About Barinthus Biotherapeutics

Vaccitech plc operates as a clinical-stage biopharmaceutical company. The company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases, cancer, and autoimmunity. The company intends to treat and prevent infectious diseases and cancer by using the company’s proprietary platforms to develop product candidates that stimulate powerful, targeted immune responses against pathogens, infected cells, and tumor cells. The company designs these product candidates to stimulate immune responses that are robust, highly specific, and are differentiated by the magnitude of the T cell populations induced, which exhibit critical functionality and durability. In the field of autoimmunity, the company uses its proprietary platform to develop product candidates that are designed to induce regulatory T cells to suppress specifically pathogenic autoimmune responses and prevent/reverse autoimmunity. The company is focused on applying its platform capabilities and the expertise of the company’s team to address significant unmet medical needs in two settings—the therapeutic setting, for the treatment of chronic infectious diseases, cancer, and autoimmunity; and the prophylactic setting, for the prevention of infectious diseases, based on the company’s platform’s ability to respond rapidly to epidemic and pandemic threats. The company has a broad pipeline of both clinical and preclinical stage therapeutic and prophylactic programs. The company’s therapeutic programs include VTP-300 for the treatment of chronic hepatitis B infection, or CHB, VTP-200 for the treatment of human papilloma virus infection, or HPV, VTP-850 for the treatment of prostate cancer, VTP-600 for the treatment of non-small cell lung cancer, or NSCLC, VTP-1000 for the treatment of celiac disease, and VTP-1100 for the treatment of HPV-associated cancers. The latter two programs are designed to utilize the company’s SNAPvax platform. The company’s prophylactic programs include VTP-400 for the prevention of herpes zoster, or shingles, and VTP-500 for the prevention of Middle East respiratory syndrome, or MERS. In addition, the company co-invented a COVID-19 vaccine with the University of Oxford, the rights to which the company assigned to Oxford University Innovation, or OUI, to facilitate the license of those rights by OUI to AstraZeneca UK Limited, or AstraZeneca. The vaccine is authorized for use under the marketing name Vaxzevria in a number of countries. AstraZeneca has exclusive worldwide rights to develop and commercialize Vaxzevria. The company’s SNAPvax tolerizing platform is consisted of several self-antigens involved in the disease associated with a tolerizing immunomodulator. It is specifically designed to induce self-antigen-specific regulatory T cells, whose main function is to control immune responses by means of direct cell-cell contact, release of soluble factors, or indirectly via antigen-presenting cells, thereby controlling hyperactive autoreactive pathogenic T cells specifically. Platforms The company’s proprietary platforms comprise several components that either 1) when combined, allow the company to develop product candidates designed to induce high and durable levels of antigen-specific T cells and B cells to prevent and treat infectious diseases and cancer, or 2) induce regulatory T cells and/or decrease T cell activation to specifically control autoreactive immune cell hyperactivity. The key elements of the company’s first platform include its proprietary modified simian adenoviral vectors, known as ChAdOx1 and ChAdOx2, as well as the well-validated Modified Vaccinia Ankara, or MVA, boost vector, both with demonstrable tolerability profiles and an inability to replicate in humans. Both ChAdOx1 and MVA have favorable tolerability profiles, based on extensive clinical testing performed by the company and others. MVA has also been administered in commercial use and in multiple clinical trials to over 130,000 people without significant safety issues, including 120,000 of whom received it as a next-generation smallpox vaccine in Germany. The combination of a ChAdOx prime with MVA boost has consistently generated significantly higher magnitudes of CD8+ T cells as compared to other technologies and approaches. The company has also developed proprietary enhancements for both the company’s ChAdOx and MVA vectors to increase T cell induction and response, and the company employs unique antigen design strategies to optimize in vivo immune presentation and maximize the desired type of immunogenicity while maintaining an optimal tolerability profile. In addition, the company’s understanding and expertise in manufacturing optimization has allowed the company to manipulate adenovirus genomes to enable rapid generation of recombinant adenoviral vectors at Good Manufacturing Practice, or GMP, standards at exceptional speed and significant scale. With the acquisition of Avidea Technologies, Inc. or Avidea, in December 2021, the company has added SNAPvax to its proprietary platforms. SNAPvax is a modular immunotherapy platform that is designed to leverage self-assembling nanoparticles containing multiple targeted peptide antigens and immunomodulators to key immune cell populations for promoting T cell immunity. A recent article in Nature Biotechnology described SNAPvax as among the most effective immunotherapy platforms for inducing T cell immunity reported to date. Another article in Nature Biotechnology reported that SNAPvax enables repeated intravenous, or IV, administration to maximize efficacy. Within oncology, the company is advancing assets based on the SNAPvax cancer immunotherapy platform, or SNAPvax CI, co-delivering tumor antigens and an immunostimulant (TLR7/8a) for use in heterologous prime-boost regimens for treating advanced cancers. SNAPvax CI is designed to provide a unique advantage as compared to other cancer immunotherapy candidates as it can be repeatedly administered to engage every stage of the cancer immunity cycle (T cell priming and expansion; tumor inflammation; T cell recruitment; and T cell licensing) to potentially maximize therapeutic benefit. Outside oncology, the company is advancing assets based on the SNAPvax tolerizing immunotherapy platform, or SNAPvax TI, to treat autoimmune diseases with known autoantigens. SNAPvax TI contains autoantigens and immunomodulators (e.g., mTOR inhibitors) to specifically induce regulatory T cells, crucial to maintaining tolerance to self-antigens. Its unique design allows for trafficking to lymphoid organs and local tissues, where Treg induction occurs and their activity is required to maximize therapeutic benefit. The company has several therapeutic programs in the company’s pipeline focusing on infectious diseases, oncology and immune tolerance. Pipeline VTP-300: An Immunotherapeutic Targeting Chronic HBV Infection In May 2022, the company completed the last patient visit in the company’s HBV001 Phase 1 clinical trial in the United Kingdom. Two types of participants were enrolled: healthy participants and participants with CHB whose infection has been suppressed with oral antiviral therapies. The primary objective of the HBV001 trial is to evaluate the safety and tolerability of different doses of a single vaccination of ChAdOx1-HBV. In addition, the secondary objectives are to determine the immunogenicity of ChAdOx1-HBV and to determine the effect of ChAdOx1-HBV on the level of HBsAg in the participants with chronic HBV infection. All cohorts of healthy volunteers and patients with chronic HBV infection have completed treatment and follow up. No serious adverse events have been reported as of the date of this report. The company has used genotype C HBV antigen sequences in the company’s VTP-300 vectors to target the most prevalent CHB genotype. However, VTP-300 