[January 08, 2018] |
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Moderna Announces an Array of Clinical Advances and Outlines 2018 Priorities; 19 Development Candidates, including 10 Clinical Programs, Highlight Productivity of mRNA Platform
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 high unmet medical needs
in patients, today announced important advances in its mRNA development
pipeline, demonstrating the increasing productivity of its platform,
including its first mRNA program to enter phase 2, new infectious
disease vaccine and oncology programs entered into Phase 1 clinical
studies, and the ongoing expansion of its pipeline with several new
development candidates (DCs). A leader in mRNA science and development,
Moderna continues to make notable progress across its broad, diverse
pipeline, which now includes 19 mRNA drug candidates spanning infectious
diseases, immuno-oncology, rare diseases and cardiovascular diseases.
Moderna's Chief Executive Officer Stéphane Bancel detailed company
strategy and progress today at the 36th Annual J.P. Morgan Healthcare
Conference in San Francisco.
The company today announced several new advances including:
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A Phase 2a study of mRNA AZD8601, a localized mRNA therapeutic
encoding for vascular endothelial growth factor, VEGF-A, being
developed in partnership with AstraZeneca. Information on the clinical
study, including design and target indication, will be detailed in the
coming weeks. Led by AstraZeneca, this will be Moderna's first phase 2
study.
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A new development candidate, mRNA-3927, for a rare disease within the
liver modality. mRNA-3927 directs liver expression of a deficient
enzyme in patients with propionic acidemia (PA), a serious and
potentially life-threatening rare disease, which is part of a family
of disorders known as organic acidemias. There are no approved
therapies or ongoing clinical trials for PA. In September, Moderna
announced its first rare disease DC, mRNA-3704, to treat methylmalonic
acidemia, or MMA, another serious and often deadly organic acidemia.
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The filing of an investigational new drug (IND) application for
mRNA-5671, a KRAS cancer vaccine. KRAS is one of the most frequently
mutated oncogenes in human cancer (approximately 30 percent of all
cases). mRNA-5671 encodes for the four most commonly found KRAS
mutations, which will cover most of the mutations that occur in
non-small cell lung cancer, colorectal cancer and pancreatic cancer.
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The initiation of two phase 1 prophylactic vaccine studies for
mRNA-1647, a cytomegalovirus (CMV) vaccine, and mRNA-1653, a human
metapneumovirus and parainfluenza virus type 3 (HMPV+PIV3) combination
vaccine. CMV is the most common cause of newborn disability and the
most frequent viral disease in transplant recipients, often leading to
transplant failure. mRNA-1647 is made of 6 mRNAs, one coding for the
herpesvirus glycoprotein (gB) antigen and 5 coding for the pentamer.
HMPV and PIV3 are the second and third most common causes,
respectively, of lower respiratory hospitalizations in children,
behind respiratory syncytial virus (RSV). Currently, there are no
approved vaccines for CMV, HMPV or PIV3.
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A new development candidate, mRNA-1944, which directs liver expression
of an antibody that can potentially neutralize chikungunya virus
circulating in the blood. Moderna has a Phase 1 study underway for a
prophylactic vaccine, mRNA-1388, to prevent infection from the
chikungunya virus. An antibody approach would be more desirable in
certain settings, such as in immuno-compromised populations, when
rapid post-exposure treatment or prophylaxis is warranted, or when
protection is needed only for short periods of time. This program is
sponsored by DARPA.
"We are proud of the progress we have made over the past year as we
continue to see real development pipeline momentum and productivity from
our platform, and continue to deliver to the clinic important advances
in mRNA science. We have achieved critical milestones in R&D, having
gone from four clinical programs at the beginning of the year to now
having 10 medicines in human testing, and our intention is to continue
to rapidly advance our pipeline with an array of new development
programs," said Bancel. "2016 was the year of mRNA vaccines in the
clinic. 2017 was the year of several mRNA therapeutics in the clinic. In
2018, we will continue to evolve our pipeline of mRNA therapeutics,
specifically focusing on discovering new rare disease drug candidates,
while remaining committed to advancing new vaccine development
candidates to address serious unmet needs. We also will continue to work
toward a summer 2018 opening and rolling scale-up of our GMP clinical
mRNA manufacturing facility, which is a cornerstone of our long-term
strategy to move multiple development programs simultaneously into and
through phase 1, phase 2, and phase 3 clinical studies."
As of today, nearly 700 subjects have been dosed across Moderna's
internally developed and partnered clinical programs with AstraZeneca
and Merck. Moderna's
full pipeline can be found here.
