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Item 1. Business

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We are a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases, cancer, and autoimmunity.

We aim to treat and prevent infectious diseases and cancer by using our proprietary platforms to develop product candidates that stimulate powerful, targeted immune responses against pathogens, infected cells, and tumor cells.

We design 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, we use our proprietary platform to develop product candidates that are designed to induce regulatory T cells to suppress specifically pathogenic autoimmune responses and prevent/reverse autoimmunity.

We are focused on applying our platform capabilities and the expertise of our 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 our platform’s ability to respond rapidly to epidemic and pandemic threats.

We have a broad pipeline of both clinical and preclinical stage therapeutic and prophylactic programs.

Our current 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 treatment of celiac disease, and VTP-1100 for treatment of HPV-associated cancers.

The latter two programs are designed to utilize our SNAPvax TM platform.

Our current 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, we co-invented a COVID-19 vaccine with the University of Oxford, the rights to which we assigned to Oxford University Innovation, or OUI, to facilitate the license of those rights by OUI to AstraZeneca UK Limited, or AstraZeneca.

The vaccine, formerly referred to as AZD1222, is now authorized for use under the marketing name Vaxzevria in a number of countries.

AstraZeneca has exclusive worldwide rights to develop and commercialize Vaxzevria.

Scientists have successfully harnessed the immune system to prevent and treat diseases using a wide range of approaches over hundreds of years.

In the prophylactic setting, vaccines aim to create long-lasting protective immunity, while in the therapeutic setting, immunotherapeutics aim to balance the body’s immune response either by strengthening it to enable clearance of pathogens and infected or cancerous cells, or by dampening it to limit inflammation and tissue damage due to autoimmune hyperactivity.

A key element of the immune system is specialized white blood cells, or lymphocytes.

We are a clinical-stage biopharmaceutical company developing novel T cell immunotherapeutic candidates designed to guide the immune system to overcome chronic infectious diseases, autoimmunity and cancer.

Helping patients and their families is the guiding principle at the heart of Barinthus Bio.

We stand apart through our broad pipeline, built around four proprietary platform technologies;

two viral vector platforms, ChAdOx and MVA;

and two versions of the synthetic SNAP platform, SNAP-TI (SNAP-Tolerance Immunotherapy) and SNAP-CI (SNAP-Cancer Immunotherapy), previously referred to collectively as SNAPvax TM .

These platforms are enabling us to develop antigen-specific immunotherapeutic candidates designed to optimize the disease-fighting capabilities of T cells and guide them towards a healthy balance.

Our immunotherapeutic candidates are designed to work by increasing disease-specific CD8+ T cell activity in the case of chronic infectious diseases and cancers, or by dampening autoreactive CD4+ and CD8+ T cells, and increasing regulatory T cells in autoimmunity.

Harnessing our range of proprietary platform technologies, we are advancing a pipeline of four product candidates across a diverse range of therapeutic areas, including:

VTP-300, a Phase 2 immunotherapeutic candidate designed as a potential component of a functional cure for chronic hepatitis B viral ("HBV") infection;

VTP-200, a Phase 2 non-surgical product candidate for persistent high-risk human papillomavirus ("HPV") with near term clinical read-outs;

VTP-1000, our first preclinical autoimmune candidate designed to utilize the SNAP-TI platform to treat patients with celiac disease;

and VTP-850, a second-generation Phase 2 immunotherapeutic candidate designed to treat recurrent prostate cancer.

Alongside these proprietary programs, we have partnerships in place to advance three additional prophylactic and therapeutic product candidates in Middle East Respiratory Syndrome ("MERS"), Zoster and Non-Small Cell Lung Cancer (NSCLC).

We also co-invented Vaxzevria, a COVID-19 vaccine with the University of Oxford, which has been exclusively licensed worldwide to AstraZeneca UK Limited ("AstraZeneca").

The co-invention of the COVID-19 vaccine demonstrated our ability to navigate a changing environment with speed and efficiency and lead the way in responding to urgent medical needs, as well as providing a strong proof-of-concept for the ChAdOx platform.

We believe our proven scientific expertise, diverse portfolio and focus on product candidate development uniquely positions us to navigate towards delivering treatments for patients with infectious diseases, autoimmune disorders and cancers that have a significant impact on their everyday lives.

Scientists have successfully harnessed the strengths of the immune system to prevent and treat diseases using a wide range of approaches over hundreds of years.

The most widely known application of such approaches is prophylactic vaccines, which aim to create long-lasting immunity largely via the generation of protective antibodies.

More recently, approaches targeting the immune system to treat diseases have emerged with many immunotherapeutics aiming to balance the body’s immune response.

These immunotherapeutic approaches can broadly fit into two categories:

those that are designed to strengthen the immune system to enable clearance of pathogens and infected or cancerous cells, or those that are designed to dampen the immune system to limit inflammation and tissue damage due to autoimmune hyperactivity or uncontrolled inflammation.

A key element of the immune system is specialized white blood cells, also called lymphocytes.

B cells and T cells are the two main types of lymphocytes.

B cells are responsible for generating antibodies while T cells assist in the clearance of acute and chronic infections, such as hepatitis B virus and HPV, and are involved in killing cells that become cancerous.

B cells are responsible for generating antibodies while T cells assist in the clearance of acute and chronic infections, such as HBV and HPV, and are involved in killing cells that become cancerous.

Although designed to be protective, these immune cells can also be hyperactive and, when targeted against self, they are responsible for tissue-specific damage in many autoimmune conditions.

Over the past three decades, hundreds of trials have examined a wide variety of approaches that induce the production of cytotoxic, or CD8+, T cells against infected and cancerous cells.

Over the past three decades, hundreds of trials have examined a wide variety of approaches that induce the production of cytotoxic CD8+ T cells against infected and cancerous cells.

These trials have demonstrated that different approaches induce different breadths and magnitudes of immune response.

While there have been many successes, certain diseases requiring a robust CD8+ T cell response have remained resistant to existing approaches.

Infected or cancerous cells are recognized through specific molecules, or antigens, which induce an immune response in the human body.

Our platforms are designed to stimulate the production of very high levels of T cells, in addition to antibodies, against such antigens.

Our approach for the treatment or prevention of a disease with a known target antigen is to prime the immune system with an initial injection of a proprietary platform encoded with the target antigen.

In the therapeutic setting, this is typically followed by a boost with a second, different, platform encoded with the same antigen.

This is known as a heterologous prime-boost, or a mix and match approach.

We employ unique antigen design strategies to optimize immune presentation and maximize the desired type of antibody and/or T cell immunogenicity that we are seeking to induce.

This heterologous prime-boost approach has been shown to provide the highest magnitude and durable immunogenic CD8+ T cell response induced in humans to date.

Our platforms are further differentiated by their flexibility, applicability across diseases in both the therapeutic and prophylactic setting, favorable tolerability profile and proven rapid production on a large scale.

Infected or cancerous cells are recognized as a “danger” by the immune system through their expression of specific antigens, which elicit a targeted immune response, largely led by T cells, to eliminate the “danger.” Our platforms are designed to stimulate the production of very high levels of functional T cells, in addition to antibodies, against such antigens.

Our approach for the treatment of a disease with known target antigens is to attempt to elicit a strong and specific immune response against these antigens using a combination of two proprietary platforms encoded with the target antigens, each administered one month apart.

We employ unique antigen design strategies designed to optimize antigen presentation to the

immune system and maximize the desired type of immune response we are seeking to induce.

This specific combination approach has been shown to provide a very high magnitude and durable CD8+ T cell response induced in humans to date.

Our platforms are further differentiated by their flexibility, applicability across diseases, favorable tolerability profile and proven rapid production on a large scale.

Autoimmunity develops when the tolerance checkpoints meant to maintain a state of unresponsiveness of our immune system towards self-antigens are lost.

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A far less aggressive approach is to restore immune tolerance to self-antigens, in an antigen-specific manner, enabling to selectively blunt autoinflammation and control the disease without impairing protective immunity to pathogens and cancer.

Our SNAPvax tolerizing platform is comprised 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.

Our SNAP-TI platform is designed to exactly do that:

restore immune tolerance to self.

The platform is comprised of several self-antigens involved in the target disease associated with a tolerizing immunomodulator, enabling presentation of the disease antigens in a tolerizing context, which will potentially lead to dampening T cell hyperactivity and/or inducing self-antigen-specific regulatory T cells, whose main function is to control immune responses.

We believe SNAP-TI is further differentiated from its competitors by its high antigen loading capacity, controlled size, and self-assembling nature for ease of manufacturing.

In 2023, we achieved a number of strategic, operational, and financial objectives, which we believe positions us to deliver on our long-term plans:

● In January, Cancer Research UK, Vaccitech and the Ludwig Institute for Cancer Research (Ludwig), announced the first patient dosed in the MAGE trial, which is testing a novel immunotherapeutic, VTP-600, in patients with the most common type of lung cancer.

● In April, we announced the commencement of royalty payments relating to commercial sales of Vaxzevria.

The Company’s share of milestone and royalty payments received by OUI from AstraZeneca recognized as revenue for the year ended December 31, 2022, amounted to $43.7 million.

● In April, the Company launched two programs utilizing our proprietary SNAPvax platform:

an immunostimulatory one to target HPV-associated cancer utilizing the SNAPvax platform and moved forward with a tolerizing one designed to induce regulatory T cells in patients with celiac disease.

IND applications are expected to be filed for VTP-1100, in HPV cancer, and VTP-1000, targeting celiac disease during the second half of 2023.

● In April, we received scientific advice from the EMA defining a licensure pathway for the candidate MERS vaccine, VTP-500, which helps the Company to both plan and estimate expenses of the development pathway more accurately and completely.

● In May, we completed enrollment for a Phase 1b/2a clinical trial, HBV002, to evaluate the safety and immunogenicity of VTP-300, both as monotherapy and in combination with an anti-PD-1 blocking agent, in patients with chronic Hepatitis B whose HBV infection has been suppressed with oral antiviral medication.

We expect to announce final topline data in the first quarter of 2023.

● In June, Arbutus Biopharma Corporation (Arbutus) dosed the first patient in a randomized, multi-center, blinded, Phase 2a clinical trial to evaluate the safety, antiviral activity and immunogenicity of the combination of Arbutus’ RNAi therapeutic candidate, AB-729, with the Company’s T-cell stimulating immunotherapeutic, VTP-300, and standard-of-care nucelos(t)ide reverse transcriptase inhibitor therapy for the treatment of patients with virology-suppressed chronic HBV infection.

We expect to announce interim efficacy data in the fourth quarter of 2023.

● In June, at the 2022 EASL International Liver Congress™, the Company presented HBV002 data showing that VTP-300, both as monotherapy and in combination with a single low dose of Nivolumab (PD1 blocker) at the time of the booster dose, induced sustained reductions of HBV surface antigen (HBsAg) in some patients, and a robust T cell response, of which CD8+ T cells were predominant, against all encoded antigens in patients with chronic HBV infection.

● In June, the Company entered into a lease agreement for approximately 19,700 square feet in Germantown, Maryland.

The site will house the Company’s state-of-the-art wet laboratory and office space in the United States.

● In July, the Company enrolled the 60th patient into the Company’s Phase 1b/2 clinical trial of VTP-200, HPV001, to evaluate a potential treatment for persistent high-risk HPV infection.

● In July, we completed the relocation of our headquarters to Harwell, Oxfordshire, United Kingdom.

● In August, the Company filed a Registration Statement on Form S-3, as amended, or the Shelf, with the Securities and Exchange Commission in relation to the registration and potential future issuance of ordinary shares, including ordinary shares represented by ADSs, debt securities, warrants and/or units of any combination thereof in the aggregate amount of up to $200.0 million.

The Shelf was declared effective on August 17, 2022.

We also simultaneously entered into a sales agreement with Jefferies LLC, as sales agent, providing for the offering, issuance and sale by us of up to an aggregate of $75.0 million of our ordinary shares represented by ADSs from time to time in “at-the-market” offerings under the Shelf.

As of December 31, 2022, we sold 307,139 ordinary shares represented by ADSs under the sales agreement, amounting to gross proceeds of $0.7 million.

● In October, we announced the publication of research from VTP-1100 in Cell that demonstrated anti-tumor activity achieved with intravenous (IV) administration of a SNAPvax construct in an animal model.

The study demonstrated that IV administration of SNAPvax targeted and expanded antigen-specific T cells and reversed suppression in the tumor microenvironment, which promotes T cell infiltration and tumor cell killing.

● In October, we announced the dosing of the first patient in HBV003, a Phase 2b clinical trial of VTP-300 designed to evaluate different regimens of low dose nivolumab and the impact of additional doses of the MVA boost, with the aim of maximizing a sustained decline in HBsAg.

● In November, Dr.

Young-Suk Lim, Professor of Gastroenterology in the Liver Center at University of Ulsan College of Medicine, presented a poster reporting interim HBV0002 Phase 1b/2a clinical trial data on VTP-300 at AASLD.

The poster presentation showed VTP-300 immunotherapy, as monotherapy and when combined with low dose nivolumab at the boosting time point, was immunogenic and showed a sustained reduction in HBsAg in well-controlled CHB patients, and was administered with no treatment related SAEs and infrequent transient transaminitis.

Two of five patients dosed in cohort 3 (ChAdOx1-HBV + MVA-HBV with low dose nivolumab given at the boost) with starting HBsAg levels below 100 achieved non-detectable levels of surface antigen at the data cutoff.

● In December, the FDA cleared our IND for VTP-850 to be evaluated in PCA001, a Phase 1/2 open-label clinical trial of in patients with rising PSA after definitive local therapy for prostate cancer.

We expect to announce the first patient dosed in the second quarter of 2023.

● In December, the Company completed enrollment into the Phase 1b/2 clinical trial of VTP-200, HPV001, to evaluate a potential treatment for persistent high-risk HPV infection.

We expect to announce the full data from this trial in the first quarter of 2024.

Our Platforms

Our proprietary platforms comprise several components that either 1) when combined, allow us 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 our first platform include our 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.

We believe both ChAdOx1 and MVA have favorable tolerability profiles, based on extensive clinical testing performed by us 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.

We have also developed proprietary enhancements for both our ChAdOx and MVA vectors to increase T cell induction and response, and we employ 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, our understanding and expertise in manufacturing optimization has allowed us 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, we have added SNAPvax to our 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, we are 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, we are 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.

We have several therapeutic programs in our pipeline focusing on infectious diseases, oncology and immune tolerance.

• In January, we announced the appointment of Nadège Pelletier, Ph.D., as Chief Scientific Officer.

• In March, we announced favorable topline interim data from the HPV001 Phase 1b/2 clinical trial of VTP-200 in high risk HPV ("hrHPV") infection, and positive topline final data from the HBV002 Phase 1b/2 clinical trial for VTP-300 in chronic HBV.

• In April, we presented interim data from the VTP-200 APOLLO (HPV001) Phase 1b/2 clinical trial in hrHPV infection at the 35 th Annual International Papillomavirus Conference ("IPVC").

The interim data showed VTP-200 induced high T cell responses to HPV antigens.

VTP-200 was generally well-tolerated with no product-related grade 3 unsolicited events and no product-related SAE s.

• In June, we announced the dosing of the first patient in the Phase 1/2 PCA001 clinical trial for VTP-850 in prostate cancer.

• In June, we presented positive final data from the Phase 1b/2a HBV002 clinical trial for VTP-300 in chronic Hepatitis B (CHB) at the European Association for the Study of the Liver ("EASL") Congress 2023 – The International Liver Congress TM .

The data showed meaningful, durable reductions of Hepatitis B Surface Antigen (HBsAg) in all participants with a >0.5 log10 reduction in HBsAg who received VTP-300 alone (Group 2) or in combination with a single administration of low-dose PD-1 inhibitor, nivolumab (Group 3).

Two of five patients with baseline HBsAg below 100 IU/mL in Group 3, developed a non-detectable HBsAg level, which continued eight months after last dose.

• In June, we completed the move of our U.S.

facility to Germantown, Maryland, which houses a state-of-the art wet laboratory and office space.

• In November, we announced our renaming as Barinthus Biotherapeutics plc to represent the evolution and expansion of its focus beyond vaccines.

As part of the renaming, we announced the ticker on Nasdaq was changed to "BRNS," which became effective on November 7, 2023.

• In November, we conducted an oral presentation of interim data from the Phase 2b HBV003 clinical trial for VTP-300 in CHB at the American Association for the Study of Liver Diseases ("AASLD") – The Liver Meeting ® 2023, which indicated that VTP-300 in combination with nivolumab continued to show sustained HBsAg reductions, particularly in patients with HBsAg levels below or equal to 200 IU/mL at screening.

• In November, interim data from the Phase 2a AB-729-202 clinical trial in collaboration with Arbutus Biopharma Corporation in CHB patients were presented via poster presentation at AASLD, showing that imdusiran in combination with VTP-300 demonstrated meaningful and sustained declines in HBsAg levels.

• In December, we announced we signed an agreement with the Coalition for Epidemic Preparedness Innovations ("CEPI") and the University of Oxford, aiming to fast-track the development of a vaccine candidate known as

VTP-500 for the prevention of MERS.

This agreement includes CEPI investing funding of up to $34.8 million with Barinthus Biotherapeutics (UK) Limited in addition to funds previously committed to the University of Oxford to develop and stockpile a ready reserve of emergency MERS vaccine candidate, VTP-500.

• In December 2023, we submitted an Australian ethics submission and regulatory notification to the Alfred Research Review Committee for the Phase 1 GLU001 study in Celiac disease.

The Key Elements of Our Antigen-Delivery Platforms

Our proprietary platforms are comprised of several components that are designed to be either immunostimulatory or tolerizing.

When combined, our immunomodulatory platforms (ChAdOx, MVA and SNAP-CI) allow us to develop product candidates designed to induce high and durable levels of antigen-specific polyfunctional T cells and B cells to prevent and treat infectious diseases and cancer.

Our tolerizing platform (SNAP-TI) is designed to restore immune tolerance by a mechanism of action that includes the induction of regulatory T cells and/or decrease of T cell activation to specifically restore a beneficial T regulatory to T effector ratio and control autoreactive immune cell hyperactivity, while maintaining the desired tolerability profile.

The key elements of our viral vector platforms, which include ChAdOx and MVA, are:

• Proprietary simian vectors :

ChAdOx1 and ChAdOx2 are modified simian adenoviral vectors which deliver target antigens into cells to generate a specific immune response.

These viruses were originally isolated from chimpanzees to avoid pre-existing immunity issues affecting the use of human adenovirus vectors.

Researchers at the Jenner Institute modified the ChAdOx viruses to be non-replicating and to have an increased antigen-carrying capacity.

To date, we have developed several candidates with the ChAdOx vectors, each carrying antigens that are specific to the targeted pathogens and diseases.

Adenoviral vectors have demonstrable safety profiles and have induced the desired immune responses in all age groups evaluated to date.

• Well-validated follow-up vector :

MVA is a highly attenuated vaccinia virus used to deliver target antigens into cells to generate de novo or amplify an existing immune response.

MVA has a large antigen-carrying capacity and generates a particularly strong immune response when used secondarily, in sequential combination, to an alternative viral vector carrying the same antigen load (ChAdOx in this case).

MVA is replication-deficient and has a well-documented safety profile in hundreds of thousands of people, and is licensed as a smallpox vaccine in both Europe and the US.

• Proprietary promoters and enhancers:

Promoters and molecular enhancers are genetic codes that influence antigen expression.

For our adenoviral vectors, we use a proprietary promoter that is modified from cytomegalovirus.

The use of this modified promoter has been shown to increase both antigen expression and the associated immune response.

For our MVA vector, we use a proprietary promoter to control expression of recombinant antigens and thereby further enhance T cell induction levels.

