A Phase 3, Randomized, Observer-blind, Active-controlled, Case-driven Study to Investigate the Safety, Efficacy, and Immunogenicity of mRNA-1010 Candidate Seasonal Influenza Vaccine Compared With a Licensed Inactivated Seasonal Influenza Vaccine in Adults ≥50 Years of Age

The primary objectives of this study are to evaluate the safety and reactogenicity of mRNA-1010, and to evaluate relative vaccine efficacy (rVE) of mRNA-1010 versus an active comparator against protocol-defined influenza-like illness (ILI) caused by any influenza A or B strains.

Start Date16 Sep 2024

Sponsor / Collaborator

ModernaTX, Inc.

NCT05868382 / CompletedPhase 2

A Phase 2, Randomized, Active-Controlled, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA Vaccine Candidate Variations in Healthy Adults 18 to 49 Years of Age

The main purpose of the study is to evaluate the safety, reactogenicity, and the immunogenicity of mRNA-1010 vaccine candidate variations.

Start Date15 May 2023

Sponsor / Collaborator

ModernaTX, Inc.

NCT05827978 / CompletedPhase 3

A Phase 3, Randomized, Stratified, Observer-Blind, Active-Controlled Study to Evaluate the Immunogenicity, Reactogenicity and Safety of mRNA-1010 Seasonal Influenza Vaccine in Adults 18 Years and Older

This study includes 3 parts: Parts A, B, and C. The purpose of this study is to evaluate the immunogenicity and safety of mRNA-1010 seasonal influenza vaccine in adults.

Start Date17 Apr 2023

Sponsor / Collaborator

ModernaTX, Inc.

100 Clinical Results associated with mRNA-1010

100 Translational Medicine associated with mRNA-1010

100 Patents (Medical) associated with mRNA-1010

Literatures (Medical) associated with mRNA-1010

01 Sep 2024·LANCET INFECTIOUS DISEASES

Safety and immunogenicity of mRNA-based seasonal influenza vaccines formulated to include multiple A/H3N2 strains with or without the B/Yamagata strain in US adults aged 50–75 years: a phase 1/2, open-label, randomised trial

Article

Author: Sanchez-Crespo, Nelia E ; Avanesov, Andrei ; Jayaraman, Akila ; Jorquera, Patricia ; Chen, Hui Ling ; Bhupathy, Vellore ; Hsu, Denise ; Choi, Angela ; Nachbagauer, Raffael ; Ananworanich, Jintanat ; Pucci, Alicia ; Du, Evelyn ; Wadsworth, L Tyler ; Koslovsky, Kindra ; Mancini, Kevin ; Arunkumar, Guha Asthagiri ; Henry, Carole ; Joshi, Riya ; Mao, Xuezhou ; Stadlbauer, Daniel ; Vakil, Jignesh

BACKGROUND:

Inclusion of additional influenza A/H3N2 strains in seasonal influenza vaccines could expand coverage against multiple, antigenically distinct, cocirculating A/H3N2 clades and potentially replace the no longer circulating B/Yamagata strain. We aimed to evaluate the safety and immunogenicity of three next-generation seasonal influenza mRNA vaccines with different compositions that encode for haemagglutinins of multiple A/H3N2 strains, with or without the B/Yamagata strain, in adults.

METHODS:

This randomised, open-label, phase 1/2 trial enrolled healthy adults aged 50-75 years across 22 sites in the USA. Participants were randomly assigned (1:1:1:1:1:1:1) via interactive response technology to receive a single dose of mRNA-1011.1 (pentavalent; containing one additional A/H3N2 strain [Newcastle]), mRNA-1011.2 (quadrivalent; B/Yamagata replaced with one additional A/H3N2 strain [Newcastle]), mRNA-1012 at one of two dose levels (pentavalent; B/Yamagata replaced with two additional A/H3N2 strains [Newcastle and Hong Kong]), or one of three quadrivalent mRNA-1010 controls each encoding one of the A/H3N2 study strains. The primary outcomes were safety, evaluated in all randomly assigned participants who received a study vaccination (safety population), and reactogenicity, evaluated in all participants from the safety population who contributed any solicited adverse reaction data (solicited safety population). The secondary outcome was humoral immunogenicity of investigational mRNA vaccines at day 29 versus mRNA-1010 control vaccines based on haemagglutination inhibition antibody (HAI) assay in the per-protocol population. Here, we summarise findings from the planned interim analysis after participants had completed day 29. The study is registered with ClinicalTrials.gov, NCT05827068, and is ongoing.

