© 2020 Moderna

mRNA-1273 Clinical Development Program 

Jacqueline M. Miller, M.D., F.A.A.P. 

August 26, 2020 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

© 2020 Moderna

Forward-looking statements and disclaimer 

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 timing, design, objectives and other parameters of the Phase 1, Phase 2 and Phase 3 clinical studies of mRNA-1273. 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 forwardlooking 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 class of medicines such 

as mRNA, and therefore our preclinical programs or development candidates may be delayed, terminated, or may never advance to or in the clinic; no 

commercial product using mRNA technology has been approved, 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; despite having ongoing interactions with the U.S. Food and Drug 

Administration (FDA), European Medicines Agency (EMA) or other regulatory agencies, the FDA, EMA or such other regulatory agencies may not agree with 

Moderna’s regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data 

submitted; 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 clinical trials, preclinical work, 

overall operations, regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy; 

and those 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 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. 

Slide 
mRNA-1273 encodes for the full-length Spike Protein in the Pre-fusion 

Conformation (S-2P) 

© 2020 Moderna

Slide 3 
 

 

 

 

 

 

 

 

Confidential and Proprietary © 2020 Moderna

Pre-clinical data 

support human 

clinical trials with 

mRNA-1273 

1. Corbett KS, Edwards D, Leist SR, et al. SARS-CoV-2 mRNA vaccine 

development enabled by prototype pathogen preparedness. 

Nature 2020; Nature 2020; DOI: 10.1038/s41586-020-2622-0 

2. Corbett KS, Flynn B, Foulds KE, et al. Evaluation of the mRNA-1273 

vaccine against SARS-CoV-2 in nonhuman primate. N Engl J Med. 

28 July 2020; DOI: 10.1056/NEJMoa2024671. 

· 

 Robust neutralizing antibody responses in mice1, aged 

mice, and non-human primates (NHPs)2 have been 

induced 

 mRNA-1273 demonstrated robust protection against 

lung challenge in mice1, and pulmonary and nasal 

challenge in NHPs2 

 No indication of enhanced respiratory disease after 

viral challenge even when subprotective doses of 

mRNA-1273 are used2 

 A Th1-dominant phenotype of CD4+ T-cells has 

induced in mice1 and NHPs2 

Slide 4 
 

 

-

2020 2021 

Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 

Study end dates are estimated 

P201 Phase 2 Safety and Immunogenicity Trial 

P101 First in Human and Dose Ranging (NIH Sponsored) 

P301 Phase 3 Pivotal Safety, Efficacy, and Immunogenicity Trial 

Nonclinical 

mRNA-1273 Clinical Development Plan 

Data Package Required Prior to Start P301 

Safety & immunogenicity from P101 

(post-dose 2 data for 100ug cohorts) 

P201 safety report from SMC 

Animal model data demonstrating nAbs, 

protection from challenge, Th-1-biased 

CD4+ T-cells and protection from ERD 

Other populations for further evaluation (timing TBD) 

Pediatrics 

Pregnant women 

Immunocompromised populations 

Dose Selection for P301

Safety and 

immunogenicity P101 

Response relative to 

convalescent sera 

Slide 

© 2020 Moderna 

5 
 

 

 

 

 

 

 

 

 

 

mRNA-1273 NIH-Sponsored, Phase 1, Safety and Dose-Ranging Study 

(N=120) 

Phase 1 trial overview (NCT04283461) 

Protocol Title Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-nCoV Vaccine (mRNA-1273) in 

Healthy Adults 

Study Groups Cohorts1 Age groups Dosage (D1, D29) Sample size Enrollment status 

1-3 18 to 55 25, 100, 250 mcg 45 Fully enrolled (45/45) 

4, 5 56 to 70 25, 100 mcg 20 Fully enrolled (20/20) 

7, 8 

10-13 

≥71

18-55, 56-70, ≥71

25, 100 mcg 

50 mcg 

20 

35 

Fully enrolled (20/20) 

Fully enrolled (35/35) 

Population Healthy males and females at or above 18 years of age 

“All-comers” with regard to SARS-CoV-2 serostatus (baseline serology will be collected) 

Study Endpoints Safety (solicited AR x 7 days post each injection; unsolicited AE 28 days post-vaccination; SAE and MAAE) 

