Moderna, Inc. · NASDAQ:MRNA
Moderna — 8th ReSViNET Conference (RSVVW 2024)
32 slides from Moderna's conference presentation, Feb 15, 2024
Slide 1: Efficacy and Safety of mRNA-1345, an RSV Vaccine, in Older Adults
Efficacy and Safety of mRNA-1345, an RSV Vaccine, in Older Adults: Results through ≥6 Months of Follow-up and Evaluation of Correlate of Protection Against RSV February 15, 2024 Presented at the 8th ReSViNET Conference (RSVVW 2024) Mumbai, India © 2024 M oderna, Inc. Confidential. All rights reserve
Slide 2: Forward-Looking Statements and Disclaimer
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 potential development candidate applications, development candi
Slide 3: Disclosures and Acknowledgments
Disclosures and Acknowledgments • EW, JG, FP, NL, NLC, SKS, CAP, AK, LW, JD, LL, CR, HZ, CM, SG, CAS, LZ, JMM and RD are employees of Moderna, Inc., and hold stock/stock options in the company • Medical writing and editorial assistance were provided by Louansha Nandlal, PhD, and Jennifer McKinney, P
Slide 4: Efficacy and Safety of mRNA-1345 in Older Adults
Efficacy and Safety of mRNA-1345, an RSV Vaccine, in Older Adults: Results through ≥6 Months of Follow-up Eleanor Wilson, Jaya Goswami, Pablo Alexis Doreski, Gonzalo Perez Marc, Gilberto Jimenez, Frances Priddy, Nina Lin, Nancy Le Cam, Karen Slobod, Sonia K. Stoszek, Catherine A. Panozzo, Archana Ka
Slide 5: Investigational RSV Vaccine (mRNA-1345) Designed to Encode for a Stabilized Prefusion F Glycoprotein
Investigational RSV Vaccine (mRNA-1345) Designed to Encode for a Stabilized Prefusion F Glycoprotein • LNP encapsulated mRNA-based vaccine encoding the RSV fusion (F) glycoprotein stabilized in the prefusion conformation • Prefusion F elicits potent neutralizing antibody response1,2 • Antibodies to
Slide 6: mRNA-1345 Pivotal Phase 2/3 Clinical Trial: Population/Study Design
mRNA-1345 Pivotal Phase 2/3 Clinical Trial: Population/Study Design Ongoing phase 2/3, double-blind, placebo-controlled study (NCT05127434) in 22 countries1 Population Individuals with Comorbidities • Healthy adults including those with chronic, stable medical – COPD – CHF conditions, and/or frailty
Slide 7: Key Efficacy Endpoints
Key Efficacy Endpoints Phase 2/3 Safety and Efficacy Study of mRNA-1345 Primary Efficacy Objectives – Vaccine efficacy to prevent first episode of RSV-LRTD (Lower Respiratory Tract Disease) between 14 days and 12 months post-injection – ≥2 signs/symptoms – ≥3 signs/symptoms Key Secondary Efficacy Ob
Slide 8: Definitions of LRTD and ARD
Definitions of LRTD and ARD Phase 2/3 Safety and Efficacy Study of mRNA-1345 RSV Lower Respiratory Tract Disease (LRTD) New or Worsening of ≥2 or ≥3 of Signs/Symptoms for ≥24 Hours Shortness Sputum Tachypnea of Breath Production Wheezing and/or rales and/or Fever and/ Pleuritic rhonchi Hypoxemia or
Slide 9: Primary and Additional Efficacy Analyses
Primary and Additional Efficacy Analyses US 2021-2023 RSV Hospitalization Rates (RSV-NET) in Adults ≥65 Years1 Vaccination Period November 2021 – December 2022 ▪ RSV efficacy study conducted across 2021 – 2022 and 7 Primary Analysis 2022 – 2023 seasons November 2021 – November 2022 6 Median 3.7 Mont
Slide 10: Primary Analysis: Vaccine Efficacy for Primary and Key Secondary Endpoints
Primary Analysis: Vaccine Efficacy for Primary and Key Secondary Endpoints Met Success Criterion (>20% Lower Bound of CI ) Study 301 Per Protocol Analysis, 14 Days – 12 Months After Vaccine/Placebo Cases, n (%) RSV Vaccine (mRNA-1345) Placebo Vaccine Efficacy (%) (N = 17,572) (N = 17,516) Based on H
Slide 11: Additional Analysis: Demographics Well-Matched Across Groups
Additional Analysis: Demographics Well-Matched Across Groups; Enrollment Included Those at Highest Risk of Severe RSV (Safety Set) RSV Vaccine (mRNA-1345) Placebo Characteristic (N = 18,245) (N = 18,184) Median Age, years 68.5 68.5 60 – 69 years 11,314 (62%) 11,253 (62%) 70 – 79 years 5,493 (30%) 5,
