What changed in this filing

/stocks — the workspaceLOADING

Item 1. Business

2025-03-20 compared with 2024-03-20 · 434 added, 499 removed, 798 unchanged (54% of the section changed)

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.

We are a clinical-stage biopharmaceutical company focused on developing novel immunotherapeutic drug candidates for treating auto-immune and inflammatory diseases within the immunology and inflammation ("I&I") space.

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 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 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 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.

It results in abnormal immune reaction against our own tissues, causing tissue damage and disease.

Although the past two decades have seen incredible progress in the treatment of chronic inflammatory and autoimmune diseases, current therapies still rely heavily on the use of non-specific immunosuppressive agents and supportive therapies.

These may efficiently dampen inflammation and compensate organ dysfunction to some degree, but they require lifelong treatment and their lack of specificity for the pathogenic mechanism only can lead to several, sometimes life-threatening, side effects.

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 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, 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.

We aim to achieve this by developing truly transformational and highly disease-specific immunotherapies.

We are prioritizing the development of a pipeline for I&I indications enabled by our proprietary and highly differentiated platform for promoting immune tolerance, referred to as SNAP-TI, that are designed to guide patient's T cells to reduce inflammation and restore the natural state of immune non-responsiveness to healthy tissue.

Our lead candidate, VTP-1000, is designed to restore immune non-responsiveness to gluten in patients with celiac disease, and is currently being assessed in a Phase 1 clinical trial.

Based on encouraging preclinical data, we believe that the SNAP-TI platform has the potential to impact multiple other I&I indications.

We are also evaluating two product candidates to treat infectious diseases and cancer that harness our proprietary viral vector platform technologies, consisting of ChAdOx and MVA;

these technologies are designed to increase disease-specific CD8+ T cells.

These include:

VTP-300, a Phase 2 immunotherapeutic treatment modality that is a component of a treatment regimen to establish functional cure in patients who are chronically infected by the hepatitis B virus, and VTP-850, a second-generation immunotherapeutic candidate for the prevention of recurrence of prostate cancer.

VTP-850 is being tested in patients in a Phase 1 clinical trial in prostate cancer after surgical resection.

We intend to progress the development of these product candidates by completing the ongoing clinical trials, and seek a partner or collaborator for continuing development.

Alongside these proprietary programs, we have partnerships in place to advance additional prophylactic and therapeutic product candidates utilizing our viral vector platforms, including VTP-500 for Middle East Respiratory Syndrome, or MERS, VTP-400 for Herpes Zoster infections, and VTP-600 with potential for multiple cancer indications, including Non-Small Cell Lung Cancer ("NSCLC"), and Squamous Esophageal Cancer.

We also co-invented a COVID-19 vaccine with the University of Oxford, which was exclusively licensed worldwide to AstraZeneca U.K.

Limited ("AstraZeneca").

We believe our core capabilities at the intersection of T cell immunology and immunotherapeutic technology platforms combined with our track record of successfully executing development path activities uniquely position us to navigate towards delivering promising new treatments for patients with auto-immune and inflammatory diseases and building value for shareholders.

We are leveraging the latest understanding of how the immune system's T cells naturally function to control disease.

Research has shown that T cells are key to our body’s ability to identify and respond to threats through recognition of antigens.

Disease can occur when the T cell response is either inappropriate, as occurs in auto-immunity, or inadequate, as often occurs in chronic viral infections or cancer.

Many auto-immune and inflammatory diseases are characterized by an inappropriate or overactive immune response caused by an imbalance in the T cell population.

T effector ("Teff") cells that normally fight infections and cancer can inappropriately attack the body and overwhelm the regulatory T ("Treg") cells that are meant to prevent inflammation.

While there has been incredible progress in the treatment options over the last two decades, current therapies still rely heavily on the use of non-specific immunosuppressive agents and supportive therapies.

These may efficiently dampen inflammation and slow disease progression, but they often require lifelong treatment and their lack of specificity for the pathogenic mechanism can lead to several, sometimes life-threatening, side effects.

Therefore, there remains a need for more targeted, curative therapies that directly address the T cell (Treg/Teff) imbalance underlying many auto-immune and inflammatory diseases.

Fortunately, improved understanding of the cause of inflammatory diseases is allowing the identification of the specific antigens that Teff cells are attacking.

In auto-immunity, Teff cells recognize and attack tissues harboring self-antigens, such as pancreatic beta islet cell associated antigens in type-1 diabetes.

Knowledge of the problematic antigens that the Teff cells are responding to allows for the development of highly specific treatments that only target the T cells involved in the disease and may provide a less aggressive and potentially curative approach.

We aim to directly address the disease process underlying auto-immunity and other inflammatory diseases by developing antigen-specific immune tolerance ("ASIT") therapies based on our proprietary SNAP-TI technology platform.

Our approach is to use SNAP-TI to provide the immune system with problematic antigens within an appropriate tolerogenic context that promotes a reduction in Teff cells and increase in Treg cells, aiming to restore the natural state of immune tolerance and control over disease.

Properties that differentiate SNAP-TI from other ASIT therapies are the use of synthetic, self-assembling nanoparticles to improve manufacturability of multiple antigen compositions;

ability to administer by preferred intramuscular or subcutaneous routes;

and use of an immunomodulator that aims to improve the Treg/Teff ratio and prevent unwanted inflammation associated with the treatment.

For chronic viral infections and cancer, we use a different platform and approach but still leverage T cells.

Our viral vector platforms are designed to stimulate the production of very high levels of Teff cells, such as CD8+ T cells that can recognize viral antigens or tumor antigens.

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

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

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

Our approach for treating chronic viral infections or cancers is to attempt to elicit a strong and specific immune response against key viral or tumor antigens, respectively, using a combination of two proprietary platforms encoded with the target antigens, each administered one month apart.

We employ unique antigen design strategies intended 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.

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

In 2024, we achieved a number of strategic, operational, and financial objectives, which we believe position us to deliver on our long-term plans:

• In April 2024, we received clearance from the FDA on an Investigational New Drug ("IND") application, as well as from the Australian regulatory authorities, to progress VTP-1000 in a first in human clinical trial in celiac disease.

AVALON is a randomized, placebo-controlled Phase 1 trial with a controlled gluten challenge to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000 in adults with celiac disease.

The primary endpoint is assessment of the safety and tolerability of single and multiple dosing, and determination of a dose and schedule for further investigation.

The trial also aims to demonstrate proof-of-principle of induction of immune tolerance and early proof-of-concept for VTP-1000, as a potential treatment for celiac disease, based on assessment of pharmacodynamics and preliminary efficacy determined by means of a controlled gluten challenge.

• In April 2024, we announced top-line final data from the APOLLO trial (also known as HPV001), a Phase 1b/2 randomized, placebo-controlled, multi-center dose-ranging trial of VTP-200 in 108 participants across the U.K.

and EU evaluating the safety, tolerability and immunogenicity of VTP-200 in women aged 25-55 with persistent high-risk human papillomavirus ("hrHPV") infections and low-grade cervical lesions.

The trial was designed to assess the effect of VTP-200 on clearance of hrHPV infection and cervical lesion(s), as well as defining select appropriate doses for further development.

• In May 2024, we appointed Dr.

Leon Hooftman, M.D., as our Chief Medical Officer, effective as of June 2, 2024.

Hooftman brings significant drug development expertise across a broad array of therapeutic areas including oncology, infectious diseases, and inflammation.

• In June 2024, we presented interim data on two Phase 2 trials of VTP-300.

Across both studies, 19% of participants had undetectable HBsAg levels.

The majority of patients who were assessed reached very low levels of HBsAg and eligibility for NUC discontinuation.

Management believe these data are further evidence that VTP-300 could be a critical component of a functional cure regimen.