may induce cross-reactive T cell responses with other prevalent genotypes. Therefore, the company also intends to determine if the T cell responses induced by the ChAdOx1-HBV viral vector used in this trial can potentially cross-react with other common HBV genotypes. In addition, the company is conducting a Phase 1b/2a clinical trial, HBV002, to evaluate the safety and reactogenicity of VTP-300 with or without a low-dose (0.3 m/kg) anti-PD-1 in CHB patients whose infection has been suppressed with oral antiviral medication. HBV002 enrollment was completed in May 2022. In the HBV002 trial, the company enrolled CHB patients in four treatment groups. The primary objective of this trial is to determine the safety and reactogenicity of the following in participants with chronic HBV infection and virally suppressed with oral antiviral medication: 1. MVA-HBV (prime-boost); 2. ChAdOx1-HBV and MVA-HBV (prime-boost); 3 and 4 ChAdOx1-HBV and MVA-HBV and nivolumab (prime-boost + anti-PD-1). The secondary objectives are to evaluate immunogenicity, PD-1 blockade timing, and the effect on the levels of hepatitis B markers, including HBsAg, hepatitis B surface antibody seroconversion, hepatitis B DNA, HBeAg, in CHB patients. The majority of the patients were recruited in Taiwan and South Korea and these territories were selected due to the high prevalence of HBV genotype C virus in Asia. Patients were also enrolled in the United Kingdom. Since the participants are already infected with HBV, the company thought it was possible that natural priming could eliminate the need for the prime-boost regimen. Hence, Group 1 of the HBV002 trial was designed to compare MVA-HBV given twice with the ChAdOx1-HBV plus MVA-HBV heterologous approach used in Group 2. The company expected that the regimen given to Group 2 would be more immunogenic and planned to further explore this prime/boost regimen in Groups 3 and 4. The dosing regimen was ChAdOx1-HBV (day 0) and MVA-HBV and low-dose nivolumab (day 28) for Group 3 and ChAdOx1-HBV and low-dose nivolumab (day 0) and MVA-HBV and low-dose nivolumab (day 28) for Group 4. In the cancer field, the use of an anti-PD-1 prior to vaccination has been reported to result in diminished T cell responses as compared to later administration. Whether the anti-PD-1 can be given simultaneously with the priming dose, or should follow it, is yet to be determined. Thus, in this protocol, the company evaluated both regimens. Group 3 employed the low dose nivolumab given only at the boost, whereas Group 4 administered the nivolumab at both the prime and the boost dose. Nivolumab has been used in earlier immunotherapy trials at 1/10 the licensed dose for oncology indications and has been shown to give full peripheral blood T cell receptor occupancy for up to over one month. An interim analysis of HBV002 was conducted in November 2021, after which the protocol was amended to stop enrollment in two cohorts: those receiving MVA prime and boost, Group 1, and those receiving VTP-300 with low dose nivolumab administered with both the ChAdOx1 prime and the MVA booster dose, Group 4. Enrollment continued in the cohort receiving VTP-300 as a monotherapy and the cohort receiving VTP-300 with a single low dose of nivolumab administered with the MVA booster dose. The interim analysis from the HBV002 Phase 1b/2a suggests that VTP-300 could become part of a regimen that can attain a functional cure. In October 2022, the company dosed its first patient in HBV003, a Phase 2b clinical trial to explore the optimal regimen. Although VTP-300 encodes genotype C antigens, many of these peptides are also expressed by other HBV genotypes. The company’s data indicate that VTP-300 is capable of inducing responses to non-genotype C HBVs, so the company will intend to demonstrate activity against non-genotype C infected patients. The company will also plan to evaluate additional combination regimens, such as next-generation modalities, including RNA interference molecules, and may evaluate further potential collaboration partnerships. The company may also evaluate VTP-300 in a trial in mainland China. EASL and AASLD Poster Update to Interim Analysis of Safety and Efficacy Data from HBV002 Study On June 22, 2022, the company announced an update to the interim analysis of safety and efficacy data from the HBV002 study (NCT04778904). On November 7, 2022, the company announced an update to the interim analysis of safety and efficacy data from the HBV002 study (NCT04778904). Future Development In October 2022, the company dosed the first patient in HBV003, a Phase 2b clinical trial of VTP-300 (NCT05343481) to explore the impact of different regimens of low dose Nivolumab and additional doses of the MVA boost component of VTP-300. In addition, a trial that uses a lead-in of the Arbutus siRNA AB-729, followed by a blinded randomization to either placebo or VTP-300, is now underway under Arbutus sponsorship with a planned enrollment of 20 patients per arm (placebo vs VTP-300 after the 6 month siRNA lead-in). The trial also plans a prospective, well-defined, nucleotide discontinuation protocol for those patients who reach substantial reduction in the level of hepatitis B surface antigen. The company expects to announce interim efficacy data from both the HBV003 study and the combination study with siRNA from Arbutus in the fourth quarter of 2023. VTP-200: Developing a Potential Non-Invasive Treatment for Persistent High-Risk HPV The company is developing VTP-200 as a potential curative treatment for persistent high-risk HPV infection and associated pre-cancerous lesions. An estimated 291 million women worldwide are carriers of HPV DNA, which can progress to pre-cancerous cervical lesions if untreated. Enrollment in the company’s Phase 1b/2 clinical trial of VTP-200, HPV001 (NCT04607850), was completed in December 2022. Preclinical Studies Extensive preclinical studies were conducted using VTP-200, with resulting data showing that VTP-200 was well tolerated in preclinical toxicology studies; and VTP-200 was highly immunogenic in inbred and outbred mice. Toxicology Studies In a GLP-compliant toxicology study, outbred mice were dosed with ChAdOx1-HPV and MVA-HPV at dose levels approximating the maximum anticipated clinical dose. Dosing resulted in an immune response, but with no significant toxicology findings. Immunogenicity Studies In preclinical immunogenicity studies, the HPV antigen was delivered by plasmid DNA, ChAdOx1 and MVA vectors in prime-boost regimens to inbred and outbred mice. ChAdOx1-HPV prime followed by MVA-HPV boost was shown to induce higher magnitude and more durable HPV-specific T cell responses than other regimens, as shown in the figure below. VTP-200-induced T cells were polyfunctional and persisted at high frequencies for at least six weeks. In the preclinical immunogenicity studies, HPV-specific effector CD8+ T cells were detected in the cervix following systemic administration of ChAdOx1-HPV prime and followed by MVA-HPV boost. Finally, T cells specific for the HPV-encoded antigens were detected in women with or past hrHPV infections, confirming the presence of immunogens relevant to natural immune control. The MVA vector assessed in initial studies contains the HPV antigen at the thymidine kinase locus under the control of the p7.5 promoter. However, a more immunogenic MVA vector, which contains the HPV antigen under the control of the endogenous F11 promoter, was constructed. The company determined that the T cell immunogenicity of the more immunogenic MVA promoter was superior to the MVA vector assessed in the initial preclinical studies and decided to use the next-generation vector in the company’s clinical trials. Clinical Development The company’s HPV001 Phase 1b/2 clinical trial of VTP-200 was designed to assess the