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Item 1. Business

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Overview and Strategy

Powering the Immune System to Transform Lives.

Vir Biotechnology, Inc.

(including its subsidiaries, referred to as “Vir,” “the Company,” “we,” “our” or “us”) is an immunology company focused on combining cutting-edge technologies to treat and prevent serious infectious diseases and other serious conditions, including viral-associated diseases.

At Vir, we have a bold vision – powering the immune system to transform lives.

We aim to achieve this in two fundamental ways – first, through developing powerful antibody therapeutics and second, by generating unique T cell responses in vivo through our T cell-based viral vector platform.

Our growth and pursuit of scientific innovation is fueled by our world-class leading monoclonal antibody (mAb) platform that has a proven track record and is further strengthened by our artificial intelligence-led mAb optimization and engineering capabilities.

Our current clinical development pipeline consists of product candidates targeting hepatitis delta virus (HDV), hepatitis B virus (HBV), and human immunodeficiency virus (HIV).

The most advanced preclinical candidates in our pipeline include those targeting influenza A and B, coronavirus disease 2019 (COVID-19), respiratory syncytial virus (RSV), human metapneumovirus (MPV), and human papillomavirus (HPV).

We have assembled two technology platforms that modulate the immune system by exploiting critical observations of natural immune processes— a mAb discovery platform and a T cell-based viral vector platform.

Additionally, Vir is evaluating small interfering RNA (siRNA) through a collaboration with Alnylam Pharmaceuticals, Inc., or Alnylam, in our hepatitis clinical trials.

We have established our own internal process development, analytical development, manufacturing, supply chain and quality capabilities and work with contract development and manufacturing organizations (CDMOs) to develop, manufacture, test and supply our early- and late-stage product candidates.

We have an industry-leading management team and board of directors with significant immunology and infectious diseases experience, including a proven track record of progressing product candidates from early-stage research through clinical development, and worldwide regulatory approval and commercialization experience.

Given the global impact of infectious diseases and other serious conditions, we are committed to providing broad access to our therapeutics.

We are leveraging our core capabilities to drive patient impact and growth in infectious disease treatments and beyond to areas such as viral-associated and immune-mediated diseases, focusing our capital and resources on areas where Vir can be best-in-class.

Our core capabilities include our deep immunology and virology expertise.

In addition, our proven world-class mAb platform with artificial intelligence (AI) driven protein engineering capabilities allows us to discover and engineer next-generation antibodies with enhanced properties.

Our cytomegalovirus (CMV) based viral vector platform is designed with the goal of generating unique, potent and long-lasting T cell responses.

The core elements of our business strategy include:

• Advancing our pipeline .

We are conducting multiple clinical trials in multiple therapeutic areas including hepatitis and HIV.

• Expanding our pipeline .

We are leveraging our two platforms (mAbs and CMV) to discover and develop novel product candidates targeting HDV, HBV, HIV, influenza A & B viruses, COVID-19, RSV/MPV, precancerous HPV lesions, and additional viral-associated and immune-mediated diseases.

We anticipate moving additional preclinical candidates into the clinic in the next 12 to 24 months.

• Disciplined approach to capital allocation .

We are thoughtfully leveraging our strong balance sheet to ensure advancement of our multiple product candidates through major inflection points and invest in our people, processes and systems across the Company, while maintaining the ability to invest in external innovation.

• Augmenting our pipeline and capabilities by accessing external assets and innovation.

We actively monitor the external innovation landscape to identify technologies and assets to license or acquire that could complement our existing pipeline and enhance our capabilities.

• Partnering for success.

We have established relationships with organizations such as the Bill & Melinda Gates Foundation (BMGF), the Biomedical Advanced Research and Development Authority (BARDA), the National Institute of Health (NIH), and the National Health Service (NHS) to further facilitate access to our potential future medicines and to support our clinical development efforts.

We will continue to pursue similar alliances that help achieve our strategy with a focus on patient impact and value creation.

Our current product and product candidates are summarized by disease are in the chart below:

PEG-IFN-α = peg-interferon alfa-2a;

HVTN = HIV Vaccine Trials Network;

NIAID= National Institute of Allergy and Infectious Diseases

1 MARCH trial (Part B);

*Per the collaboration agreement announced in February 2021, Vir and GSK are continuing to advance new monoclonal antibody therapeutics for other respiratory viruses, including RSV

† Sotrovimab for early treatment by IV currently has marketing approval, temporary authorization or emergency use authorization in >30 countries.

In April 2022, the FDA deauthorized sotrovimab’s use in all U.S.

Sotrovimab incorporates Xencor’s Xtend™ technology.

Tobevibart incorporates Xencor’s Xtend™ and other fragment crystallizable technologies.

Our Clinical Product Portfolio

According to a 2020 article in the Journal of Hepatology and the World Health Organization’s July 2023 hepatitis D Factsheet, approximately 12 million people globally are infected with HDV, representing approximately 5% of the HBV population, and other studies show up to an estimated 72 million people living with HDV globally, many of which are likely undiagnosed.

HDV is considered the most severe and aggressive form of viral hepatitis leading to increased rates of cirrhosis, hepatocellular carcinoma, hepatic decomposition, and liver failure.

People with HDV are four times more likely to develop liver cancer than people with HBV and more than half of people with HDV will die of liver disease within 10 years of diagnosis.

There are no approved therapies for HDV in the U.S.

Hepcludex (bulevirtide), a once daily subcutaneous injection, has approval in the European Union (EU) and the United Kingdom (U.K.).

Pegylated interferon alpha (IFN-α) has been used off-label with limited success due to its tolerability profile and low rates of sustained virologic response.

Our current internal estimates project the HDV treatment market could be as large as $2 billion annually.

We are developing tobevibart, a monoclonal antibody also known as VIR-3434, and elebsiran, an siRNA also known as VIR-2218, for the treatment and suppression of chronic HDV.

Hepatitis B surface antigen (HBsAg) is a critical component necessary for the HDV lifecycle and both tobevibart and elebsiran act independently to inhibit the replication of HDV by targeting HBsAg.

Tobevibart binds to a conserved region of HBsAg, which helps eliminate HDV virions from the blood and also blocks the infection of hepatocytes with HDV.

