Moderna : 2024 ESCMID (mRNA-1010)

Safety and Immunogenicity of an mRNA-Based

Seasonal Influenza Vaccine (mRNA-1010) in Healthy Adults

Mieke Soens, Raffael Nachbagauer, Bryony Hicks, Greg Livermore, Kristi Schaefers, Carole Henry, Angela Choi, Andrei Avanesov, Ren Chen, Evelyn Du, Alicia Pucci, and Jintanat Ananworanich

April 29, 2024

Presented at the 34th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024)

Barcelona, Spain

© 2024 Moderna, Inc. All rights reserved.

Disclosures and Acknowledgments

• Mieke Soens, Raffael Nachbagauer, Bryony Hicks, Greg Livermore, Kristi Schaefers, Carole Henry, Angela Choi, Andrei Avanesov, Ren Chen, Evelyn Du, Alicia Pucci, and Jintanat Ananworanich are employees of Moderna, Inc., and may hold stock or stock options
• Medical writing and editorial assistance were provided by Aliscia Daniels, PhD, of MEDiSTRAVA in accordance with Good Publication Practice guidelines (GPP 2022), funded by Moderna, Inc., and under the direction of the authors
• This study was funded by Moderna, Inc.
• Additional information
• • Please scan the QR code for a copy of the oral presentation
  • Copies of this oral presentation obtained through the QR code are for personal use only and may not be reproduced without written permission of the authors
  • For additional information please contact Mieke Soens ([e-mail])

2 © 2024 Moderna, Inc. All rights reserved.

Forward-Looking Statements

• This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: target product profile; efficacy and safety; and the potential for regulatory approval. 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 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 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 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 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.

3 © 2024 Moderna, Inc. All rights reserved.

mRNA-1010: A Quadrivalent mRNA-Based Seasonal Influenza Vaccine Candidate

• Licensed seasonal influenza vaccines (produced by egg-,cell-, or recombinant-based methods) show variable effectiveness,1-3 particularly due to antigenic mismatch with circulating strains such as A/H3N24,5
• mRNA-basedvaccines have the potential to address several of the limitations associated with currently licensed vaccines3
• In prior phase 1/2 and phase 3 trials, the mRNA-1010 vaccine demonstrated no safety concerns in over 14,000 adults6,7
• Preliminary findings from phase 3 trials showed mRNA-1010 elicited strong immune responses against influenza A strains, with lower immune responses against influenza B strains, as compared to a licensed comparator7
• An updated mRNA-1010 formulation to improve influenza B responses is now under investigation

mRNA-1010 is an mRNA-based vaccine candidate

encoding membrane-bound haemagglutinin of influenza

strains recommended seasonally by WHO

We present findings from a phase 3 trial that assessed the safety, reactogenicity, and immunogenicity

of an optimised mRNA-1010 formulation in adults

HA, haemagglutinin; WHO, World Health Organization.

1. World Health Organization. Wkly Epidemiol Rec. 2022;19(97):185-208. 2. Barr IG, et al. NPJ Vaccines. 2018;3:44. 3. Dolgin E. Nat Rev Drug Discov. 2021;20:801-803. 4. Okoli GN, et al. Vaccine. 2021;39:1225-1240. 5. Centers for Disease Control and Prevention. Vaccine Effectiveness: How Well Do Flu Vaccines Work? https://www.cdc.gov/flu/vaccines-work/vaccineeffect.htm 6. Lee IT, et al. Nat Commun. 2023; 14:3631. 7. Moderna Inc. R&D Day and business updates.2023. https://s29.q4cdn.com/435878511/files/doc_presentations/2023/09/13/2023-Moderna-R-D-Day-Final-online-version.pdf.

4 © 2024 Moderna, Inc. All rights reserved.

Phase 3 Study of mRNA-1010 in Adults (NCT05827978)

A Randomised, Observer-Blind, Active Controlled Study Evaluating the Safety, Reactogenicity, and Immunogenicity of an Optimised mRNA-1010 Formulation in Adults

Participants

• 2416 adults ≥18 years old who have not received influenza vaccination within 5 months prior to Day 1

Vaccination schedule

• Randomised (1:1) to receive single-dose vaccination
• • mRNA-101050 µg (n =1227)
  • Active Comparator (Fluarix® Quadrivalent; n = 1189)

Stratified by

• Age (18-49,50-64, and ≥65 years)
• Influenza vaccine status in prior 12 months (received or not received)

Site location

• United States (Northern Hemisphere)

Duration

• 181 days (study initiated in April 2023)

Safety End Points

• Solicited local and systemic ARs within 7 days after vaccination
• Unsolicited AEs within 28 days after vaccination
• SAEs, AESIs, MAAEs, and AEs leading to study discontinuation from Day 1 to the end of study (Day 181)

Primary Immunogenicity End Point

• Noninferiority of mRNA-1010 versus active comparator based on GMR and SCR differences against each vaccine-matched influenza straina

AE, adverse event; AESI, adverse event of special interest; AR, adverse reaction; GMR, geometric mean ratio; GMT, geometric mean titre; HAI, haemagglutination inhibition; MAAE, medically attended adverse event; SAE, serious adverse event; SCR, seroconversion rate.

aNoninferiority was demonstrated if the lower boundaries of the 95% CI were >0.667 for the GMRs and greater than −10% for SCR differences.