FINDINGS:

Between March 27 and May 9, 2023, 1183 participants were screened for eligibility, 699 (59·1%) were randomly assigned, and 696 (58·8%) received vaccination (safety population, n=696; solicited safety population, n=694; per-protocol population, n=646). 382 (55%) of the 696 participants in the safety population self-reported as female and 314 (45%) as male. Frequencies of solicited adverse reactions were similar across vaccine groups; 551 (79%) of 694 participants reported at least one solicited adverse reaction within 7 days after vaccination and 83 (12%) of 696 participants reported at least one unsolicited adverse event within 28 days after vaccination. No vaccine-related serious adverse events or deaths were reported. All three next-generation influenza vaccines elicited robust antibody responses against vaccine-matched influenza A and B strains at day 29 that were generally similar to mRNA-1010 controls, and higher responses against additional A/H3N2 strains that were not included within respective mRNA-1010 controls. Day 29 geometric mean fold rises in HAI titres from day 1 against vaccine-matched A/H3N2 strains were 3·0 (95% CI 2·6-3·6; Darwin) and 3·1 (2·6-3·8; Newcastle) for mRNA-1011.1; 3·3 (2·7-4·1; Darwin) and 4·2 (3·4-5·2; Newcastle) for mRNA-1011.2; 3·4 (2·9-4·0; Darwin), 4·5 (3·6-5·5; Newcastle), and 5·1 (4·2-6·2; Hong Kong) for mRNA-1012 50·0 μg; and 2·6 (2·2-3·1; Darwin), 3·7 (3·0-4·6; Newcastle), and 4·1 (3·3-5·1; Hong Kong) for mRNA-1012 62·5 μg. Inclusion of additional A/H3N2 strains did not reduce responses against influenza A/H1N1 or influenza B strains, and removal of B/Yamagata did not affect responses to B/Victoria.

INTERPRETATION:

These data support the continued clinical development of mRNA-based next-generation seasonal influenza vaccines with broadened influenza A/H3N2 strain coverage.

FUNDING:

Moderna.

19 Jun 2023·Nature communicationsQ1 · CROSS-FIELD

Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis.

Q1 · CROSS-FIELD

ArticleOA

Author: Schwartz, Howard ; Schrempp, Daniela Ramirez ; Lee, Ivan T ; Schaefers, Kristi ; Stadlbauer, Daniel ; Ananworanich, Jintanat ; Paris, Robert ; Chen, Ren ; Huang, Wenmei ; Ensz, David ; Avanesov, Andrei ; Henry, Carole ; Nachbagauer, Raffael ; Carmona, Lizbeth

Despite vaccine availability, influenza remains a substantial global public health concern. Here, we report interim findings on the primary and secondary objectives of the safety, reactogenicity, and humoral immunogenicity of a quadrivalent messenger RNA (mRNA) vaccine against seasonal influenza, mRNA-1010, from the first 2 parts of a 3-part, first-in-human, phase 1/2 clinical trial in healthy adults aged ≥18 years (NCT04956575). In the placebo-controlled Part 1, a single dose of mRNA-1010 (50 µg, 100 µg, or 200 µg) elicited hemagglutination inhibition (HAI) titers against vaccine-matched strains. In the active-comparator-controlled Part 2, mRNA-1010 (25 µg, 50 µg, or 100 µg) elicited higher HAI titers than a standard dose, inactivated seasonal influenza vaccine for influenza A strains and comparable HAI titers for influenza B strains. No safety concerns were identified; solicited adverse reactions were dose-dependent and more frequent after receipt of mRNA-1010 than the active comparator. These interim data support continued development of mRNA-1010.

JOURNAL OF INFECTIOUS DISEASES

Safety and Immunogenicity of mRNA-1010, an Investigational Seasonal Influenza Vaccine, in Healthy Adults: Final Results From a Phase 1/2 Randomized Trial

Article

Author: Lee, Ivan T ; Henry, Carole ; Nachbagauer, Raffael ; McGrath, Shannon ; Choi, Angela ; Kuo, Hsiao-Hsuan ; Chen, Ren ; Paris, Robert ; Huang, Wenmei ; Stadlbauer, Daniel ; Ensz, David ; Avanesov, Andrei ; Pucci, Alicia ; Schaefers, Kristi ; Ananworanich, Jintanat ; Carmona, Lizbeth

Abstract:

Background:

Seasonal influenza remains a global public health concern. A messenger RNA (mRNA)–based quadrivalent seasonal influenza vaccine, mRNA-1010, was investigated in a first-in-human, phase 1/2 clinical trial conducted in 3 parts.