• In June 2024, we announced a strategic pipeline prioritization following positive interim data from VTP-300 in Chronic Hepatitis B virus infections, prioritizing the development of VTP-300 in chronic Hepatitis B, and VTP-1000 in celiac disease.

• In September 2024, we announced that the first patient/participant was entered into the Phase 1 AVALON clinical trial for VTP-1000 in celiac disease.

The AVALON trial aims to enroll 42 participants with celiac disease and will be conducted in two parts:

a randomized double-blind placebo controlled single ascending dose ("SAD") part,

followed by a randomized double-blind placebo-controlled multiple ascending dose part, incorporating a controlled gluten challenge to assess the impact of VTP-1000 administration on patients’ exposure to gluten.

• In October 2024, we announced that enrollment had completed in the Phase 2b HBV003 clinical trial for VTP-300 in chronic hepatitis B as well as the Phase 1 PCA001 clinical trial for VTP-850 in prostate cancer, respectively.

The Phase 2b trial with VTP 300 enrolled 121 adult participants and is designed to obtain critical dosing information for a potential functional cure regimen for chronic hepatitis B, with participants receiving VTP-300 and low-dose ("LD") nivolumab.

The Phase 1 PCA001 clinical trial enrolled 22 participants and is designed to determine the recommended Phase 2 dosing regimen of VTP-850 as well as evaluate safety and efficacy, as measured by PSA and T cell responses.

• In November 2024, we presented positive updated interim data from the Phase 2b HBV003 clinical trial for VTP-300.

The new data showed that as of the data cut off date of September 30, 2024, eight participants demonstrated complete HBsAg loss (defined as HBsAg levels below the lower limit of quantitation [<LLOQ, 0.05 IU/mL]) and two participants met the criteria for functional cure.

Uniquely, two of the eight participants with HBsAg loss, became positive for anti-hepatitis B antibodies ("HBsAb", so called seroconversion) that they did not have before, including one of those who met functional cure criteria.

• In November 2024, we presented interim data from Group C of the Phase 2a IM-PROVE II clinical trial in collaboration with Arbutus Biopharma Corporation ("Arbutus") (NASDAQ:

ABUS), in people with chronic hepatitis B receiving imdusiran followed by VTP-300 and low-dose nivolumab.

The data indicated that Group C participants receiving nivolumab and VTP-300 experienced increased rates of HBsAg loss at Week 48 (3/13) compared to Group A and B participants who received imdusiran and VTP-300 or placebo.

• In November 2024, we announced the promotion of Geoffrey Lynn, M.D., Ph.D., to Chief Scientific Officer, effective as of December 1, 2024, following the departure of Nadège Pelletier, Ph.D.

Lynn is a seasoned biotech innovator and executive with over 15 years of experience leading immunotherapeutic R&D from discovery through early development.

The Key Elements of Our Immunotherapy Platforms

We have two distinct technology platforms that are designed to either promote immune tolerance for treating auto-immunity and inflammatory diseases or induce CD8+ T cells to fight chronic viral infectious disease and cancer.

Our immune tolerance platform, SNAP-TI, is designed to restore immune tolerance by a mechanism of action that includes the induction of Treg cells and/or decrease of Teff cells to specifically restore a beneficial Treg/Teff ratio.

Our viral vector platforms (ChAdOx and MVA) by contrast allow us to develop product candidates designed to induce high and durable levels of antigen-specific polyfunctional T cells, particularly CD8+ T cells, and B cells to prevent and treat infectious diseases and cancer.

Key elements of SNAP-TI:

• Self-assembling nanoparticles based on amphiphilic peptides as a tolerance immunotherapy ("SNAP-TI") is a synthetic platform that leverages self-assembly to co-deliver multiple disease-specific peptide antigens and immunomodulators in nanoparticles of uniform size (~20 nm) and composition that are designed to access immune cells that promote tolerance following intramuscular or subcutaneous routes of administration.

• Use of self-assembly is a key differentiator of SNAP-TI that allows for co-delivery of multiple antigens and an immunomodulator at up to about 50% loading by particle mass.

This relatively high loading enables dosing by intramuscular or subcutaneous routes.

The small size of SNAP-TI particles allows them to enter different lymphoid organs and promote uptake by the key immune cells that help to promote immune tolerance.

Importantly, the co-delivered immunomodulator provides a tolerogenic context to prevent any unwanted inflammation and to promote an increased Treg/Teff ratio.

• SNAP-TI has shown promising data on protection from disease in multiple mouse models of autoimmunity and is now being assessed in clinical studies as a product candidate (VTP-1000) for treating celiac disease.

We expect that the modularity of the SNAP-TI platform could allow for a growing pipeline of candidates for I&I indications.

Antigen selection and design for SNAP-TI candidates:

• We are prioritizing the research and development of candidates for treating autoimmune and inflammatory diseases that are at least in part driven by Teff cells and preferably have a known human leukocyte antigen ("HLA") association.

This focus allows us to select specific I&I indications and patients who are most likely to benefit from therapy with SNAP-TI.

For each indication, we undertake a rigorous antigen selection process to identify key antigens that are recognized by Teff cells involved in disease pathology or present in disease tissue that may be helpful for inducing bystander Tregs.

Our pipeline integrates clinical precedent, in silico bioinformatics and ex vivo screening of candidate antigens with patient derived Teff cells.

The result of this screening process is the selection of antigens to include in SNAP-TI with the aim of inducing antigen-specific immune tolerance tailored to the specific disease indication.

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

8 unchanged sentences

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.

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 U.S.

• Proprietary promoters and enhancers:

10 unchanged sentences

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.

Antigen selection and design for our viral vectors :

• We select full-length and/or subunit antigen sequences involved in or associated with targeted infectious disease 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.

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.

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

1 unchanged sentence

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:

We have several product candidates in our pipeline focusing on I&I indications, infectious diseases, and oncology.

Our Proprietary I&I Pipeline:

The chart below provides key information about our program using the SNAP-TI platform.

*We have worldwide rights for this product candidate.

1 Based on Management's current estimates on expected clinical data milestones.

Antigen-specific Immune Tolerance 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 designed to suppress the unwanted immune response to gluten by restoring a beneficial regulatory T cell to effector T cell 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 that promote tolerance.

The immunomodulator is a key component of VTP-1000 and is intended to drive regulatory T cell expansion and prevent pro-inflammatory responses.

Clinical Development

AVALON - Currently enrolling, ongoing Phase 1

The AVALON clinical trial is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of VTP-1000.

The trial aims to enroll 42 participants with celiac disease and will be conducted in two parts:

a randomized double-blind placebo-controlled single ascending dose ("SAD") part, followed by a randomized double-blind placebo-controlled multiple ascending dose ("MAD") part, incorporating a controlled gluten challenge to assess the impact of VTP-1000 administration on patients’ exposure to gluten.

In the AVALON trial, we are enrolling adults with celiac disease in the two-part trial, as described in the table below.

Future Development

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

Our Proprietary Infectious Disease and Oncology Pipeline:

*We have worldwide rights for all product candidates, except where indicated.

† Based on Management's current estimates on expected clinical data milestones.

An Immunotherapeutic Targeting Chronic HBV Infection

Patients with chronic hepatitis B infection live with the disease in the absence of symptoms for decades after initial infection.

However, as the disease progresses and symptoms occur, it can cause serious health problems, including development of hepatocellular carcinoma or liver cirrhosis, especially if left untreated.

There is an urgent need to develop an effective therapeutic strategy for chronic hepatitis B infection as less than 10% of patients achieve a functional cure with existing therapies.

Experts agree that achieving functional cure in chronic Hepatitis B patients will likely require a combination of agents with complementary mechanisms of action.

VTP-300 has been designed to be one of those components by stimulating a highly potent and polyfunctional disease-specific immune response, mostly led by disease-specific effector T-cells.

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.

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.

