Oncorus, Inc. (Nasdaq: ONCR), a clinical stage biopharmaceutical
company developing next-generation, systemically active viral
immunotherapies to transform outcomes for cancer patients,
announced today the recent publication of preclinical data
supporting the clinical development of its lead oncolytic Herpes
Simplex Virus (oHSV) clinical candidate, ONCR-177. In the paper,
entitled, “ONCR-177, an Oncolytic HSV-1 Designed to Potently
Activate Systemic Antitumor Immunity” (Haines, et al., 2020),
published online in the journal Cancer Immunology Research,
ONCR-177 demonstrated potent and durable antitumor activity in
multiple immune-competent tumor models. The preclinical findings
demonstrate that the activity of ONCR-177, an intratumorally
administered viral immunotherapy engineered for systemic activity
currently in a Phase 1 study, is driven by Oncorus’ unique
combination of five complementary immunomodulatory transgene
payloads in addition to its retention of γ34.5. A herpes simplex
virus 1 (HSV-1) gene, γ34.5 allows the virus to replicate in the
presence of host antiviral immune responses. ONCR-177’s safety
strategies and their ability to enhance oHSV tolerability without
impeding potency were previously characterized in a paper published
by Oncorus in September 2020 in Molecular Therapy on ONCR-159, the
unarmed version of ONCR-177, (Kennedy et al., 2020) titled, “Design
of an Interferon-Resistant Oncolytic HSV-1 Incorporating Redundant
Safety Modalities for Improved Tolerability.”
“We are pleased to share these encouraging preclinical findings,
which supported our advancement of ONCR-177 into clinical
development last year. These data give important insight into how
our proprietary engineering of ONCR-177 may enable systemic
activity without compromising safety, and position us to advance
our mission to realize the full potential of this therapeutic class
for cancer patients,” said Theodore (Ted) Ashburn, M.D., Ph.D.,
President and Chief Executive Officer at Oncorus. “We believe viral
immunotherapies as a class are a proven modality and represent the
most promising approach in development today to activate multiple
arms of the immune system and improve outcomes for cancer
patients.”
Oncorus is conducting a Phase 1 study to evaluate the safety and
tolerability of ONCR-177 as well as to evaluate preliminary
antitumor activity in patients with solid tumors (NCT04348916) as a
monotherapy and in combination with Merck’s anti-PD-1 therapy,
KEYTRUDA® (pembrolizumab) via a clinical trial collaboration and
supply agreement signed with Merck in July 2020. Oncorus expects to
report initial interim data from the monotherapy dose escalation
part of this trial in the second half of 2021 with addition data
readouts through the second half of 2022.
Christophe Quéva, Ph.D., Oncorus’ Chief Scientific Officer and
Senior Vice President, Research, commented, “We have designed our
proprietary oHSV Platform to safely maximize the impact of viral
immunotherapies to foster the development of a potent systemic
antitumor activity. With our Phase 1 study of ONCR-177 now well
underway, we look forward to the potential of these preclinical
findings translating into improving patient outcomes.”
In addition to ONCR-177, Oncorus plans to nominate a second
intratumorally administered oHSV clinical candidate to specifically
target cancers of the central nervous system, including
glioblastoma multiforme, in the second half of 2021 (ONCR-GBM). In
the first half of 2021, Oncorus plans to nominate intravenously
administered Synthetic Coxsackievirus A21 and Synthetic Seneca
Valley Virus clinical candidates from its Synthetic Virus Platform
for difficult-to-inject tumors such as those of the lung.
Preclinical Data Highlights
Highlights from Oncorus’ preclinical data described in these
papers include:
- The murine version of ONCR-177
(mONCR-171) demonstrated durable complete tumor regressions and
abscopal activity in four syngeneic tumor models: A20, MC38, CT26
and B16F10N1.
- Durable survival was achieved in
both A20 and CT26 models versus the unarmed version of ONCR-177
(i.e., ONCR-159), specifically demonstrating the impact that
ONCR-177’s arming strategy has in driving systemic activity in
these in vivo models of cancer. Re-challenge experiments in long
term responders to mONCR-171 demonstrated that tumor
antigen-specific protective memory responses were achieved.
- The retention of a gene coding for
γ34.5 demonstrated more robust replication in the presence of
interferon-γ versus viruses that do not contain this gene. Of note,
ONCR-159, which also retains γ34.5 expression, demonstrated
statistically significant improvement in an in vivo bi-lateral CT26
model of survival.
- The addition of systemic anti-PD-1
augmented the activity of mONCR-171, particularly for un-injected
tumors, suggesting that utilizing systemic anti-PD-1 immunotherapy
may augment the systemic antitumor effect of ONCR-177.
- Directional viral promoters, CAG and
MND, were shown to elicit strong transgene expression in injected
tumors. Furthermore, the addition of the five complementary
immunomodulatory transgenes and other modifications in ONCR-177
remain potently oncolytic in vitro in cancer cell lines. The
oncolytic activity of ONCR-177 is on par with what has been
reported for talimogene laherparepvec (IMLYGIC®), which is commonly
referred to as “T-VEC”.1
- In vivo biodistribution analyses
suggest that viral DNA and transgene expression were relegated
primarily to the injected tumor. As previously disclosed, no dose
limiting toxicities were observed in the first four patients dosed
with ONCR-177 suggesting that the safety strategies incorporated
into ONCR-177 are working as intended.