Elebsiran targets a conserved region of the HBV genome and inhibits production of all HBV proteins including HBsAg.

In September 2022, we initiated the Phase 2 SOLSTICE trial evaluating tobevibart and elebsiran as monotherapy and in combination for the chronic treatment of people living with HDV.

The trial is assessing the safety and ability of the regimens to reduce HDV viremia and normalize alanine aminotransferase (ALT):

endpoints that may indicate improved clinical outcomes.

The current endpoint for regulatory approval is a combined endpoint consisting of a 2 log10 decline in HDV RNA or undetectable HDV RNA and ALT normalization.

Initial data presented in November 2023 demonstrated median HDV RNA reductions of -2.0 log10 and -1.4 log10 with once monthly subcutaneous (SC) doses of tobevibart and elebsiran monotherapy, respectively, for 12 weeks.

Once monthly SC combination therapy after 12 weeks of monotherapy with either tobevibart or elebsiran achieved -4.3 log10 reduction.

As of January 2024, of the participants entering combination therapy with tobevibart and elebsiran, data on 6 participants through week 20 of combination therapy was available.

Of these, 6/6 achieved HDV RNA < lower limit of quantitation (LLOQ) and 5/6 achieved HDV RNA < limit of detection (LOD) 12 weeks after starting combination therapy, which was maintained through week 20.

One participant in the tobevibart monotherapy arm achieved the combined endpoint with ALT normalization and two participants receiving combination therapy achieved the combined endpoint at week 12, which was maintained through week 20.

These data support continued evaluation of tobevibart and elebsiran for the chronic treatment of chronic hepatitis delta (CHD).

Tobevibart + elebsiran for HDV

(including its subsidiaries, referred to as “VirBio,” “the Company,” “we,” “our” or “us”) is a clinical-stage biopharmaceutical company focused on powering the immune system to transform lives by discovering and developing medicines for serious infectious diseases and cancer.

These diseases represent formidable challenges to human health.

Under normal conditions, our immune system is naturally equipped to protect us by identifying and eradicating both cancer cells and viruses.

However, these threats have evolved sophisticated mechanisms to evade our immune defenses.

When cancer cells or viruses successfully bypass our immune system, they have the potential to cause diseases that may be life-threatening.

We are focused on developing therapies that enhance the immune system’s ability to overcome these evasion tactics, effectively powering the immune system to combat viruses and fight cancer.

We believe our unified approach of leveraging our deep understanding of immunology to address seemingly disparate threats distinguishes us in the field.

Our mission is to develop innovative therapies that can transform patients' lives by addressing areas of high unmet medical need.

Our clinical development pipeline consists of investigational therapies targeting hepatitis delta virus (HDV) and various solid tumors.

In hepatitis delta, our phase 3 ECLIPSE registrational program evaluating the combination of tobevibart and elebsiran is scheduled to commence in the first half of 2025.

Should the ECLIPSE program yield positive results that support regulatory approval and subsequent commercial launch, we believe the combination has the potential to be a new standard of care for hepatitis delta patients, for whom approved treatment options are either limited or unavailable.

In oncology, we are advancing phase 1 clinical studies for our dual-masked T-cell engagers (TCEs):

VIR-5818 in patients with HER2-expressing tumors and VIR-5500 in patients with PSMA-expressing metastatic castration-resistant prostate cancer (mCRPC).

We are also advancing our third TCE program, VIR-5525, in patients with EGFR-expressing tumors, with phase 1 clinical studies are expected to begin in the first half of 2025.

We are also developing therapeutic candidates in hepatitis B virus (HBV), HIV cure, and other solid tumors, leveraging our expertise and platform strengths.

Advancement of our HBV program beyond the current MARCH study is contingent upon securing a worldwide (excluding People’s Republic of China, Taiwan, Hong Kong and Macau, collectively the “China Territory”) development and commercialization partner.

Our HIV broadly neutralizing antibodies (bnAbs) are being developed as a potential long-acting treatment or cure in combination with existing or investigational regimens.

These research and development efforts are driven by two core technology platforms—an advanced antibody discovery and protein engineering platform, and the exclusive PRO-XTEN ™ dual-masked TCE platform (a trademark of Amunix Pharmaceuticals, Inc., a Sanofi company (PRO-XTEN ™ )), which we in-licensed from Sanofi for worldwide rights in oncology and infectious diseases.

These platforms, individually and in combination, enable us to modulate the immune system in innovative ways, harnessing its power to combat viruses and fight cancer.

Our antibody platform leverages artificial intelligence and machine learning (collectively referred to as AI) for optimization, while the PRO-XTEN ™ platform allows for the development of potentially best-in-class TCEs with improved safety and efficacy profiles across multiple therapeutic areas.

We have an industry-leading management team and board of directors with significant immunology, infectious diseases and oncology experience, including a proven track record of progressing product candidates from early-stage research through clinical development, and worldwide regulatory approval and commercialization experience.

Given the global impact of infectious diseases and cancer, we are committed to developing transformative therapies that can make a meaningful difference in patients' lives.

Our Research and Development Pipeline

Millions of people suffer from infectious diseases and cancer, where a key factor is evasion of the innate immune system.

Our strategy leverages this commonality to power the immune system to fight back.

We use our world-class capabilities in antibody discovery and engineering, coupled with our proprietary AI engine (data AI structure and antibody system, or dAIsY ™ system), and the PRO-XTEN ™ masking technology, to quickly and effectively discover and optimize potential new medicines.

We have built a strong foundation based on cutting-edge core scientific capabilities and a world-class team of experts who bring deep knowledge and experience to our R&D efforts.

This has enabled us to make significant strides in developing treatments for infectious diseases and strategically expand our approach to address critical oncology indications with limited treatment options.

Our pipeline includes multiple candidates in clinical development stages for diseases with significant unmet medical need, which is summarized by disease area in the chart below.

Masked TCEs licensed from Sanofi

Human Immunodeficiency Virus;

peg-interferon alfa-2a;

monoclonal antibody;

small interfering RNA;

human epidermal growth factor receptor 2;

prostate-specific membrane antigen;

epidermal growth factor receptor.

Tobevibart incorporates Xencor’s Xtend TM and other Fc technologies.

Infectious Diseases

Molecular Characteristics and Preclinical Data .

