Immunogenicity and safety of JENVAC and JEEV vaccines administered for prevention of Japanese encephalitis in an interchangeable dosing schedule among healthy Indian children: A multicentric, phase IV, open-labeled, randomized controlled trial - Nil

Start Date10 Nov 2023

Sponsor / Collaborator

Indian Council of Medical Research

NCT05568953 / RecruitingPhase 2

An Experimental Medicine Decipher of a Minimum Correlate of Cellular Immunity

We hypothesize that a high CD4+ and CD8+ T cell count will reduce viremia upon challenge with a structurally heterologous virus, and correspondingly result in reduced magnitude of host response to challenge infection.
Primary Objective: To compare, after challenge with a structurally heterologous vaccine, the differences in levels of viremia between healthy adults who received primary vaccination with either YF17D vaccine, chimeric JE-YF17D vaccine, or inactivated JE vaccine.
58 subjects will be randomised into 1 of 2 arms (Arm B1 and Arm B2) in a 1:1 ratio, in a double-blind fashion. Subjects in Arm B1 will receive JE-YF17D vaccine (Imojev, Sanofi Pasteur) on Day 0 followed by YF17D vaccine (Stamaril, Sanofi Pasteur) on Day 28. Subjects in Arm B2 will receive Stamaril on Day 0 followed by Imojev on Day 28. Arm B3 will be conducted as a separate single-arm open label design in 14 subjects. Subjects in Arm B3 will receive inactivated JE vaccine (Ixiaro, Valneva) on Day 0 followed by Stamaril on Day 28.
The rationale for these three study arms is as follows: Arm B1 will show the impact low levels of viremia, and the resultant low levels of virus-specific CD4+ and CD8+ T cells, would have on YF17D infection. In contrast, YF17D vaccination in Arm B2 would produce high levels of viremia, and in turn high levels virus-specific T cells, thus likely ameliorating JE-YF17D infection. Arm B3 will serve as the control arm, as vaccination with inactivated JE vaccine would not produce any YF17D-specific T cell response. Notably, the first vaccination in Arms B1 and B2 would also provide the viremia response in the absence of virus-specific T cells, which would serve as a reference point to interpret the outcome of the second vaccination.

Start Date28 Sep 2022

Sponsor / Collaborator

Singapore General Hospital Pte Ltd.

[+1]

EUCTR2016-002894-36-AT / Unknown statusPhase 4IIT

An open, monocentric, uncontrolled phase 4 trial to characterise cellular and humoral immune responses following the first booster immunisation with the inactivated, purified Japanese Encephalitis vaccine IXIARO® in elderly compared to young individuals. - Immune responses after a booster immunisation with IXIARO® in elderly compared to young individuals.

Start Date22 Dec 2017

Sponsor / Collaborator

Medical University of Vienna

100 Clinical Results associated with Japanese encephalitis vaccine, inactivated(Valneva SE)

100 Translational Medicine associated with Japanese encephalitis vaccine, inactivated(Valneva SE)

100 Patents (Medical) associated with Japanese encephalitis vaccine, inactivated(Valneva SE)

141

Literatures (Medical) associated with Japanese encephalitis vaccine, inactivated(Valneva SE)

01 Jul 2024·Virus Research

Japanese encephalitis virus E protein domain III immunization mediates cross-protection against Zika virus in mice via antibodies and CD8+ T cells

Article

Author: Zou, Wei-Wei ; Wen, Jin-Sheng ; Chen, Dong ; Duan, Zhi-Liang ; Zhu, Jia-Yang

Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are antigenically related flaviviruses that co-circulate in many countries/territories. The interaction between the two viruses needs to be determined. Recent findings by ourselves and other labs showed that JEV-elicited antibodies (Abs) and CD8⁺T cells exacerbate and protect against subsequent ZIKV infection, respectively. However, the impact of JEV envelope (E) protein domain III (EDIII)-induced immune responses on ZIKV infection is unclear. We show here that sera from JEV-EDIII-vaccinated mice cross-react with ZIKV-EDIII in vitro, and transfer of the same sera to mice significantly decreases death upon lethal ZIKV infection at a dose-dependent manner. Maternally acquired anti-JEV-EDIII Abs also significantly reduce the mortality of neonatal mice born to JEV-EDIII-immune mothers post ZIKV challenge. Similarly, transfer of ZIKV-EDIII-reactive IgG purified from JEV-vaccinated humans increases the survival of ZIKV-infected mice. Notably, transfer of an extremely low volume of JEV-EDIII-immune sera or ZIKV-EDIII-reactive IgG does not mediate the Ab-mediated enhancement (ADE) of ZIKV infection. Similarly, transfer of JEV-EDIII-elicited CD8⁺T cells protects recipient mice against ZIKV challenge. These results demonstrate that JEV-EDIII-induced immune components including Abs and T cells have protective roles in ZIKV infection, suggesting EDIII is a promising immunogen for developing effective and safety JEV vaccine.

16 Apr 2024·Journal of Virology

Epitope(s) involving amino acids of the fusion loop of Japanese encephalitis virus envelope protein is(are) important to elicit protective immunity

Article

Author: Ke, Yuan-Dun ; Chiou, Shyan-Song ; Chang, Gwong-Jen J ; Fan, Yi-Chin ; Chen, Jo-Mei ; Chen, Yi-Ying

ABSTRACT Dengue vaccine candidates have been shown to improve vaccine safety and efficacy by altering the residues or accessibility of the fusion loop on the virus envelope protein domain II (DII FL ) in an ex vivo animal study. The current study aimed to comprehensively investigate the impact of DII FL mutations on the antigenicity, immunogenicity, and protective efficacy of Japanese encephalitis virus (JEV) virus-like particles (VLPs) in mice. We found the DII FL G106K/L107D (KD) and W101G/G106K/L107D (GKD) mutations altered the binding activity of JEV VLP to cross-reactive monoclonal antibodies but had no effect on their ability to elicit total IgG antibodies in mice. However, JEV VLPs with KD or GKD mutations induced significantly less neutralizing antibodies against JEV. Only 46% and 31% of the KD and GKD VLPs-immunized mice survived compared to 100% of the wild-type (WT) VLP-immunized mice after a lethal JEV challenge. In passive protection experiments, naïve mice that received sera from WT VLP-immunized mice exhibited a significantly higher survival rate of 46.7% compared to those receiving sera from KD VLP- and GKD VLP-immunized mice (6.7% and 0%, respectively). This study demonstrated that JEV DII FL is crucial for eliciting potently neutralizing antibodies and protective immunity against JEV. IMPORTANCEIntroduction of mutations into the fusion loop is one potential strategy for generating safe dengue and Zika vaccines by reducing the risk of severe dengue following subsequent infections, and for constructing live-attenuated vaccine candidates against newly emerging Japanese encephalitis virus (JEV) or Japanese encephalitis (JE) serocomplex virus. The monoclonal antibody studies indicated the fusion loop of JE serocomplex viruses primarily comprised non-neutralizing epitopes. However, the present study demonstrates that the JEV fusion loop plays a critical role in eliciting protective immunity in mice. Modifications to the fusion loop of JE serocomplex viruses might negatively affect vaccine efficacy compared to dengue and zika serocomplex viruses. Further studies are required to assess the impact of mutant fusion loop encoded by commonly used JEV vaccine strains on vaccine efficacy or safety after subsequent dengue virus infection.

01 Feb 2024·Vaccine

Development of a live-attenuated chimeric vaccine against the emerging Usutu virus

Article

Author: Zhang, Rong-Rong ; Wang, Zheng-Jian ; Qin, Cheng-Feng ; Li, Xiao-Feng ; Wu, Mei ; Zhao, Hui ; Ye, Qing

Usutu virus (USUV) is an emerging arthropod-borne flavivirus that has expanded into multiple European countries during the past several decades. USUV infection in human has been linked to severe neurological complications, and no vaccine is now available against USUV. In this work, we develop a live-attenuated chimeric USUV vaccine (termed ChinUSUV) based on the full-length infectious cDNA clone of the licensed Japanese encephalitis virus (JEV) vaccine strain SA14-14-2. In vitro studies demonstrate that ChinUSUV replicates efficiently and maintains its genetic stability. Remarkably, ChinUSUV exhibits a significant attenuation phenotype in multiple mouse models even compared with the licensed JEV vaccine. A single immunization with ChinUSUV elicits potent IgG and neutralizing antibody responses as well as T cell response. Passive transfer of sera from ChinUSUV-immunized mice confers significant protection against lethal homologous challenge in suckling mice. Taken together, our results suggest that ChinUSUV represents a potential USUV vaccine candidate that merits further development.