safety and efficacy of VTP-200 and determine the optimal immunotherapeutic dose regimen. The company enrolled a total of 108 healthy women with low grade lesions who had persistent high-risk HPV, or hrHPV, for at least six months. Patients with high-grade squamous intraepithelial lesions, or HSIL, or early cancer were excluded. The trial was run in the United Kingdom and the European Union. The company recently announced the topline initial interim immunogenicity and safety data of 58 patients in the main phase of the trial that reached their six-month evaluation timepoint. The company expects to announce full data from this trial in the first quarter of 2024. The HPV001 Phase 1b/2 clinical trial was designed to identify an efficacious dose based on a joint response index of CD8+ T cell magnitude, CD4+T cell magnitude and CD4+ T cell avidity. The primary objective of the trial was to evaluate the safety and tolerability of ChAdOx1-HPV plus MVA-HPV when administered in a prime-boost regimen. The secondary objectives of the trial were to determine the optimal dose and to evaluate the efficacy of HPV001 on the clearance of hrHPV infection and on the cervical intraepithelial neoplasia, or CIN. Future Development Following the HPV001 Phase 1b/2 clinical trial, if successful, the company intends to initiate further clinical trials of VTP-200. The company’s next trials would potentially be a Phase 2/3 trial in healthy women with early grade CIN (squamous intraepithelial lesions, or LSIL) and additional trials in patients with more advanced CIN, vulval intraepithelial neoplasia, or VIN, and anal intraepithelial neoplasia, or AIN. The company is also in the early stages of collaborating on an NIH-funded trial that would be conducted by the University of California San Francisco in more advanced CIN and AIN in human immunodeficiency virus, or HIV, positive patients, to be recruited in Mexico and Puerto Rico. VTP-850: The company’s Next-Generation Immunotherapeutic Candidate for Prostate Cancer The company is developing VTP-850, its next-generation prostate cancer product candidate, to improve upon VTP-800. Both VTP-800 and VTP-850 are composed of a heterologous prime-boost regimen with ChAdOx1 prime and MVA boost; however, VTP-800 encodes only one antigen, 5T4, while VTP-850 encodes four antigens, PSA, PAP, STEAP1 and 5T4. The company designed VTP-850 to induce a broader immune response by encoding multiple antigens to reduce the ability of cancer cells to evade the immune response by mutating or losing expression of any one antigen. The antigens the company encodes in VTP-850 are expressed in most prostate cancers but have little or no expression on healthy tissues other than prostate. Clinical Development Phase 1 and Phase 2 clinical trials of VTP-800 were sponsored and conducted by the University of Oxford in the United Kingdom. VANCE was a first-in-human, open-label, randomized, Phase 1 clinical trial designed to evaluate the safety and immunogenicity of heterologous prime-boost ChAdOx1-MVA administration as compared with homologous prime-boost with MVA alone, with and without low dose cyclophosphamide in localized prostate cancer. Thirty-nine patients with early stage localized, castration-sensitive prostate cancer were treated. Thirty-three patients received heterologous prime-boost with ChAdOx1-5T4 and MVA-5T4, while six patients received homologous prime-boost with MVA-5T4 alone. Patients received both regimens alone or with cyclophosphamide preconditioning. VTP-800 was generally well tolerated, with side effects of local injection site pain, fatigue, feverishness, and myalgia, which are consistent with those observed for these vectors in other clinical trials. There were no reported treatment-related serious adverse events. T Cell Response in Patients ADVANCE was an open-label, non-randomized Phase 2 clinical trial of VTP-800 in combination with anti-PD-1 checkpoint inhibitor, nivolumab, in 23 patients with metastatic prostate cancer. The primary objectives of the ADVANCE trial were to assess the safety and response rate of VTP-800 when administered in combination with nivolumab. The secondary objectives were to assess the immune responses in peripheral blood and to evaluate radiographic progression-free survival and overall survival. Patients received ChAdOx1-5T4 prime and MVA-5T4 boost one month later. Nivolumab was administered at months one, two and three. In most patients, VTP-800 was also given at months three and four. All patients received 2.5 x 10^10 vp of ChAdOx1-5T4, 2.0 x 10^10 pfu of MVA-5T4 and 480mg of nivolumab. VTP-800 was generally well tolerated. The most common treatment emergent adverse events were bone pain, injection site pain, muscle pain, stomatitis, and constipation, and most were mild and grade 1 or 2. The only grade 3 adverse event was a chest infection, which was not related to study drug. There were no grade 4 or 5 treatment-related adverse events. Three of eight patients with measurable disease had partial tumor responses. Future Development The FDA accepted the company’s IND for VTP-850 to be evaluated in PCA001, a Phase 1/2 open-label clinical trial in patients with rising PSA after definitive local therapy for prostate cancer, commencing in the first quarter of 2023. The company plans to conduct the trial in several countries, including the United States. The trial will involve a Phase 1 dose finding stage with boost dose administered either intramuscularly or intravenously to determine the Phase 2 recommended dose and route of administration, followed by a two-stage expansion phase to evaluate immunogenicity and anti-tumor activity of VTP-850. VTP-1100: The company’s first product utilizing SNAPvax CI platform for HPV16+ cancers VTP-1100 is the company’s first product candidate leveraging the SNAPvax platform technology – brought into Vaccitech following the acquisition of Avidea in December 2021 – that will enter clinical testing. VTP-1100 differs from VTP-200 in composition and patient population targeted: VTP-1100 will use a configuration of SNAPvax that is designed to elicit antigen-specific CD8+ T cells against HPV16+ cancers, either when administered alone or when used in a potent heterologous prime-boost regimen with the established ChAdOx1 platform. Preclinical studies in mice have shown that the SNAPvax-ChAdOx prime-boost induced superior T cell responses as compared with single or dual agent therapies. Status and Future Development VTP-1100 is in the preclinical stage with GMP manufacturing and pivotal IND-enabling studies underway. The company received pre-IND feedback from the FDA in July 2022, and based on the agency’s feedback expect to file an IND in the second half of 2023. VTP-1000: Antigen-specific tolerizing immunotherapy candidate for celiac disease Patients with celiac disease have an unwanted immune response against gluten proteins and can become severely ill following exposure to gluten found in various cereal grains, especially wheat. VTP-1000 is a tolerizing immunotherapy that is designed to induce antigen-specific regulatory T cells (Tregs) that promote tolerance and suppress the unwanted immune response to gluten. VTP-1000 is the second product candidate based on the SNAPvax platform, designed to leverage its plug-and-play modularity to induce an entirely different type of T cell compared to the configuration utilized in VTP-1100. VTP-1000 comprises multiple gluten antigens (representing the key epitopes linked to celiac disease) and an immunomodulator co-delivered in nanoparticles of precise size and composition that are optimized to target immune cells that prime and expand Tregs. While the SNAPvax tolerizing immunotherapy is based on the same platform technology as the SNAPvax cancer immunotherapy enabling VTP-1100, an important distinction is that