mRESVIA (respiratory syncytial virus vaccine) / Moderna - LARVOL DELTA

Moderna Reports First Quarter 2025 Financial Results… (Moderna Press Release) - "COVID-19: The Company reported $84 million in Spikevax sales in the first quarter of 2025, which includes $29 million of U.S. sales and $55 million of international sales. As previously reported, Moderna entered into a tender opportunity in January to compete for COVID vaccine business in the EU; RSV: The Company reported $2 million in mRESVIA sales in the first quarter of 2025. Moderna's RSV vaccine for adults aged 60 years and older has been recently approved in Australia, Switzerland, Taiwan and the UK....Research and development expenses for the first quarter of 2025 decreased by 19% to $856 million, compared to the first quarter in 2024. The decrease was primarily driven by lower clinical development costs across respiratory programs due to timing of trial activities and program wind-downs. This reduction was partially offset by increased investment in Moderna's individualized neoantigen therapy (mRNA-4157)...and norovirus programs."

Commercial • Sales • Bladder Cancer • Melanoma • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Respiratory Syncytial Virus Infections

Editorial: Surveillance of Seasonal Respiratory Syncytial Virus (RSV) Infection in Children and Vulnerable Adults Drives Vaccine Development and New Immunization Programs. (PubMed, Med Sci Monit) - "There are currently three available RSV vaccines that include an AS01E-adjuvanted RSV prefusion F vaccine (Arexvy), a non-adjuvanted bivalent RSV prefusion F vaccine (Abrysvo), and an mRNA vaccine (MResvia)...The long-acting monoclonal antibody, nirsevimab (Beyfortus), targets the surface F protein of RSV and is effective in late preterm and term infants...Recent modeling and clinical studies have begun to address some of the concerns regarding the safety and efficacy of new RSV vaccines in children, pregnant women, and the elderly. This editorial aims to describe how global surveillance of increasing seasonal RSV respiratory tract infections has driven the development of new vaccines and immunization programs for infants, children, pregnant women, and vulnerable adults."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

The Potential Public Health and Economic Benefit of an mRNA-Based RSV Vaccine, mRNA-1345, Among High-Risk Adults Aged 18–59 Years in the US: A Modeling Study (ISPOR 2025) - "Vaccinating adults aged 18-59 years at increased risk of severe RSV disease could substantially alleviate the public health burden of RSV, potentially saving over $1.7 billion in direct treatment cost and nearly $1 billion in productivity losses."

Clinical • HEOR • Cardiovascular • Chronic Kidney Disease • Diabetes • Genetic Disorders • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Influenza • Metabolic Disorders • Nephrology • Obesity • Pulmonary Disease • Renal Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Shared clinical and immunologic features of mRNA vaccines: preliminary results from a comparative clinical study. (PubMed, Front Immunol) - P1 | "This ongoing, open-label, phase 1 trial randomized healthy adults (18-75 years) to receive a single dose of mRNA-1273.222 (bivalent COVID-19), mRNA-1345 (RSV), mRNA-1010 (influenza), and FLUAD (active influenza comparator) or 2 or 3 doses of mRNA-1647 (CMV). This suggests that the observed reactogenicity of mRNA vaccines may be related to shared features of the mRNA platform (LNP platform). ClinicalTrials.gov, identifier NCT05397223."

Clinical • Journal • Infectious Disease • Inflammation • Influenza • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • CCL4 • CCL8 • CD4 • CD8 • CXCL9 • IFNG • IL1R1 • IL2RA • IL6

SAFETY AND IMMUNOGENICITY OF INVESTIGATIONAL MRNA-BASED RSV AND RSV/HMPV VACCINES IN CHILDREN 5 TO 7 MONTHS OF AGE (ESPID 2025) - "Two 15µg doses of mRNA-1345 and mRNA-1365 were immunogenic; however, a potential imbalance in severe/hospitalised RSV/hMPV-LRTI led to a study pause and cessation of further dosing or enrolment. Ongoing safety and immunogenicity assessments aim to better understand severe RSV/hMPV-LRTI in in this age group."