We may use molecular adjuvants to enhance the CD8+ T cell response.

• Rapid vector generation and manufacturing :

We employ manipulation of adenovirus genomes to enable rapid generation of recombinant adenoviral vectors to meet GMP standards.

We believe our sequencing techniques have the potential to result in safer, more stable, product candidates.

We believe that our adenovirus product candidates can be manufactured quickly and to significant scale, as demonstrated by Vaxzevria, a prophylactic vaccine for the prevention of COVID-19 infection.

Vaxzevria, which is based on the ChAdOx1 vector, was designed, constructed and manufactured for human use within three months.

Normal GMP production processes typically take six to ten months each for adenovirus and for MVA.

The key elements of our synthetic platforms, which include SNAP-TI and SNAP-CI, are:

• Synthetic nanoparticle technology:

SNAP is a modular immunotherapy platform that is designed to co-deliver multiple targeted peptide antigens and immunomodulators in self-assembling nanoparticles to key immune cell populations for promoting the appropriate T cell immunity.

SNAP’s unique design allows for trafficking to lymphoid organs and local tissues to engage with local immunity.

The large antigen loading capacity is designed to allow for subcutaneous or intramuscular administration.

It can be administered as a monotherapy or in combination with the viral vectors.

Its synthetic nature allows for repeated administration.

has shown promising data on protection from disease in a mouse model of autoimmunity.

We are advancing assets based on the SNAP-TI platform designed to treat autoimmune diseases with known autoantigens.

SNAP-TI contains autoantigens and immunomodulators ( e.g.

, mTOR inhibitors).

Its putative mechanism of action includes both dampening of pathogenic T effector activity and induction of regulatory T cells, crucial to restore immune tolerance to self-antigens and maximize therapeutic benefit.

An article in Nature Biotechnology described SNAP as among the most efficient immunotherapy platforms for inducing T cell immunity reported to date.

Another article in Nature Biotechnology reported that SNAP enabled repeated intravenous ("IV") administration to maximize clinical effect.

SNAP-CI has been observed to induce high magnitude, functional CD8+ T cells, especially when given sequentially with ChAdOx1 in preclinical studies in mice and non-human primates.

It contains cancer-specific antigens and immunomodulator ( e.g ., Toll-like receptor agonists).

Antigen selection and design across all platforms :

We select full-length and/or subunit antigen sequences involved in or associated with targeted infectious diseases, autoimmune diseases, or cancer.

We employ unique antigen design strategies to optimize in vivo antigen presentation and maximize the desired type of immune responses while maintaining the desired tolerability profile.

For example, some targeted diseases may require a greater CD8+ T cell-mediated response, whereas others may require a more balanced T and B cell response, and others require the induction of regulatory T cells.

We use cutting-edge bioinformatics methods to design and optimize our antigen load.

For example, to select antigen targets for pathogens, we use databases to rank options based on factors including global distribution of genetic strains, evolutionary competitive advantage, known pathogenicity and sequence upload bias;

and design our final antigens to achieve maximal antigen presenting cell processing to elicit CD8+ T cells.

We have several product candidates in our pipeline focusing on infectious diseases, oncology and immune tolerance.

Our Proprietary Pipeline:

The chart below provides key information about our programs.

We have worldwide rights for all product candidates.

These are estimated timelines only and are subject to change.

Our Partnered Pipeline:

An Immunotherapeutic Targeting Chronic HBV Infection

In May 2022, we completed the last patient visit in our 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.

We have used genotype C HBV antigen sequences in our VTP-300 vectors to target the most prevalent CHB genotype.

However, we believe VTP-300 may induce cross-reactive T cell responses with other prevalent genotypes.

Therefore, we also aim 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.

The criteria for CHB patients to be enrolled in this trial were (i) infection that has been suppressed with oral antiviral medication (HBV DNA < 40 copies/mL) and (ii) relatively low levels of cccDNA markers (HBsAg < 10,000 IU/ml).

As higher levels of CD8+ T cell induction are likely to occur in healthy controls, these samples are utilized to map the responses induced by VTP-300, to assess cross-reactivity with peptides, representing consensus sequences from genotypes B and D, which are more common in both the United States and Europe.

In addition, we are 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, we 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:

MVA-HBV (prime-boost);

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, we 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.

We 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, we 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.

VTP-300 is composed of two viral vectors (ChAdOx and MVA), both encoding the same antigen sequence based on HBV genotype C antigen sequences that are administered intramuscularly one month apart, with the potential for additional administrations subsequently, depending upon outcome.

HBV002 – Completed Phase 1b/2a

In March 2023, we announced topline results from the Phase 1b/2a clinical trial, HBV002, to evaluate the safety and reactogenicity of VTP-300 with or without a low-dose (0.3 mg/kg) anti-PD-1 (nivolumab) in CHB patients whose infection has been suppressed with oral antiviral medication.

In the HBV002 trial, we enrolled CHB patients in four treatment groups as described in the table below.

Since the participants were already infected with HBV, we thought it was possible that natural exposure could eliminate the need for the an initial ChAdOx1 dose.

Hence, Group 1 of the HBV002 trial was designed to compare MVA-HBV given twice with the ChAdOx1-HBV plus MVA-HBV combination approach used in Group 2.

We expected that the regimen given to Group 2 would be more potent and planned to further explore this specific regimen in Groups 3 and 4 with the addition of PD1 blockade.

In the cancer field, the timing of PD-1 blockade has been reported to be critical as its administration prior to immune stimulation has been observed to result in diminished T cell responses as compared to later administration.

Hence, Groups 3 and 4 evaluated the impact of the timing of PD1 blockade, administered either with the MVA dose (Group 3) or with both the ChAdOx1 and the MVA doses (Group 4).

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.

We believe that 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, we dosed our 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.

Our data indicate that VTP-300 is capable of inducing responses to non-genotype C HBVs, so we will aim to demonstrate activity against non-genotype C infected patients.

We will also plan to evaluate additional combination regimens, such as next-generation modalities including RNA interference molecules, and may evaluate further potential collaboration partnerships.

We 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, we announced an update to the interim analysis of safety and efficacy data from the HBV002 study (NCT04778904), which was presented as a poster at the 2022 EASL International Liver Congress TM.

The updated analysis, which included 39 patients with three-months of follow up, showed that VTP-300 as a monotherapy or in combination with low-dose nivolumab was administered with no treatment-related serious adverse events and that two patients experienced mild, rapidly resolving transaminitis.

Meaningful and durable reductions of HBsAg were seen in some patients who received VTP-300 as either a monotherapy or in combination with a single low dose of nivolumab at the time of booster dose.

Declines were most prominent in patients with lower baseline HBsAg at the time of enrollment.

In all patients who had a HBsAg decline greater than 0.5 log10, the reductions of HBsAg were durable until the last measurement (up to eight months after the last dose).

A robust T cell response against all encoded antigens, measured by overnight stimulation, was observed following VTP-300 administration, notable for marked CD8+ T cell predominance.

Enrollment in the HBV002 study is complete with 55 patients enrolled.

On November 7, 2022, we announced an update to the interim analysis of safety and efficacy data from the HBV002 study (NCT04778904), which was presented as a poster at the 2022 American Association for the Study of Liver Disease (AASLD) - The Liver Meeting® by Dr.

Young-Suk Lim, Professor of the Department of Gastroenterology and the Liver Center, Asian Medical Center, University of Ulsan College of Medicine, Korea.

The updated analysis, which included 55 patients with three months of follow up, showed that VTP-300 induced meaningful, sustained reductions of HBV surface antigen (HBsAg) in people with chronic HBV.

Declines were most prominent in patients with lower baseline HBsAg.

HBsAg is a hallmark of chronic HBV infection.

Fewer than 10% of patients on current standard-of-care HBV therapies achieve sustained HBsAg decrease or loss, a state associated with functional cure of the disease.

Group 3 (N=18) patients received VTP-300 in combination with a single low dose of nivolumab at the time of the booster dose, and the mean log10 reduction in HBsAg was 0.8 (n=18) at 3 months, 0.9 (n=10) at 6 months, and 1.3 (n=7) at 9 months, with more prominent declines observed in patients with baseline HBsAg lower than 1,000 IU/mL.

Five patients in this group had baseline HBsAg lower than 100 IU/mL, of which four had declines over 0.6 log10.

Moreover, two of those patients developed non-detectable HBsAg at 3 months, and one of the patients, who has been evaluated at 6 and 9 months, continued to maintain non-detectable HBsAg.

The secondary objectives of this study were to evaluate the HBV-specific T cell response and the effect on the levels of hepatitis B markers, including HBsAg, hepatitis B surface antibody seroconversion, HBV DNA and HBeAg.

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.

An interim analysis of HBV002 was conducted in November 2021, after which the protocol was amended to stop enrollment in cohorts 1 and 4 as no meaningful T cell responses nor meaningful reduction of HBsAg were observed with these regimen.

Enrollment continued in the cohort receiving VTP-300 as a monotherapy (Group 2) and the cohort receiving VTP-300 with a single low dose of nivolumab administered with the MVA dose (Group 3).

EASL Poster to Present Final Analysis of Safety and Efficacy Data from the HBV002 Study

In June 2023, we announced final safety and efficacy data from the HBV002 study (NCT04778904), which was presented as a poster at the EASL Congress 2023 – The International Liver Congress TM .

In the HBV002 study, 55 participants were randomized into four groups to receive combinations of VTP-300 and low-dose nivolumab, with follow-up for eight months post-final dose.

VTP-300 as monotherapy and in combination with low-dose nivolumab was administered with no treatment-related serious adverse events.

As reported previously, two out of 55 participants experienced transient transaminase flares.

Both incidents occurred in participants with HBsAg declines, but not in any of the participants who cleared HBsAg (<0.05 IU/mL).

Meaningful, durable reductions of HBsAg were seen in Group 2 (receiving VTP-300 monotherapy, N=18).

Three participants had 0.7, 0.7, and 1.4 log10 declines two months post-final dose, with durable responses continuing eight months post-final dose.

These participants all had baseline HBsAg <50 IU/mL.

A robust T cell response was generated and was highest in this group and there was a relation demonstrated between ELISpot response and HBsAg decline.

Those in Group 3 received VTP-300 followed by a single low dose of nivolumab together with Modified Vaccinia Ankara (MVA)-HBV (N=18).

Two months post-final dose, the mean reduction in HBsAg was 0.76 log10 (p<0.001).

This effect persisted with a mean decline of 0.98 log10 at eight months (p<0.001) after the last dose and was most prominent with starting values HBsAg <1,000 IU/mL.

Two participants developed non-detectable HBsAg levels, which continued eight months after last dose.

Pre-genomic RNA levels were observed to decrease significantly in the majority of participants in this group only, consistent with the decline in HBsAg levels.

Groups 1 and 4

No meaningful reductions in HBsAg were observed in Group 1, in which participants received two doses of MVA-HBV without ChAdOx1-HBV, or in Group 4, in which participants received low-dose nivolumab with both doses of VTP-300.

These groups were discontinued following interim analysis, as previously announced in June 2022.

Importantly, VTP-300, based on HBV genotype C sequences, was observed to lead to a decline in HBsAg in both genotype B- and C-infected CHB patients.

Additionally, T cell responses to HBV core protein induced by VTP-300 in healthy subjects were shown to cross-react with other prevalent genotypes (A to E).

Together, these results highlighted that T cell responses induced by VTP-300, based on genotype C, were cross-reactive to other common HBV genotypes.

HBV003 – Ongoing Phase 2b

HBV003 is designed to obtain critical information on treatment dosing regimen with patients receiving VTP-300 and low-dose nivolumab.

Our first patient was dosed in October 2022.

In the HBV003 trial, we are enrolling CHB patients in three treatment groups as described in the table below.

The study design directly builds from HBV002 to evaluate PD-1 inhibition timing, and includes criteria for discontinuation of standard-of-care nucleos(t)ide reverse transcriptase inhibitor (NUC) to obtain information on the durability of the response in the absence of treatment.

AASLD Oral Presentation on Interim Data from the HBV003 Study

In November 2023, we announced interim data from HBV003 (NCT05343481) as of October 10, 2023, which was presented as an oral presentation at The AASLD – The Liver Meeting® 2023.

Seventy-four out of a planned 120 virally suppressed CHB patients on stable NUC therapy had been enrolled in the trial and 57 had reached Day 113.

VTP-300 in combination with nivolumab led to HBsAg declines in all treatment groups, particularly in participants with screening HBsAg levels ≤200 IU/mL.

>0.5 and >1 log drops were observed in all groups at Day 113 in 23% and 9% of participants, respectively.

Participants with an HBsAg level of ≤200 IU/mL at screening were more likely to have >1 log HBsAg reductions (31%) compared to those with HBsAg levels >200 IU/mL at Day 1 (2%).

Greater mean HBsAg log reductions were observed in Group 2 (ChAdOx-HBV Day 1;

MVA-HBV and nivolumab Day 29 and Day 85) but insufficient data were available for a definitive conclusion.

Seven participants had met the criteria for NUC discontinuation;

three had discontinued and two had restarted NUC therapy.

One remained off NUC therapy at the time of analysis, retaining undetectable HBsAg 16 weeks post-NUC discontinuation.

Preliminary safety data suggested that VTP-300 in combination with nivolumab was generally well tolerated, with no treatment-related SAEs observed or reported.

Thyroid dysfunction was reported in seven participants attributed to nivolumab administration which had returned to normal in four patients.

We observed the highest rate of response in participants with screening HBsAg ≤200 IU/mL in the preliminary data.

The HBV003 trial protocol has since been amended to include only participants with screening HBsAg ≤200 IU/mL and people with thyroid autoantibodies, family history of autoimmune thyroiditis, or abnormal thyroid levels have been excluded from trial eligibility to minimize the risk of thyroiditis and improve the overall risk/benefit ratio.

AB-729-202 – Ongoing Phase 2a in collaboration with Arbutus Biopharma Corporation

AB-729-202 is an ongoing Phase 2a clinical trial in collaboration with Arbutus Biopharma Corporation (NASDAQ:

ABUS) to evaluate Arbutus’ RNAi therapeutic candidate, imdusiran or AB-729, in combination with VTP-300 for the treatment of patients with chronic HBV infection.

The clinical trial is designed to evaluate whether decreasing HBsAg levels with imdusiran prior to VTP-300 treatment, leads to a more sustained HBsAg reduction over treatment with imdusiran alone for CHB patients.

Primary endpoints are evaluating the safety, antiviral activity and immunogenicity of VTP-300 administered after AB-729.

The trial is designed to enroll 60 CHB patients as shown in the table below.

All patients receive imdusiran (60mg every 8 weeks) plus NUC therapy for 24 weeks.

At week 24, treatment with AB-729 stops and patients are randomized to receive either placebo (Group B) or VTP-300 (Groups A & C) at week 26 and 30 (and conditionally at week 38 if they experienced a >0.5log10 decline in HBsAg between week 26 and 34).

Group C receives in addition low dose nivolumab together with their MVA dose.

At week 48 all participants are evaluated for eligibility to either discontinue or remain on NUC therapy.

AASLD Poster Presentation on Interim Data from the AB-729-202 Study

On November 9, 2023, we announced interim data from the AB-729-202 trial (ACTRN12622000317796) as of October 13, 2023, which was presented as a late-breaking poster presentation at AASLD.

The preliminary data included a subset of patients from groups A and B (28/40 patients) and available follow-up data to week 48 (12/40 patients) and showed that robust reductions of HBsAg were observed during the imdusiran treatment period (-1.86 log10 mean reduction from baseline after 24 weeks of treatment).

This decline in HBsAg was comparable to the declines seen with imdusiran in other clinical trials conducted to date.

97% of the imdusiran treated patients (33/34) had HBsAg <100 IU/mL at the time of the first VTP-300/placebo dose.

VTP-300 treatment appeared to contribute to the maintenance of low HBsAg levels in the early post-treatment period, as the mean HBsAg levels in the placebo group began to increase starting approximately 12 weeks after the last dose of imdusiran.

All VTP-300 treated patients, with available follow-up data to week 48, maintained HBsAg <100 IU/mL through week 48, 60% have maintained HBsAg <10 IU/mL, and all qualified to stop NUC therapy.

Preliminary immunology data for those patients through to week 48 for which samples met the quality threshold and were available to be analyzed, suggested HBV-specific T cell IFN-γ production was enhanced in patients receiving imdusiran plus VTP-300 compared to placebo.

The preliminary safety data from this trial demonstrated that imdusiran and VTP-300 were both generally well-tolerated.

As of October 12, 2023, there were no serious adverse events, Grade 3 or 4 adverse events or treatment discontinuations.

We believe that the interim analysis from the HBV003 Phase 2b and the AB-729-202 Phase 2a studies suggest that VTP-300 could become part of a regimen that can attain a functional cure.

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.

We expect to announce interim efficacy data from both the HBV003 study and the combination study with siRNA from Arbutus in the fourth quarter of 2023.

We expect to announce interim efficacy data from both the HBV003 study and the AB-729-202 combination study with Arbutus in the second quarter of 2024.

Developing a Potential Non-Invasive Treatment for Persistent High-Risk HPV

We are developing VTP-200 as a potential curative treatment for persistent high-risk HPV infection and associated pre-cancerous lesions.

We are developing VTP-200 as a potential curative treatment for persistent hrHPV 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 our 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;

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 current 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.

We 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 our clinical trials.

Enrollment in our Phase 1b/2 APOLLO (HPV001) clinical trial of VTP-200, (NCT04607850), was completed in December 2022 and the last visit of the final patient to the clinic was in January 2024.

VTP-200 is composed of two viral vectors (ChAdOx1 and MVA), both encoding the same HPV antigens ( i.e.

E1, E2, E4, E5, E6, E7), designed to elicit an antigen-specific T cell immune response to HPV.

Both vectors are administered intramuscularly and sequentially, one month apart.

Clinical Development

Our 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.

We 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.

Our Phase 1b/2 APOLLO trial is designed to assess the safety and efficacy of VTP-200 and determine the optimal dosing regimen.

We have enrolled a total of 108 healthy women with low grade lesions who had persistent hrHPV for at least six months.

Patients with high-grade squamous intraepithelial lesions ("HSIL") or early cancer were excluded.

The trial was run in the United Kingdom and the European Union.

We 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.

We expect to announce full data from this trial in the first quarter of 2024.

The diagram below provides an overview of the Phase 1b/2 clinical trial design.

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.

The primary objective of the trial is to evaluate the safety and tolerability of VTP-200.

The secondary objectives of the trial are to determine the optimal dose and to evaluate the efficacy of HPV001 on the clearance of hrHPV infection and on the cervical intraepithelial neoplasia ("CIN").

We announced the topline initial interim safety and immunogenicity data of 58 patients in the main phase of the trial that reached their six-month evaluation timepoint in April 2023, and presented a poster at the 35th IPVC.

IPVC Poster Presentation on Interim Data from the APOLLO (HPV001) Trial

The poster presentation in April 2023 showed interim data for 42 women at Day 35, 7 days after the MVA dose of VTP-200, split by active treatment versus placebo.

VTP-200 was generally well-tolerated and was administered with no product-related grade 3 unsolicited adverse events and no product-related SAEs.

While the placebo group showed no antigen-specific T cell responses as measured by IFNg ELISpot, 26 of 29 women receiving varying doses of VTP-200 showed a response.

The pooled active groups showed meaningful responses, with the average being greater than 1,000 spot-forming units per million peripheral blood mononuclear cells.

Responses were strongest to the E1, E2 and E6 antigens.

In addition, intracellular cytokine staining data from the active groups showed both CD4+ and CD8+ responses.

Future Development

Following the HPV001 Phase 1b/2 clinical trial, if successful, we intend to initiate further clinical trials of VTP-200.

