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REGENERON AT A GLANCE
2 0 1 6 A N N U A L R E P O R T
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< MENU >< MENU > DEAR FELLOW SHAREHOLDERS,
In 2016, we reaffirmed our core strategy of growth through innovation and continued to advance our mission
of consistently and repeatedly bringing important new medicines to patients in need.
Turning science into important drugs is one of the most difficult activities
Turning to our currently marketed medicines, we continue to bring EYLEA®
an organization can undertake. Despite thousands of biopharmaceutical
(aflibercept) Injection, our market-leading therapy for the treatment of serious
companies in the United States and billions in R&D spend, only 22 novel
vision-threatening diseases, to more and more indicated patients. In 2016,
drugs were approved by the U.S. Food and Drug Administration (FDA) in
EYLEA global net sales were $5.2 billion, including $3.3 billion in U.S. net
2016. Of these, only eight were first in class, and even fewer targeted
sales. We continue to work to improve outcomes in serious retinal diseases
major diseases affecting millions of people. With this background, it is quite
and have an ongoing Phase 3 trial with EYLEA in diabetic retinopathy, as well
a testament to the Regeneron team that, by the end of 2017, we anticipate
as a combination program evaluating EYLEA co-formulated with nesvacumab,
having five new medicines approved since 2011, all of which are first- or
an investigational ANG-2 antibody.
second-in-class therapies.
We laid important groundwork last year that has positioned us for a
demonstrated gradual sales growth in 2016, reaching $116 million in global
potentially transformational year in 2017, with two important new drug
net sales. This growth was hampered by significant
launches. Dupixent® (dupilumab) Injection was approved on March 28,
access challenges and a desire from payers
Praluent® (alirocumab) Injection, our therapy for uncontrolled LDL cholesterol,
studies in eosinophilic esophagitis.
2017, by the FDA and the launch is ongoing. Moderate-to-severe atopic
and physicians to see positive
dermatitis is a serious inflammatory disease with limited treatment options.
outcomes data. We expect to
Patients suffer with widespread rash, debilitating itching, and other
complete our 18,000-patient
challenges. We believe Dupixent, which the FDA had designated a
Breakthrough Therapy, represents an important scientific advance and,
most importantly, new hope for patients in need. We also recently
ODYSSEY OUTCOMES
study by the end of 2017.
Together with our
resubmitted our U.S. application for Kevzara® (sarilumab) for the treatment
collaborators at Sanofi,
of moderately to severely active rheumatoid arthritis, and expect an FDA
decision later in 2017.
we continue to
defend our position
By the end of 2017,
we anticipate having five
new medicines approved
since 2011, all of which are first-
or second-in-class therapies.
2 0 1 6 A N N U A L R E P O R T
4
in the ongoing patent litigation related to Praluent. We believe the controlling
We also have a late-stage program ongoing for fasinumab, our antibody to
law and facts support our position and look forward to a timely resolution of
Nerve Growth Factor (NGF) for osteoarthritis pain and chronic lower back
this matter.
pain, and in 2016, we entered a major new global collaboration with Teva for
the development of this product candidate, which will help us advance this
Our pipeline continues to grow with potential innovations across a number
program. Our late-stage pipeline is rounded out with suptavumab, our
of serious diseases. Dupilumab, in particular, has the potential to represent
antibody to respiratory syncytial virus (RSV), a serious respiratory infection in
a pipeline in a single compound as the therapy targets a key signaling
infants, and our PD-1 antibody, REGN2810, for the treatment of non-small cell
pathway that is believed to drive a number of allergic diseases. We expect
lung cancer (NSCLC) and a serious skin cancer.
top-line Phase 3 results for dupilumab in patients with asthma, followed by a
potential U.S. regulatory submission in this indication by year-end 2017. We
Our early-to-mid-stage programs also continue to make important progress.
are also studying dupilumab in late-stage trials of patients with nasal polyps,
Programs include evinacumab, our Angptl-3 antibody for homozygous familial
pediatric asthma, and pediatric atopic dermatitis, in addition to earlier-stage
hypercholesterolemia, an inherited lipid disorder; additional immuno-oncology
candidates, including a bi-specific antibody for blood cancers; and an Activin
A antibody for a rare and extremely serious disease known as Fibrodysplasia
Ossificans Progressiva.
We continue to prioritize ongoing investment in technology and innovation,
which we believe will position us to bring needed new medicines to patients for
many years to come. One of these efforts is the Regeneron Genetics Center
(RGC), which in just a little over three years after launch has sequenced more
than 150,000 consented individuals. In March 2017, the RGC embarked on an
important collaboration in the United Kingdom with the goal of sequencing all
the participants in the UK Biobank, the world’s most comprehensive
health resource, which includes samples and medical records from
500,000 volunteer participants. Importantly, the RGC efforts have
already identified exciting new targets for drug development.
< MENU >< MENU > Turning science into important drugs is one of the most difficult activities
Turning to our currently marketed medicines, we continue to bring EYLEA®
an organization can undertake. Despite thousands of biopharmaceutical
(aflibercept) Injection, our market-leading therapy for the treatment of serious
companies in the United States and billions in R&D spend, only 22 novel
vision-threatening diseases, to more and more indicated patients. In 2016,
drugs were approved by the U.S. Food and Drug Administration (FDA) in
EYLEA global net sales were $5.2 billion, including $3.3 billion in U.S. net
2016. Of these, only eight were first in class, and even fewer targeted
sales. We continue to work to improve outcomes in serious retinal diseases
major diseases affecting millions of people. With this background, it is quite
and have an ongoing Phase 3 trial with EYLEA in diabetic retinopathy, as well
a testament to the Regeneron team that, by the end of 2017, we anticipate
as a combination program evaluating EYLEA co-formulated with nesvacumab,
having five new medicines approved since 2011, all of which are first- or
an investigational ANG-2 antibody.
second-in-class therapies.