2018 Strategic Priorities
During today's presentation, Mr. Bancel outlined Moderna's key strategic
priorities for 2018 which include:
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Effective execution of the development pipeline by continuing to
advance programs through clinical study and by moving additional
development programs into the clinic;
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Emphasis on the discovery of new rare disease development candidates
and new prophylactic vaccines to address high unmet medical needs;
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Continued investment in the evolution of the company's mRNA platform,
including exploring new modalities to expand the application of its
technology in new therapeutic areas;
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Completion of construction of the company's 200,000 square foot GMP
mRNA clinical manufacturing facility in Norwood, Mass., with an
anticipated opening in the summer of 2018 and subsequent rolling
scale-up of the facility.
Detailed Q4 2017 Clinical and Development
Program Updates
Moderna's pipeline spans five modalities: prophylactic vaccines,
therapeutic vaccines, intratumoral immuno-oncology therapeutics,
localized therapeutics and liver therapeutics. Following are advances
from across modalities since the company's September business update:
Commercial Prophylactic Vaccines
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Initiation of Phase 1 study of mRNA-1647, a cytomegalovirus (CMV)
vaccine: The Phase 1, placebo-controlled multi-center study of
mRNA-1647 began dosing patients in November 2017, and will assess
safety, tolerability and immunogenicity. [clinicaltrials.gov
listing]. A complex vaccine, mRNA-1647 consists of six mRNAs,
including five proteins (gH, gL, UL128, UL130 and UL131A) designed to
express the pentamer complex, and another CMV antigen, the herpesvirus
glycoprotein (gB) protein.
CMV is the most common cause of
newborn disability, leading to deafness, microcephaly (small, not
fully developed heads and severe disabilities), vision loss and mental
deficiencies, among other serious complications. It is also the most
frequent viral disease in transplant recipients, often leading to
transplant failure. Currently, there is no approved vaccine for CMV.
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Initiation of Phase 1 study of mRNA-1653, a combination human
metapneumovirus and parainfluenza virus type 3 (HMPV+PIV3) vaccine:
The placebo-controlled, multi-site Phase 1 study of mRNA-1653 began
dosing patients in December 2017 and will assess for safety,
tolerability, and immunogenicity.
HMPV and PIV3 typically
cause mild respiratory illness, but can become severe in young
children, the elderly and other immunocompromised adults. HMPV and
PIV3 are the second and third most common causes, respectively, of
lower respiratory hospitalizations in children, behind RSV. Currently,
there is no approved vaccine for either HMPV or PIV3.
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Publications: in September, Moderna announced a publication
in the August issue of Molecular Therapy that provides
mechanistic insights about its mRNA prophylactic vaccines. The
research, led by Professor Karin Loré, Ph.D., and her group at
the Karolinska Institutet in Stockholm, Sweden, characterizes how
Moderna's vaccines target key antigen-presenting cells, leading to
both B cell and T cell activation, which yields a potent immune
response. Two additional papers based on Dr. Lore's work offer
additional insights into the method of action of Moderna's vaccine
technology. A paper published
in November 2017 in Frontiers in Immunology demonstrates that
Moderna vaccine technology is able to stimulate a type of B cell that
makes high-quality, antigen-specific antibodies consistent with high
seroconversion rates in humans. A second paper published
in November in the Journal of Immunology, shows that Moderna's
vaccine technology produces a desirable kinetic immune activation and
subsequent suppression by myeloid derived suppressor cells (MDSCs),
which are major regulators of T- cell responses.
Moderna also continues to advance vaccines in collaboration with
government agencies and non-government organizations to address major
public health issues. The company is furthering its efforts through its
current contract with the Biomedical Advanced Research and Development
Agency (BARDA) - part of the Office of the Assistant Secretary for
Preparedness and Response at the U.S. Department of Health and Human
Services - to develop an mRNA Zika vaccine, now including a head-to-head
comparison of two potential mRNA candidates (mRNA 1325 and mRNA 1893)
through Phase 1, after which it will determine the best candidate for
further clinical development to BLA submission for licensure.
Therapeutic Vaccines
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Initiation of Phase 1 study of personalized cancer vaccine (PCV),
mRNA-4157 (KEYNOTE-603): In November, Moderna announced
that it has initiated dosing for a Phase
1 study of its PCV. The Phase 1 open-label, dose escalation,
multicenter study in the United States will assess the safety,
tolerability and immunogenicity of mRNA-4157 alone in subjects with
resected solid tumors and in combination with KEYTRUDA®
(pembrolizumab), an anti-PD-1 therapy, marketed by Merck (known as MSD
outside the U.S. and Canada) in subjects with unresectable solid
tumors. Moderna has a strategic collaboration
with Merck to develop PCVs in collaboration with KEYTRUDA®.