News (Medical) associated with Japanese encephalitis vaccine, inactivated(Valneva SE)

13 Aug 2024

·www.globenewswire.com

Valneva Reports Half Year 2024 Financial Results and Provides Corporate Updates

First-Half Sales Performance in Line with Full-Year 2024 Guidance Total revenues of €70.8 million, including product sales of €68.3 million, in line with anticipated supply and sales phasingNet Profit of €34.0 million, including proceeds from PRV sale Operating profit of €46.7 million compared to an operating loss of €35.0 million in the first half of 2023 Cash position of €131.4 million Substantially lower cash burn expected in the second half of 2024 as Valneva completed its cost contributions to the agreed R&D budget for its partnered Lyme disease program in the second quarterSignificantly extended cash runway with update of debt financing agreement1 Full-year 2024 Financial Guidance Confirmed Expected total revenues between €170 million and €190 million, including €160 million to €180 million of product sales Expected R&D investments between €60 million and €75 millionExpected Other income between €100 million and €110 million, including €95 million from the PRV sale Strategic Pipeline Expansion, Strong Clinical and Regulatory Execution Exclusive worldwide license for S4V Shigella vaccine candidate, adding an attractive Phase 2 clinical asset to Valneva’s R&D pipeline without impacting full-year or mid-term financial guidance2Additional marketing authorizations for single-shot IXCHIQ® granted in Europe and Canada ahead of initial guidance; Ongoing regulatory reviews in the UK and Brazil; Recommended by ACIP and adopted by U.S. CDC3New CEPI grant4 of $41.3 million contributes significantly to Phase 4 costs and other studies supporting broader access to the world’s first chikungunya vaccineReported positive six-month data for Phase 3 adolescent study of IXCHIQ®5; expects to submit label extensions for 12 to 17 years old in the U.S., Europe and Canada in the second half of 2024 IXCHIQ® two-year antibody persistence data published in the Lancet Infectious DiseasesIXCHIQ® pediatric Phase 2 study fully enrolledCompleted primary vaccinations (three doses) of VALOR Lyme disease Phase 3 trial participants6Initiated Phase 1 clinical trial for second-generation Zika vaccine candidate7 Financial Information(Unaudited results, consolidated per IFRS) € in million 6 months ended June 30, 2024 2023 Total revenues 70.8 73.7 Product sales 68.3 69.7 Net profit / loss 34.0 (35.0) Adjusted EBITDA8 56.2 (28.3) Cash 131.4 204.4 Saint-Herblain (France), August 13, 2024 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today reported its consolidated financial results for the first half of the year, ended June 30, 2024. The half year financial report, including the condensed consolidated interim financial report and the half year management report, is available on the Company’s website (Financial Reports – Valneva). Valneva will provide a live webcast beginning at 3 p.m. CEST / 9 a.m. EDT today. This webcast will also be available on the Company’s website. Please refer to this link: https://edge.media-server.com/mmc/p/mmuf83o5 Peter Bühler, Valneva’s Chief Financial Officer, commented, “Our first half sales performance is in line with our expectations. We aim to further capitalize on the travel industry recovery as we focus on ramping up sales for IXCHIQ® to support our commercial growth, while continuing to execute on our key R&D and regulatory milestones. The successful sale of our PRV and deferral of our loan reimbursement allow us to maintain a solid cash position and, with completion of our payments for the Lyme disease program in the second quarter, we anticipate a significantly lower cash burn in 2024.”Commercial Portfolio Valneva’s commercial portfolio is composed of three travel vaccines, IXIARO®/JESPECT®, DUKORAL® and recently launched IXCHIQ®. The Company also distributes certain third-party products in countries where it operates its own marketing and sales infrastructure. Valneva’s sales in the first half of 2024 were €68.3 million compared to €69.7 million (€64.0 million excluding final COVID-19 vaccine sales) in the first half of 2023. While product sales grew meaningfully in the second quarter and included first sales for IXCHIQ®, first half 2024 sales were affected by previously reported supply constraints for IXIARO® and third-party products. JAPANESE ENCEPHALITIS VACCINE IXIARO®/JESPECT® In the first half of 2024, IXIARO®/JESPECT® sales increased by 38% to €41.9 million compared to €30.3 million in the first half of 2023. The increase primarily reflects sales to the U.S. military, which were minimal in the first half of 2023, as well as increased sales to travelers. CHOLERA / ETEC9-DIARRHEA VACCINE DUKORAL® In the first half of 2024, DUKORAL® sales were €14.9 million compared to €17.1 million in the first half of 2023. The decrease was due to reduced marketing investments while Valneva’s new manufacturing site in Sweden underwent regulatory evaluation and approval. CHIKUNGUNYA VACCINE IXCHIQ® IXCHIQ® is the world’s first and only licensed chikungunya vaccine available to address this significant unmet medical need. The vaccine is now approved in the U.S. 10, Europe11, and Canada12 for the prevention of disease caused by the chikungunya virus in individuals 18 years of age and older. The U.S. launch is underway while first sales in Canada and Europe are anticipated in the fourth quarter of 2024. Following adoption of the U.S. Advisory Committee on Immunization Practices (ACIP)’s recommendations by the U.S. Centers for Disease Control and Prevention (CDC)13 at the beginning of March 2024, Valneva recognized initial sales of €1.0 million in the first half of 2024. Key launch metrics, including stocking and re-stocking across all sales channels, active customer accounts, as well as reimbursement for IXCHIQ® by commercial and MediCare insurance plans continue to track in line with expectations. In addition to ramping up sales, Valneva is focusing on expanding the vaccine’s label and access. The Company expects marketing authorizations in the UK and Brazil in the second half of 2024 and recently expanded its partnership with CEPI14 to support broader access to the vaccine in Low Middle-Income Countries (LMICs), post-marketing trials and potential label extensions in children, adolescents and pregnant women. CEPI will provide Valneva up to $41.3 million of additional funding over the next five years, with support from the European Union’s (EU) Horizon Europe program. Based on positive pivotal six-month Phase 3 data reported in May 202415, Valneva expects to file for potential label extensions for use in adolescents aged 12 to 17 years in the second half of 2024. These data show that a single-dose vaccination with IXCHIQ® induces a high and sustained immune response in 99.1% of adolescents, and that the vaccine was generally well tolerated. Conducted in Brazil in collaboration with Instituto Butantan, the trial is also expected to support licensure of the vaccine in Brazil, which would be the first potential approval for use in endemic populations. Additionally, Valneva recently completed enrollment of a Phase 2 pediatric trial, VLA1553-221, in children aged 1 to 11 years16, designed to support a Phase 3 pivotal pediatric study and potential future label extension to this age group. The peer-reviewed medical journal, The Lancet Infectious Diseases, also just published the vaccine’s Phase 3 antibody persistence results two years after vaccination with a single dose. The data show that IXCHIQ®’s robust immune response was sustained for two years by 97% of participants and was equally durable in younger and older adults17. These data, which further support the anticipated long-term durability of the immune response, will also be used to potentially expand the vaccine’s current label. Valneva will continue to measure antibody persistence for a period of at least five years and expects to report three-year durability results later this year. THIRD-PARTY DISTRIBUTION Valneva distributes certain third-party vaccines in countries where it operates its own marketing and sales infrastructure. During the first half of 2024, third-party sales decreased by 37% to €10.5 million compared to €16.5 million in the first half of 2023 as a result of anticipated supply constraints. Valneva expects third-party sales to gradually wind down to less than 5% of overall product sales by 2026/2027, allowing the Company to improve gross margins. Clinical Vaccine Candidates LYME DISEASE VACCINE CANDIDATE – VLA15 Phase 3 primary vaccination completed Valneva and Pfizer are developing VLA15, a Phase 3 vaccine candidate targeting Borrelia, the bacterium that causes Lyme disease. VLA15 is the only Lyme disease program in late-stage clinical development today and has received Fast Track designation from the FDA. VLA15 is a multivalent recombinant protein vaccine that targets six serotypes of Borrelia representing the most common strains found in the United States and Europe. Valneva and Pfizer reported results for the Phase 2 clinical trials of VLA15 in both adult and pediatric populations, in which high levels of antibodies against all six serotypes were observed. Results of Phase 2 trials VLA15-201 and VLA15-202 were published in the peer-reviewed medical journal, the Lancet Infectious Diseases, in June 202418. Additional 18-month booster results from Study VLA15-202 were also published in the same journal in July 202419. In July 2024, Valneva and Pfizer announced completion of primary vaccinations (three doses) of over 9,000 participants in the Phase 3 trial “Vaccine Against Lyme for Outdoor Recreationists” (VALOR)20. Completion of the VALOR trial is still expected by the end of 2025, with the aim for Pfizer to submit a Biologic License