Tobevibart is an investigational neutralizing mAb that has been engineered for immune engagement and targets a conserved region on HBsAg that allows it to neutralize strains from all 10 HBV genotypes.

Tobevibart is an investigational neutralizing monoclonal antibody (mAb) that has been engineered for immune engagement and targets a conserved region on the hepatitis B surface antigen (HBsAg), a protein which is required for the HDV viral life cycle.

Tobevibart specifically targets the antigenic loop (AGL) on HBsAg.

The AGL helps the virus bind to hepatocytes and subsequently infect these liver cells.

By binding to the AGL, tobevibart prevents viral entry, which prevents the spread of HDV to uninfected hepatocytes.

Tobevibart’s proprietary fragment crystallizable (Fc) Gamma engineering enhances its ability to engage immune cells, promoting the removal of antibody-virion complexes.

The AGL helps HBV bind to hepatocytes and subsequently infect these cells.

By binding to the AGL, tobevibart is designed to prevent viral entry, which prevents the spread of HDV to uninfected hepatocytes.

It has been engineered to neutralize strains from all 10 HBV genotypes.

Tobevibart, through a process called opsonization, also helps remove HBV virions and sub-viral particles (SVPs) from the blood.

Tobevibart was identified using our proprietary antibody discovery platform.

Tobevibart’s proprietary fragment crystallizable (Fc) engineering enhances its ability to engage immune cells, promoting the removal of antibody-virion complexes.

Tobevibart also incorporates Xencor’s Xtend ™ neonatal Fc receptor technology, which extends its half-life.

Tobevibart was identified using Vir’s proprietary mAb discovery platform.

Elebsiran is an investigational HBV-targeted siRNA that reduces HBsAg, a protein which is required for the HDV viral life cycle.

Elebsiran is a single siRNA targeting a conserved sequence of HBV that allows for predicted activity against 99.7% of the strains of HBV, including all 10 HBV genotypes.

Because this conserved sequence falls within a specific region of the X gene of HBV that exists within all four HBV RNA transcripts, elebsiran is able to degrade each transcript, and consequently decrease the expression of all proteins produced by the virus:

Tobevibart has the potential to activate the immune system to fight the virus via three different processes.

First, due to specialized mutations in the Fc domain, tobevibart has the potential to act as a T-cell vaccine, inducing the production of protective T-cells and promoting immunity.

This is based on a mechanism by which tobevibart could capture virions and SVPs, deliver them to dendritic cells and instruct these cells to mature and stimulate T-cells that can then eliminate HBV infected hepatocytes.

Second, tobevibart has the potential to act via antibody-dependent cell cytotoxicity (ADCC).

In this process, by binding to HBsAg at the cell surface, tobevibart recruits natural killer cells to eliminate infected hepatocytes.

The Fc domain of tobevibart has been engineered to promote ADCC.

Third, when large quantities of HBV proteins are released into the blood, especially HBsAg, they can be immunosuppressive.

Tobevibart has the potential to activate the immune system by reducing the amount of HBsAg in the blood, decreasing the ability of HBV to suppress the immune system and further enabling the natural immune response to the virus.

Molecular Characteristics and Preclinical Data .

Elebsiran is an investigational HBV-targeted small interfering RNA (siRNA) that reduces HBsAg.

Elebsiran targets a conserved sequence of HBV that allows for predicted activity against 99.7% of the strains of HBV, including all 10 HBV genotypes.

Because this conserved sequence falls within a specific region of the X gene of HBV that exists within all four HBV RNA transcripts, elebsiran is designed to degrade each transcript, and consequently decrease the expression of all proteins produced by the virus:

X, polymerase, S, and core.

Elebsiran is thus potentially a potent antiviral.

HBV DNA can become integrated into human DNA as intDNA.

Once inside the infected cell, DNA from the HBV virus can become integrated into human DNA as integrated DNA (intDNA).

Because elebsiran targets a region of HBV that is conserved in the large majority of HBV intDNA, this single siRNA is predicted to be able to prevent the production of HBV proteins derived from intDNA, as well as the production of all other HBV proteins from covalently closed circular DNA (cccDNA).

MOA = mechanism of action;

NRTI = nucleotide reverse transcriptase inhibitor;

RNP = ribonucleoprotein;

SVP = subviral particle

Tobevibart has been shown to neutralize HDV infection with pan-genotypic activity.

Single and combination treatments with tobevibart and elebsiran of HBV/HDV-co-infected primary human hepatocytes in vitro reduced HBV antigens as well as secreted infectious HDV virions.

In vivo , the parental molecule of tobevibart reduced the levels of HBsAg, HDV and HBV viremia in HBV/HDV-co-infected liver-chimeric mice.

These data support the clinical evaluation of tobevibart and elebsiran in HDV.

Phase 2 Trial of tobevibart in combination with elebsiran.

In September 2022, we initiated the Phase 2 SOLSTICE trial evaluating tobevibart and elebsiran as monotherapy and in combination for the chronic treatment of people living with HDV.

The trial is assessing the safety and ability of the combination to reduce HDV viremia (2 log10 decline in HDV RNA or undetectable HDV RNA) and normalize ALT, the current combined endpoints used for regulatory approval.

The SOLSTICE trial initially evaluated once monthly SC injections of either tobevibart or elebsiran as monotherapy for 12 weeks.

If participants did not achieve the primary endpoint of virologic response (2 log10 IU/mL decline or undetectable HDV RNA) and ALT normalization, participants were eligible to initiate combination therapy.

Median decline of HDV RNA in participants receiving tobevibart or elebsiran as monotherapy were -2.0 log10 and -1.4 log10 IU/mL, respectively after 12 weeks of treatment.

Six participants entered combination treatment.

As of the January 2024 data cutoff, data was available on all 6 participants through week 20 of combination therapy or day 225 of any therapy.

At week 12 of combination therapy, a median reduction in HDV RNA of -4.29 log10 from baseline was observed.

At that time, 6/6 achieving HDV RNA <LLOQ and 5/6 participants achieving HDV RNA <LOD, which has continued through Week 20.

One participant in the tobevibart monotherapy arm achieved the combined endpoint with ALT normalization and 2 participants also achieved the combined endpoint after the initial 12 weeks of combination therapy, which was maintained through week 20.