Moderna
first identifies neoepitopes present in a patient's tumor and then
creates an mRNA-based PCV encoding for approximately 20 neoepitopes.
When injected into the patient, the mRNA-based PCV directs the
patient's cells to express the selected neoepitopes. In turn, this may
help the patient's immune system better recognize cancer cells as
foreign and eradicate them. mRNA-4157 also has the potential to
enhance clinical outcomes associated with checkpoint inhibitor
therapies. Leveraging its rapid cycle time, small-batch manufacturing
technique and digital infrastructure, Moderna plans to manufacture and
supply each individually tailored and manufactured PCV to patients
within weeks.
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Investigational new drug (IND) application filed for mRNA-5671, a
KRAS cancer vaccine: KRAS is one of the most frequently mutated
oncogenes in human cancer (approximately 30% of all cases). KRAS
mutations are found principally in non-small cell lung cancer (NSCLC),
colorectal cancer and pancreatic cancer, and are associated with worse
outcomes. Hotspots of KRAS mutations are found in different tumor
types and can serve as tumor rejection epitopes. Presentation of these
epitopes to the immune system may elicit a robust anti-tumor response.
mRNA-5671 encodes for the four most commonly found KRAS mutations,
which will cover most of the mutations that occur in NSCLC, colorectal
cancer and pancreatic cancer.
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National Cancer Institute (NCI) to study mRNA-based PCV: In
collaboration with Moderna, the Surgery Branch of the NCI's Center for
Cancer Research plans to sponsor a Phase 1/2 study to investigate the
safety and immunogenicity of mRNA-based PCVs for patients under the
direction of Steven A. Rosenberg, M.D., Ph.D., Chief of Surgery, NCI.
As part of this collaboration, Moderna will manufacture mRNA-based
personalized cancer vaccines (NCI-4650) for up to 12 patients with
advanced-stage, metastatic cancers.
Localized Therapeutics
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Phase 2a study of mRNA AZD-8601: Phase 2a study of mRNA
AZD8601: Dosing of patients is anticipated for early in the first
quarter of 2018 for the Phase 2a study of mRNA AZD8601, a localized
mRNA therapeutic encoding for vascular endothelial growth factor,
VEGF-A. The mRNA AZD8601 program is led by AstraZeneca.
Data
from a Phase 1 randomized, double-blind, placebo-controlled, single
ascending dose study that assessed the safety, tolerability and
pharmacokinetics (PK) of mRNA AZD8601 after single dose administration
in male patients with Type 2 diabetes mellitus are expected to be
presented at a scientific congress and published in 2018.
Liver Therapeutics
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Naming of pre-clinical development candidate mRNA-3927, encoding an
intracellular enzyme to treat Propionic Acidemia (PA): PA is a
rare, autosomal recessive organic acidemia/aciduria caused by a
mitochondrial enzyme deficiency in propionyl-CoA carboxylase (PCC) due
to mutations in PCCA (PA type I) or PCCB (PA type II). mRNA-3927
combines mRNA-encoded proteins for both the PCCA and PCCB enzyme
components with the goal of addressing all PA subtypes. PA is a
natural follow-on to the MMA program, as both are organic acidemias
with defective enzymes along the same metabolic pathway.
PA
is a rare disease with no approved therapy. The disorder typically
impacts newborn children, and patients with PA often present acutely
with metabolic acidosis, cardiac arrhythmias and hyperammonemia
causing severe central nervous system dysfunction.
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Naming of pre-clinical development candidate mRNA-1944, encoding an
antibody against the chikungunya virus: mRNA-1944 encodes for an
antibody that can neutralize the chikungunya virus circulating in the
blood. Moderna has a Phase 1 study underway for a prophylactic mRNA
vaccine (mRNA-1388) to prevent infection from chikungunya
virus. However, in certain situations, such as in immuno-compromised
populations, when rapid post-exposure treatment or prophylaxis is
warranted, or when protection is needed only for short periods (three
to six months), an antibody approach is desirable.
Chikungunya
typically causes mild fever and transient joint pain. In approximately
15 percent of infected patients, it can cause long-term, severe
arthritis. Chikungunya historically has been limited to warmer
climates in Asia and Africa, but recent cases have been identified in
the Americas and Europe. There is no approved vaccine or treatment for
chikungunya.
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Collaboration for mRNA AZD-7970, encoding the secreted protein
relaxin to treat heart failure: In November, Moderna and
AstraZeneca announced a new strategic agreement to co-develop and
co-commercialize mRNA AZD-7970, which is designed to instruct cells in
the body to produce and express relaxin, a secreted protein with
systemic effect. Heart failure occurs when the heart is weakened and
cannot pump enough blood to meet the body's needs. Biologic functions
for relaxin suggest that expression of the hormone may directly impact
underlying conditions that exacerbate heart failure, leading to the
regrowth of heart tissue, controlling inflammation, reordering the
extracellular matrix, improving renal function, and relieving hepatic
portal pressure.