Our 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.

We are 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.

We expect to announce full data from the APOLLO trial at the beginning of the second quarter of 2024.

Following the HPV001 Phase 1b/2 clinical trial, if successful, we intend to review options to initiate further clinical trials of VTP-200, whether that is directly funded by the company or through external parties via partnerships, collaborations or grant funding.

Our next trials would potentially be a Phase 2/3 trial in healthy women with early grade CIN (squamous intraepithelial lesions ("LSIL")) and additional trials in patients with more advanced CIN, vulval intraepithelial neoplasia, or VIN, and anal intraepithelial neoplasia ("AIN").

Our Next-Generation Immunotherapeutic Candidate for Prostate Cancer

We are developing VTP-850, our 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;

Both VTP-800 and VTP-850 are composed of two viral vectors (ChAdOx1 and MVA, both encoding the same antigen sequences);

however, VTP-800 encodes only one antigen, 5T4, while VTP-850 encodes four antigens, PSA, PAP, STEAP1 and 5T4.

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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.

Phase 1 (VANCE) and Phase 2 (ADVANCE) clinical trials of VTP-800 were sponsored and conducted by the University of Oxford in the United Kingdom.

VTP-800 was generally well tolerated in both studies, with no treatment-related serious adverse events reported in VANCE or ADVANCE.

One grade 3 adverse event was reported in ADVANCE (chest infection), which was deemed not related to study drug.

There were no grade 4 or 5 treatment-related adverse events.

VANCE was a first-in-human, open label, randomized, Phase 1 clinical trial designed to evaluate the safety and immunological response of VTP-800 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.

Thirty-three patients received sequential administration of ChAdOx1-5T4 and MVA-5T4, one month apart, while six patients received MVA-5T4 alone.

Patients received both regimens alone or with cyclophosphamide preconditioning.

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There were no reported treatment-related serious adverse events.

It was also observed that 59% of participants had no detectable T cell response at baseline and developed a new 5T4-specific T cell response, as measured by an ex vivo gamma interferon ELISpot.

Two patients had a baseline response, and the frequency of 5T4-specific T cells was increased following administration.

The mean peak response of the 5T4-specific T cells in the responders was 198 cells per one million PBMCs, which is notable given that the 5T4 is a self-antigen.

Data showed that 59% of participants had no detectable T cell response at baseline and developed a 5T4-specific T cell response de novo.

Two patients had a baseline response, and the frequency of 5T4-specific T cells was observed to increase following administration.

T cell infiltration into the resected prostate was also observed.

The figure below shows the 5T4-specific T cell responses to VTP-800 in the responding patients.

The peak response, expressed as the number of 5T4-specific T cells secreting IFN-γ per one million PBMCs, in each patient who mounted a 5T4-specific T cell response following administration was compared to the 5T4 response detected prior to the first dose.

The bars represent medians.

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.

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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.

Patients received sequential administration of ChAdOx1-5T4 followed by MVA-5T4 one month later.

Nivolumab was administered at months one, two and three.

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There were no grade 4 or 5 treatment-related adverse events.

Three of eight patients with measurable disease had partial tumor responses.

Five of 23, or 22%, of patients had greater than 50% reduction of prostate specific antigen, or PSA, at any timepoint, as shown in the figure below.

PSA Reduction in Patients

Data showed that three of eight patients with measurable disease had partial tumor responses.

Five of 23, or 22%, of enrolled patients had greater than 50% reduction of prostate specific antigen ("PSA") at any timepoint.

PSA Reduction in Patients from ADVANCE Phase 2 Clinical Trial

In June 2023, we dosed our first patient with VTP-850 in PCA001, an ongoing Phase 1/2 clinical trial designed to determine the recommended Phase 2 regimen and evaluate the safety, efficacy, as measured by prostate-specific antigen (PSA) response, and induced T cell response of VTP-850 monotherapy in men with rising PSA after definitive local therapy for their disease (i.e., biochemical recurrence).

PCA001 builds on the previous promising data from the University of Oxford Phase 1 VANCE and Phase 1/2 ADVANCE clinical trials of VTP-800.

The trial involves a Phase 1 lead-in dose finding stage testing 2 doses of ChAdOx-PCA with follow-up MVA-PCA dose administered either intramuscularly or intravenously to determine the Phase 2 recommended dose and route of administration, followed by a two-stage expansion Phase 2 to evaluate immunogenicity and anti-tumor activity of VTP-850.

The diagram below provides an overview of the Phase 1/2 clinical trial design for PCA001.

The first phase of the trial is enrolling participants in the US.

Future Development

The FDA accepted our 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.

We plan 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.

Our first product utilizing SNAPvax CI platform for HPV16+ cancers

VTP-1100 is our 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 (see figure below).

Status and Future Development

VTP-1100 is currently in the preclinical stage with GMP manufacturing and pivotal IND-enabling studies underway.

We 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.

We expect to announce futility data from the lead-in phase of PCA001 in 2025, which will allow us to determine how we will progress with the PCA001 trial.

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.

VTP-1000 is a tolerizing immunotherapy candidate that is designed to restore tolerance and suppress the unwanted immune response to gluten by restoring a beneficial T regulatory to T effector ratio.

It is based on SNAP-TI and comprises multiple gluten antigens (representing the key antigens linked to celiac disease) and an immunomodulator co-delivered in nanoparticles of precise size and composition that are optimized to target the appropriate immune cells.

The immunomodulator is a key component of VTP-1000 and is intended to drive Treg expansion and prevent proinflammatory responses.

Status and Future Development

VTP-1000 is currently in preclinical development.

Preclinical lead optimization studies were recently completed and the product is entering engineering manufacturing, which we expect will enable us 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 our first product candidate directed towards the treatment of an inflammatory disease, we believe 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.

We submitted a filing to an Australian Research Ethics Committee and received approval for the study to proceed in the first quarter of 2024.

This application process will now be completed with a Clinical Trial Notification to the Australian Regulatory Authorities.

We also intend to file an IND with the FDA, and initiate the Phase 1 clinical trial in the second quarter of 2024.

We intend for the trials to be run in Australia and/or the U.S.

We plan to include pharmacodynamic analysis as part of the Phase 1 study to provide an indication that the immunotherapy is inducing Tregs and/or decreasing Teffectors.

Importantly, we also intend to include a controlled gluten challenge in the Phase 1 study to assess as an early signal whether VTP-1000 suppresses pathological response to gluten ingestion.

As VTP-1000 is our first product candidate directed towards the treatment of an inflammatory disease, we believe demonstration of Treg induction and/or suppression of unwanted immune responses to gluten would pave the way for other therapeutic candidates based on SNAP-TI, including those for alternative autoimmune indications.

Our Immunotherapeutic Candidate Targeting MAGE-A3 and NY-ESO1 Antigens

We are developing VTP-600, our 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.

We are developing VTP-600, our immunotherapy candidate encoding the tumor-associated antigens MAGE-A3 and NY-ESO1, initially as a potential first line 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.

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NY-ESO1 has been shown to have an expression rate of 27% across all NSCLC types.

We 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.

A Prophylactic Vaccine Product Candidate for Shingles

Beyond our therapeutic programs, we are also developing several prophylactic vaccine candidates.

VTP-400 is our 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.

Our regional partner in China and Southeast Asia, CanSino, plans to initiate a Phase 1 clinical trial of VTP-400 for shingles prevention.

We initiated a first-in-human Phase 1/2a trial in the first quarter of 2022, in collaboration with Cancer Research UK ("CRUK"), which is sponsoring and funding this study.

A Prophylactic Vaccine Candidate to Prevent MERS

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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.

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 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 our non-exclusive licensee, the University of Oxford.

On December 21, 2023, we announced a project with the CEPI and the University of Oxford, aiming to fast-track the development of VTP-500 for the prevention of MERS.

The project includes CEPI contributing funding of up to $34.8 million to Barinthus Bio, in addition to funds previously committed to the University of Oxford to develop and stockpile a ready reserve of emergency MERS vaccine candidate, VTP-500.

Due to VTP-500’s potential in significantly addressing the unmet need for MERS, the EMA confirmed support for the program through PRIME designation in December 2023.

The EMA’s PRIME designation enhances support for the development of medicines that target an unmet medical need, offering early and proactive support to medicine developers to optimize the generation of robust data on a medicine's benefits and risks and enable accelerated assessment of medicines applications.

A Prophylactic Vaccine Candidate for Shingles

VTP-400 is our 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.

Our regional partner in China and Southeast Asia, CanSino, initiated a Phase 1 clinical trial of VTP-400 in Canada in November 2023 to evaluate both T cell-mediated and B cell-mediated immune responses resulting from VTP-400.

A Prophylactic Vaccine for the Prevention of COVID-19 Infection

We believe our platform also positions us 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.

We co-invented our first-generation COVID-19 vaccine candidate VTP-900, now Vaxzevria, in partnership with the University of Oxford’s Jenner Institute, which we 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.

The speed of the development of Vaxzevria (formerly VTP-900 and AZD1222) for the prevention of COVID-19, which entered the clinic within three months from initial antigen design, demonstrated that our ChAdOx platform positions us well to develop future products, if approved, rapidly.

We co-invented VTP-900 in partnership with the University of Oxford’s Jenner Institute, which we assigned to Oxford University Innovation (OUI) to facilitate the licensing of those rights by OUI to AstraZeneca.

As of November 2022, more than 3 billion doses of Vaxzevria have been supplied across 180 countries globally.

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We are eligible to receive a share of royalties and other revenue received by OUI pursuant to its agreement with AstraZeneca for Vaxzevria.

There is no guarantee that further payments will be received pursuant to the agreement in the future and, if such payments are made, that we will be notified of such payments in a timely manner.

Our History and Team

We were founded in May 2016 as a spin-out from a leading institution in the United Kingdom, the Jenner Institute at the University of Oxford, with the aim of developing and commercializing innovative immunotherapeutics and vaccines to treat and prevent infectious diseases and cancer.

Our platform uses technologies that were developed at the Jenner Institute over 15 years and through clinical trials involving thousands of participants.

The ChAdOx1 and MVA platforms use technologies that were developed at the Jenner Institute over 15 years and through clinical trials involving thousands of participants.

Our scientific founders, Professor Adrian Hill KBE, FRCP, FRS and Professor Dame Sarah Gilbert DBE, are leaders in the fields of infectious diseases, immunology, vaccine development and viral vectors.

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She was the Oxford Project Lead for the Oxford/AstraZeneca COVID-19 vaccine project.

Our strategic trajectory has grown with the acquisition of Avidea Technologies, Inc.

("Avidea") and the SNAP platform in 2021, expanding our product candidate pipeline and strengthening our scientific leadership in immunotherapies and the autoimmune space.

We have assembled a management team with extensive expertise in building and operating biopharmaceutical organizations that have discovered, developed and delivered innovative medicines to patients.

Our management team has broad experience and successful track records in biopharmaceutical research, clinical development, regulatory affairs, manufacturing and commercialization, as well as in business, operations, and finance.

Our management team’s experience was gained at leading institutions that include Agalimmune, Akamis Bio, Altimmune, Aptiv Solutions, Ernst & Young, GenVec, IAVI, Kite Pharma, Pfizer, Merck-Serono, Novartis and Roche.

Our management team has broad experience and successful track records in biopharmaceutical drug discovery, clinical development, regulatory affairs, manufacturing and commercialization, as well as in business, operations, and finance.

Our management team’s experience was gained at leading institutions that include Agalimmune, Altimmune, Ernst & Young, GenVec, Merck-Serono, Novartis and Roche.

Our board of directors has extensive expertise in the fields of science, business, and finance.

Our scientific advisory board, or SAB, works with our management team in the planning and development of scientific, clinical, and research and development initiatives and strategies.

Our scientific advisory board ("SAB") works with our management team in the planning and development of scientific, clinical, and research and development initiatives and strategies.

The SAB is composed of scientific and clinical thought leaders in the fields of immunotherapy, vaccine development, immunology, infectious diseases, immunotolerance and oncology.

The Key Elements of Our Platform

Our proprietary platforms comprise several components that either 1) when combined, allow us 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) in the case of SNAPvax, induce regulatory T cells and/or decrease T cell activation to specifically control autoreactive immune cell hyperactivity, while maintaining the desired tolerability profile.

Our immunostimulatory platforms generate excellent immunogenicity in terms of B cell and T cell responses and are differentiated by their ability to induce very high numbers of functional and durable CD8+ T cells.

Our tolerizing platform is designed to restore immune tolerance by a mechanism of action, which includes the induction of regulatory T cells.

The key elements of our platforms are:

● Proprietary Simian Vectors:

ChAdOx1 and ChAdOx2 are modified simian adenoviral vectors which deliver target antigens into cells to generate a specific immune response.

These viruses were originally isolated from chimpanzees to avoid pre-existing immunity issues affecting the use of human adenovirus vectors.

Researchers at the Jenner Institute modified the ChAdOx viruses to be non-replicating and to have an increased antigen-carrying capacity.

To date, we have developed several vaccine and immunotherapy candidates with the ChAdOx vectors, each carrying target antigens that are specific to desired pathogens and diseases.

Adenoviral vectors have demonstrable safety profiles and are immunogenic in all age groups evaluated to date.

● Well-Validated Boost Vector:

MVA is a highly attenuated vaccinia virus used to deliver target antigens into cells to generate or boost an immune response.

MVA has a large antigen-carrying capacity and is especially immunogenic when used as a boosting vector in a heterologous prime- boost regimen.

MVA is replication-deficient and has a well-documented safety profile in hundreds of thousands of people, and is licensed as a smallpox vaccine in both Europe and the US.

● Proprietary Promoters and Enhancers:

Promoters and molecular enhancers are genetic codes that influence antigen expression.

For our adenoviral vectors, we use a proprietary promoter that is modified from cytomegalovirus.

The use of this modified promoter has been shown to increase antigen expression and also the resulting immune response.

For our MVA vector, we use a proprietary promoter to control expression of recombinant antigens and thereby enhance T cell induction levels.

We may use molecular adjuvants to enhance the CD8+ T cell response.

● Antigen Selection and Design:

We select full-length and subunit antigenic sequences from targeted pathogens, autoimmune targets or cancer targets.

We employ unique antigen design strategies to optimize in vivo immune presentation and maximize the desired type of immunogenicity while maintaining the desired tolerability profile.

For example, some target diseases may require a greater T cell-mediated response, whereas others may require a more balanced T and B cell response.

We use cutting-edge bioinformatics methods to design and optimize our antigen-encoding vectors.

To select antigen targets for pathogens, we use databases to rank options based on factors including global distribution of genetic strains, evolutionary competitive advantage, known pathogenicity and sequence upload bias.

We design our antigens to achieve maximal antigen presenting cell processing to elicit T cells.

● Rapid Vector Generation and Manufacturing:

We employ manipulation of adenovirus genomes to enable rapid generation of recombinant adenoviral vectors to meet GMP standards.

We believe our sequencing techniques have the potential to result in safer, more stable, product candidates.

Our adenovirus product candidates can be manufactured at exceptional speed and to significant scale, as it has been demonstrated with the COVID-19 vaccine Vaxzevria.

Vaxzevria, which is based on the ChAdOx1 vector, was designed, constructed and manufactured for human use within three months.

Normal GMP production processes typically take six to ten months each for adenovirus and for MVA.

● The Syntholytic and SNAPvax platforms allow for the presentation of essentially any chosen peptide to the immune system on a nanoparticle.

This platform allows for small molecules, such as Toll-like receptor agonists or inducers of T regulatory cells, to be co-delivered to the target cells.

The immunostimulatory SNAPvax platform has induced high magnitude, functional CD8+ T cells, especially when given as part of a prime-boost combination with ChAdOx1 in preclinical studies in mice and non-human primates.

The tolerizing SNAPvax platform has shown promising data on protection from disease in a mouse model of autoimmunity.

The products can be delivered by either the intramuscular or intravenous route, can modify innate immune function, and can be given repeatedly.

Our Collaboration and License Agreements

2016 License Agreement with OUI

In March 2016, we 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.

In March 2016, we entered into a license agreement ("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.

We refer to these areas together as the “Field.”

Pursuant to the 2016 OUI License Agreement, OUI granted us 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.

Pursuant to the 2016 OUI License Agreement, OUI granted us 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 (the "2016 Licensed Technology") to develop, manufacture, use and commercialize licensed products.

The rights are exclusive in certain fields and non-exclusive in others.

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If we sublicense the 2016 Licensed Technology, we will be required to pay OUI a mid-single-digit royalty on any royalties paid to us by the sublicensee and a high single-digit royalty on non-royalty sublicensing income (excluding milestone payment income overlapping with milestone payments paid to OUI and income used to fund research and development).

In the event that the royalties (excluding the royalty on sublicensing income) owed to OUI do not amount to a specified minimum ranging from the mid five figures to low six figures based on the license year in each year following March 2020, we must also pay OUI the difference between the royalty paid and the applicable minimum sum payable.

In March 2021 we therefore paid £38,750 to OUI, being the difference between royalties paid and the minimum sum payable.

In the event that the royalties (excluding the royalty on sublicensing income) owed to OUI do not amount to a specified minimum ranging from the mid five figures to low six figures based on the

license year in each year following March 2020, we must also pay OUI the difference between the royalty paid and the applicable minimum sum payable.

In addition, we are required to pay OUI milestone payments of up to an aggregate of £14.8 million upon the achievement of specified development, regulatory and commercial milestones.

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Upon termination of the 2016 OUI License Agreement, we are required to, among other things, grant to OUI an irrevocable, transferable, non-exclusive license to develop, make and use any improvements to the 2016 Licensed Technology which we made prior to the second anniversary of the date of the agreement.

2017 License Agreement with OUI

In September 2017, we 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, we 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.

2017 License Agreement with OUI (Barinthus Biotherapeutics (UK) Limited)

In September 2017, we entered into a further license agreement with OUI (the "2017 OUI License Agreement") for the development and commercialization of immunotherapies for HBV and HPV.

Pursuant to the 2017 OUI License Agreement, we 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 (the "2017 Licensed Technology"), to develop, manufacture, use and commercialize licensed products.

The rights are exclusive in some fields and non-exclusive in others.

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Unless earlier terminated, the 2017 OUI License Agreement will continue until the later of the expiration of the last claim of a licensed patent or 20 years from the date of the agreement.

The last patent under the 2017 OUI License Agreement, if granted, is expected to expire in August 2038, without giving effect to any potential patent term extensions or patent term adjustments.

The last patent under the 2017 OUI License Agreement, if

granted, is expected to expire in August 2038, without giving effect to any potential patent term extensions or patent term adjustments.

Either party may terminate for the uncured breach of the other party.

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Upon termination of the 2017 OUI License Agreement, we are required to, among other things, grant to OUI an irrevocable, transferable, non-exclusive license to develop, make and use any improvements to the 2017 Licensed Technology which we made prior to the second anniversary of the date of the agreement.

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 us 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.

2017 License Agreement with OUI (Barinthus Biotherapeutics North America, Inc.)

In March 2017, Avidea entered into a license agreement with OUI (the "March 2017 OUI License Agreement") 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 this March 2017 OUI License Agreement were assumed by Barinthus Bio NA following the acquisition of Avidea by Barinthus Biotherapeutics plc on December 10, 2021.

Pursuant to the March 2017 OUI License Agreement, OUI granted us a worldwide license under certain patent rights of OUI related to the use of thermo-responsive adjuvant scaffolds, among other rights (the "March 2017 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.

Pursuant to the 2017 OUI License Agreement, all intellectual property rights resulting from improvements made by us belong to us.

The March 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 and conditions.

Pursuant to the March 2017 OUI License Agreement, all intellectual property rights resulting from improvements made by us belong to us.

