8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

PURSUANT TO SECTION 13 OR 15(d)

OF THE SECURITIES EXCHANGE ACT OF 1934

Date of Report (Date of earliest event reported): September 12, 2019

 

 

MODERNA, INC.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-38753   81-3467528
(State or other jurisdiction
of Incorporation)
  (Commission
File Number)
  (IRS Employer
Identification Number)

 

200 Technology Square

Cambridge, MA

  02139
(Address of registrant’s principal executive office)   (Zip code)

(617) 714-6500

(Registrant’s telephone number, including area code)

N/A

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 203.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading symbol(s)

 

Name of each exchange on which registered

Common stock, par value $0.0001 per share   MRNA   The NASDAQ Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.

Emerging growth company  ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☐

 

 

 


Item 7.01 Regulation FD Disclosure

On September 12, 2019, Moderna, Inc. (the “Company”) issued press releases announcing positive interim results from its Phase 1 cytomegalovirus (CMV) vaccine (mRNA-1647) study and positive Phase 1 results for the first systemic messenger RNA therapeutic encoding a secreted protein (mRNA-1944). Copies of the press releases are attached as Exhibit 99.1 and Exhibit 99.2 to this Current Report on Form 8-K and are incorporated herein by reference in this Item 7.01.

As previously announced, the Company will give a live webcast today, September 12, 2019, in conjunction with its 2019 R&D Day. The R&D Day webcast will include a slide presentation, which is attached as Exhibit 99.3 to this Current Report on Form 8-K and incorporated by reference in this Item 7.01. The R&D Day webcast will be available on the Company’s website for 30 days following the event. The information contained on the Company’s website is not part of this Form 8-K and is not incorporated by reference into this Form 8-K.

The information in this Item 7.01 to this Current Report on Form 8-K, and in Exhibits 99.1, 99.2, and 99.3 furnished herewith, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall such information be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit
No.

  

Description

99.1    Press release issued by Moderna, Inc. dated September 12, 2019 (mRNA-1647)
99.2    Press release issued by Moderna, Inc. dated September 12, 2019 (mRNA-1944)
99.3    Slide presentation to be presented at the Moderna, Inc. R&D Day on September 12, 2019


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Date: September 12, 2019     MODERNA, INC.
    By:   /s/ Lori Henderson
      Lori Henderson
      General Counsel and Corporate Secretary
EX-99.1

Exhibit 99.1

Moderna Announces Positive Interim Results from Phase 1 Cytomegalovirus (CMV) Vaccine (mRNA-1647) Study

and Progress Toward Phase 2 and Pivotal Trials

Vaccination immunized seronegative participants to levels consistent with or above seropositive titers and boosted

baseline titers in seropositive participants

Vaccine was generally well-tolerated

Phase 2 study to confirm dose to be initiated in near term, with planned interim analysis through 3 months; Phase 3 study

planning is underway

CMV is the most common infectious cause of birth defects in the U.S.; there is no approved vaccine to prevent CMV

CAMBRIDGE, Mass., September 12, 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 positive data from the three-month interim analysis of safety and immunogenicity of the Phase 1 study of its investigational cytomegalovirus (CMV) vaccine (mRNA-1647). mRNA-1647 is a wholly owned program in Moderna’s prophylactic vaccine portfolio.

Based on these data, Moderna is advancing mRNA-1647 to a dose-confirmation Phase 2 study in the near term. Preparation has also begun for a pivotal Phase 3 study designed to evaluate the efficacy of mRNA-1647 against primary CMV infection. The Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary lipid nanoparticle (LNP) used in this Phase 1 study.

mRNA-1647 is a vaccine combining six mRNAs in a single vial, which encode for two antigens on the surface of CMV: five mRNAs encoding the subunits that form the membrane-bound pentamer complex and one mRNA encoding the full-length membrane-bound glycoprotein B (gB). Both the pentamer and gB are essential for CMV to infect barrier epithelial surfaces and gain access to the body. mRNA-1647 is designed to produce an immune response against both the pentamer and gB for the prevention of CMV infection.

“I am very encouraged by the ability of mRNA-1647 to induce high levels of durable immune responses that can reach or exceed the levels generated by natural CMV infection,” said Tal Zaks, M.D., Ph.D., chief medical officer at Moderna. “We recognize there is an urgent need for a preventative vaccine against congenital CMV and will be advancing mRNA-1647 into a Phase 2 study in the near term to confirm the appropriate dose, while we plan for a pivotal Phase 3 study.”

“Cytomegalovirus is the leading infectious cause of birth defects, and there is a great need for a vaccine that blocks transmission of the virus from the mother to the fetus,” said Sallie Permar, M.D., Ph.D., Associate Dean of Physician Scientist Development and Professor of Pediatrics, Immunology, and Molecular Genetics and Microbiology at Duke Medical School. “These interim data are exciting because mRNA-1647 has shown the ability to induce immune responses in seronegative individuals that are greater than what is seen in those naturally infected with CMV, which is important in that natural immunity is not completely protective against congenital CMV transmission.”

The Phase 1 study, which has completed enrollment, is evaluating the safety and immunogenicity of mRNA-1647 in 169 healthy adult volunteers. The study population includes those who were naïve to CMV infection (CMV-seronegative) and those who had previously been infected by CMV (CMV-seropositive). Participants were randomized to receive either placebo, or 30, 90, 180 or 300 µg of mRNA-1647 on a dosing schedule of 0, 2 and 6 months. This first planned interim


analysis assessed safety and immunogenicity of the first three dose levels (30, 90, and 180 µg) at three months, one month after the second vaccination and before the third vaccination. Neutralizing antibody titers (levels of circulating antibodies that block infection1) were assessed in two assays utilizing epithelial cells and fibroblasts, which measure immune response to the pentamer and gB vaccine antigens, respectively. Seropositive baseline titers are associated with lower rates of congenital CMV transmission.

In seronegative participants:

 

   

A dose-related increase in neutralizing antibody titers was observed in both epithelial cell and fibroblast assays.

 

   

In epithelial cells, after the second vaccination, neutralizing antibody titers were 3 to 5 times higher than CMV-seropositive baseline titers at the 90 and 180 µg dose levels.

 

   

In fibroblasts, after the second vaccination, neutralizing antibody titers were equivalent to CMV-seropositive baseline titers at the 90 and 180 µg dose levels.

 

   

For the 12 sentinel participants who received mRNA-1647 under an earlier arm of the protocol (Phase A) and who received three doses (at 0, 2 and 6 months), neutralizing antibody titers were further boosted at 7 months and were sustained at or above CMV-seropositive baseline levels for at least 12 months.

In seropositive participants:

 

   

A dose-related increase in neutralizing antibody titers was observed in both epithelial cell and fibroblast assays.

 

   

In epithelial cells, the second vaccination boosted neutralizing antibody titers to a level of 10-fold to 19-fold baseline titers in all dose groups.

 

   

In fibroblasts, the second vaccination boosted neutralizing antibody titers to a level of 2-fold to 4-fold baseline titers in all dose groups.

A safety analysis indicated that the vaccine was generally well-tolerated. There were no vaccine-related serious adverse events (SAEs). The most common solicited local adverse event (AE) was injection site pain. The most common solicited systemic AEs were headache, fatigue, myalgia, chills and fever. In general, solicited systemic AEs occurred more frequently after the second dose compared to the first, and were more common in the seropositive cohorts compared to the seronegative cohorts. The most common Grade 3 solicited AEs in seropositive participants were myalgia (9-33% of a given dose cohort), chills and fatigue (9-27% of a given dose cohort) and fever (0-27% of a given dose cohort). There was a single Grade 4 AE of an isolated lab finding of elevated partial thromboplastin time (PTT), which was elevated at baseline (Grade 1) and self-resolved on the next lab test with no associated clinical findings.

A similar overall safety and tolerability profile was observed in an earlier arm of the protocol (Phase A), for which data are available out to 12 months. Additionally, the 300 µg cohort has completed the second vaccination without study pause; interim analysis of safety and immunogenicity is pending.

“We are very pleased with these strong interim results and the immunogenicity demonstrated by our CMV vaccine. The Moderna research, development and manufacturing teams have been working to ensure this program can transition in the near term to a dose-confirmation Phase 2 study, while also preparing for a pivotal Phase 3 study with the goal of ensuring commercial readiness,” said Stéphane Bancel, Moderna’s chief executive officer. “Given the urgent need for CMV prevention around the world, we believe mRNA-1647 has the potential to be a blockbuster commercial opportunity for Moderna. This is the sixth positive Phase 1 readout for a Moderna investigational prophylactic vaccine, and underscores why I believe our vaccine platform will be an important pillar of our future growth.”

 

1 

Centers for Disease Control and Prevention.

 

2


About mRNA-1647

mRNA-1647 is a two-antigen vaccine designed to protect against CMV infection. It combines six mRNAs in a proprietary LNP in a single vial and encodes for two immuno-dominant proteins of CMV. mRNA-1647 comprises five mRNAs encoding the subunits of the pentamer complex and one mRNA encoding the glycoprotein B (gB) target antigen. The pentamer is important for CMV entry into a variety of cells, including epithelial and endothelial cells, while gB is important for entry into all susceptible cells including fibroblasts.2 A vaccine that produces an immune response against both the pentamer and gB has the potential to prevent CMV entry into cells and thus prevent congenital infections. Unlike a protein-based vaccine, mRNA-1647 instructs cells to specifically make the pentamer and gB antigens with a structure that mimics the ones presented to the immune system by the virus during a natural infection.

Preclinical data previously published in Vaccine showed that vaccination with mRNA-1647 in animal models elicited potent and durable neutralizing antibody titers.

About the Phase 1 Study

This randomized, observer-blind, placebo-controlled, dose-ranging study is designed to evaluate the safety and immunogenicity of mRNA-1647 in healthy adults. The study is investigating a three-dose vaccination schedule (0, 2 and 6 months) of mRNA-1647 at four dose levels (30, 90, 180 and 300 µg) in both CMV-seronegative and CMV-seropositive participants. Primary outcome measures include solicited AEs. Secondary outcome measures include anti-CMV neutralizing antibody titers against epithelial cell infection and fibroblast cell infection.

About mRNA-1647 Development

The first planned interim analysis of the Phase 1 study includes data from one month after the second vaccination with mRNA-1647 at 30, 90 and 180 µg dose levels. Forthcoming data from the Phase 1 study will include safety and immunogenicity analyses of the 300 µg dose group as well as data from the third vaccination of all participants at the 30, 90 and 180 µg dose levels. Full Phase 1 data will be presented at a future medical meeting.

Based on these Phase 1 interim data, Moderna is advancing mRNA-1647 into a Phase 2 dose-confirming study in the near term, where the first interim safety and immunogenicity analysis is planned at 0, 2 and 6 months. This Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary lipid nanoparticle (LNP) used in this Phase 1 study. In parallel, preparation is underway for the pivotal Phase 3 study designed to evaluate mRNA-1647 for the prevention of primary CMV infection in a population that includes women of childbearing age. The design of this Phase 3 study is subject to FDA and global regulatory feedback.

About Cytomegalovirus (CMV)

CMV is a common pathogen and member of the herpesvirus family. Congenital (present at or before birth) CMV infection results when infected mothers transmit the virus to their unborn child, and it is the leading infectious cause of birth defects in the United States with approximately 25,000 newborns in the U.S. infected every year.3,4 Birth defects occur in approximately 20 percent of infected babies and include neurodevelopmental disabilities such as hearing loss, vision impairment, varying degrees of learning disability and decreased muscle strength and coordination.5 There is currently no approved vaccine for the prevention of CMV infection.

 

2 

McVoy, Michael A. Cytomegalovirus vaccines. Clinical Infectious Diseases. 2013; 57(Suppl 4): S196-S199.

3 

Congenital CMV and Hearing Loss. Centers for Disease Control and Prevention. Available at: https://www.cdc.gov/cmv/hearing-loss.html.

4 

Schleiss et al. Progress toward development of a vaccine against congenital cytomegalovirus infection. Clinical and Vaccine Immunology. 2017; 24(12): e00268-17.

5 

Congenital CMV and Birth Defects. American Pregnancy Association. Available at: https://americanpregnancy.org/birth-defects/congenital-cmv-birth-defects/.

 

3


CMV is spread through saliva, mucus and urine and is common in healthy babies and toddlers; as a result, young children can be a major source of infection for pregnant women, particularly mothers, daycare workers, preschool teachers, therapists and nurses. Efforts to create a vaccine began in the 1970s, and in 1999 the Institute of Medicine (now National Academy of Medicine) designated CMV as a “highest priority” category for vaccine development. Prior studies of investigational vaccines that did not protect against the CMV pentamer antigen demonstrated limited efficacy against CMV infection and limited durability of immune response.

About Moderna’s Prophylactic Vaccines Modality

Moderna scientists designed the Company’s prophylactic vaccines modality to prevent or control infectious diseases. This modality now includes eight development candidates, all of which are vaccines against viruses. The potential advantages of an mRNA approach to prophylactic vaccines include the ability to mimic natural infection to stimulate a more potent immune response, combining 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 currently has five development candidates for potential commercial uses in this modality, including: respiratory syncytial virus (RSV) vaccine (mRNA-1777 and mRNA-1172 or V172 with Merck), cytomegalovirus (CMV) vaccine (mRNA-1647), human metapneumovirus and parainfluenza virus type 3 (hMPV+PIV3) vaccine (mRNA-1653) and Zika vaccine (mRNA-1893) with the Biomedical Advanced Research and Development Authority (BARDA). Three development candidates in this modality are being explored for potential global health uses including: influenza H10N8 vaccine (mRNA-1440), influenza H7N9 vaccine (mRNA-1851) and chikungunya vaccine (mRNA-1388) with the Defense Advanced Research Projects Agency (DARPA).

To date, Moderna has demonstrated positive Phase 1 data readouts for six prophylactic vaccines (H10N8, H7N9, RSV, chikungunya virus, hMPV+PIV3 and CMV). Moderna’s investigational Zika vaccine (mRNA-1893), currently in a Phase 1 study, was recently granted FDA Fast Track designation.

R&D Day Webcast Today

The Company also announced positive Phase 1 data for mRNA-1944 (mRNA encoding for antibody against chikungunya virus) today. A summary of data from both of these Phase 1 trials 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 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.

 

4


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: advancing mRNA-1647 into a dose-confirmation Phase 2 study; preparation for a pivotal Phase 3 study of mRNA-1647 against primary CMV infection; the potential blockbuster commercial opportunity for mRNA-1647; the potential for Moderna’s vaccine platform to support its future growth; and mRNA-1647’s potential to protect against CMV infection and prevent congenital CMV infection. 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: whether the interim results for mRNA-1647 will be predictive of the final results for the ongoing study or any future clinical studies; whether mRNA-1647 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 our 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.

Moderna Contacts:

Media:

Colleen Hussey

Senior Manager, Corporate Communications

203-470-5620

Colleen.Hussey@modernatx.com

Dan Budwick

1AB

973-271-6085

dan@1abmedia.com

Investors:

Lavina Talukdar

Head of Investor Relations

617-209-5834

Lavina.Talukdar@modernatx.com

 

5

EX-99.2

Exhibit 99.2

Moderna Announces Positive Phase 1 Results for the First Systemic Messenger RNA Therapeutic Encoding a

Secreted Protein (mRNA-1944)

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

CAMBRIDGE, Mass., September 12, 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 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 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 pre-medication 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 the further exploration of 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 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.”

 

2


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).

 

3


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,”

 

4


“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.

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

 

5

EX-99.3

Slide 1

Encoded mRNA(s) Ribosome Protein chain(s) Encoded mRNA(s) Nucleus Endoplasmic Reticulum Cytosol hMPV+PIV3 OX40L IL12 IL36γ Relaxin Mitochondrion Fabry PA PKU Systemic intracellular therapeutics Intratumoral immuno- oncology Localized regenerative therapeutics Systemic secreted therapeutics Lysosome Fabry MMA CMV VEGF-A Ab against Chikungunya virus IL23 Flu H10N8 H7N9 RSV Prophylactic vaccines Zika VLP Chikungunya VLP KRAS PCV neoantigens Cancer vaccines GSD1a R&D Day September 12, 2019 Exhibit 99.3


Slide 2

Welcome and Introduction Stéphane Bancel Chief Executive Officer


Slide 3

This presentation 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 potential approval and commercial launch of Moderna’s development candidates, including CMV vaccine (mRNA-1647); Moderna’s belief that Phase 1 clinical data from mRNA-1944 provides support for the continued development of Moderna’s rare disease therapeutic modality; clinical program next steps; development candidate activities; future clinical study commencement, progression, enrollment, and conclusion, including the Phase 2 clinical study start and Phase 3 preparation for mRNA-1647; manufacturing capacity and scalability; regulatory submissions and approvals; risk management; estimates and forward-looking projections with respect to Moderna or its anticipated future performance or events, including the commercial opportunity and gross margins for mRNA-1647. In some cases, forward-looking statements can be identified by terminology such as “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 presentation 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 category of medicines such as mRNA, and therefore Moderna’s 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 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 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 presentation 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. Note Regarding Trademarks Moderna is the owner of various U.S. federal trademark registrations (“®”) of and other trademarks (“TM”). Certain other trademarks, trade names and service marks appearing in this presentation are the property Moderna’s strategic collaborators. Solely for convenience, the trademarks and trade names in this presentation may be referred to without the ® and TM symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. Forward-looking statements


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Large product opportunity Higher probability of technical success Accelerated research and development timelines Greater capital efficiency over time vs. recombinant technology mRNA as a potential new class of medicines


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Risk management is essential to building a new class of medicines Increasing biology risk Varying technology risk


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Risk management is essential to building a new class of medicines Increasing biology risk Varying technology risk De-risk technology with first program in a modality Diversify biology risk by working on multiple programs in parallel within a modality Stage risk, build on learnings over time Our approach is to develop technology modalities


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Risk management is essential to building a new class of medicines Increasing biology risk Localized regenerative therapeutics Intratumoral immuno-oncology Cancer vaccines Systemic secreted therapeutics Systemic intracellular therapeutics Prophylactic vaccines Varying technology risk De-risk technology with first program in a modality Diversify biology risk by working on multiple programs in parallel within a modality Stage risk, build on learnings over time Our approach is to develop technology modalities


Slide 8

Risk management is essential to building a new class of medicines Chikungunya Antibody Increasing biology risk VEGF-A (no LNP) Localized regenerative therapeutics Intratumoral immuno-oncology OX40L OX40L+ IL23+IL36g (Triplet) Cancer vaccines Personalized cancer vaccine Systemic secreted therapeutics Fabry Systemic intracellular therapeutics CMV vaccine Prophylactic vaccines Flu vaccines (H7, H10) Varying technology risk MMA


Slide 9

Two important positive clinical milestones in two modalities announced today Cytomegalovirus (CMV) vaccine (mRNA-1647) Positive interim phase 1 data Successfully immunized seronegatives and boosted seropositives Generally well tolerated Phase 2 to start in the near term Preparations underway for the phase 3 Moderna owns the global commercial rights to mRNA-1647 Antibody against Chikungunya virus (mRNA-1944) Positive phase 1 data Observed dose dependent protein expression Achieved expected therapeutic levels at a well tolerated dose (0.3mg/kg) Observed expected translation from NHP to human


Slide 10

Body of clinical data from Moderna’s platform to date Chikungunya Antibody Increasing biology risk VEGF-A (no LNP) Localized regenerative therapeutics Intratumoral immuno-oncology OX40L OX40L+ IL23+IL36g (Triplet) Cancer vaccines Personalized cancer vaccine Systemic secreted therapeutics Fabry Systemic intracellular therapeutics CMV vaccine Prophylactic vaccines Flu vaccines (H7, H10) Varying technology risk MMA Moderna platform investments in research, manufacturing and clinical have enabled 16 investigational medicines to start clinical trials in the last 3.5 years We have enrolled more than 1,300 subjects and patients across five modalities. We have administered repeat doses to patients through multiple cycles in our immuno-oncology programs (OX40L & PCV) Across 5 modalities we have shown that our development candidates: have an acceptable safety profile and are generally well tolerated* result in consistent protein expression** encode functional proteins translate from preclinical models to humans *Common Adverse Events by Modality - Prophylactic Vaccines: injection site pain, myalgia, and fatigue; Cancer Vaccines: for PCV, the most common grade 2 adverse events were fatigue, soreness at the injection site, colitis, and myalgias; Intratumoral Immuno-Oncology: for OX40L, multiple grade 2 and a single grade 3 transient reversible injection related reactions; Localized Regenerative Therapeutics: for VEGF-A, mild injection-site reactions; and Systemic Secreted Therapeutics: see the section below titled Systemic Therapeutics – Secreted and Intracellular. **Only mRNA-1325, our initial Zika vaccine did not elicit desired pharmacologic effect


Slide 11

KRAS+Sting Vaccine hMPV+PIV3 vaccine Zika Vaccine mRNA-1893 CMV vaccine IL12 PCV OX40L+IL23+IL36g (Triplet) Chikungunya antibody Open IND Moderna’s development pipeline at IPO Pre-Clinical Development *Data in some cases are interim; positive data means the data warrant continued advancement within a trial or for further development OX40L solid tumors Phase 1 H7 vaccine H10 vaccine Chikungunya vaccine RSV (1777) vaccine Phase 2 VEGF-A PKU PA Fabry Relaxin MMA OX40L VEGF-A Positive Phase 1 Data* Phase 2 planning 3 systemic intracellular therapeutics programs 3 Systemic secreted therapeutics programs 1 Localized regenerative therapeutics program 3 Intratumoral immuno- oncology programs 2 Cancer vaccine programs 7 Prophylactic vaccine programs RSV (1777) vaccine Chikungunya vaccine Zika Vaccine mRNA-1325 VZV


Slide 12

PCV KRAS Vaccine hMPV+PIV3 vaccine Zika vaccine CMV vaccine RSV (1172) vaccine IL12 PCV PCV hMPV+PIV3 vaccine OX40L+IL23+IL36g (Triplet) Chikungunya antibody Open IND Moderna’s development pipeline today (9 months since IPO) Pre-Clinical Development *Data in some cases are interim; positive data means the data warrant continued advancement within a trial or for further development OX40L solid tumors Phase 1 H7 vaccine H10 vaccine Chikungunya vaccine RSV (1777) vaccine Phase 2 VEGF-A PKU PA Fabry Relaxin GSD1a MMA OX40L VEGF-A Positive Phase 1 Data* Phase 2 planning OX40L ovarian 4 Systemic intracellular therapeutics programs 3 Systemic secreted therapeutics programs 1 Localized regenerative therapeutics program 3 Intratumoral immuno- oncology programs 2 Cancer vaccine programs 7 Prophylactic vaccine programs RSV (1777) vaccine Chikungunya vaccine CMV vaccine Chikungunya antibody CMV vaccine


Slide 13

Moderna in September 2019 Programs in Development 4 Vaccines for major unmet needs CMV preparing Phase 2 hMPV+PIV3 – positive interim Ph 1 data RSV and Zika in Ph 1 5 Immuno-Oncology PCV in Ph 2 OX40L preparing for Ph 2 cohort Triplet, IL2, KRAS in Ph 1 5 Rare Disease First systemic therapeutic: Chik antibody: positive Ph 1 MMA – Ph 1 actively recruiting PA, PKU, Fabry & GSD1a in GLP Tox Foundations >1,300 Healthy volunteers and patients enrolled >800 employees A fully-integrated 200,000 sq. ft. GMP site operational in Norwood, MA Leading Biopharma Partners $1.44 bn of cash, cash equivalents, as of June 30, 2019 (unaudited) Pipeline 4 In or preparing for Ph 2 12 Ph 1 trials ongoing 10 Positive Ph1 readouts: 6 vaccines, PCV, OX40L, VEGF, Chik ab


Slide 14

R&D Day 2019 agenda Sign-in, Coffee, Breakfast 7:30–8:30 AM 60 min Introduction Stéphane Bancel 8:30–8:40 AM 10 min CMV Tal Zaks, MD, PhD Sallie Permar, MD, PhD, Duke University School of Medicine Tal Zaks, MD, PhD Juan Andres Mark Schleiss, MD, University of Minnesota Laura Riley, MD, Weill Cornell Medical College Stéphane Bancel 8:40–10:00 AM 70 min Q&A 10:00–10:30 AM 30 min Break 10:30–10:40AM 10 min Immuno-oncology Tal Zaks, MD, PhD Keith Flaherty, MD, Massachusetts General Hospital 10:40–11:10 AM 30 min Antibody against Chikungunya virus Tal Zaks, MD, PhD 11:10–11:50AM 40 min Methylmalonic acidemia Gregory Enns, MD, Stanford University 11:50–12:20 AM 30 min Conclusion Stéphane Bancel 12:20–12:30 PM 10 min Q&A Moderna Team 12:30–1:00 PM 30 min Lunch September 12, 2019


Slide 15

Prophylactic vaccines Tal Zaks, MD, PhD Chief Medical Officer


Slide 16

Progress by modality Intratumoral immuno-oncology Prophylactic vaccines Cancer vaccines Localized regenerative therapeutics Systemic intracellular therapeutics Systemic secreted therapeutics


Slide 17

Modality ID # Program Preclinical dev elopment Phase 1 Phase 2 Phase 3 and commercial Moderna rights Prophylactic vaccines – Commercial programs Prophylactic vaccines- Global health programs mRNA-1172/ RSV vaccine Merck V172 Merck to pay milestones and royalties mRNA-1777RSV vaccine mRNA-1653hMPV+PIV3 vaccinePhase 1bPhase 1Worldwide (pediatrics)(adults) Worldw ide mRNA-1893 Zika vaccine BARDA funded Worldw ide mRNA-1851Influenza H7N9 vaccineAdvancing subject to funding mRNA-1440 Influenza H10N8 vaccine Worldwide Advancing subject to funding Worldw ide mRNA-1388Chikungunya vaccineAdvancing subject to funding Prophylactic Vaccines mRNA-1647 CMV vaccine Worldwide


Slide 18

Our mRNA platform has significant advantages for the development of infectious disease vaccines mRNA mimics natural infection to activate the immune system and achieve a potentially potent response Multiple mRNAs in one vaccine for more compelling product profiles Faster discovery, ability to respond rapidly to emerging pandemic threats Single process and single, multi-product facility for all vaccines


Slide 19

Immunogenicity at sufficient levels to warrant further study Clinical safety and tolerability Dose dependent pharmacology NHP protein expression Antigen complexity Positive readouts from six prophylactic vaccines Phase 1 safety and immunogenicity data (H10N8, H7N9, RSV, Chikungunya virus, hMPV+PIV3, CMV) Progress in the prophylactic vaccines platform to date Clinical Preclinical H10N8 mRNA-1440 H7N9 mRNA-1851 RSV mRNA-1777 Zika mRNA-1325 RSV mRNA-1172 Chik mRNA-1388 hMPV+PIV3 mRNA-1653 CMV mRNA-1647 Prophylactic vaccines Zika mRNA-1893 Ongoing Ongoing Ongoing Ongoing


Slide 20

Modality ID # Program Preclinical dev elopment Phase 1 Phase 2 Phase 3 and commercial Moderna rights Prophylactic vaccines – Commercial programs Prophylactic vaccines- Global health programs mRNA-1172/ RSV vaccine Merck V172 Merck to pay milestones and royalties mRNA-1777RSV vaccine mRNA-1653hMPV+PIV3 vaccinePhase 1bPhase 1Worldwide (pediatrics)(adults) Worldw ide mRNA-1893 Zika vaccine BARDA funded Worldw ide mRNA-1851Influenza H7N9 vaccineAdvancing subject to funding mRNA-1440 Influenza H10N8 vaccine Worldwide Advancing subject to funding Worldw ide mRNA-1388Chikungunya vaccineAdvancing subject to funding Prophylactic Vaccines mRNA-1647 CMV vaccine Worldwide


Slide 21

Cytomegalovirus (CMV) vaccine (mRNA-1647): Review of interim phase 1 data Tal Zaks, MD, PhD Chief Medical Officer


Slide 22

Congenital CMV vaccine includes 6 mRNAs 5 encode the Pentamer, 6th encodes gB antigen Fibroblasts Epithelial cells


Slide 23

CMV vaccine (mRNA-1647) Phase 1 trial design Key Objective: To assess the safety, reactogenicity, and immunogenicity of different dose levels of mRNA-1647 Primary endpoint: Safety Secondary endpoints: Neutralizing antibodies against CMV infection of epithelial cells and fibroblasts Binding antibodies to gB and Pentamer antigens Trial progress: FSFV: December 2017 Enrollment completed June 2019 (N=169) Phase B – 2nd vaccination completed May 2019; interim data available Phase B – 3rd vaccination completed August 2019; interim data not yet available Phase C – 2nd vaccination completed August 2019; interim data not yet available


Slide 24

CMV Vaccine (mRNA-1647) Phase 1 Interim Analysis Immunogenicity in CMV-seronegative participants, per-protocol set GMT = geometric mean titer; CMV-seropositive benchmark values derived from baseline values of all CMV-seropositive participants Seronegative subjects successfully immunized to generate neutralizing titers against CMV Dose-related increase in neutralizing antibodies After the 2nd vaccination, GMTs of the 90 μg and 180 μg dose levels achieved or exceeded the CMV-seropositive benchmark Subject n at each timepoint Placebo 30 µg 90 µg 180 µg Baseline 13 17 13 15 Post 1st vaccination 12 17 10 15 Post 2nd vaccination 11 14 12 12 Variable Neutralizing Antibodies Against Epithelial Cell Infection Placebo 30 μg 90 μg 180 μg Baseline GMT 8 8 8 8 GMT post 1st vaccination 8 37 708 1,387 GMT post 2nd vaccination 12 3,263 15,305 30,743 GMT/benchmark ratio --- 0.6 2.7 5.5 CMV-seropositive GMT benchmark = 5,588 Variable Neutralizing Antibodies Against Fibroblast Infection Placebo 30 μg 90 μg 180 μg Baseline GMT 8 8 8 8 GMT post 1st vaccination 8 8 24 10 GMT post 2nd vaccination 10 305 1,141 1,264 GMT/benchmark ratio --- 0.2 0.9 1.0 CMV-seropositive GMT benchmark = 1,295


Slide 25

CMV Vaccine (mRNA-1647) Phase 1 Interim Analysis Immunogenicity in CMV-seropositive participants, per-protocol set GMT = geometric mean titer; GMR = geometric mean ratio, defined here as the average of the ratio between Baseline/post 2nd vaccination for each participant Seropositive subjects effectively boosted beyond levels seen in natural infection Dose-related increase in neutralizing antibody titers mRNA-1647 boosted neutralizing antibody titers against epithelial cells to 10-fold or higher in all treatment groups Subject n at each timepoint Placebo 30 µg 90 µg 180 µg Baseline 14 13 12 13 Post 1st vaccination 14 13 12 13 Post 2nd vaccination 12 10 9 9 Variable Neutralizing Antibodies Against Epithelial Cell Infection Placebo 30 μg 90 μg 180 μg Baseline GMT (Benchmark = 5,588) 8,169 3,614 5,634 5,700 GMT post 1st vaccination 7,890 24,752 39,020 52,775 GMT post 2nd vaccination 7,490 47,435 62,400 119,829 GMR post 2nd vaccination 0.9 13.2 9.9 19.4 Variable Neutralizing Antibodies Against Fibroblast Infection Placebo 30 μg 90 μg 180 μg Baseline GMT (Benchmark = 1,295) 1,298 1,094 1,458 1,371 GMT post 1st vaccination 1,278 2,654 3,885 3,879 GMT post 2nd vaccination 1,451 2,935 3,891 5,578 GMR post 2nd vaccination 1.1 2.3 3.0 4.1


Slide 26

CMV Serostatus at Baseline CMV-seronegative CMV-seropositive Placebo n=13 30 μg n=15 90 μg n=16 180 μg n=15 Placebo n=13 30 μg n=12 90 μg n=11 180 μg n=11 Pain - 11 (73%) - 13 (81%) 2 (13) 12 (80%) 2 (13) - 9 (75%) 1 (8) 8 (73%) - 10 (91%) 3 (27) Redness - - - 3 (21) - - - - 2 (18) 1 (9) Swelling - - - - - - - 1 (9) - Headache 3 (23) - 5 (33) - 10 (63) - 9 (60) 2 (13) 2 (15) - 4 (33) 1 (8) 4 (36) - 9 (82) 2 (18) Fatigue 2 (15) - 5 (33) 1 (7) 8 (50) 1 (6) 11 (73) 1 (7) 1 (8) - 7 (58) 3 (25) 7 (64) 1 (9) 8 (73) 3 (27) Myalgia 1 (8) - 5 (33) 1 (7) 8 (50) 3 (19) 11 (73) 2 (13) - 5 (42) 4 (33) 7 (64) 1 (9) 7 (64) 2 (18) Chills 1 (8) - 3 (20) 1 (7) 7 (43) 1 (6) 11 (73) 3 (20) - 6 (50) 1 (8) 7 (64) 1 (9) 9 (82) 3 (27) Fever - 3 (20) - 3 (19) 1 (6) 5 (33) - - 2 (17) - 6 (55) 3 (27) 6 (55) 2 (18) Local AEs Most common systemic AEs Values represent n (%) participants reporting each AE, red text=grade 3 AEs CMV vaccine (mRNA-1647) Phase 1 Interim Analysis Solicited adverse events (AE) post 2nd vaccination, solicited safety set Solicited AEs after the second vaccination higher than after the first vaccination After the first vaccination, AEs higher in the seropositives relative to seronegatives One event triggered Study Pause: asymptomatic Grade 4 elevation in partial thromboplastin time (PTT) at 7 days post 2nd vaccination in a subject with Grade 1 PTT elevations throughout study, PTT normal on repeat testing No vaccine-related serious adverse events (SAEs)


Slide 27

CMV vaccine (mRNA-1647) Phase 1 Interim Analysis Durable immunogenicity demonstrated in initial cohort followed to one year


Slide 28

A phase 2, randomized, observer-blind, placebo-controlled, dose-confirmation trial to evaluate the safety and immunogenicity of Cytomegalovirus vaccine mRNA-1647 in healthy adults Evaluate intended phase 3 formulation (same LNP) at 3 dose levels (50µg, 100µg, 150µg) N = 252 adult females and males 18 – 40yrs of age 180 CMV-seronegative 72 CMV-seropositive Vaccination schedule: 0, 2, 6 months Randomization: 3:1 mRNA-1647 vs placebo US sites only: up to 12 clinical investigator sites First interim analysis: safety and immunogenicity through 1 month after 2nd vaccination STUDY DESIGN Protocol finalized and under review with FDA Core vendors and suppliers on-board: PPD selected as clinical contract research organization (CRO) Other key vendors selected, including expanded, new partnerships for critical study activities Investigator selection and initiation progressing well with robust interest in the program: Clinical site feasibility complete On-site investigator qualification visits complete 12 clinical investigator sites selected, including back-up sites as risk mitigation to slow enrollment rates = Selected investigator site location STUDY STATUS CMV vaccine (mRNA-1647) Phase 2 study to be initiated in the near term


Slide 29

CMV vaccine (mRNA-1647) Phase 3 pivotal trial preparations are underway Solicited and received Type C meeting feedback from FDA Primary endpoint: prevention of primary CMV infection in a population that includes women of child bearing age (WOCBA) We believe we can achieve this objective with a trial with <8,000 subjects Country and site feasibility: outreach to 285 sites in 18 countries across North America, Europe and Asia Pac with robust positive response, feasibility assessments continue


Slide 30

CMV vaccine supply plans for late stage development and commercialization Juan Andres Chief Technical Development, Manufacturing, Quality Officer


Slide 31

Moderna’s Internal Manufacturing Site, Norwood MA Pre-clinical, clinical & personalized cancer vaccine production Built and operationalized in 22 months 1st clinical batch manufactured in Aug ’18, 70 batches manufactured to date


Slide 32


Slide 33

Internalizing manufacturing to enable focus on quality, speed and scale Norwood now provides the scalability we need for our growing pipeline Plasmid mRNA Lipid Nano-particle (LNP) Form, Fill, Finish (FFF) Quality Control 2011-2013 No GMP needs in this horizon CMO 2014-2015 Sourced entirely by CMOs CMO CMO CMO Out-sourced CMO CMO CMO CMO Out-sourced Cam-bridge Cam-bridge 2016-2018 Sourced by Moderna & CMOs Norwood Norwood Norwood Norwood Norwood CMO + 2H 2018+ Norwood as primary, CMOs as back-up External/ CMO Internal Moderna


Slide 34

Manufacturing in Norwood brings a competitive advantage to CMV vaccine (mRNA-1647) Cost at economical scale (anticipated 90+ % Gross Margin for mRNA-1647 in US) Enables fast scale up mRNA technology : Platform allows similar manufacturing process across all products Process improvements implemented fast to platform processes Cell-free process to make mRNA Less future capital investment


Slide 35

CMV vials already produced for phase 2 trial Same lyophilized image intended for phase 3 Norwood site can produce mRNA and LNP for phase 3 Norwood site can support commercial launch (FFF to be done at CMO) Potential for >10+ million doses/year from Norwood


Slide 36

CMV commercial opportunity Stéphane Bancel Chief Executive Officer


Slide 37

Preparing for the pivotal phase 3 trial Near-term initiation of the dose-confirmation phase 2 (supply and clinical operations preparation is already advanced) Rapid phase 2 with 252 healthy subjects and a three-month interim analysis (IA) endpoint Phase 3 to demonstrate prevention of CMV infection in a sub-8,000 participant study in healthy women Our development plan for our CMV vaccine mRNA-1647


Slide 38

Large unmet medical need with no approved vaccine CMV is a blockbuster commercial opportunity


Slide 39

Large unmet medical need with no approved vaccine Indication expansion opportunity CMV is a blockbuster commercial opportunity Women of child bearing age (WOCBA) ~ 8 million (USA+EU only) Adolescents HPV vaccine precedent Infants Early vaccination Rubella precedent (ubiquitous MMR vaccine)


Slide 40

Large unmet medical need with no approved vaccine Indication expansion opportunity Total addressable market could be as high as 40-70 million vaccinations per year CMV is a blockbuster commercial opportunity


Slide 41

2030 Birth Cohort Opportunity Size 2040 Birth Cohort Opportunity Size Accessible male & female birth cohort exceeding 20 million around the anticipated time of potential launch 2050 Birth Cohort Opportunity Size Further market maturation grows the addressable cohort to more than 70 million by 2050 10 years later, improved market access expands the cohort to over 40 million CMV vaccine infant cohort opportunity size Source: UN Population Division; INED; UNICEF. Region Births U.S. ~3.6 M Europe ~5.4 M Japan ~0.9 M 10% of China ~1.4 M 10% of India ~2.5 M 10% of ROW ~8.8 M Total ~22.6 M Region Births U.S. ~3.7 M Europe ~4.7 M Japan ~0.9 M 25% of China ~3.4 M 25% of India ~6.3 M 25% of ROW ~22.3 M Total ~41.3 M Region Births U.S. ~3.7 M Europe ~4.7 M Japan ~0.9 M 50% of China ~6.6 M 50% of India ~12.7 M 50% of ROW ~44.7 M Total ~73.3 M


Slide 42

Large unmet medical need with no approved vaccine Indication expansion opportunity Total addressable market could be as high as 70 million vaccinations per year Focused sales effort: OBGYN and Pediatricians CMV is a blockbuster commercial opportunity


Slide 43

Large unmet medical need with no approved vaccine Indication expansion opportunity Total addressable market could be as high as 70 million vaccinations per year Focused sales effort: OBGYN and Pediatricians Opportunity to leverage social media during Phase 3 for pre-launch activities to educate a motivated initial target population, women of childbearing age (WOCBA) CMV is a blockbuster commercial opportunity


Slide 44

We aim to raise CMV awareness in the medical community and the public to accelerate trial recruitment and launch uptake Source: ClearView Partner with national and regional CMV advocacy groups 1 Educate OB/GYNs, pediatricians, and PCPs about congenital CMV infection 2 Distribute educational materials to key populations through physicians 3 Promote awareness of mRNA-1647 5 Strategic Initiatives Description Establishing early relationships with advocacy groups to influence policy and guidelines Educating physicians in the near term, particularly with PCPs who have limited awareness Informational pamphlets on risks of congenital CMV infection and current prevention tactics can be distributed through OB/GYN, pediatrician, and PCP offices to engage key populations Emphasizing antibody titer profile of mRNA-1647 Beneficial to Trial Recruitment Leverage online platforms to raise CMV awareness in key populations 4 Additional raising of awareness of CMV and its consequences in key populations


Slide 45

Large unmet medical need with no approved vaccine Indication expansion opportunity Total addressable market could be as high as 70 million vaccinations per year Focused sales effort: OBGYN and Pediatricians Opportunity to leverage social media during Phase 3 for pre-launch activities to educate a motivated initial target population, women of childbearing age (WOCBA) Pricing power for innovative vaccines due to value proposition (GARDASIL* US pricing=$450) CMV is a blockbuster commercial opportunity *GARDASIL ® is a registered trademark of Merck & Co., Inc.


Slide 46

Large unmet medical need with no approved vaccine Indication expansion opportunity Total addressable market could be as high as 70 million vaccinations per year Focused sales effort: OBGYN and Pediatricians Opportunity to leverage social media during Phase 3 for pre-launch activities to educate a motivated initial target population, women of childbearing age (WOCBA) Pricing power for innovative vaccines due to value proposition (GARDASIL* US pricing=$450) Vaccine sales are annuity-like, scaling with population growth CMV is a blockbuster commercial opportunity *GARDASIL ® is a registered trademark of Merck & Co., Inc.


Slide 47

Large unmet medical need with no approved vaccine Indication expansion opportunity Total addressable market could be as high as 70 million vaccinations per year Focused sales effort: OBGYN and Pediatricians Opportunity to leverage social media during Phase 3 for pre-launch activities to educate a motivated initial target population, women of childbearing age (WOCBA) Pricing power for innovative vaccines due to value proposition (GARDASIL* US pricing=$450) Vaccine sales are annuity-like, scaling with population growth Innovative vaccines have EBIT margins of approximately 50% CMV is a blockbuster commercial opportunity Moderna owns global commercial rights to mRNA-1647 Norwood now provides the scalability we need for our growing pipeline *GARDASIL ® is a registered trademark of Merck & Co., Inc.


Slide 48

Q&A


Slide 49

R&D Day 2019 agenda Sign-in, Coffee, Breakfast 7:30–8:30 AM 60 min Introduction Stéphane Bancel 8:30–8:40 AM 10 min CMV Tal Zaks, MD, PhD Sallie Permar, MD, PhD, Duke University School of Medicine Tal Zaks, MD, PhD Juan Andres Mark Schleiss, MD, University of Minnesota Laura Riley, MD, Weill Cornell Medical College Stéphane Bancel 8:40–10:00 AM 70 min Q&A 10:00–10:30 AM 30 min Break 10:30–10:40AM 10 min Immuno-oncology Tal Zaks, MD, PhD Keith Flaherty, MD, Massachusetts General Hospital 10:40–11:10 AM 30 min Antibody against Chikungunya virus Tal Zaks, MD, PhD 11:10–11:50AM 40 min Methylmalonic acidemia Gregory Enns, MD, Stanford University 11:50–12:20 AM 30 min Conclusion Stéphane Bancel 12:20–12:30 PM 10 min Q&A Moderna Team 12:30–1:00 PM 30 min Lunch September 12, 2019


Slide 50

Cancer vaccines and Intratumoral immuno-oncology Tal Zaks, MD, PhD Chief Medical Officer


Slide 51

Modalities Intratumoral immuno-oncology Prophylactic vaccines Cancer vaccines Localized regenerative therapeutics Systemic intracellular therapeutics Systemic secreted therapeutics


Slide 52

mRNA-4157 Phase 1 ongoing, dose expansion cohorts recruiting. Protocol for randomized Phase 2 filed with FDA. NCI-4650 Phase 1 ongoing (investigator-initiated, single-arm trial sponsored by the NCI). KRAS vaccine mRNA-5671 CRC, NSCLC,50-50 global profit pancreatic cancersharing with Merck Note: NCI-4650 differs from mRNA-4157 in its neoantigen selection process Modality Program # Program Indication Preclinical development Phase 1 Phase 2 Phase 3 and commercial Moderna rights Cancer vaccines mRNA-4157 Personalized cancer vaccine (PCV) 50-50 global profit sharing with Merck NCI-4650 Personalized cancer vaccine (PCV) Cancer Vaccines V941


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Natural cellular processing (antigen presentation, membrane proteins) Combinations (neoantigens, immuno-stimulatory agents) Single process and single, multi-product facility enables rapid production and economies of scale Transient, localized immuno-stimulatory effect at the tumor site mRNA sequences can be engineered to reduce off-target effects mRNA advantages in immuno-oncology


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mRNA opportunity in immuno-oncology Combining with PD1/PDL1 inhibitors to improve the benefit to patients Powerful antitumor responses can be achieved by activating antigen specific T cells  Checkpoint inhibitors available to unleash tumor-reactive T cells and provide significant benefit to a subset of patients However, majority of patients with epithelial cancers do not respond fully or at all to checkpoint inhibitors Our vaccines focused on expressing neoantigens found in a particular cancer Potential to improve efficacy of checkpoint inhibitors by increasing number and antitumor activity of T cells that recognize neoantigens Immuno-oncology today Cancer vaccines Intratumoral immuno-oncology Focused on activating T cells and transforming the tumor micro-environment to drive anti-cancer response In combination with checkpoint inhibitors


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Moderna’s mRNA vaccines elicit T cell activation for curative intent cancer therapy


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Personalized cancer vaccine (mRNA-4157) Designed to target an individual patient’s unique tumor mutations Partnered with Merck (Keytruda combo) Interim Phase 1 data presented at ASCO 2019 Dosed for up to 9 cycles Randomized Phase 2 trial in adjuvant melanoma started and major histocompatibility complex


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Personalized Cancer Vaccines mRNA-4157: Phase 1 data Clinical & regulatory update Continuing to enroll patients in phase 1 safety, tolerability and immunogenicity trial monotherapy and in combination with pembrolizumab Part C&D: Continuing to enroll patients Interim safety, tolerability immunogenicity data presented at ASCO 20191 First patients consented for phase 2 Randomized Controlled Trial Select clinical data1 Safety: mRNA-4157 is well tolerated at all dose levels studied with no DLTs reported. No mRNA-4157 related grade 3/4 AE or SAE was reported. The most common grade 2 adverse events were fatigue, soreness at the injection site, colitis and myalgias. Activity: Neoantigen specific CD8 T-cell responses were detected in 10 out of 18 class I neoantigens in patient 40033, the first patient dosed at 1 mg who underwent apheresis. 100% of positive CD8 T-cell responses post vaccination were to neoantigens with a high predicted binding affinity of <500 nm Early clinical: Clinical responses have been seen in 6 out of 20 patients treated with mRNA-4157/pembrolizumab combination. Of these 6 patients, 2 responses have been seen in patients previously treated with PD-(L)1 inhibitor and 1 patient achieved CR prior to vaccination 1 Data cutoff as of May 10, 2019 Patient 40033 apheresis data


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KRAS opportunity: mutation is present in >20% of human cancers KRAS is a key regulator of cell proliferation and survival; mutations cause dysregulated cell proliferation One of the most frequently mutated oncogenes in human cancers Mutations found principally in pancreatic cancer, lung cancer, and colorectal cancer Most prevalent KRAS mutations G12D, G12V, G13D, and G12C 80-90% of KRAS mutations KRAS Mutation Prevalence (% with KRAS mutation) Patients whose tumors harbor KRAS mutations have worse outcomes Histology G12C G12D G13D G12V Colorectal 3% 13% 7% 9% Lung Adenocarcinoma 13% 4% 1% 5% Pancreatic 1% 34% <1% 28% Percentage of KRAS mutation type by histology


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KRAS Vaccine mRNA-5671/Merck V941: KRAS Overview: KRAS is a key regulator of cell proliferation and survival; mutations cause dysregulated cell proliferation One of the most frequently mutated oncogenes in human cancers; mutation is present in >20% of human cancers Mutations found principally in pancreatic, lung and colorectal cancers Recognition of mutated KRAS epitopes by T-cells can lead to cancer cell regression as proven by adoptive T-cell transfer1 mRNA-5671/Merck V941: Codes for the four most prevalent KRAS mutations G12D, G12V, G13D, and G12C covering 80-90% of KRAS mutations 1 T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer, NEJM, Eric Tran, Ph.D., et al.


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KRAS vaccine (mRNA-5671)/Merck V941 Patients dosed in Phase 1 trial Phase 1 study overview A Phase 1, Open-Label, Multicenter Study to Assess the Safety and Tolerability of mRNA-5671/Merck V941 as a Monotherapy and in Combination With Pembrolizumab in Participants With KRAS Mutant Advanced or Metastatic Non-Small Cell Lung Cancer, Colorectal Cancer or Pancreatic Adenocarcinoma Selecting for HLA subtypes (HLA-A*1101 and/or HLA-C*0802) most likely to respond


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OX40L+IL23+IL36γ mRNA-2752(Triplet)Worldwide Solid tumors/lymphoma 50-50 U.S. profit MEDI1191IL12sharing; AZ to pay Solid tumorsroyalties on ex-U.S. sales Modality Program # Program Indication Preclinical development Phase 1 Phase 2 Phase 3 and commercial Moderna rights Intratumoral immuno- oncology mRNA-2416 OX40L Solid tumors/lymphoma Advanced ovarian Cancer Worldwide Intratumoral Immuno-Oncology


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OX40L (mRNA-2416) OX40L Overview: OX40L is a potent co-stimulator, which promotes T-cell proliferation and enhanced survival in the presence of antigen mRNA-2416: mRNA-2416 encodes for OX40L, which is a membrane protein that we believe cannot be manufactured by recombinant technologies


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Clinical: Interim analysis SITC 2018: mRNA-2416 is tolerable at all dose levels studied with no DLTs reported and the majority of AE’s being grade 1 or 2 A clear increase in OX40L protein expression from mRNA-2416 was observed in both tumor and stromal regions in three out of the five post-treatment biopsies collected from injected tumors  Repeat dosing through 12 doses (6 cycles) continues at highest levels (8mg) in phase 1 Phase 2 cohort in patients with ovarian cancer, including in combination with durvalumab is being prepared OX40L (mRNA-2416) OX40L expression demonstrated: progressing to phase 2 cohort PRE administration DAPI/Cytokeratin/OX40L OX40L QIF score= 558.2 POST administration DAPI/Cytokeratin/OX40L OX40L QIF score= 7047.1 Ovarian carcinoma 1 mg dose OX40L protein production in tumor cells of an injected lesion of a patient with ovarian cancer


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OX40L+IL23+IL36(Triplet) (mRNA-2752)   OX40L+IL23+IL36(Triplet) Overview: OX40L powerful co-stimulatory protein that enhances T-cell expansion, function and memory formation IL23 and IL36 have established roles in mediating immune responses mRNA-2752: mRNA-2752 encodes for OX40L which is a membrane protein and secreted pro-inflammatory cytokines IL-23 and Il-36  


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OX40L+IL23+IL36γ (Triplet) (mRNA-2752) Phase 1 ongoing; First patient dosed in combination durvalumab Key Objectives Evaluate safety and tolerability of mRNA-2752 administered alone and in combination with checkpoint inhibitors Define MTD and recommended dose for expansion for mRNA-2752 alone and in combination with durvalumab Intended to assess: Anti-tumor activity Protein expression in tumors Pharmacokinetics Patients dosed in combination arm


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IL12 (MEDI1191) IL12 Overview: IL12 is a potent immune modulator associated with type 1 immune response and production of interferon gamma MEDI1191: Encodes for IL12, a secreted cytokine that acts locally in the tumor microenvironment (TME)


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Clinical: Phase 1, open-label, multicenter, dose escalation and expansion study of MEDI1191 administered intratumorally as monotherapy and in combination with durvalumab in subjects with advanced solid tumors Key objectives to evaluate safety and tolerability in monotherapy and combination arms and objective response rate in patients within expansion arms First patient dosed with IL12 monotherapy in phase 1 trial IL12 (MEDI1191) First patient dosed in phase 1 Preclinical: Slide


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Systemic Therapeutics - Secreted and Intracellular Tal Zaks, MD, PhD Chief Medical Officer


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Progress by modality Intratumoral immuno-oncology Prophylactic vaccines Cancer vaccines Localized regenerative therapeutics Systemic intracellular therapeutics Systemic secreted therapeutics


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Systemic secreted therapeutics 50-50 U.S. profit AZD7970Relaxinsharing; AZ to pay Heart failureroyalties on ex-U.S. sales mRNA-3630 -GAL Worldw ide Fabry disease   Modality ID # Program Indication Preclinical dev elopment Phase 1 Phase 2 Phase 3 and commercial Moderna rights Systemic secreted therapeutics mRNA-1944 Antibody against Chikungunya virus Worldw ide DARPA funded


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Systemic secreted therapeutics 50-50 U.S. profit AZD7970Relaxinsharing; AZ to pay Heart failureroyalties on ex-U.S. sales mRNA-3630 -GAL Worldw ide Fabry disease   Modality ID # Program Indication Preclinical dev elopment Phase 1 Phase 2 Phase 3 and commercial Moderna rights Systemic secreted therapeutics mRNA-1944 Antibody against Chikungunya virus Worldw ide DARPA funded


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Antibody against Chikungunya virus (mRNA-1944) mRNA-1944 contains two mRNAs that encode for the heavy and light chains of CHKV-24 antibody, which may confer passive immunity Expected protective level in mice2