Application (BLA) to the FDA and a Marketing Authorization Application (MAA) to the EMA in 2026, subject to positive data. Based on the agreement with Pfizer, Valneva’s agreed-upon cost contributions for the Lyme disease program were completed in the second quarter of 2024, contributing to a substantially lower expected cash burn in the second half of 2024. SHIGELLA VACCINE CANDIDATE – S4V Valneva recently entered into a strategic partnership and exclusive licensing agreement with LimmaTech Biologics AG for the development, manufacturing and commercialization of Shigella4V (S4V), a tetravalent bioconjugate vaccine candidate against shigellosis21. Shigellosis, caused by Shigella bacteria, is the second leading cause of fatal diarrheal disease worldwide. It is estimated that up to 165 million cases of disease and an estimated 600,000 deaths are attributed to Shigella each year22, particularly among children in Low- and Middle-Income Countries (LMICs). No approved Shigella vaccine is currently available and the development of Shigella vaccines has been identified as a priority by the World Health Organization (WHO)23. Shigellosis also affects international travelers from high-income countries and deployed military personnel in endemic regions. The global market for a vaccine against Shigella is estimated to exceed $500 million annually24. Under the terms of the agreement with Valneva, LimmaTech will receive an upfront payment of €10 million and be eligible to receive additional regulatory, development and sales-based milestone payments of up to €40 million as well as low double-digit royalties on sales. LimmaTech will conduct a Phase 2 Controlled Human Infection Model study (CHIM) in the U.S. and a Phase 2 pediatric study in LMICs. Both clinical trials are expected to begin in the second half of 2024. Valneva will assume all further development, including CMC (chemistry, manufacturing and controls) and regulatory activities, and be responsible for its commercialization worldwide if approved. The anticipated development path follows a staggered and risk-mitigated strategy, allowing an efficient capital allocation in line with Valneva’s communicated plan of having a new R&D program in Phase 3 by 2027. ZIKA VACCINE CANDIDATE – VLA1601Phase 1 ongoing with second-generation vaccine candidate VLA1601 is a second-generation adjuvanted inactivated vaccine candidate against the mosquito-borne disease caused by the Zika virus (ZIKV). In March 2024, Valneva initiated a Phase 1 clinical trial to investigate the safety and immunogenicity of VLA160125. The randomized, placebo-controlled, Phase 1 trial, VLA1601-102, is planned to enroll approximately 150 participants aged 18 to 49 years in the United States. Participants will receive a low, medium or high dose of VLA1601. In addition, the low dose of VLA1601 will be evaluated with an additional adjuvant. Topline data from the trial are expected in the first half of 2025. Zika disease outbreaks have been reported in tropical Africa, Southeast Asia, the Pacific Islands, and, since 2015, in the Americas. Zika virus transmission persists in several countries in the Americas and in other endemic regions. To date, a total of 89 countries and territories have reported evidence of mosquito transmitted Zika virus infection26; however, surveillance remains limited globally. There are no preventive vaccines or effective treatments available and, as such, Zika remains a public health threat and is included in the FDA’s Tropical Disease Priority Review Voucher Program27. A vaccine against ZIKV could be a valuable addition to Valneva’s portfolio against mosquito-borne diseases, which already includes IXCHIQ® and IXIARO®. First Half 2024 Financial Review (Unaudited, consolidated under IFRS) RevenuesValneva’s total revenues were €70.8 million in the six months ended June 30, 2024 compared to €73.7 million in the six months ended June 30, 2023. Valneva’s total product sales reached €68.3 million in the six months ended June 30, 2024 compared to €69.7 million in the same period of 2023. The impact of currency fluctuations of €0.1 million was minimal.Excluding final COVID-19 vaccine sales in the six months ended June 30, 2023, travel vaccine sales show a growth of €4.3 million or 7% year-over-year.IXIARO®/JESPECT® sales were €41.9 million in the six months ended June 30, 2024 compared to €30.3 million in the six months ended June 30, 2023. The 38% increase primarily reflects sales to the U.S. military, which were minimal in the first half of 2023, as well as increased sales to travelers. The impact of foreign currency movements in IXIARO®/JESPECT® sales was negligible. DUKORAL® sales were €14.9 million in the six months ended June 30, 2024 compared to €17.1 million in the comparative period of 2023. This 13% decrease was due to reduced marketing investments while Valneva’s new manufacturing site in Sweden underwent regulatory evaluation and approval. Foreign currency fluctuations had an immaterial impact on DUKORAL® sales.Following adoption of the U.S. Advisory Committee on Immunization Practices (ACIP)’s recommendations by the U.S. Centers for Disease Control and Prevention (CDC) at the beginning of March 2024, Valneva recognized initial sales for IXCHIQ® of €1.0 million in the first half of 2024.Third Party product sales were €10.5 million in the six months ended June 30, 2024 compared to €16.5 million in the six months ended June 30, 2023. This 37% decrease was mainly driven by lower sales of Rabipur®/RabAvert® and Encepur®, under the distribution agreement with Bavarian Nordic, due to supply shortages. Other revenues, including revenues from collaborations, licensing and services amounted to €2.5 million in the six months ended June 30, 2024 compared to €4.1 million in the same period of 2023. The reduction mainly resulted from lower revenue recognition related to the R&D collaboration activities for chikungunya with Instituto Butantan and the divestment of the CTM unit in Sweden in July 2023. Operating Result and adjusted EBITDA Costs of goods and services sold (COGS) were €45.6 million in the six months ended June 30, 2024. The gross margin on commercial product sales, excluding IXCHIQ®, amounted to 47.7% compared to 40.0% in the six months ended June 30, 2023. COGS of €17.8 million related to IXIARO® product sales, yielding a product gross margin of 57.5%. COGS of €9.7 million related to DUKORAL® product sales, yielding a product gross margin of 34.8%. Product gross margins are expected to improve in the second half of the year as the supply shortages during the first half have been resolved. Of the remaining COGS in 2024, €7.7 million related to the third-party products distribution business, €4.0 million to IXCHIQ®, €2.1 million to idle capacity costs and €4.6 million to cost of services. In 2023, overall COGS were €53.8 million, of which €48.4 million related to cost of goods and €5.5 million related to cost of services. Research and development expenses amounted to €29.7 million in the six months ended June 30, 2024, compared to €26.0 million in the six months ended June 30, 2023. This increase was mainly driven by higher costs related to the ongoing transfer of operations into the new Almeida manufacturing facility and higher R&D costs for IXCHIQ®. Marketing and distribution expenses in the first six months of 2024 amounted to €23.2 million compared to €20.0 million in the first six months of 2023. The increase is mainly related to €9.8 million of expenses associated with launch activities for IXCHIQ® (first half of 2023: €7.8 million). In the six months ended June 30, 2024, general and administrative expenses remained stable at €22.8 million after €22.9 million in the same period of 2023. The largest expense categories were employee-related expenses of €10.5 million and consulting and other services of €9.6 million.During the first half of 2024, a net gain of €90.8 million from the sale of the PRV was recorded. The gross proceeds of $103 million were reduced by transaction costs as well as contractual payment obligations related to the sale of the PRV.Other income, net of other expenses decreased to €6.4 million in the six months ended June 30, 2024 from €14.0 million in the six months ended June 30, 2023. In the first half of 2023, Valneva recorded income from grants and tax credits for research and development totaling €14.9 million, of which €8.7 million were awarded by Scottish Enterprise (SE) for non-COVID-19 vaccine development (IXCHIQ® and IXIARO®).Valneva recorded an operating income of €46.7 million in the six months ended June 30, 2024 compared to an operating loss of €35.0 million in the comparative period of 2023. The increase was mainly the result of the PRV sale.Adjusted EBITDA (as defined below) profit in the six months ended June 30, 2024 was €56.2 million, whereas in the six months ended June 30, 2023 an adjusted EBITDA loss of €28.3 million was recorded. Net Result In the six months ended June 30, 2024, Valneva generated a net profit of €34.0 million, mainly resulting from the sale of the PRV in February 2024. This compared to a net loss of €35.0 million in the first half of 2023.Finance expense and currency effects in the first half of 2024 resulted in a net finance expense of €12.8 million, compared to a net finance expense of €3.9 million in the first half of 2023. This increase was mainly due to €5.7 million higher interest expenses on loans resulting from the amendment of the Deerfield Management Company and OrbiMed (D&O) loan facility. Additionally foreign exchange losses of €1.7 million were recorded in the first half of 2024 compared to gains of €4.5 million observed in the first half of 2023, primarily related to the development of the USD and GBP exchange rates to the EUR. Cash Flow and Liquidity Net cash used in operating activities amounted to €66.3 million in the six months ended June 30, 2024 compared to €65.4 million of cash used in operating activities in the same period of 2023. Cash outflows in the first half of 2024 were largely derived from the operating loss for the period (net of gains from PRV sale) amounting to €56.9 million and from working capital in the amount of €31.2 million, which includes all payments to the Lyme disease clinical program as per the R&D budget agreed between Pfizer and Valneva. In 2023, changes in working capital were higher, mainly related to higher payments to Pfizer in conjunction with the Lyme disease program, reducing the refund liability. Cash inflows from investing activities amounted to €87.6 million in the six months ended June 30, 2024 compared to cash outflows of €6.6 million in the six months ended June 30, 2023. While both years include outflows from construction activities across production sites in Scotland and Sweden, the sale of the PRV positively impacted 2024 by €90.8 million.Net cash used in financing activities increased to €16.6 million in the six months ended June 30, 2024 from €9.5 million in the six months ended June 30, 2023. This increase was primarily due to €5.4 million higher interest payments resulting from the increase in the D&O loan facility. Cash and cash equivalents were €131.4 million as at June 30, 2024, compared to €126.1 million at December 31, 2023. Non-IFRS Financial Measures Management uses and presents IFRS results as well as the non-IFRS measure of Adjusted EBITDA to evaluate and communicate its performance. While non-IFRS measures should not be construed as alternatives to IFRS measures, management believes non-IFRS measures are useful to further understand Valneva’s current performance, performance trends, and financial condition. Adjusted EBITDA is a common supplemental measure of performance used by investors and financial analysts. Management believes this measure provide additional analytical tools. Adjusted EBITDA is defined as net profit / (loss) for the period before income tax, finance income/expense, foreign exchange (gain)/loss, amortization, depreciation, and impairment (excluding impairment loss of disposal). A reconciliation of Adjusted EBITDA to operating loss, which is the most directly comparable IFRS measure, is set forth below: € in million 6 months ended June 30 (unaudited results, consolidated per IFRS) 2024 2023 Net profit / (loss) 34.0 (35.0) Add: Income tax benefit (0.2) (3.8) Total Finance income (0.8) (0.5) Total Finance expense 12.0 8.9 Foreign exchange (gain)/ loss – net 1.7 (4.5) Amortization 2.5 3.2 Depreciation 7.0 5.4 Impairment, excluding impairment loss of disposal - (1.9) Adjusted EBITDA 56.2 (28.3) About Valneva We are a specialty vaccine company that develops, manufactures, and commercializes prophylactic vaccines for infectious diseases addressing unmet medical needs. We take a highly specialized and targeted approach, applying our deep expertise across multiple vaccine modalities, focused on providing either first-, best- or only-in-class vaccine solutions. We have a strong track record, having advanced multiple vaccines from early R&D to approvals, and currently market three proprietary travel vaccines, including the world’s first and only chikungunya vaccine, as well as certain third-party vaccines. Revenues from our growing commercial business help fuel the continued advancement of our vaccine pipeline. This includes the only Lyme disease vaccine candidate in advanced clinical development, which is partnered with Pfizer, the world’s most clinically advanced Shigella vaccine candidate, as well as vaccine candidates against the Zika virus and other global public health threats. More information is available at www.valneva.com. Valneva Investor and Media ContactsLaetitia Bachelot-FontaineVP, Global Communications and European Investor RelationsM +33 (0)6 4516 7099Laetitia.bachelotfontaine@valneva.com Joshua Drumm, Ph.D.VP, Global Investor Relations M +001 917 815 4520joshua.drumm@valneva.com Forward-Looking StatementsThis press release contains certain forward-looking statements relating to the business of Valneva, including with respect to guidance for certain financial results in fiscal year 2024 and mid-term outlook on financial results, cash position, and other business developments, including results of ongoing clinical trials, the timing and possible occurrence of further or initial regulatory approvals of its product candidates, the anticipated size of markets for approved products and sales of those products, receipt of funding from external sources, supply of products sold by Valneva, and relationships with current business partners. In addition, even if the actual results or development of Valneva are consistent with the forward-looking statements contained in this press release, those results or developments of Valneva may not be indicative of future results. In some cases, you can identify forward-looking statements by words such as "could," "should," "may," "expects," "anticipates," "believes," "intends," "estimates," "aims," "targets," or similar words. These forward-looking statements are based on the current expectations of Valneva as of the date of this press release and are subject to a number of known and unknown risks and uncertainties and other factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievement expressed or implied by these forward-looking statements. These risks and uncertainties include those developed or identified in any public documents filed with the French financial markets authority (Autorité des marchés financiers) and the U.S. Securities and Exchange Commission made or to be made by Valneva. In particular, the expectations of Valneva could be affected by, among other things, uncertainties involved in the development and manufacture of vaccines (including in relation to organic or strategic expansion of Valneva’s clinical pipeline), unexpected clinical trial results, unexpected regulatory actions or delays, competition in general, currency fluctuations, the impact of the global and European financial crisis and other global economic or political events, the ability to obtain or maintain patent or other proprietary intellectual property protection, the cancellation of existing contracts, the impact of a pandemic, and changes in the regulatory environment in which Valneva operates. The occurrence of any of these risks and uncertainties could substantially harm Valneva’s business, financial condition, prospects and results of operations. In light of these risks and uncertainties, there can be no assurance that the forward-looking statements made during this presentation will in fact be realized. Valneva is providing the information in this press release as of the date hereof and disclaims any intention or obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. 1 Valneva Announces Extension of the Interest-Only Period of Its Debt Facility with Deerfield and OrbiMed - Valneva2 Valneva and LimmaTech Enter into a Strategic Partnership to Accelerate the Development of the World’s Most Clinically Advanced Tetravalent Shigella Vaccine Candidate - Valneva3 ACIP Vaccine Recommendations and Schedules | CDC4 CEPI Expands Partnership with Valneva with a $41.3 Million Grant to Support Broader Access to the World’s First Chikungunya Vaccine - Valneva5 Valneva Reports Further Positive Pivotal Phase 3 Data in Adolescents for its Single-Shot Chikungunya Vaccine - Valneva6 Phase 3 VALOR Lyme Disease Trial: Valneva and Pfizer Announce Primary Vaccination Series Completion - Valneva7 Valneva Initiates Phase 1 Trial of Second-Generation Zika Vaccine Candidate - Valneva8 For additional information on Adjusted EBITDA, please refer to the “Non-IFRS Financial Measures” section at the end of the PR9 Indications differ by country - Please refer to Product / Prescribing Information (PI) / Medication Guide approved in your respective countries for complete information, incl. dosing, safety and age groups in which this vaccine is licensed, ETEC = Enterotoxigenic Escherichia coli (E. Coli) bacterium.10 Valneva Announces U.S. FDA Approval of World’s First Chikungunya Vaccine, IXCHIQ® - Valneva11 Valneva Receives Marketing Authorization in Europe for the World’s First Chikungunya Vaccine, IXCHIQ® - Valneva12 Valneva Announces Health Canada Approval of the World’s First Chikungunya Vaccine, IXCHIQ® - Valneva13 ACIP Vaccine Recommendations and Schedules | CDC14 CEPI Expands Partnership with Valneva with a $41.3 Million Grant to Support Broader Access to the World’s First Chikungunya Vaccine - Valneva15 Valneva Reports Further Positive Pivotal Phase 3 Data in Adolescents for its Single-Shot Chikungunya Vaccine - Valneva16 Valneva Vaccinates First Participant in Pediatric Trial of Single-Shot Chikungunya Vaccine - Valneva17 https://www-thelancet-com.libproxy1.nus.edu.sg/journals/laninf/article/PIIS1473-3099(24)00357-8/fulltext 18 Valneva Announces Publication of Lyme Disease Phase 2 Trials in the Lancet Infectious Diseases - Valneva19 Immunogenicity and safety of an 18-month booster dose of the VLA15 Lyme borreliosis vaccine candidate after primary immunisation in healthy adults in the USA: results of the booster phase of a randomised, controlled, phase 2 trial - The Lancet Infectious Diseases20 Phase 3 VALOR Lyme Disease Trial: Valneva and Pfizer Announce Primary Vaccination Series Completion - Valneva21 LimmaTech Biologics AG22 Shigellosis | CDC Yellow Book 202423 Immunization, Vaccines and Biologicals (who.int)24 Valneva’s Initial internal assessment 25 Valneva Initiates Phase 1 Trial of Second-Generation Zika Vaccine Candidate - Valneva26 Zika virus disease (who.int)27 Tropical Disease Priority Review Voucher Program | FDA Full-year 2024 Financial Guidance Confirmed Attachment 2024_08_13_VLA_H1_Results_EN_Final

