TARRYTOWN, N.Y., June
24, 2020 /PRNewswire/ --
First publication to demonstrate benefit of combining CD28
costimulatory bispecifics with anti-PD-1 therapy, overcoming
resistance to anti-PD-1 monotherapy and endowing long-term T-cell
memory in multiple preclinical cancer models
An earlier publication highlighted benefit of combining CD28
costimulatory bispecifics with CD3 bispecifics for prostate and
Regeneron anticipates having three CD28 costimulatory
bispecifics in the clinic by the end of 2020
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN)
announced new scientific findings have been highlighted today in a
Science Translational Medicine cover publication. The
preclinical research in animal models found that combining
Regeneron's novel class of CD28 costimulatory bispecific antibodies
with the anti-PD-1 therapy Libtayo® (cemiplimab)
markedly enhanced anti-tumor activity in multiple cancer models,
led to long-term T-cell memory against the tumors, and was not
associated with systemic cytokine release.
CD28 offers a well-known and powerful pathway to fully activate
T-cells. Regeneron's CD28 costimulatory bispecifics are designed to
bridge T-cells to cancers cells, thereby selectively activating
T-cells at the tumor site via the CD28 pathway and synergistically
enhancing the anti-tumor activity of anti-PD-1 therapies and/or CD3
bispecifics. The potential of this therapeutic approach has now
been featured on two Science Translational
Medicine covers, including a prior publication in
January 2020 that highlighted the
benefit of combining CD28 costimulatory bispecifics with CD3
bispecifics for prostate and ovarian cancers.
As detailed in the new Science Translational Medicine
paper, combining CD28 costimulatory bispecifics with Libtayo for
prostate or other epithelial cancers led to synergistic increases
in tumor-killing by T-cells in animal models and cell cultures.
Most importantly, the combination overcame the resistance of both
cancers to anti-PD-1 monotherapy. In addition, T-cells acquired
long-term memory of the cancers after treatment, as demonstrated by
genetic analyses of T-cells and successfully re-challenging mice
with tumors following initial treatment with the combination. This
long-term T-cell immune memory was limited when Libtayo was
"Preclinical research shows that when combined with other
immunotherapies, our novel CD28 costimulatory bispecifics can
trigger targeted tumor killing in cancers that are generally
resistant to current monotherapy regimens," said Dimitris Skokos, Ph.D., Senior Director, Cancer
Immunology Research at Regeneron. "Adding CD28 costimulatory
bispecifics to Libtayo activated T-cells against tumors more deeply
and durably than Libtayo treatment alone. In addition, we did not
observe systemic cytokine release syndrome in our animal studies.
Systemic cytokine release has historically been a challenge with
Regeneron's decision to develop novel CD28 costimulatory
bispecifics was based on the knowledge that T-cells' ability to
kill cancer is controlled by numerous stimulatory and inhibitory
signals. T-cells must receive at least two different stimulatory
signals to become fully activated for cancer killing. The first
stimulatory signal is received when T-cells "recognize" foreign
proteins on the cancer cell via the T-cell receptor/CD3 complex.
This enables T-cells to optimally respond to the second
"costimulatory" signal, which occurs most powerfully when T-cell
CD28 costimulatory receptors interact with antigen presenting
In 2020, Regeneron plans to enroll patients in clinical trials
investigating three different CD28 costimulatory bispecific
candidates. Regeneron's first costimulatory bispecific trial,
investigating the combination of PSMAxCD28 (REGN5678) and Libtayo
for prostate cancer, is underway and has treated patients in
several dose-escalation cohorts. Before the end of the year,
Regeneron plans to begin a clinical trial with EGFRxCD28 (REGN7075)
and Libtayo in solid tumors that may include non-small cell lung
cancer, head and neck squamous cell carcinoma, cutaneous squamous
cell carcinoma and colorectal cancer. Another clinical trial will
investigate MUC16xCD28 (REGN5668) in combination with either
Libtayo or MUC16xCD3 (REGN4018) for ovarian cancer.
"Our novel CD28 costimulatory bispecifics are designed to be
customized to target a diverse range of antigens, potentially
enhancing treatment for multiple cancers," said Israel Lowy, M.D., Ph.D., Senior Vice President,
Translational and Clinical Sciences, Oncology, at Regeneron. "Given
these impressive preclinical findings, we are advancing multiple
CD28 costimulatory bispecifics into the clinic. We hope to share
initial data from our prostate cancer trial investigating REGN5678
in combination with Libtayo in 2021."
