Valneva Stock

Valneva SE (Valneva) operates as a specialty vaccine company.

The company focuses on the development, manufacturing and commercialization of prophylactic vaccines for infectious diseases. The company takes a highly specialized and targeted approach to vaccine development by focusing on vaccine solutions addressing unmet needs to ensure the company can make a difference in peoples’ lives. The company applies its deep understanding of vaccine science, including the company’s expertise across multiple vaccine modalities, and the company’s established vaccine development capabilities, to develop vaccines against diseases which are not yet vaccine-preventable, or for which there are limited effective treatment options. The company is leveraging its expertise and capabilities to rapidly advance a broad range of vaccines into and through the clinic, including candidates against the chikungunya virus and Lyme disease.

The company’s clinical portfolio is composed of a number of highly differentiated vaccine candidates that are designed to provide preventative solutions to diseases with high unmet need. VLA1553, targeting the chikungunya virus, is the first and only chikungunya vaccine candidate to report positive Phase 3 topline data and the first for which a Biologics License Application, or BLA, has been submitted to the U.S. Food and Drug Administration, or FDA. As a live-attenuated vaccine, VLA1553 is particularly well suited to target long-lasting protection compared to other chikungunya assets being evaluated in clinical trials. Chikungunya has spread to more than 100 countries and infected more than 3 million people in the Americas since first arriving there in 2013. VLA15 is a Phase 3 vaccine candidate targeting Borrelia, the bacterium that causes Lyme disease, under development in collaboration with Pfizer, and it is the only active vaccine candidate against Lyme disease undergoing clinical trials. VLA15 targets the six most prevalent serotypes, or variations, of Borrelia in the United States, where approximately 476,000 people are diagnosed with Lyme disease each year and in Europe, where at least a further 200,000 cases occur annually.

The company has already successfully licensed and commercialized a portfolio of traveler vaccines, which is composed of IXIARO (also marketed as JESPECT in Australia and New Zealand), indicated for the prevention of Japanese encephalitis in travelers and military personnel, and DUKORAL, indicated for the prevention of cholera and, in Canada, Switzerland, New Zealand and Thailand, prevention of diarrhea caused by Enterotoxigenic Escherichia coli, or ETEC, the leading causes of travelers’ diarrhea. The company also distributes vaccines for third parties in selected countries where the company has a commercial infrastructure.

The company has a highly developed, nimble and sophisticated manufacturing infrastructure with facilities across Europe to meet the company’s clinical and commercial needs, including BioSafety Level 3 manufacturing and R&D facilities. The company has assembled a team of experts with deep scientific, clinical and business expertise in biotechnology and specifically in vaccine development, manufacturing and commercialization. The company’s senior leadership team has extensive experience and demonstrated ability to move vaccines through the clinic and into successful commercialization. Members of the company’s team have previously worked at industry leaders such as Novartis, Chiron, GlaxoSmithKline and Daiichi Sankyo.

Pipeline and Proprietary Commercial Portfolio

The company’s pipeline consists of assets at all stages of research & development. The company’s intention is to develop vaccine candidates that are first- or best-in class and address unmet needs in infectious diseases. The company’s intention is to either develop them for future commercialization in-house or through and with partners.

The company’s clinical pipeline includes:

VLA1553 – a vaccine candidate against the chikungunya virus, or CHIKV, a mosquito-borne virus that has spread to more than 100 countries with the potential to rapidly expand further. There are no preventive vaccines or effective treatments for the chikungunya virus available and VLA1553 is the only chikungunya vaccine candidate that successfully completed pivotal Phase 3 studies and the first chikungunya vaccine candidate for which a regulatory filing process is ongoing with the FDA. Additionally, as a live-attenuated vaccine, VLA1553 is particularly well suited to target long-lasting protection compared to other chikungunya assets being evaluated in clinical trials. In the company’s Phase 1 clinical trial, it observed development of antibodies to chikungunya virus resulting in 100% seroconversion of the 120 healthy participants, which results were sustained after 12 months. VLA1553 advanced directly to a Phase 3 clinical trial, for which the company reported final results in March 2022, final lot-to-lot consistency data in May 2022 and 12-month antibody persistence data in December 2022. In the pivotal Phase 3 trial, the company observed a very high seroconversion level of 98.9% in participants 28 days after receiving the single administration, and this immunogenicity profile was maintained over time, with 99% of participants showing protective CHIKV neutralizing antibodies twelve months after receiving a single vaccination in a dedicated antibody persistence trial. The company initiated BLA rolling submission with the FDA for approval of VLA1553 in persons aged 18 years and above in August 2022 and completed the submission in December 2022. In February 2023, the FDA accepted the filing and classified the review as Priority. VLA1553 has been assigned a Prescription Drug User Fee Act, or PDUFA, review goal date at the end of August 2023, which is the date by which the FDA intends to take action on the application. VLA1553 previously received FDA Fast Track and Breakthrough Therapy designations in 2018 and 2021, respectively. The sponsor of the first chikungunya vaccine BLA to be approved in the United States will be eligible to receive a Priority Review Voucher, or PRV. VLA1553 was also granted PRIority MEdicine, or PRIME, designation by the European Medicines Agency, or EMA, in 2020, and the company plan to make regulatory submissions for VLA1553 in Europe in the second half of 2023. The company also initiated a Phase 3 trial in adolescents conducted in Brazil by Instituto Butantan, which may support future regulatory submissions in this age group following a potential initial regulatory approval. In February 2023, Valneva completed enrollment and vaccination of 254 adolescents and first results are expected mid-2023.

VLA15 – a vaccine candidate against 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 advanced clinical development today and has received Fast Track designation from the FDA. The company reported initial results for three Phase 2 clinical trials of VLA15 in both adult and pediatric populations, in which the company observed high levels of antibodies against all six strains. In August 2022, the company initiated a Phase 3 clinical study, ‘Vaccine Against Lyme for Outdoor Recreationists (VALOR)’, to investigate the efficacy, safety and immunogenicity of VLA15 in participants five years of age and older in highly endemic regions in the United States and Europe. In February 2023, Pfizer, as the study sponsor, decided to discontinue half of the total enrolled participants in the trial following violations of Good Clinical Practice, or GCP, at certain clinical trial sites run by a third party clinical trial site operator. The clinical trial remains ongoing with other sites not operated by the third party. The companies intend to work with regulatory authorities, and as previously announced, aim for Pfizer to potentially submit a BLA to the FDA and a Marketing Authorization Application, or MAA, to the EMA in 2025, pending successful completion of the Phase 3 studies and subject to the agreement of these regulatory agencies to proposed modifications of the clinical trial plan. According to the terms of the company’s collaboration with Pfizer, Pfizer will lead late phase development of VLA15. If VLA15 is approved, Pfizer will have sole control over its commercialization and the company will be eligible to receive milestone and royalty payments.