Phase 3Phase 2VaccineClinical ResultPhase 1

07 May 2024

·www.globenewswire.com

Valneva Reports First Quarter 2024 Financial Results and Provides Corporate Updates

Valneva Reports First Quarter 2024 Financial Results and Provides Corporate Updates Q1 financial highlights Total revenues of €32.8 million, including sales of €32.1 million, on track to meet anticipated full year guidance Cash position of €176.6 million, including €95 million from sale of Priority Review Voucher (PRV)1. Significantly extended cash runway with recent update of debt financing agreement2Substantially lower cash burn expected in 2024 as Valneva expects to complete its cost contributions for the Lyme disease Phase 3 study in the second quarter Net Profit of €58.9 million, reflecting PRV sale 2024 financial guidance confirmed Expected total revenues between €170 million and €190 million, including: €160 million to €180 million of sales driven by growth of Valneva’s proprietary products Expected R&D investments between €60 million and €75 million, mostly dedicated to ongoing chikungunya development activities, the Zika trial and advancement of pre-clinical programsExpected Other income between €100 million and €110 million, reflecting €95 million in proceeds from the PRV sale Strong R&D execution Single-shot chikungunya vaccine IXCHIQ® recommended by ACIP and adopted by U.S. CDC3; Regulatory processes with the European, Canadian and Brazilian authorities on track; Six-month data for Phase 3 adolescent study of IXCHIQ® to be reported shortly and label extensions to be submitted based on results; Enrolment of children for pediatric Phase 2 study on track; Primary vaccinations for all participants in the VALOR Lyme disease Phase 3 trial expected to be completed in Q2;Phase 1 clinical trial for second-generation Zika vaccine candidate initiated4. Financial Information(Unaudited results, consolidated per IFRS) € in million 3 months ending March 31 2024 2023 Product sales 32.1 32.1 Total revenues 32.8 33.5 Net profit/(loss) 58.9 (18.1) Adjusted EBITDA (profit/loss) 73.0 (12.3) Cash 176.6 254.5 Saint-Herblain (France), May 7, 2024 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today reported its financial results for the first quarter ending March 31, 2024, and provided corporate updates. The condensed consolidated interim financial results are available on the Company’s website (Financial Reports – Valneva). Valneva will host a live webcast of its first quarter 2024 results conference call at 3 p.m. CEST/9 a.m. EDT today. This webcast will also be available on the Company’s website. Please refer to this link: https://edge.media-server.com/mmc/p/wrc2a7s3. Peter Bühler, Valneva’s Chief Financial Officer, commented, “The first quarter performance has been in line with our expectations. We are aiming to further capitalize on the travel industry recovery during the rest of the year including ramping-up sales for IXCHIQ® to support our commercial sales growth while executing on our key R&D milestones. The successful sale of our PRV and deferral of our loan reimbursement in Q1 allowed us to maintain a solid cash position and, with the expected completion of our payments for the Lyme Phase 3 trial in the second quarter, we anticipate a significantly lower cash burn in 2024.” Commercial Portfolio Valneva’s commercial portfolio is composed of three travel vaccines, IXIARO®/JESPECT®, DUKORAL® and IXCHIQ®. The Company also distributes certain third-party products in countries where it operates its own marketing and sales infrastructure. JAPANESE ENCEPHALITIS VACCINE IXIARO®/JESPECT®In the first quarter of 2024, IXIARO®/JESPECT® sales were €16.6 million compared to €17.4 million in the first quarter of 2023. Sales to the U.S. military counterbalanced most of the supply constraints experienced during the period. These constraints have now been resolved, and as communicated last month in its full-year publication5, Valneva expects double-digit annual growth for IXIARO® sales for at least the next three years. CHOLERA / ETEC6-DIARRHEA VACCINE DUKORAL® In the first quarter of 2024, DUKORAL® sales increased by 10.3% to €11.3 million compared to €10.2 million in the first quarter of 2023, as the vaccine continued to benefit from the significant recovery in the private travel markets. CHIKUNGUNYA VACCINE IXCHIQ® IXCHIQ® is the world’s first and only licensed chikungunya vaccine available to address this significant unmet medical need. Following adoption of the U.S. Advisory Committee on Immunization Practices (ACIP)’s recommendations7 by the U.S. Centers for Disease Control and Prevention (CDC)8 at the beginning of March 2024, Valneva has focused on launching its single-dose chikungunya vaccine in the U.S. and recorded initial sales of €0.2 million in the first quarter. IXCHIQ® is also under regulatory review in Canada, Brazil and Europe, where it was granted accelerated assessment by the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP). Decisions on these submissions are expected in 2024. A clinical study in adolescents, VLA1553-321, is ongoing. Valneva reported initial safety data in August 20239 and expects to report six-month data in the coming weeks. Funded by the Coalition for Epidemic Preparedness Innovations (CEPI) and conducted in Brazil in collaboration with Instituto Butantan, the VLA1553-321 adolescent trial is intended to support the label extension to this age group following initial approvals in adults. The trial is also expected to support licensure of the vaccine in Brazil, which would be the first potential approval for use in endemic populations. Additionally, the Company initiated a Phase 2 pediatric trial, VLA1553-221, in children aged 1 to 11 years, in January 202410. This is designed to support a Phase 3 pivotal pediatric study and potentially extend the label to this age group following initial regulatory approvals in adults and possibly in adolescents. THIRD-PARTY DISTRIBUTION Valneva distributes certain third-party vaccines in countries where it operates its own marketing and sales infrastructure. During the first quarter of 2024, third-party sales decreased by 8.9% to €4.1 million compared to €4.5 million in the first quarter of 2023 as a result of anticipated supply constraints. Valneva expects that third-party sales will gradually wind down to less than 5% of overall product sales by 2026/2027, allowing the Company to improve gross margins. Clinical Stage Vaccine Candidates LYME DISEASE VACCINE CANDIDATE – VLA15 Phase 3 study ongoing Valneva and Pfizer are developing VLA15, a Phase 3 vaccine candidate targeting Borrelia, the bacterium that causes Lyme disease. VLA15 is a multivalent recombinant protein vaccine that targets six serotypes of Borrelia representing the most common strains found in the United States and Europe. VLA15 is the only Lyme disease program in late-stage clinical development today and has received Fast Track designation from the FDA. Vaccinations across the two cohorts of the Phase 3 trial “Vaccine Against Lyme for Outdoor Recreationists” (VALOR) are on track and Valneva and Pfizer expect all participants (9,437) to complete primary vaccinations (three doses) in the coming weeks. Topline data from the VALOR trial are expected by the end of 2025, with the aim for Pfizer to submit a Biologic License Application (BLA) to the FDA and a Marketing Authorization Application (MAA) to the EMA in 2026, subject to positive data. Valneva’s cost contributions for the Lyme disease Phase 3 study are expected to be completed in the second quarter of 2024. All remaining payments to Pfizer are included in current refund liability at December 31, 2023, and will not impact the Profit & Loss statement in 2024. ZIKA VACCINE CANDIDATE – VLA1601Phase 1 ongoing with second-generation vaccine candidate VLA1601 is a second-generation adjuvanted inactivated vaccine candidate against the mosquito-borne viral disease caused by the Zika virus (ZIKV). In March 2024, Valneva initiated a Phase 1 clinical trial to investigate the safety and immunogenicity of VLA160111. The randomized, placebo-controlled, Phase 1 trial, VLA1601-102, is planned to enroll approximately 150 participants aged 18 to 49 years in the United States. Participants will receive a low, medium or high dose of VLA1601. In addition, the low dose of VLA1601 will be evaluated with an additional adjuvant. Topline data from the trial are expected in the first half of 2025. Zika disease outbreaks have been reported in tropical Africa, Southeast Asia, the Pacific Islands, and, since 2015, in the Americas. Zika virus transmission persists in several countries in the Americas and in other endemic regions. To date, a total of 89 countries and territories have reported evidence of mosquito transmitted Zika virus infection12; however, surveillance remains limited globally. There are no preventive vaccines or effective treatments available and, as such, Zika remains a public health threat and is included in theFDA’s Tropical Disease Priority Review Voucher Program13. A vaccine against ZIKV would be a valuable addition to Valneva’s portfolio of travel vaccines against mosquito-borne diseases, which already includes IXCHIQ® and IXIARO®. First Quarter 2024 Financial Review (Unaudited, consolidated under IFRS) Revenues Valneva’s total revenues were €32.8 million in the first quarter of 2024 compared to €33.5 million in the first quarter of 2023. Valneva’s sales reached €32.1 million in the first quarter of 2024 and remained comparable to the first quarter of 2023. Currency fluctuations had an immaterial impact on sales compared to the comparator period. IXIARO®/JESPECT® sales were €16.6 million in the first quarter of 2024 compared to €17.4 million in the first quarter of 2023. The 4% decrease in sales is primarily the result of constrained supplies, which temporarily impacted sales during the first quarter and are now resolved. DUKORAL® sales were €11.3 million in the first quarter of 2024 compared to €10.2 million in the first quarter of 2023. This 10% increase results from the continued recovery in the private travel markets primarily driven by Canada, and price increases. IXCHIQ® sales were €0.2 million in the first quarter of 2024. The U.S. CDC adopted recommendations by the ACIP14 at the beginning of March 2024. Third Party product sales were €4.1 million in the first quarter of 2024 compared to €4.5 million in the first quarter of 2023, a 9% decrease which was mainly driven by supply constraints of Rabipur®/RabAvert® and Encepur® sold under the distribution agreement with Bavarian Nordic. Other revenues, including revenues from collaborations, licensing and services amounted to €0.6 million in the first quarter of 2024 compared to €1.4 million in the first quarter of 2023 with the reduction mainly resulting from lower revenue recognition related to the R&D collaboration activities for chikungunya with Instituto Butantan. Operating Result and adjusted EBITDA Costs of goods and services sold (COGS) were €22.2 million in the first quarter of 2024. The gross margin on commercial product sales amounted to 43.9% (excluding IXCHIQ®) compared to 48.4% in the first quarter of 2023. COGS of €8.0 million related to IXIARO® sales, yielding a product gross margin of 52.0%, which was impacted by €1.7 million recorded as write-offs for failed batches. COGS of €7.0 million related to DUKORAL® sales, yielding a product gross margin of 37.9%. Of the remaining COGS in the first quarter of 2024, €3.0 million related to the third-party products distribution