Clinical Development

HBV002 – Completed Phase 1b/2a Trial

In June 2023, we announced positive final safety and efficacy data from the HBV002 trial (NCT04778904).

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

Meaningful, durable reductions of HBsAg were seen in Group 2 (receiving VTP-300 monotherapy, N=18) and Group 3 (receiving VTP-300 followed by a single low dose of nivolumab together with MVA, N=18).

In Group 3, two participants developed non-detectable HBsAg levels, which continued eight months after last dose.

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.

1 unchanged sentence

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.

HBV003 – Fully Enrolled, Ongoing Phase 2b Trial

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

Participant enrollment was completed in October 2024.

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

The trial design directly builds on HBV002 to evaluate PD-1 inhibition timing, and includes criteria for discontinuation of maintenance therapy with standard-of-care nucleos(t)ide reverse transcriptase inhibitors ("NUC") to obtain information on the durability of the response in the absence of such treatment.

Interim Data from the HBV003 Trial

In November 2024, we reported updated data with another interim analysis of the ongoing HBV003 trial (NCT05343481) (with data as of September 30, 2024, for laboratory data and October 8, 2024, for clinical data).

One hundred and twenty-one virally suppressed CHB patients on stable NUC therapy have been enrolled in the fully recruited trial, and this interim analysis focused on the 69 virally-suppressed participants who had entered the trial with HBsAg levels below 200 IU/mL.

These most recent data showed that as of data cut off date of September 30, 2024, eight participants demonstrated complete HBsAg loss (defined as HBsAg levels below the lower limit of quantitation [<LLOQ, 0.05 IU/mL]).

Among these eight participants, three discontinued their NUC treatment, of which two met the criteria for functional cure, defined as undetectable HBV DNA and undetectable HBsAg for at least six months post-NUC treatment discontinuation.

Uniquely, two of the eight participants with HBsAg loss, seroconverted to anti-HBsAb, including one of those who met functional cure criteria.

The data from this ongoing trial indicate that stronger responses may happen in participants treated with the combination of VTP-300 and a low dose of the anti-PD1 antibody nivolumab given simultaneously (Groups 1 and 2) rather than separately (Group 3).

VTP-300 in combination with nivolumab led to durable HBsAg declines in all treatment groups (as shown in graphs below).

1 The curves shown herewith are derived from the interim intent to treat ("ITT") comparison of the 3 treatment groups in HBV003.

Preliminary safety data indicated that VTP-300 in combination with low-dose nivolumab was generally well tolerated with no treatment-related SAEs observed or reported as of the data cut off date of September 30, 2024.

IM-PROVE II – Fully Enrolled, Ongoing Phase 2a Trial in Collaboration with Arbutus

IM-PROVE II, or AB-729-202, is an ongoing Phase 2a clinical trial in collaboration with Arbutus 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 following imdusiran but prior to VTP-300 treatment, lead to a more sustained HBsAg reduction compared to treatment with imdusiran alone, for CHB patients.

Primary endpoints are evaluating the safety, antiviral activity and T cell activity of VTP-300 administered post imdusiran treatment.

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 24, treatment with imdusiran 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 to the above a low dose nivolumab concomitantly 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.

Interim Data from the IM-PROVE II Trial

In November 2024, we announced new interim data from Group C of the IM-PROVE II trial (ACTRN12622000317796).

Group C enrolled a total of 22 non-cirrhotic, virally suppressed cHBV participants with HBsAg ≥100 to <5,000 IU/mL at screening.

The data indicated that Group C participants receiving nivolumab experienced increased rates of HBsAg loss (defined as HBsAg <LLOQ [0.05 IU/mL]) compared to Group A and B participants who received imdusiran and VTP-300 or placebo.

The preliminary data from Group C included data to Week 48 (20/22 participants) and, as shown in the graph below, showed that imdusiran lead-in treatment led to a mean decline from baseline in HBsAg consistent with data from Groups A and B.

Significantly greater mean declines in HBsAg levels (p <0.017) were seen in Group C participants, who received imdusiran and VTP-300 with nivolumab, at Week 48 compared with Groups A and B and Group C without nivolumab.

23% of participants (3/13) in the group receiving imdusiran, VTP-300 and low-dose nivolumab achieved HBsAg loss by Week 48.

Increases in soluble immune biomarkers associated with immune checkpoint proteins, inflammation, and T-cell activation were observed in participants who had HBsAg loss at any point through Week 48.

The Group C treatment regimen with nivolumab was generally well tolerated and did not result in any immune-related adverse events.

Future Development

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 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 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.

We believe that the interim analysis from the HBV003 Phase 2b and the IM-PROVE II Phase 2a studies suggest that VTP-300 contributes to HBsAg loss, and could become part of a regimen that can attain and maintain functional cure.

We are actively seeking a partner to take advantage of VTP-300's differentiated ability to achieve sustained HBsAg loss and functional cure in patients with low levels of HBsAg.

We expect to report out more definitive data of a complete primary analysis of both the HBV003 trial and the IM-PROVE II combination trial with Arbutus in the second quarter of 2025.

A Potential Non-Invasive Treatment for Persistent High-Risk HPV (hr-HPV)

VTP-200 is a potential curative treatment for persistent hrHPV infection and associated pre-cancerous lesions.

An estimated 291 million women worldwide are carriers of human papillomavirus ("HPV") DNA, which can progress to pre-cancerous cervical lesions if untreated.

The last clinical visit of the final patient in our Phase 1b/2 APOLLO (HPV001) clinical trial of VTP-200, (NCT04607850), took place in January 2024.

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

2 unchanged sentences

Clinical Development

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.

APOLLO (HPV001) - Completed Phase 1b/2 Trial

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

We 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.

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

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

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.

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

The secondary objective of this trial was 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").

In April 2024, we announced topline data from 108 participants with low grade lesions who had persistent hrHPV for at least six months.

The APOLLO trial met its primary safety endpoint, demonstrating that VTP-200 was generally well-tolerated and was administered with no treatment-related grade 3 or higher unsolicited AEs and no treatment-related SAEs.

The highest hrHPV clearance rate of 60% at Month 12 was observed in Group 2, which included the highest dose of ChAdOx, compared to a 33% clearance rate in the placebo group.

Groups 1, 3, 4 and 5 showed 12%, 11%, 33% and 36% hrHPV clearance rates, respectively.

The trial also evaluated cervical lesion clearance rates in participants with both reported lesions at screening and visualization of the cervical transformation zone at 12 months (n=57).

The highest cervical lesion clearance rate of 67% was observed in Group 2 and Group 5, both received the highest dose of ChAdOx, compared to 39% in the placebo group.

Groups 1, 3 and 4 showed 40%, 20% and 33% cervical lesion clearance rates, respectively.

Pooled data from the five active dose groups showed no significant improvement in hrHPV clearance or cervical lesion clearance rates in comparison to the placebo group.

Future Development

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").

The clinical development of VTP-200 is expected to be progressed by external parties via licensing or partnership, if a partner can be identified.

We will not continue to develop this product candidate.

Our Next-Generation Immunotherapeutic Candidate for Prostate Cancer

6 unchanged sentences

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 - Completed Phase 1

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.

7 unchanged sentences

T cell infiltration into the resected prostate was also observed.

ADVANCE - Completed Phase 2

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.

7 unchanged sentences

The most common treatment emergent adverse events were bone pain, injection site pain, muscle pain, stomatitis, and constipation, and most were mild and grade 1 or 2.

The only grade 3 adverse event was a chest infection, which was not related to study drug.

The only grade 3 adverse event was a chest infection, which was not related to trial drug.