Slide 12: Additional Analysis: Solicited Local Reactions within 7 Days
Additional Analysis: Solicited Local Reactions within 7 Days After RSV Vaccine vs Placebo Study 301 - Solicited Safety Set – Adults ≥60 Years Injection Injection Site Injection Site Axillary Swelling Site Pain Erythema Swelling or Tenderness RSV Vaccine 100% (mRNA-1345) Grade 1 80% Grade 2 Grade 3 6
Slide 13: Additional Analysis: Solicited Systemic Reactions within 7 Days
Additional Analysis: Solicited Systemic Reactions within 7 Days After RSV Vaccine vs Placebo Study 301 - Solicited Safety Set – Adults ≥60 Years Fever Headache Fatigue Myalgia Arthralgia Nausea / Chills Vomiting RSV Vaccine 100% (mRNA-1345) Grade 1 80% Grade 2 Grade 3 + 4 60% Placebo 40% 30.8% 26.7%
Slide 14: Unsolicited Adverse Event Within 28 Days After Injection
Unsolicited Adverse Event Within 28 Days After Injection, Regardless of Relationship to Vaccine/Placebo Study 301 - Solicited Safety Set – Adults ≥60 Years RSV Vaccine (mRNA-1345) Placebo (N = 18,245) (N = 18,184) All, n (%) 3,749 (20.5%) 3,412 (18.8%) Serious 115 (0.6%) 111 (0.6%) Fatal 1 (<0.1%) 6
Slide 15: Adverse Events of Special Interest (AESI)
Adverse Events of Special Interest (AESI) Study 301 – Adults ≥60 Years • Neurological Disorders – No cases of Guillain Barre syndrome or acute disseminated encephalomyelitis (ADEM) – No imbalance observed for other neurological disorders including Bell’s palsy/facial paralysis • Cardiac Events – No
Slide 16: Efficacy of mRNA-1345 Against RSV LRTD and RSV ARD Among Adults ≥60 Years
Efficacy of mRNA-1345 Against RSV LRTD and RSV ARD Among Adults ≥60 Years: Additional Analysis (April 30, 2023-Data Cutoff) Per Protocol Analysis, 14 Days – 12 Months After Vaccine/Placebo Cases, n (%) RSV Vaccine (mRNA-1345) Placebo Vaccine Efficacy (%) (N = 18,112) (N = 18,045) Based on Hazard Rat
Slide 17: Vaccine Efficacy Against RSV-A and RSV-B by Endpoint
Vaccine Efficacy Against RSV-A and RSV-B by Endpoint Among Adults ≥60 Years – Additional Analysis (April 30, 2023-Data Cutoff) Per Protocol Analysis, 14 Days – 12 Months After Vaccine/Placebo Numbers of Events RSV Vaccine (mRNA-1345) Placebo Vaccine Efficacy (N = 18,112) (N = 18,045) (CI) Overall 47
Slide 18: Vaccine Efficacy Against RSV LRTD ≥2 Symptoms Across Subgroups
Vaccine Efficacy of mRNA-1345 Against RSV LRTD ≥2 Symptoms Across Subgroups – Additional Analysis (April 30, 2023-Data Cutoff) Per Protocol Analysis, 14 Days – 12 Months After Vaccine/Placebo Numbers of Events RSV Vaccine (mRNA-1345) Placebo Vaccine Efficacy RSV LRTD with ≥2 Symptoms (N = 18,112) (N
Slide 19: Efficacy Against Severe, Medically Attended RSV-LRTD, and Hospitalizations
Efficacy Against Severe (Based on Shortness of Breath), Medically Attended RSV-LRTD, and Hospitalizations Among Adults ≥60 Years – Additional Analysis Post Hoc Analysis and Per Protocol Analysis, 14 Days – 12 Months After Vaccine/Placebo Cases, n (%) RSV Vaccine (mRNA-1345) Placebo Vaccine Efficacy
Slide 20: Conclusions from Additional Analysis
Conclusions from Additional Analysis • mRNA-1345 is well-tolerated; acceptable safety profile in adults aged ≥60 years – No events of Guillain Barre syndrome or acute disseminated encephalomyelitis reported • Single dose of mRNA-1345 continued to demonstrate efficacy across spectrum of RSV disease –
Slide 21: Evaluation of Correlate of Protection Against RSV
Evaluation of Correlate of Protection Against RSV Chong Ma, Jiejun Du, Lan Lan, Archana Kapoor, Sanjay Garg, Sonia K. Stoszek, Christine A. Shaw, Jaya Goswami, Eleanor Wilson, Rituparna Das, Honghong Zhou, Lingyi Zheng © 2024 M oderna, Inc. Confidential. All rights reserved.
