[D66] Update Covid-19 vaccin (Wuhan Coronavirus 2019-nCoV #194)

[Dr. Marc-Alexander Fluks]

Bron:  Business Wire / Moderna
datum: 18 mei 2020
URL:   https://www.businesswire.com/news/home/20200518005348/en/


Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine
(mRNA-1273) Against Novel Coronavirus
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* After two doses all participants evaluated to date across the 25 mug 
and 100 mug dose cohorts seroconverted with binding antibody levels at 
or above levels seen in convalescent sera
* mRNA-1273 elicited neutralizing antibody titer levels in all eight 
initial participants across the 25 mug and 100 mug dose cohorts, 
reaching or exceeding neutralizing antibody titers generally seen in 
convalescent sera
* mRNA-1273 was generally safe and well tolerated
* mRNA-1273 provided full protection against viral replication in the 
lungs in a mouse challenge model
* Anticipated dose for Phase 3 study between 25 mug and 100 mug; 
expected to start in July
* Conference call to be held on Monday, May 18 at 8:30 a.m. ET

CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 18, 2020-- 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 interim clinical data of mRNA-1273, its vaccine candidate 
against novel coronavirus (SARS-CoV-2), from the Phase 1 study led by 
the National Institute of Allergy and Infectious Diseases (NIAID), part 
of the National Institutes of Health (NIH).

Immunogenicity data are currently available for the 25 mug and 100 mug 
dose level (ages 18-55) after two doses (day 43) and at the 250 mug 
level (ages 18-55) after one dose (day 29). Dose dependent increases in 
immunogenicity were seen across the three dose levels, and between prime 
and boost within the 25 mug and 100 mug dose levels. All participants 
ages 18-55 (n=15 per cohort) across all three dose levels seroconverted 
by day 15 after a single dose. At day 43, two weeks following the second 
dose, at the 25 mug dose level (n=15), levels of binding antibodies were 
at the levels seen in convalescent sera (blood samples from people who 
have recovered from COVID-19) tested in the same assay. At day 43, at 
the 100 mug dose level (n=10), levels of binding antibodies 
significantly exceeded the levels seen in convalescent sera. Samples are 
not yet available for remaining participants.

At this time, neutralizing antibody data are available only for the 
first four participants in each of the 25 mug and 100 mug dose level 
cohorts. Consistent with the binding antibody data, mRNA-1273 
vaccination elicited neutralizing antibodies in all eight of these 
participants, as measured by plaque reduction neutralization (PRNT) 
assays against live SARS-CoV-2. The levels of neutralizing antibodies at 
day 43 were at or above levels generally seen in convalescent sera.

mRNA-1273 was generally safe and well tolerated, with a safety profile 
consistent with that seen in prior Moderna infectious disease vaccine 
clinical studies. The sole incidence of a grade 3 adverse event in the 
25 mug and 100 mug dose cohorts was a single participant at 100 mug who 
experienced grade 3 erythema (redness) around the injection site. To 
date, the most notable adverse events were seen at the 250 mug dose 
level, comprising three participants with grade 3 systemic symptoms, 
only following the second dose. All adverse events have been transient 
and self-resolving. No grade 4 adverse events or serious adverse events 
have been reported.

Preclinical results from a viral challenge study in mice conducted in 
collaboration with NIAID and its academic partners are also available. 
In this study, vaccination with mRNA-1273 prevented viral replication in 
the lungs of animals challenged with SARS-CoV-2. Neutralizing titers in 
Phase 1 clinical trial participants at the 25 mug and 100 mug dose 
levels were consistent with neutralizing titers that were protective in 
the mouse challenge model.

Based on the interim Phase 1 data, the Moderna-led Phase 2 study will be 
amended to study two dose levels, 50 mug and 100 mug, with the aim of 
selecting a dose for pivotal studies. The NIAID-led Phase 1 study is 
being amended to include a 50 mug dose level cohort across each of the 
three age groups. Moderna anticipates the dose for the Phase 3 study to 
be between 25 mug and 100 mug and expects Phase 3 trial initiation in 
July, subject to finalization of the clinical trial protocol.

'These interim Phase 1 data, while early, demonstrate that vaccination 
with mRNA-1273 elicits an immune response of the magnitude caused by 
natural infection starting with a dose as low as 25 mug,' said Tal Zaks, 
M.D., Ph.D., Chief Medical Officer at Moderna. 'When combined with the 
success in preventing viral replication in the lungs of a pre-clinical 
challenge model at a dose that elicited similar levels of neutralizing 
antibodies, these data substantiate our belief that mRNA-1273 has the 
potential to prevent COVID-19 disease and advance our ability to select 
a dose for pivotal trials.'

'With today's positive interim Phase 1 data and the positive data in the 
mouse challenge model, the Moderna team continues to focus on moving as 
fast as safely possible to start our pivotal Phase 3 study in July and, 
if successful, file a BLA,' said Stephane Bancel, Chief Executive 
Officer at Moderna. 'We are investing to scale up manufacturing so we 
can maximize the number of doses we can produce to help protect as many 
people as we can from SARS-CoV-2.'

Funding 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), supported the planning for the Phase 2 and 
Phase 3 studies of mRNA-1273 and will also support the execution of 
these studies, as well as the scale-up of mRNA-1273 manufacturing both 
at the Company's facilities and that of its strategic collaborator, 
Lonza Ltd.