Methods:

In parts 1 to 3 of this stratified observer-blind study, adults aged ≥18 years were randomly assigned to receive a single dose (6.25–200 µg) of mRNA-1010 or placebo (part 1) or an active comparator (Afluria; parts 2 and 3). Primary study objectives were assessment of safety, reactogenicity, and humoral immunogenicity of mRNA-1010, placebo (part 1), or active comparator (parts 2 and 3). Exploratory end points included assessment of cellular immunogenicity (part 1) and antigenic breadth against vaccine heterologous strains (A/H3N2; parts 1 and 2).

Results:

In all study parts, solicited adverse reactions were reported more frequently for mRNA-1010 than placebo or Afluria, and most were grade 1 or 2 in severity. No vaccine-related serious adverse events or deaths were reported. In parts 1 and 2, a single dose of mRNA-1010 (25–200 µg) elicited robust day 29 hemagglutination inhibition titers that persisted through 6 months. In part 3, lower doses of mRNA-1010 (6.25–25 µg) elicited day 29 hemagglutination inhibition titers that were higher or comparable to those of Afluria for influenza A strains. When compared with Afluria, mRNA-1010 (50 µg) elicited broader A/H3N2 antibody responses (part 2). mRNA-1010 induced greater T-cell responses than placebo at day 8 that were sustained or stronger at day 29 (part 1).

Conclusions:

Data support the continued development of mRNA-1010 as a seasonal influenza vaccine.

Clinical Trials Registration:

NCT04956575 (https://clinicaltrials.gov/study/NCT04956575).