Immunogenicity (e.g., ELISA, pseudoneutralization, live virus neutralization and intracellular cytokine staining assay) 

Study duration Approximately 13 months for each participant corresponding to a 12-month follow up after the last vaccine administration 

1. Cohorts 6 and 9 (250 mcg cohorts) will not be enrolled on this study 

Jackson L, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2- preliminary report. N Engl J Med. 14 Jul 2020; DOI: 10.1056/NEJMoa2022483 Slide 

© 2020 Moderna 

6 
Pseudovirus neutralization assay titers (ID50): age 18 – 55 Years 

Range of 

convalescent sera 

Dose selection of 100 mcg was based on 

comparable nAb titers to 250 mcg with improved 

safety profile 

 

 

 

 

 

 

 

Key Takeaways 

 Day 14 post-dose 2, 

nAbs were 

observed in all 

participants 

 The lowest 

responses were 

in the 25 mcg dose 

group 

 Responses in the 

100 mcg and 250 

mcg groups were 

similar to the upper 

half of the range of 

convalescent sera 

Jackson L, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2- preliminary report. N Engl J Med. 14 Jul 2020; DOI: 10.1056/NEJMoa2022483 Slide 

© 2020 Moderna 

7 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Feverishness

Interim unpublished data 

100 mcg mRNA-1273 Well-Tolerated Across Age Groups 

Phase 1: No Vaccine-Related SAEs Have Been Reported 

Solicited Local and Systemic Symptoms Followed for 7 Days Post-vaccination 

Majority of symptoms resolved within 2 days, some persisted as long as 5 days 

Grade 1 (mild) Grade 2 (moderate) Grade 3 (severe) 

Symptom Age group2 Vaccination 1 Vaccination 2 Symptom Age group2 Vaccination 1 Vaccination 2 

Any systemic 

symptom 

18-55 

56-70 

71+ 

Arthralgia 

18-55 

56-70 

71+ 

Fatigue 

18-55 

56-70 

71+ 

Fever1 

18-55 

56-70 

71+ 

Chills 18-55 

56-70 

71+ 

Headache 

18-55 

56-70 

71+ 

Myalgia 

18-55 

56-70 

71+ 

Nausea 

18-55 

56-70 

71+ 

Any local 

symptom 

18-55 

56-70 

71+ 

Erythema, 

redness 

measurement 

18-55 

56-70 

71+ 

Induration/ 

swelling 

measurement 

18-55 

56-70 

71+ 

Pain 

18-55 

56-70 

71+ 

0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100 0 20 40 60 80 100 

Percentage of severity Percentage of severity Percentage of severity Percentage of severity 

1. Fever percentages reflect the number of subjects with at least one measurement available in the data system as the denominator. This 

denominator may differ from other systemic symptoms, which are solicited in-clinic at the post-dose assessment 

2. 18-55: N=15; 56-70: N=10; 71+: N=10; N = All subjects receiving Dose 1 with any solicited event data recorded in the database 

Jackson L, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2- preliminary report. N Engl J Med. 14 Jul 2020; DOI: 10.1056/NEJMoa2022483 Slide 8 

© 2020 Moderna 
– –

Anti-S-2P Binding Ab (ELISA) Comparable Across Age 

Strata and to Convalescent Sera at one month PD2 

S-2P binding antibodies (ELISA)- 100 μg at Day 1 and Day 29 

18 55 years 56 70 years 71+ years 

Range of 

convalescent sera 

 

 

PD1= Post-dose 1; PD2= Post-dose 2 

Vaccination administered at Day 1 and Day 29 

Interim unpublished data 

Key Takeaways 

 100 mcg two-dose series 

seroconverted all 

participants PD1 

 PD1 AUC for all age 

groups exceeded the 

median of convalescent 

sera 

 PD2 all age groups is 

equivalent to high-titer 

convalescent sera (i.e., 

upper quartile) 

Jackson L, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2- preliminary report. N Engl J Med. 14 Jul 2020; DOI: 10.1056/NEJMoa2022483 

Interim Immunogenicity Report Slide 

© 2020 Moderna 

9 
 

 

– –

SARS-CoV-2 nAb Comparable Across Age Strata 

and to Convalescent Sera out to Day 57 PD2 

Pseudovirus neutralization assay titers (ID50)- 100 μg at Day 1 and Day 29 

18 55 years 

D57 GMT: 267 

95% CI: 186, 385 

56 70 years 

D57 GMT: 324 

95% CI: 212, 496 

71+ years 

D57 GMT: 242 

95% CI: 147, 399 

Range of 

convalescent sera 

 

 

 

D57: one month post-dos e 2

GMT: geometric mean antibody titer 

95% CI: 95% confidence interval 

PD2= Post-dose 2 

Vaccination administered at Day 1 and Day 29 

Jackson L, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2- preliminary report. N Engl J Med. 14 Jul 2020; DOI: 10.1056/NEJMoa2022483 

Interim unpublished data 

Key Takeaways 

 PD2 pseudovirus 

neutralization responses 

were detected in all 

participants 

 PsV titers were comparable 

across age groups 

 PsV median titer for 56-70 

and 71+ YOA above 

convalescent sera median 

titer at Day 57 PD2 

Slide 10 

© 2020 Moderna 
– –

mRNA-1273 induces CD4+ T-cells of the Th-1 Phenotype 14 days PD2 

Any Th-1 response IL-2 

Interferon-γ TNF-α Th1 CD4+ T cell response, S1 peptide pool (100 μg at Day 1 and 29)

0.0 

0.2 

0.4 

0.6 

0.8 

Day 1 Day 29 Day 43 

% CD4 T cells 

18 55 years 56 70 years 71+ years 

 

Interim unpublished data 

Key Takeaways 

 Vaccination with 100 mcg mRNA-1273 led a Th1-biased CD4+ T-cell response across all age groups 

 Th2 phenotype was rare (data not shown) 

Jackson L, Anderson EJ, Rouphael NG, et al. An mRNA vaccine against SARS-CoV-2- preliminary report. N Engl J Med. 14 Jul 2020; DOI: 10.1056/NEJMoa2022483 Slide 11 

© 2020 Moderna 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

mRNA-1273 Phase 2 Study will Evaluate Safety and Immunogenicity of 

50 mcg and 100 mcg (N=600) 

Phase 2 trial overview (NCT04405076) 

Protocol Title A Phase 2a, Randomized, Observer-Blind, Placebo-Controlled, Dose-Finding Study to Evaluate the Safety, Reactogenicity, and 

Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older 

Study Groups Cohorts Age groups Dosage IM (D1, D29) 1:1:1 Sample size Enrollment status 

Cohort 1 18 to <55 50mcg, 100mcg, placebo 300 Fully enrolled (300/300) 

Cohort 2 Sentinel ≥55 50mcg, 100mcg, placebo 50 Fully enrolled (50/50) 

Cohort 2 Full ≥55 50mcg, 100mcg, placebo 250 Fully enrolled (250/250) 

Participant 

Population 

Healthy males and females at or above 18 years of age 

“All-comers” with regard to SARS-CoV-2 serostatus (baseline serology will be collected) 

Study Endpoints Safety (solicited AR x 7 days post each injection; unsolicited AE to day 57; SAE and MAAE throughout the study); assessment of 

any cases of Covid-19; potential assessment for asymptomatic infection 

Immunogenicity (ELISA, nAb) 

Study Duration Approximately 13 months for each participant corresponding to a 12-month follow up after the last vaccine administration 

© 2020 Moderna 

Slide 12 
Study Groups Strata Dosage IM (D1, D29) 1:1 Sample Size Enrollment status 

≥ 65 years 100mcg, placebo Started July 27 

< 65 years at increased risk for complication of 

COVID-19 (“at risk”)

100mcg, placebo 

25-40% 

Started July 27 

< 65 years and not at risk 100mcg, placebo 60-75% Started July 27 

 

 

 

 

 

 

Pivotal Phase 3 Efficacy, Safety and Immunogenicity Study (N=30,000) 

Phase 3 trial overview (NCT04470427) 

Protocol Title A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and 

Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older 

Participant 

Population 

Approximately 30,000 participants (case driven) whose locations or circumstances put them at appreciable risk of acquiring 

COVID-19 and/or SARS-CoV-2 infection 

“All-comers” with regard to SARS-CoV-2 serostatus (baseline serology will be collected) 

Study 

Objectives 

To demonstrate the efficacy of mRNA 1273 to prevent COVID 19 

To evaluate the safety and reactogenicity of 2 injections of the mRNA-1273 vaccine given 28 days apart 