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

2 unchanged sentences

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 - Fully Enrolled, Phase 1 Trial

In October 2024, we announced enrollment was complete for PCA001 (NCT05617040), our ongoing Phase 1 clinical trial designed to determine the recommended dosing regimen of VTP-850 as well as evaluate safety and efficacy, as measured by prostate-specific antigen (PSA), 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 trial involves a Phase 1 dose finding stage testing 2 doses of ChAdOx-PCA with follow-up MVA-PCA dose administered either intramuscularly or intravenously to determine potential Phase 2 recommended dose and route of administration.

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

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

Future Development

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 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.

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.

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.

We expect to announce topline data from the PCA001 clinical trial in the second quarter of 2025.

The future clinical development of VTP-850 is expected to be progressed by external parties via licensing or partnership, if a partner can be identified.

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

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.

VTP-600 is an 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.

2 unchanged sentences

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 ("CRUK"), which is sponsoring and funding this study.

We initiated a first-in-human Phase 1/2a trial in collaboration with Cancer Research U.K.

("CRUK"), who are sponsoring and funding this trial.

In 2024, CRUK opened a squamous esophageal cancer cohort with the intention of recruiting up to 17 participants.

As squamous esophageal cancer is suitable for biopsy, we believed that the trial in this cohort could enable the observation of

changes in T cell immunity both in the periphery and in the tumor micro-environment between pre- and post-VTP-600 treatment.

Recruitment into both the NSCLC and squamous esophageal arms stopped in September 2024 and patients are in follow-up.

No toxicity was observed during the trial and safety was not a factor in deciding to stop the trial.

Together with our strategic collaborators, Ludwig Institute for Cancer Research (the "Ludwig Institute"), and CRUK, we are looking for other routes to continue development of VTP-600.

A Prophylactic Vaccine Candidate to Prevent MERS

2 unchanged sentences

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.

In November 2021, VTP-500 results from the Saudi Arabia Phase 1 trial 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.

On December 21, 2023, we announced a project with Coalition for Epidemic Preparedness Innovations ("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.

1 unchanged sentence

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

A Prophylactic Vaccine Candidate for Shingles (Herpes Zoster)

VTP-400 is our vaccine candidate in development to prevent shingles in adults aged 50 years and older.

2 unchanged sentences

A Prophylactic Vaccine for the Prevention of COVID-19 Infection

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.

It has been estimated that over 6.5 million lives have been saved worldwide, and between 37.7 and 122.4 million hospitalizations were prevented.

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.

In May 2024, AstraZeneca announced it had made the strategic decision to initiate the withdrawal of marketing authorization for Vaxzevria within Europe, citing decline in demand as the reason for the decision.

In October 2024, we were informed of $15.0 million due to the Company from OUI in relation to the Company's share of royalties received by OUI as a result of prior commercial sales of Vaxzevria by AstraZeneca.

We do not expect to receive any further payments relating to future commercial sales of Vaxzevria.

Our History and Team

1 unchanged sentence

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.

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.

Professor Hill is the founding Director of the Jenner Institute at the University of Oxford and is also the Lakshmi Mittal and Family Professor of Vaccinology at the University of Oxford.

2 unchanged sentences

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.

("Avidea") and the SNAP-TI 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 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 management team’s experience was gained at leading institutions that include Agalimmune, Altimmune, Celltech, Ernst & Young, GenVec and Roche.

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

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

Our Collaboration and License Agreements

17 unchanged sentences

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 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 2024, we paid £100,000 to OUI, representing 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 £14.8 million upon the achievement of specified development, regulatory and commercial milestones.

5 unchanged sentences

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 (Barinthus Biotherapeutics (UK) Limited)

2017 License Agreement with OUI (Barinthus Biotherapeutics (U.K.) 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.

14 unchanged sentences

In the event that such sales royalties 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 September 2020, we must also pay OUI the difference between the royalty paid and the applicable minimum sum payable.

In 2024, we paid £100,000 to OUI, representing the difference between royalties paid and the

minimum sum payable.

If we sublicense the 2017 Licensed Technology, we will be required to pay OUI a mid-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).

1 unchanged sentence

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.

18 unchanged sentences

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.

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

In 2024, we paid £55,000 to OUI, representing 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.

4 unchanged sentences

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 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.

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)

13 unchanged sentences

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.

Unless earlier terminated, the CRADA will expire on February 23, 2025.

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.

The CRADA gave us the option to exclusively license any further inventions made under the CRADA.

The CRADA expired on February 23, 2025.

2019 License Agreement with NIH (Barinthus Bio NA)

3 unchanged sentences

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.

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-TI and SNAP-CI platforms, 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.

7 unchanged sentences

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.

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

In 2024, we paid $20,000 to NIH, representing 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 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.

5 patent families licensed under the 2019 License Agreement with NIH that cover the SNAP-TI and SNAP-CI platforms, 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.

24 unchanged sentences

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 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 SNAP-TI and SNAP-CI platforms, 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.

4 unchanged sentences

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 OUI 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 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 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.

In addition, if we develop at least two products in the Field, we are required to pay OUI milestone payments of up to an aggregate of £1.9 million upon the achievement of specified development, regulatory and commercial milestones.

Subject to earlier termination, the 2019 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 2019 OUI License Agreement, if granted, is expected to expire in August 2039, 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.

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.

The 2019 OUI License set out various royalty payments due in certain circumstances and a minimum sum that would be payable based on the license year in each year following January 2022.

In 2024, we paid £100,000 to OUI, representing the difference between royalties paid and the minimum sum payable.

In September 2024, we provided notice of termination of the 2019 OUI License Agreement to OUI.

Termination took effect on December 26, 2024.

No improvements had been made to this technology prior to the second anniversary of the agreement, and consequently no license was granted to OUI on termination.

No further payments are due to OUI under or in relation to the 2019 OUI License Agreement.

2018 License Agreement with OUI and Oxford

3 unchanged sentences

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.

Janssen Vaccines & Prevention B.V.

Furthermore, we agreed that the rights retained by OUI under the 2016 OUI License Agreement include the right to allow Oxford to use the MERS Technology to carry out research activities (including in collaboration with other parties) up to and including the performance of Phase 1/2 clinical trials and related activities, and the generation of Licensed Product for research use (but excluding any commercial use or sale of such Licensed Product).

6 unchanged sentences

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.

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.

On February 2, 2024, following the entry by Barinthus Biotherapeutics (U.K.) Limited and Oxford into a funding agreement with CEPI (described below), Oxford, OUI and Barinthus Biotherapeutics (U.K.) 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 (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.

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.

12 unchanged sentences

AstraZeneca announced that as of January 13, 2022, the vaccine had 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.

It also had Emergency Use Listing from the World Health Organization, which accelerated the pathway to access in up to 144 countries through the COVAX Facility.

In May 2024, AstraZeneca withdrew the marketing authorization for Vaxzevria within Europe, citing decline in demand as the reason for the decision.

Pursuant to the OUI License Agreement Amendment, we received $2.4 million in July 2020 as our share of the upfront fee paid by AstraZeneca.

We are also entitled to receive a share of certain regulatory and sales milestones and royalties on net sales of Vaxzevria, as well as a portion of any sublicensing income payable by AstraZeneca.

We were also entitled to receive a share of certain regulatory and sales milestones and royalties on net sales of Vaxzevria, as well as a portion of any sublicensing income payable by AstraZeneca.

Our share of the royalties on net sales of Vaxzevria is approximately 1.4%.

Our understanding is that we were not entitled to receive any royalties or payments from sub-licensees from the commercialization of Vaxzevria until after the pandemic period, which was defined as a period that would end on July 1, 2021 (or such later date when AstraZeneca, in good faith, determines that the COVID-19 pandemic is over).

However, our understanding is that we would be entitled to receive our share of any regulatory milestone payments during the pandemic period.

The royalty term for net sales of Vaxzevria commenced in 2022 and will continue, on a country-by-country basis, until the later of (i) the date upon which the vaccine is no longer subject to patent protection in such country, (ii) expiration of regulatory exclusivity for the vaccine in such country or (iii) ten years from the first commercial sale of the vaccine in such country.