the tolerance immunotherapy includes an immunosuppressive immunomodulator that drives Treg expansion and prevents proinflammatory responses. Status and Future Development VTP-1000 is in preclinical development. Preclinical lead optimization studies were recently completed and the product is entering engineering manufacturing, which the company expects will enable the company to enter first-in-human testing in a dose-escalation and challenge study by the end of 2023, pending submission and FDA clearance of an IND. Vaccitech plans to include pharmacodynamic analysis as part of the Phase 1 study to provide an indication that the immunotherapy is inducing Tregs. Importantly, Vaccitech also intends to include a controlled gluten challenge in the Phase 1 study (for example, see Goel G, et al. Science Advances (2019) Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease). This controlled gluten challenge is intended to provide an early biologic signal that VTP-1000 suppresses pathological response to gluten ingestion. As VTP-1000 is the company’s first product candidate directed towards the treatment of an inflammatory disease, the demonstration of Treg induction and/or suppression of unwanted immune responses to gluten would pave the way for other therapies based on the SNAPvax tolerizing immunotherapy platform, including those for allergies and other autoimmune indications. VTP-600: The company’s Immunotherapeutic Candidate Targeting MAGE-A3 and NY-ESO1 Antigens The company is developing VTP-600, its immunotherapy candidate designed to encode the tumor-associated antigens MAGE-A3 and NY-ESO1 initially for the treatment of NSCLC in combination with standard of care treatment, chemotherapy and pembrolizumab. Lung cancer is the most common cancer diagnosis and cause of cancer death worldwide, with 85% of cases classified as NSCLC. About 25% to 30% of NSCLC patients have squamous histology and the remainder have non-squamous histology. MAGE-A3 is expressed in 48% of squamous NSCLC and 24% of non- squamous NSCLC. NY-ESO1 has been shown to have an expression rate of 27% across all NSCLC types. The company initiated a first-in-human Phase 1/2a trial in the first quarter of 2022, in collaboration with Cancer Research UK, or CRUK, which is sponsoring and funding this study. VTP-400: A Prophylactic Vaccine Product Candidate for Shingles Beyond the company’s therapeutic programs, the company is also developing several prophylactic vaccine candidates. VTP-400 is the company’s vaccine candidate in development to prevent shingles in adults aged 50 years and older. There are an estimated 140 million cases globally of shingles each year, which can result in significant post-infection pain, known as post-herpetic neuralgia, or even death. The company’s regional partner in China and Southeast Asia, CanSino, plans to initiate a Phase 1 clinical trial of VTP-400 for shingles prevention. VTP-500: A Prophylactic Vaccine Candidate to Prevent MERS The company is developing VTP-500 as a vaccine product candidate to prevent infection and subsequent disease caused by the MERS coronavirus. Although human-to-human transmission appears to be rare, MERS coronavirus has the potential to cause epidemics, infecting hundreds of thousands of people and causing significant morbidity and mortality in 34% of infected individuals. Clinical efficacy trials to prevent MERS are challenging to execute due to the sporadic nature of infection, however studies have demonstrated positive Phase 1 safety and immunogenicity infections data. In November 2021, VTP-500 results from the Saudi Arabia Phase 1 study were published in The Lancet Microbe. The Phase 1 data showed that VTP-500 was generally well tolerated in patients, and further development of the product candidate is planned by the company’s non-exclusive licensee, the University of Oxford. Vaxzevria: A Prophylactic Vaccine for the Prevention of COVID-19 Infection The company’s platform also positions the company to develop vaccines rapidly to address epidemic and pandemic threats, as demonstrated by the speed of the initiation of clinical trials of Vaxzevria (formerly VTP-900 and AZD1222) for the prevention of COVID-19, which entered the clinic within three months from initial antigen design. The company co-invented its first-generation COVID-19 vaccine candidate VTP-900, now Vaxzevria, in partnership with the University of Oxford’s Jenner Institute, which the company assigned to OUI to facilitate the licensing of those rights by OUI to AstraZeneca. Vaxzevria, uses the ChAdOx1 vector, and encodes the SARS-CoV2 spike protein. On June 28, 2021, a sub-analysis from the Oxford-led COV001 and COV002 trials showed that Vaxzevria induced strong immune responses following either a prolonged second dose interval of up to 45 weeks or following a third boosting dose. The results, published by the University of Oxford in The Lancet on September 1, 2021, demonstrated that antibody levels remain elevated from baseline for at least one year following a single dose. An extended interval between the first and second dose of Vaxzevria of up to 45 weeks, resulted in up to an 18-fold increase in antibody response, measured 28 days after the second dose. With a 45 week dosing interval between the first and second dose, antibody titres were four times higher than with a 12 week interval, demonstrating that a longer dosing interval is not detrimental but can derive stronger immunity. In addition, a third dose of Vaxzevria, given at least 6 months after a second dose, boosted antibody levels six-fold and maintained T cell response. A third dose also resulted in higher neutralising activity against the Alpha, Beta, and Delta variants. On January 13, 2022, AstraZeneca announced positive results from a preliminary analysis of an ongoing safety and immunogenicity trial which showed that Vaxzevria, when given as a third dose booster, increased the immune response to Beta, Delta, Alpha and Gamma SARS-CoV-2 variants, while a separate analysis of samples from the trial showed increased antibody response to the Omicron variant. The results were observed among individuals previously vaccinated with either Vaxzevria or an mRNA vaccine. AstraZeneca also announced that the vaccine has been granted a conditional marketing authorization or emergency use in more than 90 countries. It also has Emergency Use Listing from the World Health Organization, which accelerates the pathway to access in up to 144 countries through the COVAX Facility. Collaboration and License Agreements 2016 License Agreement with OUI In March 2016, the company entered into a license agreement, or the 2016 OUI License Agreement (as amended in January 2019 and April 2020), with OUI (previously known as Isis Innovation Limited) for the development and commercialization of vaccines for influenza, cancer (including therapeutic and prophylactic vaccines and including cancer associated with viral infections), varicella zoster and MERS. The company refer to these areas together as the ‘Field.’ Pursuant to the 2016 OUI License Agreement, OUI granted the company a worldwide license under certain patent rights of OUI, including rights related to the use of ChAdOx1, ChAdOx2, adenoviral and MVA promoters and influenza product candidates, among other rights, or the Licensed Technology, to develop, manufacture, use and commercialize licensed products. The rights are exclusive in certain fields and non-exclusive in others. The company’s license to certain patents and applications relating to certain adenoviral vectors encoding a pathogen or tumor antigen and certain pox virus expression systems is exclusive within the Field, non- exclusive in all other fields, and excludes veterinary applications. The company’s license to certain patents and applications relating to certain compositions and methods is exclusive in all fields and excludes veterinary applications. The company’s license for the use of the ChAdOx1 vector under certain patents and applications relating to certain simian adenovirus and hybrid adenoviral vectors is exclusive in the Field, non-exclusive in all other fields, and excludes veterinary applications (apart from MERS) and certain specified indications. Furthermore, the company’s license with respect to the use of the ChAdOx2 vector under certain patents and applications relating to certain adenoviral vectors is exclusive in certain vaccine-related fields, non- exclusive in all other fields, and excludes all veterinary applications (apart from MERS) and certain other specified indications. In addition, the company obtained a license to certain clinical data generated from OUI projects and related confidential know-how to develop, manufacture, use and commercialize licensed products, and such license is exclusive in the Field, other than with respect to know-how related to ChAdOx2, which is licensed non-exclusively. The Licensed Technology is sublicensable subject to obtaining OUI’s prior written consent (such consent not to be unreasonably withheld, conditioned or delayed) and inclusion in any sublicense agreement of restrictions on further sub-licensing, among other terms and conditions. 2017 License Agreement with OUI In September 2017, the company entered into a further license agreement with OUI, or the 2017 OUI License Agreement, for the development and commercialization of immunotherapies for HBV and HPV. Pursuant to the 2017 OUI License Agreement, the company acquired a worldwide license under certain additional patent rights of OUI, including rights related to the use of HBV immunotherapy product candidates, HPV immunotherapy product candidates and shark invariant chain polypeptides, among other rights, or the 2017 Licensed Technology, to develop, manufacture, use and commercialize licensed products. The rights are exclusive in some fields and non-exclusive in others. The company’s license to certain patents and applications relating to certain HBV and HPV vaccines is exclusive in all fields. The company’s license to certain patents and applications relating to molecular adjuvants is non-exclusive in the field of HBV. The company’s license to certain patents and applications relating to certain simian and hybrid adenoviral vectors is exclusive in the fields of HPV associated diseases and HBV. Further, the company’s license to certain patents and applications relating to certain other vectors is exclusive in the field of HBV. Pursuant to the 2017 OUI License Agreement, the company also obtained a non-exclusive license under related know- how to develop, manufacture, use and commercialize licensed products in all fields. The 2017 Licensed Technology is sublicensable subject to obtaining OUI’s prior written consent (such consent not to be unreasonably withheld, conditioned or delayed) and inclusion in any sublicense agreement of restrictions on further sub-licensing, among other terms. 2017 License Agreement with OUI (Vaccitech North America, Inc.) In March 2017, Avidea Technologies Corporation (‘Avidea’) entered into a license agreement with OUI for the development and commercialization of products comprising thermo-responsive adjuvant scaffolds for use in all indications. All of Avidea’s rights, duties and obligations under the 2017 OUI License Agreement were assumed by Vaccitech North America, Inc. (‘Vaccitech NA’) following the acquisition of Avidea by Vaccitech plc. on December 10, 2021. Pursuant to the 2017 OUI License Agreement, OUI granted the company a worldwide license under certain patent rights of OUI related to the use of thermo-responsive adjuvant scaffolds, among other rights, or the Licensed Technology, to develop, manufacture, use and commercialize licensed products. The license to patent rights are exclusive in all fields, and the license to know how is non-exclusive. The Licensed Technology is sublicensable subject to obtaining OUI’s prior written consent (such consent not to be unreasonably withheld, conditioned or delayed) and inclusion in any sublicense agreement of restrictions on further sub-licensing, among other terms and conditions. 2017 Cooperative Research and Development Agreement with NIH (Vaccitech North America, Inc.) In February 2017, Avidea entered into a Cooperative Research and Development Agreement (‘CRADA’) with the U.S. National Institutes of Health (‘NIH’) to carry out collaborative research for the evaluation of Avidea’s synthetic, polymer-based vaccine technology, ‘Immunotherapeutic Nanoscaffolds’ (IMNs) for infectious disease prevention and cancer treatment in animal models. Under this CRADA Avidea committed to providing scientific staff together with materials for use in experiments to evaluate their performance in various animal models of infectious disease and cancer. Under this CRADA NIH committed to evaluating Avidea materials in animal models and to perform comprehensive immune analysis. No funding was exchanged under this CRADA. 2019 License Agreement with NIH (Vaccitech North America, Inc.) In September 2019, Avidea entered into a license agreement with the U.S. National Institutes of Health (‘NIH’) for the commercial development of products and processes for the prevention and/or treatment of cancer and infectious diseases within the scope of Licensed Patent rights that had been developed under a Cooperative Research and Development Agreement (‘CRADA’) entered into by NIH and Avidea in February 2017 and amended in March 2019, December 2020, May 2021, November 2021 and October 2022. The company is co-owners of all the Licensed Patents under this agreement, and the company has an option to exclusively license NIH rights in all inventions made under this CRADA. 2017 Research Collaboration Agreement (‘RCA’) with Institute of Macromolecular Chemistry, Prague (Vaccitech North America, Inc.) In September 2017, Avidea entered into a Research Collaboration Agreement (‘RCA’) with the Czech Institute of Macromolecular Chemistry, (‘IMC’) to carry out collaborative research for the development of polymer-based immunotherapies for cancer treatment, HIV prevention and recombinant protein delivery. Under this RCA Avidea committed to providing bioactive moecules and to developing and deploying animal models for evaluating immunotherapies. Under this RCA IMC committed to synthesizing various polymers and bioactive molecules and to linking such polymers and bioactive molecules for use in experiments to characterize their physicochemical properties. No funding was exchanged under this RCA. All of Avidea’s rights, duties and obligations under the 2017 RCA with IMC were assumed by Vaccitech North America, Inc. (‘Vaccitech NA’) following the acquisition of Avidea by Vaccitech plc. on December 10, 2021. 2022 License Agreement with IMC (Vaccitech North America, Inc.) In April 2022, the company entered into an exclusive license agreement with the Czech Institute of Macromolecular Chemistry, (‘IMC’) for the exploitation, development and commercialization of technologies and products within the scope of Licensed Patent rights that had been developed under a Research Collaboration Agreement (‘RCA’) entered into by IMC and Avidea in September 2017. The company is co-owners of all the Licensed Patents under this agreement, and the company has an option to exclusively license IMC rights in all inventions made under this RCA. Pursuant to the 2022 License Agreement with IMC, IMC granted the company a worldwide, exclusive license under certain patent rights co-owned by the company and IMC related to the use of polymer-based immunotherapies, among other rights, or the Licensed Technology, to develop, manufacture, use and commercialize licensed products. The license to patent rights is exclusive in all fields. The Licensed Technology is sublicensable. 