We laid important groundwork last year that has positioned us for a
demonstrated gradual sales growth in 2016, reaching $116 million in global
potentially transformational year in 2017, with two important new drug
net sales. This growth was hampered by significant
launches. Dupixent® (dupilumab) Injection was approved on March 28,
access challenges and a desire from payers
2017, by the FDA and the launch is ongoing. Moderate-to-severe atopic
and physicians to see positive
dermatitis is a serious inflammatory disease with limited treatment options.
outcomes data. We expect to
Patients suffer with widespread rash, debilitating itching, and other
complete our 18,000-patient
challenges. We believe Dupixent, which the FDA had designated a
Breakthrough Therapy, represents an important scientific advance and,
most importantly, new hope for patients in need. We also recently
of moderately to severely active rheumatoid arthritis, and expect an FDA
decision later in 2017.
ODYSSEY OUTCOMES
study by the end of 2017.
Together with our
we continue to
defend our position
resubmitted our U.S. application for Kevzara® (sarilumab) for the treatment
collaborators at Sanofi,
in the ongoing patent litigation related to Praluent. We believe the controlling
We also have a late-stage program ongoing for fasinumab, our antibody to
law and facts support our position and look forward to a timely resolution of
Nerve Growth Factor (NGF) for osteoarthritis pain and chronic lower back
this matter.
pain, and in 2016, we entered a major new global collaboration with Teva for
the development of this product candidate, which will help us advance this
Our pipeline continues to grow with potential innovations across a number
program. Our late-stage pipeline is rounded out with suptavumab, our
of serious diseases. Dupilumab, in particular, has the potential to represent
antibody to respiratory syncytial virus (RSV), a serious respiratory infection in
a pipeline in a single compound as the therapy targets a key signaling
infants, and our PD-1 antibody, REGN2810, for the treatment of non-small cell
pathway that is believed to drive a number of allergic diseases. We expect
lung cancer (NSCLC) and a serious skin cancer.
top-line Phase 3 results for dupilumab in patients with asthma, followed by a
potential U.S. regulatory submission in this indication by year-end 2017. We
Our early-to-mid-stage programs also continue to make important progress.
are also studying dupilumab in late-stage trials of patients with nasal polyps,
Programs include evinacumab, our Angptl-3 antibody for homozygous familial
pediatric asthma, and pediatric atopic dermatitis, in addition to earlier-stage
hypercholesterolemia, an inherited lipid disorder; additional immuno-oncology
Praluent® (alirocumab) Injection, our therapy for uncontrolled LDL cholesterol,
studies in eosinophilic esophagitis.
We continue to prioritize
ongoing investment in technology
and innovation, which we believe will
position us to bring needed new medicines
to patients for many years to come.
candidates, including a bi-specific antibody for blood cancers; and an Activin
A antibody for a rare and extremely serious disease known as Fibrodysplasia
Ossificans Progressiva.
We continue to prioritize ongoing investment in technology and innovation,
which we believe will position us to bring needed new medicines to patients for
many years to come. One of these efforts is the Regeneron Genetics Center
(RGC), which in just a little over three years after launch has sequenced more
than 150,000 consented individuals. In March 2017, the RGC embarked on an
important collaboration in the United Kingdom with the goal of sequencing all
the participants in the UK Biobank, the world’s most comprehensive
health resource, which includes samples and medical records from
500,000 volunteer participants. Importantly, the RGC efforts have
already identified exciting new targets for drug development.
2 0 1 6 A N N U A L R E P O R T
5
< MENU >< MENU > As we have grown to employ over 5,500 people, we have also grown physically —
commitment to support this program, which plays a critical role in the
we continue to expand our manufacturing facilities in Rensselaer, New York, and
development of a strong science talent pipeline for generations to come and in
Raheen, Ireland, and we also purchased an office building near our Tarrytown,
elevating the place of science in our society.
New York facility, which will help expand the footprint of our headquarters in
Westchester County, New York. Also, in early 2017, we completed a new lease
We invite you to read about our 2016 accomplishments, financial performance
financing for our Tarrytown corporate headquarters. As a result of this
and corporate citizenship efforts in our online annual report and in our 2016
transaction, we have obtained an option to buy the facility at the end of the
Annual Report on Form 10-K, which are available on the Investor Relations
five-year lease term and are poised to benefit from immediate cash savings and
portion of our website.
increased flexibility for future growth.
Finally, in 2016, we were thrilled to expand our long-standing dedication to
on our mission of developing transformative medicines for patients.
We are very much looking forward to a successful 2017 and continuing to deliver
science education with a major philanthropic commitment to inspire future
innovators. We became only the third sponsor in 75 years of the nation’s oldest
and most prestigious high school science competition, now known as the
Sincerely,
Regeneron Science Talent Search. This program was previously sponsored by
Intel, and before that, by Westinghouse. We have made a 10-year, $100 million
Len, George, and Roy
Leonard S. Schleifer, MD, PhD
President and Chief Executive Officer
George D. Yancopoulos, MD, PhD
President and Chief Scientific Officer
P. Roy Vagelos, MD
Chairman of the Board
2 0 1 6 A N N U A L R E P O R T
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< MENU >< MENU > M A R K E T E D
P R O D U CTS
M A K E G R E AT M E D I C I N E
T H E N D O I T A G A I N A N D A G A I N
2 0 1 6 A N N U A L R E P O R T
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< MENU >< MENU > EYLEA® (AFLIBERCEPT) INJECTION AND RETINAL DISEASE PROGRAMS
Market-leading anti-VEGF approved in more than 100 countries for the treatment
of key blindness-causing retinal conditions including wet age-related macular
degeneration (AMD) and diabetic macular edema (DME).