Clinical • Late-breaking abstract • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

REACTOGENICITY AND IMMUNOGENICITY OF INVESTIGATIONAL MRNA-1345 IN 8- TO 11-MONTH-OLD CHILDREN WITH AND WITHOUT PRIOR NIRSEVIMAB EXPOSURE (ESPID 2025) - "Conclusions/Learning Points No increase in RSV-A/B nAbs was observed following vaccination in the nirsevimab group, whereas a robust rise was observed in the non-nirsevimab group. The potential impact of prior nirsevimab receipt on active RSV vaccination immunogenicity necessitates evaluation of this interaction for all candidate paediatric RSV vaccines."

Clinical • Infectious Disease • Pediatrics • Respiratory Diseases • Respiratory Syncytial Virus Infections

Design of a peptide-based vaccine against human respiratory syncytial virus using a reverse vaccinology approach: evaluation of immunogenicity, antigenicity, allergenicity, and toxicity. (PubMed, Front Immunol) - "Attempts to develop an hRSV vaccine have faced safety and efficacy challenges, with only three FDA-approved vaccines (Moderna's Mresvia, Pfizer's Abrysvo, and GSK's Arexvy) available...We then characterized its kinetic properties, evaluated its structural integrity, and analyzed its interactions with Toll-like receptors (TLRs) using molecular docking, modeling, and refinement with AlphaFold3 and ClusPro...This study presents a promising peptide-based vaccine candidate against hRSV that can effectively engage the immune system, showing strong immunogenicity and antigenicity. Future in vitro and in vivo studies are essential to evaluate the ability of the multi-epitope vaccine candidate to stimulate both humoral and cell-mediated immune responses and to assess its efficacy and safety profile."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG • IL2 • TLR1 • TLR4

A Study of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in Children 2 to <18 Years of Age at High Risk of Respiratory Syncytial Virus (clinicaltrials.gov) - P2 | N=346 | Active, not recruiting | Sponsor: ModernaTX, Inc. | Trial primary completion date: Mar 2025 ➔ Jun 2025

Trial primary completion date • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Six-month Immunogenicity of mRNA-1345 RSV Vaccine in Adults Aged ≥60 Years (ESCMID Global 2025) - No abstract available

Clinical • Respiratory Syncytial Virus Infections

Safety and immunogenicity of mRNA-1345 revaccination at 24 months in adults ≥60 years (ESCMID Global 2025) - No abstract available

Clinical • Late-breaking abstract

A Study of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus in Pregnant Women and in Infants Born to Vaccinated Mothers (clinicaltrials.gov) - P2 | N=360 | Active, not recruiting | Sponsor: ModernaTX, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Respiratory Diseases • Respiratory Syncytial Virus Infections

Development, Current Status, and Remaining Challenges for Respiratory Syncytial Virus Vaccines. (PubMed, Vaccines (Basel)) - "Two protein subunit vaccines (GSK's Arexvy and Pfizer's Abrysvo) and one mRNA RSV vaccine (Moderna's mRESVIA) are now available...Furthermore, ongoing vaccine surveillance and further evaluation, particularly among immunocompromised patients, frail elderly subjects, and young infants that were under- or not represented in pivotal clinical trials, are necessary. As in the success story of combined pediatric vaccines, combination vaccines, conferring protection against several respiratory illnesses in one dose, could help improve vaccine acceptance and coverage rates in older adults."

Journal • Review • Geriatric Disorders • Pediatrics • Respiratory Diseases • Respiratory Syncytial Virus Infections

2024 Adoption Rates of RSV Preventative Measures in Infants, Pregnant Mothers, and the Elderly. (AAAAI-WAO 2025) - "Percentages of eligible infants receiving Nirsevimab, of pregnant mothers receiving Abrysvo and of elderly patients receiving Arexvy, MResvia and Abrysvo were extracted...Cases of RSV in patients who received prevention were low. Overall low rates of vaccination indicate a crucial need to increase awareness of RSV prevention among healthcare workers."

Clinical • Late-breaking abstract • Respiratory Diseases • Respiratory Syncytial Virus Infections

ROSE: Moderna Vaccine mRNA-1345 Observational Respiratory Syncytial Virus (RSV) Study (clinicaltrials.gov) - P=N/A | N=10994 | Completed | Sponsor: ModernaTX, Inc. | Active, not recruiting ➔ Completed

Trial completion • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1010 in Healthy Adults (clinicaltrials.gov) - P2 | N=325 | Recruiting | Sponsor: ModernaTX, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Influenza • Respiratory Diseases

A Study of mRNA-1345, an mRNA Vaccine Targeting Respiratory Syncytial Virus, in Children 2 to <18 Years of Age at High Risk of Respiratory Syncytial Virus (clinicaltrialsregister.eu) - P2 | N=340 | Sponsor: ModernaTX, Inc.

