Publication in Cell Demonstrates Moderna’s Zika mRNA Vaccine Prevents In Utero Transmission of Zika Virus in Mice, Protects

  Publication in Cell Demonstrates Moderna’s Zika mRNA Vaccine Prevents In
  Utero Transmission of Zika Virus in Mice, Protects Against Zika-Related
  Congenital Damage

     --First Study to Show Protection from Zika Virus during Pregnancy--

Business Wire

CAMBRIDGE, Mass. -- July 13, 2017

Moderna Therapeutics, a clinical stage biotechnology company that is
pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new
generation of transformative medicines for patients, today announced new data
demonstrating that its Zika mRNA vaccine prevented Zika virus transmission
from pregnant mice to their fetuses. The findings, which were published today
in Cell, also demonstrated that Moderna’s Zika mRNA vaccine protected the
placenta and fetus from Zika virus-induced injury.

In the study, Moderna’s Zika mRNA vaccine was evaluated in addition to a
live-attenuated vaccine candidate developed by the University of Texas Medical
Branch (UTMB). The research was conducted by scientists from the National
Institute of Allergy and Infectious Diseases (NIAID), part of the National
Institutes of Health (NIH), and Washington University School of Medicine and
UTMB.

Children born to mothers infected with Zika can develop microcephaly, a severe
disease characterized by abnormally small heads and severe neurologic
disabilities. Zika infection is also strongly associated with Guillain-Barré
Syndrome (GBS), an autoimmune disease that attacks the peripheral nervous
system, leading to rapidly progressive and potentially life-threatening muscle
weakness. GBS can lead to death caused by respiratory arrest if a patient is
not ventilated. There are no treatment options or approved vaccines for the
Zika virus or congenital Zika syndrome. This is the first study to establish
vaccine protection from the Zika virus during pregnancy.

“We’re highly encouraged by these preclinical findings demonstrating the
ability of our mRNA vaccine to provide robust prevention of maternal
transmission of Zika and protection against congenital defects,” said Giuseppe
Ciaramella, Ph.D., Chief Scientific Officer of Moderna’s infectious
disease-focused venture, Valera, and an author on the paper. “The threat to
pregnant women and women who may be planning on getting pregnant remains a
serious concern in certain regions of the U.S. and abroad. We look forward to
further study of our Zika mRNA vaccine to prevent Zika infections, with the
ultimate goal of improving outcomes for mothers, their children, and families
in the U.S. and globally.”

About the Zika mRNA Vaccine Findings

The study was designed to evaluate protection of fetuses during pregnancy in
mice. Researchers gave a cohort of non-pregnant female mice (n=20) a 10 µg
intramuscular (IM) injection of the Zika mRNA vaccine followed by a boost at
28 days. An additional cohort of non-pregnant mice (n=20) received placebo
injections at the same time points. At day 49, the mice that received the mRNA
vaccine produced high levels of neutralizing antibodies against Zika virus in
their blood compared to placebo.

Both cohorts were then mated and infected with the Zika virus. After seven
days, most fetuses in the vaccinated mice showed no evidence of having Zika
virus transmitted to them from their pregnant mothers compared to placebo. In
addition, vaccinated mice had significantly lower levels of Zika virus RNA in
maternal, placental and fetal tissues compared to placebo-injected mice,
resulting in protection against damage to the placenta and fetus.
Specifically,

  * Placenta and fetal heads from the placebo cohort showed high levels of
    viral RNA levels while corresponding tissues in mice immunized with
    Moderna’s Zika mRNA vaccine showed marked virological protection
    (placenta, 200-fold mean reduction; fetal head, 13,000-fold mean
    reduction).
  * 10 of 19 (53%) placentas and 11 of 19 (58%) fetal heads from mice who
    received Moderna’s Zika mRNA vaccine had viral RNA levels at the limit of
    detection of the assay, suggesting virtually complete protection, and the
    remainder had substantially lower levels than those detected in samples
    from mice in the placebo cohort.
  * Only three of 19 (16%) of placentas and 0 fetal heads from maternal mice
    immunized with Moderna’s mRNA Zika vaccine were positive for the
    infectious virus compared to 21 of 23 (91%) of placentas and 10 of 23
    (43%) fetal heads from placebo-vaccinated maternal mice.