News (Medical) associated with mRNA-1010

12 Sep 2024

·pipelinereview.com

Moderna R&D Day Highlights Progress and Strategic Priorities

Focuses on ten product approvals through 2027 Expects to submit next-generation COVID vaccine for approval in 2024 Expects to submit flu/COVID combination vaccine for approval in 2024 Announces positive Phase 3 results for its RSV vaccine for high-risk adults aged 18 to 59; expects to submit sBLA for U.S. approval in 2024 Announces positive Phase 3 results for its standalone flu vaccine for adults aged 65 and older relative to high-dose licensed comparator Announces norovirus vaccine advances into Phase 3 study, bringing the total of non-respiratory pivotal stage programs to five, across oncology, rare diseases and first-in-class vaccines Implements portfolio prioritization and cost efficiencies to reduce R&D expense by $1.1 billion, from $4.8 billion in 2024E to $3.6-3.8 billion in 2027 Updates and extends financial framework through 2028 CAMBRIDGE, MA, USA I September 12, 2024 I Moderna, Inc. (NASDAQ:MRNA) today announced program and financial updates demonstrating progress and strategic prioritization of its mRNA pipeline at its annual R&D Day event. The updates include data readouts in the Company’s respiratory vaccine portfolio and a revised financial framework. “Moderna now has five respiratory vaccines with positive Phase 3 results and expects to submit three for approval this year. In addition, we have five non-respiratory products in pivotal studies across cancer, rare diseases and latent vaccines with potential for approval by 2027. Our demonstrated probability of success in R&D has been higher than industry standards at every stage of development,” said Stéphane Bancel, CEO of Moderna. “The size of our late-stage pipeline combined with the challenge of launching products means we must now focus on delivering these 10 products to patients, slow down the pace of new R&D investment, and build our commercial business.” Research and Development Strategy Over the past three years, Moderna’s robust pipeline has achieved milestones across multiple late-stage clinical trials, and its early-stage portfolio has produced proof-of-concept data with multiple candidates ready for pivotal studies. Moderna’s rate of success in research and development has been higher than the traditional biopharmaceutical industry. The Company’s combined probability of success across its mid- and late-stage pipeline is approximately 66% compared to the industry average of approximately 19%.[1] Moderna’s broad clinical success and recent commercial challenges necessitate a more selective and paced approach to its research and development investment. Through portfolio prioritization and cost efficiencies, the Company expects to reduce annual research and development expense by approximately $1.1 billion starting in 2027. During this time, Moderna will expand its commercial portfolio into oncology, rare diseases, and first-in-class non-respiratory vaccines. The Company expects this strategy to yield 10 product approvals over the next three years. Specifically, in 2021-2023, Moderna invested proceeds from its pandemic-era vaccine sales into building a diverse pipeline and established the market for its COVID-19 vaccine, Spikevax®. In 2023-2026, the Company is establishing a portfolio of five commercial respiratory vaccines that address viruses with the greatest burden of disease. Its RSV vaccine mRESVIA® was approved this year, and its investigational next-generation COVID-19 vaccine, combination flu/COVID vaccine, and RSV vaccine for high-risk younger adults, are moving toward regulatory submissions in 2024. Looking ahead to 2026-2028, Moderna will expand its commercial portfolio with first-in-class vaccines and therapeutics to address non-respiratory diseases, including cytomegalovirus, norovirus, propionic acidemia, methylmalonic acidemia, and melanoma. Updates from Moderna’s late-stage portfolio and approved vaccines include: Respiratory Virus Vaccines COVID-19 According to the U.S. Centers for Disease Control and Prevention, COVID-19 causes three times more hospitalizations than flu in people aged 65 years and older.[2] Additionally, more than 95% of adults hospitalized in 2023-2024 due to COVID-19 had no record of receiving the latest vaccine.[3] People who are hospitalized may experience a significant impact on their quality of life, including loss of muscle mass, decline in daily activity, risk of hospital readmission and death. Additionally, Long COVID data also suggest even traditionally low-risk groups should be vaccinated.[4] More than 200 symptoms of Long COVID have been reported, such as anxiety, brain fog and extreme fatigue, and Long COVID can impact many different parts of the body, including the brain, heart and lungs. Moderna continues to address the needs of the endemic COVID-19 market by supporting public health efforts to drive vaccination coverage rates to reduce the substantial burden of COVID-19 as well as by advancing next-generation vaccines. The Company’s mRNA platform produced variant-matched vaccines on an accelerated time horizon to help ensure the availability of Spikevax targeting the two selected strains this season. The updated Spikevax formulas have been approved or authorized in multiple regions including the U.S., Taiwan, Japan, the UK, Switzerland, the United Arab Emirates, South Korea and Israel. Positive results from the NEXTCove Phase 3 trial in participants aged 12 years and older showed that Moderna’s next-generation COVID-19 vaccine, mRNA-1283 , demonstrated non-inferior relative vaccine efficacy (rVE) compared to Spikevax, with a positive point estimate of 9.3% (99.4% CI: -6.6, 22.8). rVE was highest at 13.5% (95% CI: -7.7, 30.6) in participants aged 65 years and older. mRNA-1283, which is designed to have enhanced stability in refrigerated conditions and will be packaged in pre-filled syringes, paves the way for a combination vaccine against flu and COVID-19, enhancing the Company’s overall respiratory portfolio. The Company expects to file for approval in 2024 and intends to use a Priority Review Voucher. Respiratory Syncytial Virus (RSV) In addition to acute mortality and morbidity, RSV infection is associated with long-term sequelae such as exacerbation of chronic obstructive pulmonary disease in older adults. In the U.S., each year there are up to 160,000 hospitalizations and 10,000 deaths in adults 65 years and older due to RSV.[5] Across high-income countries in 2019, RSV caused an estimated 5.2 million cases, 470,000 hospitalizations and 33,000 in-hospital deaths in adults 60 years and older.