Master Collaboration Agreement with CanSino Biologics Inc.

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

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 (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 ("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 Barinthus Bio Territory.

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

During the term of any project agreement entered into as contemplated by the CanSino Agreement and for three months thereafter, neither party is permitted to enter into discussions, collaborations or similar arrangements with any third parties regarding matters or products which are materially the same as set forth in the project agreement or related to the project that is the subject of the project agreement, unless such party reasonably believes such an arrangement with such third party would not be detrimental to the relevant project or project arrangement.

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 ("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.

Unless agreed otherwise in a project agreement:

(i) any improvements of a party’s Background IPR will be owned by the party with rights to such Background IPR, and will be treated as Background IPR;

and (ii) New IPR will be owned by one or both parties in accordance with the respective inventive contribution of each party as determined by the principles of United Kingdom patent law.

Where any New IPR is wholly owned by a party, that party is obliged to endeavor to file patent applications to the extent required to provide reasonable protection for the relevant product.

Where any New IPR is jointly owned by the parties, we are obliged to endeavor to file patent applications to the extent required to provide reasonable protection for the relevant product, in consultation with CanSino, with costs shared between the parties.

Before we abandon a jointly-owned patent claiming any New IPR, we must give CanSino at least three months’ notice, and CanSino can request assignment of our rights on terms to be agreed.

We are obliged to discuss with CanSino the enforcement of jointly owned patent rights but are entitled to enforce such patent rights outside the CanSino Territory.

Unless earlier terminated, the CanSino Agreement will continue for ten years from the date of the agreement.

Either party can terminate by written notice for the uncured material breach or persistent breaches of the other party.

Either party may terminate by written notice if the other party cannot pay its debts, takes any step in connection with entering administration, liquidation, or other arrangement with creditors (other than a solvent arrangement), or suspends all or part of its business;

or suffers a force majeure event that continues for 60 days.

Furthermore, a project agreement entered into pursuant to the CanSino Agreement shall automatically terminate if the 2016 OUI License Agreement or the 2017 OUI License Agreement terminates or expires, Background IPR licensed from OUI is necessary under such project agreement and the parties are unable to agree to a modification of the project or relevant collaboration product that would not require use of such Background IPR.

However, our understanding was that we were entitled to receive our share of any regulatory milestone payments during the pandemic period.

The royalty term for net sales of Vaxzevria commenced in 2022 and continues, on a country-by-country basis, until the later of (i) the date upon which the vaccine is no longer subject to patent protection in such country, (ii) expiration of regulatory exclusivity for the vaccine in such country or (iii) ten years from the first commercial sale of the vaccine in such country.

In May 2024, AstraZeneca announced the initiation of withdrawal of marketing authorization for Vaxzevria in Europe as demand had declined, and therefore we do not expect to receive any further payments relating to future commercial sales of Vaxzevria and, if such payments are due, that we will be notified of such payments in a timely manner.

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 (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.

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 U.K.

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

21 unchanged sentences

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.

The trial opened in the first quarter of 2022 across multiple clinical sites in the U.K.

VOLT is our oncology focused strategic collaboration with the Ludwig Institute for Cancer Research, an international non-profit organization that conducts innovative cancer research and is looking to enable the clinical development of new treatments that induce and harness CD8+ T cells of the immune system to fight cancer.

1 unchanged sentence

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.

5 unchanged sentences

The exclusive rights granted under the VTP 600 License are subject to the right of certain third-party contributors associated with the Clinical Trial, CRUK and scientists funded or employed by CRUK to use the Exclusive Results for non-commercial scientific or clinical research purposes and to publish the Exclusive Results and the results of non-commercial research performed using the Exclusive Results (subject to the publication process set out in the Clinical Trial Agreement).

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.

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 £40.8 million.

15 unchanged sentences

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.

5 unchanged sentences

Either party may terminate for the uncured material breach or insolvency of the other party.

In the event of termination of the 2016 OUI License Agreement, we may terminate the VOLT License Agreement in respect of any of the VOLT Licensed Technology that is licensed to us by OUI, and VOLT and OUI shall enter into a direct license containing the same obligations and liabilities as set forth in the VOLT License Agreement.

In the event of termination of the 2016 OUI License Agreement, we may terminate the VOLT License Agreement in respect of any of the VOLT Licensed Technology that is licensed to us

by OUI, and VOLT and OUI shall enter into a direct license containing the same obligations and liabilities as set forth in the VOLT License Agreement.

The VOLT License Agreement was subsequently amended in July 2019 by two separate agreements for the research, development, and commercialization of cancer immunotherapy targeting MAGE-A3 and NY-ESO-1 for the treatment of various forms of cancer under the VOLT Licensed Technology.

1 unchanged sentence

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”).

On December 20, 2023, we, the Chancellors, Masters and Scholars of the University of Oxford (“Oxford,” together with us, the “Partners”) and 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.

7 unchanged sentences

(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.

We 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.

We are 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”).

9 unchanged sentences

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.

As of March 14, 2025, we control a patent portfolio comprising in-licensed and co-owned patent families relating to our key SNAP-TI, SNAP-CI and syntholytic technology platforms and product candidates, including 10 pending U.S.

patent applications, six issued foreign patents, 50 pending foreign patent applications and two pending PCT patent applications.

We also own a patent family relating to our novel prime-boost regimens that includes one pending U.S.

patent application and one pending foreign patent application together with one pending Patent Cooperation Treaty ("PCT") patent application relating to our novel viral vectored products.

In addition, we have in-licensed certain patent families relating to our viral vectored technology platforms and product candidates, including 13 issued U.S.

patents, six pending U.S.

patent applications, at least 30 issued foreign patents and at least 60 pending foreign patent applications.

Universal Vector Technology Platforms

6 unchanged sentences

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 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

8 unchanged sentences

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.

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

As of March 14, 2025, we in-license a patent family from OUI that includes one pending U.S.

patent application and one pending European patent application that are expected to expire in 2035, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

As of March 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, 2025, 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, 2025, 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.

patent application, one pending European patent application and 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.

12 unchanged sentences

As of March 14, 2025, 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.

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

2 unchanged sentences

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.

As of March 14, 2025, 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.

4 unchanged sentences

As of March 14, 2025, we co-own a patent family that includes one pending U.S.

patent application, one pending European patent application and a further 6 pending foreign patent applications that are expected to expire in 2040, without giving effect to any potential patent term extensions and patent term adjustments and assuming payment of all appropriate maintenance, renewal, annuity or other governmental fees.

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

1 unchanged sentence

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

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

Product Candidates

1 unchanged sentence

We in-license from OUI a patent family directed to the HPV antigen with claims directed to a nucleic acid encoding a polypeptide comprising certain peptide sequences based on certain HPV proteins.

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

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.

As of March 14, 2025, the patent family includes two issued U.S.

patents, three issued foreign patents and seven 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.

1 unchanged sentence

Our VTP-300 product candidate comprises a ChAdOx1-HBV vector and a MVA-HBV vector, where each vector incorporates an engineered HBV antigen.

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.

As of March 14, 2025, we in-license from OUI a patent family with claims directed to a multi-HBV immunogen viral vector vaccine that includes five issued foreign patents, one pending U.S.

patent application and 12 foreign patent applications pending in jurisdictions including Europe, Australia, Canada and China.

3 unchanged sentences

We in-license from Ludwig Institute a patent family with claims directed to a chimpanzee adenovirus vector encapsulating a nucleic acid molecule encoding a MAGE antigen, a NY- ESO1 antigen or both a MAGE antigen and a NY-ESO1 antigen.

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

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.

As of March 14, 2025, the patent family includes one granted U.S.

patent and 11 foreign patent applications pending in jurisdictions including Europe, Australia, Canada, China, and Japan.