No serious adverse events (SAEs) were reported with few treatments emergent adverse events across cohorts with most being Grade 1 and 2.

No ALT elevations above baseline were observed to Week 20 with the tobevibart/elebsiran combination therapy regardless of baseline HBsAg or HDV RNA.

Additional cohorts evaluating the combination of tobevibart and elebsiran and tobevibart monotherapy are currently ongoing with additional data anticipated to be available in 2024.

LLOQ = 63 IU/mL;

LOD = 14 IU/mL

1 Cohort 2C has 6 total participants enrolled.

As of January 2024, from the 6 participants who have reached day 225 (week 20 of combination therapy), 5 participants achieved HDV RNA < LLOQ.

According to the Hepatitis B Foundation, approximately 300 million people globally are chronically infected with HBV and approximately 900,000 die from HBV-associated complications each year.

There is a significant unmet medical need for more effective therapies that lead to life-long control of the virus after a finite duration of therapy, which is the definition of a functional cure.

Currently, a year-long course of IFN-α is the best available curative therapy and has a low functional cure rate of approximately 3% to 7%.

Alternatively, suppressive therapy with daily nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs) is commonly used, but patients often require a lifetime of therapy and NRTI therapy does not eliminate the risk of cirrhosis or hepatocellular carcinoma.

Our two therapeutic candidates, tobevibart and elebsiran, are both antivirals and potential immunomodulators.

We believe that a functional cure for HBV will require an effective immune response, in addition to antiviral activity, based on the observation that severe immunosuppression can reactivate HBV disease.

Our hypothesis is that the large amount of HBV protein that is transcribed in liver cells can suppress the immune system.

There are at least two potential mechanisms by which suppression occurs.

There are at least two potential mechanisms by which the large amount of HBV protein that is transcribed in liver cells can suppress the immune system.

The first mechanism is T-cell tolerance and exhaustion by the presentation of intracellular HBV antigens on hepatocytes.

The second is the large quantities of HBV proteins that are released into the blood, especially HBsAg, which may also be immunosuppressive.

We therefore believe that tobevibart and elebsiran have the potential to play a critical role in interrupting the mechanisms of immunosuppression and reactivating the immune response to deliver high functional cure rates.

Tobevibart and elebsiran demonstrated declines in HBsAg and were generally well tolerated in dose-escalation Phase 1 studies in healthy volunteers and adults with HBV.

Phase 2 clinical trials evaluating tobevibart and elebsiran are in progress and described below.

A Phase 2 clinical trial evaluating elebsiran in combination with PEG-IFN-α for 24 and up to 48 weeks showed that 25.8% (8/31) of the participants receiving up to 48 weeks of elebsiran plus IFN-α treatment achieved higher rates of HBsAg seroclearance with hepatitis B surface antibodies (anti-HBs) seroconversion by the end of treatment, with 16.1% (5/31) maintaining seroclearance 24 weeks after end of treatment.

The treatment regimens were generally well tolerated and resulted in no new safety signals.

These initial results support our hypothesis of combining an antiviral with an immunomodulator to achieve HBsAg seroclearance and seroconversion.

In July 2021 we initiated a two-part study to evaluate the combination of tobevibart and elebsiran in virally suppressed HBV patients.

Part A evaluated short treatment courses of tobevibart and elebsiran to rapidly evaluate safety, PK and HBsAg suppression when tobevibart is given weekly concomitantly with or after pre-treatment with elebsiran.

By directly reducing the amount of HBV proteins made, elebsiran has the potential to decrease the ability of HBV to suppress the immune system and enable the natural immune response to the virus.

In mice models, siRNAs that are able to reduce HBsAg expression can transform an otherwise ineffective therapeutic HBV vaccine into one that can functionally cure the mice of HBV, suggesting that HBsAg suppression has the ability to enhance the immune response against HBV.

We believe that elebsiran is the only HBV-targeting siRNA currently in development that includes enhanced stabilization chemistry (ESC+) technology and preclinical modeling.

Initial clinical data suggest this technology may be able to enhance the safety profile of elebsiran.

Simplified mechanism of action representation of tobevibart and elebsiran.

covalently closed circular DNA, HBsAg:

hepatitis B virus surface antigen, HBV:

hepatitis B virus, HDV:

hepatitis D virus, Int:

integrated, NRTI:

nucleoside/nucleotide reverse transcriptase inhibitor, RNP:

ribonucleoprotein, SVP:

subviral particle

Chronic Hepatitis Delta (CHD)

CHD is a chronic, progressive liver disease caused by the HDV, which requires HBV for its replication.

This means that hepatitis delta infection cannot occur in the absence of HBV.

HDV-HBV coinfection is the most severe form of chronic viral hepatitis.

CHD increases the risk of liver cancer and accelerates progression to cirrhosis and liver failure, which often occurs within 5 years of infection.

There is no approved CHD treatment in the U.S., and options are limited in the European Union and globally.

VirBio is working to develop a chronic suppressive therapy to help address this significant unmet medical need, based on a combination of our investigational antibody, tobevibart, and a siRNA, elebsiran.

Tobevibart + elebsiran for CHD

Phase 2 Trial of tobevibart, both alone and in combination with elebsiran in hepatitis delta .

SOLSTICE is a Phase 2 study to evaluate the safety, tolerability, and efficacy of tobevibart, alone or in combination with elebsiran, in people with CHD.

This Phase 2 study is a multi-center, open-label, randomized study.

Primary endpoints include proportion of participants with protocol defined virologic endpoint (defined as HDV RNA equal or greater than 2 log 10 decrease from baseline or below limit of detection) up to week 24, alanine aminotransferase (ALT) normalization (defined as ALT below upper limit of normal) up to week 24, and treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) up to 118 weeks.

Secondary endpoints include proportion of participants with undetectable HDV RNA and different timepoints up to 192 weeks.

Clinical trial participants have been randomized to receive tobevibart 300 mg monotherapy every two weeks (n=33) or a combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination de novo arm, n=32).

In addition, the participants from previous tobevibart or elebsiran monotherapy cohorts could rollover to receive the combination of tobevibart 300 mg and elebsiran 200 mg every four weeks (combination rollover , n=13).