About ONCR-177
ONCR-177, Oncorus’ lead viral immunotherapy candidate, is
designed to mount a multidimensional attack on cancer. It induces
immunogenic cancer cell death and ignites innate and adaptive
immunity to drive a lasting and systemic anti-tumor response.
Five Complementary Immunomodulatory Transgene Payloads to
Recruit Multiple Arms of Immune System
ONCR-177 is armed with five complementary transgenes with strong
clinical and preclinical validation, IL-12, FLT3LG, CCL4, anti-PD-1
and anti-CLTA-4, which were selected by Oncorus to comprehensively
drive the Cancer-Immunity Cycle2 at multiple nodes:
- IL-12 is known to activate and expand CD8, CD4 TH1 and natural
killer (NK) cells.
- FLT3LG is well understood to expand
antigen cross-presenting classical dendritic cells, and CCL4 is
known facilitate dendritic and CD8 T cell recruitment.
- ONCR-177’s local expression of
agonists to PD-1 (via a proprietary PD-1 nanobody) and CTLA-4
(using the ipilimumab sequence) is intended to counteract
compensatory upregulation of key immune checkpoints.
γ34.5 Retention to Enable Resistance to Host Antiviral Immune
Responses and Additional Innovations
ONCR-177 also retains a copy of γ34.5 to enable resistance to
host antiviral interferon responses. γ34.5 is known to play a more
central role in inhibition of antiviral response than US11.3
Furthermore, ONCR-177 contains a gB:N/T mutation in a surface
fusion protein shown to broaden tropism beyond Herpesvirus entry
mediator (HVEM) and nectin-1 to include nectins-2, 3 and 4 and
enhance infectivity.4 Lastly, ONCR-177 contains inactivating null
mutations in ICP47 intended to improve antigen presentation.5
Orthogonal Safety Strategies to Enable Selective Attenuation and
Retention of γ34.5
Oncorus’ oHSV platform incorporates two complementary and
proprietary approaches to limit viral replication in normal
tissues. First, Oncorus’ microRNA attenuation strategy leverages
the known differential expression of certain microRNA in tumors
versus normal tissues to allow unencumbered viral replication in
tumor cells, while preventing replication in healthy tissues. This
microRNA attenuation strategy allows ONCR-177 to retain the ability
to express the gene encoding for γ34.5, a feature unique among
oHSV-based therapies such as T-VEC and others in development today.
In addition, ONCR-177 also has engineered proprietary mutations
into UL37 to eliminate the virus’ ability to transport, replicate
and establish latency inside neurons.6
About Oncorus
At Oncorus, we are focused on driving innovation to deliver
next-generation, systemically active viral immunotherapies to
transform outcomes for cancer patients. We are advancing a
portfolio of intratumorally and intravenously administered viral
immunotherapies for multiple indications with significant unmet
needs based on our oncolytic Herpes Simplex Virus (oHSV) Platform
and Synthetic Virus Platform. Designed to deliver next-generation
viral immunotherapy impact, our oHSV Platform improves upon key
characteristics of this therapeutic class to enhance potency
without sacrificing safety, including greater capacity to encode
transgenes to drive systemic immunostimulatory activity, retention
of full replication competency to enable high tumor-killing
potency, and orthogonal safety strategies to restrict viral
activity in tumor cells. Oncorus’ lead oHSV program, ONCR-177, is
designed to be directly administered into a tumor, resulting in
high local concentrations of the therapeutic agent, as well as low
systemic exposure to the therapy, which we believe could
potentially limit systemic toxicities. Please visit us at
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: expectations with respect to
Oncorus’ ability to advance its clinical and
preclinical pipelines, including statements regarding the
clinical development of ONCR-177 and timing and anticipated data
read-outs for the ongoing Phase 1 clinical trial; Oncorus’
expectations regarding upcoming milestones for its other potential
product candidates, including the timing for nomination of clinical
candidates from its two Synthetic Virus Platform development
programs and its second oHSV Platform clinical candidate; and the
therapeutic potential and clinical benefits of Oncorus’ existing
and potential product candidates. 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: the impact of COVID-19 on
Oncorus’ operations and the timing and anticipated results of its
ongoing and planned preclinical studies and clinical trials; the
risk that the preliminary results of preclinical studies or
clinical trials may not be predictive of future results in
connection with future clinical trials; Oncorus’ ability to
successfully demonstrate the safety and efficacy of ONCR-177 and
obtain regulatory approval and that Oncorus’ other preclinical or
clinical programs do not advance or result in approved products on
a timely or cost effective basis or at all; 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’ Quarterly Report on
Form 10-Q for the quarter ended September 30, 2020, which was filed
with the Securities and Exchange Commission on November 12, 2020,
as well as discussions of potential risks, uncertainties, and other
important factors in the other filings that Oncorus makes with the
Securities and Exchange Commission 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. No representations or warranties (expressed or
implied) are made about the accuracy of any such forward-looking
statements.
Investor
Contact:
Alan Lada
Solebury Trout
617-221-8006 alada@soleburytrout.com
|
Media
Contact: Liz
Melone
liz.melone@oncorus.com |
___________________________________________________
1 Moesta, et al, Cancer Research 20172 Chen and Mellman,
Immunity 2013 3 Mulvey et al., J. Virol. 2004 and Peters et al., J.
Virol. 20184 Uchida, J. Virol. 20105 Twumasi-Boateng, Nat. Rev.
Cancer 20186 Richards et al., PLoS Pathog. 2017
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