In addition to the company’s clinical-stage assets, its portfolio includes a series of pre-clinical assets against disease targets that reflect the company’s strategy of providing prophylactic solutions to significant diseases that lack a preventative and effective therapeutic treatment option. These include VLA2112, a vaccine candidate targeting the Epstein-Barr virus, or EBV, which is one of the most common human viruses. EBV can cause infectious mononucleosis and is strongly associated with the development of several types of cancer and multiple sclerosis. The company has also been working on a vaccine candidate targeting the human metapneumovirus, or hMPV, which is a major worldwide respiratory pathogen that causes acute upper and lower respiratory tract infection and the company is exploring potential partnering opportunities. Additionally, the company initiated pre-clinical work on vaccine candidates targeting parvovirus B19, a virus most commonly causing fifth disease, and Campylobacter, a bacterium often associated with food poisoning.

The company commercializes its fully owned travel vaccines IXIARO/JESPECT and DUKORAL and have supplied the company’s inactivated COVID-19 vaccine VLA2001 under government contracts. Sales from these products are complemented by sales from the distribution of third-party products in markets where Valneva operates its own marketing and sales infrastructure (the United States, Canada, Nordic countries, the United Kingdom, Austria and France):

IXIARO – an inactivated Vero cell culture-derived Japanese encephalitis vaccine that is the only Japanese encephalitis vaccine licensed and available in the United States, Canada and Europe. IXIARO is indicated for active immunization against Japanese encephalitis, the most prevalent cause of viral encephalitis in Asia, for adults, adolescents, children and infants aged two months and older. In September 2020, the Defense Logistics Agency, or DLA, awarded the company a new contract for the supply of IXIARO. The terms of the agreement contemplated an initial base year followed by two option years, each with a range of minimum and maximum potential dose orders. Due to the impact of the COVID-19 pandemic on Department of Defense operations, the option terms for the first year were amended in 2021 and the DLA did not exercise the second option year in 2022. This was partly offset in 2022 by the significant recovery of the private travel markets.

DUKORAL – an oral vaccine for the prevention of diarrhea caused by Vibrio cholera and, in Canada and other countries, heat-labile toxin producing ETEC, the leading cause of travelers’ diarrhea. Sales in 2022 benefited from a significant recovery in the travel markets after being impacted by the COVID-related decline in travel in 2020 and 2021. DUKORAL is authorized for use in the European Union and Australia to protect against cholera and in Canada, Switzerland, New Zealand and Thailand to protect against cholera and ETEC.

VLA2001 – the only inactivated whole-virus COVID-19 vaccine approved in Europe and the first COVID-19 vaccine to receive a full marketing authorization from the European Medicines Agency. It has been produced using the company’s established Vero cell platform, leveraging the manufacturing technology for the company’s commercial Japanese encephalitis vaccine, IXIARO. In addition to its marketing approval in Europe, the company’s COVID-19 vaccine received conditional marketing authorization in the United Kingdom and emergency use authorization in the United Arab Emirates and Kingdom of Bahrain. During the third quarter of 2022, the World Health Organization, or WHO, also issued recommendations for use of the vaccine, including for a booster dose of VLA2001 four to six months after completion of the primary series. In November 2021, the company signed an advance purchase agreement with the European Commission, or EC, to provide up to 60 million doses of VLA2001 in 2022 and 2023. In December 2021, the company signed an advance purchase agreement with the Kingdom of Bahrain to provide one million doses of VLA2001 in 2022. An amendment to the purchase agreement with the European Commission in July 2022 reduced the orders of VLA2001 to 1.25 million doses, which the company delivered to participating EU Member States (Germany, Austria, Denmark, Finland, and Bulgaria). VLA2001 sales in Europe and Bahrain amounted to €29.6 million in the year ended December 31, 2022. In August 2022, the company had suspended manufacturing of the vaccine in light of the reduced order volume from EU Member States. The company is continuing discussions on potential additional supply agreements with various other governments around the world to deploy the remaining eight to ten million doses of inventory. VLA2001’s shelf life is expected to be extended to up to 24 months, compared to 21 months.

Strategy

The company’s strategy supports its intention to contribute to a world in which no one dies or suffers from a vaccine preventable disease. The company’s strategy is based on an integrated business model that has allowed the company to build a portfolio of differentiated clinical and pre-clinical assets, as well as a growing commercial business. The company is focused on utilizing its proven and validated product development capabilities to rapidly advance solutions addressing unmet needs in infectious diseases towards regulatory approval, with the goal of becoming first- best- or only-in-class, and commercialization. The company has strategically entered into partnerships with other well-established pharmaceutical companies to leverage their clinical and commercial capabilities to optimize the potential value of select assets. As the company advances its late stage portfolio, the company also remains focused on investing in the company’s research and development pipeline in order to develop the company’s earlier stage assets, as well as identify new targets and indications where the company can make a significant difference.

VLA1553—The company’s Vaccine Candidate Targeting the Chikungunya Virus

VLA1553 is a vaccine candidate for chikungunya virus, a mosquito-borne virus that has spread to more than 100 countries with the potential to rapidly expand further through infected travelers who carry the virus to their home countries.

In the company’s Phase 1 clinical trial, the company observed that VLA1553 led to the development of antibodies to chikungunya virus resulting in 100% seroconversion of the 120 healthy participants in the trial and that these levels were sustained after 12 months. Based on this Phase 1 dataset the company was able to advance directly into Phase 3 clinical development and concluded a pivotal Phase 3 trial in over 4,000 healthy adults. The company received confirmation from the FDA and EMA for the company’s proposal to seek licensure under the accelerated approval pathway. Under this pathway, the company plans to seek licensure of VLA 1553 based on a surrogate endpoint (seroresponse rate) agreed with the FDA and the EMA. The surrogate endpoint is an immune response that is reasonably likely to predict protection from chikungunya infection. This eliminates the need to execute a time-intensive and costly field trial where a group of patients receiving a placebo is compared to groups of patients receiving VLA1553. However, this approach requires that vaccine effectiveness, i.e. the proof that the vaccine can prevent cases of disease, is demonstrated post-licensure. The company reported positive topline results of the company’s pivotal Phase 3 trial involving over 4,000 healthy adults in August 2021, final results, including six-month follow-up data, in March 2022 and twelve-month antibody persistence data in December 2022. These antibody persistence results confirmed a very high level of seroconversion, with 99% of participants showing protective CHIKV neutralizing antibodies twelve months after receiving a single vaccination. The final Phase 3 clinical trial data that the company announced in March 2022 indicated a seroresponse rate of 98.9% at 28 days compared to the 70% threshold (for non-acceptance) agreed with the FDA.

The sponsor of the first chikungunya vaccine BLA to be approved in the United States will be eligible to receive a PRV. VLA1553 has received Fast Track and Breakthrough Therapy designation from the FDA and PRIME designation from the EMA. In August 2022, the company initiated BLA rolling submission with the FDA for approval of VLA1553 in persons aged 18 years and above and completed the submission in December 2022. This BLA submission is part of the accelerated approval pathway agreed with the FDA in 2020. In February 2023, the FDA accepted the filing and classified the review as Priority. VLA1553 has been assigned a PDUFA review goal date at the end of August 2023, which is the date by which the FDA intends to take action on the application. If VLA1553 is approved, the company intends to market it as a traveler vaccine in North America and Europe.