Study Duration Approximately 25 months for each participant corresponding to a 24-month follow up after the last vaccine administration 

Slide 13 

© 2020 Moderna 
 

 

 

 

 

 

 

 

 

Primary Efficacy Endpoint: COVID-19 Disease Case Definition 

To be considered a case of COVID-19 for the evaluation of the Primary Efficacy Endpoint, two 

criteria must be met: 

1 The participant must have experienced: 

 At least TWO of the following systemic symptoms: fever (≥ 38oC), chills, myalgia, headache,

sore throat, new olfactory and taste disorder(s) 

OR 

 At least ONE of the following respiratory signs/symptoms: cough, shortness of breath or 

difficulty breathing, OR clinical or radiographical evidence of pneumonia 

AND 

2 The participant must have at least one NP swab, nasal swab or saliva sample (or respiratory 

sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR 

Primary analysis set is seronegative and negative NP swab at baseline without major PD (Per Protocol) 

Slide 14 

© 2020 Moderna 
 

 

 

 

 

 

 

MODERNA NATIONAL INSITITUTES OF

HEALTH

OPERATION WARP

SPEED

COVPN US DEPARTMENT

OF VETERAN AFFAIRS

FAITH COMMUNITY

COVE D&I Advisory Committee 

Remit and Role of Advisory Committee: 

1. Review enrollment, race, and ethnicity 

demographics on a weekly basis 

2. Review current outreach activities and outcomes 

3. Review strategies to ensure participation of 

individuals from communities significantly impacted 

by COVID-19 

4. Support the development and implementation of 

retention strategies 

• National Institute on Allergy and 

Infectious Diseases 

• National Institute on Minority 

Health and Health Disparities 

• NIH, Tribal Health Research Office 

• NHLBI 

Slide 

© 2020 Moderna 
© 2020 Moderna

Limitations of Research 

 Limited safety and immunogenicity data in a fairly homogeneous population 

 Further evaluation needed in terms of vaccine use in: 

‒ Pediatric subjects 

‒ Pregnant women 

‒ Immunocompromised patients 

 The ongoing COVE Study will provide significantly more data 

Slide 16 
 

 

 

 

 

 

Summary 

 mRNA-1273 encodes the pre-fusion-stabilized Spike protein (S-2P) in a Lipid Nanoparticle 

designed for delivery to the APCs of the lymph node 

 Pre-clinical data have demonstrated induction of neutralizing Abs and protection 

against viral challenge in mice and NHPs 

 Interim data from Phase 1 study indicate that a 100 mcg dose of vaccine: 

‒ Is generally well-tolerated across age strata, with solicited symptoms mostly mild-tomoderate in severity and self-limited duration 

‒ Induces neutralizing Abs in the upper half of the range of convalescent serum across 

age strata, with the induction of Th-1 biased, CD4+ T-cells 

 Phase 2 and the Phase 3 COVE study are underway 

APC – Antigen presenting cells NHP – Nonhuman primate 

Slide 17 

© 2020 Moderna 
Thank you to our collaborators 

P101 P201 COVE Study (P301) 

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

















Division of Microbiology and Infectious 

Diseases, NIAID 

Vaccine Research Center (VRC), NIAID 

Coalition for Epidemic Preparedness 

Innovation 





BARDA 

Study sites, investigators, and 

subjects 













BARDA 

Operation Warp Speed 

NIAID and the COVID-19 

Prevention Network 

Principal Investigators, Drs. Lisa Jackson 

(Kaiser Permanente Washington), Evan 

Anderson (Emory University School of 

Medicine), Nadine Rouphael (Emory 

University School of Medicine), Alicia Widge 

(VRC) 

Members of Diversity and 

Inclusion Panel 

Principal Investigators, Drs. 

Brandon Essink (Meridian Clinical 

Research), Lindsey Baden 

(Brigham and Women’s Hospital), 

Hana El Sahly (Baylor College of 

Medicine) 

The Emmes Company 

Denison Lab, Vanderbilt University 

Baric Lab, University of North Carolina 

Suthar Lab, Emory University 

Vaccine Immunology Program, NIAID 

Study sites, investigators, and 

subjects 

Study sites, investigators and subjects Slide 18 

© 2020 Moderna