OUI retains the right for the University of Oxford, the U.S.

National Institutes of Allergy and Infectious Diseases (“NIAID”), the Instutite of Macromolecular Chemistry of the Czech Republic (“IMC”) and any person who works or has worked on the Licensed Technology to use the Licensed Technology and any licensee improvements for non-commercial use.

Furthermore, the University of Oxford, NIAID or IMC may publish the Licensed Technology and those improvements without our consent provided that they have first given us advance notice and delayed the publication if necessary for us to obtain patent protection.

In addition, OUI retains the right to grant academic and research licenses to any third parties under the Licensed Technology to encourage basic research for education and limited clinical patient care but may not grant licenses for commercialization of the Licensed Technology that is exclusively licensed to us, nor for development or marketing or products or services that are produced or supplied using the Licensed Technology.

Upon execution of the 2017 OUI License Agreement, we paid OUI a one-time upfront fee of £3,000.

We are obligated to pay OUI a low single-digit royalty on net sales of any product or process produced by or using the Licensed Technology.

If we sublicense the

Licensed Technology, we will be required to pay OUI a mid-single-digit royalty on any non-royalty sublicensing income.

National Institutes of Allergy and Infectious Diseases (“NIAID”), the Institute of Macromolecular Chemistry of the Czech Republic (“IMC”) and any person who works or has worked on the March 2017 Licensed Technology to use the March 2017 Licensed Technology and any licensee improvements for non-commercial use.

Furthermore, the University of Oxford, NIAID or IMC may publish the March 2017 Licensed Technology and those improvements without our consent provided that they have first given us advance notice and delayed the publication if necessary for us to obtain patent protection.

In addition, OUI retains the right to grant academic and research licenses to any third parties under the March 2017 Licensed Technology to encourage basic research for education and limited clinical patient care but may not grant licenses for commercialization of the March 2017 Licensed Technology that is exclusively licensed to us, nor for development or marketing or products or services that are produced or supplied using the March 2017 Licensed Technology.

Upon execution of the March 2017 OUI License Agreement, we paid OUI a one-time upfront fee of £3,000.

We are obligated to pay OUI a low single-digit royalty on net sales of any product or process produced by or using the March 2017 Licensed Technology.

If we sublicense the March 2017 Licensed Technology, we will be required to pay OUI a mid-single-digit royalty on any non-royalty sublicensing income.

As of March 14, 2024, OUI has not been paid any royalties under the 2017 OUI License Agreement.

In the event that the royalties (excluding the royalty on sublicensing income) owed to OUI do not amount to a specified minimum ranging from the low to mid five figures based on the license year in each year following March 2020, the licensee must also pay OUI the difference between the royalty paid and the applicable minimum sum payable.

In March 2021 £10,000 was paid to OUI, being the difference between royalties paid and the minimum sum payable.

In March 2023 £40,000 was paid to OUI, being the difference between royalties paid and the minimum sum payable.

For 2023, £55 thousand was paid to OUI, being the difference between royalties paid and the minimum sum payable.

In addition, we are required to pay OUI milestone payments of up to an aggregate of £2.43 million upon the achievement of specified development, regulatory and commercial milestones.

Unless earlier terminated, the 2017 OUI License Agreement will continue for as long as anything within the definition of the licensed patent remains in effect or 20 years from the date of the agreement.

The patent licensed under the 2017 OUI License Agreement, if granted, is expected to expire in October 2035, without giving effect to any potential patent term extensions or patent term adjustments.

The patent licensed under the March 2017 OUI License Agreement, if granted, is expected to expire in October 2035, without giving effect to any potential patent term extensions or patent term adjustments.

Either party may terminate for the uncured breach of the other party.

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OUI may terminate the agreement upon us filing for bankruptcy or in the event of liquidation or receivership proceedings, or upon 30 days’ prior written notice upon the occurrence of certain other events.

Upon termination of the 2017 OUI License Agreement, we are required to, among other things, grant to OUI an irrevocable, transferable, non-exclusive license to develop, make and use any improvements to the Licensed Technology which we made prior to the second anniversary of the date of the agreement.

2017 Cooperative Research and Development Agreement with NIH (Vaccitech North America, Inc.)

Upon termination of the March 2017 OUI License Agreement, we are required to, among other things, grant to OUI an irrevocable, transferable, non-exclusive license to develop, make and use any improvements to the March 2017 Licensed Technology which we made prior to the second anniversary of the date of the agreement.

2017 Cooperative Research and Development Agreement with NIH (Barinthus Biotherapeutics NA)

In February 2017, Avidea entered into a Cooperative Research and Development Agreement (“CRADA”) with the U.S.

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In November 2021, the CRADA was further amended (“4th CRADA Amendment”) to expand the scope of the collaborative research to evaluate the therapeutic potential of Avidea’s polymer-based vaccine technology, “Immunotherapeutic Nanoscaffolds” (IMNs), including Star polymers and self-assembling nanoparticles based on amphiphilic polymers (SNAP), in preclinical animal models for cancer, infectious and inflammatory diseases (e.g., induction of suppression and/or tolerance for treating or preventing allergies, autoimmunity, and transplant rejection).

In October 2022, the CRADA was further amended (“5th CRADA Amendment”) to acknowledge that all of Avidea’s rights, duties and obligations under the CRADA were assumed by Vaccitech North America, Inc.

(“Vaccitech NA”) following the acquisition of Avidea by Vaccitech plc.

on December 10, 2021.

Under the CRADA as amended we own inventions made solely by our staff, and we have an option to enter an exclusive or nonexclusive license to any inventions made solely by NIH staff or made jointly by our staff and NIH under the CRADA.

In October 2022, the CRADA was further amended (“5th CRADA Amendment”) to acknowledge that all of Avidea’s rights, duties and obligations under the CRADA were assumed by Barinthus Bio NA following the acquisition of Avidea by Barinthus Biotherapeutics plc on December 10, 2021.

NIH retains rights on behalf of the U.S.

Government in the Licensed Technology as required by statute and NIH policy.

Government in the CRADA Licensed Technology as required by statute and NIH policy.

We have an option to exclusively license any further inventions made under the CRADA.

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The parties may terminate the CRADA by mutual consent, or either party may unilaterally terminate the CRADA at any time upon 60 days’ prior written notice.

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.

2019 License Agreement with NIH (Barinthus Bio NA)

In September 2019, Avidea entered into a license agreement with the 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 CRADA entered into by NIH and Avidea in February 2017 and amended in March 2019, December 2020, May 2021, November 2021 and October 2022.

We are co-owners of all the Licensed Patents under this agreement, and we have an option to exclusively license NIH rights in all inventions made under this CRADA.

All of Avidea’s rights, duties and obligations under the 2019 License Agreement with NIH were assumed by Vaccitech North America, Inc.

(“Vaccitech NA”) following the acquisition of Avidea by Vaccitech plc.

on December 10, 2021.

The 2019 License Agreement with NIH was amended in September 2022 to note Vaccitech NA’s rights, duties and obligations and also to include newly filed patents developed under the 2017 CRADA as amended.

Pursuant to the 2019 License Agreement with NIH, NIH granted us a worldwide exclusive license under certain patent rights co-owned by us and NIH related to the use of the SNAPvax and syntholytic technology platforms, among other rights, or the Licensed Technology, to develop, manufacture, use and commercialize licensed products.

All of Avidea’s rights, duties and obligations under the 2019 License Agreement with NIH were assumed by Barinthus Bio NA following the acquisition of Avidea by Barinthus Biotherapeutics plc on December 10, 2021.

The 2019 License Agreement with NIH was amended in September 2022 to note Barinthus Bio NA’s rights, duties and obligations and also to include newly filed patents developed under the 2017 CRADA as amended.

Pursuant to the 2019 License Agreement with NIH, NIH granted us a worldwide exclusive license under certain patent rights co-owned by us and NIH related to the use of the SNAP platform, among other rights (the "2019 Licensed Technology"), to develop, manufacture, use and commercialize licensed products.

The license to patent rights are exclusive in all fields.

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In the event that the royalties (excluding the royalty on sublicensing income) owed to NIH do not amount to a specified minimum ranging from the low to mid five figures based on the license year in each year following September 2019, the licensee must also pay NIH the difference between the royalty paid and the applicable minimum royalty payment.

Within 60 days of execution of the 2019 License Agreement with NIH we paid $5,000 to NIH.

Within 60 days of January 1, 2020 $5,000 was paid to NIH, being the difference between royalties paid and the minimum sum payable.

Within 60 days of January 1, 2021 $5,000 was paid to NIH, being the difference between royalties paid and the minimum sum payable.

Within 60 days of January 1, 2022 $10,000 was paid to NIH, being the difference between royalties paid and the minimum sum payable.

Within 60 days of January 1, 2023 $10,000 was paid to NIH, being the difference between royalties paid and the minimum sum payable.

For 2023, $10 thousand was paid to NIH, being the difference between royalties paid and the minimum sum payable.

In addition, we are required to pay NIH milestone payments of up to an aggregate of $3.24 million upon the achievement of specified development, regulatory and commercial milestones for each Licensed Product.

Unless earlier terminated, the 2019 License Agreement with NIH will continue until expiry of the last to expire Licensed Patent.

5 patent families licensed under the 2019 License Agreement with NIH that cover the SNAPvax platform, if granted, are expected to expire in April 2038, in May 2039, in October 2039, in February 2042 and in June 2042, without giving effect to any potential patent term extensions or patent term adjustments.

5 patent families licensed under the 2019 License Agreement with NIH that cover the SNAP platform, if granted, are expected to expire in April 2038, in May 2039, in October 2039, in February 2042 and in June 2042, without giving effect to any potential patent term extensions or patent term adjustments.

Two patent families licensed under the 2019 License Agreement with NIH that cover the syntholytic platform, if granted, are expected to expire in April 2040 and in October 2041, without giving effect to any potential patent term extensions or patent term adjustments.

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NIH may terminate the agreement upon the occurrence of certain events.

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.

2017 Research Collaboration Agreement (“RCA”) with Institute of Macromolecular Chemistry, Prague (Barinthus Biotherapeutics NA)

In September 2017, Avidea entered into a RCA with the 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 molecules 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.

All of Avidea’s rights, duties and obligations under the 2017 RCA with IMC were assumed by Barinthus Bio NA following the acquisition of Avidea by Barinthus Biotherapeutics plc on December 10, 2021.

Under the RCA we own inventions made solely by our staff, and we have an exclusive option to enter an exclusive or nonexclusive license to any inventions made solely by IMC staff or made jointly by our staff and IMC under the RCA.

We have secured exclusive

rights in two patent families that we co-own with IMC under the 2022 License Agreement with IMC as described below.

We have secured exclusive rights in two patent families that we co-own with IMC under the 2022 License Agreement with IMC as described below.

We have an exclusive option to exclusively license any further inventions made under the RCA.

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Our rights in inventions made under the RCA survive expiry of the RCA.

2022 License Agreement with IMC (Vaccitech North America, Inc.)

In April 2022, we 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.

2022 License Agreement with IMC (Barinthus Bio NA)

In April 2022, we entered into an exclusive license agreement with the IMC for the exploitation, development and commercialization of technologies and products within the scope of Licensed Patent rights that had been developed under a RCA entered into by IMC and Avidea in September 2017.

We are co-owners of all the Licensed Patents under this agreement, and we have an option to exclusively license IMC rights in all inventions made under this RCA.

Pursuant to the 2022 License Agreement with IMC, IMC granted us a worldwide, exclusive license under certain patent rights co-owned by us 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.

Pursuant to the 2022 License Agreement with IMC, IMC granted us a worldwide, exclusive license under certain patent rights co-owned by us and IMC related to the use of polymer-based immunotherapies, among other rights (the "2022 Licensed Technology"), to develop, manufacture, use and commercialize licensed products.

The license to patent rights is exclusive in all fields.

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Unless earlier terminated, the 2022 License Agreement with IMC will continue until expiry of the last valid claim of the Licensed Patents.

One patent family licensed under the 2022 License Agreement with IMC that covers the SNAPvax platform, if granted, is expected to expire in September 2041, without giving effect to any potential patent term extensions or patent term adjustments.

One patent family licensed under the 2022 License Agreement with IMC that covers the SNAP platform, if granted, is expected to expire in September 2041, without giving effect to any potential patent term extensions or patent term adjustments.

One patent family licensed under the 2022 License Agreement with IMC that covers the syntholytic platform, if granted, is expected to expire in April 2040, without giving effect to any potential patent term extensions or patent term adjustments.

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2019 License Agreement with OUI

In January 2019, we entered into an additional license agreement with OUI, or the 2019 OUI License Agreement.

Pursuant to the 2019 OUI License Agreement, OUI granted us 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.

In January 2019, we entered into an additional license agreement with OUI (the "2019 OUI License Agreement").

Pursuant to the 2019 OUI License Agreement, OUI granted us 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 (the "2019 OUI 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.

Pursuant to the 2019 OUI License Agreement, all intellectual property rights resulting from improvements made prior to the second anniversary of the agreement (i) to the licensed patent rights by the inventor belong to OUI, and (ii) to the 2019 Licensed Technology by us belong to us.

OUI retains the right for the University of Oxford and any person who works or has worked on the Licensed Technology to use the 2019 Licensed Technology, as well as any improvements that we make to that technology during the first two years of the license, for education, research and limited clinical patient care.

Furthermore, the University of Oxford may publish the 2019 Licensed Technology and those improvements without our consent provided that they have first given us advance notice and delayed the publication if necessary for us to obtain patent protection.

In addition, OUI retains the right to grant academic and research licenses to any third parties under the 2019 Licensed Technology to encourage basic research for education and limited clinical patient care but may not grant licenses for commercialization of the 2019 Licensed Technology that is exclusively licensed to us, nor for development or marketing or products or services that are produced or supplied using the 2019 Licensed Technology.

OUI retains the right for the University of Oxford and any person who works or has worked on the 2019 OUI Licensed Technology to use the 2019 OUI Licensed Technology, as well as any improvements that we make to that technology during the first two years of the license, for education, research and limited clinical patient care.

Furthermore, the University of Oxford may publish the 2019 OUI Licensed Technology and those improvements without our consent provided that they have first given us advance notice and delayed the publication if necessary for us to obtain patent protection.

In addition, OUI retains the right to grant academic and research licenses to any third parties under the 2019 OUI Licensed Technology to encourage basic research for education and limited clinical patient care but may not grant licenses for commercialization of the 2019 OUI Licensed Technology that is exclusively licensed to us, nor for development or marketing or products or services that are produced or supplied using the 2019 OUI Licensed Technology.

Upon execution of the 2019 OUI License Agreement, we paid OUI a nominal upfront fee.

We are required to pay OUI a variable low single-digit royalty on net sales of products we develop using the 2019 Licensed Technology, which varies depending on whether the sales are within or outside of the field of personalized cancer vaccines for therapeutic use in humans.

While we are continuing to develop the 2019 Licensed Technology, no product candidate that we are currently developing incorporates this technology.

If we sublicense the 2019 Licensed Technology, we will be required to pay OUI a 15% or 7% royalty (for licensed products within the field and outside the field respectively) on any royalties paid to us by the sublicensee and 15% or 7.5% of non-royalty sublicensing income (for sublicenses granted before or after three years after the date of the agreement respectively).

We are required to pay OUI a variable low single-digit royalty on net sales of products we develop using the 2019 OUI Licensed Technology, which varies depending on whether the sales are within or outside of the field of personalized cancer vaccines for therapeutic use in humans.

While we are continuing to develop the 2019 OUI Licensed Technology, no product candidate that we are currently developing incorporates this technology.

If we sublicense the 2019 OUI Licensed Technology, we will be required to pay OUI a 15% or 7% royalty (for licensed products within the field and outside the field respectively) on any royalties paid to us by the sublicensee and 15% or 7.5% of non-royalty sublicensing income (for sublicenses granted before or after three years after the date of the agreement respectively).

In the event that the aforementioned royalties (excluding the royalty on non-royalty sublicensing income) owed to OUI do not amount to a specified minimum ranging from the mid five figures to low six figures based on the license year in each year following January 2022, we must also pay to OUI the difference between the royalty paid and the applicable minimum sum payable.

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At any time after the third anniversary of the agreement, we may terminate the agreement at any time upon three months’ prior written notice.

may terminate the agreement upon us filing for bankruptcy or in the event of liquidation or receivership proceedings, or upon 30 days’ prior written notice upon the occurrence of certain other events.

Upon termination of the 2019 OUI License Agreement, we are required to, among other things, grant to OUI an irrevocable, transferable, non- exclusive license to develop, make and use any improvements (to the technology embodied by the relevant licensed patent and know-how) which we made prior to the second anniversary of the date of the agreement.

2018 License Agreement with OUI and Oxford

In September 2018, we 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.

In September 2018, we entered into a license agreement (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 us 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.

Pursuant to the 2018 License Agreement, we agreed to grant to Oxford a fully-paid-up, worldwide, non- exclusive license under the Licensed Technology, as defined in the 2016 OUI License Agreement, and developments and improvements to such technology controlled by us during the term of the 2016 OUI License Agreement, or the MERS Technology, in the Field solely for the purpose of enabling Oxford to develop any product or process which uses or is within the scope of the MERS Technology, or Licensed Product.

The 2018 License Agreement enables Oxford to grant a further sublicense to CEPI in the field of MERS (the "Field") and to enable Oxford to conduct related activities.

Pursuant to the 2018 License Agreement, we agreed to grant to Oxford a fully-paid-up, worldwide, non- exclusive license under the Licensed Technology, as defined in the 2016 OUI License Agreement, and developments and improvements to such technology controlled by us during the term of the 2016 OUI License Agreement (the "MERS Technology") in the Field solely for the purpose of enabling Oxford to develop any product or process which uses or is within the scope of the MERS Technology ("Licensed Product").

This license includes the right to generate investigational stockpiles, but excludes any commercial use or sale of Licensed Products and is sublicensable by Oxford solely to its collaborators under the framework agreement entered into on or about the same date as the 2018 License Agreement between Oxford, CEPI and Janssen Vaccines & Prevention B.V.

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Pursuant to the 2018 License Agreement, OUI agreed that, notwithstanding our payment obligations under the 2016 OUI License Agreement, we are not obligated to make any payment to OUI in connection with the 2018 License Agreement.

Unless earlier terminated, the 2018 License Agreement shall remain in full force until the expiry or termination of the 2016 OUI License Agreement.

We may terminate the 2018 License Agreement immediately upon notice to Oxford in the event of Oxford’s uncured material breach.

In the event of termination of the 2018 License Agreement, provided that CEPI is not in breach of the terms of its sublicense, we shall at CEPI’s request grant it a sublicense under the MERS Technology in the Field solely of the scope outlined above and on materially the same terms, to the extent that we are able to do so.

On February 2, 2024, following the entry by Barinthus Biotherapeutics (UK) Limited and Oxford into a funding agreement with CEPI (described below), Oxford, OUI and Barinthus Biotherapeutics (UK) Limited entered into a termination agreement, pursuant to which the 2018 License Agreement was terminated other than obligations that have accrued prior to the termination or were expressly intended to survive, including certain confidentiality obligations.

OUI License Agreement Amendment

In April 2020, we 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 us 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.

In April 2020, we entered into an amendment, assignment and revenue share agreement (the "OUI License Agreement Amendment") with OUI to amend the 2016 OUI License Agreement.

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 us and the University of Oxford’s Jenner Institute to be negotiated with a suitable pharmaceutical partner.