Additionally, in May 2020, the company partnered with the Instituto Butantan in Brazil to develop, manufacture and market VLA1553 in low and middle income countries. As part of this collaboration, the company initiated an adolescent clinical trial of VLA1553 in 754 healthy volunteers in Brazil in 2022, which has been approved by the local regulatory agency, ANVISA, and is sponsored by Instituto Butantan. In February 2023, Valneva announced enrollment completion and vaccination of the 754 adolescents. First results are expected mid-2023.

In addition to VLA1553, there are two third-party advanced chikungunya vaccine candidates. The first is an inactivated vaccine candidate manufactured by Bharat Biotech of India, which has initiated a seamless Phase 2/3 clinical trial in August 2021. The second is a virus-like particle vaccine candidate developed by Emergent BioSolutions, which has announced initiation of Phase 3 clinical trials in October 2021. All of these potential vaccine candidates may face limitations relative to VLA1553, including VLA1553 being designed to only require a single administration, while Bharat’s and potentially Emergent BioSolutions’ vaccine candidates are likely to require multiple shots to either reach or maintain high levels of effectiveness.

VLA1553 Approach

VLA1553 is a live-attenuated chikungunya vaccine candidate based on the East, Central and Southern African, or ECSA, strain which has spread across the Indian Ocean. It is cross-reactive with other strains, meaning that it is designed to protect against those as well, including the strain of Asian lineage which is rapidly spreading across the Americas as observed in pre-clinical studies. Additionally, given that the company has engineered VLA1553 as a live-attenuated vaccine, it may confer life-long immunity.

VLA1553 is engineered using a strain of chikungunya, where specific segments of the virus have been deleted, thereby weakening, or attenuating, the virus. This approach enables VLA1553 to catalyze the patient’s immune system into generating the antibodies necessary to provide protection against the virus while the weakened strain does not cause the patient to develop significant symptoms. In the company’s pre-clinical studies, growth of this strain on Vero cells resulted in a viral titer 35 times lower than observed with the original unattenuated strain, demonstrating the attenuation of the company’s chikungunya strain. The deleted segment also remained absent following replication of the virus in the Vero cells, suggesting that the weakness of the virus is sustained.

Phase 1 Clinical Trial and Results

The company conducted a single blind, randomized dose-escalation Phase 1 clinical trial of VLA1553 in 120 adults, at multiple centers in the United States, the results of which were published in Lancet in 2020. In this trial the company examined three doses of VLA1553: a low dose having a viral titer of 3.2 x 103, a medium dose of 3.2 x 104, and a high dose of 3.2 x 105. Participants in the low and medium dose cohorts and half of the patients in the high-dose cohort received a single dose of VLA1553 on Day 0 through intramuscular injection and a re-vaccination at 12 months. Half of the patients in the high-dose cohort received a re-vaccination at six months instead of 12 months. The primary endpoint of the trial was evaluation of safety measures, including frequency and severity of injection site and systemic reactions.

Phase 3 Clinical Trials

VLA1553-301 Clinical Trial

In September 2020, the company initiated its pivotal Phase 3 clinical trial, VLA1553-301, in the United States. In this double-blind, multi-center, randomized Phase 3 clinical trial, 4,115 participants aged 18 years and above were randomized 3:1 into two groups to receive either VLA1553 0.5mL or placebo. Immunogenicity was determined with a µPRNT50 assay.

Additionally, VLA1553 was highly immunogenic in elderly study participants (65 years of age or older), who achieved equally high seroconversion rates and neutralizing antibody titers over time as younger adults.

VLA1553-302 Clinical Trial

The company also initiated a lot-to-lot consistency Phase 3 trial, VLA1553-302, in February 2021 to show manufacturing consistency of VLA1553, which is a requirement for licensure. The company announced the completion of recruitment for this trial in June 2021, positive topline and final data from this trial in December 2021 and May 2022, respectively.

VLA1553-302 was a prospective, multicenter, randomized, pivotal Phase 3 clinical trial. Participants in the VLA1553-302 trial were randomized and followed for a total of six months. The objective of the trial was to show manufacturing consistency of the vaccine by demonstrating that three consecutively manufactured lots elicit equivalent immune responses measured by neutralizing antibody titers on Day 29 after vaccination. Lyophilized VLA1553 were administered as a single intramuscular immunization. Equivalence of immune responses were determined based on neutralizing antibody titers.

The VLA1553-302 trial met its primary endpoint, demonstrating that three consecutively manufactured vaccine lots elicited equivalent immune responses measured by neutralizing antibody titer GMT ratios on Day 29 after vaccination. The trial included 408 participants aged 18 to 45 and confirmed the excellent immunogenicity profile observed in the pivotal Phase 3 trial, VLA1553-301. All three lots were equally well tolerated and the safety profile was consistent with results in VLA1553-301. The trial therefore confirmed clinical equivalencem, as well as manufacturing consistency of the three lots.

The lot-to-lot data were part of the company’s submission to the FDA, which the company completed in December 2022.

VLA1553-303 Clinical Trial

In April 2021, the company initiated an antibody persistence trial that will follow annually up to 375 subjects in the immunogenicity subset of the VLA1553-301 trial for a period of five years. VLA1553-303 is a prospective, multicenter trial.

In December 2022, the company reported twelve-month data for this trial. 99% of participants retained neutralizing antibody titers above the seroresponse threshold of 150 twelve months after the single-dose vaccination.

VLA1553-321 Clinical Trial

In January 2022, the company announced the initiation of a Phase 3 trial of VLA1553 in adolescents. The VLA1553-321 trial is funded by CEPI and is intended to support the label extension in this age group following a potential initial regulatory approval in adults from the FDA. This trial is also expected to support licensure of VLA1553 in Brazil, which would be the first potential approval for use in endemic populations.

Conducted in Brazil by Instituto Butantan, VLA1553-321 is a prospective, double-blinded, multi-center, randomized and placebo-controlled Phase 3 trial. On February 14, 2023, the company announced recruitment completion with 754 adolescents from 12 to 17 years old randomized at a 2:1 ratio to receive either VLA1553 or placebo. The primary objective of the trial is to evaluate safety and immunogenicity following a single vaccination with VLA1553. Participants will be evaluated after 28 days and followed up to 12 months. The study will also provide safety and immunogenicity data in participants previously exposed to chikungunya.

