checkmate 037, pneumonitis, including interstitial lung disease,
occurred in 3.4% (9/268) of patients receiving OPDIVO and none of the
102 patients receiving chemotherapy. Immune-mediated pneumonitis
occurred in 2.2% (6/268) of patients receiving OPDIVO; Grade 3 (n=1) and
Grade 2 (n=5). In Checkmate 057, immune-mediated pneumonitis, including
interstitial lung disease, occurred in 3.4% (10/287) of patients
receiving OPDIVO as a single agent: Grade 3 (n=5), Grade 2 (n=2), and
Grade 1 (n=3). Across the clinical trial experience in 188 patients with
melanoma who received OPDIVO in combination with YERVOY, in Checkmate
069 (n=94) and an additional dose-finding study (n=94), fatal
immune-mediated pneumonitis occurred in 0.5% (1/188) of patients. In
Checkmate 069, there were six additional 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, pneumonitis, including interstitial lung disease,
occurred in 10% (9/94) of patients receiving OPDIVO in combination with
YERVOY and 2.2% (1/46) of patients receiving YERVOY. Immune-mediated
pneumonitis occurred in 6% (6/94) of patients receiving OPDIVO in
combination with YERVOY: Grade 5 (n=1), Grade 3 (n=2) and Grade 2 (n=3).
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. In combination with
YERVOY, withhold OPDIVO for Grade 2 and permanently discontinue for
Grade 3 or 4 or recurrent colitis upon restarting OPDIVO. In Checkmate
037, diarrhea or colitis occurred in 21% (57/268) of patients receiving
OPDIVO and 18% (18/102) of patients receiving chemotherapy.
Immune-mediated colitis occurred in 2.2% (6/268) of patients receiving
OPDIVO; Grade 3 (n=5) and Grade 2 (n=1). In Checkmate 057, diarrhea or
colitis occurred in 17% (50/287) of patients receiving OPDIVO as a
single agent. 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
069, diarrhea or colitis occurred in 57% (54/94) of patients receiving
OPDIVO in combination with YERVOY and 46% (21/46) of patients receiving
YERVOY. Immune-mediated colitis occurred in 33% (31/94) of patients
receiving OPDIVO in combination with YERVOY: Grade 4 (n=1), Grade 3
(n=16), Grade 2 (n=9), and Grade 1 (n=5).
In a separate YERVOY Phase 3 study, 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
037, there was an increased incidence of liver test abnormalities in the
OPDIVO-treated group as compared to the chemotherapy-treated group, with
increases in AST (28% vs 12%), alkaline phosphatase (22% vs 13%), ALT
(16% vs 5%), and total bilirubin (9% vs 0). Immune-mediated hepatitis
occurred in 1.1% (3/268) of patients receiving OPDIVO; Grade 3 (n=2) and
Grade 2 (n=1). In Checkmate 057, one patient (0.3%) developed
immune-mediated hepatitis. In Checkmate 069, immune-mediated hepatitis
occurred in 15% (14/94) of patients receiving OPDIVO in combination with
YERVOY: Grade 4 (n=3), Grade 3 (n=9), and Grade 2 (n=2).
In a separate YERVOY Phase 3 study, 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 YERVOY Phase 3 study, 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 Neuropathies
In a separate YERVOY Phase 3 study, 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, and thyroid disorders can occur
with OPDIVO treatment. Monitor patients for signs and symptoms of
hypophysitis, signs and symptoms of adrenal insufficiency during and
after treatment, and thyroid function prior to and periodically during
treatment. 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.
In Checkmate 069, hypophysitis occurred in 13% (12/94) of patients
receiving OPDIVO in combination with YERVOY: Grade 3 (n=2) and Grade 2
(n=10). Adrenal insufficiency occurred in 1% (n=555) of patients
receiving OPDIVO as a single agent. In Checkmate 069, adrenal
insufficiency occurred in 9% (8/94) of patients receiving OPDIVO in
combination with YERVOY: Grade 3 (n=3), Grade 2 (n=4), and Grade 1
(n=1). In Checkmate 069, hypothyroidism occurred in 19% (18/94) of
patients receiving OPDIVO in combination with YERVOY. All were Grade 1
or 2 in severity except for one patient who experienced Grade 3
autoimmune thyroiditis. Grade 1 hyperthyroidism occurred in 2.1% (2/94)
of patients receiving OPDIVO in combination with YERVOY. In Checkmate
037, Grade 1 or 2 hypothyroidism occurred in 8% (21/268) of patients
receiving OPDIVO and none of the 102 patients receiving chemotherapy.
