mRNA-1944 successfully encoded for functional
antibody (CHKV-24) in humans at all dose levels tested (0.1, 0.3
and 0.6 mg/kg)
Antibody level predicted to protect against
chikungunya infection achieved within hours; projected to be
maintained for at least 16 weeks at the middle and high doses
No significant adverse events were observed at
the low and middle doses; infusion-related adverse events were
observed at the high dose, which resolved spontaneously without
treatment
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 positive data in the first analysis of
safety and activity in its Phase 1 study evaluating escalating
doses of mRNA-1944 administered via intravenous infusion in healthy
adults. mRNA-1944 encodes for an antibody (CHKV-24) with activity
against chikungunya virus. At all three dose levels, the
administration of mRNA-1944 led to detectable levels of CHKV-24
antibody in all participants, ranging from 1 µg/mL to 14 µg/mL.
These results mark the first systemic mRNA therapeutic to show
production of a secreted protein in humans.
mRNA-1944 is being developed with financial support from the
Defense Advanced Research Projects Agency (DARPA), an agency of the
U.S. Department of Defense. mRNA-1944 is the first development
candidate from the Company’s systemic therapeutics modality to
start clinical testing and utilizes the same lipid nanoparticle
(LNP) formulation as the Company’s rare disease program for
methylmalonic acidemia (mRNA-3704).
A total of 22 healthy adults have been enrolled in the study to
date. The initial analysis evaluated the safety and pharmacology of
intravenous administration of mRNA-1944 at three dose levels of 0.1
mg/kg (n=6), 0.3 mg/kg (n=6) and 0.6 mg/kg (n=4); six participants
received placebo.
Administration of mRNA-1944 resulted in dose-related increases
in CHKV-24 antibody levels, with average Cmax antibody levels of
2.0, 7.9 and 10.2 ug/mL at the low, middle and high doses,
respectively. At all doses, all participants exceeded the levels of
antibody expected to be protective against chikungunya infection
(> 1 µg/mL) following a single dose, with the middle and high
doses projected to maintain antibody levels above protective levels
for at least 16 weeks. All participants also showed circulating
neutralizing antibody activity against chikungunya virus
replication in an NT50 assay, demonstrating that mRNA-1944 resulted
in the production of fully functional protein in vivo.
All participants in the study received antihistamine
premedication. No participants received corticosteroids either as
premedication or treatment.
None of the participants treated with mRNA-1944 at the low (0.1
mg/kg) or middle (0.3 mg/kg) doses experienced significant adverse
events (AEs). Three of the four participants at the high (0.6
mg/kg) dose had infusion-related AEs, with the highest grade by
subject being Grade 1 (n=1), Grade 2 (n=1) and Grade 3 (n=1). The
Grade 3 AEs were tachycardia and an elevated white blood cell
count. The same participant experienced Grade 2 AEs of nausea,
emesis, fever and inverted T waves on a routine EKG (without
associated cardiac symptoms and which later resolved). The fourth
participant at the high dose had no related adverse events. There
were no meaningful changes in liver or kidney laboratory results.
There have been no serious AEs in the study. All AEs were transient
and resolved spontaneously without treatment.
“These Phase 1 data represent a significant scientific
breakthrough: this study shows for the first time the ability to
generate therapeutic levels of a complex protein in humans through
systemic administration of an mRNA, essentially instructing the
body to make its own medicines,” said Tal Zaks, M.D., Ph.D., chief
medical officer at Moderna. “The findings not only show the
potential of mRNA-1944 to protect against chikungunya infection at
a well-tolerated dose, but also the ability of our platform to
translate therapeutically relevant pharmacology from preclinical
species to humans.”
This is an interim analysis of an ongoing study. At this time,
the Company has not enrolled the last two participants at the 0.6
mg/kg dose. The Company is evaluating further exploration of the
safety and pharmacology of mRNA-1944, which may include repeat
dosing or dosing in combination with commonly used steroid
premedications to prevent infusion-related reactions.
CHKV-24, the antibody encoded by mRNA-1944, was isolated from B
cells of a patient with potent immunity against chikungunya
infection by scientists at Vanderbilt University Medical Center.
mRNA-1944 is composed of two mRNAs that encode respectively for the
heavy and light chains of CHKV-24 that are formulated within
Moderna’s proprietary LNP technology for systemic intravenous
injection.
“Protection against infectious diseases like chikungunya is
urgently needed around the world. While we are often able to
identify protective antibodies to emerging infections, a major
challenge is the ability to rapidly scale such discoveries into
humans,” said James Crowe Jr., M.D., director of the Vanderbilt
Vaccine Center. “These exciting data demonstrate a new way to
address infectious diseases that uses mRNA to make antibodies in
humans, establishing a powerful technology that could be deployable
in a pandemic setting.”
“DARPA has been advancing nucleic-acid-based technologies for
infectious disease for several years, and the results of this
clinical trial validate that approach," said Dr. Amy Jenkins, the
DARPA program manager supporting the research. "The researchers
have demonstrated that it is feasible to use mRNA sequences to
produce and scale a highly potent antibody response against an
infectious disease target. DARPA is encouraged by the prospects of
creating a new, platform-based prophylactic and therapeutic
approach that might better protect civilians and service members
alike against the relentless threat of pandemic disease.”