The latest data from the ongoing clinical trial was presented in an oral session at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting ® , in San Diego, CA, in November 2024.

The data included rates of virologic suppression and ALT normalization evaluated at Week 24, and Weeks 36, 48 and 60 in those participants that had reached each timepoint.

The trial assesses the combined endpoint of HDV RNA decrease ≥ 2 log 10 compared to baseline or HDV RNA below LOD and ALT normalization, which is the current combined endpoint used for regulatory approval.

At the same time, HDV RNA below the lower limit of quantification (< LLOQ), target not detected (HDV RNA TND) and the composite endpoint of HDV RNA TND and ALT normalization is also being monitored to assess efficacy.

100% of participants across combination arms achieved an HDV RNA ≥2 log 10 decrease or below LOD at Week 24, and this rate was sustained over time in all participants at Weeks 36 (22/22) and those in the combination rollover cohort that reached Week 60 (5/5).

HDV RNA TND was achieved in 41% (13/32) of participants across combination arms at Week 24 and this rose to 64% (14/22) at Week 36.

By week 60, this had risen further with 80% (4/5) of participants in the combination rollover cohort having achieved no detectable viral RNA.

ALT decreased in most participants between Day 1 and Week 24 and normalized in 47% (15/32) of participants in the combination de novo cohort and 56% (5/9) in the combination rollover cohort by Week 24.

These rates were sustained at Week 36.

The protocol defined combined endpoint of HDV RNA decrease ≥ 2 log 10 compared to baseline or HDV RNA below LOD and ALT normalization at Week 24 was observed in 47% (15/32) of participants in the combination de novo arm.

The more stringent composite endpoint of HDV RNA TND and ALT normalization was achieved in 19% (6/32) of participants in the combination de novo arm at Week 24, which increased to 27% (6/22) by Week 36.

This trend was reflected in the combination rollover cohort in which 33% (3/9) of participants achieved this endpoint at Week 24 and 40% (2/5) at Week 60.

Rates of HDV RNA suppression and ALT normalization were similar between non-cirrhotic and cirrhotic participants across combination arms.

The safety profile of tobevibart and elebsiran is consistent with previous studies.

TEAEs were generally mild or moderate and transient across all treatment groups, with influenza-like symptoms being the most common event.

No ALT flares were observed.

There were no study-related discontinuations in the combination arms, and no treatment-related SAEs were reported.

A Phase 3 registrational clinical program, ECLIPSE, which will evaluate the tobevibart and elebsiran combination in people living with CHD, is expected to commence in the first half of 2025.

The trial will include three randomized, controlled trials designed to evaluate the combination therapy in comparison to deferred treatment or bulevirtide.

All studies will enroll both cirrhotic and non-cirrhotic participants.

The combination of tobevibart and elebsiran have now been recognized by the U.S.

Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for their potential to address the critical unmet need in CHD.

In June 2024, the combination received Fast Track designation from the FDA, which was followed by Breakthrough Therapy designation in December 2024.

In addition, the combination received a Priority Medicines (PRIME) designation from the EMA, and orphan drug designation from the European Commission (EC), each in December 2024.

Chronic Hepatitis B (CHB)

CHB is a long-lasting, inflammatory liver disease caused by the HBV.

The World Health Organization estimates that 254 million people live with CHB, and an estimated 1.1 million yearly deaths are associated with the disease.

Complications from CHB may include liver cirrhosis, liver failure and liver cancer.

The rate of functional cure (lifelong control of the virus after a finite duration of treatment) with current approved treatments is 3%-7%.

Alternatively, suppressive therapy with daily nucleotide/nucleoside transcriptase inhibitors (NRTIs) is commonly used, and CHB patients often require a lifetime of therapy, and NRTIs reduce but do not eliminate the risk of further progression and developing end-stage liver disease complications such as cirrhosis or cancer.

We are pursuing a functional cure for CHB based on a combination regimen of tobevibart and elebsiran with or without pegylated interferon alpha (PEG-IFNα).

Tobevibart + elebsiran ± PEG-IFNα for CHB

Phase 2 Trial of tobevibart in combination with elebsiran alone (doublet regimen) or in combination with PEG-IFNα (triplet regimen) .

In July 2021 we initiated the MARCH two-part study to evaluate the combination of tobevibart and elebsiran in virally suppressed HBV patients.

MARCH Part A evaluated short treatment courses of tobevibart and elebsiran to rapidly evaluate safety, pharmacokinetics and HBsAg suppression when tobevibart is given weekly concomitantly with or after pre-treatment with elebsiran.

Results from MARCH Part A in 2022 showed that the combination of tobevibart and elebsiran resulted in an approximate 3 log 10 IU/mL decline in HBsAg with no safety signals.

2 unchanged sentences

MARCH Part B includes cohorts treated for 24- and 48-weeks with monthly doses of tobevibart plus elebsiran with and without PEG-INF-α.

In November 2023, we announced initial 24-week treatment arm results from MARCH Part B that evaluated the combination of tobevibart and elebsiran with and without IFN-α.

End of treatment results at 24-weeks demonstrated 15.0% (3/20) and 14.3% (3/21) of participants achieving HBsAg seroclearance in the tobevibart+elebsiran and tobevibart+elebsiran+IFN-α arms, respectively.

This was higher than what was observed with elebsiran+IFN-α in which 5.6% of participants achieved HBsAg seroclearance after 24 weeks, demonstrating that tobevibart improved the rate of HBsAg seroclearance.

At 12 weeks after end of treatment, all participants who achieved HBsAg seroclearance in the tobevibart+elebsiran arm had rebounded while 2 of 3 participants in the tobevibart+elebsiran+IFN-α arm maintained HBsAg seroclearance.

End of treatment data from the 48-week arms of tobevibart+elebsiran and tobevibart+elebsiran+IFN-α are expected in the fourth quarter of 2024.

The Phase 2 PREVAIL platform trial evaluating the efficacy and safety of tobevibart and elebsiran in participants with chronic HBV infection is ongoing evaluating inactive carriers and immune active, treatment-naïve patients.

In November 2024, we presented 48-week end-of-treatment data from MARCH Part B that evaluated the combination of tobevibart and elebsiran alone or with IFN-α (doublet and triplet regimens, respectively) in an oral session at the AASLD The Liver Meeting ® , in San Diego, CA.

This analysis included data from 51 participants in the doublet regimen arm and 27 participants in the triplet regimen arm at the end of treatment.

The study demonstrated promising rates of HBsAg loss (seroclearance, defined as HBsAg below the lower limit of quantification) in participants with low baseline HBsAg (<1000 IU/mL) in both combination regimens.

The efficacy and safety profile support continued development to evaluate the potential to achieve a functional cure.

The doublet and triplet regimens resulted in HBsAg loss at the end of treatment in 39% (7/18) and 46% (5/11) of participants with baseline HBsAg<1,000 IU/mL, respectively.

The proportion of participants with varying baseline HBsAg levels who achieved HBsAg loss at end of treatment was 16% (8/51) for the doublet and 22% (6/27) for the triplet regimen.

The doublet regimen resulted in 50% (4/8) of participants who had achieved HBsAg loss also achieving anti–hepatitis B surface antibody (anti-HBs) seroconversion.

All participants with HBsAg loss at the end of treatment who received the triplet regimen achieved anti-HBs seroconversion (100%, 6/6).

Participants with HBsAg seroclearance at end of treatment who meet eligibility criteria will discontinue treatment.

Functional cure assessment will occur 24 weeks after treatment discontinuation.

Functional cure data is expected in the first half of 2025.

The Phase 2 PREVAIL platform trial evaluating the efficacy and safety of tobevibart and elebsiran in participants with CHB is ongoing.

This trial is designed to evaluate combinations of tobevibart, elebsiran and/or PEG-IFNα in two patient populations:

immune-active but treatment-naïve and inactive carriers.

Elebsiran is also being evaluated in additional Phase 2 clinical trials with collaborators.

Brii Bio is the sponsor for the Phase 2 trial of elebsiran in combination with BRII-179, an investigational therapeutic vaccine, for the treatment of chronic HBV infection.

Treatment has completed in this trial.

Treatment with elebsiran alone or in combination with BRII-179 with and without coadjuvant IFN-α was generally well tolerated.

Although the combination of elebsiran and BRII-179 had greater anti-HBs responses and improved HBsAg-specific T-cell responses, comparable HBsAg reduction was observed in all cohorts at end of treatment (-1.7-1.8 log10 IU/mL).

As described in further detail below under the heading “Our Collaboration, License and Grant Agreements,” we granted Brii Bio an option to obtain exclusive rights to develop and commercialize elebsiran and tobevibart in China, Taiwan, Hong Kong and Macau, or collectively the China Territory, for the treatment, palliation, diagnosis, prevention or cure of acute and chronic diseases of infectious pathogen origin or hosted by pathogen infection, or the Field of Use.

In December 2021, we and Gilead (study sponsor) initiated a Phase 2 clinical trial of elebsiran in combination with GS-9688 (selgantolimod), Gilead’s investigational TLR-8 agonist, and nivolumab in both NRTI-suppressed patients and viremic patients.

Patients with HBV treatment experience also may receive tenofovir alafenamide, or TAF.

In February 2023, nivolumab was discontinued in cohorts evaluating nivolumab in combination with elebsiran and GS-9688 due to immune-related adverse events associated with nivolumab, which are consistent with the safety profile of the class.

HBV Life Cycle and Undetectable HBsAg as a Clinical Endpoint

After infecting a cell, the virus forms cccDNA.

This form of HBV DNA is located in the nucleus of hepatocytes and acts like a mini-chromosome.

HBV DNA can also integrate into the patient’s DNA.

This form of HBV DNA is known as integrated DNA, or intDNA.

HBV releases infectious virions and subviral particles (SVPs) from infected cells.

Both virions and SVPs include forms of an HBV protein called HBsAg, a blood biomarker that indicates that the HBV cccDNA and/or intDNA in that patient’s hepatocytes are actively making HBV RNA and HBV proteins.

The formal endpoint accepted by the FDA for functional cure is undetectable HBsAg, defined as less than 0.05 IU/mL, as well as HBV DNA less than the lower limit of quantification, in the blood six months after the end of therapy.

Achievement of this endpoint has been shown to predict improved clinical outcomes and the lack of need for further therapy.

Limitations of Current Standard of Care

There is a significant unmet medical need for finite versus chronic therapies that achieve functional cure.

The most commonly used therapy for chronic HBV is life-long suppressive therapy with daily oral NRTIs, like tenofovir or entecavir.

However, NRTIs rarely achieve functional cure, defined as the sustained loss (seroclearance) of detectable HBsAg and HBV DNA in serum, after a finite course of treatment.

NRTIs prevent HBV ribonucleic acid, or RNA, from being transcribed into HBV DNA, which is a process known as reverse transcription.

NRTIs therefore have little to no direct impact on covalently closed circular DNA(cccDNA) the reservoir for HBV or HBsAg production.

It has been reported that after a year of therapy with NRTIs, zero to 3% of patients experience a functional cure.

Additionally, NRTIs reduce, but do not eliminate, the risk of HBV associated liver failure and liver cancer.

Despite its low utilization rate, suppressive therapy with NRTIs for HBV represented approximately $500 million in the U.S.

alone in 2022, according to IQVIA (Midas data).

An alternative treatment option for chronic HBV is a year-long course of IFN-α therapy, which has poor tolerability and low functional cure approximately 3% to 7% of the time.

The mechanisms by which IFN-α, an immune cytokine, achieves a functional cure are not known, but there is additional evidence supporting the need for immune stimulation to achieve a functional cure.

Of the hundreds of millions of people with chronic HBV worldwide, only about 10% are diagnosed, and of those diagnosed, only about 22% are treated.

New, functional cure therapies have potential to increase diagnosis and treatment rates.

Our current internal estimates project the global HBV functional cure market could be as large as $10 billion annually.

Tobevibart for HBV

Brii Biosciences Offshore Limited (“Brii Bio”) is the sponsor for the Phase 2 trial of elebsiran in combination with BRII-179, an investigational therapeutic vaccine, for the treatment of chronic HBV infection.