5 © 2024 Moderna, Inc. All rights reserved.

Disposition and Demographics

• 2416 participants were randomly assigned; 2401 (99%) received mRNA-1010 or active comparator and were included in the full analysis set
• Baseline demographics and characteristics were comparable between vaccine groups
• • Most participants were White, and not Hispanic or Latino

	Active Comparator	mRNA-1010
	n = 1180	n = 1221
Age, years, n (%)
18-49	577 (48.9)	593 (48.6)
50-64	335 (28.4)	353 (28.9)
≥65	268 (22.7)	275 (22.5)
Sex, n (%)
Female	623 (52.8)	660 (54.1)
Race, n (%)
White	851 (72.1)	920 (75.3)
Black/African American	270 (22.9)	248 (20.3)
Ethnicity, n (%)
Not Hispanic or Latino	940 (79.7)	937 (76.7)

The full analysis set consisted of all randomly assigned participants who received the investigational product.

6 © 2024 Moderna, Inc. All rights reserved.

mRNA-1010 Met All Primary Immunogenicity End Points

Geometric Mean Ratios to Active Comparator at Day 29

Immunogenicity criteria for licensure according to regulatory guidance were met for all coprimary end points

• A trend towards higher GMRs with mRNA-1010 versus the comparator was observed in the older age group (≥ 65 years)
• Additionally, although not prespecified, GMRs were consistent with superiority for all age groups and for all 4 strains (based on superiority

criteria,1 the lower bounds of the 95% CI for GMR exceeded 1)

	ANCOVA, analysis of covariance; GMR, geometric mean ratio; GMT, geometric mean titres; HAI, haemagglutination inhibition; LLOQ, lower limit of quantitation; ULOQ, upper limit of quantitation.
	Per-protocol immunogenicity set. Measured by HAI assay on Day 29. Antibody values reported as below the LLOQ are replaced by 0.5 × LLOQ. Values greater than the ULOQ are converted to the ULOQ. The log-transformed antibody levels were analysed using an ANCOVA model with
	vaccination group as the fixed variable, log-transformed baseline HAI titres as a fixed covariate, if applicable, adjusting for the randomisation stratification factor(s): age group (18-49,50-64, and 65+ years) and flu vaccine status in the past 5-12 months for the total analysis; and adjusting for
	the actual stratification factor(s): age group (18-49,50-64, and 65+ years) and/or flu vaccine status in the past 5-12 months, as appropriate for the subgroup analysis. The noninferiority in GMT in the mRNA-1010 group compared with that of Fluarix group is demonstrated by the lower bound of
	the 95% CI of the GMR >0.667. The GMR and its corresponding 95% CI based on the model are obtained by transforming the least squares mean estimate and its CI back to the original scale for presentation.
7	1. Hu J, et al. Front Immunol. 2023;14:1241153.
© 2024 Moderna, Inc. All rights reserved.

mRNA-1010 Met All Primary Immunogenicity End Points

Seroconversion Rate Differences to Active Comparator at Day 29

Immunogenicity criteria for licensure according to regulatory guidance were met for all coprimary end points

• Based on prespecified noninferiority criteria, noninferiority was met for all strains; although not prespecified, SCR differences were consistent with superiority (based on superiority criteria1, the lower bounds of 95% CI > 0) for 3 of the 4 strains (except for the B/Yamagata strain in the ≥65 years age group)

HAI, haemagglutination inhibition; LLOQ, lower limit of quantitation; SCR, seroconversion rate; ULOQ, upper limit of quantitation.

Per-protocol immunogenicity set. Antibody values reported as below the LLOQ are replaced by 0.5 × LLOQ. Values greater than the ULOQ are converted to the ULOQ. Rate of seroconversion (mRNA-1010 vs Fluarix) is defined as the proportion of participants with either a baseline HAI titer <1:10 and a post-baseline titer ≥1:40 or a baseline HAI titer ≥1:10 and a minimum 4-fold rise in post-baseline HAI antibody titer. The noninferiority in SCR in the mRNA-1010 group compared with that of Fluarix group is demonstrated by the lower bound of the 95% CI of the SCR difference exceeding −10%. 95% CI is calculated using the Miettinen-Nurminen (score) method.

1. Hu J, et al. Front Immunol. 2023;14:1241153.

8 © 2024 Moderna, Inc. All rights reserved.

Solicited Local Adverse Reactions

Grade 1		Grade 2		Grade 3

• Most local adverse reactions were grade 1 or 2 in severity and resolved within 2 to 3 days
• No grade 4 local adverse reactions were reported
• Pain and axillary swelling were the most commonly reported local adverse reactions

AR, adverse reaction.

Solicited safety set. Fluarix, n = 1180; mRNA-1010, n = 1221.

9 © 2024 Moderna, Inc. All rights reserved.

Solicited Systemic Adverse Reactions

Grade 1		Grade 2		Grade 3		Grade 4

• Most systemic adverse reactions were grade 1 or 2 in severity and resolved within 2 days
• There were 2 grade 4 events, both of which were fever in the mRNA-1010 group
• Fatigue, myalgia, and headache were the most commonly reported systemic adverse reactions

AR, adverse reaction.

Solicited safety set. Fluarix, n = 1180; mRNA-1010, n = 1221.

10 © 2024 Moderna, Inc. All rights reserved.