About the Regeneron Bispecific Antibody Platform
of Regeneron's bispecifics are designed to closely resemble natural
human antibodies and bind to two different targets. They are
derived from a next-generation version of Regeneron's proprietary
VelocImmune technology and created using the company's
Veloci-Bi® platform. These allow for the
creation of bispecifics with no linkers or artificial sequences.
Additionally, Regeneron bispecifics are manufactured using similar
approaches used for human antibody medicines, with similar
There are eight Regeneron investigational bispecific antibodies
for multiple blood cancers and solid tumors that will be in
clinical trials by the end of the year. These bispecifics fall into
- CD3 bispecifics are designed to bridge T-cells and
tumor cells. At the tumor site, they activate T-cells via their CD3
receptors and promote T-cell killing of the cancer cells.
Investigational candidates include:
- CD20xCD3 (odronextamab) for non-Hodgkin B-cell lymphomas;
- Two distinct BCMAxCD3s (REGN5458 and REGN5459) for multiple
- MUC16xCD3 (REGN4018) for ovarian cancer.
- CD28 costimulatory bispecifics are also designed to
bridge T-cells and tumor cells. At the tumor site, they costimulate
T-cells via their CD28 receptors and may synergize with anti-PD-1
therapies and/or CD3 bispecifics. Investigational candidates
- PSMAxCD28 (REGN5678) in combination with Libtayo for prostate
- MUC16xCD28 (REGN5668) in combination with Libtayo for ovarian
- EGFRxCD28 (REGN7075) in combination with Libtayo for solid
- Tumor-targeted bispecifics are designed
to target proteins only on the cancer cell. In this way, they
may affect various signaling pathways to hamper the cancer cells'
ability to survive and proliferate. Investigational candidates
- METxMET(REGN5093) for non-small cell lung cancer that is driven
by MET mutations and/or amplifications. REGN5093 targets two
different parts of the MET receptor on cancer cells to degrade the
receptor and block its ability to trigger cell proliferation.
The bispecifics mentioned in this release are currently under
clinical development, and their safety and efficacy have not been
evaluated by any regulatory authority. As part of a global
collaboration agreement, Regeneron and Sanofi are jointly
developing the BCMAxCD3 and MUC16xCD3 bispecific programs.
Libtayo is a fully-human monoclonal
antibody targeting the immune checkpoint receptor PD-1 on T-cells.
By binding to PD-1, Libtayo has been shown to block cancer cells
from using the PD-1 pathway to suppress T-cell activation.
Libtayo is the first and only immunotherapy approved in the
U.S., EU, and other countries for adults with metastatic cutaneous
squamous cell carcinoma (CSCC) or locally advanced CSCC who are not
candidates for curative surgery or curative radiation. In the U.S.,
the generic name for Libtayo in its approved indication is
cemiplimab-rwlc, with rwlc as the suffix designated in accordance
with Nonproprietary Naming of Biological Products Guidance for
Industry issued by the U.S. Food and Drug Administration.
The extensive clinical program for Libtayo is focused on
difficult-to-treat cancers. In skin cancer, this includes a pivotal
trial in advanced basal cell carcinoma and additional trials in
adjuvant and neoadjuvant CSCC. Libtayo is also being investigated
in pivotal Phase 3 trials in non-small cell lung cancer and
cervical cancer, as well as in trials combining Libtayo with novel
therapeutic approaches for both solid tumors and blood cancers.
These potential uses – either as monotherapy or in combination with
bispecifics – are investigational, and their safety and efficacy
have not been evaluated by any regulatory authority.
Libtayo is being jointly developed by Regeneron and Sanofi under
a global collaboration agreement. Libtayo was invented using
Regeneron's proprietary VelocImmune® technology
that utilizes a proprietary genetically-engineered mouse platform
endowed with a genetically-humanized immune system to produce
optimized fully-human antibodies. VelocImmune technology has
been used to create multiple antibodies including
Dupixent® (dupilumab), Praluent® (alirocumab)
and Kevzara® (sarilumab), which are approved in multiple
countries around the world. Regeneron previously used these
technologies to rapidly develop a treatment for Ebola virus
infection, which is currently under review by the FDA, and is now
being used in efforts to create preventative and therapeutic
medicines for COVID-19.
IMPORTANT SAFETY INFORMATION AND INDICATION FOR U.S.
What is Libtayo?
Libtayo is a prescription
medicine used to treat people with a type of skin cancer called
cutaneous squamous cell carcinoma (CSCC) that has spread or cannot
be cured by surgery or radiation.
It is not known if Libtayo is safe and effective in
What is the most important information I should know about
Libtayo is a medicine that may treat a type of skin
cancer by working with your immune system. Libtayo can cause your
immune system to attack normal organs and tissues in any area of
your body and can affect the way they work. These problems can
sometimes become severe or life-threatening and can lead to death.
