Document text
Overview of Moderna’s Investigational
Next Generation COVID -19 Vaccine,
mRNA -1283, in Individuals ≥12 Years of Age
© 2025 Moderna, inc. All rights reserved.ACIP
Bishoy Rizkalla, PhD
April 15, 20251
2
COVID -19 Remains a Leading Cause of Hospitalization
among Respiratory Viruses in the US
Adults ≥65 years account for:
•>60% of COVID -19 hospitalizations
(since 2023 )2
•~76% of deaths (since 2020)3•95% of adults hospitalized with
COVID -19 have ≥1 underlying
medical conditionRisk Factors for Severe COVID Infection in the US1
Advancing Age Pre-Existing Chronic Conditions4
© 2025 Moderna, inc. All rights reserved.Effective prophylactic approaches to address the burden
of disease in vulnerable populations remain a high priority
1.https:// www.cdc.gov/covid/hcp/clinical -care/underlying -conditions.html
2.https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network
3.https://covid.cdc.gov/covid -data -tracker/#demographics
4.https:// www.cdc.gov/pcd/issues/2021/21_0123.htm
3
Design of mRNA -1283
Investigational Next Generation COVID -19 Vaccine
7-amino acid flexible linker
N-terminal
Domain
(NTD)Receptor
Binding
Domain
(RBD)
Lower mRNA dose (10 µg; 1/5th of dose of Spikevax)
© 2025 Moderna, inc. All rights reserved.1.Piccoli et al, Cell 2020 doi: 10.1016/j.cell.2020.09.037
2.Dejnirattisai et al, Cell 2021 doi: 10.1016/j.cell.2021.03.055
3.Cerutti et al, Cell Host Microbe 2021 doi: 10.1016/j.chom.2021.03.005
Pivotal Safety, Immunogenicity
and Relative Vaccine Efficacy
Study
© 2025 Moderna, inc. All rights reserved.Study 3014
Chalkias et al. Lancet ID, in press, 2025
5
Study Design & Primary Objectives
Randomized, blinded, active -controlled phase 3 trial
Participants ≥12 years
mRNA -1283 (10 µg)
Original: Omicron BA.4/BA.5
Bivalent Vaccine
SPIKEVAX (mRNA -1273 - 50 µg)
Original: Omicron BA.4/BA.5
Bivalent VaccineStratified
randomization:
Age groups
(12-17, 18-64, and
≥65)N = 5,728
N = 5,7261:1
Primary Objectives
Safety and
Reactogenicity
mRNA -1283 & SPIKEVAXNon-Inferior
Immunogenicity
mRNA -1283 vs SPIKEVAXNon-Inferior Relative
Vaccine Efficacy (rVE)
mRNA -1283 vs SPIKEVAX
(based on CDC COVID -19 definition)
© 2025 Moderna, inc. All rights reserved.
6
© 2025 Moderna, inc. All rights reserved.Demographics and Baseline Characteristics Balanced
Between Groups
Study 301 - Safety SetmRNA -1283 (10 µg)
N = 5706SPIKEVAX (50 µg)
N = 5711
Mean age, years (range) 51.1 (12, 96) 51.2 (12, 90)
Median age, years 56 55
Age subgroup, % (n)
12-17 years 8.7% (497) 8.7% (495)
18-64 years 62.7% (3575) 62.6% (3576)
≥65 years 28.6% (1634) 28.7% (1640)
Race/Ethnicity, % (n)
White 81.8% (4670) 82.5% (4711)
Black or African American 11.2% (640) 11.1% (635)
Asian 3.9% (225) 3.2% (183)
Hispanic or Latino 13.5% (769) 13.0% (741)
≥1 pre-existing COVID -19 comorbidity (CDC definition) 46.0% (2626) 46.6% (2664)
Race/ethnicity generally representative of US population