business, €0.8 million to IXCHIQ®, €1.0 million to idle capacity costs and €2.4 million to cost of services. In the first quarter of 2023, overall COGS were €20.5 million, of which €17.9 million related to cost of goods and €2.6 million related to cost of services. Research and development expenses amounted to €13.1 million in the first quarter of 2024, compared to €14.1 million in the first quarter of 2023. This decrease was mainly driven by lower spend on Valneva’s COVID-19 vaccine, VLA2001 as well as lower spend on IXCHIQ® following licensure in the fourth quarter of 2023. At the same time, costs related to the ongoing transfer of operations into the new Almeida manufacturing facility resulted in higher R&D spend on commercial products. Marketing and distribution expenses in the first quarter of 2024 amounted to €11.3 million compared to €9.0 million in the first quarter of 2023. The increase is mainly related to €4.9 million of expenses associated with launch activities for IXCHIQ® (first quarter of 2023: €3.4 million). In the first quarter of 2024, general and administrative expenses increased to €11.7 million from €10.0 million in the first quarter of 2023, mainly resulting from higher costs related to the Company’s stock-based employee compensation program, higher recruiting charges and higher costs for digitalization & automation initiatives. During the first quarter of 2024, a net gain of €90.8 million from the sale of the PRV was recorded in the income statement. The net proceeds of $103 million were reduced by transaction costs as well as contractual payment obligations related to the sale of the PRV. Other income, net of other expenses, decreased to €2.9 million in the first quarter of 2024 from €3.5 million in the first quarter of 2023. The decrease was mainly driven by lower R&D tax credits recorded in the first quarter of 2024 following the reduction in eligible R&D spend. Valneva recorded an operating profit of €68.2 million in the first quarter of 2024 compared to an operating loss of €16.6 million in the first quarter of 2023. The significant improvement is largely related to the proceeds from the sales of the PRV recorded in the income statement in the first quarter of 2024. Adjusted EBITDA (as defined below) profit in the first quarter of 2024 was €73.0 million, compared to an EBITDA loss of €12.3 million in the first quarter of 2023. Net Result In the first quarter of 2024, Valneva generated a net profit of €58.9 million compared to a net loss of €18.1 million in the first quarter of 2023. Finance expenses and currency effects in the first quarter of 2024 resulted in a net finance expense of €9.3 million, compared to a net finance expense of €1.7 million in the first quarter of 2023. The increase in finance expenses, net was mainly due to foreign exchange losses of €2.5 million in the first quarter of 2024 compared to a profit of €3.2 million in the first quarter of 2023, primarily related to the development of the USD / EUR exchange rate. In addition, interest charges increased to €7.0 million in the first quarter of 2024 compared to €5.1 million in the first quarter of 2023 following the increase of the Deerfield Management Company and OrbiMed (D&O) loan facility during the second half of 2023. Cash Flow and Liquidity Net cash used in operating activities amounted to €28.4 million in the first quarter of 2024 compared to €24.3 million in the first quarter of 2023. Cash outflows in the first quarter of 2024 were mainly a result of the net loss for the period excluding proceeds from the sale of the PRV and by increases in working capital. Cash inflows from investing activities amounted to €86.7 million in the first quarter of 2024 compared to cash outflows of €3.6 million in the first quarter of 2023. Cash inflows in the first quarter of 2024 were driven by €90.8 million net proceeds from the sale of the PRV, partly offset by construction activities in the Almeida manufacturing site in Scotland as well as equipment purchases. Net cash used in financing activities increased to €7.5 million in the first quarter of 2024 from €3.8 million in the first quarter of 2023. The increase in cash outflows in the first quarter of 2024 were primarily due to increased interest payments and transaction costs resulting from the upsized loan facility provided by D&O. Cash and cash equivalents were €176.6 million as at March 31, 2024, compared to €126.1 million as at December 31, 2023. Non-IFRS Financial Measures Management uses and presents IFRS results as well as the non-IFRS measure of Adjusted EBITDA to evaluate and communicate its performance. While non-IFRS measures should not be construed as alternatives to IFRS measures, management believes non-IFRS measures are useful to further understand Valneva’s current performance, performance trends, and financial condition. Adjusted EBITDA is a common supplemental measure of performance used by investors and financial analysts. Management believes this measure provide additional analytical tools. Adjusted EBITDA is defined as earnings (loss) for the period before income tax, finance income/expense, foreign exchange gain/(loss), amortization, depreciation, and impairment (excluding impairment loss of disposal). A reconciliation of Adjusted EBITDA to net loss for the period, which is the most directly comparable IFRS measure, is set forth below: € in million Three months ending March 31 (consolidated per IFRS) 2024 2023 Profit/(Loss) for the period 58.9 (18.1) Add: Income tax expense - (0.1) Total Finance income (0.3) (0.3) Total Finance expense 7.0 5.1 Foreign exchange gain/(loss) – net 2.5 (3.2) Amortization 1.3 1.6 Depreciation 3.5 2.6 Impairment - - Adjusted EBITDA 73.0 (12.3) About Valneva SEWe are a specialty vaccine company that develops, manufactures, and commercializes prophylactic vaccines for infectious diseases addressing unmet medical needs. We take a highly specialized and targeted approach, applying our deep expertise across multiple vaccine modalities, focused on providing either first-, best- or only-in-class vaccine solutions. We have a strong track record, having advanced multiple vaccines from early R&D to approvals, and currently market three proprietary travel vaccines, including the world’s first and only chikungunya vaccine, as well as certain third-party vaccines. Revenues from our growing commercial business help fuel the continued advancement of our vaccine pipeline. This includes the only Lyme disease vaccine candidate in advanced clinical development, which is partnered with Pfizer, as well as vaccine candidates against the Zika virus and other global public health threats. About IXCHIQ®In the U.S., IXCHIQ® is a live-attenuated vaccine indicated for the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 years of age and older who are at increased risk of exposure to CHIKV. As for all products approved under FDA’s accelerated approval pathway, continued approval for this indication is contingent upon verification and description of clinical benefit in confirmatory studies. Please click here for full Prescribing Information for IXCHIQ®. Valneva Investor and Media ContactsLaetitia Bachelot-FontaineVP, Global Communications and European Investor RelationsM +33 (0)6 4516 7099investors@valneva.com Joshua Drumm, Ph.D.VP, Global Investor Relations M +001 917 815 4520joshua.drumm@valneva.com Forward-Looking StatementsThis press release contains certain forward-looking statements relating to the business of Valneva, including with respect to guidance for certain financial results in fiscal year 2024 and mid-term outlook on financial results, cash position, and other business developments, including results of ongoing clinical trials, the timing and possible occurrence of further or initial regulatory approvals of its product candidates, the anticipated size of markets for its approved products and sales of those products, receipt of funding from external sources, supply of products sold by Valneva, and relationships with current business partners. In addition, even if the actual results or development of Valneva are consistent with the forward-looking statements contained in this press release, those results or developments of Valneva may not be indicative of future results. In some cases, you can identify forward-looking statements by words such as "could," "should," "may," "expects," "anticipates," "believes," "intends," "estimates," "aims," "targets," or similar words. These forward-looking statements are based on the current expectations of Valneva as of the date of this press release and are subject to a number of known and unknown risks and uncertainties and other factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievement expressed or implied by these forward-looking statements. These risks and uncertainties include those developed or identified in any public documents filed with the French financial markets authority (Autorité des marchés financiers) and the U.S. Securities and Exchange Commission made or to be made by Valneva. In particular, the expectations of Valneva could be affected by, among other things, uncertainties involved in the development and manufacture of vaccines (including in relation to organic or strategic expansion of Valneva’s clinical pipeline), unexpected clinical trial results, unexpected regulatory actions or delays, competition in general, currency fluctuations, the impact of the global and European credit crisis and other global economic or political events, the ability to obtain or maintain patent or other proprietary intellectual property protection, the cancellation of existing contracts, the impact of a pandemic, and changes in the regulatory environment in which Valneva operates. The occurrence of any of these risks and uncertainties could substantially harm Valneva’s business, financial condition, prospects and results of operations. In light of these risks and uncertainties, there can be no assurance that the forward-looking statements made during this presentation will in fact be realized. Valneva is providing the information in this press release as of the date hereof and disclaims any intention or obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. 1 Valneva Announces Sale of Priority Review Voucher for $103 Million - Valneva2 Valneva Announces Extension of the Interest-Only Period of Its Debt Facility with Deerfield and OrbiMed - Valneva3 ACIP Vaccine Recommendations and Schedules | CDC4 Valneva Initiates Phase 1 Trial of Second-Generation Zika Vaccine Candidate - Valneva5 Valneva Reports Full Year 2023 Results and Provides Business Updates and Outlook - Valneva6 Indications differ by country - Please refer to Product / Prescribing Information (PI) / Medication Guide approved in your respective countries for complete information, incl. dosing, safety and age groups in which this vaccine is licensed, ETEC = Enterotoxigenic Escherichia coli (E. Coli) bacterium.7 ACIP Vaccine Recommendations and Schedules | CDC8 ACIP Vaccine Recommendations and Schedules | CDC9 Valneva Reports Positive Initial Phase 3 Safety Data in Adolescents for its Single-Shot Chikungunya Vaccine Candidate - Valneva10 Valneva Vaccinates First Participant in Pediatric Trial of Single-Shot Chikungunya Vaccine - Valneva11 Valneva Initiates Phase 1 Trial of Second-Generation Zika Vaccine Candidate - Valneva12 Zika virus disease (who.int)13 Tropical Disease Priority Review Voucher Program | FDA14 ACIP Vaccine Recommendations and Schedules | CDC Attachment 2024_05_07_VLA_Q1_Results_PR_EN_Final