2019 License Agreement with OUI In January 2019, the company entered into an additional license agreement with OUI, or the 2019 OUI License Agreement. Pursuant to the 2019 OUI License Agreement, OUI granted the company a worldwide, license under an additional patent application of OUI related to the rapid production of recombinant adenovirus constructs, to be used as personalized cancer vaccines or emerging pathogen vaccines, and related confidential know-how, or the 2019 Licensed Technology, to develop, manufacture, use and commercialize licensed products. The license is exclusive in the field of personalized cancer vaccines for therapeutic use in humans, non- exclusive in in all other fields and excludes veterinary applications (apart from MERS) and certain other specified indications. The license is sublicensable subject to obtaining OUI’s prior written consent (such consent not to be unreasonably withheld, conditioned or delayed) and inclusion in any sublicense agreement of restrictions on further sub-licensing, among other terms. 2018 License Agreement with OUI and Oxford In September 2018, the company entered into a license agreement, or the 2018 License Agreement, with The Chancellor, Masters and Scholars of the University of Oxford, or Oxford, and OUI. Pursuant to the 2016 OUI License Agreement, OUI had granted the company certain exclusive rights related to the Licensed Technology, as defined in the 2016 OUI License Agreement, in the field of diagnosis, prevention and treatment of MERS. The 2018 License Agreement enables Oxford to grant a further sublicense to CEPI in the field of MERS, or the Field, and to enable Oxford to conduct related activities. OUI License Agreement Amendment In April 2020, the company entered into an amendment, assignment and revenue share agreement, or the OUI License Agreement Amendment, with OUI to amend the 2016 OUI License Agreement. Pursuant to the 2016 OUI License Agreement and among other rights and obligations, OUI granted to the company a non-exclusive license to certain patent applications relating to its ChAdOx1 and ChAdOx2 vaccine vectors and the adenovirus long promoter for use in certain fields, or the Field, including SARS-CoV2, which is the virus known to cause COVID-19. The OUI License Agreement Amendment was entered into to enable a single exclusive license agreement for a COVID-19 vaccine co-developed by the company and the University of Oxford’s Jenner Institute to be negotiated with a suitable pharmaceutical partner. Master Collaboration Agreement with CanSino Biologics Inc. In September 2018, the company entered into a master collaboration agreement, or the CanSino Agreement, with CanSino Biologics Inc., or CanSino. The CanSino Agreement provides a framework under which the company can agree with CanSino (in separate project agreements) the details of one or more collaborative projects for the development and commercialization of certain products, and carry out those projects under the terms of the CanSino Agreement and the respective project agreements in the company’s respective territories. Under the CanSino Agreement, the CanSino Territory includes China (including Taiwan, Hong Kong and Macao), Malaysia, Thailand, Myanmar, Indonesia, Laos, Vietnam, and the Philippines, while the company’s territory, or the Vaccitech Territory, includes the rest of the world. 2018 ChAdOx Zoster Project Agreement (under the CanSino Agreement) Pursuant to the CanSino Agreement, the company entered into a project agreement in September 2018 with CanSino, or the ChAdOx Zoster Project Agreement, with the intention of developing a Zoster vaccine to become a competitor to Shingrix. Under the ChAdOx Zoster Project Agreement, the company is responsible for funding and undertaking various development tasks, including (subject to availability of funding) conducting a Phase 1 clinical trial in the UK. CanSino is responsible for funding and undertaking various development tasks, including conducting a Phase 1 clinical trial in China. Clinical Trial and Option Agreement with Cancer Research UK In December 2019, Vaccitech Oncology Limited, or VOLT, entered into a clinical trial and option agreement, or the Clinical Trial Agreement, with CRUK and CRUK’s subsidiary, Cancer Research Technology Limited, or CRT, relating to the conduct of a Phase 1/2a clinical trial of VOLT’s VTP-600 immunotherapy product in patients with non-small cell lung cancer, or the Clinical Trial. The trial opened in the first quarter of 2022 across multiple clinical sites in the U.K. VOLT is the company’s oncology focused strategic collaboration with the Ludwig Institute for Cancer Research, an international non-profit organization that conducts innovative cancer research and is looking to enable the clinical development of new treatments that induce and harness CD8+ T cells of the immune system to fight cancer. VOLT has a license to the company’s proprietary CD8+ T cell induction platform and research by Benoit Van den Eynde’s group at the Ludwig Oxford Branch. Pursuant to the Clinical Trial Agreement, CRUK is responsible for, among other things, designing, preparing, carrying out and sponsoring the Clinical Trial, at its cost, and VOLT has granted to CRUK a license under its intellectual property to enable CRUK to perform such activities. VOLT is responsible for supplying agreed quantities of its VTP-600 immunotherapy product. VOLT retains the right to continue the development of the product during the Clinical Trial, provided that the parties have first agreed appropriate terms for sharing of safety data. CRUK owns all results, including all intellectual property therein, generated in the performance of the Clinical Trial. Upon the completion of the Clinical Trial, VOLT has the option to obtain a license to use such results, or the VTP-600 License. The terms of the VTP-600 License have been pre-agreed and are set out in the Clinical Trial Agreement. VOLT License Agreement In November 2018, the company entered into a license agreement, or the VOLT License Agreement, with VOLT. Pursuant to the VOLT License Agreement, the company granted to VOLT a non-exclusive worldwide license under certain patent rights, know-how and materials related to the use of ChAdOx1, ChAdOx2, adenoviral and MVA promoters, and the TR293 Tet-Repressed Cell Line, or the VOLT Licensed Technology, to manufacture, use and commercialize any product which uses or is within the scope of the VOLT Licensed Technology, or VOLT Licensed Product. In part, the rights granted are a sublicense of rights granted to the company by OUI under the 2016 OUI License Agreement. The license is sublicensable subject to obtaining OUI’s prior consent with respect to sublicensing of any of the VOLT Licensed Technology licensed to the company by OUI (with such consent not to be unreasonably withheld). The VOLT License Agreement was subsequently amended in July 2019 by two separate agreements for the research, development, and commercialization of cancer immunotherapy targeting MAGE-A3 and NY-ESO-1 for the treatment of various forms of cancer under the VOLT Licensed Technology. Intellectual Property As of March 23, 2023, the company owned a patent family relating to its novel regimens that includes two pending U.S. patent applications, two pending foreign patent applications and one pending Patent Cooperation Treaty, or PCT, patent application. In addition, the company has in-licensed certain patent families relating to its key technology platforms and product candidates, including eight issued U.S. patents, eight pending U.S. patent applications, 16 issued foreign patents and 80 pending foreign patent applications. Following the acquisition of Avidea in December 2021, the