TARRYTOWN, N.Y., Jan.
8, 2020 /PRNewswire/ --
Preclinical results published in Science Translational
Medicine show that adding CD28 costimulatory bispecifics
to CD3 bispecifics led to synergistic anti-tumor activity without
inducing cytokine storm
First costimulatory bispecific clinical trial initiated for
prostate cancer; multiple additional costimulatory bispecifics to
enter the clinic this year
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today
announced a publication featured on the cover of Science
Translational Medicine describing the potential of a new class
of cancer immunotherapy known as "costimulatory bispecific
antibodies." Regeneron and others have previously shown that CD3
bispecifics can result in meaningful clinical responses in
previously untreatable cancer settings. The results
published today show that adding a novel class of CD28
costimulatory bispecifics to Regeneron's CD3 bispecifics can lead
to synergistic anti-tumor activity in multiple cell culture and
animal model experiments, without inducing systemic cytokine
release (cytokine storm).
"This novel class of CD28 costimulatory bispecifics are key to
our strategy of developing a broad oncology portfolio – based on
rational combinations to efficiently engage the immune system – to
address a broad range of cancers, including those that are not
responsive to currently available immunotherapy," said George D. Yancopoulos, M.D., Ph.D., Co-Founder,
President and Chief Scientific Officer at Regeneron. "We have dosed
prostate cancer patients with our first CD28 costimulatory
bispecific, REGN5678, in combination with Libtayo®
(cemiplimab), and we plan to advance additional CD28 costimulatory
bispecifics into the clinic for other cancers this year, including
in combinations with CD3 bispecifics."
The rationale for combining CD3 and CD28 bispecific antibodies
is based on the fact that T-cells require two signals to fully
activate. The first "recognition" signal occurs when the T-cell
identifies a foreign or mutated protein (antigen), via its T-cell
receptor/CD3 complex. However, the T-cell is only fully activated
for cancer cell killing after it receives a second "costimulatory"
signal, most powerfully via the CD28 costimulatory receptor.
Regeneron's CD3 and CD28 investigational bispecifics are designed
to bridge T-cells to cancer cells and simultaneously provide
activation through these two signals. The publication demonstrates
that this combination approach can drive markedly enhanced T-cell
killing of prostate and ovarian tumors in sophisticated
genetically-humanized animal models.
"Cancer researchers have long known that CD28-targeted therapies
have the ability to supercharge T-cells against cancer, but little
progress was made in harnessing this powerful opportunity given
historic safety findings with CD28 superagonists. Our goal was to
engage the CD28 pathway in a completely novel and targeted way to
avoid the issues with generalized CD28 activation," said
Dimitris Skokos, Ph.D., Senior
Director, Cancer Immunology Research at Regeneron.
"Costimulatory bispecifics offered an innovative solution that
allowed us to design antibodies with molecular controls to use CD28
to boost T-cell activation only in the presence of cancer cells and
after the 'recognition' signal had been received. To see this
design work preclinically is gratifying, and we are excited to see
if these results will translate in human clinical trials."
CD28 superagonists were investigational CD28-targeted monoclonal
antibodies. In a Phase 1 trial conducted in 2006 by another
company, a CD28 superagonist overactivated T-cells throughout the
bodies of healthy volunteers. This caused life-threatening levels
of cytokine release syndrome (known as cytokine storm), leading to
multiple organ failure. As a result, clinical research into
CD28-based treatments was largely stopped.
This led Regeneron to carefully select CD28 costimulatory
bispecific antibody candidates that would only activate T-cells
when they were bridged to cancer cells and after having received
the first "recognition" signal. Regeneron also tested the safety of
its CD28 costimulatory bispecifics in several animal models and
showed they did not induce cytokine storm when administered as
monotherapy or in combination. These findings support the further
investigation of CD28 costimulatory bispecifics in combination with
other treatments.