As described in further detail below under the heading “Our Collaboration, License and Grant Agreements,” we granted Brii Bio an option to obtain exclusive rights to develop and commercialize elebsiran and tobevibart in the China Territory, for the treatment, palliation, diagnosis, prevention or cure of acute and chronic diseases of infectious pathogen origin or hosted by pathogen infection, or the Field of Use.

One in five people worldwide develop cancer during their lifetime, and although tremendous strides have been made in cancer prevention and treatment, cancer still remains the second-leading cause of death globally and remains the leading or second-leading cause of premature death (before age 70 years) in 112 countries.

While major advances have been made in immunotherapies for hematologic malignancies, a large unmet need remains for novel and tolerable therapeutics for patients with solid tumors.

TCEs are potent anti-tumor agents that direct the immune system, specifically T-cells, to attack cancer cells.

VirBio’s bi-specific TCE is comprised of two antibody fragments:

a tumor-associated antigen (TAA) binding domain and a CD3 binding domain.

They are designed to simultaneously recruit T-cells and TAA expressing cancer cells, directing the cytotoxic activity of T-cells against the tumor.

However, if the antigen is also expressed on healthy cells, bi-specific TCEs can similarly bind to TAAs present in non-cancerous cells or healthy tissue, driving on-target, off-tumor toxicity, including cytokine release syndrome (CRS), thus limiting the potential therapeutic index of TCEs.

Masking of TCEs is a strategy designed to circumvent these limitations.

This technology specifically leverages overactivity of proteases in the tumor microenvironment (whereas proteases are tightly regulated by protease inhibitors elsewhere in the body).

By attaching masks joined by protease cleavable linkers to the TCE, VirBio’s TCEs are designed to remain inactive until they reach the tumor microenvironment.

Once in the tumor microenvironment, tumor-specific proteases can cleave off the mask and release the unmasked TCE, which can bind to both T-cell and tumor cells expressing the TAA, and lead to killing of cancer cells.

By limiting the unmasking of the TCEs to the tumor microenvironment, we aim to limit the toxicity of these agents in the periphery and potentially increase their safety and efficacy.

We are currently advancing three clinical-stage dual-masked TCEs, VIR-5818 (phase 1), VIR-5500 (phase 1), and VIR-5525 (IND cleared, initiating phase 1), that leverage the PRO-XTEN ™ masking technology with TCEs targeting CD3 on T-cells, and HER2, PSMA and EGFR, respectively, on tumor cells.

VIR-5818 ± pembrolizumab for the treatment of HER2-positive solid tumors

Molecular Characteristics and Preclinical Data .

Tobevibart is an investigational neutralizing mAb that has been engineered for immune engagement and targets a conserved region on the antigenic loop (AGL) of HBsAg that allows it to neutralize strains from all 10 HBV genotypes.

The AGL helps the virus bind to hepatocytes and subsequently infect these liver cells.

By binding to the AGL, tobevibart prevents viral entry, which prevents the spread of HBV to uninfected hepatocytes.

Tobevibart, through a process called opsonization, also helps remove HBV virions and SVPs from the blood.

Hepatitis B immunoglobulin (HBIG) an approved therapy for preventing reinfection after transplantation and which consists of polyclonal antibodies against HBV, acts by similar mechanisms.

In vitro, tobevibart demonstrates approximately 5,000-fold greater potency than HBIG in neutralization assays.

Tobevibart also has the potential to activate the immune system, via three different processes.

First, due to specialized mutations in the Fc domain, tobevibart, has the potential to act as a T cell vaccine.

Tobevibart has been engineered with mutations that enhance binding to the Fc receptor (FcR) IIa activating receptor and diminish binding to the FcR IIb inhibitory receptor.

As such, tobevibart is designed to capture virions and SVPs, deliver such virions and SVPs to dendritic cells (DCs), and instruct these DCs to mature and stimulate T cells that can eliminate HBV infected hepatocytes.

Second, tobevibart has the potential to act via antibody-dependent cell cytotoxicity (ADCC).

In this process, by binding to HBsAg at the cell surface, tobevibart recruits natural killer cells to eliminate infected hepatocytes.

The Fc domain of tobevibart has been engineered to promote ADCC.

Third, by reducing the amount of HBsAg in the blood, tobevibart has the potential to remove a brake on the immune system by decreasing the ability of HBV to suppress it.

Additionally, tobevibart, incorporates Xencor’s Xtend TM to extend serum half-life.

Phase 1 Trial of tobevibart.

The trial was an adaptive clinical trial designed to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of tobevibart.

The Phase 1 clinical trial had four parts.

Part A was a single ascending dose design in healthy volunteers, with Parts B and C as single ascending dose designs in adults with chronic HBV on NRTIs.

Part B included patients with HBsAg levels less than 1,000 IU/ml for the 6 mg cohort and less than 3,000 IU/mL for the other dose cohorts.

Part C included patients with HBsAg levels greater than or equal to 3,000 IU/mL.

Part D included patients with HBV DNA greater than or equal to 1,000 IU/mL who were not receiving NRTI therapy.

The primary endpoints across all parts of the trial were safety and tolerability.

The key secondary endpoint in Parts B and C was the maximum reduction of serum HBsAg from baseline.

In Part D, an additional key secondary endpoint was the maximum change of HBV DNA from baseline.

Across all study parts, tobevibart up to 3,000 mg intravenously, or IV, was generally well tolerated with no clinical safety concerns observed.

In Part B, most participants achieved a ≥1 log10 IU/mL reduction from baseline in HBsAg within 1-3 days.

Mean HBsAg reductions in the 6 mg, 18 mg, 75 mg, and 300 mg groups were 1.30, 1.27, 1.96, and 2.21 log10 IU/mL, respectively, at nadir.

All participants who received 75 mg or 300 mg of tobevibart achieved HBsAg <100 IU/mL and 5/6 (83%) in the 300 mg group achieved HBsAg <10 IU/mL.

In Part D, single doses of 75 mg or 300 mg was associated with rapid reductions in HBsAg and HBV DNA in the majority of participants.

Across both cohorts, 11/12 participants receiving tobevibart achieved a >1 log10 IU/mL decline in HBsAg and 11/12 achieved a >1 log10 IU/mL decline in HBV DNA with the changes in HBsAg and HBV DNA showing similar kinetics.