If a patent were to issue from such patent applications, it 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.

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

As of March 14, 2025, the patent family includes one granted foreign patent, one pending U.S.

patent application and 10 foreign patent applications pending in jurisdictions including Europe, Australia, Canada, China, and Japan.

5 unchanged sentences

We in-license from OUI a patent family with claims directed to an adenoviral vector comprising a nucleic acid encoding the varicella-zoster virus antigen.

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

As of March 14, 2025, the patent family includes one granted foreign patent, one pending U.S.

patent application and 12 foreign patent applications pending in jurisdictions including Europe, Australia, Canada, China, and Japan.

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.

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 SNAP-CI platform technology to target HPV16+ cancers.

15 unchanged sentences

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.

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

Our patents 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.

2 unchanged sentences

Government Regulation

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.

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

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;

3 unchanged sentences

We are required to invest significant time and financial resources in policies, procedures, processes, and systems to ensure compliance with these laws, rules, and regulations, and our failure to do so may result in the imposition of substantial monetary or other penalties by federal or state regulatory agencies, give rise to reputational harm, or otherwise have a material adverse effect on our results of operations and financial condition.

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:

Drug and 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 drugs and biological products.

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

• 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;

1 unchanged sentence

• 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);

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

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;

• preparation of and submission to the FDA of an NDA or 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 NDA or BLA (unless a fee waiver applies);

• a determination by the FDA within 60 days of its receipt of a NDA or 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 investigational product’s identity, strength, quality and purity, and of selected clinical trial sites that generated the data in support of the application 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.

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

Before testing any investigational 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.

7 unchanged sentences

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 involve the administration of the investigational 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 (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.

13 unchanged sentences

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.

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 an NDA or 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.

7 unchanged sentences

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients.

Concurrent with clinical trials, companies usually complete additional animal studies and also must develop additional information about the chemistry and physical characteristics of the biological product and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP.

Concurrent with clinical trials, companies usually complete additional animal studies and also must develop additional information about the chemistry and physical characteristics of the investigational product and finalize a process for manufacturing the product in commercial quantities in accordance with cGMP.

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.

2 unchanged sentences

Review and Approval Processes

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or more indications.

The BLA must include results of product development, laboratory and animal studies, human trials, information on the manufacture and composition of the product, proposed labeling and other relevant information.

Within 60 days following submission of the application, the FDA reviews a BLA submitted to determine if it is substantially complete before the FDA accepts it for filing.

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 required additional information.

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development, nonclinical studies and clinical trials are submitted to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications.

This application must include results of product development, laboratory and animal studies, human trials, information on the manufacture and composition of the product, proposed labeling and other relevant information.

Within 60 days following submission of the application, the FDA reviews an NDA or BLA submitted to determine if it is substantially complete before the FDA accepts it for filing.

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

In this event, the application 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 ("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.

In most cases, the submission of an NDA or 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 ("PDUFA") for original applications, 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 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.

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

The FDA reviews the NDA or 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 investigational 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 investigational products or 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 ("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;

the FDA will not approve the BLA without a REMS, if required.

Before approving a BLA, the FDA typically will inspect the facilities at which the product is manufactured.

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 product.

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

the FDA will not approve the NDA or BLA without a REMS, if required.

Before approving an NDA or BLA, the FDA typically will inspect the facilities at which the product is manufactured.

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.

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.

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.

Additionally, before approving an NDA or 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") an NDA, BLA or supplement to either for a novel product ( e.g.

, new active ingredient, new indication, etc.) must contain data to assess the safety and effectiveness of the 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.

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.

A Complete Response Letter will describe all of the deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the Complete Response Letter without first conducting required inspections, testing submitted product lots, and/or reviewing proposed labeling.

In issuing the Complete Response Letter, the FDA may recommend actions that the applicant might take to place the BLA in condition for approval, including requests for additional information or clarification.

The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

After the FDA evaluates an NDA or 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.

A Complete Response Letter will describe all of the deficiencies that the FDA has identified in the application, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the Complete Response Letter without first conducting required inspections, testing submitted product lots, and/or reviewing proposed labeling.

In issuing the Complete Response Letter, the FDA may recommend actions that the applicant might take to place the application in condition for approval, including requests for additional information or clarification.

The FDA may delay or refuse approval of an NDA or BLA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, including to subpopulations of patients, which could restrict the commercial value of the product.

7 unchanged sentences

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.

Orphan product designation must be requested before submitting a marketing application 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 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 product 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 qualified clinical testing expenses and a waiver of the BLA application user fee.

Among the other benefits of orphan drug designation are tax credits for qualified clinical testing expenses and a waiver of the NDA or 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.

4 unchanged sentences

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 that disease or condition.

Fast track designation applies to the combination of the product and the specific indication for which it is being studied.

Fast track designation applies to the combination of the product and the specific indication for which

it is being studied.

The sponsor of a new drug or biologic may request the FDA to designate the drug or biologic as a fast track product at any time during the clinical development of the product.

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.

However, the review of the BLA does not formally start until the full application has been received by the FDA.

However, the review of the marketing application (NDA or 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.

11 unchanged sentences

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.

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

Rigorous and extensive FDA regulation of biological products continues after approval, particularly with respect to cGMP requirements, as well as requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product.

Rigorous and extensive FDA regulation of drugs and biological products continues after approval, particularly with respect to cGMP requirements, as well as requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product.

We currently rely, and may continue to rely, on third parties for the production of clinical and commercial quantities of any products that we may commercialize.

Manufacturers of our products are required to comply with applicable requirements in the cGMP regulations, including quality control and quality assurance and maintenance of records and documentation.

Other post-approval requirements applicable to biological products include reporting of cGMP deviations that may affect the identity, potency, purity and overall safety of a distributed product, record-keeping requirements, reporting of adverse effects, reporting updated safety and efficacy information, and complying with electronic record and signature requirements.

Other post-approval requirements applicable to drugs and biological products include reporting of cGMP deviations that may affect the identity, potency, purity and overall safety of a distributed product, record-keeping requirements, reporting of adverse effects, reporting updated safety and efficacy information, and complying with electronic record and signature requirements.

As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution.

After a BLA is approved for a biological product, the product also may be subject to official lot release.

If the product is subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA together with a release protocol showing a summary of the history of manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot.

and the results of all of the manufacturer’s tests performed on the lot.

The FDA also may perform certain confirmatory tests on lots of some products before releasing the lots for distribution by the manufacturer.

5 unchanged sentences

Any agency or judicial enforcement action could have a material adverse effect on us.

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.

Drug and biological product manufacturers and other entities involved in the manufacture and distribution of approved 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.

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.

Discovery of problems with a product after approval may result in restrictions on a product, manufacturer, or holder of an approved NDA or BLA, including withdrawal of the product from the market.

In addition, changes to the manufacturing process or facility generally require prior FDA approval before being implemented and other types of changes to the approved product, such as adding new indications and additional labeling claims, are also subject to further FDA review and approval.

From time to time, legislation is drafted, introduced, passed in Congress and signed into law that could significantly change the statutory provisions governing the approval, manufacturing, and marketing of products regulated by the FDA.

In addition to new legislation, FDA regulations, guidance, and policies are often revised or reinterpreted by the agency in ways that may significantly affect the manner in which pharmaceutical products are regulated and marketed.

Marketing Exclusivity

2 unchanged sentences

However, patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date.

The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of a BLA plus the time between the submission date of a BLA and the approval of that application.

Only one patent applicable to an approved biological product is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent.

The patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of a marketing application (NDA/BLA) plus the time between the submission date of an NDA or BLA and the approval of that application.

Only one patent applicable to an approved product is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent.

In addition, a patent can only be extended once and only for a single 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.