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Publications: In December, Moderna announced the publication of
preclinical data supporting its first rare disease development
program, mRNA-3704, a therapeutic for methylmalonic acidemia (MMA), a
serious and often life-threatening organic acidemia disorder. The
data, published in the journal Cell Reports, demonstrate that
intravenous (IV) administration of an mRNA therapeutic encoding for
human methylmalonyl-CoA mutase (hMUT), the enzyme most
frequently mutated in MMA, enabled liver expression of hMUT in
MMA mouse models, leading to a significant reduction in methylmalonic
acid and complete survival of treated mice versus control group with a
dramatic improvement in weight gain. Repeat IV dosing did not increase
markers of liver toxicity or inflammation. The study was conducted in
partnership with researchers at the Medical
Genomics and Metabolic Genetics Branch of the National Human
Genome Research Institute at the National Institutes of Health.
Q4 2017 AND RECENT BUSINESS/FINANCIAL UPDATES
Board of Directors and Organizational Updates
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John Mendlein joined Moderna as President, Corporate and Product
Strategy. Earlier this month, Moderna announced
that John Mendlein, Ph.D., joined the company as President, Corporate
and Product Strategy. In this role, Dr. Mendlein will be responsible
for corporate strategy, product advancement and strategy, partnering
and product protection. He will serve on Moderna's Executive Committee
and report to Chief Executive Officer Stéphane Bancel. Dr. Mendlein
has helped start and lead numerous innovative life sciences companies.
He is Vice Chairman of the Board and a founder of Fate Therapeutics,
Inc., and holds board positions with Editas Medicine, Inc., and
Axcella Health, Inc. He also serves on the Biotechnology Industry
Organization ("BIO") emerging companies board. Dr. Mendlein previously
served as the Chief Executive Officer of aTyr Pharma, and Fate
Therapeutics, as well as Adnexus Therapeutics, Inc., (acquired by
BMS). Before that, he served as Chairman and Chief Executive Officer
of Affinium Pharmaceuticals, Ltd. (acquired by Debiopharm Group), and
as a board member, General Counsel and Chief Knowledge Officer at
Aurora Bioscience Corporation (acquired by Vertex (News - Alert) Pharmaceuticals).
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Stephen Berenson appointed to Board of Directors. In October,
Moderna announced
that Stephen Berenson was joining the company's Board of Directors.
Mr. Berenson, who joined Flagship Pioneering in June of 2017,
previously served for 12 years as the Vice Chairman of Investment
Banking at J.P. Morgan, and focused on providing high-touch strategic
advice and complex transaction execution to leading companies across
all industries globally. In total, Mr. Berenson spent more than 33
years with J.P. Morgan as an investment banker, where he worked across
all major geographies, product areas and industry groups. He played
key roles in building J.P. Morgan's M&A, equities and technology
investment banking businesses.
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Continued growth across organization: In 2016, Moderna expanded
its headcount from approximately 500 to nearly 600 team members.
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Continued strong cash position: Moderna maintained a
strong cash position in 2017. As of December 31, 2017, the company had
approximately $910 million in cash, as compared to $1.306 billion in
cash as of December 31, 2016.
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2017 cash inflows: From reimbursement, product milestones and
investment income was approximately $55 million.
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Significant investments in the business: Moderna's cash
operating expense and capital expenditures in 2017 totaled
approximately $455 million.
About Moderna Therapeutics
Moderna pioneers the discovery and development of messenger RNA (mRNA)
therapeutics and vaccines, an entirely new class of medicines that
directs the body's cells to produce intracellular or secreted proteins
that can have a therapeutic or preventive benefit for both patients and
healthy individuals. With its breakthrough platform, Moderna is creating
mRNA medicines for a wide range of diseases and conditions, in many
cases by addressing currently undruggable targets or underserved areas
of medical need. Moderna is developing its innovative mRNA medicines for
infectious diseases, immuno-oncology, rare diseases, and cardiovascular
diseases, through solely controlled programs and collaborations with
strategic partners.
Headquartered in Cambridge, Mass., privately held Moderna currently has
strategic relationships with AstraZeneca, Plc. (AZ), Merck, Inc (MRK)
and Vertex Pharmaceuticals (VRTX), 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. In
2017 Moderna was ranked a top biopharma industry employer by Science
Magazine and a Top Places to Work by the Boston
Globe. To learn more, visit www.modernatx.com.
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