https:// www.cdc.gov/covid/risk -factors/index.html;; https:// www.census.gov/quickfacts/fact/table/US/RHI225223
7Prior SARS -CoV-2 Infection and Time Since Last COVID -19
Vaccination Balanced Between Groups
Study 301 - Safety Set
•Eligibility criteria:
•All study participants previously received primary series of COVID -19 vaccine
•Adults ≥18 years received ≥1 dose beyond primary series
mRNA -1283 (10 µg)
N = 5706
© 2025 Moderna, inc. All rights reserved.SPIKEVAX (50 µg)
N = 5711
Prior SARS -CoV -2 Infection1 73.8% 74.8%
Months since last COVID -19 vaccination,
median (Q1, Q3)9.8 (7.6, 16.9) 9.8 (7.7, 16.7)
1.Evidence of SARS -CoV -2 infection pre-study vaccination (defined by a positive RT-PCR test, and/or a positive serology test based
on binding antibody specific to SARS -CoV -2 nucleocapsid)
2.Q - quartile
Safety Results
© 2025 Moderna, inc. All rights reserved.Study 3018
9
Primary Safety Endpoints and Duration of Follow -up
Study 301 Safety Set – Median 8.8 Months Follow -up
Active Safety
SurveillanceSolicited Local and
Systemic Adverse
Reactions
Unsolicited Adverse Events
Medically Attended AEs, Serious AEs Including Death, AEs Leading to Discontinuations
Adverse Events of Special Interest
(including Myocarditis, Pericarditis, Thrombocytopenia, Neurologic Events1, and Anaphylaxis)
7 Days 28 Days 12 months
© 2025 Moderna, inc. All rights reserved.Trial overseen by independent Data and Safety Monitoring Board (DSMB)
1. Neurologic events of interest include Guillain -Barre syndrome, acute disseminated encephalomyelitis, Bell’s palsy, and seizures; 2. AE – adverse event
10
Solicited Local Adverse Reactions within 7 Days of Vaccination
with mRNA -1283 and SPIKEVAX
Study 301 – Solicited Safety Set
69%78%
2%4% 4%6%20% 18%
0%20%60%
40%80%100%
mRNA -
1283mRNA -
1273mRNA -
1283mRNA -
1273mRNA -
1283mRNA -
1273mRNA -
1283mRNA -
1273Pain Erythema Swelling Axillary Swelling
or Tenderness
1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX
Grade 3
Grade 2
Grade 1
© 2025 Moderna, inc. All rights reserved.•Pain at the injection site was most frequently observed solicited local adverse reaction for both groups
•1 – 2 days median duration for local adverse reactions
Feb 23, 2024 data cutoff; mRNA -1283, N = 5702; mRNA -1273, N = 5706; no grade 4 reactions
11
Solicited Systemic Adverse Reactions within 7 Days of Vaccination
with mRNA -1283 and SPIKEVAX
Study 301 – Solicited Safety Set
6% 5%44%41%50% 49%
38% 37%
30%28%
12% 11%23%20%
20%40%60%80%100%Nausea/
VomitingFever Headache Fatigue Arthralgia Chills
0%
1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX
Myalgia
Grade 3
Grade 2
Grade 1
•Fatigue, headache, and myalgia most frequently observed solicited systemic adverse reactions for both groups
•1-2 days median duration for systemic adverse reactions
© 2025 Moderna, inc. All rights reserved.Feb 23, 2024 data cutoff; mRNA -1283, N = 5702; mRNA -1273, N = 5706. One participant in the mRNA -1273 group had a grade 4 fever. No grade 4 reactions.