VaccinePhase 3Financial StatementPhase 2Phase 1

26 Mar 2024

·www.biospace.com

Valneva Initiates Phase 1 Trial of Second-Generation Zika Vaccine Candidate

Saint-Herblain (France), March 26, 2024 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, today announced the initiation of a Phase 1 clinical trial to investigate the the safety and immunogenicity of VLA1601, its second-generation adjuvanted inactivated vaccine candidate against the Zika virus (ZIKV). There are currently no preventive vaccines or effective treatments available against ZIKV. As such, this mosquito-borne disease remains a public health threat and is included in the Food and Drug Administration’s Tropical Disease Priority Review Voucher Program1. The randomized, placebo-controlled, Phase 1 trial, VLA1601-102, is planned to enroll approximately 150 participants aged 18 to 49 years in the United States. Participants will receive a low, medium or high dose of VLA1601. In addition, the low dose of VLA1601 will be evaluated with an additional adjuvant, either the CpG 1018® adjuvant from Dynavax Technologies Corporation or 3M-052-AF adjuvant from the Access to Advanced Health Institute (AAHI). Topline data from the trial are expected in the first half of 2025. VLA1601 is being developed on the original manufacturing platform of Valneva’s licensed Japanese encephalitis (JE) vaccine IXIARO®, which was further optimized to develop the Company’s inactivated, adjuvanted COVID-19 vaccine VLA2001, the first COVID-19 vaccine to receive a standard marketing authorization in Europe. Phase 1 results from Valneva’s first-generation Zika vaccine candidate were reported in 2018 showing a favorable safety pro immunogenicity in all tested doses and schedules2. Juan Carlos Jaramillo M.D., Chief Medical Officer of Valneva, said, “Valneva’s commitment to our vision – to live in a world in which no one dies or suffers from a vaccine-preventable disease – fuels our pursuit for preparedness solutions against the Zika virus. As global temperatures rise and rainfall increases, the habitat for disease-carrying mosquitoes expands, presenting an ongoing public health challenge.” A vaccine against ZIKV would nicely complement Valneva’s portfolio of travel vaccines against mosquito-borne diseases. The Company received U.S. approval for its chikungunya vaccine IXCHIQ®, the world first and only chikungunya vaccine to address this unmet medical need, in November 2023, and has been commercializing its JE vaccine IXIARO®, for over ten years. Some health authorities and scientific leaders in the field have indicated a preference for a purified inactivated vaccine method compared to other vaccine technologies. This preference stems from the understanding that the primary recipients of a Zika vaccine are anticipated to be women of childbearing age, potentially including those who are pregnant. About the Zika Virus The Zika virus (ZIKV) is a mosquito-borne flavivirus that was first discovered in 1947. The first human cases were detected in 1952. Since then, disease outbreaks have been reported in tropical Africa, Southeast Asia, the Pacific Islands, and, in 2015, in the Americas. Zika virus is currently circulating in Mexico, Central and South America, many countries and territories in the Caribbean region, and in a small number of geographically limited areas of the continental United States. To date, a total of 89 countries and territories have reported evidence of mosquito transmitted Zika virus infection; however, surveillance remains limited globally. According to the World Health Organization, there is scientific consensus that ZIKV is a cause of microcephaly and Guillain-Barré syndrome. Since 2013, 31 countries and territories have reported cases of microcephaly and other central nervous system malformations associated with ZIKV infection. About VLA1601 VLA1601 is a highly purified inactivated vaccine candidate against the Zika virus (ZIKV), developed on the original manufacturing platform of Valneva’s licensed Japanese encephalitis vaccine IXIARO®, which was further optimized to develop the Company’s inactivated, adjuvanted COVID-19 vaccine VLA2001, the first COVID-19 vaccine to receive a standard marketing authorization in Europe. Valneva reported positive Phase 1 results for VLA1601 in 20183. The vaccine candidate was immunogenic and showed a favorable safety pro all tested doses and schedules that was comparable to IXIARO® and other clinical stage ZIKV vaccines. About IXIARO®/JESPECT® Valneva’s Japanese encephalitis vaccine is indicated for active immunization for the prevention of the disease for people who travel to, or live in, endemic areas. It received marketing approval in the U.S., Europe, Canada, Hong Kong, Singapore, and Israel under the trade name IXIARO® and in Australia and New Zealand where it is marketed as JESPECT®. It is the only vaccine available to the U.S. military for Japanese Encephalitis. IXIARO® is approved for use in individuals two months of age and older in the U.S. and EU member states, Canada, Norway, Liechtenstein, Iceland, Singapore, Hong Kong, Japan, the Republic of Korea and Israel. In all other licensed territories, IXIARO®/JESPECT® is indicated for use in persons aged 18 years or more. About IXCHIQ® In the U.S., IXCHIQ® is a live-attenuated vaccine indicated for the prevention of disease caused by chikungunya virus (CHIKV) in individuals 18 years of age and older who are at increased risk of exposure to CHIKV. As for all products approved under FDA’s accelerated approval pathway, continued approval for this indication is contingent upon verification and description of clinical benefit in confirmatory studies. Pleaseclick herefor full Prescribing Information for IXCHIQ®. About Valneva SE We are a specialty vaccine company that develops, manufactures, and commercializes prophylactic vaccines for infectious diseases addressing unmet medical needs. We take a highly specialized and targeted approach, applying our deep expertise across multiple vaccine modalities, focused on providing either first-, best- or only-in-class vaccine solutions. We have a strong track record, having advanced multiple vaccines from early R&D to approvals, and currently market three proprietary travel vaccines as well as certain third-party vaccines leveraging our established commercial infrastructure. Revenues from our growing commercial business help fuel the continued advancement of our vaccine pipeline. This includes the only Lyme disease vaccine candidate in advanced clinical development, which is partnered with Pfizer, as well as vaccine candidates against the Zika virus and other global public health threats. Valneva Investor and Media Contacts Laetitia Bachelot-Fontaine VP, Global Communications and European Investor Relations M +33 (0)6 4516 7099 communications@valneva.com Joshua Drumm, Ph.D. VP, Global Investor Relations M +001 917 815 4520 joshua.drumm@valneva.com Forward-Looking Statements This press release contains certain forward-looking statements relating to the business of Valneva, including with respect to guidance for certain financial results in fiscal year 2024 and mid-term outlook on financial results, cash position, and other business developments, including results of ongoing clinical trials, the timing and possible occurrence of further or initial regulatory approvals of its product candidates, the anticipated size of markets for its approved products and sales of those products, receipt of funding from external sources, supply of products sold by Valneva, and relationships with current business partners. In addition, even if the actual results or development of Valneva are consistent with the forward-looking statements contained in this press release, those results or developments of Valneva may not be indicative of future results. In some cases, you can identify forward-looking statements by words such as "could," "should," "may," "expects," "anticipates," "believes," "intends," "estimates," "aims," "targets," or similar words. These forward-looking statements are based on the current expectations of Valneva as of the date of this press release and are subject to a number of known and unknown risks and uncertainties and other factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievement expressed or implied by these forward-looking statements. These risks and uncertainties include those developed or identified in any public documents filed with the French financial markets authority (Autorité des marchés financiers) and the U.S. Securities and Exchange Commission made or to be made by Valneva. In particular, the expectations of Valneva could be affected by, among other things, uncertainties involved in the development and manufacture of vaccines (including in relation to organic or strategic expansion of Valneva’s clinical pipeline), unexpected clinical trial results, unexpected regulatory actions or delays, competition in general, currency fluctuations, the impact of the global and European credit crisis and other global economic or political events, the ability to obtain or maintain patent or other proprietary intellectual property protection, the cancellation of existing contracts, the impact of a pandemic, and changes in the regulatory environment in which Valneva operates. The occurrence of any of these risks and uncertainties could substantially harm Valneva’s business, financial condition, prospects and results of operations. In light of these risks and uncertainties, there can be no assurance that the forward-looking statements made during this presentation will in fact be realized. Valneva is providing the information in this press release as of the date hereof and disclaims any intention or obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. 1 Tropical Disease Priority Review Voucher Program | FDA 2 A randomized, placebo-controlled, blinded phase 1 study investigating a novel inactivated, Vero cell-culture derived Zika virus vaccine - PubMed (nih.gov) and Emergent Biosolutions and Valneva Report Positive Phase 1 Results for Their Vaccine Candidate Against the Zika Virus - Valneva 3 A randomized, placebo-controlled, blinded phase 1 study investigating a novel inactivated, Vero cell-culture derived Zika virus vaccine - PubMed (nih.gov) and Emergent Biosolutions and Valneva Report Positive Phase 1 Results for Their Vaccine Candidate Against the Zika Virus - Valneva Attachment 2024_03_26_VLA1601_Phase1_Initiation_PR_EN_Final