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 NDA or BLA.

Certain of our product candidates are regulated as biologics.

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.

1 unchanged sentence

Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms of safety, purity, and potency, can be shown through analytical studies, animal studies, and a clinical trial or trials.

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.

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.

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.

5 unchanged sentences

As a result, the ultimate implementation and impact of the BPCIA is subject to significant uncertainty.

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 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.

A new drug or biological product can also obtain pediatric market exclusivity in the United States.

Pediatric exclusivity, if granted, adds six months to existing exclusivity for all formulations, dosage forms, and indications of the most active moiety and, for drugs, patent terms.

This six-month exclusivity, which runs from the end of other exclusivity protection, and, for drugs, 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, provided that at the time pediatric exclusivity is granted there is not less than nine months of term remaining.

Additional Regulation

9 unchanged sentences

Certain countries outside of the United States have a similar process that requires the submission of a clinical trial application much like the IND prior to the commencement of human clinical trials.

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.

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 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:

In April 2014, the EU adopted the Clinical Trials Regulation (EU) No 536/2014, which replaced the current Clinical Trials Directive 2001/20/EC on January 31, 2022.

The Regulation, which is directly applicable in all EU 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 main characteristics of the Regulation include:

a streamlined application procedure via a single-entry point through the Clinical Trials Information System ("CTIS");

1 unchanged sentence

and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts (Part I contains scientific and medicinal product documentation and Part II contains the national and patient-level documentation).

Part I is assessed by a coordinated review by the competent authorities of all European Union Member States in which an application for authorization of a clinical trial has been submitted (Concerned Member States) of a draft report prepared by a Reference Member State.

Part II is assessed separately by each Concerned Member State.

Part I is assessed by a coordinated review by the competent authorities of all European Union Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned) of a draft report prepared by a Reference Member State.

Part II is assessed separately by each Member State concerned.

Strict deadlines have also been established for the assessment of clinical trial applications.

4 unchanged sentences

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 ("MAA") either under a centralized procedure administered by the EMA or one of the procedures administered by competent authorities in the European Union:

To obtain regulatory approval of a new 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.

A marketing authorization may be granted only to an applicant established in the European Economic Area (comprising the EU Member States plus Norway, Iceland and Liechtenstein) ("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 EEA.

3 unchanged sentences

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.

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.

Clock stops may extend the timeframe of evaluation of an MAA considerably beyond 210 days.

2 unchanged sentences

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.

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.

If the product has not received a national marketing authorization in any Member State at the time of application, it can be approved simultaneously in various European Union Member States through the decentralized procedure.

If the product has not received a national marketing authorization in any European Union Member State at the time of application, it can be approved simultaneously in various European Union Member States through the decentralized procedure.

As with the centralized procedure, the competent authorities of the European Union Member States assess the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy before granting the marketing authorization.

The application used to submit the BLA in the United States is similar to that required in the European Union, with certain exceptions.

Directive 2001/83/EC and the laws in the Member States transposing this Directive into national law set out the requirements for an MAA.

An MAA for a biological medicinal product must contain certain additional requirements to applications for other medicinal products, such as a description of the origin and history of the starting materials used for the product.

The marketing application (BLA/NDA) submitted in the United States is similar to that required in the European Union, with certain exceptions.

Directive 2001/83/EC and the laws in the European Union Member States transposing this Directive into national law set out the requirements for an MAA.

An MAA for a biological medicinal product must contain certain additional requirements to compared applications for other medicinal products, such as a description of the origin and history of the starting materials used for the product.

Data and Marketing Exclusivity

The European Union also provides opportunities for market exclusivity.

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 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.

Upon receiving marketing authorization in the European Union, innovative medicinal products (reference products), approved on the basis of a complete and independent package of data, generally receive eight years of data exclusivity and an additional two years of market exclusivity.

Data exclusivity 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.

8 unchanged sentences

The criteria for designating an “orphan medicinal product” in the European Union are similar in principle to those in the United States.

Under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as an orphan medicinal product if it meets the following criteria:

In the European Union under Article 3 of Regulation (EC) 141/2000, a medicinal product may be designated as an orphan medicinal product if it meets the following criteria:

(i) it is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition;

2 unchanged sentences

Orphan medicinal products are eligible for financial incentives such as reduction of fees or fee waivers made available by the European Union and its Member States to support research into, and the development and availability of, orphan medicinal products.

The application for orphan designation must be submitted before the application for marketing authorization.

The applicant will receive a fee reduction for the MAA if the orphan drug designation has been granted, but not if the designation is still pending at the time the marketing authorization is submitted.

The application for orphan designation must be submitted before the MAA.

The applicant will receive a fee reduction for the MAA if the orphan drug designation has been granted, but not if the designation is still pending at the time the MAA is submitted.

Orphan designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process.

Orphan medicine marketing exclusivity may be revoked only in very select cases, specifically:

• if it is established that a similar medicinal product is safer, more effective or otherwise clinically superior;

A marketing authorization may be granted to a similar medicinal product to an authorized orphan product during the period of market exclusivity only in very select cases, specifically:

• if it is established that a similar medicinal product is safer, more effective or otherwise clinically superior to the authorized orphan product;

• with consent from the marketing authorization holder for the authorized orphan product;

1 unchanged sentence

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 ("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 ("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.

14 unchanged sentences

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.

VTP‑500, under development for the prevention of MERS caused by the MERS coronavirus, was accepted onto the PRIME scheme by the EMA in December 2023.

Post-Approval Controls

3 unchanged sentences

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.

• All new MAAs must include a risk management plan ("RMP") describing the risk management system that the company will put in place 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.

4 unchanged sentences

Although general requirements for advertising and promotion of medicinal products are established under European Union directives, the details are governed by regulations in each European Union Member State and can differ from one country to another.

The aforementioned EU rules are generally applicable in the EEA.

All of the aforementioned EU rules are generally applicable in the EEA.

Brexit and the Regulatory Framework in the United Kingdom

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 ("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.

At present, Great Britain has implemented European Union legislation on the marketing, promotion and sale of medicinal products through the Human Medicines Regulations 2012 (as amended) (under the Northern Ireland Protocol, the European Union regulatory framework will continue to apply in Northern Ireland).

The regulatory regime in Great Britain therefore largely aligns with current European Union regulations, however it is possible that these regimes will diverge in future now that Great Britain’s regulatory system is independent from the European Union and the TCA does not provide for mutual recognition of United Kingdom and European Union pharmaceutical legislation.

For example, the United Kingdom has implemented the now repealed Clinical Trials Directive 2001/20/EC into national law through the Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended).

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, 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, 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.

The MHRA also offers a 150 day assessment timeline for all high quality applications for a UK, Great Britain or Northern Ireland marketing authorization.

The 150 day timeline does not, however, include a “clock-off” period which may occur if issues arise or points require clarification following an initial assessment of the application.

Such issues should be addressed within a 60 day period, although extensions may be granted in exceptional cases.

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 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).

formally left the EU on January 31, 2020.

As a result of the Northern Ireland protocol, following Brexit, the EMA remained responsible for approving novel medicines for supply in Northern Ireland under the EU centralized procedure, and a separate authorization was required to supply the same medicine in Great Britain (England, Wales and Scotland).

On February 27, 2023, the U.K.

government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”.

The Windsor Framework was approved by the EU-UK Joint Committee on March 24, 2023, and the medicines aspects of the Windsor Framework have applied since January 1, 2025.

This new framework fundamentally changes the previous system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the U.K.

In particular, the MHRA is now responsible for approving all medicinal products destined for the U.K.

market (i.e., Great Britain and Northern Ireland), and the EMA no longer has any role in approving medicinal products destined for Northern Ireland under the EU centralized procedure.

A single U.K.-wide marketing authorization will be granted by the MHRA for all novel medicinal products to be sold in the U.K., enabling products to be sold in a single pack and under a single authorization throughout the U.K.