Slide 22: Assessment of Correlate of Risk/Protection
Assessment of Correlate of Risk/Protection Phase 2/3 Safety and Efficacy Study of mRNA-1345 Antibodies have been demonstrated to play a role in protection from RSV in both adults and children1-4 • Preplanned case-cohort design for correlates assessment – Samples collected on Day 1 (baseline) & 29 fr
Slide 23: Case-cohort sampling plan for antibody marker assessment
Case-cohort sampling plan for antibody marker assessment Case-Cohort Immunogenicity Analysis Set Planned Number of participants in per-protocol immunogenicity subset (Total N=1920)* Baseline Covariate Strata S1 S2 S3 S4 S5 S6 S7 + RSV-ARD cases mRNA-1345 50 µg 200 200 400 200 200 200 200 Placebo 40
Slide 24: RSV Baseline Risk Model
RSV Baseline Risk Model • RSV Baseline risk model was fitted by using the placebo recipients’ baseline data • 17 baseline covariates were preselected for fitting the RSV baseline risk model • Baseline factors which were correlated were included once in the model Efficacy and Safety of mRNA-1345, an
Slide 25: RSV Baseline Risk Model – based on SuperLearner
RSV Baseline Risk Model – based on SuperLearner (Machine Learning Application) • The baseline risk model developed using data from the placebo arm only by regressing the outcome of RSVs on preselected baseline covariates • 7 learners were used for all eligible baseline covariates and screened baseli
Slide 26: Distribution of Biomarker on D1/D29
Distribution of Biomarker on D1/D29 Baseline and D29 PreF IgG RSV A RSV B D1 Neutralizing Ab Neutralizing Ab PreF IgG Distribution of vaccine and placebo arm match RSV A RSV B D29 Neutralizing Ab Neutralizing Ab PreF IgG Distribution of vaccine and placebo arm Separated Efficacy and Safety of mRNA-1
Slide 27: Cumulative Risk for LRTD2+ through 345 Days Post Day 29 Visit
Cumulative Risk for LRTD2+ through 345 Days Post Day 29 Visit by vaccine group and Low/Medium/High RSV-A, RSV-B nAb, PreF IgG bAb concentration RSV A Neutralizing Ab RSV B Neutralizing Ab PreF IgG Efficacy and Safety of mRNA-1345, an RSV Vaccine, in Older Adults: Results through ≥6 M onths of Follow
Slide 28: Summary of RSV CoR Models using Day 29 Antibody Markers
Summary of RSV CoR Models using Day 29 Antibody Markers • Day 29 antibody markers correlate with the RSV endpoints (RSV-LRTD 2+ shown) – The treatment effect become insignificant conditional on the Day 29 marker, • Day 29 RSV A Neutralizing Ab is a potential CoR/CoP biomarker for all RSV endpoints •
Slide 29: Correlate of Risk and Correlate of Protection – RSV-LRTD 2+
Correlate of Risk and Correlate of Protection – RSV-LRTD 2+ Comparable CVE by Day 29 RSV-A nAb and Day 29 RSV Pre-F IgG Ab RSV A Neutralizing Ab Conclusions: • Both neutralizing (RSV-A and RSV-B) and binding (pre-F) antibodies at Day 29 correlate with the risk of RSV: the higher the antibody level,
Slide 30: Thank you
Thank you ▪ All investigators and study site personnel ▪ Clinical and laboratory personnel who supported study design and data collection ▪ Most importantly, the individuals who participated in the trial © 2024 M oderna, Inc. Confidential. All rights reserved.
Slide 31: Backups
Backups © 2024 Moderna, inc. All rights reserved.
Slide 32: Durability of RSV-A and RSV-B Neutralizing Antibody Response with mRNA-1345 and Revaccination
CP-32 Durability of RSV-A and RSV-B Neutralizing Antibody Response with mRNA-1345 and Revaccination Study 101 – Adults, 65-79 Years RSV-A Neutralizing Antibody RSV-B Neutralizing Antibody GMFR from Day 0 10.1 6.9 6.8 5.5 2.7 7.3 7.0 6.4 6.8 5.8 4.5 2.5 5.2 4.5 100000 100000 10000 10000 GMT (95% CI)