company controls a further patent portfolio comprising in-licensed and co-owned patent families, including eight pending U.S. patent applications, (including two pending U.S. provisional patent applications), four issued foreign patents, 30 pending foreign patent applications and four pending PCT patent applications. Universal Vector Technology Platforms ChAdOx-1 Expression Vector As of March 23, 2023, with regard to the company’s ChAdOx1 expression vector, the company in-licensed from OUI a patent family that includes two issued U.S. patents with claims directed to the composition of matter of the ChAdOx1 adenovirus vector and methods of using such a vector, and 9 issued foreign patents granted in such jurisdictions as Australia, Canada, China, Europe (validated in 12 countries, including Denmark, France, Germany, Italy, Spain, and Great Britain), India, Japan, Singapore and South Africa. A second granted European patent with further claims directed to the composition of matter of ChAdOx adenovirus vector is validated in France, Germany and Great Britain. This patent family also includes a pending U.S. patent application. The granted patents and pending applications, if issued, 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. Patent term extension applications are pending in Japan and 11 European Patent Convention countries, including the United Kingdom, France, Germany, Italy and Spain, based on marketing authorizations received by AstraZeneca for Vaxzevria, and patent term extension has been granted in Australia. Adenoviral Promoter Certain of the company’s ChAdOx1 vectors incorporate a proprietary adenoviral promoter, which is covered by a patent family that the company in-licenses from OUI. As of March 23, 2023, the patent family includes two issued U.S. patents and one granted patent in Europe (validated in 7 countries including France, Germany, Italy, Spain, and Great Britain). The patents in this family are expected to expire in 2028, 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. MVA-poxvirus Promoter The company’s MVA vector incorporates a proprietary poxvirus promoter, or MVA-poxvirus promoter, which is covered by a patent family that the company in-licenses from OUI. As of March 23, 2023, the patent family includes two issued U.S. patents and one granted European patent (validated in 9 countries including Denmark, France, Germany, Italy, Spain, and Great Britain) that 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. SNAPvax The company’s proprietary SNAPvax technology is covered by a patent portfolio that includes one patent family the company owns, 6 patent families that the company co-owns and one patent family that the company in-licenses from OUI. As of March 23, 2023, the company in-licensed a patent family from OUI that includes one pending U.S. patent application and one pending European patent application that are expected to expire in 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. As of March 23, 2023, the company owned a patent family that includes four issued foreign patents that are expected to expire in 2030, 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 March 23, 2023, the company co-owned a patent family that includes one pending U.S. patent application, one pending European patent application and a further 10 pending foreign patent applications that 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. The company has exclusively licensed rights in this patent family, which resulted from work carried out under a Collaborative research and Development Agreement, or CRADA, between Avidea and the U.S. National Institutes of Health (‘NIH’). As of March 23, 2023, the company co-owned a patent family that includes one pending U.S. patent application, one pending European patent application and a further 5 pending foreign patent applications that are expected to expire in 2039, 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 exclusively licensed rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH. As of March 23, 2023, the company co-owned a patent family that includes one pending U.S. patent application, one pending European patent application and a further 2 pending foreign patent applications that are expected to expire in 2039, 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 exclusive rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH. As of March 23, 2023, the company co-owned a patent family that includes one pending international PCT patent application that is expected to expire in 2042, 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 exclusive rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH. As of March 23, 2023, the company co-own a patent family that includes one pending international PCT patent application and one further pending foreign patent applications that are expected to expire in 2042, 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 exclusive rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH. As of March 23, 2023, the company co-owned a patent family that includes one pending U.S. patent application, one pending foreign patent application and one pending international PCT patent application that 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 has licensed exclusive rights in this patent family, which resulted from work carried out under a Research Collaboration Agreement, or RCA, between Avidea and the Institute of Macromolecular Chemistry, Prague (‘IMC’). Syntholytic The company’s proprietary Syntholytic technology is covered by a patent portfolio that includes one patent family the company own, 2 patent families that the company co-own and one patent family that the company in-licenses from OUI. As of March 23, 2023, the company in-licensed a patent family from OUI that includes one pending U.S. patent application and one pending European patent application that are expected to expire in 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. As of March 23, 2023, the company owned a patent family that includes four issued foreign patents that are expected to expire in 2030, 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 March 23, 2023, the company co-owned a patent family that includes one pending U.S. patent application, one pending European patent application and a further 6 pending foreign patent applications that 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. The company has exclusively rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH, and the company has licensed exclusive rights in this patent family, which resulted from work carried out under a RCA between Avidea and the IMC. As of March 23, 2023, the company co-owned a patent family that includes one pending international PCT patent application that is 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 has exclusively rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH. Product Candidates The company’s VTP-200 product candidate comprises a ChAdOx1HPV vector and a MVA-HPV vector, where each vector incorporates an engineered HPV antigen. The company in-license from OUI a patent family directed to the HPV antigen with claims directed to a nucleic acid encoding a polypeptide comprising certain peptide sequences based on certain HPV proteins. As of March 23, 2023, the patent family includes one issued U.S. patent, one pending U.S. patent application and ten foreign patent applications pending in jurisdictions including Europe, Australia, Canada, China, and Japan. If patents were to issue from such patent applications, they would be expected to expire in 2038, without giving effect to any potential patent term extensions or patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. In addition, the company relies on patent protection afforded by the patent family directed to the ChAdOx1 expression