New P2 trial • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Reply: FDA Approved mRESVIA: Embracing the New Era of RSV Prevention With Advanced mRNA Technology. (PubMed, Ann Pharmacother) - No abstract available

FDA event • Journal • Metastases

FDA Approves mRESVIA: Embracing the New Era of RSV Prevention With Advanced mRNA Technology. (PubMed, Ann Pharmacother) - No abstract available

FDA event • Journal • Metastases

RSVictory: A Study of mRNA-1345 Vaccine Targeting Respiratory Syncytial Virus (RSV) in Adults ≥50 Years of Age (clinicaltrials.gov) - P3 | N=3800 | Completed | Sponsor: ModernaTX, Inc. | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1010 in Healthy Adults (clinicaltrials.gov) - P2 | N=325 | Active, not recruiting | Sponsor: ModernaTX, Inc. | N=98 ➔ 325

Enrollment change • Infectious Disease • Influenza • Respiratory Diseases

Safety and immunogenicity of mRNA-1345 RSV vaccine coadministered with an influenza or COVID-19 vaccine in adults aged 50 years or older: an observer-blinded, placebo-controlled, randomised, phase 3 trial. (PubMed, Lancet Infect Dis) - P3 | "Coadministered mRNA-1345 plus SIIV4 or mRNA-1273.214 vaccines had acceptable safety profiles and elicited mostly non-inferior immune responses compared to individual vaccines in adults aged 50 years or older; only the seroresponse rate difference in nAbs against RSV-A in part A did not meet the non-inferiority criterion. Overall, these data support coadministration of mRNA-1345 with these vaccines in this population; longer-term evaluation continues in this study."

Journal • P3 data • Infectious Disease • Influenza • Novel Coronavirus Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Assessing the Public Health Benefit of a mRNA-Based Respiratory Syncytial Virus Vaccine (mRNA-1345) Among Adults ≥65 Years in France (ISPOR-EU 2024) - "These findings highlight the potential of mRNA-1345 to substantially reduce RSV disease burden among French older adults aged ≥ 6 5 yea rs, with model-predicted reductions of 36 % for RSV-LRTD hospitalizations and deaths compared to no vaccination."

Clinical • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Assessing the Potential Public Health Impact of the mRNA-Based Respiratory Syncytial Virus (RSV) Vaccine, mRNA-1345, With a Broad Vaccination Campaign Among Older Adults in the United Kingdom: Modelling Study (ISPOR-EU 2024) - "A broad mRNA-1345 vaccination campaign against RSV targeting older adults aged ≥60 in the UK could substantially reduce the number of RSV infections, associated hospitali s ations and deaths . Efforts to improve vaccine access are essential to ensure a substantial long-term decrease in the burden of RSV on individuals and the healthcare system ."

Clinical • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Potential Public Health Impact of Respiratory Syncytial Virus (RSV) Vaccines for Prevention of Lower Respiratory Tract Disease (LRTD) Due to RSV Among Older Adults in Canada (ISPOR-EU 2024) - "Moderna’s mRNA-1345 would reduce cases by 98,488, deaths by 1,136, and medical care costs by $198.8M. RSV vaccines have the potential to substantially reduce the clinical and economic burden of RSV-LRTD in older adults. Of the three vaccines, Pfizer’s RSVpreF would provide the greatest benefit due to its high year 2 efficacy and anticipated extended protection."

Clinical • Geriatric Disorders • Respiratory Diseases • Respiratory Syncytial Virus Infections

The Potential Public Health and Economic Benefit of an mRNA-Based Respiratory Syncytial Virus Vaccine Among Adults ≥60 Years in the United States (ISPOR-EU 2024) - "mRNA-1345 could substantially reduce RSV -related public health burden in adults ≥60 years . If RSV vaccin ation coverage in the US was increased to match influenza, the n the model predicted reductions of 43% for RSV-LRTD hospitalizations and deaths and 3 5 % of total RSV -related costs ."

Clinical • HEOR • Infectious Disease • Influenza • Respiratory Diseases • Respiratory Syncytial Virus Infections