DARPA’s financial support of mRNA-1944 is part the Agency’s
ADEPT: PROTECT (Autonomous Diagnostics to Enable Prevention and
Therapeutics: Prophylactic Options to Environmental and Contagious
Threats) initiative. The goal is to develop platform technologies
that can be deployed safely and rapidly to provide the U.S.
population with near-immediate protection against emerging
infectious diseases and engineered biological weapons, even in
cases when the pathogen or infectious agent is unknown. For more
information about DARPA, visit
http://www.darpa.mil/about-us/about-darpa.
“These data represent another critical milestone for the
validation of Moderna’s mRNA platform in humans,” said Stéphane
Bancel, Moderna’s chief executive officer. “This is the fifth
modality for which we have shown translation from preclinical
research to humans and the first demonstration of mRNA as a
systemic therapeutic capable of creating high levels of protein at
a well-tolerated dose. We believe these results further validate
our approach, the scientific platform we have built and the
potential of mRNA to become a new class of medicines. We look
forward to learning from the ongoing Phase 1/2 study of mRNA-3704
for methylmalonic acidemia, the first of our rare disease programs
to enter the clinic, as it utilizes the same technology
demonstrated in this chikungunya study.”
About the Study
The randomized, placebo-controlled Phase 1 study is designed to
evaluate the safety and tolerability of up to four escalating doses
(0.1, 0.3, 0.6 and 1 mg/kg) of mRNA-1944 administered via
intravenous infusion to healthy adults. Secondary objectives are to
determine the pharmacology of mRNA-1944 and to evaluate whether the
antibodies produced neutralize chikungunya virus in vitro, thereby
confirming the potential for passive immunization of individuals
via the production of functional circulating antibody. Passive
immunity provides transient but rapid protection against an
infectious disease and is particularly important when immediate
protection is needed, such as in a pandemic setting.
More information about the study can be found at
ClinicalTrials.gov. Full Phase 1 data will be presented at a future
medical meeting.
About mRNA-1944
mRNA-1944 encodes a fully human IgG antibody originally isolated
from B cells of a patient with a prior history of potent immunity
against chikungunya infection. It is composed of two mRNAs that
encode the heavy and light chains of this anti-chikungunya antibody
within Moderna’s proprietary lipid nanoparticle (LNP) technology.
Preclinical data published in Science Immunology have shown
mRNA-1944 was well-tolerated, resulted in linear dose-dependent
protein expression and provided 100% protection in animal
models.
About Chikungunya
Chikungunya is a mosquito-borne virus that poses a significant
public health problem in tropical and subtropical regions. The
disease is characterized by an acute onset of fever, rash, muscle
pain and sometimes debilitating pain in multiple joints. There are
no vaccines approved to prevent chikungunya infection or disease,
and effective mosquito control is challenging. Currently, people
infected with chikungunya are treated with non-steroidal
anti-inflammatory drugs to relieve some symptoms. In addition to a
systemic secreted antibody that could provide passive immunity,
Moderna is also exploring using mRNA to encode viral antigens as a
prophylactic vaccine against the chikungunya virus (mRNA-1388).
R&D Day Webcast Today
Moderna also announced positive interim Phase 1 data for
mRNA-1647 (cytomegalovirus or CMV vaccine) today. A summary of data
from both the antibody against chikungunya virus and CMV vaccine
programs will be presented at the Company’s annual R&D Day,
being held today in New York City beginning at 8:30 a.m. ET. A live
webcast will be available under “Events & Presentations” in the
Investors section of the Moderna website at
https://investors.modernatx.com. A replay of the webcast will be
archived on Moderna’s website for 30 days following the
presentation.
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 have a therapeutic or preventive
benefit with 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 and 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: predicted levels to protect against chikungunya
infection; projected protection against chikungunya infection for
at least sixteen weeks at the 0.3 and 0.6 mg/kg doses of mRNA-1944;
Moderna's evaluation of whether to further explore the safety and
pharmacology of mRNA-1944, which may include repeat dosing or
dosing in combination with commonly used steroid pre-medications to
prevent infusion reactions; the Phase 1 results for mRNA-1944 as an
indicator of the potential of mRNA-1944 to protect against
chikungunya virus infection and the ability of Moderna’s platform
to translate therapeutically relevant pharmacology from preclinical
species to humans; and the potential of mRNA-based vaccines as
powerful technology that could be deployable in a pandemic setting.
In some cases, forward-looking statements can be identified by
terminology such as “will,” “may,” “should,” “could,” “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:
whether the Phase 1 results for mRNA-1944 will be predictive of any
future clinical studies for mRNA-1944 or other development
candidates with the same or similar LNP formulation, including
mRNA-3704 for methylmalonic acidemia; whether mRNA-1944 will be
unsafe or intolerable during further clinical studies; the fact
that clinical development is lengthy and uncertain, especially for
a new class of medicines such as mRNA, and therefore Moderna’s
clinical programs or development candidates may be delayed,
terminated, or may never advance; 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 risks and uncertainties described
under the heading “Risk Factors” in Moderna’s most recent Annual
Report on Form 10-K filed with the U.S. Securities and Exchange
Commission (SEC) and in subsequent filings made by Moderna with the
SEC, which are available on the SEC’s website 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20190912005422/en/
Moderna Contacts:
Media: Colleen Hussey Senior Manager, Corporate
Communications 203-470-5620 Colleen.Hussey@modernatx.com
Dan Budwick Founder, 1AB Media 973-271-6085
dan@1abmedia.com
Investors: Lavina Talukdar Head of Investor
Relations 617-209-5834
Lavina.Talukdar@modernatx.com
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