VLA15— The company’s vaccine candidate targeting Lyme disease

The company is developing VLA15 as a vaccine against Borrelia, the bacterium that causes Lyme disease. VLA15 is a recombinant protein vaccine that targets six serotypes of Borrelia representing the most common strains found in the United States and Europe. The company has reported initial results of three Phase 2 clinical trials of VLA15 in over 900 healthy adults and interim analyses have demonstrated the presence of high titers of antibodies against all six strains. In August 2022, together with Pfizer, the company initiated a Phase 3 clinical study, ‘Vaccine Against Lyme for Outdoor Recreationists (VALOR)’, to investigate the efficacy, safety and immunogenicity of VLA15 in participants five years of age and older in highly endemic regions in the United States and Europe. In February 2023, the company announced that Pfizer, as the study sponsor, decided to discontinue half of the total recruited participants in the trial following violations of GCP at certain clinical trial sites run by a third-party clinical trial site operator. The clinical trial remains ongoing with other sites not operated by the third party. The discontinuation of these participants was not due to any safety concerns with the investigational vaccine and was not prompted by a participant-reported adverse event. The companies intend to work with regulatory authorities, and as previously announced, aim for Pfizer to potentially submit a BLA to the FDA and an MAA to EMA in 2025, pending successful completion of the Phase 3 studies and subject to the agreement of these regulatory agencies to proposed modifications of the clinical trial plan.

Phase 1 Clinical Trial and Results

The company evaluated VLA15 in a partially randomized, multi-center dose escalation Phase 1 clinical trial conducted in Belgium and the United States in 179 healthy adults below 40 years of age. The first 24 subjects were included in an open-label trial in which they participated in a staggered dose escalation design. The remaining 155 subjects were enrolled in one of six blinded treatment groups, receiving VLA15 at a dose of either 12 µg, 48 µg or 90 µg, with or without alum as an adjuvant, by intramuscular injection on Days 0, 28 and 56. The trial was designed to investigate the safety and tolerability, as well as immunogenicity of VLA15. The primary endpoint was safety and tolerability of VLA15 up to three months after enrollment (Day 84).

Phase 2 Clinical Trials and Results

The company has evaluated the safety and immunogenicity of VLA15 at different dosage levels and schedules in three Phase 2 clinical trials in Europe and the United States. Together, these trials enrolled 1443 healthy adults of 5 to 65 years of age.

VLA15-201 Clinical Trial and Results

The company’s first Phase 2 clinical trial, VLA15-201, was a randomized, observer-blind, placebo-controlled, multi-center Phase 2 clinical trial conducted in Belgium, Germany and the United States, consisting of a ‘run-in phase’ and a ‘main study phase.’ In the run-in phase, a total of 120 subjects aged 18-40 were randomized into one of four groups: a placebo group and three groups at different dosage levels of VLA15 with alum (90 µg, 135 µg or 180 µg). The subjects received intramuscular injections on Days 1, 29 and 57. Based on the elicited higher antibody responses across all serotypes observed from the run-in phase, the company selected the two higher VLA15 dose levels to be evaluated in the main study phase. A total of 452 subjects aged 18-65 were randomized 2:2:1 to receive one of two VLA15 doses (135 µg or 180 µg) or placebo, and received intramuscular injections on Days 1, 29 and 57. The primary endpoint for the trial was GMTs for IgG against each OspA serotype ST1 to ST6. Secondary endpoints examined SCR, geometric mean fold rise, or GMFR, and occurrence of adverse events.

In July 2020, the company announced results from its Phase 2 clinical trial of VLA15-201 in which the company observed VLA15 was immunogenic across all dose groups tested. Compared to results from the Phase 1 clinical trial, the higher doses used in the company’s Phase 2 clinical trial elicited higher antibody responses across all serotypes than those observed after the primary series in the Phase 1 clinical trial. SCR in the highest dose ranged from 81.5% (ST1) to 95.8% (ST2) on Day 85. No statistically significant differences between 135 µg and 180 µg treatment groups were observed.

VLA15-202 Clinical Trial and Results

The company’s second Phase 2 clinical trial, VLA15-202, was a randomized, observer-blind, placebo-controlled multi-center Phase 2 clinical trial conducted in the United States with 246 healthy volunteers aged 18-65. The subjects were randomized 2:2:1 to receive either VLA15 with alum (either 135 µg or 180 µg) or placebo, administered through intramuscular injection at month zero, two and six. The primary endpoint of the trial was GMTs for IgG against each OspA serotype, measured at month 7 to highlight the importance of further increases in OspA-specific IgG titers after the primary immunization series, which are likely necessary to achieve a successful vaccine candidate. Secondary endpoints evaluated SCRs, GMFRs and the occurrence of adverse events.

On October 20, 2020, the company reported interim results from VLA15-202. Compared to VLA15-201, immunogenicity was further enhanced using an immunization schedule of vaccinating at zero, two and six months. SCRs, after completion of the primary vaccination series, showed similar responses and ranged from 93.8% (ST1) to 98.8% (ST2, ST4).

Antibody responses were comparable in the two dose groups tested as of Day 208. The immunological response in older adults, one of the main target groups for a Lyme vaccine, was consistent with the company’s observations in VLA15-201. Furthermore, results did not indicate that prior exposure to Borrelia burgdorferi sensu lato (Bb sl), the bacteria that causes Lyme disease (baseline Bb sl sero-positivity) has an impact on immunogenicity or safety, also consistent with the company’s observations in VLA15-201.

Unlike the company’s previous trials, the company also performed a Serum Bactericidal Assay, or SBA, assessing the functional immune response against Lyme disease after vaccination with VLA15. Assays, such as SBAs, are commonly used to enable a potential prediction of vaccine efficacy via the measurement of vaccine-induced functional immune responses. Over the course of the company’s trial, the SBAs demonstrated functionality of antibodies against all OspA serotypes.

VLA15 was generally well tolerated across all doses and age groups tested in VLA15-202. On September 28, 2021, the company announced further positive results from VLA15-202.

VLA15-221 Clinical Trial

On December 2, 2020, the company announced the acceleration of the pediatric development of VLA15. The Phase 2 clinical trial VLA15-221, which commenced in March 2021, is the first clinical trial of VLA15 that includes a pediatric test population between 5 and 17 years old. The company announced completion of recruitment for VLA15-221 in July 2021 and reported topline data in February 2022.

VLA15-221 is a randomized, observer-blind, placebo-controlled Phase 2 clinical trial. A total of 625 participants, 5 to 65 years of age and in groups with age ranges of 5-11, 12-17 and 18-65, were randomized to receive VLA15 at Month 0-2-6 or Month 0-6 (approximately 200 volunteers each) or placebo at Month 0-2-6 (approximately 200 volunteers). The trial was conducted at sites in the U.S., which are located in areas where Lyme disease is endemic and has enrolled volunteers with a cleared past infection with Borrelia burgdorferia as well as Borrelia burgdorferi-naïve volunteers. Participants received VLA15 at a dose of 180µg, which was selected based on data generated in the two previous Phase 2 clinical trials.

In April 2022, together with Pfizer, the company reported positive pediatric data for the VLA15-221 trial. In pediatric participants (5-17 years old) who received VLA15 in either the two-dose schedule (N=93) or three-dose schedule (N=97), VLA15 was found to be more immunogenic than in adults with both vaccination schedules tested. The safety and tolerability profile observed in the 5- to 17-year age group was similar to the previously reported profile in adult participants. No vaccine-related serious adverse events (SAEs) were observed. Like in adults, the immunogenicity and safety data supported a three-dose primary vaccination schedule in pediatric participants in the Phase 3 trial.