vector, which is expected to expire in 2032, and the patent family directed to the company’s MVA-poxvirus promoter, which is expected to expire in 2031. The company’s VTP-300 product candidate comprises a ChAdOx1HBV vector and a MVA-HBV vector, where each vector incorporates an engineered HBV antigen. As of March 23, 2023, the company in-licensed from OUI a patent family with claims directed to a multi-HBV immunogen viral vector vaccine that includes one pending U.S. patent application and 17 foreign patent applications pending in jurisdictions, including Europe, Australia, Canada, China, and Japan. If patents were to issue from such patent applications, they would be expected to expire in 2038, without giving effect to any potential patent term extensions or patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. In addition, the company relies on patent protection afforded by the patent family directed to the ChAdOx1 expression vector, which is expected to expire in 2032, and the patent family directed to the company’s MVA-poxvirus promoter, which is expected to expire in 2031. The company’s VTP-600 product candidate comprises a ChAdOx1MAGE-NYESO vector, a MVA-MAGE vector, and a MVA-NYESO vector. The company in-licenses from Ludwig Institute a patent family with claims directed to a chimpanzee adenovirus vector encapsulating a nucleic acid molecule encoding a MAGE antigen, a NY- ESO1 antigen or both a MAGE antigen and a NY-ESO1 antigen. As of March 23, 2023, the patent family includes one pending U.S. patent application and 8 foreign patent applications pending in jurisdictions, including Europe, Australia, Canada, China, and Japan. If a patent were to issue from a patent application claiming the benefit of this PCT application, such a patent would be expected to expire in 2039, without giving effect to any potential patent term extensions or patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. In addition, the company relies on patent protection afforded by the patent family directed to the ChAdOx1 expression vector, which is expected to expire in 2032, the patent family directed to the company’s adenoviral promotor, which is expected to expire in 2028, and the patent family directed to the company’s MVA-poxvirus promoter, which is expected to expire in 2031. The company’s VTP-800 and VTP-850 product candidate comprises a ChAdOx15T4 vector and a MVA5T4 vector, where each vector incorporates an engineered 5T4 antigen in combination with additional antigens. The company in-license from OUI a patent family with claims directed to a composition for inducing a T Cell response comprising a MVA vector expressing the 5T4 antigen polypeptide. As of March 23, 2023, the patent family includes one pending U.S. patent application and 11 foreign patent applications pending in jurisdictions including Europe, Australia, Canada, China, and Japan. If a patent were to issue from a patent application claiming the benefit of this PCT application, such a patent would be expected to expire in 2039, without giving effect to any potential patent term extensions or patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. In addition, the company relies on patent protection afforded by the patent family directed to the ChAdOx1 expression vector, which is expected to expire in 2032, the patent family directed to the company’s adenoviral promotor, which is expected to expire in 2028, and the patent family directed to the company’s MVA-poxvirus promoter, which is expected to expire in 2031. The company’s VTP-500 product candidate comprises a ChAdOx1MERS vector that incorporates an engineered MERS antigen. The company relies on patent protection afforded by the patent family directed to the ChAdOx1 expression vector, which is expected to expire in 2032 and the patent family directed to the company’s adenoviral promotor, which is expected to expire in 2028, as discussed above. The company’s VTP-400 product candidate comprises a ChAdOx1VZVgE vector that incorporates an engineered VZVgE antigen. The company in-licenses from OUI a patent family with claims directed to an adenoviral vector comprising a nucleic acid encoding the varicella-zoster virus antigen. As of March 23, 2023, the patent family includes one pending U.S. patent application and 13 foreign patent applications pending in jurisdictions, including Europe, Australia, Canada, China, and Japan. If a patent were to issue from a patent application claiming the benefit of this PCT application, such a patent would be expected to expire in 2039, without giving effect to any potential patent term extensions or patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The company also relies on patent protection afforded by the patent family directed to the ChAdOx1 expression vector, which is expected to expire in 2032 and the patent family directed to the company’s adenoviral promotor, which is expected to expire in 2028, as discussed above. The company’s VTP-1100 product candidate includes SNAPvax technology to target HPV16+ cancers. The company co-owns a patent family with claims directed to methods of treating cancers using SNAPvax compositions. As of March 23, 2023, the patent family included one pending U.S. provisional patent application. If a patent were to issue from a patent application claiming the benefit of this U.S. provisional application, such a patent would be expected to expire in 2043, without giving effect to any potential patent term extensions or patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. The company has exclusive rights in this patent family, which resulted from work carried out under a CRADA between Vaccitech and the NIH. In addition, the company relies on patent protection afforded by the patent families directed to the SNAPvax platform technology, which are expected to expire between 2030 and 2042, as discussed above. The company’s VTP-1000 product candidate includes SNAPvax technology to provide tolerizing immunotherapy for celiac disease. The company co-owns a patent family with claims directed to compositions and methods for treating celiac disease. As of March 23, 2023, the patent family included one pending U.S. provisional patent application. If a patent were to issue from a patent application claiming the benefit of this U.S. provisional application, such a patent would be expected to expire in 2043, without giving effect to any potential patent term extensions or patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees. In addition, the company relies on patent protection afforded by the patent families directed to the SNAPvax platform technology, which are expected to expire between 2030 and 2042, as discussed above. The company owns the Vaccitech registered trademark for the United Kingdom. Government Regulation Manufacturers of the company’s products are required to comply with applicable requirements in the cGMP regulations, including quality control and quality assurance and maintenance of records and documentation. In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect the company’s business. To obtain regulatory approval of a biological medicinal product under the European Union regulatory system, the company must submit a marketing authorization application, or MAA, either under a centralized procedure administered by the European Medicines Agency, or EMA, or one of the procedures administered by competent authorities in the European Union: the decentralized procedure, national procedure, or mutual recognition procedure. Research and Development The company’s research and development expenses were $42.4 million for the year ended December 31, 2022. History The company was founded in 2016. It was incorporated in 2021. The company was formerly known as Vaccitech Rx Limited and changed its name to Vaccitech plc in March 2021.