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Species: Mouse Antibody against Chikungunya virus (mRNA-1944) Preclinical evidence that mRNA-1944 encodes for functional antibody against Chikungunya virus Expected protective level Therapeutic level for autoimmune and oncology drugs Expression of antibody against Chikungunya virus with repeat dosing of mRNA-1944 in non-human primate study Species: NHP Expression of antibody against Chikungunya virus Survival after prophylactic vaccination with mRNA-1944 mRNA-1944 produces an antibody against Chikungunya virus that is Functional Protective Translates between pre-clinical species


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Key Objectives Safety: Evaluate safety and tolerability of escalating doses of  mRNA-1944 administered via intravenous infusion Translation of protein: Evaluate pharmacology of mRNA-1944 Activity: Determine ability of antibody to neutralize viral infection Antibody against Chikungunya virus (mRNA-1944) Trial design Randomized, placebo-controlled, single ascending dose study in healthy adults All subjects received premedication with antihistamines No subjects received corticosteroids (permitted by protocol)


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Antibody against Chikungunya virus (mRNA-1944) Protective antibody levels of >1µg/mL expected to endure at least 16 weeks at the middle dose of 0.3 mg/kg Pharmacology Administration of mRNA-1944 resulted in dose-related increase in levels of CHKV-24 Half life (t1/2) of antibody was 62 days Middle and high dose (0.3 and 0.6 mg/kg) projected to exceed 1 µg/mL target for at least 16 weeks Cohort 0.1 mg/kg (N=6)  0.3 mg/kg (N=6) 0.6 mg/kg (N=4) Cmax (µg/mL) 2.0 7.9 10.2 Cmax  range  (µg/mL) 1.1-3.1 6.3-10.0 7.0-14.2 Cmax   % CV 40.6% 18.2% 29.7%


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Antibody against Chikungunya virus (mRNA-1944) mRNA-1944 driven protein expression results in functional antibody (CHKV-24) Neutralizing antibody titers observed at all dose levels, indicating functional antibody production by mRNA-1944 All placebo subjects below the lower limit of detection 100% of subjects administered 0.3 and 0.6 mg/ kg had titers >100 Serum neutralization activity 48 hr after mRNA-1944 administration Dose Level (mg/kg) Percent of Subjects Achieving NT50 >100


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Antibody against Chikungunya virus (mRNA-1944) Summary of related adverse events Cohort Grade 1 Grade 2 Grade 3 Placebo (N=6) None None None mRNA-1944 0.1 mg/kg (N=6) Feeling of warmth, transient (1) None None mRNA-1944 0.3 mg/kg (N=6) None None None mRNA-1944 0.6 mg/kg (N=4) Subject 1 Sinus tachycardia, fever, infusion associated shivering, lightheadedness, hypotension None None Subject 2 None Nausea, emesis None Subject 3 None None None Subject 4 Chills, headache, lightheadedness, gaseousness EKG abnormal (T wave inversion), emesis, nausea, fever Sinus tachycardia, elevated WBC All AEs were transient and resolved spontaneously without treatment  No serious AEs in the study No meaningful changes in liver or kidney laboratory results


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Antibody against Chikungunya virus (mRNA-1944) Translation from preclinical species to humans Solid line = Median predicted Shaded area = 90% prediction interval Symbols = Individual participant observations CHKV-24 IgG concentration (µg/mL)


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Conclusions: mRNA-1944 achieved the target level of functional protein translation at a well tolerated dose Administration of mRNA-1944 resulted in dose-dependent increases in levels of  antibody against Chikungunya (CHKV-24)  Neutralizing antibodies were observed at all dose levels, indicating functional antibody production by mRNA-1944 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) mRNA-1944 at 0.3 mg/kg and 0.6 mg/kg provides antibody levels that are expected to be protective against Chikungunya infection (>1 µg/mL) for at least 16 weeks, supporting further development. mRNA to protein translation in human was predicted by preclinical data


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MRNA-1944 enables Moderna's systemic therapeutics For the first time, the systemic administration of an mRNA containing LNP has been demonstrated to produce a fully functional complex protein in humans Dose dependent pharmacology has been fully predicted from preclinical species with no loss of potency Target therapeutic concentrations have been achieved at a well tolerated dose in a healthy volunteer population We believe these data strongly support the continued development of our systemic rare disease therapeutic modality that targets both secreted and intracellular proteins


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Phase 1/2 Recruiting patients IND Open Natural history study initiated Successful IND-enabling GLP toxicology studies Pre-clinical activity and dose dependent pharmacology in animal models Sites open for MMA phase 1/2 trial and actively recruiting patients MMA (mRNA-3704) utilizes the same LNP formulation as antibody against Chikungunya virus (mRNA-1944) Progress in the systemic intracellular therapeutics modality to date Clinical Preclinical Systemic intracellular therapeutics MMA mRNA-3704 PA mRNA-3927 PKU mRNA-3283 N/A Ongoing GSD1a mRNA-3745 Ongoing N/A


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Conclusion Stéphane Bancel Chief Executive Officer


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Two important positive clinical milestones in two modalities announced today Cytomegalovirus (CMV) vaccine (mRNA-1647) Positive interim phase 1 data Successfully immunized seronegatives and boosted seropositives Generally well tolerated Phase 2 to start in the near term Preparations underway for the phase 3 Moderna owns the global commercial rights to mRNA-1647 Antibody against Chikungunya virus (mRNA-1944) Positive phase 1 data Observed dose dependent protein expression Achieved expected therapeutic levels at a well tolerated dose (0.3mg/kg) Observed expected translation from NHP to human


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Moderna continues to mature and clinical data are validating the quality and relevance of our science 4 programs in or preparing for phase 2 10 positive phase 1 studies (6 vaccines, PCV, OX40, VEGF and Chikungunya antibody) 12 programs in phase 1 Vaccine modality: Six vaccines with positive phase 1 data, including CMV CMV, RSV, hMPV+PIV3 in clinical trials, each as a potential blockbuster opportunity 5 I/O programs dosing patients in Phase 2 or Phase 1: PCV and KRAS with Merck (50/50 global profit share) IL12 with AstraZeneca (50/50 US profit share) OX40L and Triplet wholly owned by Moderna Antibody against Chikungunya virus (mRNA-1944) phase 1 data validates: mRNA approach for making a functional IgG antibody LNP delivery technology shared by rare disease pipeline candidates


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We believe innovative vaccines are a great business Me too vaccines (i.e., Tetanus, …) Innovative vaccines (i.e., Prevnar, HPV…) Public health vaccines (i.e., Yellow Fever…) Moderna will not fund, but might partner Moderna will fund or partner Moderna will partner with governments and foundations to pursue social and public health goals Pricing: $ $$$ $ %EBIT: 10-25% ~50% 0-25%


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Several vaccines have realized this value-add with strong, recurring revenues Source: EvaluatePharma Top selling vaccines, by 2024 projected sales Vaccine Indication Company Launch Year 2018 WW Sales 2024E WW Sales Prevnar 13* Pneumococcus Pfizer 2000 (PCV7) $5.8 bn $6.7 bn GARDASIL** HPV Merck 2006 $3.2 bn $5.9 bn SHINGRIX*** Herpes zoster GSK 2017 $1.0 bn $3.5 bn *Prevnar 13 ® is a registered trademark of Wyeth LLC. **GARDASIL ® is a registered trademark of Merck & Co., Inc. ***Shingrix is a registered trademark of GSK


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Build a strong vaccine business based on innovative vaccines like CMV, RSV, hMPV+PIV3, Zika… Execute the clinical research plans on 5 I/O programs to potentially improve on PD1/PDL1 mono therapy Build a rare disease business, with an initial focus on metabolic diseases Expand into new therapeutic areas Our strategy for the mid-term


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Large product opportunity Higher probability of technical success Accelerated research and development timelines Greater capital efficiency over time vs. recombinant technology Moderna’s vision is intact: more than ever, we believe mRNA could be a potential new class of medicines


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Our Mission To deliver on the promise of mRNA science to create a new generation of transformative medicines for patients.


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Thank you