Conference Call and Webcast Information

Moderna will host a live conference call and webcast at 8:30 a.m. ET on 
Monday, May 18, 2020. To access the live conference call, please dial 
866-922-5184 (domestic) or 409-937-8950 (international) and refer to 
conference ID 2186342. A webcast of the call will also be available 
under 'Events and Presentations' in the Investors section of the Moderna 
website at investors.modernatx.com. The archived webcast will be 
available on Moderna's website approximately two hours after the 
conference call.


About mRNA-1273

mRNA-1273 is an mRNA vaccine against SARS-CoV-2 encoding for a prefusion 
stabilized form of the Spike (S) protein, which was selected by Moderna 
in collaboration with investigators from Vaccine Research Center (VRC) 
at the National Institute of Allergy and Infectious Diseases (NIAID), a 
part of the NIH. The first clinical batch, which was funded by the 
Coalition for Epidemic Preparedness Innovations, was completed on 
February 7, 2020 and underwent analytical testing; it was shipped to NIH 
on February 24, 42 days from sequence selection. The first participant 
in the NIAID-led Phase 1 study of mRNA-1273 was dosed on March 16, 63 
days from sequence selection to Phase 1 study dosing.

On May 6, the U.S. Food and Drug Administration (FDA) completed its 
review of the Company's Investigational New Drug (IND) application for 
mRNA-1273 allowing it to proceed to a Phase 2 study, which is expected 
to begin shortly. On May 12, the FDA granted mRNA-1273 Fast Track 
designation. Moderna is finalizing the protocol for a Phase 3 study, 
expected to begin in July 2020. A summary of the company's work to date 
on SARS-CoV-2 can be found here.


About Moderna's Prophylactic Vaccines Modality

Moderna scientists designed the company's prophylactic vaccines modality 
to prevent infectious diseases. More than 1,400 participants have been 
enrolled in Moderna's infectious disease vaccine clinical studies under 
health authorities in the U.S., Europe and Australia. Clinical data 
demonstrate that Moderna's proprietary vaccine technology has been 
generally well-tolerated and can elicit durable immune responses to 
viral antigens. Based on clinical experience across Phase 1 studies, the 
company designated prophylactic vaccines a core modality and is working 
to accelerate the development of its vaccine pipeline.

The potential advantages of an mRNA approach to prophylactic vaccines 
include the ability to combine multiple mRNAs into a single vaccine, 
rapid discovery to respond to emerging pandemic threats and 
manufacturing agility derived from the platform nature of mRNA vaccine 
design and production. Moderna has built a fully integrated 
manufacturing plant which enables the promise of the technology 
platform.

Moderna currently has nine development candidates in its prophylactic 
vaccines modality, including:

Vaccines against respiratory infections
* Respiratory syncytial virus (RSV) vaccine for older adults (mRNA-1777 
and mRNA-1172 or V172 with Merck)
* RSV vaccine for young children (mRNA-1345)
* Human metapneumovirus (hMPV) and parainfluenza virus type 3 (PIV3) 
vaccine (mRNA-1653)
* Novel coronavirus (SARS-CoV-2) vaccine (mRNA-1273)
* Influenza H7N9 (mRNA-1851)

Vaccines against infections transmitted from mother to baby
* Cytomegalovirus (CMV) vaccine (mRNA-1647)
* Zika vaccine (mRNA-1893 with BARDA)

Vaccines against highly prevalent viral infections
* Epstein-Barr virus (EBV) vaccine (mRNA-1189)

To date, Moderna has demonstrated positive Phase 1 data readouts for 
seven prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus, 
hMPV/PIV3, CMV and Zika). Moderna's CMV vaccine is currently in a Phase 
2 dose-confirmation study. Moderna's investigational Zika vaccine 
(mRNA-1893), currently in a Phase 1 study, was granted FDA Fast Track 
designation in August 2019.


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. The company's 
platform builds on continuous advances in basic and applied mRNA 
science, delivery technology and manufacturing, providing Moderna 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 & Co., 
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 five years. To learn more, visit 
http://www.modernatx.com.


Forward Looking Statement

This press release contains forward-looking statements within the 
meaning of the Private Securities Litigation Reform Act of 1995, as 
amended, including regarding the Company's development of a potential 
vaccine against the novel coronavirus, the parameters and timing of the 
Phase 1 and planned Phase 2 and 3 studies of mRNA-1273, the Company's 
investment in manufacturing, and the Company's intentions regarding 
vaccine dose production. 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: the fact that there has never 
been a commercial product utilizing mRNA technology approved for use; 
the fact that the rapid response technology in use by Moderna is still 
being developed and implemented; the fact that the safety and efficacy 
of mRNA-1273 has not yet been established; potential adverse impacts due 
to the global COVID-19 pandemic such as delays in regulatory review, 
manufacturing and supply chain interruptions, adverse effects on 
healthcare systems and disruption of the global economy; and those other 
risks and uncertainties described under the heading 'Risk Factors' in 
Moderna's most recent Quarterly Report on Form 10-Q 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 at 
www.sec.gov. Except as required by law, Moderna disclaims any intention 
or responsibility for updating or revising any forward-looking 
statements contained 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.


Contacts

Moderna
Media:
Colleen Hussey
Senior Manager, Corporate Communications
203-470-5620
Colleen.Hussey at modernatx.com

Dan Budwick
1AB
973-271-6085
Dan at 1abmedia.com

Investors:
Lavina Talukdar
Head of Investor Relations
617-209-5834
Lavina.Talukdar at modernatx.com

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