Published in Science Translational Medicine, study demonstrates mRNAs
encoding IL23, IL36γ and OX40L can activate immunologically “cold” tumor
microenvironments
Moderna’s mRNA-2752 (the “Triplet”) now in an ongoing Phase 1 study
as a monotherapyand in combination with checkpoint inhibitors in
patients with advanced or metastatic solid tumors or lymphoma
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 30, 2019--
Moderna, Inc., (Nasdaq: MRNA) a clinical stage biotechnology company
pioneering messenger RNA (mRNA) therapeutics and vaccines to create a
new generation of transformative medicines for patients, today announced
the publication of pre-clinical data that shows the therapeutic
potential of mRNA-2752, an investigational mRNA immuno-oncology therapy
that encodes a novel combination of three immunomodulators designed to
activate the immune system to recognize and eradicate tumors that are
resistant to checkpoint inhibitors.
The study, published in the scientific journal Science Translational
Medicine, found that the local delivery of mRNA encoding the
secreted cytokines IL23 and IL36γ and the membrane-bound T-cell
co-stimulator OX40L, induced a broad immune response promoting tumor
regression in both injected lesions and distant un-injected tumors in
mice. When combined with checkpoint inhibitors, mRNA-2752 boosted
complete response rates in immunosuppressive and in immunologically
barren tumor models that are otherwise unresponsive to checkpoint
inhibitors.
“These pre-clinical data are important because they show how we can
utilize multiple mRNAs encoding for immune modulators in a single
therapy to activate a robust, systemic immune response against cancer in
immunosuppressive and in so-called ‘cold’ tumors that are resistant to
checkpoint inhibitors,” said Joshua Frederick, Ph.D., Moderna’s head of
oncology research. “We were pleased to discover the cooperation of the
components encoded by this mRNA mixture in engaging innate immune cells,
innate-like lymphocytes and effector T cells, ultimately resulting in
complete tumor regressions and protective immunity in our mouse models
of cancer.”
“Unlike conventional biologics, we believe mRNA therapies can uniquely
alter the tumor microenvironment to make cancers more susceptible to
checkpoint inhibitors via a paracrine effect by producing high, local
therapeutic concentrations of membrane-bound and secreted
immunomodulators, both of which are believed to play a critical role in
the immune response against cancer,” said Tal Zaks, M.D., Ph.D., chief
medical officer at Moderna. “This important study highlights why we are
excited to have started our Phase 1 clinical study for mRNA-2752, as we
believe the combination of these immune signals has the potential to
help patients for whom checkpoint inhibitors alone have been
insufficient.”
The study showed that in a MC38-R mouse cancer model that is considered
immunosuppressive and found to be unresponsive to checkpoint inhibitor
immunotherapy, a single dose of the Triplet administered intratumorally
led to complete responses (defined as the absence of all detectable
cancer). After multiple injections in the immunosuppressive tumor model,
complete response rates increased to a majority of the treated animals.
In addition, a single dose of the Triplet led to near-complete control
of both injected tumors and distal untreated tumors. The addition of
anti-PD-L1, anti-PD-1 or anti-CTLA-4 checkpoint inhibitors to a single
dose of the Triplet improved complete response rates over either mRNA or
antibody treatment alone.
Moderna has advanced mRNA-2752 into a Phase 1 study (ClinicalTrials.gov
Identifier: NCT03739931) and has started dosing patients with
advanced or metastatic solid tumor malignancies or lymphoma. The open
label, multi-center study is evaluating the safety and tolerability of
mRNA-2752 as a monotherapy or in combination with either AstraZeneca’s
durvalumab (anti-PD-L1 antibody) or tremelimumab (anti-CTLA-4 antibody)
and will assess anti-tumor activity, protein expression in tumors and
pharmacokinetics and exploratory endpoints that include assessment of
immunological response.
A link to the publication, Durable anti-cancer immunity from
intratumoral administration of IL-23, IL-36γ and OX40L mRNAs (S. L.
Hewitt, et. al.), can be found here.
About Moderna
Moderna is advancing messenger RNA (mRNA) science to create a new class
of transformative medicines for patients. mRNA medicines are designed to
direct the body’s cells to produce intracellular, membrane or secreted
proteins that can have a therapeutic or preventive benefit and have the
potential to address a broad spectrum of diseases. Moderna’s platform
builds on continuous advances in basic and applied mRNA science,
delivery technology and manufacturing, providing the Company the
capability to pursue in parallel a robust pipeline of new development
candidates. Moderna is developing therapeutics and vaccines for
infectious diseases, immuno-oncology, rare diseases and cardiovascular
diseases, independently and with strategic collaborators.
Headquartered in Cambridge, Mass., Moderna currently has strategic
alliances for development programs with AstraZeneca, Plc. and Merck,
Inc., as well as the Defense Advanced Research Projects Agency (DARPA),
an agency of the U.S. Department of Defense; the Biomedical Advanced
Research and Development Authority (BARDA), a division of the Office of
the Assistant Secretary for Preparedness and Response (ASPR) within the
U.S. Department of Health and Human Services (HHS). Moderna has been
ranked in the top ten of Science’s list of top biopharma industry
employers for the past four years. To learn more, visit www.modernatx.com.
Special 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, but not limited to, statements concerning: the belief
that mRNA therapies can uniquely alter the tumor microenvironment to
make cancers more susceptible to checkpoint inhibitors and play a
critical role in the immune response against cancer, and the potential
for mRNAs encoding for immune modulators to ignite a robust, systemic
immune response against cancer in immunosuppressive and tumors resistant
to checkpoint inhibitors. In some cases, forward-looking statements can
be identified by terminology such as “will,” “may,” “should,” “expects,”
“intends,” “plans,” “aims,” “anticipates,” “believes,” “estimates,”
“predicts,” “potential,” “continue,” or the negative of these terms or
other comparable terminology, although not all forward-looking
statements contain these words. The forward-looking statements in this
press release are neither promises nor guarantees, and you should not
place undue reliance on these forward-looking statements because they
involve known and unknown risks, uncertainties and other factors, many
of which are beyond Moderna’s control and which could cause actual
results to differ materially from those expressed or implied by these
forward-looking statements. These risks, uncertainties and other factors
include, among others: preclinical and clinical development is lengthy
and uncertain, especially for a new class of medicines such as mRNA, and
therefore our preclinical programs or development candidates may be
delayed, terminated, or may never advance to or in the clinic; no mRNA
drug has been approved in this new potential class of medicines, and may
never be approved; mRNA drug development has substantial clinical
development and regulatory risks due to the novel and unprecedented
nature of this new class of medicines; and those described in Moderna’s
Prospectus filed with the U.S. Securities and Exchange Commission (SEC)
on December 7, 2018 and in subsequent filings made by Moderna with
the SEC, which are available on the SEC's website at www.sec.gov.
Except as required by law, Moderna disclaims any intention or
responsibility for updating or revising any forward-looking statements
in this press release in the event of new information, future
developments or otherwise. These forward-looking statements are based on
Moderna’s current expectations and speak only as of the date hereof.
View source version on businesswire.com: https://www.businesswire.com/news/home/20190130005631/en/
Source: Moderna, Inc.
Moderna Contacts:
Investors:
Lorence Kim
Chief
Financial Officer
617-209-5849
Lorence.kim@modernatx.com
Media:
Jason Glashow
Head, Corporate Communications
617-674-5648
Jason.glashow@modernatx.com