Grade 1 or 2 hyperthyroidism occurred in 3% (8/268) of patients
receiving OPDIVO and 1% (1/102) of patients receiving chemotherapy. In
Checkmate 057, Grade 1 or 2 hypothyroidism, including thyroiditis,
occurred in 7% (20/287) and elevated TSH occurred in 17% of patients
receiving OPDIVO as a single agent. Grade 1 or 2 hyperthyroidism
occurred in 1.4% (4/287) of patients.
In a separate YERVOY Phase 3 study, 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 037,
there was an increased incidence of elevated creatinine in the
OPDIVO-treated group as compared to the chemotherapy-treated group (13%
vs 9%). Grade 2 or 3 immune-mediated nephritis or renal dysfunction
occurred in 0.7% (2/268) of patients. In Checkmate 057, Grade 2
immune-mediated renal dysfunction occurred in 0.3% (1/287) of patients
receiving OPDIVO as a single agent. In Checkmate 069, Grade 2 or higher
immune-mediated nephritis or renal dysfunction occurred in 2.1% (2/94)
of patients. One patient died without resolution of renal dysfunction.
Immune-Mediated Rash
Immune-mediated rash can occur with OPDIVO treatment. Monitor patients
for rash. Administer corticosteroids for Grade 3 or 4 rash. Withhold for
Grade 3 and permanently discontinue for Grade 4. In Checkmate 037
(n=268), the incidence of rash was 21%; the incidence of Grade 3 or 4
rash was 0.4%. In Checkmate 057, immune-mediated rash occurred in 6%
(17/287) of patients receiving OPDIVO as a single agent including four
Grade 3 cases. In Checkmate 069, immune-mediated rash occurred in 37%
(35/94) of patients receiving OPDIVO in combination with YERVOY: Grade 3
(n=6), Grade 2 (n=10), 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. Across clinical trials of 8490
patients receiving OPDIVO as a single agent or in combination with
YERVOY, <1% of patients were identified as having encephalitis. In
Checkmate 057, fatal limbic encephalitis occurred in one patient (0.3%)
receiving OPDIVO as a single agent.
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. The following
clinically significant immune-mediated adverse reactions occurred in <2%
(n=555) of single-agent OPDIVO-treated patients: uveitis, pancreatitis,
abducens nerve paresis, demyelination, polymyalgia rheumatica, and
autoimmune neuropathy. Across clinical trials of OPDIVO administered as
a single agent at doses 3 mg/kg and 10 mg/kg, additional clinically
significant, immune-mediated adverse reactions were identified: facial
nerve paralysis, motor dysfunction, vasculitis, diabetic ketoacidosis,
and myasthenic syndrome. In Checkmate 069, the following additional
immune-mediated adverse reactions occurred in 1% of patients treated
with OPDIVO in combination with YERVOY: Guillain-Barré syndrome and
hypopituitarism. Across clinical trials of OPDIVO in combination with
YERVOY, the following additional clinically significant, immune-mediated
adverse reactions were identified: uveitis, sarcoidosis, duodenitis,
pancreatitis, and gastritis.
Infusion Reactions
Severe infusion reactions have been reported in <1% of patients in
clinical trials of OPDIVO as a single agent. In Checkmate 057, Grade 2
infusion reactions occurred in 1% (3/287) of patients receiving OPDIVO
as a single agent. In Checkmate 069, Grade 2 infusion reactions occurred
in 3% (3/94) of patients receiving OPDIVO in combination with YERVOY.
Discontinue OPDIVO in patients with severe or life-threatening infusion
reactions. Interrupt or slow the rate of infusion in patients with mild
or moderate infusion reactions.