Phase 3 Trial

In August 2022, together with Pfizer, the company announced the initiation of a Phase 3 clinical trial, Vaccine Against Lyme for Outdoor Recreationists (VALOR), to investigate the efficacy, safety and immunogenicity of VLA15.

The randomized, placebo-controlled, Phase 3 VALOR trial has been enrolling participants 5 years of age and older and is being conducted in areas where Lyme disease is highly endemic, including Finland, Germany, the Netherlands, Poland, Sweden and the United States. Participants will receive three doses of VLA15 180 µg or saline placebo (1:1 ratio) as a primary vaccination series followed by one booster dose of VLA15 or saline placebo.

In February 2023, the company and Pfizer announced that Pfizer, as the study sponsor, decided to discontinue a significant percentage of enrolled U.S. study participants following violations of good clinical practice at certain clinical trial sites run by a third-party clinical trial site operator. The companies intend to work with regulatory authorities, and as previously announced, aim for Pfizer to potentially maintain the original submission timelines, pending successful completion of the Phase 3 studies and subject to the agreement of these regulatory agencies to proposed modifications of the clinical trial plan.

VLA1601—The company’s Zika virus development program that remains on hold

The company has developed VLA1601, a highly purified inactivated vaccine candidate targeting the Zika virus, which the company developed using the same manufacturing platform as IXIARO, the company’s approved Japanese encephalitis vaccine. The company reported positive interim results for the Phase 1 study evaluating VLA1601 in November 2018. The inactivated vaccine candidate met the study’s primary endpoint showing a favorable safety profile in all doses and schedules tested. VLA1601 was also immunogenic in all treatment groups and induced both dose- and schedule-dependent neutralizing antibodies against the Zika virus with the kinetics expected for an inactivated, alum-adjuvanted whole-virus vaccine.

The company is evaluating a reactivation of this program. The incidence of Zika significantly declined after its peak in 2016 due to high population level immunity in affected countries. Back in November 2018, the company also chose to prioritize the company’s Lyme disease and chikungunya programs representing a greater health crisis. However, Zika virus transmission persists in several countries in the Americas and in other endemic regions. According to WHO, a total of 89 countries and territories have reported evidence of mosquito transmitted Zika virus infection to date but no vaccine is yet available for the prevention of Zika virus infection. As a result, the company may choose to reactivate this program in the future if warranted.

VLA84—The company’s Clostridium difficile vaccine candidate that remains on hold

The company has developed VLA84, a vaccine candidate targeting the prevention of primary symptomatic Clostridium difficile infection, or CDI, a leading cause of life-threatening, healthcare-associated infections worldwide. VLA84 is designed to produce an immune response to neutralize the effects of C. difficile toxins A and B, considered to be largely responsible for CDI. The company completed Phase 2 development of VLA84. The key objectives of the Phase 2 trial were met, the vaccine candidate generated strong immune responses against C. difficile toxins A and B, and the safety and tolerability profile was good. The company could advance into Phase 3 if the company choose to reactivate this program and find a suitable partner.

Pre-clinical Portfolio

In addition to the company’s clinical-stage assets, the company’s portfolio includes several pre-clinical assets against disease targets that reflect the company’s strategy of providing prophylactic solutions to significant diseases that lack a preventative and effective therapeutic treatment option.

The company’s pre-clinical work involves exploratory study of a given disease, including extensive review of existing literature and early data that will inform the company’s view of whether and how the company could develop a vaccine for that disease.

The company’s two most advanced pre-clinical assets target hMPV and EBV and are presented below. Additionally, the company initiated pre-clinical work on vaccine candidates targeting parvovirus B19, a virus most commonly causing fifth disease, and Campylobacter, a bacterium often associated with food poisoning.

VLA1554—The company’s vaccine candidate targeting hMPV

The company’s hMPV vaccine candidate, VLA1554, is a pre-fusion recombinant F protein subunit vaccine. It is produced in CHO cells, using an initial classical purification process that has been established with suitable production yield.

First readouts of pre-clinical proof of concept studies showed that immunization with pre-fusion A1 F protein generated a superior neutralizing antibody response against hMPV subgroups A1 and B1 as compared to pre-fusion B1 F protein. Low doses of the vaccine candidate generated hMPV-neutralizing responses that protected mice from challenge. Despite the high frequency of pneumoviral infections and over 50 years of research in this field, the virus was discovered relatively recently, and no licensed vaccine against hMPV is available. The company is exploring potential partnering opportunities for this candidate.

VLA2112 - The company’s vaccine candidate targeting Epstein-Barr Virus (EBV)

The company’s EBV vaccine candidate, VLA2112, is based on adjuvanted, subunit viral glycoproteins to elicit high titers of EBV-neutralizing antibodies.

The evaluation of external and internal antigen designs is ongoing. The vaccine candidate will comprise the combination of antigens that best neutralize infection of both epithelial cells and B cells. The addition of an adjuvant to further optimize immune responses will be investigated prior to development.

Commercial Portfolio

The company’s commercial portfolio is composed of three vaccines, the company’s travel vaccines IXIARO/JESPECT and DUKORAL, and the company’s inactivated COVID-19 vaccine, VLA2001. The company’s travel vaccines serve a wide range of potential travelers where the diseases they prevent are endemic, from business and leisure travelers to government and military personnel traveling on behalf of their government. The company also distributes certain third-party vaccines in countries where the company operates its own marketing and sales infrastructure. The company’s commercial activities have generated meaningful revenues, much of which the company has reinvested in the company’s research and development capabilities in order to advance the company’s clinical assets and drive future growth.

IXIARO—The company’s Japanese Encephalitis Vaccine

IXIARO, or JESPECT in Australia and New Zealand, is an inactivated Vero cell culture-derived Japanese encephalitis vaccine and is the only Japanese encephalitis vaccine approved for use in the United States, Canada and Europe. IXIARO is indicated for active immunization against Japanese encephalitis in adults, adolescents, children and infants aged two months and older, and is a required vaccine for U.S. military personnel who are deployed to areas of risk for Japanese encephalitis. The pediatric indication of IXIARO was granted Orphan Drug designation by the FDA.

Japanese encephalitis virus, or JEV, is spread by mosquitos and is the most important cause of viral encephalitis in Asia and the Western Pacific.

IXIARO Overview

IXIARO is an inactivated vaccine administered as two doses either seven or 28 days apart. In a randomized clinical trial, high titers of neutralizing antibodies were detected in 96.4% of adults 28 days after the last dose. The immune response to IXIARO was durable with high levels of neutralizing antibodies in 84.9% of participants three years initial immunization. A separate trial administration of a booster dose at 14 months after completion of the initial two doses resulted in 100% of participants having neutralizing antibodies.

IXIARO is approved for the prevention of disease caused by JEV in individuals two months of age and older. This intramuscular vaccine is administered in two parts, between seven and 28 days apart depending on the age of the recipient, and with the second dose completed at least a week prior to potential exposure to JEV. A booster shot may be given at least 11 months after completion of the primary immunization series if ongoing exposure or re-exposure to JEV is expected. In 2020, the FDA approved the extension of the shelf life of IXIARO from 24 months to 36 months.