These problems may happen anytime during treatment or even after
your treatment has ended.
Call or see your healthcare provider right away if you
develop any symptoms of the following problems or these symptoms
- Lung problems (pneumonitis). Signs and
symptoms of pneumonitis may include new or worsening cough,
shortness of breath, and chest pain.
- Intestinal problems (colitis) that can lead to tears or
holes in your intestine. Signs and symptoms of
colitis may include diarrhea (loose stools) or more frequent bowel
movements than usual; stools that are black, tarry, sticky or that
have blood or mucus; and severe stomach-area (abdomen) pain or
- Liver problems (hepatitis). Signs and
symptoms of hepatitis may include yellowing of your skin or the
whites of your eyes, severe nausea or vomiting, pain on the right
side of your stomach area (abdomen), drowsiness, dark urine (tea
colored), bleeding or bruising more easily than normal, and feeling
less hungry than usual.
- Hormone gland problems (especially the adrenal glands,
pituitary, thyroid and pancreas). Signs and symptoms that your
hormone glands are not working properly may include headaches that
will not go away or unusual headaches, rapid heartbeat, increased
sweating, extreme tiredness, weight gain or weight loss, dizziness
or fainting, feeling more hungry or thirsty than usual, hair loss,
feeling cold, constipation, deeper voice, very low blood pressure,
urinating more often than usual, nausea or vomiting, stomach-area
(abdomen) pain, and changes in mood or behavior, such as decreased
sex drive, irritability, or forgetfulness.
- Kidney problems, including nephritis and kidney failure.
Signs of these problems may include decrease in your amount of
urine, blood in your urine, swelling in your ankles, and loss of
- Skin problems. Signs of these problems may include rash,
itching, skin blistering, and painful sores or ulcers in the mouth,
nose, throat, or genital area.
- Problems in other organs. Signs of these problems may
include headache, tiredness or weakness, sleepiness, changes in
heartbeat (such as beating fast, seeming to skip a beat, or a
pounding sensation), confusion, fever, muscle weakness, balance
problems, nausea, vomiting, stiff neck, memory problems, seizures
(encephalitis), swollen lymph nodes, rash or tender lumps on skin,
cough, shortness of breath, vision changes, or eye pain
(sarcoidosis), seeing or hearing things that are not there
(hallucinations), severe muscle weakness, low red blood cells
(anemia), bruises on the skin or bleeding, and changes in
- Rejection of a transplanted organ. Your doctor should
tell you what signs and symptoms you should report and monitor you,
depending on the type of organ transplant that you have had.
- Infusion (IV) reactions that can sometimes be severe
and life-threatening. Signs of these problems may include
chills or shaking, itching or rash, flushing, shortness of breath
or wheezing, dizziness, fever, feeling of passing out, back or neck
pain, and facial swelling.
Getting medical treatment right away may help keep these
problems from becoming more serious.
Your healthcare provider will check you for these problems
during your treatment with Libtayo. Your healthcare provider may
treat you with corticosteroid or hormone replacement medicines.
Your healthcare provider may delay or completely stop treatment if
you have severe side effects.
Before you receive Libtayo, tell your healthcare
provider about all your medical conditions, including if
- have immune system problems such as Crohn's disease, ulcerative
colitis, or lupus;
- have had an organ transplant;
- have lung or breathing problems;
- have liver or kidney problems;
- have diabetes;
- are pregnant or plan to become pregnant; Libtayo can harm your
Females who are able to become
- Your healthcare provider will give you a pregnancy test before
you start treatment.
- You should use an effective method of birth control during your
treatment and for at least 4 months after your last dose of
Libtayo. Talk with your healthcare provider about birth control
methods that you can use during this time.
- Tell your healthcare provider right away if you become pregnant
or think you may be pregnant during treatment with Libtayo.
- are breastfeeding or plan to breastfeed. It is not known if
Libtayo passes into your breast milk. Do not breastfeed during
treatment and for at least 4 months after the last dose of
Tell your healthcare provider about all the medicines you
take, including prescription and
over-the-counter medicines, vitamins, and herbal supplements.
The most common side effects of Libtayo include tiredness, rash,
and diarrhea. These are not all the possible side effects of
Libtayo. Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088. You may also
report side effects to Regeneron Pharmaceuticals and Sanofi at
For more information, please see full Prescribing
Information, including Medication Guide.
About Regeneron Pharmaceuticals, Inc.
(NASDAQ: REGN) is a leading biotechnology company that invents
life-transforming medicines for people with serious diseases.