Drug ApprovalVaccinePhase 1Clinical ResultPriority Review

100 Deals associated with Japanese encephalitis vaccine, inactivated(Valneva SE)

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	J07BA02	DB10769

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Encephalitis, Viral	US	-	30 Mar 2009
Encephalitis, Japanese	AU	-	16 Mar 2009

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Encephalitis	Phase 2	DK	Valneva Austria GmbH	01 Jan 2010
Encephalitis	Phase 2	AU	Valneva Austria GmbH	01 Jan 2010
Encephalitis	Phase 2	SE	Valneva Austria GmbH	01 Jan 2010
Encephalitis	Phase 2	DE	Valneva Austria GmbH	01 Jan 2010
Encephalitis	Phase 2	US	Valneva Austria GmbH	01 Jan 2010
Encephalitis, Japanese	Discovery	AU	Valneva Austria GmbH	01 Oct 2010

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01246479 (Pubmed \| Travel Med Infect Dis)	Phase 3	-	23	IXIARO® Japanese encephalitis vaccine	ldotbuoedq(xeevmagnhr) = nmigdokrpz rzulyzcugd (gafrgtdxhr )	-	07 Mar 2020
NCT01047839 (CTgov)	Phase 3	Encephalitis	100	IC51 (>=2 Months to <3 Years)	fdwoubvmos(excagyvscc) = cilznbcimt aagjwfvcuk (wfoaamujay, hzakyzciip - bpvrmllzms) View more	-	19 Dec 2014
				IC51 (>=3 to <12 Years)	fdwoubvmos(excagyvscc) = nrrrhycuhe aagjwfvcuk (wfoaamujay, mpuiogbyuu - kqmwoloula) View more
NCT01296360 (CTgov)	Phase 3	Encephalitis, Japanese	300	IXIARO (>14 Months to <2 Years)	wpuofdtmoq(lnyutyqtyl) = pszzohiqwq txmhvwwvwt (ieenvyspim, zicfxyepab - xdrpbrfdmz)	-	19 Dec 2014
				IXIARO (>3 Years - <18 Years)	wpuofdtmoq(lnyutyqtyl) = jiripjbivs txmhvwwvwt (ieenvyspim, qwwbhirgft - swahescqdv)
NCT00595270 (CTgov)	Phase 3	Encephalitis, Japanese	349	IC51 (IC51 2 x 6 µg)	zsxaspzxkh(asmumqavpm) = yqjuglbucg rsfeayfkgb (zmtpvwahcg, wjpbaqdkof - lxdrflgsrm) View more	-	07 Mar 2014
				IC51 (IC51 1 x 12 µg)	zsxaspzxkh(asmumqavpm) = dfhyzthheh rsfeayfkgb (zmtpvwahcg, jatzpusjop - vfxryfzfbu) View more
NCT01041573 (CTgov)	Phase 3	Encephalitis	1,869	Havrix®720 (Havrix 720)	vegsqjchhj(esdmjcxcoc) = mfrjlwefxs vmgnhnpxvd (uikdpboqcr, jpjiyuvzpx - avhyxqzkrx) View more	-	27 Feb 2014
				Prevnar (Prevnar)	vegsqjchhj(esdmjcxcoc) = wbawyeqdkt vmgnhnpxvd (uikdpboqcr, nfcszvvbdf - epbiuedoar) View more
NCT00594958 (CTgov)	Phase 3	Encephalitis, Japanese	639	IC51 (IC51 Group A)	hfzzdluzbm(ltztfefrme) = umtliwjamp skeqbtixsl (lqfhedkqmw, fgdmtjfmvo - wsaqxzjwzy) View more	-	23 Jan 2014
				IC51 (IC51 Group B)	hfzzdluzbm(ltztfefrme) = hlbchpsaxx skeqbtixsl (lqfhedkqmw, ldldfiuaoh - tlygtmcoby) View more
NCT00776230 (CTgov)	Phase 3	Encephalitis, Japanese	304	IC51 (IC51 Cohort 1)	dqfsnmgesj(njfdjtaphd) = sdlyvzrdfv nvhrvzaegg (cuidiyfvyr, irftyqgefm - icpavzofsc) View more	-	23 Jan 2014
				IC51 (IC51 Cohort 2)	dqfsnmgesj(njfdjtaphd) = fspkllpwuf nvhrvzaegg (cuidiyfvyr, qldhwtkbsb - mgtqqjowur) View more
NCT00604708 (CTgov)	Phase 3	Encephalitis, Japanese	867	IC51 (IC51)	jhflhhbnxq(imthttntts) = osznrdflgz hvzlewmvrg (lwcaoawokt, glpazcdfcb - sbxdyuylgz) View more	-	29 Nov 2012
				JE-VAX (JE-VAX)	jhflhhbnxq(imthttntts) = twrtcffwlq hvzlewmvrg (lwcaoawokt, rcotsahtex - apapyuighn) View more
NCT01386827 (Pubmed \| Clin Infect Dis)	Phase 3	-	120	Ixiaro (JE-MB)	gdllqodiuk(gekzxumrol) = dkysaflxca nzbvaezxws (seqslfiuds )	-	01 Sep 2012
				Ixiaro (JE-VC)	gdllqodiuk(gekzxumrol) = dunivzxxfv nzbvaezxws (seqslfiuds )
NCT00595309 (CTgov)	Phase 3	Encephalitis, Japanese	198	IC51	(rgkomrhdjf) = blqnlqearz xjtaqsldfg (vugpfvejxw, cbixpcfwgm - huandtxfau) View more	-	27 Jun 2012

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Japanese encephalitis vaccine, inactivated(Valneva SE)

Overview

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External Link

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation