Last update 04 Nov 2024

Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

Last update 04 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Inactivated vaccine, Prophylactic vaccine, Multivalent vaccine

Synonyms

Fluzone Hd Quadrivalent, Fluzone, Fluzone Hd Quadrivalent, Fluzone High Dose, Fluzone Intradermal, Fluzone Quadrivalent, H1N1/H3N2/Victoria Lineage/Yamagata Lineage Influenza Vaccine(Split)(Sanofi)

+ [3]

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Influenza, HumanInfluenza A virus infectionInfluenza B virus infection

Inactive Indication-

Originator Organization

Sanofi

Active Organization

Shenzhen Sanofi Pasteur Biological Products Co. Ltd.Sanofi Pasteur, Inc.

Inactive Organization

Sanofi Pasteur

Drug Highest PhaseApproved

First Approval Date

US (09 Dec 1999),

Influenza A virus infectionInfluenza B virus infection

Regulation-

115

Clinical Trials associated with Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

NCT06291857 / Not yet recruitingPhase 3

A Randomized, Observer-Blinded, Active-Controlled Study to Evaluate the Safety and Immunogenicity of a COVID-19 Influenza Combination Nanoparticle Vaccine and a Standalone Trivalent Nanoparticle Influenza Hemagglutinin Vaccine in Participants ≥ 65 Years of Age.

The goal of this Phase 3 study is to compare the effectiveness, safety, and side effects of the CIC vaccine with approved flu vaccines and the Novavax COVID-19 Vaccine with adjuvant.

Start Date21 Oct 2024

Sponsor / Collaborator

Novavax, Inc.

NCT05947071 / RecruitingPhase 2IIT

Comparison of High vs Standard Dose Influenza Vaccines in Pediatric Solid Organ Transplant Recipients

Influenza virus is a significant pathogen in pediatric solid organ transplant (SOT) recipients. However, these individuals respond poorly to standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. One study compared HD-IIV vs. SD-IIV in adult SOT recipients and noted that HD-IIV was safe and more immunogenic; however, the median post-transplant period was 38 months. A phase I pediatric study comparing a single dose of HD-IIV vs. SD-IIV was safe with higher immunogenicity, but the study was limited by small sample size and median post-transplant vaccine administration was 26 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV one month apart compared to one-dose of SD-IIV revealed modestly increased immunogenicity when given at a median of 18 months post-transplant. Therefore, these studies lack both evaluation in the early post-transplant period and substantive pediatric populations. Additionally, the administration of two-doses of HD-IIV in the same influenza season has not been evaluated in pediatric SOT recipients. Thus, the optimal immunization strategy for pediatric SOT recipients less than 24 months post-transplant is unknown. In addition, immunologic predictors and correlates of influenza vaccine immunogenicity in pediatric SOT recipients have not been well-defined.
The central hypothesis of our proposal is that pediatric SOT recipients 1-23 months post-transplant who receive two doses of HD-quadrivalent inactivated influenza vaccine (QIV) will have similar safety but higher Hemagglutination Inhibition (HAI) geometric mean titers (GMTs) to influenza antigens compared to pediatric SOT recipients receiving two doses of SD-QIV.

Start Date26 Sep 2024

Sponsor / Collaborator

National Institute of Allergy & Infectious Diseases

NCT06229392 / RecruitingPhase 1IIT

A Phase I Study to Evaluate the Intratumoral Influenza Vaccine Administration in Patients With Breast Cancer

This Phase 1 study will assess the safety and efficacy (usefulness) of administering 2 doses of seasonal flu vaccine directly into breast cancer tissue (primary tumor), and will study the tumor and whole body response to the vaccine. If the tumor is palpable (able to fee by touch), the vaccine will be administered by a Surgeon/oncologist in the outpatient floor - both experienced and trained. If not palpable, the procedure will be done via guided Ultrasound by our Breast Radiologist -- both experienced and trained. Women with triple-negative (TNBC) and HER2+ types of breast cancer will be eligible for enrollment. Up to 18 subjects may be enrolled at Rush. Successive groups of 3 subjects per breast cancer type will be given increasing doses of vaccine. There are 3 potential dosing groups (half-dose, full dose, and high dose). Blood, stool (optional), and tumor tissue samples will be collected and tested. The active participation period is from one week prior to starting chemotherapy through three months post surgery.

Start Date28 Feb 2024

Sponsor / Collaborator

Rush University Medical Center

100 Clinical Results associated with Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

100 Translational Medicine associated with Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

100 Patents (Medical) associated with Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

108

Literatures (Medical) associated with Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

01 Oct 2024·LANCET INFECTIOUS DISEASES

Safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication influenza vaccine alone or coadministered with an inactivated influenza vaccine (Fluzone High-Dose Quadrivalent) in adults aged 65–85 years in the USA: a multicentre, randomised, double-blind, double-dummy, phase 1b trial

Article

Author: Greenberg, Harry ; Belshe, Robert ; Rhee, Margaret ; Bilsel, Pamuk ; Murray, Bryan ; Fierro, Carlos ; Marshall, David ; Neumann, Gabriele ; Coelingh, Kathleen ; Moser, Michael J ; Eiden, Joseph ; Herber, Renee ; Kawaoka, Yoshihiro ; Turner, Mark ; Davis, Matthew ; Aitchison, Roger ; White, Alexander

BACKGROUND:

Older adults (aged ≥65 years) show increased susceptibility to severe disease with influenza virus infection, accounting for 70-85% of annual influenza-related fatalities in the USA. Stimulating mucosal antibodies and T cells might enhance the low vaccine effectiveness seen in older adults for currently licensed inactivated influenza vaccines, which induce mainly serum antibodies. We aimed to evaluate the safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication (M2SR) vaccine, alone or coadministered with a licensed inactivated influenza vaccine (Fluzone High-Dose Quadrivalent; hereafter referred to as Fluzone HD), in older adults.

METHODS:

In this multicentre, randomised, double-blind, double-dummy, phase 1b trial, individuals aged 65-85 years who were considered healthy or with stable chronic conditions with no recent (<6 months) influenza vaccinations were recruited from five clinical trial sites in the USA and randomly assigned (3:3:3:1) using a permuted block design to receive the H3N2 M2SR vaccine and Fluzone HD, the H3N2 M2SR vaccine and placebo, Fluzone HD and placebo, or placebo alone. All participants received a single intranasal spray and a single intramuscular injection, whether active or placebo, to maintain masking. The primary outcome was to assess the safety of H3N2 M2SR, administered alone or with Fluzone HD, in the safety analysis set, which included all participants who were randomly assigned and received treatment. Serum and mucosal antibodies were assessed as a secondary endpoint, and cell-mediated immunity as an exploratory endpoint, in participants in the per-protocol population, which included individuals in the safety analysis set without major protocol deviations. This trial is registered with ClinicalTrials.gov, NCT05163847.

FINDINGS:

Between June 14 and Sept 15, 2022, 305 participants were enrolled and randomly assigned to receive the H3N2 M2SR vaccine plus placebo (n=89), H3N2 M2SR vaccine plus Fluzone HD (n=94), Fluzone HD plus placebo (n=92), or placebo alone (n=30). All randomly assigned participants were included in the safety analysis set. The most frequently reported local symptoms up to day 8 in groups that received M2SR were rhinorrhoea (43% [38 of 89] in the H3N2 M2SR plus placebo group and 38% [36 of 94] in the H3N2 M2SR plus Fluzone HD group), nasal congestion (51% [45 of 89] and 35% [33 of 94]), and injection-site pain (8% [seven of 89] and 49% [46 of 94]), and the most frequently reported solicited systemic symptoms were sore throat (28% [25 of 89]) for M2SR and decreased activity (26% [24 of 94]) for the M2SR plus Fluzone HD group. In the Fluzone HD plus placebo group, the most frequently reported local symptom was injection-site pain (48% [44 of 92]) and systemic symptom was muscle aches (22% [20 of 92]). The frequency of participants with any treatment-emergent adverse event related to vaccination was low across all groups (2-5%). One serious adverse event was reported, in a participant in the Fluzone HD plus placebo group. M2SR with Fluzone HD induced seroconversion (≥four-fold increase in haemagglutination inhibition antibodies from baseline to day 29) in 44 (48%) of 91 participants, compared with 28 (31%) of 90 participants who seroconverted in the Fluzone HD plus placebo group (p=0·023). M2SR with Fluzone HD also induced mucosal and cellular immune responses.

INTERPRETATION:

The H3N2 M2SR vaccine coadministered with Fluzone HD in older adults was well tolerated and provided enhanced immunogenicity compared with Fluzone HD administered alone, suggesting potential for improved efficacy of influenza vaccination in this age group. Additional studies are planned to assess efficacy.

FUNDING:

US Department of Defense.

15 May 2024·The Journal of infectious diseases

Differential Induction of Interferon-Stimulated Genes by Cell-Based Versus Egg-Based Quadrivalent Influenza Vaccines in Children During the 2018–2019 Season

Article

Author: Martin, Judith M ; Nowalk, Mary Patricia ; Alcorn, John F ; Moehling Geffel, Krissy ; Ortiz, Marianna A ; Rajasundaram, Dhivyaa ; Zimmerman, Richard K

Abstract:

Background:

Cell-based quadrivalent-inactivated influenza vaccine has been shown to have higher vaccine effectiveness than traditional egg-based quadrivalent-inactivated influenza vaccine. This is observed despite similar levels of serum hemagglutinin antibodies induced by each vaccine.

Methods:

In this study, we examine peripheral immune activation after egg-based or cell-based influenza vaccination in a clinical trial in children. Peripheral blood mononuclear cells were isolated, and ribonucleic acid was sequenced from 81 study participants (41 Fluzone, egg based and 40 Flucelvax, cell based) pre- and 7 days postvaccination. Seroconversion was assessed by hemagglutinin inhibition assay. Differential gene expression was determined and pathway analysis was conducted.

Results:

Cell-based influenza vaccine induced greater interferon-stimulated and innate immune gene activation compared with egg-based influenza vaccine. Participants who seroconverted had increased interferon-signaling activation versus those who did not seroconvert.

Conclusions:

These data suggest that cell-based influenza vaccine stimulates immune activation differently from egg-based influenza vaccine, shedding light on reported differences in vaccine effectiveness.

01 Jan 2024·Journal of immunology (Baltimore, Md. : 1950)

Distinct Functional Humoral Immune Responses Are Induced after Live Attenuated and Inactivated Seasonal Influenza Vaccination

Article

Author: Hanley, Hannah B ; Ross, Ted M ; Lingwood, Daniel ; Carlock, Michael A ; Alter, Galit ; Deng, Yixiang ; Tong, Xin ; McNamara, Ryan P ; Cizmeci, Deniz ; Fontana, Laura

Abstract:

Influenza viruses infect 5–30% of the world’s population annually, resulting in millions of incidents of hospitalization and thousands of mortalities worldwide every year. Although annual vaccination has significantly reduced hospitalization rates in vulnerable populations, the current vaccines are estimated to offer a wide range of protection from 10 to 60% annually. Such incomplete immunity may be related to both poor antigenic coverage of circulating strains, as well as to the insufficient induction of protective immunity. Beyond the role of hemagglutinin (HA) and neuraminidase (NA), vaccine-induced Abs have the capacity to induce a broader array of Ab effector functions, including Ab-dependent cellular cytotoxicity, that has been implicated in universal immunity against influenza viruses. However, whether different vaccine platforms can induce functional humoral immunity in a distinct manner remains incompletely defined. In this study, we compared vaccine-induced humoral immune responses induced by two seasonal influenza vaccines in Homo sapiens, the i.m. inactivated vaccine (IIV/Fluzone) and the live attenuated mucosal vaccine (LAIV/FluMist). Whereas the inactivated influenza vaccine induced superior Ab titers and FcγR binding capacity to diverse HA and NA Ags, the live attenuated influenza mucosal vaccine induced a more robust functional humoral immune response against both the HA and NA domains. Multivariate Ab analysis further highlighted the significantly different overall functional humoral immune profiles induced by the two vaccines, marked by differences in IgG titers, FcR binding, and both NK cell–recruiting and opsonophagocytic Ab functions. These results highlight the striking differences in Ab Fc-effector profiles induced systemically by two distinct influenza vaccine platforms.

News (Medical) associated with Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

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

27 Aug 2024

·www.fiercepharma.com

Sanofi halts flu vaccine distribution in China over fear of declining potency

Sanofi suspended the rollout of its flu vaccines in China after observing a decline in the vaccines’ potency during a routine quality follow-up test. Sanofi has temporarily stopped distributing and selling its flu shots in China out of concerns of waning potency.A Sanofi spokesperson confirmed the halt to Fierce Pharma. Supplies of the French pharma’s two China-approved split-virion flu shot brands, Vaxigrip and VaxigripTetra, are being affected for the ongoing 2024-25 influenza season.Sanofi suspended the rollout after observing a decline in the vaccines’ potency—the ability of the shots to produce the intended biological effect—during a routine quality follow-up test of doses that had been produced but not yet distributed, according to the spokesperson.“We believe the efficacy could possibly be impacted before the end of the product’s shelf life for one of the antigens in the vaccine,” the spokesperson explained.The Vaxigrip and VaxigripTetra shots Sanofi manufactures have met good manufacturing practices and Chinese standards, and “the decision to stop their supply and sale is a preventive measure,” the spokesperson said.“All vaccines already distributed meet the necessary specifications for release and are both safe and effective,” the spokesperson added.Sanofi attributed the problem to “unexpected circumstances” at the company’s influenza vaccine production line in the Chinese city of Shenzhen. The issue doesn’t appear to affect other markets, according to the Sanofi spokesperson, as the Shenzhen site makes doses exclusively for China. In the U.S., Sanofi is offering flu shots under the brands Fluzone, Fluzone High-Dose, and Flublok. Sanofi said it doesn’t expect the issue will have any major impact on overall flu protection in China. In 2023, Sanofi booked 2.67 billion euros in global flu vaccines sales, down 5.5% year over year at constant exchange rates. While the French pharma is one of the largest vaccine makers globally, the Chinese flu shot market has been dominated by local firms.Sanofi’s hiccup comes after a round of price cuts intensified competition among flu shot manufacturers in China. Flu vaccines are not included in China’s national immunization program, and people need to pay out of pocket to get inoculated.After state-run Sinopharm reduced its quadrivalent flu vaccine’s price by 31% to 88 Chinese yuan (about $12) per dose in May, Hualan Biological Vaccine—the largest flu shot supplier in China by volume by a large margin—and Sinovac followed suit in June. Sanofi’s quadrivalent shot VaxigripTetra competes directly with those domestic offerings. Meanwhile, for the 2024-25 flu season, the U.S. is transitioning to trivalent flu shots rather than the more inclusive quadrivalent options after the FDA noted that the B/Yamagata lineage of the influenza virus has not been spotted worldwide after March 2020.“Sanofi remains dedicated to supporting flu prevention in China, a commitment that has guided our efforts for nearly three decades,” the company spokesperson said. “We will continue to collaborate with our partners to ensure that influenza vaccines are available for the 2025-2026 season, protecting the health of Chinese population.”

VaccineDrug Approval

23 Jul 2024

·www.prnewswire.com

BIOVAXYS ANNOUNCES ISSUANCE OF DPX RELATED PATENT FROM THE U.S. PATENT AND TRADEMARK OFFICE

VANCOUVER, BC, July 23, 2024 /PRNewswire/ -- BioVaxys Technology Corp. (CSE: BIOV) (FRA: 5LB) (OTCQB: BVAXF) ("BioVaxys" or "Company") announced that the United States Patent and Trademark Office ("USPTO") has issued BioVaxys U.S. Patent No. 12,042,537. ("Patent") for inducing an antibody immune response from a low dose volume delivery of a B-cell epitope formulated with DPX™. This Patent was recently allowed in Japan and is currently pending in the European Union. DPX™ is a proprietary lipid-based delivery platform with no aqueous component that can be formulated with a range of packaged antigens, proteins, peptides, mRNA, or small molecules. Its unique "no release" mechanism of action allows antigen presenting cells (APCs) to be attracted to the injection site, facilitating a robust and long-duration immune response. The smallest dose of a currently approved vaccine is 0.1ml for Sanofi-Pasteur's Fluzone™ Intradermal Quadrivalent vaccine. Low dose volume delivery of DPX™ formulated B-cell epitope is designed to be delivered in single low dose volume of less than 100 µl that can package 5µL to 50 µL of of an antigen comprising a B-cell epitope. An epitope is the part of an antigen that the host's immune system recognizes, eliciting the immune response to an invading pathogen. It specifically binds to the corresponding antigen receptor on the immune cell (such as a B-cell). Whereas T-cells protect people from getting infected by destroying cancerous and infected cells, B-cells produce antibodies to fight infection. Potential applications of this technology include epitope-based vaccines for diseases such as chronic hepatitis-B, influenza, and Respiratory Syncytial Virus (RSV)---where BioVaxys' clinical study data is encouraging for product development. In a prior randomized, observer-blinded, first-in-humans Phase 1 study of a novel synthetic RSV antigen based on the ectodomain of the small hydrophobic glycoprotein (SHe) of RSV subgroup A formulated with DPX ("DPX-RSV"), the data showed that more than nine months after the last vaccination, 15 of 16 participants (93%) who received DPX-RSV demonstrated antigen-specific immune responses. One dose was tested out to one year and 100% of older adults (7/7 immune responders) maintained antigen-specific immune responses one year after receiving the booster dose. After one year, their antibody levels measured were still at peak with no sign of decrease. BioVaxys President and Chief Operating Officer Kenneth Kovan stated "Issuance of this Patent by the USPTO expands the value of our IP and DPX platform, and puts the Company on strong footing for further development and partnering with companies developing epitope-based vaccines for diseases such as chronic hepatitis-B, influenza, and RSV, where we have such promising human study results." About BioVaxys Technology Corp. BioVaxys Technology Corp. (), a biopharmaceuticals company registered in British Columbia, Canada, is a clinical-stage biopharmaceutical company dedicated to improving patient lives with novel immunotherapies based on the DPX™ immune-educating technology platform and it's HapTenix© 'neoantigen' tumor cell construct platform, for treating cancers, infectious disease, antigen desensitization, and other immunological fields. The Company's clinical stage pipeline includes maveropepimut-S which is in Phase II clinical development for advanced Relapsed-Refractory Diffuse Large B Cell Lymphoma (DLBCL) and platinum resistant ovarian cancer, and BVX-0918, a personalized immunotherapeutic vaccine using its' proprietary HapTenix© 'neoantigen' tumor cell construct platform which is soon to enter Phase I in Spain for treating refractive late-stage ovarian cancer. The Company is also capitalizing on its tumor immunology know-how and creation of a unique library of T-lymphocytes & other datasets post-vaccination with its personalized immunotherapeutic vaccines to utilize predictive algorithms and other technologies to identify new targetable tumor antigens. BioVaxys common shares are listed on the CSE under the stock symbol "BIOV" and trade on the Frankfurt Bourse (FRA: 5LB) and in the US (OTCQB: BVAXF). For more information, visit and connect with us on X and LinkedIn. ON BEHALF OF THE BOARD Signed "James Passin" James Passin, CEO +1 646 452 7054 Cautionary Statements Regarding Forward Looking Information The CSE has neither approved nor disapproved the contents of this press release. The CSE does not accept responsibility for the adequacy or accuracy of this release. This press release includes certain "forward-looking information" and "forward-looking statements" (collectively "forward- looking statements") within the meaning of applicable Canadian and United States securities legislation including the United States Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical fact, included herein, without limitation, statements relating the future operating or financial performance of the Company, are forward looking statements. Forward-looking statements are frequently, but not always, identified by words such as "expects", "anticipates", "believes", "intends", "estimates", "potential", "possible", and similar expressions, or statements that events, conditions, or results "will", "may", "could", or "should" occur or be achieved. There can be no assurance that such statements will prove to be accurate, and actual results and future events could differ materially from those expressed or implied in such forward-looking statements. These forward-looking statements reflect the beliefs, opinions and projections on the date the statements are made and are based upon a number of assumptions and estimates, primarily the assumption that BioVaxys will be successful in developing and testing vaccines, that, while considered reasonable by the Company, are inherently subject to significant business, economic, competitive, political and social uncertainties and contingencies including, primarily but without limitation, the risk that BioVaxys' vaccines will not prove to be effective and/ or will not receive the required regulatory approvals. With regards to BioVaxys' business, there are a number of risks that could affect the development of its biotechnology products, including, without limitation, the need for additional capital to fund clinical trials, its lack of operating history, uncertainty about whether its products will complete the long, complex and expensive clinical trial and regulatory approval process for approval of new drugs necessary for marketing approval, uncertainty about whether its autologous cell vaccine immunotherapy can be developed to produce safe and effective products and, if so, whether its vaccine products will be commercially accepted and profitable, the expenses, delays and uncertainties and complications typically encountered by development stage biopharmaceutical businesses, financial and development obligations under license arrangements in order to protect its rights to its products and technologies, obtaining and protecting new intellectual property rights and avoiding infringement to third parties and their dependence on manufacturing by third parties. The Company does not assume any obligation to update the forward-looking statements of beliefs, opinions, projections, or other factors, should they change, except as required by law. Logo - SOURCE BioVaxys Technology Corp.

VaccinePhase 1ImmunotherapyPhase 2Clinical Result

100 Deals associated with Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

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Indication	Country/Location	Organization	Date
Influenza, Human	CN	Shenzhen Sanofi Pasteur Biological Products Co. Ltd.	21 Feb 2023
Influenza A virus infection	US	Sanofi Pasteur, Inc.	09 Dec 1999
Influenza B virus infection	US	Sanofi Pasteur, Inc.	09 Dec 1999

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02936180 (IV-RA, CTgov)	Phase 4	Rheumatoid Arthritis \| Influenza, Human	279	SD-QIV (Standard Dose Influenza Vaccine)	paxlghduia(qauyxopvyc) = hvhqstgubq zhtaisohua (phzdvnitkp, fvikkjyuhk - drkxpazogu) View more	-	13 Aug 2024
				HD-TIV (High Dose Influenza Vaccine)	paxlghduia(qauyxopvyc) = nrzdvnylbf zhtaisohua (phzdvnitkp, ezkbtomtzt - uedxsocvxd) View more
NCT03722589 (CTgov)	Phase 4	Influenza, Human	944	Flublok (Flublok (Recombinant))	cmoauggzfo(jutxshilud) = xzgnjwxafm yjovcufsre (eipzfkfcfy, vcdtubkzfu - qxchbnguef) View more	-	22 Jul 2024
				Flucelvax (Flucelvax (Cell-based))	cmoauggzfo(jutxshilud) = wtezbwnnuh yjovcufsre (eipzfkfcfy, dnmihbmlyw - ockljeosij) View more
NCT05007041 (CTgov)	Phase 4	Pain \| Herpes Zoster \| Injection Site Reaction ... View more	267	Zoster Vaccine Recombinant (RZV) (Zoster Vaccine Recombinant (RZV) and Quadrivalent Adjuvanted Influenza Vaccine)	ptznstsrql(pvcnzinpfs): Difference in proportions = -0.96 (95% CI, -8.94 to 7.10), P-Value = 0.0037 View more	-	01 May 2024
				Zoster Vaccine Recombinant (RZV) (Zoster Vaccine Recombinant (RZV) and High-dose Quadrivalent Influenza Vaccine)
NCT03694808 (CTgov)	Phase 4	Influenza, Human	478	Fluad Vaccine (Fluad Vaccine)	bzsxeadhik(hfsaotohfb) = jqqufusnex dwvoagzbml (bwkigaoqll, kptoxexduz - mtqjkqmuvf) View more	-	30 Apr 2024
				Fluzone HD Vaccine (Fluzone Vaccine)	bzsxeadhik(hfsaotohfb) = dptznvecaq dwvoagzbml (bwkigaoqll, xuymwqqipq - jbkukgswhp) View more
NCT03603509 (CTgov)	Phase 4	Influenza, Human	241	Fluad Vaccine (Fluad Vaccine)	xhbmurrhpb(jclwlsvgat) = zhzqztpprp sshfvuuehb (gaibgsahya, jjbtnidyee - xqnbiozyhw) View more	-	16 May 2023
				Fluzone High-Dose (Fluzone Vaccine)	xhbmurrhpb(jclwlsvgat) = hcpblarnpi sshfvuuehb (gaibgsahya, oyymyzfbrw - zggrqdvbsq) View more
NCT03658629 (CTgov)	Phase 2	Influenza, Human	1,375	Placebo+NanoFlu (Quad-NIV) (Quad-NIV Bedside Mix of Antigen and Adjuvant Dose A)	mwztbgrdff(gfxcoogidc) = lnjlktouax qgqibqkemz (jhozerdgwd, adtklttmcn - bkhvcebdwp) View more	-	04 Nov 2022
				Quad-NIV (Quad-NIV Preformulated With Adjuvant Dose A)	mwztbgrdff(gfxcoogidc) = pvmfrsnocl qgqibqkemz (jhozerdgwd, qalckebkmh - lhxvmkbzcg) View more
NCT04077424 (single cell, CTgov)	Phase 4	Influenza, Human	10	Fluzone-High Dose Quadrivalent (Fluzone-High Dose)	ukldszwzgc(xtondatiwj) = nogremmhpi jdtdxvqhox (kjfzzbyucf, vjexlcikcm - ssuqgeafuy) View more	-	12 Jul 2022
				Fluad (Fluad)	ukldszwzgc(xtondatiwj) = gjjypsafdz jdtdxvqhox (kjfzzbyucf, hxjrgwhnuf - syzyuosyup) View more
NCT03068949 (CTgov)	Phase 4	Influenza, Human	413	FluBlok (FluBlok)	ewzvfvhotc(izucffpvgm) = yznwyoctvf fibgzwvtbg (cypiqrlctm, gvtrkxizwz - zarauvlwcc) View more	-	30 Nov 2021
				Fluzone (Fluzone)	ewzvfvhotc(izucffpvgm) = nyssvyfirt fibgzwvtbg (cypiqrlctm, vrxsjiwere - fcmfjxwvxq) View more
NCT03183908 (CTgov)	Phase 4	Pain \| Injection Site Reaction \| Drug-Related Side Effects and Adverse Reactions ... View more	757	FLUAD® (Adjuvanted Influenza Vaccine (FLUAD®))	ryfkehyycu(sqvbkjpmup): Difference in proportions = -2.7 (95% CI, -5.8 to 0.4) View more	-	30 Mar 2021
				Fluzone® High-Dose (High-dose Influenza Vaccine (Fluzone® HD))
NCT04109222 (GRC00097, CTgov)	Phase 4	Influenza, Human	90	Fluzone Quadrivalent vaccine, no preservative (0.5-mL), 2019-2020 formulation (Group 1: Fluzone Quadrivalent Influenza Vaccine: 6 to < 36 Months)	uulcqxvcbe(yavcjtfxqg) = ysgycthvsu fgdzidltvv (iubxbxvobr, gahyvwezns - sbfztnapvt) View more	-	17 Dec 2020
				Fluzone Quadrivalent vaccine, no preservative (0.5-mL), 2019-2020 formulation (Group 2: Fluzone Quadrivalent Influenza Vaccine: 3 to < 9 Years)	uulcqxvcbe(yavcjtfxqg) = ihxxqhgxcv fgdzidltvv (iubxbxvobr, blbslamfnj - fvczqogovt) View more

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Tetravalent influenza vaccine(Split, inactivated)(Sanofi)

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