[6] In the younger adult population, potential risk factors such as chronic obstructive pulmonary disease (COPD), asthma, diabetes and obesity may cause an increased risk for RSV disease. Moderna’s RSV vaccine, mRESVIA (mRNA-1345) , has been approved for adults aged 60 years and older in the U.S. and EU. mRNA-1345 is in an ongoing Phase 3 study (P303) designed to test immunogenicity and safety in high-risk adults 18 to 59 years of age. In the trial, mRNA-1345 met all primary immunogenicity endpoints and the 50 µg dose, which is the same for the currently approved mRESVIA vaccine for adults 60 years and above, was well tolerated with no safety concerns identified. The Company intends to file a supplemental Biologics License Application (sBLA) for U.S. approval in 2024 to extend the indicated age range of mRNA-1345 to high-risk adults 18 to 59 years old, and intends to use a Priority Review Voucher. Influenza (Flu) Worldwide, there are 3-5 million severe cases of flu and 290,000-650,000 flu-related respiratory deaths annually.[7] Two main types of influenza viruses (A and B) cause seasonal flu epidemics, and the influenza A viruses lead to most flu-related hospitalization in older adults. Moderna has several seasonal influenza vaccine candidates in clinical development. The Company’s investigational seasonal flu vaccine, mRNA-1010 , demonstrated consistently acceptable safety and tolerability across three Phase 3 trials. In the most recent Phase 3 trial (P303), which was designed to test the immunogenicity and safety of an optimized vaccine composition, mRNA-1010 met all immunogenicity primary endpoints, demonstrating higher antibody titers compared to a licensed standard-dose flu vaccine (Fluarix®). In an older adult extension study of P303, mRNA-1010 met all primary immunogenicity endpoints-including superiority for all strains-compared to a licensed enhanced flu vaccine (Fluzone HD®) and showed an acceptable reactogenicity profile. Moderna is no longer pursuing an accelerated approval pathway for the regulatory submission of its standalone flu vaccine, mRNA-1010, to focus its resources on the submission of a potentially more impactful flu/COVID combination vaccine, mRNA-1083, this year. The Company plans to start a confirmatory vaccine efficacy study for mRNA-1010 in 2024, funded by previously announced project financing through Blackstone Life Sciences. Combination Respiratory Vaccines Currently, flu and COVID-19 are responsible for thousands of hospitalizations and hundreds of deaths each week in the U.S. To address the burden of these respiratory diseases, the Company’s combination vaccine candidates are designed for increased uptake, higher compliance, consumer convenience and benefits to healthcare systems. As announced in June, the Phase 3 study of the Company’s investigational combination vaccine against flu and COVID-19, mRNA-1083 , met its primary endpoints and elicited higher immune responses against influenza virus and SARS-CoV-2 than licensed flu and COVID vaccines in adults 50 years and older, including an enhanced flu vaccine in adults 65 years and older.mRNA-1083 also showed an acceptable safety and reactogenicity profile compared to co-administered flu and COVID-19 vaccines. The Company expects to file for approval in 2024 and intends to use a Priority Review Voucher. Latent and Other Virus Vaccines Cytomegalovirus (CMV) CMV, a latent virus, is the most common infectious cause of birth defects in the U.S. and is responsible for several billion dollars in annual healthcare costs. One in 200 babies in the U.S. are born with a congenital CMV infection, and of those affected, one in five will have severe, life-altering health problems. Possible short- and long-term sequelae of CMV infection include microcephaly, chorioretinitis, seizures, sensorineural hearing loss, cognitive impairment and cerebral palsy. CMVictory is a pivotal Phase 3 trial evaluating mRNA-1647 against primary CMV infection in women 16 to 40 years of age. The trial is accruing cases, and a Data Safety Monitoring Board (DSMB) will evaluate vaccine efficacy from the interim analysis when the trial has accrued 81 confirmed cases. The Company expects a vaccine efficacy readout as early as the end of 2024. Norovirus Enteric viruses, including norovirus, are a leading cause of diarrheal diseases, resulting in significant morbidity and mortality worldwide, particularly among young children and older adults. Norovirus is highly contagious and a leading cause of diarrheal disease globally, associated with 18% of all acute gastroenteritis (AGE),[8] resulting in approximately 200,000 deaths per year and substantial healthcare costs.[9] Given the wide diversity of norovirus genotypes, a broadly effective norovirus vaccine will require a multivalent vaccine design.[10] A Phase 1 trial designed to evaluate the safety, reactogenicity and immunogenicity of a trivalent norovirus vaccinecandidate, mRNA-1403 , in participants 18 to 49 years of age and 60 to 80 years of age in the U.S. is ongoing. An interim analysis showed that a single dose of mRNA-1403 elicited a robust immune response across all dose levels evaluated with a clinically acceptable reactogenicity and safety profile. Additionally, robust histo-blood group antigen (HBGA) blocking antibody titers were observed against vaccine-matched norovirus genogroup I and II selected strains across all dose levels evaluated. Similar mRNA-1403-induced HBGA-blocking antibody titers were observed in younger adult and older adult age groups. The Company plans to initiate a pivotal Phase 3 trial imminently. Oncology Therapeutics The Company’s oncology portfolio includes the individualized neoantigen therapy (INT) being developed in partnership with Merck. Earlier this year, Moderna and Merck initiated three new randomized clinical studies in additional tumor types, including a Phase 2 adjuvant treatment in patients with renal cell carcinoma, or kidney cancer; a Phase 2 adjuvant treatment in patients with high-risk muscle-invasive bladder cancer; and a Phase 2/3 neoadjuvant and adjuvant treatment in patients with cutaneous squamous cell carcinoma, the second most common form of skin cancer. Moderna’s global clinical trial footprint for INT has grown to more than 45 countries. The Phase 3 clinical trial for adjuvant melanoma, mRNA-4157 , is substantially enrolled and has closed screening to new patients in many countries. Moderna and its partner Merck have had preliminary discussions with regulators on approval