"Checkpoint inhibitors and CAR-T cell therapy have transformed
cancer treatment over the past decade, but many patients still
don't respond to these immunotherapies. That's why it's exciting to
see Regeneron's CD28 costimulatory bispecifics emerge as promising
future off-the-shelf solutions," said Jill
O'Donnell-Tormey, Ph.D., Chief Executive Officer and
Director of Scientific Affairs at the Cancer Research Institute.
"The data published in Science Translational
Medicine show that Regeneron is helping to expand the
boundaries of what may be possible with immunotherapy."
Among the investigational medicines studied in the paper were
two CD28 costimulatory bispecifics (PSMAxCD28 and MUC16xCD28) and
two CD3 bispecifics (CD20xCD3 and MUC16xCD3).
About the Regeneron Bispecific Antibody Platform
All
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 pharmacokinetics.
There are six Regeneron investigational bispecific antibodies
currently in ongoing clinical trials for multiple blood cancers and
solid tumors. These bispecifics fall into three categories:
- 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 (REGN1979) for non-Hodgkin B-cell lymphomas;
- Two distinct BCMAxCD3s (REGN5458 and REGN5459) for multiple
myeloma;
- 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 PD-1
inhibitors and/or CD3 bispecifics. Investigational candidates
include:
-
- PSMAxCD28 (REGN5678) in combination with Libtayo for prostate
cancer.
- 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 include:
-
- 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.
Regulatory Status of Oncology Programs
The bispecifics
mentioned in this release are currently under clinical development,
and their safety and efficacy have not been evaluated by any
regulatory authority.
Libtayo in combination with REGN5678 is currently under clinical
development for prostate cancer, and its safety and efficacy have
not been evaluated by any regulatory authority for this use.
Libtayo is currently approved in the U.S. for the treatment of
patients with metastatic cutaneous squamous cell carcinoma (CSCC)
or locally advanced CSCC who are not candidates for curative
surgery or curative radiation, and in other countries for similar
indications. In the U.S., the generic name for Libtayo 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.
As part of a global collaboration agreement, Regeneron and
Sanofi are jointly developing Libtayo, as well as Regeneron's
BCMAxCD3 and MUC16xCD3 bispecific programs.
About Regeneron
Regeneron (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, infectious diseases,
pain and rare diseases.
Regeneron is accelerating and improving the traditional drug
development process through our proprietary
VelociSuite® technologies, such as
VelocImmune®, which uses a unique
genetically-humanized mouse 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
Media
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 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 REGN5678 (a
PSMAxCD28 costimulatory bispecific antibody) being studied in
combination with Libtayo® (cemiplimab) for the treatment
of prostate cancer, as well as REGN1979 (a CD20xCD3 bispecific
antibody), REGN5458 (a BCMAxCD3 bispecific antibody), REGN5459 (a
BCMAxCD3 bispecific antibody), REGN4018 (a MUC16xCD3 bispecific
antibody), REGN5093 (a METxMET bispecific antibody), and
Regeneron's earlier-stage product candidates (such as Regeneron's
other costimulatory bispecific antibodies discussed in this press
release); 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 (such as Regeneron's
bispecific antibodies and costimulatory bispecific antibodies
discussed in this press release) in clinical trials; the likelihood
and timing of achieving any anticipated development milestones
discussed or referenced in this press release; the extent to which
the results from the research and development programs conducted by
Regeneron or its collaborators may be replicated in other studies
and lead to therapeutic applications; the likelihood, timing, and
scope of possible regulatory approval and commercial launch of
Regeneron's late-stage product candidates and new indications for
marketed products; ongoing regulatory obligations and oversight
impacting Regeneron's marketed products, 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 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 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; the availability and extent of reimbursement of
the Company's products 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; 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 fiscal year ended
December 31, 2018 and its Form 10-Q
for the quarterly period ended September 30,
2019. 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).
Contacts:
|
Media Relations
Daren Kwok
Tel: +1 (914)
598-7590
Daren.Kwok@regeneron.com
Investor
Relations
Justin
Holko
Tel: +1 (914)
847-7786
Justin.Holko@regeneron.com
|
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SOURCE Regeneron Pharmaceuticals, Inc.