Sales of IXIARO

IXIARO was first approved by the FDA and European Commission in 2009.

DUKORAL—The company’s vaccine against cholera and ETEC

DUKORAL is an oral vaccine containing four inactivated strains of the bacterium Vibrio cholerae serotype O1, and part of a toxin from one of these strains as active substances. DUKORAL is authorized for use in the European Union and Australia to protect against cholera and in Canada, Switzerland, New Zealand and Thailand to protect against cholera and ETEC, the leading cause of travelers’ diarrhea. Originally licensed in Sweden by SBL Vaccines in 1991, and subsequently in the European Union in 2004 through a centralized procedure followed by other international markets, the vaccine was acquired by the company in 2015 from Janssen Pharmaceuticals as part of the company’s strategic vision to extend the company’s proprietary travel vaccine portfolio.

DUKORAL Overview

DUKORAL is intended for active immunization against cholera (and LT-ETEC diarrhea in certain jurisdictions) in adults and children from two years of age who will be visiting endemic/epidemic areas. The use of DUKORAL should be determined on the basis of official recommendations, taking into account the variability of epidemiology and the risk of contracting disease in different geographical areas and travelling conditions. DUKORAL is a drinkable vaccine that helps prevent diarrhea caused by heat-labile toxin-producing ETEC, as well as cholera.

DUKORAL is administered orally after dissolving the product in a glass of water. Vaccination requires two doses given one to six weeks apart. In an efficacy trial done in Bangladesh in 89,596 adults and children aged two years and older, the efficacy of DUKORAL against cholera was 85% in the six months after the third dose and 57% in the second year after immunization. Protective efficacy declined over the three-year trial period. DUKORAL conferred 67% protection against episodes of diarrhea caused by ETEC during the initial three months of follow-up but demonstrated no protection thereafter.

Sales of DUKORAL

DUKORAL was granted marketing authorization throughout the European Union in 2004, having previously been licensed in Sweden and Norway in 1991 through national licensure processes. DUKORAL was approved in Canada in 2003.

VLA2001—The company’s SARS-CoV-2 Vaccine

VLA2001 is the only inactivated whole-virus COVID-19 vaccine approved in Europe and the first COVID-19 vaccine to receive a full marketing authorization from the EMA. It was produced using the company’s established Vero-cell platform, leveraging the manufacturing technology for the company’s commercial Japanese encephalitis vaccine, IXIARO. In addition to its marketing approval in Europe, VLA2001 received conditional marketing authorization in the United Kingdom and emergency use authorization in the United Arab Emirates and Kingdom of Bahrain. During the third quarter of 2022, the World Health Organization also issued recommendations for use of the vaccine, including for a booster dose of VLA2001 four to six months after completion of the primary series.

Clinical Trials of VLA2001

The company previously reported data from various clinical trials of VLA2001, including:

VLA2001-201, a Phase 1/2 clinical trial,

VLA2001-301 (Cov-Compare), a pivotal Phase 3 clinical trial comparing VLA2001 to AstraZeneca’s AZD1222 vaccine,

Booster extensions of the VLA2001-201 and VLA2001-301 clinical trials, evaluating VLA2001 as a booster following primary vaccination with VLA2001 or AZD1222,

VLA2001-304, a Phase 3 clinical trial evaluating primary and booster vaccination with VLA2001 in adults aged 56 and over, and

VLA2001-307, a clinical trial evaluating VLA2001 used as a booster in participants who had received two or three doses of an mRNA vaccine, with or without previous natural SARS-CoV-2 infection.

As of December 31, 2022, the company continued to wind-down activities for the ongoing VLA2001 clinical studies VLA2001-301, VLA2001-304 and VLA2001-307, as indicated below:

VLA2001-301 (Cov-Compare): The company has updated its clinical study report to include immunogenicity, safety, and neutralization data for Day 208. The company intend to prepare a final analysis including the additional safety data that were collected in adults, as well as data from the few adolescents that were recruited, with results expected in the second quarter of 2023;

VLA2001-304: The company continues to collect safety data as per the trial protocol and expect to have final results in the second quarter of 2023.

VLA2001-307: The company recruited a total of six of the expected nine cohorts and decided to stop recruitment for the remaining three cohorts due to recruitment challenges. The company will continue to collect safety data and should have final study data by the third quarter of 2023.

Sales of VLA2001

In November 2021, the company signed an advance purchase agreement with the European Commission to provide up to 60 million doses of VLA2001 in 2022 and 2023. In December 2021, the company signed an advance purchase agreement with the Kingdom of Bahrain to provide one million doses of VLA2001 in 2022. An amendment to the purchase agreement with the European Commission in July 2022 reduced the orders of VLA2001 to 1.25 million doses, which the company delivered to participating EU Member States (Germany, Austria, Denmark, Finland, and Bulgaria). In light of reduced order volume from EU Member States, the company suspended manufacturing of the vaccine in July 2022. The company is continuing to explore potential additional supply agreements to deploy the remaining eight to ten million doses of inventory. These inventories were fully written-down as of December 31, 2022, as explained further in the Notes to the company’s financial statements. VLA2001’s shelf life is expected to be extended to up to 24 months, compared to 21 months.

Third-party Vaccines

The company distributes certain third-party vaccines in countries where the company operates its own marketing and sales infrastructure. In June 2020, the company entered into a distribution agreement with Bavarian Nordic, pursuant to which the company agreed to commercialize Bavarian Nordic’s marketed vaccines for rabies and tick-borne encephalitis, leveraging the company’s commercial infrastructure in Canada, the United Kingdom, France and Austria. In September 2022, the company also announced a partnership with VBI Vaccines for the marketing and distribution of the only 3-antigen Hepatitis B vaccine, PreHevbri, in select European markets. Valneva and VBI expect PreHevbri to be available in these countries in 2023.

Sales and Marketing

The company has a specialist commercial capability comprising approximately 50 employees for the distribution of the company’s travelers’ vaccines, IXIARO and DUKORAL, and third-party vaccines.

79

The company has established the company’s own commercial operations in certain travel vaccine markets including the United States, Canada, the United Kingdom, Sweden, France, Austria, Norway, Denmark, Finland, Belgium and the Netherlands. The company commercializes its own and third-party vaccine brands to both private and government customers, including the U.S. military. In other markets, the company has entered into marketing and distribution agreements with companies that specialize in the promotion of travel brands and/or for which there is a strategic fit with their product portfolio. Examples of such distribution partnerships include Germany (Bavarian Nordic), Eastern Europe (IMED), Israel (Kamada) and Australia and New Zealand (Seqirus/CSL).

Commercial Operations in Key Markets

The company manages nearly all of its global product sales revenues through the company’s own commercial operations. Local operations include expertise in Sales, Marketing, Medical Affairs, Governmental Affairs (U.S.), business support functions and General Management.