based on the Phase 2 results. While discussions are ongoing, initial feedback from FDA has not been supportive of accelerated approval based on the current data. The Company and its partner Merck will continue engaging with regulators on the program, and remain focused on executing the Phase 3 trial. Rare Disease Therapeutics In the prioritized portfolio, the Company’s rare disease candidates include therapies targeting two organic acidemias caused by deficient metabolic enzymes, methylmalonic acidemia (MMA) and propionic acidemia (PA), both of which are characterized by metabolic decompensation events (MDEs) that can lead to severe and life-threatening symptoms such as vomiting, lethargy, seizures and coma. Methylmalonic acidemia (MMA) therapeutic In an ongoing Phase 1/2 study designed to evaluate safety and pharmacology in trial participants with MMA , mRNA-3705 was generally well-tolerated to date with no discontinuations due to safety and no events meeting protocol-defined dose-limiting toxicity criteria. Initial data is encouraging, withreductions in methylmalonic acid and other pathway biomarkers in participants, particularly at doses of at least 0.4 mg/kg Q2W. Early results suggest potential decreases in annualized rates of MMA-related hospitalizations and MDEs compared to pre-treatment rates. Moderna is working to identify an optimal dose and continues to engage with the U.S. FDA, via the START Program , and other global regulators. The Company is on track to begin generating pivotal study data by the end of 2024. Propionic acidemia (PA) therapeutic In an ongoing Phase 1/2 study designed to evaluate safety and pharmacology in trial participants with PA, mRNA-3927 was generally well-tolerated to date with no events meeting protocol-defined dose-limiting toxicity criteria. Early results suggest potential decreases in annualized MDE frequency compared to pre-treatment, and the majority of patients have elected to continue on the open label extension study. The Company is on track to begin generating pivotal study data by the end of 2024. Programs Discontinued Based on the Company’s strategic prioritization, five programs in its pipeline are discontinued: Financial Updates Moderna expects its commercial respiratory franchise to be profitable in 2024 and beyond. In addition, the Company is updating its projected 2024 research and development expenses to approximately $4.8 billion, primarily driven by the purchase of a Priority Review Voucher, and selling, general and administrative expenses to approximately $1.2 billion. Moderna is also reducing its expected research and development investment for 2025-2028 by approximately 20%, from $20 billion for the period to $16 billion through prioritization. The Company aims to complete the majority of its respiratory investments by 2026. It is increasing research and development investments in oncology, and pacing its investments in latent and other vaccines and in rare disease therapeutics. The Company is introducing an updated financial framework for 2025 and 2026-2028. Revenue: The Company expects 2025 revenue of $2.5 billion to $3.5 billion. For 2026-2028 the Company expects a compounded annual growth rate of more than 25% or more, driven by new product launches. Cost of Sales: Cost of sales is expected to be in the range of 35% to 45% in 2025. For 2026-2028, the Company expects cost of sales to decrease as a percentage of sales with increasing revenue. Research and Development Expenses: Full-year 2025 research and development expenses are anticipated to be $4.2 billion to $4.5 billion. In the 2026-2028 period, research and development expenses are expected to be approximately $11.5 billion on a cumulative basis. Selling, General and Administrative Expenses: Selling, general and administrative expenses for 2025 are projected to be $1.0 billion to $1.2 billion. For 2026-2028, selling expenses are expected to increase incrementally as new products are brought to market, while general and administrative expenses are expected to remain flat. Income Taxes: The Company continues to expect its full-year 2025 tax expense to be negligible. Tax will also be negligible for the 2026-2028 period. Capital Expenditures: Capital expenditures for 2025 are expected to be approximately $0.3 billion. For 2026-2028, capital expenditures are expected to be flat to down from 2025 levels. Cash and Investments: Year-end cash and investments for 2025 are projected to be approximately $6 billion. Moderna plans to break even on an operating cash cost basis (which excludes stock-based compensation, depreciation and amortization expense) with $6 billion in revenue. The Company expects to achieve this in 2028. The Company has sufficient capital to fund its plans until achieving break even on a cash cost basis without raising additional equity. About Moderna Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the Company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines. Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. INDICATION (U.S.) SPIKEVAX (COVID-19 Vaccine, mRNA) is a vaccine indicated for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older. IMPORTANT SAFETY INFORMATION FOR SPIKEVAX INDICATION (U.S.) mRESVIA (Respiratory Syncytial Virus Vaccine) is a vaccine indicated for active immunization for the prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in adults 60 years of age and older. IMPORTANT SAFETY INFORMATION FOR MRESVIA Spikevax® and mRESVIA® are registered trademarks of Moderna. Fluarix® is a registered trademark of GSK. Fluzone® is a registered trademark of Sanofi Pasteur. [1] Statistics for Moderna based upon internal data from 10 Phase 2 trials, and six Phase 3 trials. Data reported as of September 12, 2024. Industry statistics derived from Phase 2 and 3 study data from Wong et al., Biostatistics (2019) 20, 2, pp 273-286. [2] https://www.cdc.gov/resp-net/dashboard/index.html. Data last updated as of September 6, 2024 for 2023-2024 season. [3] https://www.cdc.gov/respiratory-viruses/risk-factors/older-adults.html [4] https://www.yalemedicine.org/news/covid-vaccines-reduce-long-covid-risk-new-study-shows [5] https://www.cdc.gov/rsv/php/surveillance/index.html [6] https://pubmed.ncbi.nlm.nih.gov/36369772/ [7] https://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal) [8] Ahmed, S.M., et al., Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis. Lancet Infect Dis, 2014 [9] https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/norovirus [10] https://www.cdc.gov/norovirus/downloads/global-burden-report.pdf SOURCE: Moderna