Founded and led for over 30 years by physician-scientists, our
unique ability to repeatedly and consistently translate science
into medicine has led to seven FDA-approved treatments and numerous
product candidates in development, all of which were homegrown in
our laboratories. Our medicines and pipeline are designed to help
patients with eye diseases, allergic and inflammatory diseases,
cancer, cardiovascular and metabolic diseases, pain, infectious
diseases and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our proprietary
VelociSuite® technologies, such as
VelocImmune, which uses unique genetically-humanized mice to
produce optimized fully-human antibodies and bispecific antibodies,
and through ambitious research initiatives such as the Regeneron
Genetics Center, which is conducting one of the largest genetics
sequencing efforts in the world.
For additional information about the company, please visit
www.regeneron.com or follow @Regeneron on Twitter.
Regeneron Forward-Looking Statements and Use of Digital
This press release 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 impact of
SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on
Regeneron's business and its employees, collaborators, suppliers,
and other third parties on which Regeneron relies, Regeneron's and
its collaborators' ability to continue to conduct research and
clinical programs, Regeneron's ability to manage its supply chain,
net product sales of products marketed by Regeneron and/or its
collaborators (collectively, "Regeneron's Products"), and the
global economy; the nature, timing, and possible success and
therapeutic applications of Regeneron's Products and Regeneron's
product candidates and research and clinical programs now underway
or planned, including without limitation Libtayo®
(cemiplimab-rwlc), REGN5678 (a PSMAxCD28 costimulatory bispecific
antibody being studied in combination with Libtayo), and
Regeneron's other investigational bispecific antibodies discussed
in this press release; uncertainty of market acceptance and
commercial success of Regeneron's Products and product candidates
and the impact of studies (whether conducted by Regeneron or others
and whether mandated or voluntary) on the commercial success of
Regeneron's Products and product candidates; the likelihood,
timing, and scope of possible regulatory approval and commercial
launch of Regeneron's product candidates and new indications for
Regeneron's Products, such as Libtayo for the treatment
of basal cell carcinoma, adjuvant and
neoadjuvant cutaneous squamous cell carcinoma, non-small
cell lung cancer, and cervical cancer (as well as in
combination with novel therapeutic approaches for both solid tumors
and blood cancers, as applicable); unforeseen safety issues
resulting from the administration of Regeneron's Products (such as
Libtayo) and product candidates (such as Regeneron's
investigational bispecific antibodies discussed in this press
release) in patients, including serious complications or side
effects in connection with the use of Regeneron's Products and
product candidates in clinical trials; 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; ongoing
regulatory obligations and oversight impacting Regeneron's
Products, research and clinical programs, and business, including
those relating to patient privacy; the availability and extent of
reimbursement of Regeneron's Products (such as Libtayo) from
third-party payers, including private payer healthcare and
insurance programs, health maintenance organizations, pharmacy
benefit management companies, and government programs such as
Medicare and Medicaid; coverage and reimbursement determinations by
such payers and new policies and procedures adopted by such payers;
competing drugs and product candidates that may be superior to
Regeneron's Products and product candidates; the extent to which
the results from the research and development programs conducted by
Regeneron and/or its collaborators may lead to advancement
of product candidates to clinical trials or therapeutic
applications; 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 (as applicable) to perform manufacturing, filling,
finishing, packaging, labeling, distribution, and other steps
related to Regeneron's Products and product candidates;
unanticipated expenses; the costs of developing, producing, and
selling products; the ability of Regeneron to meet any of its
financial projections or guidance and changes to the assumptions
underlying those projections or guidance; 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; and
risks associated with intellectual property of other parties and
pending or future litigation relating thereto (including without
limitation the patent litigation and other related proceedings
relating to Dupixent® (dupilumab) and
Praluent® (alirocumab)), other litigation and other
proceedings and government investigations relating to the Company
and/or its operations, the ultimate outcome of any such proceedings
and investigations, and the impact any of the foregoing may have on
Regeneron's business, prospects, operating results, and financial
condition. 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 year ended
December 31, 2019 and its Form 10-Q
for the quarterly period ended March
31, 2020. 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.
Regeneron uses its media and investor relations website and
social media outlets to publish important information about the
Company, including information that may be deemed material to
investors. Financial and other information about Regeneron is
routinely posted and is accessible on Regeneron's media and
investor relations website (http://newsroom.regeneron.com) and its
Twitter feed (http://twitter.com/regeneron).
Tel: +1 (914) 598-7590
Tel: +1 (914) 847-5443
SOURCE Regeneron Pharmaceuticals, Inc.