The researchers repeated the experiment in order to determine the effects on
fetal viability at birth, again comparing maternal mice who were vaccinated
with Moderna’s mRNA vaccine (n=14) and maternal mice who received placebo
(n=14). None of the mice in the placebo group delivered pups at term due to
extensive placental injury and fetal demise. In contrast, 100% of the fetuses
from mice who received Moderna’s mRNA vaccine were born without signs of
damage, and the heads of newborn pups of mothers in this treatment group
showed no measurable levels of viral RNA.

“These are very promising findings and, as the first study to demonstrate
protection from Zika in the pregnancy setting, are an important development in
our efforts to combat Zika virus,” said Michael Diamond, M.D., Ph.D.,
Professor, Departments of Medicine, Molecular Microbiology, Pathology &
Immunology, and Associate Director, Center for Human Immunology and
Immunotherapy Program at Washington University School of Medicine, and a lead
author on the Cell paper. “This type of collaboration, fusing the expertise of
academia, government and industry, will be critical in order to speed
advancement of novel vaccines like the mRNA vaccine and live-attenuated
vaccine involved in this study.”

Moderna’s Zika mRNA vaccine, mRNA-1325, is currently in Phase 1/2 clinical
study in healthy volunteers. The company’s pipeline includes seven additional
mRNA prophylactic vaccines, all of which address infectious diseases for which
there currently are no approved vaccines.

In February 2017, a paper published in Cell demonstrated that Moderna’s mRNA
vaccine protected mice against Zika. In April 2017, Moderna published human
data for its mRNA vaccine technology in Molecular Therapy, which showed that
its first prophylactic vaccine candidate, mRNA-1440 -- an mRNA prophylactic
vaccine against avian H10N8 influenza – induced high levels of immunogenicity
and was safe and well tolerated.

About Moderna’s Zika mRNA Vaccine

Messenger RNA (mRNA) plays a fundamental role in human biology, directing
protein production in cells. When used as a drug, mRNA can direct cells to
produce therapeutic proteins (mRNA therapeutics) to fight disease or antigenic
proteins (mRNA vaccines) to prevent disease.

Moderna’s Zika mRNA vaccine encodes for viral antigenic proteins (Zika virus
prM and E) associated with the Zika virus. The mRNA directs cells to produce
and express the proteins on the cell surface, much like a native infections
would do, but without the ability to cause disease. This is because no other
viral proteins are present to enable the production of an infectious Zika
virus.

As a result, the immune system recognizes the antigenic proteins as foreign to
the body and produces antibodies that have the potential to neutralize the
Zika virus, and prevent infections in the event the vaccinated person is
exposed to the actual virus in the future.

In 2016, Moderna received a funding award of up to $125 million from 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), to accelerate
development of its Zika mRNA vaccine. Moderna’s preclinical work for mRNA-1325
was funded through a grant from the Defense Advanced Research Projects Agency
(DARPA).

About Moderna Therapeutics

Moderna is a clinical stage pioneer of messenger RNA (mRNA) therapeutics and
vaccines, an entirely new drug technology that directs the body’s cells to
produce intracellular or secreted proteins. With its breakthrough platform,
Moderna is developing a new class of mRNA medicines for a wide range of
diseases and conditions, in many cases by addressing currently undruggable
targets. Moderna is developing its innovative mRNA medicines for infectious
diseases, cancer (immuno-oncology), rare diseases, cardiovascular disease and
pulmonary disease, through proprietary development and collaborations with
strategic partners.

Headquartered in Cambridge, Mass., privately held Moderna currently has
strategic agreements with AstraZeneca, Merck, Alexion Pharmaceuticals and
Vertex Pharmaceuticals, 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); and the Bill & Melinda
Gates Foundation. To learn more, visit www.modernatx.com.

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Contact:

Moderna Therapeutics
Media:
Liz Melone, 617-674-5648
liz.melone@modernatx.com
or
Investors:
Lorence Kim, 617-209-5849
Lorence.kim@modernatx.com
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