VaccineClinical ResultPhase 3Phase 2Drug Approval

12 Sep 2024

·www.fiercebiotech.com

Moderna targets $1.1B in R&D spending cuts, drops 5 programs amid profitability pressures

As part of Thursday's announcement, Moderna axed a plan to file for accelerated approval of its standalone flu vaccine mRNA-1010. Moderna has vowed to cut R&D spending by $1.1 billion by 2027. The decision to shrink the budget by more than 20% follows commercial setbacks that have persuaded the biotech to take a “more selective and paced approach” to drug development. The mRNA specialist expects to spend $4.8 billion on R&D this year. That figure is a problem for a company that wants to turn a profit in the foreseeable future. During the COVID-19 vaccine boom, Moderna generated enough cash to defuse concerns about spending. However, with Pfizer sewing up the European COVID-19 vaccine market for now and contracts stopping Moderna’s respiratory syncytial virus (RSV) vaccine from making a mark on the U.S. this year, the biotech is contending with falling sales.Moderna set out its response ahead of an R&D day on Thursday. The headline change is the reduction in R&D spending, which the biotech wants to get down to $3.6 billion to $3.8 billion in 2027. Moderna aims to generate the savings through portfolio reprioritizations and cost efficiencies.Cutting the budget will take time, with Moderna forecasting R&D spending of $4.2 billion to $4.5 billion in 2025.The biotech disclosed a raft of pipeline changes as part of the announcement. Moderna has axed a plan to file for accelerated approval of its standalone flu vaccine mRNA-1010. The biotech was aiming to seek approval this year but has decided to focus on its flu-COVID combination shot.Moderna plans to file for approval of the combination vaccine this year and use a priority review voucher. The biotech will start a confirmatory trial of mRNA-1010 this year, using cash from its deal with Blackstone Life Sciences. Moderna also discontinued five programs. A vaccine designed to prevent endemic human coronaviruses, pathogens that Moderna has previously said cause 1 million outpatient visits a year in the U.S., will stop development before entering the clinic. The other deprioritized candidates made it into human testing. “Emerging clinical data” has derailed the company's plans to advance a pediatric RSV program and triplet oncology candidate mRNA-2752 beyond phase 1. The cancer asset encodes a T cell co-stimulator and two pro-inflammatory cytokines. AKRAS antigen-specific therapy, mRNA-5671, and heart failure prospect, mRNA-0184, also failed to make the cut.Meanwhile, Moderna is continuing development of its Merck & Co.-partnered cancer prospect mRNA-4157 but has hit a regulatory obstacle.“Initial feedback from FDA has not been supportive of accelerated approval based on the current data,” Moderna said. Talks are ongoing but plans to seek approval may be put back until the partners have data from a “substantially enrolled” phase 3 trial in adjuvant melanoma, the company said. The biotech needs to get more products to market to hit the $6 billion in sales it believes are needed to break even. The goal is to secure 10 approvals over the next three years. Based on the forecasts, the biotech now expects to break even in 2028, two years later than previously planned.