In addition, the new arrangements require all medicines placed on the U.K.

market to be labelled “U.K.

only”, indicating they are not for sale in the EU.

However, although a separate authorization is now required to market medicinal products in the U.K., under an international recognition procedure which was put in place by the MHRA on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a U.K.

marketing authorization.

There is now no pre-marketing authorization orphan designation in the U.K.

Instead, the MHRA reviews applications for orphan designation in parallel to the corresponding MAA.

The criteria are essentially the same, but have been tailored for the U.K.

market, i.e., the prevalence of the condition in U.K.

(rather than the EU) must not be more than five in 10,000.

Should an orphan designation be granted, the period of market exclusivity will be set from the date of first approval of the product in the U.K.

Coverage and Reimbursement

1 unchanged sentence

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

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.

Further, no uniform policy for coverage and reimbursement exists in the United States, and coverage and reimbursement can differ significantly from payor to payor.

40 unchanged sentences

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.

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.

11 unchanged sentences

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;

6 unchanged sentences

and the curtailment or restructuring of our operations.

Data Privacy and Security Laws

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 (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.

In addition, certain states have enacted laws that govern the privacy and security of health information and other personal information in certain circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

Data Privacy and Cybersecurity Laws

We may also be subject to data privacy and cybersecurity laws in the U.S.

and various jurisdictions around the world in which we operate or process personally identifiable information (“personal information” or “personal data”).

In addition to HIPAA U.S.

federal enforcement agencies, such as the Federal Trade Commission (the "FTC") require businesses to take appropriate steps to keep consumers’ personal information secure, subject to Section 5(a) of the Federal Trade Commission Act (the "FTCA") 15 U.S.C.

In addition, numerous U.S.

states have enacted laws that govern the privacy and security of health information and other personal information, some of which may be more stringent than HIPAA and which differ from each other in significant ways thus complicating compliance efforts.

For example, the California Consumer Privacy Act (the "CCPA") establishes certain requirements for data use, sharing and transparency, and provides California residents the ability to limit the sharing of their personal information.

Similarly comprehensive laws have passed in a number of states.

Certain states have passed or proposed more targeted privacy laws that focus on the privacy of health and medical information, such as Washington state’s My Health My Data Act, which has a private right of action that may increase potential damages for noncompliance.

Such laws are continuously evolving and are likely to add additional complexity, variation in requirements, restrictions and potential legal risk, require additional investment of resources in compliance programs, impact strategies and the availability of previously useful data and could result in increased compliance costs and/or changes in business practices and policies.

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 (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 ("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.

Any of these laws may broaden their scope in the future, and similar laws have been proposed on both a federal level and in more than half of the states in the United States.

In addition, a number of other states have proposed new privacy laws, some of which are similar to the above discussed recently passed laws.

Such proposed legislation, if enacted, may add additional complexity, variation in requirements, restrictions and potential legal risk, require additional investment of resources in compliance programs, impact strategies and the availability of previously useful data and could result in increased compliance costs and/or changes in business practices and policies.

Outside of the United States, we also face stringent privacy and data protection requirements.

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 (£17.5 million for the UK GDPR) or 4% of annual global revenues, whichever is greater.

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 U.K.

is subject to the EU General Data Protection Regulation ("EU GDPR") (with regards to the EEA) and the U.K.

General Data Protection Regulation ("U.K.

GDPR") (with regards to the U.K.), as well as applicable data protection laws in effect in the Member States of the EEA and in the U.K.

(including the U.K.

Data Protection Act 2018).

In this Annual Report, “GDPR” refers to both the EU GDPR and the U.K.

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 special categories of personal data (such as health) to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, conducting data protection impact assessments for high risk processing and taking certain measures when engaging third-party processors.

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.

5 unchanged sentences

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.

27 unchanged sentences

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.

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.

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.

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers.

Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed, and the IRA extended the moratorium on implementation until January 1, 2032.

Although a number of these and other proposed measures may require authorization through additional legislation to become effective, and the Biden administration may reverse or otherwise change these measures, both the Biden administration and Congress have indicated that they will continue to seek new legislative measures to control drug costs.

Although a number of these and other proposed measures may require additional authorization to become effective, Congress and President Biden have each indicated that they will continue to seek new legislative and/or administrative measures to control drug costs.

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.

Although a number of these and other proposed measures may require additional authorization to become effective, Congress and President Trump have indicated that they will continue to seek new measures to control drug costs including through the increased use of executive orders by the Trump administration.

Additional state and federal healthcare reform measures may be adopted in the future.

Further, it is possible that additional governmental action is taken in response to COVID-19.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

At the state level, legislatures have also increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

Employees and Human Capital Resources

12 unchanged sentences

Demographic Male Female Total

Asian 5 10 15

Black, Caribbean, or African 3 2 5

2 unchanged sentences

Total 41 64 105

In connection with the restructuring announced in January 2025, we are undertaking a reduction in headcount of approximately 65%, that impacts sites in the U.S.

The workforce reduction in the U.K.

was subject to consultation and the outcome was confirmed in February 2025.

A significant amount of the reduction in workforce will occur in the first half of 2025.

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.

1 unchanged sentence

We believe that attracting and retaining talent increases shareholder value and furthers the success of our company by motivating our employees to perform to the best of their abilities and achieve our objectives.

We employ individuals based on their experience and ability, and we are committed to promoting diversity and inclusion in our work environment.

We employ individuals based on their experience and ability.

We focus on hiring and retaining qualified candidates by promoting a supportive and inclusive working environment for all.

We believe that fostering diversity, equity, and inclusion is a key element to discovering, developing, and bringing transformative therapies to patients.

The safety of our workforce, including consultants and visitors to our office/laboratory, has and remained of paramount importance to us.

We believe that fostering a workforce with a wide range of experiences and backgrounds is a key element to discovering, developing, and bringing transformative therapies to patients.

The safety of our workforce, including consultants and visitors to our office/laboratory, has and remains of paramount importance to us.

We have a Health and Safety Committee that focuses on implementing policies and training programs to enhance workplace safety.

As we continue to grow, we also intend to expand our overall environmental, social, and governance, or ESG, efforts.

In 2022, we assigned oversight for ESG to the Nominating and Governance Committee who were tasked with performing an assessment of our ESG impacts and establishing initiatives.

Following this assessment, we have created specific goals and objectives to monitor and improve specific metrics.

These include:

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.

Carbon emissions

The group has calculated the emissions for the year ended December 31, 2023 and 2022 in tons of carbon dioxide equivalent (“tCO2e”).

The carbon footprint for the group for the years ended December 31, 2023 and 2022 are as follows:

We have calculated the emissions for the year ended December 31, 2024 and 2023 in tons of carbon dioxide equivalent (“tCO2e”).

The carbon emissions for our company for the years ended December 31, 2024 and 2023 are as follows:

December 31, 2024 December 31, 2023

6 unchanged sentences

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.

Standard emissions factors from the “U.K.

Government GHG Conversion Factors for Company Reporting (2023)” guidance were applied to estimate emissions.

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.

The increase in emissions is primarily attributable to our U.K.

laboratory and office facilities which is 31,000 square feet.

We have elected not to include the voluntary disclosure for Scope 3 emissions.

For the year ended December 31, 2024, the split of emissions by geography is as follows:

2 unchanged sentences

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:

We consider 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, 2024, and 2023 are as follows:

December 31, 2024 December 31, 2023

1 unchanged sentence

Intensity ratio 3.24 123 2.98 123

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 tons of carbon dioxide per employee has increased year on year, primarily as a result of our leased facilities in the United Kingdom and United States.

Additionally, more employees have been able to work from the office and therefore produced more greenhouse gas emissions than in 2023.

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.

8 unchanged sentences

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