Embryofetal Toxicity
Based on its mechanism of action, OPDIVO 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 OPDIVO-containing regimen
and for at least 5 months after the last dose of OPDIVO.
Lactation
It is not known whether OPDIVO 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
OPDIVO-containing regimen, advise women to discontinue breastfeeding
during treatment.
Serious Adverse Reactions
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 057, serious adverse reactions occurred
in 47% of patients receiving OPDIVO as a single agent. The most frequent
serious adverse reactions reported in ≥2% of patients were pneumonia,
pulmonary embolism, dyspnea, pleural effusion, and respiratory failure.
In Checkmate 069, serious adverse reactions occurred in 62% of patients
receiving OPDIVO; the most frequent serious adverse events with OPDIVO
in combination with YERVOY, as compared to YERVOY alone, were colitis
(17% vs 9%), diarrhea (9% vs 7%), pyrexia (6% vs 7%), and pneumonitis
(5% vs 0).
Common Adverse Reactions
In Checkmate 037, the most common adverse reaction (≥20%) reported with
OPDIVO was rash (21%). In Checkmate 057, the most common adverse
reactions (≥20%) reported with OPDIVO as a single agent were fatigue
(49%), musculoskeletal pain (36%), cough (30%), decreased appetite
(29%), and constipation (23%). In Checkmate 069, the most common adverse
reactions (≥20%) reported in patients receiving OPDIVO in combination
with YERVOY vs YERVOY alone were rash (67% vs 57%), pruritus (37% vs
26%), headache (24% vs 20%), vomiting (23% vs 15%), and colitis (22% vs
11%).
In a separate YERVOY Phase 3 study, 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%).
Please see U.S. Full Prescribing Information for OPDIVO and YERVOY,
including Boxed WARNING for YERVOY regarding
immune-mediated adverse reactions.
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, please
visit www.bms.com
or follow us on Twitter at http://twitter.com/bmsnews.
About Five Prime Therapeutics
Five Prime Therapeutics, Inc. discovers and develops innovative
therapeutics to improve the lives of patients with serious diseases.
Five Prime's comprehensive discovery platform, which encompasses
virtually every medically relevant extracellular protein, positions it
to explore pathways in cancer, inflammation and their intersection in
immuno-oncology, an area of oncology with significant therapeutic
potential and a growing focus of the company's R&D activities. Five
Prime has entered into strategic collaborations with leading global
pharmaceutical companies and has promising product candidates in
clinical and late preclinical development.
For more information, please visit www.fiveprime.com.
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 FPA008 will be
successfully developed or approved for any of the indications described
in this release or in combination with Opdivo. 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, 2014 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.
Five Prime Forward-Looking Statement
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995. Words
such as "may," "will," "expect," "plan," "anticipate," "estimate,"
"intend" and similar expressions (as well as other words or expressions
referencing future events, conditions or circumstances) are intended to
identify forward-looking statements. These forward-looking statements
are based on Five Prime's expectations and assumptions as of the date of
this press release. Each of these forward-looking statements involves
risks and uncertainties. Actual results may differ materially from these
forward-looking statements. Forward-looking statements contained in this
press release include statements regarding (i) the planned clinical
development of the combination of FPA008 with nivolumab; and (ii) Five
Prime's potential receipt of upfront and milestone payments and
royalties. Many factors may cause differences between current
expectations and actual results including unexpected safety or efficacy
data observed during clinical studies, changes in expected or existing
competition, changes in the regulatory, pricing or reimbursement
environment, and unexpected litigation or other disputes. Other
factors that may cause actual results to differ from those expressed or
implied in the forward-looking statements in this press release are
discussed in Five Prime's filings with the U.S. Securities and Exchange
Commission, including the "Risk Factors" contained therein. Except as
required by law, Five Prime assumes no obligation to update any
forward-looking statements contained herein to reflect any change in
expectations, even as new information becomes available.

Bristol-Myers SquibbMedia:Sarah Koenig, 609-252-4145sarah.koenig@bms.comorInvestors:Ranya Dajani, 609-252-5330ranya.dajani@bms.comorFive Prime Therapeutics:Amy Kendall, 415-365-5776amy.kendall@fiveprime.com