INVESTORS & MEDIA
News Release
Publication Highlights Regeneron's Costimulatory Bispecific Antibodies, an Emerging Class of Cancer Immunotherapy
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
"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
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
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
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
As part of a global collaboration agreement, Regeneron and
About Regeneron
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
This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of
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).
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Media Relations Daren Kwok Tel: +1 (914) 598-7590
Investor Relations Justin Holko Tel: +1 (914) 847-7786
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