Oncorus Presents Preclinical Data Supporting ONCR-719, an armed HSV-1 Vector engineered to use the Epidermal Growth Factor Receptor (EGFR/EGFRvIII) for viral entry in Glioblastoma, at the 2022 Society for Neuro-Oncology Annual Meeting
18 Novembre 2022 - 2:00PM
Oncorus, Inc. (Nasdaq: ONCR), a viral immunotherapy company focused
on driving innovation to transform outcomes for cancer patients,
today announced the presentation of preclinical data for ONCR-719
in a poster at the 2022 Society for Neuro-Oncology (SNO) Annual
Meeting, taking place November 17-20, 2022 in Tampa, Florida.
ONCR-719 is a novel, armed oncolytic HSV-1 vector engineered
with targeted entry via EGFR/EGFRvIII and expresses four
immunomodulatory payloads designed to reverse GBM’s
immunosuppressive tumor microenvironment. In addition, ONCR-719 is
derived from a potent HSV-1 isolate to drive oncolysis, is
engineered with fusogenic mutations to enhance viral spread, and
uses Oncorus’ clinically validated microRNA attenuation strategy to
inhibit viral replication in healthy cells.
Highlights from the preclinical poster describing ONCR-719,
previously known as ONCR-GBM, include:
- Minimal expression of HSV-1 virus entry receptor, NECTIN-1, on
human GBM samples suggests targeted oncolytic viruses are required
to effectively treat human GBM tumors.
- ONCR-719 has been engineered to enter tumor cells using either
EGFR/EGFRvIII or NECTIN-1 as an entry receptor, thereby increasing
virus tropism for GBM tumors.
- EGFR-targeting and engineered fusogenic mutations in ONCR-719
enhance virus spread and tumor immunogenicity by driving syncytia
formation in human GBM tumor cell lines.
- ONCR-719 is engineered to include IL-12, an anti-PD-1 nanobody,
15-hydroxyprostaglandin dehydrogenase (HPGD), and a novel
macrophage modulating-Fc enhanced antibody. These payloads confer
enhanced T cell recruitment and activation and target the immune
suppressive macrophages and myeloid cells in the tumor
microenvironment. Multiple payloads or transgenes were screened
using in vivo orthotopic GBM models to identify immune-modulatory
payloads to target the GBM microenvironment.
- Together, EGFR/EGFRvIII targeting, oncolytic potency, and
incorporation of rationally designed payloads within ONCR-719 leads
to enhanced anti-tumor efficacy and complete responses in
preclinical orthotopic GBM models.
- ONCR-719 is engineered for safety in the central nervous system
using multiple CNS-specific microRNA targets, Oncorus’ clinically
proven strategy to limit viral replication in healthy cells. When
injected intracranially in an HSV-1 sensitive mouse, ONCR-719
demonstrates a greater than 50,000-fold tolerability window
compared to the unattenuated strain.
“Oncolytic viruses are well-positioned to treat this aggressive
form of brain cancer. We are excited to share ONCR-719 as a
cutting-edge preclinical candidate that is engineered to improve
outcomes and can stimulate a productive and durable anti-tumor
immune response across multiple mouse models following a single
intratumoral injection,” said Theodore (Ted) Ashburn, M.D., Ph.D.,
President and Chief Executive Officer of Oncorus. “Most notably,
we’ve enabled the virus to use EGFR for entry, which is expressed
at high levels in GBM. Underscoring the importance of this advance
is our data showing that the canonical entry receptor for HSV,
NECTIN-1, is only minimally expressed in GBM cells, which arguably
makes using EGFR for entry an essential capability for such an
agent. By utilizing our clinically proven microRNA attenuation
strategy, ONCR-719 is engineered to protect healthy brain tissue
while replicating at its full potential in tumor cells.”
“GBM is the most common type of primary brain tumor in adults;
it’s a devastating disease that has a great unmet need with a
5-year overall survival of approximately 7 percent,” said Tooba
Cheema, Ph.D., Senior Director, Translational Medicine and ONCR-719
Program Leader at Oncorus. “We engineered ONCR-719 to overcome the
common impediment that this treatment class faces, limited spread
of virus in the highly immunosuppressive GBM tumor
microenvironment. We are pleased with the results demonstrated in
preclinical models and look forward to seeing how our innovations
translate into improved outcomes for GBM patients.”