The company’s commercial teams work continuously to improve service and performance, including embracing digital technology, which allows the company to better connect with travelers, physicians and other health care professionals.

The company has also continued to leverage the company’s commercial organization to distribute third-party products and aim to attract additional products to further leverage the company’s commercial infrastructure. The company entered into a partnership with Seqirus in 2016 to commercialize two differentiated flu vaccines in Austria. The company also entered into a marketing and distribution partnership with Kamada in 2018 to commercialize their Rabies immunoglobulin in Canada and with Bavarian Nordic in 2020 to commercialize their Rabipur and Encepur brands in Austria, the UK, France, Belgium, the Netherlands and Canada. In September 2022, the company announced a marketing and distribution agreement with VBI Vaccines Inc. to commercialize their Hepatitis B vaccine PreHevbri in the United Kingdom, Sweden, Norway, Denmark, Finland, Belgium, and the Netherlands.

Intellectual Property

Patents and Patent Applications

As of December 31, 2022, the company had a portfolio of 459 issued patents, including 73 granted in Germany, France, the United Kingdom, Spain and Italy, 40 issued in the United States, and 232 pending patent applications, including 18 pending in Europe and 7 pending international, or PCT, patent applications.

In countries where the company seeks legal protection through patents, the duration of legal protection for a particular product, method or use, is generally 20 years from the filing date. This protection may be extended in some countries, particularly in the European Union, China, Japan, South Korea, Australia, Canada, and the United States. The protection, which may also vary by country, depends on the type of patent and its scope. In most industrialized countries, any new active substance, formulation, indication or manufacturing process may be legally protected. The company conducts ongoing checks to protect the company’s inventions and to act against any infringement of the company’s patents.

IXIARO

In regards to the company’s Japanese encephalitis vaccine, IXIARO, the company owns a patent family that includes 5 issued U.S. patents (9,884,115; 9,895,437; 9,913,898; 10,668,146; and 11,110,170) with claims covering the aqueous composition of IXIARO and methods for preparing IXIARO, and one pending U.S. patent application. This patent family also includes two granted European patents with claims directed to compositions comprising IXIARO and/or methods for preparing IXIARO, and one pending European patent application. This patent family also included a granted European patent with claims that were directed to compositions comprising an aluminum component (with low heavy metal impurities and in particular low copper impurities) and a protein within formaldehyde inactivated virus particles, and to methods for preparing such compositions that was opposed at the EPO. In the subsequent oral hearing held in March 2020 before the EPO opposition division, the company was able to defend the company’s claims to the method of preparing said composition as granted. The company and the opposer each filed a notice of appeal. In view of the negative preliminary opinion of the Board of Appeal the company decided to withdraw the company’s consent to the patent as granted and thus the patent was revoked in March 2022.Patent applications, if issued, and patents in this family are expected to expire in 2032, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

The company also owns a pending U.S. and a European patent application with claims covering the manufacturing processes of IXIARO and potentially other vaccines. Patent applications, if issued, are expected to expire in 2040, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

DUKORAL

In regards to the company’s DUKORAL product, the company owns an International and a European patent application with claims directed to stable pharmaceutical compositions covering a non-commercialized formulation of DUKORAL and methods of use thereof, and patent applications or applications related to these applications, if issued, are expected to expire in 2041, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. Patents covering the composition of matter of DUKORAL are expired.

The company also owns a pending PCT application with claims covering the use of the cholera bacteria used in DUKORAL in the treatment or prevention of an autoimmune disease. Patent applications claiming the benefit of this PCT application, if issued, are expected to expire in 2041, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

VLA15—Borrelia Vaccine Candidate

In regards to the company’s Borrelia vaccine candidate VLA15 which is licensed to Pfizer, as of December 31, 2022 the company owned a patent family which includes five issued U.S. patents, two pending U.S. patent applications and two European patents that are validated, one in 38 of the European Patent Convention member states and the other in 12 of those member states, as well as 26 foreign patents and 2 patent applications with claims covering the composition of matter of VLA15. The company further owns a second patent family which includes three issued U.S. patents and one granted European patent, as well as 16 foreign patents and five patent applications with claims covering the composition of matter of VLA15. Patent applications, if issued, and patents in these families are expected to expire in 2033 and 2035, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

The company also owns a patent family with claims directed to immunogenic polypeptides with C-terminus domains of OspA to induce a protective immune response that includes patent applications pending in the U.S., Canada, Europe, and Hong Kong. Patent applications, if issued, in this family are expected to expire in 2038, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

As of December 31, 2022, the company also owned two patent families with claims directed to compositions comprising OspA fusion proteins, including uses thereof and to improved methods for producing a vaccine. Both families have been nationalized in Europe, the U.S. and Canada in 2022. Patent applications claiming priority to these patent applications, if issued, are expected to expire in 2041, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The company further co-owns with a third party a patent family which includes pending patent applications in Europe, the U.S. and 13 further foreign jurisdictions. Patent applications claiming priority to these patent applications, if issued, are expected to expire in 2041, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

VLA1553—Chikungunya Vaccine Candidate

In regards to the company’s chikungunya vaccine candidate, VLA1553, as of December 31, 2022, the company owned two patent families that include four granted U.S. patents with claims covering methods of preparing and methods of purifying VLA1553 and two pending European patent applications. Patent applications, if issued, and patents in this family are expected to expire in 2036, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

The company also owns a patent family with claims directed to pharmaceutical compositions of VLA1553 that includes 2 U.S. patents and over 20 pending patent applications in such jurisdictions as the U.S., Europe, Australia, Canada, China, India, Japan, and Mexico. Patent applications, if issued, and patents in this family are expected to expire in 2038, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

As of December 31, 2022, the company also owned two patent families with claims covering formulations and manufacturing processes of VLA1553. Each of these 2 families were nationalized in 17 jurisdictions and all are still pending, if issued, are expected to expire in 2040, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

VLA2001—SARS-CoV-2 Vaccine Candidate

In regards to the company’s SARS-CoV-2 vaccine candidate, VLA2001, as of December 31, 2022, the company owned one pending U.S. patent application and over twenty foreign patent applications with claims relating to the antigen and processes preparing the antigen of VLA2001, furthermore the company co-owns together with Dynavax two patent families with one U.K. patent and over twenty national patent applications with claims related to adjuvant formulation and processes of preparing the formulation of VLA2001. These patent applications, if issued, are expected to expire in 2041, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

VLA84—Clostridium Difficile Candidate

In regards to the company’s C. difficile candidate VLA84, as of December 31, 2022, the company owned a patent family with five granted U.S. patents with claims covering the composition of matter of VLA84 and methods of use thereof, one pending U.S. patent application, five granted and foreign patents and three pending foreign patent applications in such jurisdictions as Australia, China, and Japan. This patent family also includes a granted European patent validated in over 35 countries that has been opposed now has been maintained by the European Patent Office in amended form, which still covers VLA84. A second European patent has not been opposed and a third European patent application is pending. Patent applications, if issued, and patents in this family are expected to expire in 2031, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

The company also filed an opposition in a European patent owned by a third party that has claims that might cover the company’s C. difficile vaccine candidate. The European Patent Office recently revoked this patent and an appeal has been filed and is pending. The company also recently filed a further opposition against a European patent derived from the revoked patent that has claims that might cover the company’s C. difficile vaccine candidate. The European Patent Office has revoked also this patent, and an appeal has been filed and is pending.