EYLEA global net sales exceeded $5 billion in 2016. In the United States, EYLEA net sales increased
24% to $3.32 billion for the full year 2016 from $2.68 billion for the full year 2015. Outside of the United
States, where our collaborator Bayer HealthCare commercializes EYLEA, net sales were $1.87 billion in
2016, compared to $1.41 billion in 2015. Regeneron recognized $649 million from its share of net profit
outside the United States in 2016, compared to $467 million in 2015.
“We’re proud that EYLEA has helped many patients over the last
several years. We continue to work on new innovations for people
with serious vision-threatening diseases in an effort to further
improve outcomes for these patients.”
— Robert L. Vitti, MD, Vice President and Head of Ophthalmology
In 2017, we continue to enroll patients in our ongoing Phase 3 study of EYLEA in non-proliferative diabetic
retinopathy, a common eye disease that impacts many people with diabetes. In addition to this new indication,
we are exploring EYLEA in combination with nesvacumab, an anti-angiopoietin 2 antibody, in two fully enrolled
Phase 2 trials — RUBY in DME and ONYX in wet AMD. In 2016, we discontinued the development of another EYLEA
combination therapy, aflibercept + rinucumab, an anti–platelet-derived growth factor receptor beta (anti-PDGFR-beta)
antibody, which did not demonstrate improvement in best corrected visual acuity (BCVA) compared to aflibercept
monotherapy in our Phase 2 CAPELLA study. Though pre-clinical data for the co-formulation of aflibercept and nesvacumab
are more supportive, EYLEA sets a very high efficacy bar in the treatment of these disease indications.
EYLEA U.S. SALES: 24% INCREASE
$3.32 bn
$2.68 bn
$1.74 bn
2014
2015
2016
EYLEA EX-U.S. SALES: 33% INCREASE
$1.87 bn
$1.41 bn
$1.04 bn
2014
2015
2016
Sales increases represent year-over-year
growth from 2015 to 2016.
2 0 1 6 A N N U A L R E P O R T
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< MENU >< MENU > PRALUENT® (ALIROCUMAB) INJECTION
Monoclonal antibody targeting PCSK9 (proprotein convertase
subtilisin/kexin type 9) available in two doses, allowing for
dose adjustment based on patients’ LDL-C–lowering needs.
Praluent completed its first full year on the market in 2016, with $116 million in global net sales. Praluent
is a PCSK9 inhibitor approved by the FDA as adjunct to diet and maximally tolerated statin therapy for the
treatment of heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease
in adults who require additional lowering of LDL-C (often referred to as “bad cholesterol”). The effect of
Praluent on cardiovascular morbidity and mortality has not been determined.
The ongoing ODYSSEY OUTCOMES clinical trial program, which is evaluating the potential of Praluent to
prevent heart attacks, stroke and cardiac death, reached full enrollment in 2015, with more than 18,000 patients
at over 2,000 study centers. Two prespecified interim analyses were performed by an independent Data
Monitoring Committee in 2016 — the first, a futility analysis when 50% of cardiovascular events had occurred, and
the second analysis, for both futility and overwhelming efficacy, when 75% of cardiovascular events had occurred.
The trial continued as planned following both analyses, and we expect to complete the study in late 2017.
We continue to be involved in patent litigation with Amgen related to Praluent. In 2016, a District Court jury ruled
against us, upholding the validity of Amgen’s patents. In early 2017, the District Court granted a permanent
injunction requested by Amgen, preventing the marketing, selling, or commercial manufacturing of Praluent in
the United States. We have appealed both of these decisions to the U.S. Court of Appeals for the Federal
Circuit, which hears all biopharmaceutical patent litigation appeals, and the court has stayed (suspended)
the permanent injunction for Praluent that was granted by the District Court, pending appeal. This stay
ensures that Praluent will continue to be available to patients during the ongoing appeal process. We
strongly believe that the controlling law and facts support our position that Amgen’s asserted patent
claims are invalid. We look forward to pursuing our appeal over the coming months.
“After I suffered a major
heart attack and was at
risk for another one, I
was afraid I would not
be here for the future of
my two children. Now
that my bad cholesterol
is under control, I feel
like I have my life back!”
— Peggy,
Praluent patient
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< MENU > < MENU > DUPIXENT® (DUPILUMAB) INJECTION
First-in-class monoclonal antibody that treats moderate-to-severe atopic dermatitis (AD) by blocking IL-4 and
IL-13, two key cytokines involved in allergic diseases.
“I so appreciate all
the researchers
who worked on
bringing Dupixent
to atopic dermatitis
patients like me.
I now feel
confident spending
time with my family,
continuing my
music career and
living my life to
the fullest.”
— Lisa, harpist and
Dupixent patient
Dupixent has been approved in the United States and is under regulatory review in the European Union for the treatment of atopic
dermatitis (AD). It is also being studied in other allergic conditions including asthma, nasal polyps, and eosinophilic esophagitis.
In March of 2017, Dupixent was approved by the FDA for the treatment of moderate-to-severe AD in adults whose disease is not
adequately controlled with topical prescription therapies or for whom those therapies are not advisable. Dupixent can be used with
or without topical corticosteroids. With our collaborator Sanofi, we launched the product to the commercial market shortly following
approval. We are excited to provide this first-in-class medicine to adult patients who, up until the approval of Dupixent, had no
FDA-approved biologic therapies to treat their uncontrolled moderate-to-severe AD. Additionally, in December of 2016, the European
Medicines Agency (EMA) accepted for review the Marketing Authorization Application (MAA) for Dupixent for the treatment of
moderate-to-severe AD in adults who are candidates for systemic therapy. We expect a decision from the EMA later in 2017.
In 2016, we reported positive data from three Phase 3 trials of Dupixent (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, and LIBERTY
AD CHRONOS) in adult patients with moderate-to-severe AD. In these studies, treatment with Dupixent as monotherapy or as
concomitant treatment with topical medications significantly improved measures of overall disease severity, skin clearing, and itching.
We are also studying dupilumab in pediatric patients with moderate-to-severe AD, and have been granted Breakthrough Therapy
designation by the FDA for a subset of pediatric patients with moderate-to-severe AD. We began a Phase 3 trial in adolescents
(aged 12 to 17 years) with moderate-to-severe AD in the first quarter of 2017, and we expect to initiate a trial in children (aged 6 to 11
years) with severe AD later in 2017.
Our second pivotal study for the treatment of asthma, LIBERTY ASTHMA QUEST, is fully enrolled, with data expected in the second
half of 2017. We plan to submit a U.S. regulatory filing for dupilumab in this indication by year-end 2017. In the second quarter of 2017,
we anticipate beginning enrollment of a Phase 3 trial in uncontrolled, persistent asthma in children (aged 6 to 11 years).
Progress continues on our other indications as well. We have begun enrolling patients with nasal polyps in two Phase 3 trials, and
expect to begin enrolling patients with food allergies in a Phase 2 trial in the second half of 2017. We also expect Phase 2 data from
our ongoing trial in patients with eosinophilic esophagitis in the second half of 2017.
2 0 1 6 A N N U A L R E P O R T
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< MENU > < MENU > KEVZARA® (SARILUMAB) INJECTION
IL-6R antibody under U.S. and EU regulatory review for
the treatment of rheumatoid arthritis (RA). Kevzara has
been approved in Canada.
In 2016, we reported positive data from the Phase 3 SARIL-RA-MONARCH monotherapy
study, which met its primary endpoint by demonstrating that Kevzara was superior to
Humira® (adalimumab) in improving signs and symptoms in adults with active RA who were
inadequate responders to, intolerant of, or inappropriate candidates for methotrexate.
It was the first time a subcutaneously delivered IL-6 receptor blocker demonstrated
superiority over adalimumab monotherapy in RA.
In 2016, the EMA accepted for review the MAA for sarilumab, and an application for marketing
approval for sarilumab was submitted in Japan. In the United States, we, along with our
collaborator Sanofi, submitted the U.S. Biologics License Application (BLA) for Kevzara in
November 2015, and were assigned a Prescription Drug User Fee Act (PDUFA) date of
October 30, 2016. On October 28, 2016, we received a Complete Response Letter (CRL) from
the FDA related to a Sanofi manufacturing facility. In early 2017, after the facility completed a
successful FDA re-inspection, we resubmitted the Kevzara BLA. We expect an FDA decision in
the second quarter of 2017. Finally, in February 2017, Kevzara received approval and was
launched in the commercial market in Canada for the treatment of moderately to severely
active RA in adults who have had an inadequate response or intolerance to one or more
biologic or non-biologic disease-modifying antirheumatic drugs (DMARDs).
“RA impacts every aspect of
my life and when its
uncontrolled it makes me feel
like I can’t do anything I love.
I’m so glad people continue
to develop new treatments so
I can go back to doing the
things I love – playing with my
five grandchildren, quilting,
and cooking.”
— Michelle, seamstress and
RA clinical trial patient
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< MENU > < MENU > LAT E - STA G E
P I P E L I N E
N E V E R STO P
A S K I N G W H Y
2 0 1 6 A N N U A L R E P O R T
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< MENU >< MENU > PIPELINE (as of April 2017)
Regeneron has fifteen fully human monoclonal antibodies in clinical development that
were developed using our proprietary VelocImmune ® technology.
PHASE 1
REGN1908-1909
Feld1 Antibody
Allergic disease
REGN2810*
PD-1 Antibody
Cancer
REGN1979
CD20XCD3 Antibody
Cancer
(also in combination
with REGN2810)
REGN3470-3471-3479
Antibody to Ebola virus
Ebola virus infection
PHASE 2
DUPILUMAB*
IL-4R Antibody
Eosinophilic esophagitis
SARILUMAB*
IL-6R Antibody
Juvenile idiopathic
arthritis
EVINACUMAB
Angptl3 Antibody
Homozygous familial
hypercholesterolemia
FASINUMAB†
NGF Antibody
Pain due to chronic
lower back pain
TREVOGRUMAB
GDF8 Antibody
(in combination
with REGN2477)
REGN2477
Activin A Antibody
Fibrodysplasia
ossificans progressiva
(also in combination
with trevogrumab)
REGN3500*
IL-33 Antibody
Inflammatory diseases
REGN3767*
LAG-3 Antibody
Cancer (also in combination
with REGN2810)
* in collaboration with Sanofi
^ in collaboration with Bayer HealthCare ex-U.S.
†
in collaboration with Mitsubishi Tanabe Pharma Corporation (Asia) and Teva
NESVACUMAB +
AFLIBERCEPT^
Ang2 Antibody +
Aflibercept
Wet age-related
macular degeneration,
diabetic macular
edema
REGN2810*
PD-1 Antibody
Advanced
cutaneous squamous
cell carcinoma
PHASE 3
ALIROCUMAB*
PCSK9 Antibody
Hypercholesterolemia
SARILUMAB*
IL-6R Antibody
Rheumatoid arthritis
DUPILUMAB*
IL-4R Antibody
Atopic dermatitis in
children, asthma in
adults and children,
nasal polyps
AFLIBERCEPT
VEGF-Trap
Diabetic retinopathy
without diabetic
macular edema
SUPTAVUMAB
RSV Antibody
Respiratory syncytial
virus infection
FASINUMAB†
NGF Antibody
Pain due to
osteoarthritis
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< MENU >< MENU > SUPTAVUMAB
Fully human monoclonal antibody being investigated for
the prevention of serious lower respiratory tract infections
associated with respiratory syncytial virus (RSV).
In 2016, we continued enrollment of the Phase 3 NURSERY-preterm trial that is evaluating the efficacy, safety,
pharmacokinetics (PK) and immunogenicity of suptavumab in infants born at a gestational age of 35 weeks or
less who are younger than 6 months. We expect to report topline data from this trial in the second half of 2017.
FASINUMAB
Nerve growth factor–targeting antibody being evaluated for novel,
non-opioid approach to certain chronic pain conditions.
In 2016, we announced a global collaboration to develop and commercialize fasinumab with Teva, a leading
global pharmaceutical company with expertise in pain therapeutics. Under a previously announced collaboration
agreement with Regeneron, Mitsubishi Tanabe Pharma Corporation (MTPC) has exclusive development and
commercial rights to fasinumab in Japan, Korea, and nine other Asian countries. We believe both Teva and
MTPC will be strong partners in potentially bringing fasinumab to the market and those patients in need.
We launched a large Phase 3 clinical program studying fasinumab for pain due to osteoarthritis (OA) in 2016
and continue to enroll patients. The FDA placed our Phase 2 trial in chronic lower back pain (CLBP) on hold
in the fourth quarter of 2016, following the observation of a case of rapidly progressing OA in a patient who
was receiving high-dose fasinumab and had a history of advanced OA of the knee. This event prompted
an unplanned interim analysis of the study, which had completed 70% of its targeted enrollment and
showed clear evidence of efficacy and improvement in pain scores for all dosing groups. Following
communications with the FDA, we plan to continue development of fasinumab in CLBP without
advanced OA. In collaboration with Teva, we expect to initiate a Phase 3 trial in 2017.
“An RSV infection can be serious and
very frightening for parents of infants
and young children — we’re evaluating
a therapeutic candidate to see if it has
the potential to prevent these
infections before they start.”
— Leah Lipsich, PhD, Vice President,
Strategic Program Direction
80%
of people with OA
report some degree
of movement
limitation2
OA affects
more than
30 MILLION
adults in
the U.S.1
Back pain is the
MOST COMMON
type of pain among
adults in the U.S.3*
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*Includes low back pain, severe headache or migraine and neck pain. < MENU >< MENU > A D D I T I O N A L
P I P E L I N E P R O G R A M S
O U R G R E AT E ST D I S C O V E R I E S
H AV E Y E T TO B E D E F I N E D
2 0 1 6 A N N U A L R E P O R T
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< MENU >< MENU > IMMUNO-ONCOLOGY
Our portfolio in this rapidly developing field grew in 2016, through
both new product candidates and new indications for existing
candidates, supported by our ongoing collaboration with Sanofi.
Our growing clinical-stage immuno-oncology pipeline now includes three antibodies: a PD-1
inhibitor, a CD20xCD3 bi-specific antibody, and an antibody to LAG3.
In 2016, we presented Phase 1 data from our PD-1 program, which helped us determine the
therapeutic dose for our ongoing, potentially pivotal Phase 2 trial in cutaneous squamous cell
carcinoma. This study is currently enrolling patients. In 2017, we plan to initiate a Phase 3 study
in non-small cell lung cancer, as well as a potentially pivotal study in basal cell carcinoma.
We also presented interim data from our CD20xCD3 bi-specific program in 2016. The CD20xCD3
antibody is currently in clinical trials both as a monotherapy and as a combination therapy with
our PD-1 antibody.
We are also conducting studies of REGN3767, our antibody to LAG3, both as a monotherapy
and as a combination therapy with our PD-1 antibody. A number of additional immuno-oncology
antibodies are expected to enter the clinic in 2017 and 2018, and we continue to pursue business
development opportunities with novel immuno-oncology approaches that have potential to be
combined with antibodies.
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< MENU >< MENU >
RARE DISEASES
We are expanding our research into rare diseases, where serious unmet
medical needs provide the opportunity to deliver on our mission of
turning science into life-changing medicine.
Our most clinically advanced rare disease antibody, evinacumab, an antibody to Angptl-3, is in clinical
development for the treatment of homozygous familial hypercholesterolemia (HoFH), which is the most severe form
of hypercholesterolemia. Patients with this disease are at a significantly higher risk of serious cardiac events,
including heart attack and stroke. In the first half of 2016, we presented positive interim data from a Phase 2
proof-of-concept study of evinacumab in patients with HoFH.
We also entered REGN2477, our antibody to Activin A, into clinical development for the treatment of fibroplasia
ossificans progressiva (FOP). FOP is a progressive, severely disabling, and ultimately fatal disease in which muscles,
ligaments, tendons, and other connective tissues are transformed into bone. We entered the drug into a Phase 1
study in healthy volunteers in 2016, and expect to move into a Phase 2 trial in 2017. We also initiated a Phase 1 study
of REGN2477 in combination with REGN1033, our antibody to GDF8, in 2016. REGN2477 has been granted orphan
drug designation status by the FDA.
In pre-clinical development we have a number of indications and programs identified, including transthyretin-related
amyloidosis (TTR), juvenile X-Linked retinoschisis, and a C5 complement inhibitor for the treatment of paroxysmal
nocturnal hemoglobinuria (PNH). We are working to advance these programs further in 2017.
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< MENU >< MENU > RAPID RESPONSE + INFECTIOUS DISEASE
Regeneron’s rapid response capabilities leverage our core
VelociSuite® technologies to significantly compress the time
required for discovery and pre-clinical validation of potential
treatments for emerging infectious diseases.
In 2016, work continued on our antibodies to the Ebola virus (REGN3470-3471-3479), where we began
a Phase 1 study in healthy volunteers in the first half of 2016, and the antibody was granted orphan
designation status by the FDA. This program is in development with the Biomedical Advanced
Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services.
In pre-clinical development, we also have antibodies to Middle Eastern respiratory virus (MERS) and
the Zika virus.
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< MENU >< MENU > REGENERON GENETICS CENTER
The Regeneron Genetics Center (RGC) is one of the world’s largest
genetic sequencing initiatives, providing important insights into target
identification and clinical development.
The Regeneron Genetics Center (RGC) is a leader in human genetics research. Our RGC scientists have
sequenced more than 150,000 consented individuals, entered into more than 30 academic collaborations, and
have continuously supported our clinical development efforts. We expect these efforts to help us discover new
targets, indications and biomarkers that could better predict drug response, and help de-risk the process of
bringing new medicines into the clinic. We ended 2016 with two simultaneous publications in Science, one of
which provided the first overall description of the Geisinger-Regeneron Genetics Center (RGC) collaboration
known as DiscovEHR, and the other demonstrated the underdiagnosis and undertreatment of familial
hypercholesterolemia (FH) through pairing genetic variants causing FH with their de-identified medical histories.
In March 2017, we announced a major new RGC initiative with UK Biobank and GSK, in which we will be
sequencing 500,000 individuals in the UK Biobank’s health resource. We expect new and important
publications and continued RGC progress in 2017.
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< MENU >< MENU > G R OWT H
B E A N E N G I N E O F I N V E N T I O N
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< MENU >< MENU > GROWTH
Be an engine of invention.
In 2016, we continued to grow, adding both employees and other important assets.
As a result of this transaction, we have obtained an option to buy the facility at the
Our manufacturing facilities in Rensselaer and Raheen both grew — in Rensselaer
end of the five-year lease term and are poised to benefit from immediate cash
we expanded our product manufacturing operations, and in Raheen we continued
savings and increased flexibility for future growth. Finally, we welcomed our 5,000th
construction and hired new employees for the site. We also expanded our
Regeneron employee in 2016. Each employee helps us continually deliver on our
headquarters, purchasing an office building near our Tarrytown facility, and in early
mission to help patients with serious diseases, and reminds us that our people are
2017, we completed new lease financing for our Tarrytown corporate headquarters.
what make Regeneron great.
REVENUE
$4.860 bn
$4.104 bn
$2.820 bn
FULL-TIME EMPLOYEES
5,400*
4,300
18 %
increase
2,925
26 %
increase
R&D INVESTMENT†
$2.052 bn
$1.621 bn
$1.271 bn
27%
increase
2014
2015
2016
2014
2015
2016
2014
2015
2016
*700 hold a PhD and/or
MD or PharmD degree.
†Generally Accepted Accounting
Principles R&D Expenses
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< MENU >< MENU > C I T I Z E N S H I P
M A K I N G A D I F F E R E N C E
B E YO N D O U R LA B S
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< MENU >< MENU > FOCUSED ON CREATING A BETTER TOMORROW
In addition to our dedication to patients and the development of life-transforming
medicines, we are committed across the organization to our four pillars of citizenship:
FOSTERING
the future of
scientific innovation
CULTIVATING
sustainable
communities
SUPPORTING
patient
communities
NURTURING
our high-engagement
high-integrity culture
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< MENU >< MENU > FOSTERING THE FUTURE OF SCIENTIFIC INNOVATION
We believe in future scientists’ power to advance societal progress, solve
our most pressing global challenges, and create a healthier tomorrow.
REGENERON SCIENCE TALENT SEARCH
In 2016, Regeneron became the new sponsor of the Science Talent Search (STS), a program of
the Society for Science & the Public, and our nation’s most prestigious science and math
competition for high school seniors. This 76-year-old program was previously sponsored by
Westinghouse and then by Intel. We made a 10-year, $100-million commitment, and nearly
doubled the competition’s overall award distribution to $3.1 million annually. We are committed
to expanding and diversifying the Science Technology Engineering and Math (STEM) talent pool,
and have consequently earmarked $30 million for Society programs aiming to increase access
to STEM education and resources for underrepresented populations.
In addition to the Regeneron STS, we focus our
STEM education efforts across three areas of impact:
WESTINGHOUSE (1942-1998)
INTEL (1998-2016)
ATTRACTING EXCELLENCE
WIDENING THE POOL
AMPLIFYING A MOVEMENT
Progress thrives when
the brightest minds go into
science. We support these
sharp young students by
Recruiting a more diverse STEM workforce
As a company founded with the
starts with awareness and equity. We focus
goal of transforming lives through
on capacity-building programs that bridge
science, we are committed to
access to quality science education and
promoting the important role of
funding programs such as the
address systemic change in science
science in our society. We are
Regeneron-Westchester
instruction. The BioBus, STEM Teaching
sharing our deep commitment to
Science and Engineering Fair,
Fellowship and Science News in High
science education and leading a
Regeneron Prize for Creative
Schools are just a few of the ways we drive
movement to drive greater
Innovation and high school
deeper interest in science, support
collective action across our industry,
research mentorship programs.
scientific literacy, and facilitate discovery.
communities, and country.
2,190
hours of teacher
development
4,000
high school subscriptions
to Science News
298
Regeneron interns
~1,700
Regeneron STS entrants
4,062
hours of science
instruction aboard the
BioBus (made possible
by Regeneron funding)
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< MENU >< MENU > CULTIVATING SUSTAINABLE COMMUNITIES
We proudly expand on our mission to improve human life with our efforts to strengthen our
communities through environmental and social action.
COMMUNITY INVOLVEMENT
ENVIRONMENTAL SUSTAINABILITY
At Regeneron, volunteering is an essential part of the employee experience.
We empower our people to give back and create meaningful change in our
communities through Regeneron In the Community, our company volunteer
As we continue to grow, environmental stewardship and responsible growth remain
at our core. In 2013, we set five-year targets in four major focus areas to
measure and monitor our environmental progress. With just two years remaining,
program. Not only do our employees donate their time, talent and leadership to
we are on track to meet or exceed each of these goals. With our evolving global
help tackle some of our communities’ most pressing problems, but their
collaborations and new product development efforts, we remain committed to
involvement also inspires communal action.
monitoring and reducing the environmental impact of our business.
1,263
volunteers
5,697
hours
650
organizations
supported,
including our
Matching Gifts Program
91%
of employees feel good
about the ways we contribute
to the community
— Great Places to Work® Survey
PROGRESS ON FIVE-YEAR GOALS, 2013-2016:
CARBON*
Reduced our greenhouse
gas emissions per
employee by 31%,
exceeding our expanded
2018 goal of 30%
WASTE
68% of our waste
avoids the landfill,
moving toward our
2018 goal of 90%
ELECTRICITY*
Reduced our
consumption per
employee by 2%,
moving toward our
2018 goal of 10%
HAZARDOUS
CHEMICAL WASTE
At 53% reduction per
lab employee, we are
just short of our 2018
goal of 60%
*Carbon and Electricity baselines are reported based on the original Carbon Disclosure Project (CDP)
reporting year; 2013 information noted above corresponds to June 2013 — May 2014 reporting year.
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< MENU >< MENU > SUPPORTING PATIENT COMMUNITIES
Regeneron is committed to supporting patients with serious diseases
and ensuring that patients are able to access the medicines they need.
BRINGING ATTENTION TO A DEBILITATING DISEASE
The Understand AD national initiative aims to increase awareness and understanding of atopic dermatitis (AD), in
partnership with the National Eczema Association (NEA) and the Dermatology Nurses’ Association (DNA). The
most common form of eczema, AD is a chronic inflammatory disease with symptoms often appearing as a rash
on the skin. The initiative offers a glimpse into the daily struggle of life with AD and connects people to
helpful resources such as the NEA.
EDUCATION & AWARENESS FOR CHOLESTEROL MANAGEMENT
In 2016, Regeneron and Sanofi committed to support the American Heart Association’s cholesterol
education program, Check.Change.Control.Cholesterol, which aims to drive millions of Americans to
better cholesterol management. The three-year program will engage patients, caregivers and healthcare
practitioners, and provide valuable educational resources to communities across the country.
PARTNERING TO FIGHT A RARE DISEASE
Fibrodysplasia ossificans progressiva (FOP) is an exceedingly rare disease in which bone forms in the
muscle and connective tissue. Over time, people living with FOP gradually lose the ability to move and even
breathe as their rib cage loses flexibility. When Regeneron discovered that the protein Activin-A played a role
in triggering FOP, we made it a priority to reach out to the small but strong FOP community to understand their
daily struggles and treatment expectations. Since then, organizations such as the International Fibrodysplasia
Ossificans Progressiva Association (IFOPA) and the National Organization for Rare Disorders (NORD) have been
integral to informing the development of our investigational candidate REGN2477 and to helping us keep patient
needs front and center in our efforts. We’ve also given back to the FOP community with grants and by sharing our
genetically modified FOP mouse model with other scientists to advance basic and translational research. Through these
mutually supportive relationships, we have come together with the FOP community to fight this devastating disease.
OUR MEDICINES:
ENSURING ACCESS
AND EDUCATION
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< MENU >< MENU > NURTURING OUR HIGH-ENGAGEMENT, HIGH-INTEGRITY CULTURE
Creating a one-of-a-kind culture of collaboration and holding ourselves
to the highest ethical standards are essential to our company vision.
We believe in the power of original thinking. As a company built on breakthrough ideas, we foster
collaboration, curiosity, openness, and inspiration from within — and we do it with an unwavering
commitment to ethics. Each of us plays an active role in transforming people’s lives through our work,
and we pursue this goal with passion and vigor, never losing focus on integrity. Regeneron’s people
make us who we are, and we are truly more than a company — we’re a community.
93% of employees say
– Great Places to Work® Survey
“I’m proud to tell others I work here”
“Our culture is rooted in doing the right thing, even when it may not
be easy. In the long run, acting ethically and with integrity is
essential to the safety of our patients and to our business success.”
— Leonard S. Schleifer, MD, PhD, President and CEO
#1
Biopharma Employer,
Science
3RD
Most Innovative Company,
Forbes
3RD CONSECUTIVE YEAR
100 Best Companies to Work For,
Fortune
WORLD’S BEST
World’s Best CEOs,
Barron’s
R+D
Team of the Year,
Scrip
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< MENU >< MENU > FORWARD-LOOKING STATEMENTS
This Annual Report includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc.
(“Regeneron” or the “Company”), and actual events or results may differ materially from these forward-looking statements. Words such as “anticipate,” “expect,” “intend,” “plan,”
“believe,” “seek,” “estimate,” variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements
contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the nature, timing, and possible success and therapeutic
applications of Regeneron’s products, product candidates, and research and clinical programs now underway or planned, including without limitation EYLEA® (aflibercept) Injection,
PRALUENT® (alirocumab) Injection, DUPIXENT® (dupilumab) Injection, KEVZARA® (sarilumab) Injection, fasinumab, suptavumab (REGN2222), REGN2810 (antibody to programmed
cell death protein 1), Regeneron’s earlier-stage product candidates, Regeneron’s immuno-oncology program, and the use of human genetics in Regeneron’s research process; the
extent to which the results from Regeneron’s research programs or preclinical testing may lead to advancement of product candidates to clinical trials or therapeutic applications;
unforeseen safety issues resulting from the administration of products and product candidates in patients, including serious complications or side effects in connection with the use
of Regeneron’s product candidates in clinical trials; the likelihood and timing of possible regulatory approval and commercial launch of Regeneron’s late-stage product candidates
and new indications for marketed products, including without limitation EYLEA, PRALUENT, DUPIXENT, KEVZARA, fasinumab, suptavumab, and REGN2810; risks associated with
intellectual property of other parties and pending or future litigation relating thereto, including without limitation the patent litigation relating to Praluent, the permanent injunction
granted by the United States District Court for the District of Delaware that, if upheld on appeal, would prohibit Regeneron and Sanofi from marketing, selling, or commercially
manufacturing Praluent in the United States, the outcome of any appeals regarding such injunction, the ultimate outcome of such litigation, and the impact any of the foregoing may
have on Regeneron’s business, prospects, operating results, and financial condition; the likelihood and timing of achieving any of the anticipated milestones described in this Annual
Report; ongoing regulatory obligations and oversight impacting Regeneron’s marketed products (such as EYLEA, PRALUENT, and DUPIXENT), research and clinical programs, and
business, including those relating to patient privacy; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron’s ability to
continue to develop or commercialize Regeneron’s products and product candidates; competing drugs and product candidates that may be superior to Regeneron’s products and
product candidates; uncertainty of market acceptance and commercial success of Regeneron’s products and product candidates; the ability of Regeneron to manufacture and
manage supply chains for multiple products and product candidates; the ability of Regeneron’s collaborators, suppliers, or other third parties to perform filling, finishing, packaging,
labelling, distribution, and other steps related to Regeneron’s products and product candidates; coverage and reimbursement determinations by third-party payers, including
Medicare and Medicaid; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its sales or other financial
projections or guidance and changes to the assumptions underlying those projections or guidance; and the potential for any license or collaboration agreement, including
Regeneron’s agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), to be cancelled or terminated without
any further product success. A more complete description of these and other material risks can be found in Regeneron’s filings with the U.S. Securities and Exchange Commission,
including its Form 10-K for the fiscal year ended December 31, 2016, including in the section thereof captioned “Item 1A. Risk Factors.” Any forward-looking statements are made
based on management’s current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not
undertake any obligation to update publicly any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information,
future events, or otherwise.
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< MENU >< MENU > CORPORATE INFORMATION
Common Stock and Related Matters
Our Common Stock is traded on The NASDAQ Global Select Market under the symbol “REGN.” Our Class A Stock is not publicly quoted or traded.
The following table sets forth, for the periods indicated, the range of high and low sales prices for the Common Stock as reported by The NASDAQ Global Select Market.
2014
First Quarter
Second Quarter
Third Quarter
Fourth Quarter
HIGH
$352.49
$320.00
$369.31
$437.64
LOW
$262.97
$269.50
$285.06
$320.06
2015
First Quarter
Second Quarter
Third Quarter
Fourth Quarter
HIGH
$495.50
$544.00
$605.93
$592.59
LOW
$393.00
$433.47
$435.52
$448.10
2016
First Quarter
Second Quarter
Third Quarter
Fourth Quarter
HIGH
$532.91
$433.93
$443.99
$452.96
LOW
$348.96
$329.09
$348.43
$325.35
As of April 13, 2017, there were 193 shareholders of record of our Common Stock and 18 shareholders of record of our Class A Stock. The closing sales price for the
Common Stock on that date was $370.37.
We have never paid cash dividends and do not anticipate paying any in the foreseeable future.
SEC Form 10-K
A copy of our 2016 Annual Report on Form 10-K filed with the Securities and Exchange
Commission (which accompanies and forms part of this 2016 Annual Report to Shareholders)
is available without charge from the Regeneron Investor Relations Department.
2017 Annual Shareholder Meeting
The 2017 Annual Shareholder Meeting will be held on Friday,
June 9, 2017, at 10:30 a.m. at the Westchester Marriott Hotel,
670 White Plains Road, Tarrytown, New York 10591.
Shareholders’ Inquiries
Inquiries relating to stock transfer or lost certificates and notices of changes of address should be directed to our Transfer Agent, American Stock Transfer & Trust Co.,
6201 15th Avenue, Brooklyn, New York 11219, (800) 937-5449, . General information regarding the Company, recent press releases and SEC
filings are available on our website at or can be obtained by contacting our Investor Relations Department at (914) 847-7741.
Corporate Office
777 Old Saw Mill River Road
Tarrytown, New York 10591-6707
(914) 847-7400
Transfer Agent and Registrar
American Stock Transfer & Trust Co.
6201 15th Avenue
Brooklyn, New York 11219
Independent Registered Public Accounting Firm
PricewaterhouseCoopers LLP
REGENERON®, Science to Medicine® and the following are registered trademarks of Regeneron Pharmaceuticals, Inc.: ARCALYST®, EYLEA®, VelociGene®, and VelocImmune®.
Praluent®, Dupixent®, and Kevzara® are registered trademarks of Sanofi.
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< MENU >< MENU >
REFERENCES
1. Osteoarthritis Fact Sheet. CDC Website. Available at: . Accessed March 30, 2017.
2. Semanik P, Chang RW, Dunlop DD. PMR. 2012;4(50):S37–S44.
3. National Center for Health Statistics. Health, United States, 2015. Hyattsville, MD, 2016.
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