12
© 2025 Moderna, inc. All rights reserved.Similar Frequency of Unsolicited AEs Within 28 Days After Injection,
Regardless of Relationship to Vaccine, Between mRNA -1283 and SPIKEVAX
Study 301 – Safety Set
mRNA -1283 (10 µg)
N = 5706SPIKEVAX (50 µg)
N = 5711
All, % (n) 12% (701) 12% (680)
Serious 0.2% (13) 0.3% (18)
Fatal 0% (0) 0.02% (1)
Medically -Attended 7% (425) 7% (422)
Leading to Study Discontinuation 0% (0) 0.02% (1)
Any Adverse Event of Special Interest (AESI) 0.05% (3) 0.1% (6)
Myocarditis/Pericarditis 0% (0) 0% (0)
Feb 23, 2024 data cutoff
Safety Summary through Median 8.8 Months of Follow -up
© 2025 Moderna, inc. All rights reserved.•No imbalances in any adverse events between the vaccine groups
•No myocarditis or pericarditis in recipients of mRNA -1283
•No safety concerns identified13
Immunogenicity
© 2025 Moderna, inc. All rights reserved.Study 30114
15mRNA -1283 Elicited Higher Antibody Response at Day 29
Compared to SPIKEVAX
Study 301 – Per-Protocol Immunogenicity Set (Randomly Selected Subset)
0 1 2GMC (95% CI)1mRNA -1283
(10 µg)
N = 621SPIKEVAX
(50 µg)
N = 568GMR (95% CI)
of mRNA -1283 over SPIKEVAX
Original SARS -CoV-210632
(9960, 11349)8577
(8013, 9180)1.2 (1.1, 1.4)
1.3 (1.2, 1.5)
BA.4/BA.52341
(2167, 2529)1754
(1618, 1901)
0.667
20 25Seroresponse Rate, % (95% CI) Seroresponse Rate Difference (95% CI)
Original SARS -CoV-283.6% 72.9% 10.7% (6.0, 15.4)
(80.4, 86.4) (69.0, 76.5)
BA.4/BA.579.9% 65.5% 14.4% (9.3, 19.4
(76.5, 83.0) (61.4, 69.4))
-25 -20 -15 -10 -5 0 5 10 15
•GMR: Lower 95% CI of GMR was >0.667
•Seroresponse rate difference: Lower 95% CI of difference >–10%
© 2025 Moderna, inc. All rights reserved.Noninferiority
Success Criteria Met
Seroresponse rate defined as antibody value change from baseline below lower limit of quantification (LLOQ) to ≥4 × LLOQ, or ≥4-fold rise if baseline ≥ LLOQ and <4 × LLOQ,
or ≥2-fold rise if baseline is ≥4 × LLOQ; GMC – geometric mean concentration; GMR – geometric mean ratio
1. GMC estimated based on ANCOVA model
16
Highest BA.4/BA.5 Neutralizing Antibody Geometric Mean Ratio
(GMR) at Day 29 in Adults ≥65 Years Old
Study 301 – Per Protocol Immunogenicity (Randomly Selected Subset)
≥ 65 Years
3732340
2971327
D1 D29
N = 152D1 D29
N = 1593252121
3191661
D1 D29
N = 378D1 D29
N = 3164793561
5933399
101001000
D1 D29 D1 D291.8 (1.4, 2.2) 1.3 (1.1, 1.5)SPIKEVAX (50 µg)
18-64 Years
N = 91 N = 93GMC1
(95% CI)mRNA -1283 (10 µg)
12-17 Years
GMR (95% CI) = 1.0 (0.8, 1.3)
10000
1. GMC estimated based on ANCOVA model
© 2025 Moderna, inc. All rights reserved.
17
mRNA -1283 Elicited Consistently Higher Antibody Responses
Compared to SPIKEVAX Over Time - Adults ≥65 Years of Age
D29 D29 D29 D29 D29 D29Day 29 Day 91 Day 181
GMR (95% CI) = 1.8 (1.4, 2.2) 1.8 (1.5, 2.3) 1.7 (1.3, 2.2)
10000
2340GMC1 1566
Against 1327 1086
Omicron 863
BA.4 / BA.5 1000 634
(95% CI)
100
mRNA -1283 SPIKEVAX mRNA -1283 SPIKEVAX mRNA -1283 SPIKEVAX
(10 µg) (50 µg) (10 µg) (50 µg) (10 µg) (50 µg)
N = 152 N = 159 N = 149 N = 155 N = 122 N = 1421086
634
D29 D29 mRNA -1283
(10 µg)
N = 122SPIKEVAX
(50 µg)
N = 1421566
863
D29 D29 mRNA -1283
(10 µg)
N = 149SPIKEVAX
(50 µg)
N = 155GMC1
Against
Omicron
BA.4 / BA.5
(95% CI)1327
1001000
D29 D29 mRNA -1283
(10 µg)
N = 152SPIKEVAX
(50 µg)
N = 159Study 301 – Per-Protocol Immunogenicity Set (Randomly Selected Subset)
Day 29 Day 91 Day 181
GMR (95% CI) = 1.8 (1.4, 2.2) 1.8 (1.5, 2.3) 1.7 (1.3, 2.2)
10000
2340
1. GMC estimated based on ANCOVA model
© 2025 Moderna, inc. All rights reserved.