VLA1601—Zika Vaccine Candidate

In regards to the company’s Zika vaccine candidate VLA1601, as of December 31, 2022, the company owned a patent family with two granted U.S. patents with claims covering the formulation VLA1601, one pending U.S. patent application, and over 10 pending foreign patent applications and four foreign patents. Patent applications, if issued, and patents in this family are expected to expire in 2036, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The company has received a third party observation against the European patent application of the above case.

The company also owns two patent families that include one granted U.S. patent and three U.S. patents with claims covering methods of preparing and methods of purifying VLA1601 and two pending European patent applications. Patent applications, if issued, and patents in these families are expected to expire in 2036, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. One of the granted U.S. patents has recently been the object of an Inter Partes Proceeding by a third party wherein the proceeding has not been instituted yet.

Trademarks

The company’s key products, technologies and product candidates, namely IXIARO, JESPECT, DUKORAL, EB66 and IC31, and the number of trademarks related to these products held by the company as of December 31, 2022.

The company also holds registrations for the company’s different entities names, as well as the slogan and logo which constitute the company’s graphic charter. The company defend the company’s trademark rights by filling a notice of opposition against applications for identical or similar trademarks, and initiate, if such is the case, legal actions to have the company’s rights recognized.

‘VALNEVA’ Trademark

Valneva SE and the company KRKA, tovarna zdravil, d.d., Novo Mesto signed a co-existence agreement on January 20, 2014, with respect to KRKA’s earlier trademark DALNEVA covering goods of Class 5.

The company agreed on restricting the specification of goods for the trademark Valneva, by adding the limitation ‘none of the afore-mentioned goods for the treatment of cardiovascular diseases’ to the European Union Trademark (EUTM) application No. 011441268, and to any future applications.

Moreover, the company also filed a notice of opposition before the European Union Intellectual Property Office, or EUIPO, against the trademark application VALNECOR (application No. 13.519889) of the company Vetpharma Animal Health S.L., for Class 5, invoking articles 8(1)b and 8(4) of the Regulation (EC) No. 207/2009 on the Community trademark (EUTMR—as amended). On February 19, 2016, the Opposition Division of the EUIPO decided in the company’s favor and upheld the opposition (No. B 2508755) for all the contested goods in Class 5.

The company and Boehringer Ingelheim International GmbH also signed a prior rights agreement on July 28, 2016.

The company filed a notice of opposition before EUIPO against the trademark application VALNOBI n°17579525 made in Class 5 in the name of Bayer AG. On February 4, 2019, the Opposition Division of the EUIPO decided in the company’s favor and upheld the opposition (No. B 3 047 941) for all the contested goods in Class 5.

The company filed notices of opposition against the EU trademark application VALENA no. 017895207 and the Austrian trademark application VALENA no. 295810. The Austrian trademark application was withdrawn and the EU trademark application was rejected to a large part of the contested goods and services, and in particular to all of the goods in class 5.

‘IXIARO’ Trademark

On October 30, 2015, Valneva Austria GmbH acquired from GSK (GlaxoSmithKline Biologics SA, GlaxoSmithKline GmbH and CO.KG) the trademark ‘IXIARO’ and the related trademarks and domain names, for all jurisdictions. No co-existence or prior rights agreements exist for the trademark IXIARO.

OxARO v IXIARO

The company filed an Opposition in 2021 and signed a prior rights agreement with the result that SafeRx withdrew the application OxARO in the U.S. The Settlement Agreement was signed on January 26, 2022. According to the Settlement Agreement SafeRx undertakes to refrain from asserting rights deriving from U.S. Application Serial No. 90/233,007 or use of the trademark OXARO for pharmaceutical preparations and agrees to expressly abandon U.S. Application Serial No. 90/233,007. SafeRx agrees never to use OXARO by itself on a product distributed in the marketplace and will instead use ‘OxARO ER’ and ‘OxARO IR’. SafeRx may use OXARO solely for fundraising for product development and FDA review, but once through FDA review, SafeRx agrees never to use the mark OXARO by itself, but instead will use the marks ‘OxARO ER’ and ‘OxARO IR’.

‘DUKORAL’ Trademark

Various prior rights agreements related to the trademark ‘DUKORAL’ were executed in the years 1996 to 2002. A further prior rights and delimitation agreement between Crucell Sweden AB, now Valneva Sweden AB, and Berlin-Chemie AG was signed on June 29, 2012. For mutual settlement of the opposition filed by then Crucell Sweden AB, Berlin Chemie AG undertakes not to derive any rights from the registration and use of their German trademark DUCORA against the Community Trademark registration of DUKORAL, and to tolerate new applications and modifications of the prior DUKORAL trademark, provided that Crucell Sweden AB shall not apply for the trademark DUCORA. Berlin-Chemie AG restricted the goods and services of their German registration of DUCORA. Then Crucell agreed to the registration or use of German trademark DUCORAL under the conditions specified and to withdraw the opposition. Since this agreement is effective worldwide, the party who possesses prior rights in any country agrees to consent to the registration or use of the other party’s respective mark under the same conditions as mentioned in this agreement.

Domain Names

As of December 31, 2022, the company held 147 domain names (reserved or in the process of being reserved).

Government Regulation

The company’s operations are subject to regulation by various federal, state, and local authorities in addition to the FDA, including but not limited to the Centers for Medicare & Medicaid Services, or CMS, the Department of Health and Human Services, or HHS, (including the Office of Inspector General, Office for Civil Rights and the Health Resources and Services Administration), the U.S. Department of Justice, or DOJ, and individual U.S. Attorney offices within the DOJ, and state and local governments.

The company’s fully owned property, comprising approximately 65,000 square feet of operational manufacturing space, operates under a Manufacturers License from MHRA. The site is qualified to meet required quality standards of several regulatory bodies including FDA, the European Commission, EMA, TGA and Health Canada.

The company’s Solna facility can operate on a multi-product basis and comprises approximately 12,000 square meters. The site is qualified to meet required standards of several regulatory bodies including the competent Swedish authorities, Health Canada and TGA.

The company’s Solna site is operated on a long-term lease under a Manufacturers License from MPA.

The company’s facility in Vienna includes a dedicated Quality unit for Quality control (in vitro and in vivo) and Quality Assurance. This unit covers both proprietary and third party products. As such, this facility is registered with the FDA and operated under respective licenses from the Austrian Agency for Health and Food Safety. In Vienna, where the company has centralized its product development capabilities the company also has a GMP technical development unit that establishes the company’s new vaccines prior to the final industrialization stage.

Research and Development

The company’s research and development expenses were €104.9 million for the year ended December 31, 2022.

History

Valneva SE was founded in 1998. The company was incorporated in France in 1999.