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In addition, we assigned to OUI our rights to a jointly owned U.K.

patent application relating to the composition of matter related to a ChAdOx1 vector-based or a ChAdOx2 vector-based vaccine to prevent COVID-19, or the Assigned Patent Application, as well as certain other intellectual property rights related to any ChAdOx1 vector-based or ChAdOx2 vector-based COVID-19 vaccine covered by the Assigned Patent Application and its manufacture, including rights to the variations, improvements and modifications thereof, whether existing at or arising after the date of the OUI License Agreement Amendment.

patent application relating to the composition of matter related to a ChAdOx1 vector-based or a ChAdOx2 vector-based vaccine to prevent COVID 19 (the "Assigned Patent Application"), as well as certain other intellectual property rights related to any ChAdOx1 vector-based or ChAdOx2 vector-based COVID 19 vaccine covered by the Assigned Patent Application and its manufacture, including rights to the variations, improvements and modifications thereof, whether existing at or arising after the date of the OUI License Agreement Amendment.

In consideration of the rights granted by us, OUI agreed to pay us approximately 24% of payments, including royalties and milestones, received by OUI in connection with the commercialization of any ChAdOx1 vector-based or ChAdOx2 vector-based vaccine in the field of SARS-CoV2 covered by or disclosed in the Assigned Patent Application.

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Impact of OUI’s Agreement with AstraZeneca

OUI has entered into an exclusive research collaboration and worldwide license agreement, or the AstraZeneca License Agreement, with AstraZeneca UK Limited, or AstraZeneca.

OUI has entered into an exclusive research collaboration and worldwide license agreement (the "AstraZeneca License Agreement") with AstraZeneca.

The following description of the impact of AstraZeneca License Agreement with respect to our rights under the OUI License Agreement Amendment is based solely on an extract of the AstraZeneca License Agreement provided by the parties to that agreement.

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Moreover, there can be no assurance that the AstraZeneca License Agreement is an enforceable agreement, that the parties thereto will comply with their obligations under that agreement (including any obligations of AstraZeneca to make milestone or royalty payments to OUI), or that the terms of that agreement (including royalty rates and other economic terms) will not be modified by the parties in the future.

Accordingly, these and other factors could cause amounts received by OUI pursuant to the AstraZeneca License Agreement to differ from those described below, and any such differences could be material.

The AstraZeneca License Agreement allows AstraZeneca to pursue, among other things, the commercialization of a vaccine product candidate for the prevention of COVID 19 containing one or more of the ChAdOx1 or ChAdOx2 vectors or their derivatives.

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Master Collaboration Agreement with CanSino Biologics Inc.

In September 2018, we entered into a master collaboration agreement, or the CanSino Agreement, with CanSino Biologics Inc., or CanSino.

The CanSino Agreement provides a framework under which we 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 our 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 our territory, or the Vaccitech Territory, includes the rest of the world.

Under the CanSino Agreement, each party grants to the other party a royalty-free, non-exclusive license to use its relevant background intellectual property rights, or Background IPR, solely to perform the project in the other party’s territory, together with a right to sub-license to any agreed-upon subcontractor performing services for and on behalf of the other party.

In September 2018, we entered into a master collaboration agreement (the "CanSino Agreement") with CanSino Biologics Inc.

products, and carry out those projects under the terms of the CanSino Agreement and the respective project agreements in our 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 our territory (the "Barinthus Bio Territory") includes the rest of the world.

Under the CanSino Agreement, each party grants to the other party a royalty-free, non-exclusive license to use its relevant background intellectual property rights ("Background IPR") solely to perform the project in the other party’s territory, together with a right to sub-license to any agreed-upon subcontractor performing services for and on behalf of the other party.

For any collaborative project, each party is obliged to provide to the other party all applicable materials specified in that project agreement and to grant to the other party a non-exclusive license to use such materials solely for the purpose of that project.

In addition, each party grants to the other party a non-exclusive license to use its Background IPR and an exclusive license to any new intellectual property created in the course of activities performed by such party in relation to a project or otherwise under the CanSino Agreement, or New IPR, to the extent necessary to commercialize and exploit collaboration products in the other party’s territory.

In addition, each party grants to the other party a non-exclusive license to use its Background IPR and an exclusive license to any new intellectual property created in the course of activities performed by such party in relation to a project or otherwise under the CanSino Agreement ("New IPR") to the extent necessary to commercialize and exploit collaboration products in the other party’s territory.

Such commercialization licenses are sublicensable (without further right to sub-license) and subject to the payment of royalties and milestones as set out in the relevant project agreement.

CanSino is permitted to commercialize such products only in the CanSino Territory and we are entitled to commercialize such products in the Vaccitech Territory.

CanSino is permitted to commercialize such products only in the CanSino Territory and we are entitled to commercialize such products in the Barinthus Bio Territory.

Both parties are under obligations to use commercially reasonable efforts to maximize sales of products that are the subject of collaboration.

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Furthermore, unless agreed otherwise in a project agreement, for any product which we collaboratively develop, CanSino has the exclusive and sub-licensable right to manufacture and supply all master virus seed and clinical adenoviral material necessary for the development and sale of any products by either party in their respective territories.

CanSino will supply any such material to be used by us for the manufacture of products to be sold by us (or our sub-licensees) at the price of 15% to 30% over cost of goods sold, or COGS.

CanSino will supply any such material to be used by us for the manufacture of products to be sold by us (or our sub-licensees) at the price of 15% to 30% over cost of goods sold ("COGS").

COGS is equal to the reasonable COGS for equivalent material manufactured by CanSino or its subcontractors for sale by CanSino or its sub-licensees.

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2018 ChAdOx Zoster Project Agreement (under the CanSino Agreement)

Pursuant to the CanSino Agreement, we entered into a project agreement in September 2018 with CanSino, or the ChAdOx Zoster Project Agreement, with the goal of developing a Zoster vaccine to become a competitor to Shingrix.

Under the ChAdOx Zoster Project Agreement, we are 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.

Pursuant to the CanSino Agreement, we entered into a project agreement in September 2018 with CanSino (the "ChAdOx Zoster Project Agreement") with the goal of developing a Zoster vaccine to become a competitor to Shingrix.

Under the ChAdOx Zoster Project Agreement, we are responsible for funding and undertaking various development tasks, including

(subject to availability of funding) conducting a Phase 1 clinical trial in the UK.

CanSino was responsible for funding and undertaking various development tasks, including conducting a Phase 1 clinical trial in China.

The ChAdOx Zoster Project Agreement was amended on August 31, 2023 following the parties’ agreement that the Phase 1 clinical trial to be conducted by CanSino as Sponsor should be carried out in Canada (rather than China).

It was also agreed that the parties would each be responsible for 50% of the budgeted cost of the Phase 1 clinical trial (rather than each being responsible for funding or securing funding for any Phase 1 clinical trial in its respective country).

The amendment further expanded the scope of the ChAdOx Zoster Project Agreement to cover potential administration of the product by inhalation.

The parties’ rights and responsibilities in relation to Phase 2 and 3 clinical trials are pending, subject to further negotiation.

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If the parties cannot agree upon such supply agreement, they must follow a specified dispute resolution process set forth in the CanSino Agreement.

For all products manufactured by CanSino under a supply agreement that we wish to sell in the Vaccitech Territory, we have agreed to pay the costs incurred by CanSino to manufacture the products plus 20% of such costs.

For all products manufactured by CanSino under a supply agreement that we wish to sell in the Barinthus Bio Territory, we have agreed to pay the costs incurred by CanSino to manufacture the products plus 20% of such costs.

We received an upfront payment of £50,000 under this project agreement.

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If CanSino sublicense their rights in the product to a non-affiliate third party, we are also entitled to receive a mid-teens royalty on the transaction value (excluding royalties).

We must pay to CanSino mid-single-digit royalties on the net sales of the product by or on behalf of us or our sub-licensees in the Vaccitech Territory.

We must pay to CanSino mid-single-digit royalties on the net sales of the product by or on behalf of us or our sub-licensees in the Barinthus Bio Territory.

A party will benefit from a reduction of its royalties (in the low single digits) where it requires a license from a third party to sell the product in its territory.

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Upon the expiration of the term, we agreed to grant CanSino a royalty-free, perpetual, sub-licensable, non-exclusive license to use our Background IPR and our New IPR used to develop, incorporated in, or referenced in any products that are the subject of the project agreement to the extent necessary for CanSino to undertake research, develop, manufacture and commercialize such products in the CanSino Territory.

Pursuant to the CanSino Agreement, upon the expiration or earlier termination of the project agreement, except for termination by CanSino for our breach, CanSino agreed to grant us a royalty-free, perpetual, sub-licensable, non-exclusive license to use their Background IPR and New IPR used to develop, incorporated in, or referenced in any products that are the subject of the project agreement to the extent necessary for us to undertake research, develop, manufacture and commercialize such products in the Vaccitech Territory.

Unless we terminate the project agreement early for CanSino’s breach, upon early termination after completion of a Phase 1 trial, we will continue to pay CanSino a low single-digit royalty on net sales of the product by us or our sub-licensees in the Vaccitech Territory, for the remainder of the Term.

Unless we terminate the project agreement early for CanSino’s breach, upon early termination after completion of a Phase 1 trial, we will continue to pay CanSino a low single-digit royalty on net sales of the product by us or our sub-licensees in the Barinthus Bio Territory, for the remainder of the Term.

If such early termination is after completion of a Phase 2 trial, the royalty we must pay rises to mid-single digit.

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.

Clinical Trial and Option Agreement with CRUK

In December 2019, Vaccitech Oncology Limited ("VOLT"), entered into a clinical trial and option agreement (the "Clinical Trial Agreement") with CRUK and CRUK’s subsidiary, Cancer Research Technology Limited ("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 UK.

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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 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.

Upon the completion of the Clinical Trial, VOLT has the option to obtain a license to use such results (the "VTP 600 License").

The terms of the VTP 600 License have been pre-agreed and are set out in the Clinical Trial Agreement.

If VOLT exercises the option to take the VTP-600 License, CRT agrees to grant VOLT an exclusive license under the results of the Clinical Trial that exclusively relate to the VTP-600 immunotherapy product, or the Exclusive Results, and a non-exclusive license under any results that are not Exclusive Results, in each case, to develop and commercialize any product which makes use of the results of the Clinical Trial in an application for regulatory authorization, contains the relevant active ingredients, or is covered by the patent application PCT/EP2019/070555, or the Product.

If VOLT exercises the option to take the VTP 600 License, CRT agrees to grant VOLT an exclusive license under the results of the Clinical Trial that exclusively relate to the VTP 600 immunotherapy product (the "Exclusive Results") and a non-exclusive license under any results that are not Exclusive Results, in each case, to develop and commercialize any product which makes use of the results of the Clinical Trial in an application for regulatory authorization, contains the relevant active ingredients, or is covered by the patent application PCT/EP2019/070555 (the "Product").

The rights under the VTP 600 License are sublicensable (except to a tobacco company).

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Upon exercise of the option, VOLT is required to pay a one-time upfront fee of an amount in pounds Sterling in the high six-digits.

VOLT is also obligated to make future milestone payments upon the achievement of development, regulatory and commercial milestones, with an aggregate total value of £40,750,000.

VOLT is also obligated to make future milestone payments upon the achievement of development, regulatory and commercial milestones, with an aggregate total value of £40.8 million.

VOLT is required to pay to CRT a low single-digit royalty on net sales of Products sold by VOLT or its sublicensees.

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CRT may also terminate the VTP 600 License as a whole if no Product is being actively developed or commercialized.

If VOLT does not exercise the option to take the VTP-600 License, or if the VTP-600 License or Clinical Trial Agreement is subsequently terminated by CRUK (as described below) VOLT will enter into a step-in agreement with CRT, or the Step-In Agreement.

If VOLT does not exercise the option to take the VTP 600 License, or if the VTP 600 License or Clinical Trial Agreement is subsequently terminated by CRUK (as described below) VOLT will enter into a step-in agreement with CRT (the "Step-In Agreement").

Pursuant to the Step-In Agreement, the terms of which have been pre-agreed and are set out in the Clinical Trial Agreement, VOLT will assign to CRT certain know- how and materials owned or controlled by VOLT.

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VOLT License Agreement

In November 2018, we entered into a license agreement, or the VOLT License Agreement, with VOLT.

Pursuant to the VOLT License Agreement, we 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 November 2018, we entered into a license agreement (the "VOLT License Agreement") with VOLT.

Pursuant to the VOLT License Agreement, we 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 (the "VOLT Licensed Technology"), to manufacture, use and commercialize any product which uses or is within

the scope of the VOLT Licensed Technology (the "VOLT Licensed Product").

In part, the rights granted are a sublicense of rights granted to us by OUI under the 2016 OUI License Agreement.

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Such amendments further elaborated on the parties’ respective rights and obligations, including with respect to VOLT’s payment obligations to us.

2023 CEPI Funding Agreement

On December 20, 2023, we, the Chancellors, Masters and Scholars of the University of Oxford (“Oxford,” together with us, the “Partners”) and the CEPI entered into a Funding Agreement (the “Funding Agreement”) pursuant to which CEPI will provide funding of up to $34.8 million to us to advance the development of VTP-500, our vaccine candidate against MERS (such development activities, the “Project”).

In December 2023, VTP-500 received PRIority MEdicines (“PRIME”) designation by the EMA.

Under the Funding Agreement, the Partners have agreed to use reasonable endeavors to achieve the deliverables, milestones and timelines for the vaccine development activities under discrete “Work Packages” mutually agreed to by the parties from time to time.

Under the initial Work Package, we have agreed, subject to the achievement of certain milestones, including a successful Phase 2 clinical trial of VTP-500, that it will manufacture or have manufactured an investigational ready reserve of 100,000 doses of VTP-500 to be rapidly deployed for a clinical trial in the event of a substantial outbreak of MERS.

During the Term (as defined below), we have also agreed to certain collaboration obligations in the event of a regional or national public health emergency or preparation need for an impending outbreak of MERS.

Pursuant to the Funding Agreement, we will retain ownership of its intellectual property owned or controlled throughout the term of the Funding Agreement, subject to the rights of CEPI under the Funding Agreement.

We will also own any intellectual property invented by or on behalf of us in connection with the activities contemplated by the Funding Agreement, as well as all tangible materials and results made or developed by or on behalf of us in connection with the Funding Agreement.

Any amounts funded by CEPI to the Partners under the Funding Agreement in accordance with each Work Package will be paid in tranches covering six-month periods based on mutually agreed project-based budgets and subject to certain conditions as set forth in the Funding Agreement including the achievement of identified milestones.

Pursuant to the Funding Agreement, we have agreed to pay CEPI on a country-by-country basis increasing mid-single digit percentage royalties of net sales and net income with respect to future cash sales of VTP-500, less certain deductions, for a period starting on December 20, 2023 (“Effective Date”) and ending the later of:

(i) the expiration of the last valid patent claim included in intellectual property developed under the Project covering VTP-500 in such country, (ii) the expiration of Regulatory Exclusivity (as defined in the Funding Agreement) for VTP-500 in such country, and (iii) the tenth (10th) anniversary of the first commercial sale of VTP-500 (the “Royalty Term”).

The Company shall also pay CEPI a mid-double digit percentage of net revenue earned on VTP-500 until CEPI has received payments from us under the Funding Agreement equaling the total amount of funding paid by CEPI to us and a low double-digit percentage of such net revenue thereafter.

Sales for the benefit of end users in specified low and middle income countries (“LMICs”) and upper and middle

income countries (“UMICs”) are excluded from the calculations of net sales and net revenue.

Sales of product for the benefit of end users in LMICs and UMICs are subject to tiered discounted pricing requirements under the Funding Agreement.

The Company is further required to pay a mid-double digit percentage of any proceeds earned on any priority review voucher related to VTP-500 during the Royalty Period.

The Funding Agreement will commence on the Effective Date and will continue until the fifth (5th) anniversary of the Effective Date, unless the parties agree to extend the Funding Agreement for a period of up to twenty-four (24) months unless all activities under the Funding Agreement have been completed (“Term”).

Either Partner or CEPI can terminate the Funding Agreement following an insolvency event or material breach by the other party that is not cured within forty-five (45) business days, in the event of termination by a Partner, or thirty (30) business days, in the event of termination by CEPI.

Pursuant to the Funding Agreement, CEPI also has certain discretionary termination rights, including if CEPI determines that we are involved in material safety, regulatory, scientific misconduct, or ethical issues or is no longer able to fulfill its obligations under the Funding Agreement.

Neither CEPI, us nor Oxford may assign its rights or obligations under the Funding Agreement without the other parties’ consent;

provided that CEPI may do so to an organization of equivalent charitable mission and technical capabilities.

Intellectual Property

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We also rely on trade secrets, know-how, continuing technological innovation and in-licensing of third-party intellectual property to develop and maintain our proprietary position.

We, or our collaborators and licensors, file patent applications directed to our key product candidates in an effort to establish intellectual property positions to protect our product candidates as well as uses of our product candidates for the prevention and/or treatment of diseases.

As of March 23, 2023, we own a patent family relating to our 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, we have in-licensed certain patent families relating to our 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 we control 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.

We, or our licensors, file patent applications directed to our key product candidates in an effort to establish intellectual property positions to protect our product candidates as well as uses of our product candidates for the prevention and/or treatment of diseases.

As of March 14, 2024, we own a patent family relating to our novel regimens that includes one pending U.S.

patent application, two pending foreign patent applications and one pending Patent Cooperation Treaty ("PCT") patent application together with one pending U.S.

provisional patent application relating to our novel products.

In addition, we have in-licensed certain patent families relating to our key technology platforms and product candidates, including ten issued U.S.

patents, nine pending U.S.

patent applications, at least 20 issued foreign patents and at least 70 pending foreign patent applications.

Following the acquisition of Avidea in December 2021 we control a further patent portfolio comprising in-licensed and co-owned patent families, including 10 pending U.S.

patent applications, six issued foreign patents, 48 pending foreign patent applications and two pending PCT patent applications.

Universal Vector Technology Platforms

ChAdOx 1 Expression Vector

As of March 23, 2023, with regard to our ChAdOx1 expression vector, we in-license from OUI a patent family that includes two issued U.S.

As of March 14, 2024, with regard to our ChAdOx1 expression vector, we in-license from OUI a patent family that includes three 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.

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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 authorisations received by AstraZeneca for Vaxzevria, and patent term extension has been granted in Australia.

Patent term extensions have been granted in Australia until February 16, 2036 and in Japan for an additional 1 year, 1 month and 24 days, based on marketing authorisations received by AstraZeneca for Vaxzevria.

Adenoviral Promoter

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MVA-poxvirus Promoter

Our MVA vector incorporates a proprietary poxvirus promoter, or MVA-poxvirus promoter, which is covered by a patent family that we in-license from OUI.

Our MVA vector incorporates a proprietary poxvirus promoter ("MVA-poxvirus promoter") which is covered by a patent family that we in-license from OUI.

As of March 14, 2024, 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.

Our proprietary SNAPvax technology is covered by a patent portfolio that includes one patent family we own, 6 patent families that we co-own and one patent family that we in-license from OUI.

Synthetic SNAP platform (SNAP-TI TM and SNAP-CI TM )

Our proprietary synthetic SNAP platform is covered by a patent portfolio that includes one patent family we own, seven patent families that we co-own and one patent family that we in-license from OUI.

As of March 14, 2024, we in-license a patent family from OUI that includes one pending U.S.

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As of March 14, 2024, we own 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 14, 2024, we co-own a patent family that includes two issued foreign patents, one pending U.S.

patent application, one pending European patent application and a at least 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.

We have exclusively licensed rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

As of March 14, 2024, we co-own 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.

We have 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”).

We have exclusively licensed rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

As of March 14, 2024, we co-own 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.

We have exclusively licensed rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

As of March 14, 2024, we co-own a patent family that includes one pending U.S.

We have 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, we co-own 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.

We have 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, we 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH.

patent application, one pending European patent application and a further nine 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

As of March 14, 2024, we co-own 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.

We have 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”).

patent application, one pending European patent application and a further three 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

As of March 14, 2024, we co-own a patent family that includes one pending U.S.

patent application, one pending foreign patent application and a further two pending foreign patent applications 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.

We have licensed exclusive rights in this patent family, which resulted from work carried out under a RCA with the IMC.

As of March 14, 2024, we co-own a patent family that includes one pending U.S.

patent application and one pending international PCT patent application that are expected to expire in 2043, 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

As of March 14, 2024, we co-own a patent family that includes one pending international PCT patent application that is expected to expire in 2043, 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

Our proprietary Syntholytic technology is covered by a patent portfolio that includes one patent family we own, 2 patent families that we co-own and one patent family that we in-license from OUI.

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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.

We have exclusively rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH, and we have 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, we co-own 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.

We have exclusively rights in this patent family, which resulted from work carried out under a CRADA between Avidea and the NIH.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA with the NIH, and we have licensed exclusive rights in this patent family, which resulted from work carried out under a RCA with the IMC, Prague.

As of March 14, 2024, we co-own a patent family that includes one pending U.S.

patent application, one pending European patent application and a further two pending foreign patent applications 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA with the NIH.

Product Candidates

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As of March 14, 2024, 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.

patent, two issued foreign patents, one pending U.S.

patent application and eight foreign patent applications pending in jurisdictions including Europe, Australia, Canada, 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.

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Our 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, we in-license 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.

As of March 14, 2024, we in-license from OUI a patent family with claims directed to a multi-HBV immunogen viral vector vaccine that includes two issued foreign patents, one pending U.S.

patent application and 15 foreign patent applications pending in jurisdictions including Europe, Australia, Canada and China.

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As of March 14, 2024, 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, we also rely 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 our adenoviral promotor, which is expected to expire in 2028, and the patent family directed to our MVA-poxvirus promoter, which is expected to expire in 2031, as discussed above.

Our 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.

patent application and at least 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, we also rely 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 our adenoviral promotor, which is expected to expire in 2028, and the patent family directed to our MVA-poxvirus promoter, which is expected to expire in 2031, as discussed above.

Our VTP-800 and VTP-850 product candidates comprise a ChAdOx15T4 vector and a MVA5T4 vector, where each vector incorporates an engineered 5T4 antigen and in VTP-850 the 5T4 antigen is also in combination with additional antigens.

We 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.

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We also rely 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 our adenoviral promotor, which is expected to expire in 2028, as discussed above.

Our VTP-1100 product candidate includes SNAPvax technology to target HPV16+ cancers.

We co-own a patent family with claims directed to methods of treating cancers using SNAPvax compositions.

As of March 23, 2023, the patent family includes 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA between Vaccitech and the NIH.

In addition, we rely 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.

Our VTP-1000 product candidate includes SNAPvax technology to provide tolerizing immunotherapy for celiac disease.

Our VTP-1100 product candidate includes SNAP-CI platform technology to target HPV16+ cancers.

We co-own a patent family with claims directed to methods of treating cancers using SNAP-CI compositions.

As of March 14, 2024, the patent family includes one pending international PCT patent application.

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 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.

We have exclusive rights in this patent family, which resulted from work carried out under a CRADA between Barinthus Bio and the NIH.

In addition, we rely on patent protection afforded by the patent families directed to the SNAP technology platforms, which are expected to expire between 2030 and 2042, as discussed above.

Our VTP-1000 product candidate includes SNAP-TI platform technology to provide tolerizing immunotherapy for celiac disease.

We co-own a patent family with claims directed to compositions and methods for treating celiac disease.

As of March 14, 2024, the patent family includes one pending U.S.

provisional patent application.

If a patent were to issue from a patent application claiming the benefit of this U.S.

In addition, we rely 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.

patent application and one pending international PCT patent application.

If a patent were to issue from either of these pending applications or from a patent application claiming the benefit of either of these applications, 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, we rely on patent protection afforded by the patent families directed to the SNAP technology platforms, which are expected to expire between 2030 and 2042, as discussed above.

Individual patents have terms for varying periods depending on the date of filing of the patent application or the date of patent issuance and the legal term of patents in the countries in which they are obtained.

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The actual protection afforded by a patent may vary on a product by product basis, from country to country and can depend upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions and the availability of legal remedies in a particular country and the validity and enforceability of the patent.

Our patents and patent applications may be subject to procedural or legal challenges by others.

and patent applications may be subject to procedural or legal challenges by others.

We may be unable to obtain, maintain and protect the intellectual property rights necessary to conduct our business, and we may be subject to claims that we infringe or otherwise violate the intellectual property rights of others, which could materially harm our business.

For more information about the risks associated with our efforts to obtain adequate intellectual property protection for our product candidates, and the enforcement of such intellectual property rights, as well as the risks associated with third party intellectual property rights, see the section titled “Risk Factors — Risks Related to Our Intellectual Property.” With regard to our VTP-300 product candidate, we are aware of third- party patents in the United States with claims which may be relevant to this product candidate.

For more information about the risks associated with our efforts to obtain adequate intellectual property protection for our product candidates, and the enforcement of such intellectual property rights, as well as the risks associated with third party intellectual property rights, see the section titled “Risk Factors — Risks Related to Our Intellectual Property.” With regard to our VTP-300 and VTP-850 product candidates, we are aware of third-party patents in the United States with claims which may be relevant to these product candidates.

See “Risk Factors — Risks Related to Intellectual Property — The intellectual property landscape around immunotherapeutics and viral-vector based vaccines is crowded and dynamic, and third parties may initiate legal proceedings alleging that we are infringing, misappropriating or otherwise violating their intellectual property rights and such claims may be costly and time-consuming and may prevent or delay our product discovery and development efforts.”

Government Regulation

In the United States, biological products are subject to regulation under the Federal Food, Drug, and Cosmetic Act (the “FD&C Act”), and the Public Health Service Act (the “PHS Act”), and other federal, state, local and foreign statutes and regulations.

Both the FD&C Act and the PHS Act and their corresponding regulations govern, among other things, the research, development, clinical trial, testing, manufacturing, quality control, approval, safety, efficacy, labeling, packaging, storage, record keeping, distribution, reporting, marketing, promotion, export and import, advertising, post-approval monitoring, and post-approval reporting involving biological products.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources and we may not be able to obtain the required regulatory approvals.

In the United States, biological products are subject to regulation under the Federal Food, Drug, and Cosmetic Act (the “FD&C Act”), the Public Health Service Act (the “PHS Act”), and other federal, state, and local statutes and regulations.

Both the FD&C Act and the PHS Act and their corresponding regulations govern, among other things, the research, development, testing, manufacturing, quality control, approval, safety, efficacy, labeling, packaging, storage, record keeping, distribution, reporting, marketing, promotion, export and import, advertising, post-approval monitoring, and post-approval reporting involving biological products.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations, and international guidelines require the expenditure of substantial time and financial resources and we may not be able to obtain the required regulatory approvals.

Further, even if we obtain the required regulatory approvals for our products, pharmaceutical companies are subject to myriad federal, state, and foreign healthcare laws, rules, and regulations governing all aspects of our operations, including, but not limited to, our relationships with healthcare professionals, healthcare institutions, distributors of our products, and sales and marketing personnel;

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Biological Products Development Process

In the United States, the FDA is responsible for enforcing the laws in place to protect public health by ensuring the safety, efficacy, and security of biological products.

The process required by the FDA before a biological product may be marketed in the United States generally involves the following:

● completion of nonclinical laboratory tests and animal studies according to GLPs and applicable requirements for the humane use of laboratory animals or other applicable regulations;

● submission to the FDA of an application for an IND which must become effective before human clinical trials may begin;

● approval of the protocol and related documentation by an independent institutional review board, or IRB, or ethics committee at each clinical trial site before each trial may be initiated;

● performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as good clinical practices, or GCPs, and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed biological product for its intended use;

● preparation of and submission to the FDA of a biologics license application, or BLA, for marketing approval that includes sufficient evidence of establishing the safety, purity, and potency of the proposed biological product for its intended indication, including from results of nonclinical testing and clinical trials;

● satisfactory completion of an FDA inspection of the manufacturing facility or facilities where the biological product is produced to assess compliance with current good manufacturing practices, or cGMPs, to assure that the facilities, methods and controls are adequate to preserve the biological product’s identity, strength, quality and purity;

● potential FDA audit of the nonclinical study and clinical trial sites that generated the data in support of the BLA;

● review of the product candidate by an FDA advisory committee, where appropriate and if applicable;

• completion of extensive preclinical laboratory tests and animal studies performed in accordance with applicable regulations, including the FDA’s Good Laboratory Practices (GLPs), regulations and standards;

• submission to the FDA of an IND, which must become effective before clinical trials may begin;

• approval by an independent institutional review board ("IRB") or ethics committee representing each clinical site before the trial is commenced;

• performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations, Good Clinical Practices ("GCPs"), and other clinical trial-related regulations to establish the safety, purity and potency of the proposed biological product candidate for its intended purpose;

• preparation of and submission to the FDA of a BLA, which includes not only the results of the clinical trials, but also, detailed information on the chemistry, manufacture and quality controls for the product candidate and proposed labeling;

• payment of user fees for FDA review of the BLA (unless a fee waiver applies);

● FDA review and approval of the BLA, resulting in the licensure of the biological product for commercial marketing.

Before testing any biological product candidate, in humans, the product candidate enters the preclinical testing stage.

Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of the product’s biological characteristics, chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the product candidate.

The conduct of the preclinical tests must comply with federal regulations and requirements including GLPs.

Prior to commencing an initial clinical trial in humans with a product candidate in the United States, an IND must be submitted to the FDA and the FDA must allow the IND to proceed.

An IND is an exemption from the FD&C Act that allows an unapproved product candidate to be shipped in interstate commerce for use in an investigational clinical trial and a request for FDA allowance that such investigational product may be administered to humans in connection with such trial.

Such authorization must be secured prior to interstate shipment and administration.

In support of a request for an IND, applicants must submit a protocol for each clinical trial and any subsequent protocol amendments must be submitted to the FDA as part of the IND.

In addition, the results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature to support the use of the biological product and plans for clinical trials, among other things, must be submitted to the FDA as part of an IND.

An IND must become effective before human clinical trials may begin.

Once submitted, the IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.

In such a case, the IND may be placed on clinical hold or partial clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before clinical trials can begin.

Submission of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

• a determination by the FDA within 60 days of its receipt of a BLA to file the application for review;

• satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with current Good Manufacturing Practice requirements ("cGMPs") and to assure that the facilities, methods and controls are adequate to preserve the biological product’s

identity, strength, quality and purity, and of selected clinical trial sites that generated the data in support of the BLA to assess compliance with the FDA’s GCPs;

• satisfactory completion of an FDA Advisory Committee review, if applicable;

• FDA review and approval, or licensure, of a BLA to permit commercial marketing of the product for particular indications for use in the United States.

Before testing any biological product candidate in humans, the product candidate enters the preclinical development stage.

The preclinical development stage generally involves laboratory evaluations of drug chemistry, formulation and stability, as well as studies to evaluate toxicity in animals, which support subsequent clinical testing.

The conduct of the preclinical studies must comply with federal regulations, including GLPs.

The sponsor must submit the results of the preclinical studies, together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, as well as other information, to the FDA as part of the IND.

An IND is a request for authorization from the FDA to administer an investigational drug product to humans.

The central focus of an IND submission is on the general investigational plan and the protocol(s) for human trials.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the proposed clinical trials and places the IND on clinical hold within that 30-day time period.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

The FDA may also impose clinical holds on a drug product candidate at any time before or during clinical trials due to safety concerns, non-compliance, or other issues affecting the integrity of the trial.

Accordingly, we cannot be sure that submission of an IND will result in the FDA allowing clinical trials to begin, or that, once begun, issues will not arise that could cause the trial to be suspended or terminated.

Clinical trials involve the administration of the biological product candidate to healthy volunteers or patients under the supervision of qualified investigators which generally are physicians not employed by, or under the control of, the trial sponsor.

Clinical trials are conducted under written trial protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria and the parameters and criteria to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur.

Clinical trials are conducted under written trial protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection (inclusion and exclusion criteria) and the parameters and criteria to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur.

Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.

An IRB representing each institution participating in the clinical trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the trial at least annually.

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Some trials are overseen by an independent group of qualified experts organized by the trial sponsor, known as a data safety monitoring board or committee.

This group provides authorization as to whether or not a trial may move forward at designated check points based on access that only the group maintains to available data from the trial and may recommend halting the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

This group provides authorization as to whether or not a trial may move forward at designated check points based on access that only the group maintains to available data (if blinded) or to data available also to the sponsor (unblinded) from the trial and may recommend halting the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

Certain information about certain clinical trials must also be submitted within specific timeframes to the NIH for public dissemination on its ClinicalTrials.gov website.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined:

The investigational product is initially introduced into healthy human subjects and tested for safety.

In the case of some products for severe or life-threatening diseases, the initial human testing is often conducted in patients.

The investigational product is initially introduced into healthy human volunteers or patients with the target disease or condition.

Phase 1 clinical trials are typically designed to test the safety, dosage tolerance, absorption, metabolism and distribution of the investigational product in humans, including any side effects associated with increasing doses, and, if possible, to gain early evidence of effectiveness.

The investigational product is evaluated in a limited patient population to identify possible adverse side effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance, optimal dosage and dosing schedule.

Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical trials.

The investigational product is administered to an expanded patient population to further evaluate dosage, clinical efficacy, potency, and safety in an expanded patient population at geographically dispersed clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and provide an adequate basis for approval and product labeling.

In some cases, FDA may require, or firms may voluntarily pursue, post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, after initial marketing approval.

The investigational product is administered to an expanded patient population to further evaluate dosage, to provide substantial evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed clinical trial sites.

These clinical trials are intended to establish the overall benefit:risk

ratio of the investigational product and to provide an adequate basis for physician labeling.

Generally, two adequate and well-controlled Phase 3 clinical trials are required by the FDA for approval of a BLA.

In some cases, the FDA may require, or companies may voluntarily pursue, post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, after initial marketing approval.

These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up.

During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators.

During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical trial activities, clinical data, and clinical trial investigators.

Annual progress reports detailing the results of the clinical trials must be submitted to the FDA.

Written IND safety reports must be promptly submitted to the FDA and the investigators for serious and unexpected adverse events, any findings from other studies, tests in laboratory animals or in vitro testing that suggest a significant risk for human subjects, or any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

The sponsor must submit an IND safety report within 15 calendar days after the sponsor determines that the information qualifies for reporting.

The sponsor also must notify the FDA of any unexpected fatal or life-threatening suspected adverse reaction within seven calendar days after the sponsor’s initial receipt of the information.

Written IND safety reports must be submitted to the FDA and the investigators fifteen days after the trial sponsor determines the information qualifies for reporting for serious and unexpected suspected adverse events, findings from other studies or animal or in vitro testing that suggest a significant risk for human volunteers and any clinically important increase in the rate of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

The sponsor must submit an IND safety report within seven days of the sponsor’s initial receipt of the information of any unexpected fatal or life-threatening suspected adverse reaction.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all.

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To help reduce the risk of the introduction of adventitious agents with use of biological products, the PHS Act emphasizes the importance of manufacturing control for products whose attributes cannot be precisely defined.

The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, the sponsor must develop methods for testing the identity, strength, quality, potency and purity of the final biological product.

The manufacturing process must be capable of consistently producing high quality batches of the product candidate and, among other things, the sponsor must develop methods for testing the identity, strength, quality, potency, stability, and purity of the final biological product.

Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the biological product candidate does not undergo unacceptable deterioration over its shelf life.

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The FDA may refuse to file any BLA that it deems incomplete or not properly reviewable at the time of submission and may request additional information.

In this event, the BLA must be resubmitted with the additional information.

In this event, the BLA must be resubmitted with the required additional information.

The resubmitted application also is subject to review to determine if it is substantially complete before the FDA accepts it for filing.

In most cases, the submission of a BLA is subject to a substantial application user fee, although the fee may be waived under certain circumstances.

Under the performance goals and policies implemented by the FDA under the Prescription Drug User Fee Act, or PDUFA, for original BLAs, the FDA targets ten months from the filing date in which to complete its initial review of a standard application and respond to the applicant, and six months from the filing date for an application with priority review.

The FDA does not always meet its PDUFA goal dates, and the review process is often significantly extended by FDA requests for additional information or clarification.

Under the performance goals and policies implemented by the FDA under the Prescription Drug User Fee Act ("PDUFA") for original BLAs, the FDA targets ten months from the filing date in which to complete its initial review of a standard application and respond to the applicant, and six months from the filing date for an application with priority review.

The FDA does not always meet its PDUFA goal dates, and the review process can be significantly extended by FDA requests for additional information or clarification.

Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA.

The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, pure and potent for its intended use, and whether the product is being manufactured in accordance with cGMP to ensure its continued safety, purity and potency.

The FDA may refer applications for novel biological products or biological products that present difficult or novel questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.

The FDA reviews the BLA to determine, among other things, whether the proposed product is safe and effective for its intended use, conducting a benefit-risk assessment based on the information provided as to whether the benefits (with their uncertainties) of the biological product outweigh the risks (with their uncertainties and approaches to managing risks) under the conditions of use described in the proposed product labeling, and whether the product is being manufactured in accordance with cGMP to ensure its continued safety, purity and potency.

The FDA may refer applications for novel biological products or biological products that present difficult or novel questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians, patient representatives, and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.

The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation Strategy, or REMS, is necessary to assure the safe use of the biological product.

During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation

Strategy ("REMS") is necessary to assure the safe use of the biological product.

If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS;

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The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.

Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure that the clinical trials were conducted in compliance with IND trial requirements and GCP requirements.

To assure cGMP and GCP compliance, an applicant must incur significant expenditure of time, money and effort in the areas of training, record keeping, production and quality control.

Under the Pediatric Research Equity Act, or PREA, a BLA or supplement to a BLA for a novel product ( e.g.

Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure that the clinical trials were conducted in compliance with the protocol and following GCP.

Under the Pediatric Research Equity Act ("PREA") a BLA or supplement to a BLA for a novel product ( e.g.

, new active ingredient, new indication, etc.) must contain data to assess the safety and effectiveness of the biological product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.

The FDA may grant deferrals for submission of data or full or partial waivers.

Unless otherwise required by regulation, PREA does not apply to any biological product for an indication for which orphan designation has been granted.

After the FDA evaluates a BLA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a Complete Response Letter.

After the FDA evaluates a BLA and conducts inspections of manufacturing facilities where the drug substance and/or drug product for commercial supply will be produced, the FDA may issue an approval letter or a Complete Response Letter.

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

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Orphan Drug Designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States, or 200,000 or more individuals in the United States and for which there is no reasonable expectation that the cost of developing and making a drug or biological product available in the United States for this type of disease or condition will be recovered from sales of the product.

Orphan product designation must be requested before submitting a BLA.

Under section 526 of the FD&C Act, the FDA may grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which is defined as a disease or condition that affects fewer than 200,000 individuals in the United States, or 200,000 or more individuals in the United States and for which there is no reasonable expectation that the cost of developing and making available in the United States a drug or biological product for such disease or condition will be recovered from sales of the product in the United States of such drug.

Orphan product designation must be requested before submitting a BLA for the orphan indication.

After the FDA grants orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.

Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan drug designation subsequently receives the first FDA approval for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated.

If a product that has orphan drug designation subsequently receives the first FDA approval for a particular active ingredient for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity or if the FDA finds that the holder of the orphan drug exclusivity has not shown that it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was designated.

Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.

Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the BLA application user fee.

A designated orphan drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it received orphan designation.

Among the other benefits of orphan drug designation are tax credits for qualified clinical testing expenses and a waiver of the BLA application user fee.

A designated orphan drug may not receive orphan drug exclusivity if the approved indication for a use is broader than the indication for which it received orphan designation.

In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or, as noted above, if the second applicant demonstrates that its product is clinically superior to the approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

Orphan drug designation may also entitle a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers.

Orphan drug designation may also entitle a party to additional financial incentives such as opportunities for grant funding towards clinical trial costs.

Expedited Development and Review Programs

The FDA has various programs, including fast track designation, breakthrough therapy designation, accelerated approval and priority review, that are intended to expedite or simplify the process for the development and FDA review of drugs and biologics that are intended for the treatment of serious or life- threatening diseases or conditions.

To be eligible for fast track designation, new drugs and biological product candidates must be intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition.

Fast track designation applies to the combination of the product and the specific indication for which it is being studied.

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One benefit of fast track designation, for example, is that the FDA may consider for review sections of the marketing application on a rolling basis before the complete application is submitted if certain conditions are satisfied, including an agreement with the FDA on the proposed schedule for submission of portions of the application and the payment of applicable user fees before the FDA may initiate a review.

Under the FDA’s breakthrough therapy program, a sponsor may seek FDA designation of its product candidate as a breakthrough therapy if the product candidate is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that it may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

However, the review of the BLA does not formally start until the full application has been received by the FDA.

Under the FDA’s breakthrough therapy program, a sponsor may seek FDA designation of its product candidate as a breakthrough therapy if the product candidate is intended, alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that it may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, defined as those that measure an effect on irreversible morbidity or mortality or on symptoms that represent serious consequences of the disease.

Breakthrough therapy designation comes with all of the benefits of fast track designation.

The FDA may take other actions appropriate to expedite the development and review of the product candidate, including holding meetings with the sponsor and providing timely advice to, and interactive communication with, the sponsor regarding the development program.

A product candidate is eligible for priority review if it treats a serious or life-threatening disease or condition and, if approved, would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious disease or condition.

A product candidate is eligible for priority review if when approved, it would provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious disease or condition.

The FDA will attempt to direct additional resources to the evaluation of an application for a new drug or biological product designated for priority review in an effort to facilitate the review.

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As a condition of approval, the FDA generally requires that a sponsor of a drug or biological product receiving accelerated approval perform adequate and well-controlled post-marketing clinical trials to verify the clinical benefit in relationship to the surrogate endpoint or ultimate outcome in relationship to the clinical benefit.

Under the Food and Drug Omnibus Reform Act of 2022, or FDORA, the FDA is now permitted to require, as appropriate, that such trials be underway prior to approval or within a specific time period after the date of approval for a product granted accelerated approval.

Under the Food and Drug Omnibus Reform Act of 2022 ("FDORA") the FDA is now permitted to require, as appropriate, that such trials be underway prior to approval or within a specific time period after the date of approval for a product granted accelerated approval.

Sponsors are also required to send updates to the FDA every 180 days on the status of such studies, including progress toward enrollment targets, and the FDA must promptly post this information publicly.

Under FDORA, the FDA has increased authority for expedited procedures to withdraw approval of a drug or indication approved under accelerated approval if, for example, the sponsor fails to conduct such studies in a timely manner and send the necessary updates to the FDA, or if a confirmatory trial fails to verify the predicted clinical benefit of the product.

In addition, the FDA currently requires, unless otherwise informed by the agency, pre-approval of promotional materials for products receiving accelerated approval, which could adversely impact the timing of the commercial launch of the product.

The FDA may withdraw approval of a drug or indication approved under accelerated approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product.

In addition, the FDA currently requires sponsors, unless otherwise informed by the agency, to request pre-approval of promotional materials for products receiving accelerated approval, which could adversely impact the timing of the commercial launch of the product.

The FDA may withdraw approval of a drug or

indication approved under accelerated approval if, for example, the confirmatory trial fails to verify the predicted clinical benefit of the product.

Post-approval Requirements

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Biological product manufacturers and other entities involved in the manufacture and distribution of approved biological products are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws, including applicable tracking and tracing requirements.

Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain

cGMP compliance.

Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.

Discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or holder of an approved BLA, including withdrawal of the product from the market.

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Marketing Exclusivity

Depending upon the timing, duration and specifics of the FDA approval of the use of our product candidates, some of our United States patents may be eligible for limited patent term extension under the Hatch-Waxman Amendments.

The Hatch-Waxman Amendments permit a patent restoration term of up to five years as compensation for patent term lost during product development and the FDA regulatory review process.

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In addition, a patent can only be extended once and only for a single product.

PTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

In the future, we may intend to apply for restoration of patent term for one of our patents, if and as applicable, to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA.

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product.

The United States Patent and Trademark Office (the "USPTO") in consultation with the FDA, reviews and approves the application for any patent term extension or restoration.

In the future, we may intend to apply for restoration of patent term for one of our patents, if and as applicable, to add patent life beyond

its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA.

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the "ACA") includes a subtitle called the Biologics Price Competition and Innovation Act of 2009 ("BPCIA"), which created an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product.

This amendment to the PHS Act attempts to minimize duplicative testing.

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Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product and, for products administered multiple times, the biologic and the reference biologic may be switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product, and FDA will not approve an application for a biosimilar or interchangeable product based on the reference biological product until twelve years after the date of first licensure of the reference product.

The FDA will not accept an application for a biosimilar or interchangeable product based on the reference biological product until four years after the date of first licensure of the reference product, and the FDA will not approve an application for a biosimilar or interchangeable product based on the reference biological product until twelve years after the date of first licensure of the reference product.

“First licensure” typically means the initial date the particular product at issue was licensed in the United States.

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In addition to exclusivity under the BPCIA, a biological product can obtain pediatric market exclusivity in the United States.

Pediatric exclusivity, if granted, adds six months to existing exclusivity periods, including some regulatory exclusivity periods tied to patent terms.

This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.

Pediatric exclusivity, if granted, adds six months to existing exclusivity for all formulations, dosage forms, and indications of the biologic.

This six-month exclusivity, which runs from the end of other exclusivity protection, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial, provided that at the time pediatric exclusivity is granted there is not less than nine months of term remaining.

Additional Regulation

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If our operations result in contamination of the environment or expose individuals to hazardous substances, we could be liable for damages and governmental fines.

We believe that we are in material compliance with

applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business.

We believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business.

We cannot predict, however, how changes in these laws may affect our future operations.

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In April 2014, the EU adopted the new Clinical Trials Regulation (EU) No 536/2014, which replaced the current Clinical Trials Directive 2001/20/EC on January 31, 2022.

The transitory provisions of the new Regulation offer sponsors the possibility to choose between the requirements of the previous Directive and the new Regulation if the request for authorization of a clinical trial is submitted in the year after the new Regulation became applicable.

The transitory provisions of the new Regulation offer sponsors the possibility to choose between the requirements of the previous Directive and the new Regulation if the request for

authorization of a clinical trial is submitted in the year after the new Regulation became applicable.

If the sponsor chooses to submit under the previous Directive, the clinical trial continues to be governed by the Directive until three years after the new Regulation became applicable.

If a clinical trial continues for more than three years after the Regulation became applicable, the new Regulation will at that time begin to apply to the clinical trial.

The new Regulation, which is directly applicable in all Member States (meaning that no national implementing legislation in each EU Member State is required), aims at simplifying and streamlining the approval of clinical trials in the EU.

The new Regulation, which is directly applicable in all EU Member States and those within the European Economic Area ("EEA") (meaning that no national implementing legislation in each EU Member State is required), aims at simplifying and streamlining the approval of clinical trials in the EU.

The main characteristics of the new Regulation include:

a streamlined application procedure via a single-entry point through the Clinical Trials Information System, or CTIS;

a streamlined application procedure via a single-entry point through the Clinical Trials Information System ("CTIS");

a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors;

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In the European Union, medicinal products, including biological medicinal products, are subject to extensive pre- and post-market regulation by regulatory authorities at both the European Union and national levels.

To obtain regulatory approval of a biological medicinal product under the European Union regulatory system, we 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:

To obtain regulatory approval of a biological medicinal product under the European Union regulatory system, we must submit a marketing authorization application ("MAA") either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the European Union:

the decentralized procedure, national procedure, or mutual recognition procedure.

A marketing authorization may be granted only to an applicant established in the EEA.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid throughout the entire territory of the EU and the additional Member States of the European Economic Area (Iceland, Liechtenstein and Norway), or EEA.

Pursuant to Regulation (EC) No.

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For those products for which the use of the centralized procedure is not mandatory, applicants may elect to use the centralized procedure where the product contains a new active substance not yet authorized in the European Union, and where the applicant can show that the product constitutes a significant therapeutic, scientific or technical innovation or for which a centralized process is in the interest of public health at a European Union level.

Under the centralized procedure, the Committee for Medicinal Products for Human Use, or the CHMP, established at the EMA is responsible for conducting an initial assessment of whether a product meets the required quality, safety and efficacy requirements, and whether a product has a positive benefit-risk profile.

Under the centralized procedure, the Committee for Medicinal Products for Human Use (the "CHMP"), established at the EMA is responsible for conducting an initial assessment of whether a product meets the required quality, safety and efficacy requirements, and whether a product has a positive benefit-risk profile.

Under the centralized procedure in the European Union, the maximum timeframe for the evaluation of an MAA is 210 days from receipt of a valid MAA, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions asked by the CHMP.

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If the CHMP accepts such a request, the timeframe of 210 days for assessment will be reduced to 150 days (excluding clock stops), but it is possible that the CHMP may revert to the standard time limit for the centralized procedure if it determines that the application is no longer appropriate to conduct an accelerated assessment.

For products not falling within the mandatory scope of the centralized procedure, national marketing authorizations may be obtained, which are issued by the competent authorities of the European Union Member States and only cover their respective territory.

respective territory.

Where a product has already been authorized for marketing in an European Union Member State, this national marketing authorization can be recognized in another European Union Member State through the mutual recognition procedure.

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Upon receiving marketing authorization in the European Union, innovative medicinal products, approved on the basis of a complete independent package, generally receive eight years of data exclusivity and an additional two years of market exclusivity.

Data exclusivity, if granted, prevents generic or biosimilar applicants from referencing the innovator’s pre-clinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the European Union for a period of eight years from the date on which the reference product was first authorized in the European Union.

Data exclusivity, if granted, prevents generic or biosimilar applicants from referencing the innovator’s preclinical/nonclinical and clinical trial data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the European Union for a period of eight years from the date on which the reference product was first authorized in the European Union.

During the additional two-year period of market exclusivity, a generic or biosimilar marketing authorization can be submitted, and the innovator’s data may be referenced, but no generic or biosimilar product can be marketed in the European Union until the expiration of the market exclusivity period.

The overall ten-year period will be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with currently approved therapies.

Even if an innovative medicinal product gains the prescribed period of data exclusivity, another company could nevertheless also market another version of the product if such company obtained a marketing authorization based on an MAA with a complete and independent data package of pharmaceutical tests, preclinical tests and clinical trials.

Orphan Designation and Exclusivity

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An orphan medicinal product can also obtain an additional two years of market exclusivity where an agreed pediatric investigation plan for pediatric trials has been complied with.

No extension to any supplementary protection certificate can be granted on the basis of pediatric trials for orphan indications.

No extension to any supplementary protection certificate ("SPC") can be granted on the basis of pediatric trials for orphan indications.

The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify maintenance of market exclusivity.

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Pediatric Development

In the European Union, companies developing a new medicinal product must agree upon a pediatric investigation plan, or PIP, with the EMA’s Pediatric Committee, or PDCO, and must conduct pediatric clinical trials in accordance with that PIP, unless a waiver applies, ( e.g.

, because the relevant disease or condition occurs only in adults).

In the European Union, companies developing a new medicinal product must agree upon a pediatric investigation plan, or PIP, with the EMA’s Pediatric Committee ("PDCO") and must conduct pediatric clinical trials in accordance with that PIP, unless a waiver applies, (e.g., because the relevant disease or condition occurs only in adults).

The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the product for which marketing authorization is being sought.

The PDCO can grant a deferral of the obligation to implement some or all of the measures of the PIP until there are sufficient data to demonstrate the efficacy and safety of the product in adults, in which case the pediatric clinical trials must be completed at a later date.

Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when this data is not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients.

Products that are granted a marketing authorization with the results of pediatric clinical trials conducted in accordance with the PIP are eligible for a six-month extension of the protection under a supplementary protection certificate, or SPC, provided an application for such extension is made at the same time as filing the SPC application for the product or at any point up to 2 years before the SPC expires, even where the trial results are negative.

Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when this data are not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients.

Products that are granted a marketing authorization with the results of pediatric clinical trials conducted in accordance with the PIP are eligible for a six-month extension of the protection under a SPC, provided an application for such extension is made at the same time as filing the SPC application for the product or at any point up to 2 years before the SPC expires, even where the trial results are negative.

In the case of orphan medicinal products, a two-year extension of the orphan market exclusivity may be available.

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In March 2016, the EMA, launched an initiative to facilitate development of product candidates in indications, often rare, for which few or no therapies currently exist.

The PRIority MEdicines, or PRIME, scheme is intended to encourage product development in areas of unmet medical need (where there is no satisfactory method of diagnosis, prevention or treatment in the European Union or, if there is, the new medicine will bring a major therapeutic advantage) and provides accelerated assessment of products representing substantial innovation.

The PRIME scheme is intended to encourage product development in areas of unmet medical need (where there is no satisfactory method of diagnosis, prevention or treatment in the European Union or, if there is, the new medicine will bring a major therapeutic advantage) and provides accelerated assessment of products representing substantial innovation.

The PRIME scheme is open to medicines under development and for which the applicant intends to apply for an initial MAA through under the centralized procedure.

Applicants will typically be at the exploratory clinical trial phase of development, and will have preliminary clinical evidence in patients to demonstrate the promising activity of the medicine and its potential to address to a significant extent an unmet medical need.

In exceptional cases, products from small- and medium-sized enterprises may qualify for earlier entry into the PRIME scheme than larger companies, if compelling non-clinical data in a relevant model provide early evidence of promising activity, and first in man trials indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.

In exceptional cases, products from small- and medium-sized enterprises may qualify for earlier entry into the PRIME scheme than larger companies, if compelling non-clinical data in a relevant model provide early evidence of promising activity, and first in human trials indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.

Many benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated MAA assessment once a dossier has been submitted.

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Where, during the course of development, a medicine no longer meets the eligibility criteria, support under the PRIME scheme may be withdrawn.

VTP‑500, under development for the prevention of MERS caused by the MERS coronavirus, was awarded PRIME designation in December 2023 by the EMA.

Post-Approval Controls

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• The holder of a marketing authorization must establish and maintain a pharmacovigilance system and appoint an individual qualified person for pharmacovigilance, who is responsible for oversight of that system.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.

● All new MAAs must include a risk management plan, or RMP, describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product.

Key obligations include expedited reporting of suspected serious adverse reactions and submission of periodic safety update reports ("PSURs").

• All new MAAs must include a risk management plan ("RMP") describing the risk management system that the company will put in place and documenting measures to prevent or minimize the risks associated with the product.

The regulatory authorities may also impose specific obligations as a condition of the marketing authorization.

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In June 2016, the electorate in the United Kingdom voted in favor of leaving the European Union (commonly referred to as “Brexit”), and the United Kingdom officially withdrew from the European Union on January 31, 2020.

Pursuant to the formal withdrawal arrangements agreed between the United Kingdom and the European Union, the United Kingdom was subject to a transition period until December 31, 2020, or Transition Period, during which European Union rules continued to apply.

However, the European Union and the United Kingdom have concluded a trade and cooperation agreement, or TCA, which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.

Pursuant to the formal withdrawal arrangements agreed between the United Kingdom and the European Union, the United Kingdom was subject to a transition period until December 31, 2020 ("Transition Period"), during which European Union rules continued to apply.

However, the European Union and the United Kingdom have concluded a trade and cooperation agreement ("TCA"), which was provisionally applicable since January 1, 2021 and has been formally applicable since May 1, 2021.

The TCA includes specific provisions concerning pharmaceuticals, which include the mutual recognition of GMP inspections of manufacturing facilities for medicinal products and GMP documents issued, but does not foresee wholesale mutual recognition of United Kingdom and European Union pharmaceutical regulations.

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The extent to which the regulation of clinical trials in the United Kingdom will mirror the new Clinical Trials Regulation now that has come into effect is not yet known, however the MHRA has conducted a consultation on a set of proposals designed to improve and strengthen the United Kingdom clinical trials legislation.

Great Britain is no longer covered by the European Union’s procedures for the grant of centralized marketing authorizations (as a result of the Northern Ireland Protocol, Northern Ireland will be covered by the centralized authorization procedure and can be covered as a CMS under the decentralized or mutual recognition procedures).

Great Britain is no longer covered by the European Union’s procedures for the grant of centralized marketing authorizations, however as a result of the Northern Ireland Protocol, Northern Ireland will be covered by the centralized authorization procedure and can be covered as a Center for Medicare and Medicaid Services ("CMS") under the decentralized or mutual recognition procedures.

A separate marketing authorization will therefore be required to market drugs in Great Britain.

All medicinal products with a valid centralized marketing authorization on January 1, 2021 were automatically converted into Great Britain marketing authorizations (unless the marketing authorization holder opted out of such a conversion).

For two years from 1 January 2021, the United Kingdom’s regulator, the Medicines and Healthcare products Regulatory Agency, or MHRA, may rely on a decision taking by the European Commission on the approval of a new marketing authorization in the centralized procedure, in order to more quickly grant a new Great Britain marketing authorization.

For two years from 1 January 2021, the United Kingdom’s regulator, MHRA may rely on a decision taking by the European Commission on the approval of a new marketing authorization in the centralized procedure, in order to more quickly grant a new Great Britain marketing authorization.

This is known as the EC Decision Reliance Procedure.

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Since January 1, 2021, a separate process for orphan designation has applied in Great Britain.

There is now no pre-marketing authorization orphan designation (as there is in the European Union) in Great Britain and the application for orphan designation will be reviewed by the MHRA at the time of a marketing authorization application for a United Kingdom or Great Britain marketing authorization.

There is now no pre-marketing authorization orphan designation (as there is in the European Union) in Great Britain and the application for orphan designation will be reviewed by the MHRA at the time of a MAA application for a United Kingdom or Great Britain marketing authorization.

The criteria for orphan designation are the same as in the European Union, save that they apply to Great Britain only (e.g., there must be no satisfactory method of diagnosis, prevention or treatment of the condition concerned in Great Britain, as opposed to the European Union, and the prevalence of the condition must be no more than 5 in 10,000 person in Great Britain).

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Sales of any product, if approved, depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state, and foreign government healthcare programs, commercial insurers, and managed healthcare organizations.

Decisions regarding whether to cover any of our product candidates, if approved, the extent of coverage, and amount of reimbursement to be provided are made on a plan-by-plan basis.

Decisions regarding whether to cover any of our product candidates, if approved, the extent of coverage, and amount of reimbursement to be provided are made on a plan-by-plan

Further, no uniform policy for coverage and reimbursement exists in the United States, and coverage and reimbursement can differ significantly from payor to payor.

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Additionally, separate reimbursement for the product itself or the treatment or procedure in which the product is used may not be available, which may impact physician utilization of the product.

In addition, the U.S.

government and state legislatures have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement, and requirements for substitution of generic products.

In addition, the United States government and state legislatures have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement, and requirements for substitution of generic products.