18Neutralizing Antibody Responses against Omicron XBB.1.5
with mRNA -1283 Similar to SPIKEVAX
Study 301 – Per-Protocol Immunogenicity Set - Japan
•Study assessed safety & immunogenicity of monovalent XBB.1.5 COVID -19 vaccine
GMC1 (95% CI)mRNA -1283
(10 µg)
N = 334SPIKEVAX
(50 µg)
N = 334 Geometric Mean Ratio (GMR) (95% CI)
Omicron XBB.1.51757
(1580, 1954)1470
(1322, 1635)
1
1. GMC estimated based on ANCOVA model
© 2025 Moderna, inc. All rights reserved.1.5 21.2 (1.03, 1.39)
0.5 0.667
•Lower 95% CI of GMR was >0.667Noninferiority
Success
Criteria Met
© 2025 Moderna, inc. All rights reserved.
Relative Vaccine Efficacy of
mRNA -1283 vs SPIKEVAX
(mRNA -1273)
Study 30119
20
COVID -19 Case Definition and Surveillance
CDC COVID -19 Definition1
•Virologic confirmation of SARS -CoV -2 infection via PCR
•Presence of ≥1 symptom consistent with COVID -19 within 14 days of positive PCR
•Fever or chills •Fatigue •Loss of taste or smell
•Cough •Muscle or body ache •Sore throat
•Shortness of breath or •Headache •Congestion or runny nose
difficulty breathing•Nausea or vomiting •Diarrhea
•Biweekly symptom surveillance conducted using an electronic diary prompt
•Participants with symptoms seen for clinical evaluation and collection of respiratory samples
for SARS -CoV -2 PCRCOVID -19 Surveillance
© 2025 Moderna, inc. All rights reserved.1. https://ndc.services.cdc.gov/case -definitions/coronavirus -disease -2019 -covid -19/
21Prespecified Success Criteria Met for Relative Vaccine
Efficacy of mRNA -1283 vs SPIKEVAX
Per-Protocol Set for Efficacy (Median 8 Months)
Participants with
COVID -19, % [n/N]mRNA -1283
(10 µg)SPIKEVAX
(50 µg)Relative Vaccine Efficacy
Based on Hazard Ratio (99.4% CI)1,2P-value3
Primary rVE Objective
(≥12 year)9.9%
[560/5679]10.8%
[617/5687]0.0005
-30 -20 -10 0
© 2025 Moderna, inc. All rights reserved.10 20 309.3% (-6.6, 22.8)
•Lower bound of two-sided 99.4% (alpha -adjusted) CI of rVE > -10%
(1-sided alpha spending: 0.0028)Noninferiority
Success
Criteria Met
Based on CDC COVID -19 definition
1rVE =1-hazard ratio, hazard ratio estimated using a stratified Cox proportional hazard model (stratified by age group at randomization) and with treatment group as a fixed effect.
2Alpha -adjusted 2-sided (99.4%) CI was calculated using the Lan-DeMets O’Brien -Fleming Spending function (nominal one-sided alpha of 0.0028)
3P-value based on the stratified Cox proportional hazard model to test the null hypothesis log (hazard ratio)>=log(1.1)
22Relative Vaccine Efficacy of mRNA -1283 vs SPIKEVAX
in Participants by Age
COVID -19 Events1 through 31 Jan 2024 – Per-Protocol Set for Efficacy
Participants with
COVID -19, % [n/N]mRNA -1283
(10 µg)SPIKEVAX
(50 µg)Relative Vaccine Efficacy
Based on Hazard Ratio (95% CI)1,2
12-17 Years5.9%
[29/491]4.7%
[23/490]-29.2% (-123.3, 25.3)
18-64 Years10.7%
[382/3558]11.8%
[422/3562]9.7% (-3.8, 21.3)
≥ 65 Years9.1%
[149/1630]10.5%
[172/1635]13.5% (-7.7, 30.6)
-60 -40 -20 0 20 40 60
•Highest relative vaccine efficacy in adults ≥65 years
•Limited number of COVID -19 cases in 12-17-year -olds results in imprecise relative vaccine efficacy estimate
© 2025 Moderna, inc. All rights reserved.1.Based on CDC COVID -19 definition; 2. Posthoc analysis of RVE in ≥50-year -olds (3399 received mRNA -1283, 3431 received mRNA -1273);
rVE – relative vaccine efficacy = 1-hazard ratio, hazard ratio was estimated using a Cox proportional hazard model and with treatment group as a fixed effect.