VaccinePhase 3mRNAPriority ReviewAccelerated Approval

22 Aug 2024

·firstwordpharma.com

FDA clears updated COVID-19 vaccines from Moderna, Pfizer/BioNTech

The FDA on Thursday approved updated versions of the COVID-19 vaccines Comirnaty and Spikevax — the former developed by Pfizer and BioNTech, the latter from Moderna — designed to lend better protection against the Omicron variant KP.2 strain of the virus. Both mRNA jabs were cleared for individuals ages 12 and older; paediatric dosing schedules for children between the ages of 6 months and 11 years old were granted emergency-use authorisation.“These updated vaccines meet the agency’s rigorous, scientific standards for safety, effectiveness, and manufacturing quality,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, adding that the retooled vaccines are necessary “given waning immunity of the population from previous exposure to the virus and from prior vaccination.”The regulatory clearance also marks a shifting strategy from US health officials in their efforts to combat COVID-19. Going forward, the FDA now expects vaccines against the virus will need to be assessed annually, similar to seasonal flu vaccines. Releasing different jabs every year may align with the drugmakers’ latest endeavour — a COVID-19/flu combo vaccine. Both groups have their respective combination vaccines in late-stage testing, though Moderna’s jab — dubbed mRNA-1083 — seems to have the upper hand.Comprising components of seasonal flu candidate mRNA-1010 and a next-generation COVID-19 shot, the vaccine met the primary endpoints of a Phase III study in June, eliciting a higher immune response than comparator shots used in the trial.However, BioNTech and Pfizer’s candidate, which pairs Comirnaty with a trivalent flu vaccine, had mixed results in a Phase III study. While the combination jab was comparable to Comirnaty in generating a COVID-19 immune response, and showed a trend of stronger influenza A responses versus the licensed flu shot, the companies said it appeared less effective against the influenza B strain.

VaccineClinical ResultPhase 3mRNAEmergency Use Authorization

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Indication	Highest Phase	Country/Location	Organization	Date
Influenza, Human	Phase 3	AR	ModernaTX, Inc.	06 Jun 2022
Influenza, Human	Phase 3	AU	ModernaTX, Inc.	06 Jun 2022
Influenza, Human	Phase 3	CO	ModernaTX, Inc.	06 Jun 2022
Influenza, Human	Phase 3	PA	ModernaTX, Inc.	06 Jun 2022
Influenza, Human	Phase 3	PH	ModernaTX, Inc.	06 Jun 2022
COVID-19	Phase 2	US	ModernaTX, Inc.	13 May 2022
Respiratory Syncytial Virus Infections	Phase 1	US	ModernaTX, Inc.	14 Oct 2022
Respiratory Syncytial Virus Infections	Phase 1	AU	ModernaTX, Inc.	14 Oct 2022
Respiratory Syncytial Virus Infections	Phase 1	GB	ModernaTX, Inc.	14 Oct 2022
Severe Acute Respiratory Syndrome	Phase 1	US	ModernaTX, Inc.	14 Oct 2022

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05415462 (CTgov)	Phase 3	Influenza, Human	6,102	Fluarix Tetra (Fluarix Tetra)	awxtsoyfjx(ldicbsxwme) = ccsybhavpb slrupincsd (bylffunyyb, swqpzzfgad - vrshogfqwn) View more	-	24 Sep 2024
				mRNA-1010 (mRNA-1010)	awxtsoyfjx(ldicbsxwme) = cxxhofvucg slrupincsd (bylffunyyb, fatddiusqy - certdbincp) View more
NCT04956575 (Pubmed) Manual	Phase 1/2	Influenza, Human	-	mRNA-1010	noppkzioly(mucegkltsn) = reported more frequently for mRNA-1010 than placebo or Afluria and most were grade 1 or 2 in severity. cjheehxrax (lrkqqcveet ) View more	Positive	27 Jun 2024
				Placebo
NCT05375838 (CTgov)	Phase 1/2	COVID-19 \| Influenza, Human	550	placebo+mRNA-1273 (mRNA-1273 + Placebo)	iqhpbvdsal(tqtysjdvps) = nhqzpbiypt vpwymbkvmt (anmmcqzrip, xbpyotuuvr - ljafralgih) View more	-	28 Feb 2024
				placebo+mRNA-1010 (mRNA-1010 + Placebo)	iqhpbvdsal(tqtysjdvps) = svficgchih vpwymbkvmt (anmmcqzrip, yyunmocfja - zuepzpnqwh) View more
NCT05415462 (Company_Website) Manual	Phase 3	Influenza, Human	-	mRNA-1010	becdjvcvoz(rxzavdgrze) = jtscaflcpz xiajvivxef (tlfjjcucrl )	Non-inferior	16 Feb 2023
				Fluarix Tetra	becdjvcvoz(rxzavdgrze) = dflunzrdyn xiajvivxef (tlfjjcucrl )

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