Third-party payors are increasingly challenging the prices charged for medical products and services;

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Such laws include, without limitation:

federal Anti-Kickback Statute, or AKS;

the civil False Claims Act, or FCA;

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA;

the United States federal Anti-Kickback Statute ("AKS");

the civil False Claims Act ("FCA");

the federal Health Insurance Portability and Accountability Act of 1996 ("HIPAA");

and similar foreign, federal, and state fraud and abuse, transparency, and privacy laws.

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For example, the FCA prohibits any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to the federal government or knowingly making, using, or causing to be made or used a false record or statement material to a false or fraudulent claim to the federal government.

A claim includes “any request or demand” for money or property presented to the U.S.

A claim includes “any request or demand” for money or property presented to the United States government.

Several pharmaceutical companies have been prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal healthcare programs for the product, or for subsidizing copays for patients, including indirectly through charitable patient assistance programs, as an inducement for patients to utilize their products.

, public or private) and knowingly and willfully falsifying, concealing, or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items, or services relating to healthcare matters.

HIPAA created additional federal civil and criminal liability for, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program, or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing, or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items, or services relating to healthcare matters.

Similar to the AKS, a person or entity can be found guilty of violating HIPAA’s fraud and abuse provisions without actual knowledge of the statute or specific intent to violate it.

In addition, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, impose certain requirements on HIPAA covered entities, which include certain healthcare providers, healthcare clearinghouses, and health plans, and individuals and entities that provide services on their behalf that involve individually identifiable health information, known as business associates, relating to the privacy, security, and transmission of individually identifiable health information.

In addition, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 ("HITECH") and their respective implementing regulations, impose certain requirements on HIPAA covered entities, which include certain healthcare providers, healthcare clearinghouses, and health plans, and individuals and entities that provide services on their behalf that involve individually identifiable health information, known as business associates, relating to the privacy, security, and transmission of individually identifiable health information.

In particular, regulations promulgated pursuant to HIPAA establish privacy and security standards that limit the use and disclosure of protected health information and require the implementation of administrative, physical and technological safeguards to protect the privacy of protected health information and ensure the confidentiality, integrity and availability of electronic protected health information.

Determining whether protected health information has been handled in compliance with applicable privacy standards and our contractual obligations can require complex factual and statistical analyses, and may be complicated by the fact that the applicable rules are subject to changing interpretation.

HIPAA mandates the reporting of certain breaches of health information to the U.S.

Department of Health and Human Services, or HHS, affected individuals, and if the breach is large enough, the media.

HIPAA mandates the reporting of certain breaches of health information to the United States Department of Health and Human Services ("HHS") affected individuals, and if the breach is large enough, the media.

In addition to reputational harm, entities that are found to be in violation of HIPAA as the result of a breach of unsecured protected health information, a complaint about privacy practices, or an audit by HHS, may be subject to significant civil, criminal, and administrative fines and penalties and/or additional reporting and oversight obligations if required to enter into a resolution agreement and corrective action plan with HHS to settle allegations of HIPAA non-compliance.

HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing civil actions.

federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to annually report to the Centers for Medicare and Medicaid Services, or CMS, information related to payments or other transfers of value made to physicians (currently defined to include doctors of medicine or osteopathy, dentists, optometrists, podiatrists, and chiropractors), other licensed non-physician health care practitioners, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

federal Physician Payments Sunshine Act ("Sunshine Act") requires certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to annually report to the CMSs, information related to payments or other transfers of value made to physicians (currently defined to include doctors of medicine or osteopathy, dentists, optometrists, podiatrists, and chiropractors), other licensed non-physician health care practitioners, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.

Additionally, we may be subject to federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs and federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers.

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and state and foreign laws governing the privacy and security of health information which, in some cases, differ from each other in significant ways, and may not have the same effect, thus complicating compliance efforts.

If our operations are found to be in violation of any of such laws or any other governmental regulations that apply, we or our officers, directors, employees, contractors, or agents may be subject to penalties, including, without limitation, significant civil, criminal, and administrative penalties;

If our operations are found to be in violation of any of such laws or any other governmental regulations that apply, we or our officers, directors, employees,

contractors, or agents may be subject to penalties, including, without limitation, significant civil, criminal, and administrative penalties;

exclusion from government-funded healthcare programs, such as Medicare and Medicaid or similar programs in other countries or jurisdictions;

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We may also be subject to data privacy and security laws in the United States and various jurisdictions around the world in which we operate or process personally identifiable information (“personal information” or “personal data”).

In the United States, even when HIPAA does not apply, according to the Federal Trade Commission, or the FTC, failing to take appropriate steps to keep consumers’ personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act, or the FTCA, 15 U.S.C.

In the United States, even when HIPAA does not apply, according to the Federal Trade Commission (the "FTC") failing to take appropriate steps to keep consumers’ personal information secure constitutes unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act (the "FTCA") 15 U.S.C.

The FTC’s guidance for appropriately securing consumers’ personal information is similar to what is required by the HIPAA security regulations.

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Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and private litigation as well as reputational harm.

For example, the California Consumer Privacy Act, or the CCPA, as amended by the California Privacy Rights Act, or the CPRA, went into effect on January 1, 2023.

Also, on January 1, 2023, the Virginia Consumer Data Protection Act, or the CDPA, became effective.

For example, the California Consumer Privacy Act (the "CCPA") as amended by the California Privacy Rights Act (the "CPRA") went into effect on January 1, 2023.

Also, on January 1, 2023, the Virginia Consumer Data Protection Act ("CDPA") became effective.

Further, many additional United States state privacy laws will go into effect throughout 2023:

the Colorado Privacy Act, or the CPA (July 1, 2023);

the Connecticut Data Privacy Act, or the CTDPA (July 1, 2023);

and the Utah Consumer Privacy Act, or the UCPA (December 31, 2023).

the Colorado Privacy Act ("the CPA") (July 1, 2023);

the Connecticut Data Privacy Act (the "CTDPA") (July 1, 2023);

and the Utah Consumer Privacy Act (the "UCPA") (December 31, 2023).

The CDPA, CPA, CTDPA, and UCPA are substantially similar in scope and contain many of the same requirements and exceptions as the CCPA, including a general exemption for clinical trial data and information governed by HIPAA.

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Outside of the United States, we also face stringent privacy and data protection requirements.

For example, in the European Economic Area or EEA, the collection, use, storage, disclosure, transfer, or other processing of personal information including personal health data, is subject to the GDPR, which became effective on May 25, 2018.

For example, in Europe, the collection, use, storage, disclosure, transfer, or other processing of personal data, including personal health data in the EEA and the UK is subject to the EU General Data Protection Regulation ("EU GDPR") (with regards to the EEA) and the UK General Data Protection Regulation ("UK GDPR") (with regards to the UK), as well as applicable data protection laws in effect in the Member States of the EEA and in the UK (including the UK Data Protection Act 2018).

In this Annual Report, “GDPR” refers to both the EU GDPR and the UK GDPR, unless specified otherwise.

The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors.

The GDPR also imposes strict rules on the transfer of personal data to countries outside the European Union, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater.

The GDPR also imposes strict rules on the transfer of personal data to countries outside the European Union, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million (£17.5 million for the UK GDPR) or 4% of annual global revenues, whichever is greater.

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.

In addition, the GDPR includes restrictions on cross-border data transfers.

Compliance with the GDPR will be a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities.

Data protection authorities from the different EU member states may interpret the GDPR and national laws differently and impose additional requirements, which add to the complexity of processing personal data in the EU.

In addition, further to the UK’s exit from the EU on January 31, 2020, the GDPR ceased to apply in the UK at the end of the transition period on December 31, 2020.

However, as of January 1, 2021, the UK’s European Union (Withdrawal) Act 2018 incorporated the GDPR (as it existed on December 31, 2020 but subject to certain UK specific amendments) into UK law, referred to as the UK GDPR.

The UK GDPR and the UK Data Protection Act 2018 set out the UK’s data protection regime, which is independent from but aligned to the EU’s data protection regime.

Non-compliance with the UK GDPR may result in monetary penalties of up to £17.5 million or 4% of worldwide revenue, whichever is higher.

In addition, various jurisdictions around the world continue to propose new laws that regulate the privacy and/or security of certain types of personal data.

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The United States and some foreign jurisdictions are considering or have enacted a number of reform proposals to change the healthcare system.

There is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality, or expanding access.

There is significant interest in promoting changes in healthcare systems with the stated goals of

containing healthcare costs, improving quality, or expanding access.

In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by federal and state legislative initiatives, including those designed to limit the pricing, coverage, and reimbursement of pharmaceutical and biological products, especially under government-funded healthcare programs, and increased governmental control of drug pricing.

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Supreme Court dismissed the most recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA.

Prior to the Supreme Court’s decision, President Biden issued an executive order that, in part, instructed certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

In addition, President Biden has issued multiple executive orders that have sought to reduce prescription drug costs.

It is unclear how other healthcare reform measures of the Biden administration or other efforts, if any, to challenge, repeal or replace the ACA will impact our business.

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American Taxpayer Relief Act of 2012 further reduced Medicare payments to several types of providers.

● The Right to Try Act (2018), among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval.

Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program.

There is no obligation for a pharmaceutical manufacturer to make its drug products available to eligible patients as a result of the Right to Try Act.

● The Inflation Reduction Act of 2022, or IRA, includes several provisions that will impact our business to varying degrees, including provisions that reduce the out-of-pocket cap for Medicare Part D beneficiaries to $2,000 starting in 2025;

• The Inflation Reduction Act of 2022, or IRA, includes several provisions that will impact our business to varying degrees, including provisions that require Medicare Part D plans to cover with $0 in cost sharing the cost of adult vaccines recommended by the U.S.

Advisory Committee on Immunization Practices, or ACIP.

The IRA also includes provisions that reduce the out-of-pocket cap for Medicare Part D beneficiaries to $2,000 starting in 2025;

impose new manufacturer financial liability on certain drugs in Medicare Part D, allow the U.S.

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Specifically, there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several U.S.

Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs.

At the federal level, President Biden signed an Executive Order on July 9, 2021 affirming the administration’s policy to (i) support legislative reforms that would lower the prices of prescription drug and biologics, including by allowing Medicare to negotiate drug prices, by imposing inflation caps, and, by supporting the development and market entry of lower-cost generic drugs and biosimilars;

and (ii) support the enactment of a public health insurance option.

Among other things, the Executive Order also directs HHS to provide a report on actions to combat excessive pricing of prescription drugs, enhance the domestic drug supply chain, reduce the price that the Federal government pays for drugs, and address price gouging in the industry;

and directs the FDA to work with states and Indian Tribes that propose to develop section 804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, and the FDA’s implementing regulations.

FDA released such implementing regulations on September 24, 2020, which went into effect on November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada.

On September 25, 2020, CMS stated drugs imported by states under this rule will not be eligible for federal rebates under Section 1927 of the Social Security Act and manufacturers would not report these drugs for “best price” or Average Manufacturer Price purposes.

Congressional inquiries and proposed and enacted federal

and state legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, and review the relationship between pricing and manufacturer patient programs.

For example, FDA released regulations implementing the section 804 Importation Programs in accordance with the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, which went into effect on November 30, 2020 and which provide guidance for states to build and submit importation plans for drugs from Canada.

In January 2024, FDA issued its first approval to Florida for a state plan on importation of certain drugs.

CMS has stated drugs imported by states under this rule will not be eligible for federal rebates under Section 1927 of the Social Security Act and manufacturers would not report these drugs for “best price” or Average Manufacturer Price purposes.

Since these drugs are not considered covered outpatient drugs, CMS further stated it will not publish a National Average Drug Acquisition Cost for these drugs.

If implemented, importation of drugs from Canada may materially and adversely affect the price we receive for any of our product candidates.

Further, on November 20, 2020 CMS issued an Interim Final Rule implementing the Most Favored Nation, or MFN, Model under which Medicare Part B reimbursement rates would have been be calculated for certain drugs and biologicals based on the lowest price drug manufacturers receive in Organization for Economic Cooperation and Development countries with a similar gross domestic product per capita.

However, on December 29, 2021 CMS rescinded the Most Favored Nations rule.

On November 30, 2020, HHS published a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

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Employees and Human Capital Resources

As of December 31, 2022, we had 107 full-time and part-time employees, of which 74 were located in the United Kingdom, and 33 located in the United States.

As of December 31, 2023, we had 130 full-time and part-time employees, of which 95 were located in the United Kingdom, 34 located in the United States and 1 located in Switzerland.

As of December 31, 2023, 62% of our workforce and 54% of our leadership (at Director level and above) were female.

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A breakdown of the employment statistics as of December 31, 2023 is as follows:

Position Male Female Total

Executives 3 2 5

Director/Vice President 14 18 32

Scientists & Support Functions

Managers 9 15 24

Scientists and Support Functions

Total 50 80 130

Demographic Male Female Total

Asian 5 10 15

Black, Caribbean, or African 4 3 7

Mixed, other or multiple ethnic groups 1 3 4

Not disclosed

White 40 64 104

Total 50 80 130

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and new employees, advisors and consultants.

We engage with our employees in multiple ways including through company-wide events, social events and team events.

We engage with our employees in multiple ways

including through company-wide events, social events and team events.

We also have a bonus scheme and equity incentive plan in which all employees are entitled to participate.

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The safety of our workforce, including consultants and visitors to our office/laboratory, has and remained of paramount importance to us.

We established a balance of working in both office and home environments prior to the COVID-19 pandemic, which enabled us to more smoothly transition to a consistent “work from home” policy for all but our laboratory employees.

An initial risk assessment was performed and applicable precautions were implemented for all staff and visitors.

This risk assessment was continuously reviewed to ensure top biosecurity measures were in place throughout this ongoing pandemic.

We have not yet experienced any labor force issues due to the pandemic.

Work on internal, laboratory-based projects has continued within the agreed timelines.

We have a Health and Safety Committee that focuses on implementing policies and training programs to enhance workplace safety.

During the COVID-19 pandemic, our continuing focus on safe working practices enabled us to preserve business continuity without sacrificing our commitment to keeping our colleagues and workplace visitors safe.

As we continue to grow, we also intend to expand our overall environmental, social, and governance, or ESG, efforts.

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These include:

Environmental – the impact Vaccitech has on the environment, including its assessment of carbon footprint and the reporting thereof for new facilities.

Social – the impact Vaccitech has on society, including the impact on external groups through the development of life-saving products, the impact in low- and middle-income countries and clinical trial diversity.

For internal groups the focus is on employees and how Vaccitech monitors and maintains gender pay parity, expands employee diversity, enhances engagement and morale, and minimizes staff turnover.

Environmental – the impact we have on the environment, including its assessment of carbon footprint and the reporting thereof for new facilities.

Social – the impact we have on society, including the impact on external groups through the development of life-saving products, the impact in low- and middle-income countries and clinical trial diversity.

For internal groups the focus is on employees and how Barinthus Bio monitors and maintains gender pay parity, expands employee diversity, enhances engagement and morale, and minimizes staff turnover.

Corporate Governance – how is the company run, to include diversity and inclusion within the company and the board of directors, board independence and the ratio of executive compensation to employee compensation.

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The carbon footprint for the group for the years ended December 31, 2023 and 2022 are as follows:

December 31, 2022

December 31, 2021

% Total emissions

For clarity, scope 1 emissions are direct emissions produced from activities owned or controlled by the Company.

Scope 2 emissions are indirect emissions related to the generation of the electricity consumed and purchased by Vaccitech.

December 31, 2023 December 31, 2022

Scope tCO2e % Total emissions tCO2e % Total emissions

Scope 1 6.54 2% 5.59 5%

Scope 2 360.00 98% 107.63 95%

Total 366.54 100% 113.22 100%

For clarity, scope 1 emissions are direct emissions produced from activities owned or controlled by us.

Scope 2 emissions are indirect emissions related to the generation of the electricity consumed and purchased by us.

We have used the most recent evidence or estimates provided by our energy supply partners to generate our disclosure of emissions for the period.

Standard emissions factors from the “UK Government GHG Conversion Factors for Company Reporting (2023)” guidance were applied to estimate emissions.

Electricity usage at our leased facilities in the United Kingdom and United States are responsible for the majority of our greenhouse gas emissions, with the remainder due to operations conducted within our laboratory.

The increase in emissions is attributable to incurring 12 months of emissions from the acquisition of Avidea in December 2021, which reported negligible emissions in 2021, and the overlap of leased facilities in the U.K.

in 2022, notably the fitout and relocation of our corporate headquarters in July 2022, incurring 7 months of emissions across 2 sites in the U.K.

Our corporate headquarters moved from a 5,059 square foot facility on the Oxford Science Park to an approximate 31,000 square foot facility on the Harwell Science and Innovation Campus.

Electricity, heating and cooling usage are the majority of our greenhouse gas emissions in these locations.

Electricity, heating and cooling usage at our leased facilities in the United States and the United Kingdom are responsible for a significant amount of our greenhouse gas emissions, with the remainder due to operations conducted within our laboratory.

The increase in emissions is primarily attributable to the relocation of our U.S laboratory and office facilities which completed in June 2023.

The relocation provides approximately 19,700 square foot of state-of-the-art wet laboratory and office facilities in Germantown, Maryland.

The group has elected not to include the voluntary disclosure for Scope 3 emissions.

For the year ended December 31, 2023, the split of emissions by geography is as follows:

% Total emissions

Scope Location tCO2e % Total emissions

Total 366.54 100%

1 Indicates amount less than one percent

The group considers that the intensity ratio of tons of carbon dioxide per full-time employee, as a suitable metric for its operations for the years ended December 31, 2023, and 2022 are as follows:

December 31, 2022

December 31, 2021

tCO2e /employee

Average employees

tCO2e /employee

Average employees

December 31, 2023 December 31, 2022

Ratio tCO2e /employee Average employees tCO2e /employee Average employees

Intensity ratio 2.98 123 1.26 90

The tons of carbon dioxide per employee has increased year on year, primarily as a result of an increase in the size of our leased facilities in both the UK and the US, and an increase in our average headcount of 70%.

Additionally, as we have expanded our facilities, more employees have been able to work from the office and therefore consumed more greenhouse gas emissions than in 2021, when many non-laboratory based employees were still working from home due to space limitations at the prior facilities and the COVID-19 pandemic.

The tons of carbon dioxide per employee has increased year on year, primarily as a result of an increase in the size of our leased facilities in the United States.

Additionally, as we have expanded our facilities and increased headcount, more employees have been able to work from the office and therefore consumed more greenhouse gas emissions than in 2022, when many non-laboratory based employees were still working from home due to space limitations at the prior facilities.

The directors have established that the Nominations and Corporate Governance Committee are to have oversight of the assessment and strategy on how to reduce our energy consumption and thereby reducing our carbon footprint.

Available Information

We maintain an internet website at https://www.vaccitech.co.uk/ and make available free of charge through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including exhibits and amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act of 1934, or the Exchange Act.

We maintain an internet website at https://www.Barinthusbio.com/ and make available free of charge through our website our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including exhibits and amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act of 1934, or the Exchange Act.

We make these reports available through our website as soon as reasonably practicable after we electronically file such reports with, or furnish such reports to, the SEC.

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In addition, we regularly use our website to post information regarding our business, product development programs and governance, and we encourage investors to use our website, particularly the information in the section entitled “Investors,” as a source of information about us.

The information on our website is not incorporated by reference into this Annual Report on Form 10-K and should not be considered to be a part of this Annual Report on Form 10-K.

Our website address is included in this Annual Report on Form 10-K as an inactive technical reference only.

The information on our website is not incorporated by reference into this Annual Report and should not be considered to be a part of this Annual Report.

Our website address is included in this Annual Report as an inactive technical reference only.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business