23Relative Vaccine Efficacy Favorable for mRNA -1283 for
Individuals with Comorbidities
Post Hoc Analysis – Based on CDC Definition for COVID -19 Risk1
Participants with
COVID -19, % [n/N]mRNA -1283
(10 µg)SPIKEVAX
(50 µg)Relative Vaccine Efficacy
Based on Hazard Ratio (95% CI)1
≥ 1 comorbidities10.2%
[267/2617]12.4%
[329/2658]17.5% (3.0, 29.8)
And ≥ 50 Years9.6%
[169/1755]12.4%
[228/1833]23.0% (6.1, 36.9)
And ≥ 65 years8.5%
[78/913]11.8%
[110/929]28.6% (4.6, 46.6)
-50 -40 -30 -20 -10
© 2025 Moderna, inc. All rights reserved.0 10 20 30 40 50
1. https:// www.cdc.gov/covid/risk -factors/index.html
24Relative Vaccine Efficacy of mRNA -1283 vs SPIKEVAX
Demonstrated in Prevention of Severe COVID -19
Post Hoc Analysis – Protocol Set for Efficacy, through 31 Jan 2024
•SPIKEVAX effective in prevention of severe COVID -19 in pivotal efficacy trial and real-world
effectiveness studies1-3
•55 cases of severe COVID -19 identified in this trial
•Severe criteria per FDA guidance (originally used in mRNA -1273 efficacy trial)1
•Majority (92.7%) of severe COVID -19 cases were due to blood pressure or oxygen saturation
abnormalities
Participants with Severe
COVID -19, % [n/N]mRNA -1283
(10 µg)SPIKEVAX
(50 µg)Relative Vaccine Efficacy
(95% CI)
All Participants (≥12 years)0.4%
[21/5679]0.6%
[34/5687]
-50 0 50
1. https: //www.fda.gov/regulatory -information/search -fda-guidance -documents/development -and-licensure -vaccines -prevent -covid -19; 2. Zheng et al Intl J Inf Dis 2022;
3. Link-Gelles ACIP 2024.
Severe defined as respiratory failure/ARDS, renal/hepatic/neurologic dysfunction, admission to ICU/death, or vital sign abnormalities indicative of severe systemic illness or BP
abnormalities indicative of shock (respiratory rate ≥30 per minute, heart rate ≥125 beats per minute, or SpO2 ≤93% on room air at sea level or PaO2/FiO2 <300 mmHg, systolic
BP <90 mmHg, diastolic BP <60 mmHg, or requiring vasopressors)
© 2025 Moderna, inc. All rights reserved.10038.1% (-6.7, 64.1)
© 2025 Moderna, inc. All rights reserved.
Summary25
Summary - Next Generation COVID -19 Vaccine mRNA -128326
Safety •mRNA -1283 generally well tolerated; no safety concerns identified
•Pre-specified non-inferiority objectives met
•mRNA -1283 elicited higher immune responses than SPIKEVAX
•GMR highest in participants ≥65 years old (GMR 1.8; 95% CI: 1.4, 2.2)Immunogenicity
•Prespecified rVE non-inferiority objective met
9.3% mRNA -1283 vs mRNA -1273; 99.4% CI: -6.6, 22.8
•Trend for higher rVE point estimates with advancing age and comorbidity
>65 years old:
13.5% mRNA -1283 vs mRNA -1273; 95% CI: -7.7, 30.6
>65 years old and >1 comorbidity* (Post hoc):
28.6% mRNA -1283 vs mRNA -1273; 95% CI: 4.6, 46.6Relative Vaccine
Efficacy (rVE)
•mRNA -1283 has the potential to further reduce the burden of COVID -19, particularly
among those most vulnerable to severe outcomesPublic Health
Benefit
© 2025 Moderna, inc. All rights reserved.GMR – geometric mean ratio ;
* Comorbidities associated with severe COVID -19 outcomes https:// www.cdc.gov/covid/risk -factors/index.html
THANK YOU!
© 2025 Moderna, inc. All rights reserved.•Investigators
•Study site personnel
•Laboratory personnel
•Most importantly, the individuals who
participated in these trials27