ONCR-719 is the company’s second candidate from its HSV Platform
and is developed from a clinical isolate of HSV-1 selected for
oncolytic potency across cancer cell lines. Further development of
ONCR-719 is dependent on a strategic partnership or additional
financing.
About Oncorus
At Oncorus, we are focused on driving innovation to deliver
next-generation viral immunotherapies to stimulate the immune
system and transform outcomes for cancer patients. We are advancing
a portfolio of intratumorally (iTu) and intravenously (IV)
administered viral immunotherapies for multiple indications with
significant unmet need based on our Herpes Simplex Virus (HSV) and
self-amplifying viral RNA/LNP Platforms.
Designed as a next-generation viral immunotherapy, our HSV
Platform improves upon key characteristics of this therapeutic
class to enhance systemic activity with immune stimulating
payloads. Our lead HSV program, ONCR-177, currently in the clinic,
is designed to be directly administered into a tumor, resulting in
high local concentrations of therapeutic agent and its five encoded
transgenes, as well as low systemic exposure to the therapy, which
could limit systemic toxicities. Our pioneering self-amplifying
vRNA/LNP Platform, highlighted by our product candidates ONCR-021
and ONCR-788, involves a highly innovative, novel combination of
RNA and LNP-based modalities designed to realize the potential of
RNA medicines for cancer.
Please visit www.oncorus.com to learn more.
Cautionary Note Regarding Forward-Looking
Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, implied and
express statements regarding the utility and potential of Oncorus’
HSV Platform and the engineering of ONCR-719, including its ability
to reverse GBM’s immunosuppressed tumor microenvironment, enhance
viral spread and oncolysis, inhibit viral replication in certain
healthy cells and increase virus tropism for GBM tumors; the
ability of oncolytic viruses to treat aggressive brain cancer;
ONCR-719’s ability to improve patient safety and efficacy outcomes;
and Oncorus’ ability to progress ONCR-719 into the clinic. The
words “may,” “might,” “will,” “could,” “would,” “should,” “expect,”
“plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,”
“seek,” “predict,” “future,” “project,” “potential,” “continue,”
“target” and similar words or expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words. Any forward-looking
statements in this press release are based on management’s current
expectations and beliefs and are subject to a number of risks,
uncertainties and important factors that may cause actual events or
results to differ materially from those expressed or implied by any
forward-looking statements contained in this press release,
including, without limitation, risks associated with: Oncorus’
ability to successfully demonstrate the safety, tolerability and
efficacy of its product candidates and obtain regulatory approval
thereof; the adequacy of Oncorus’ existing capital resources and
availability of financing on commercially reasonable terms;
Oncorus’ ability to obtain the requisite components for its product
candidates manufactured in accordance with regulatory requirements;
the expansion of Oncorus’ in-house manufacturing capabilities; the
impact of COVID-19 on Oncorus’ operations and the timing and
anticipated results of its ongoing and planned clinical trials; the
accuracy of the Oncorus’ estimates regarding expenses, future
revenue, capital requirements and needs for additional financing;
and Oncorus’ ability to obtain, maintain and protect its
intellectual property. These and other risks and uncertainties are
described in greater detail in the section entitled “Risk Factors”
in Oncorus’ Annual Report on Form 10-K for the year ended December
31, 2021, filed with the Securities and Exchange Commission (“SEC”)
on March 9, 2022, and Oncorus’ Quarterly Reports on Form 10-Q for
the quarters ended March 31, 2022, June 30, 2022 and September 30,
2022, filed with the SEC on May 4, 2022, August 4, 2022 and
November 2, 2022, respectively, as well as discussions of potential
risks, uncertainties, and other important factors in the other
filings that Oncorus makes with the SEC from time to time. These
documents are available under the “SEC filings” page of the
Investors section of Oncorus’ website at
http://investors.oncorus.com. Any forward-looking statements
represent Oncorus’ views only as of the date of this press release
and should not be relied upon as representing its views as of any
subsequent date. Oncorus explicitly disclaims any obligation to
update any forward-looking statements, whether as a result of new
information, future events or otherwise, except as required by law.
No representations or warranties (expressed or implied) are made
about the accuracy of any such forward-looking statements.
Oncorus Investor Contact:Stern Investor
Relations Julie SeidelJulie.seidel@sternir.com
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