Across all parts of the study, tobevibart was generally well tolerated with the majority of adverse events being mild to moderate in severity.

The rapid reductions in HBsAg after just one dose and the safety profile supported further evaluation in Phase 2.

Elebsiran for HBV

Molecular Characteristics.

Elebsiran is an investigational, single siRNA targeting a conserved sequence of HBV that allows for predicted activity against 99.7% of the strains of HBV, including all 10 HBV genotypes.

X, polymerase, S, and core.

Elebsiran is thus potentially a broad-spectrum, potent antiviral.

HBV DNA can become integrated into human DNA as intDNA.

We believe that the large amount of HBV protein that is transcribed in liver cells can suppress the immune system.

There are at least two potential mechanisms by which suppression occurs.

The first mechanism is T cell tolerance and exhaustion by the presentation of intracellular HBV antigens on hepatocytes.

The second is the large quantities of HBV proteins that are released into the blood, especially HBsAg, which may also be immunosuppressive.

By directly reducing the amount of HBV proteins made, elebsiran has the potential to decrease the ability of HBV to suppress the immune system—in effect removing a brake on the immune system.

In mice models, siRNAs that are able to reduce HBsAg expression can transform an otherwise ineffective therapeutic HBV vaccine into one that can functionally cure such mice of HBV, suggesting that HBsAg suppression has the ability to enhance the immune response against HBV.

We believe that elebsiran is the only HBV-targeting siRNA currently in development that includes enhanced stabilization chemistry (ESC+) technology and preclinical, modeling and initial clinical data suggest this technology may be able to enhance the potential safety of elebsiran.

Phase 1/2 Trial of elebsiran.

The trial was an adaptive clinical trial designed to evaluate the safety, tolerability, pharmacokinetics and antiviral activity of elebsiran.

It evaluated single ascending doses (50 mg to 900 mg) of elebsiran in healthy volunteers and multiple ascending doses (50 mg to 200 mg for 2 doses) in adults with chronic HBV suppressed on NRTI therapy.

Across healthy volunteers and chronic HBV patients, elebsiran has been generally well-tolerated.

No clinically significant ALT abnormalities, which are a marker of liver inflammation, have been observed.

In the Part A 900 mg cohort, asymptomatic Grade 1 ALT elevations with no associated changes in bilirubin, or other markers of liver function, have been observed.

Three SAEs have been reported, all in Part B.

The first, a Grade 2 headache, resolved with IV fluids and non-opioid pain medications.

This patient had additional symptoms of fever, nausea, vomiting and dehydration, assessed by us as consistent with a viral syndrome.

The second SAE, a Grade 4 depression, occurred over 50 days after the last drug dose was administered, and was assessed by us as not related to elebsiran.

The third SAE, a patient suicide, occurred 241 days after the last dose of study drug and was assessed by us as not related to elebsiran.

Three Grade 3 adverse events of upper-respiratory tract infection, chest pain and low phosphate levels in the blood have also been reported.

We did not consider any of these Grade 3 events as related to elebsiran.

Antiviral activity of elebsiran was assessed by changes in HBsAg.

The activity of elebsiran through Week 48 for each dose level is shown in the graph below.

For Parts B and C, the mean baseline HBsAg levels were 3.3 log10 IU/mL and 3.9 log10 IU/mL, respectively.

The mean decline in HBsAg across hepatitis B e-antigen (HBeAg) negative and HBeAg positive subjects at Week 16 was 1.5 log10, or an approximately 32-fold reduction.

The declines observed in HBsAg at Week 16 ranged from 0.97 log10 to 2.2 log10, or an approximately nine to 160-fold reduction, after two 200 mg doses of elebsiran given four weeks apart.

The mean HBsAg level at Week 16 was 314 IU/mL, with half of the patients achieving HBsAg values < 100 IU/mL and 5/6 achieving HBsAg values < 1000 IU/mL.

Five of the 12 patients that achieved HBsAg values of <100 IU/mL maintained it through Week 48.

Therefore, even though HBsAg levels gradually rebounded, overall, a durable effect was observed.

The ability of elebsiran to result in substantial and durable declines in HBsAg after only two doses suggests that elebsiran has the potential to play an important role in the functional cure of chronic HBV.

We have initiated additional clinical trials evaluating elebsiran in combination with other immunomodulatory agents.

Change from Baseline in HBsAg following administration of elebsiran.

Each line represents the mean decline from baseline in HBsAg for elebsiran for each dosing level or pooled placebo in Parts B and C.

HBV Combinations and New Product Candidates

Phase 2 Trial of elebsiran in combination with IFN-α.

This is a clinical trial evaluating the safety, tolerability, pharmacokinetics and antiviral activity of elebsiran alone and in combination with IFN-α in adults with chronic HBV infection on NRTIs.

The trial is evaluating multiple doses of elebsiran 200 mg, alone or in combination with IFN-α for 24 to 48 weeks.

The trial cohorts are shown below.

EOT = end of treatment;

LLOD = lower limit of detection;

QW = every week

a HBsAg assay LLOQ and LLOD are 0.05 IU/mL.

Elebsiran in combination with IFN-α for 24 weeks from Day 1 (Cohort 3) resulted in a more rapid and substantial decline in HBsAg compared to elebsiran alone (Cohort 1) and elebsiran lead-in followed by concomitant administration with IFN-α from Week 12-24 (Cohort 2).

Through Week 24, mean HBsAg change from baseline were -1.9, -2.0, and -2.4 log10 IU/mL in Cohorts 1, 2, and 3, respectively, with greater than 1 log10 decline in HBsAg maintained at Week 48.

Cohorts 4 and 5 evaluated treatment beyond 24 weeks.

In both Cohorts 4 and 5, participants took elebsiran and IFN-α from Day 1 through Week 24.

In Cohort 4, participants were eligible to continue IFN-α up to 48 weeks if they did not achieve HBsAg less than the lower limit of quantitation, or LLOQ, and participants in Cohort 5 were able to continue elebsiran and IFN-α up to Week 48 if they did not achieve HBsAg <LLOQ.

If a participant in Cohorts 4 or 5 achieved HBsAg <LLOQ at 2 consecutive visits, they were eligible to stop therapy.

Through Week 48, mean HBsAg change from baseline were -1.8 and -2.9 log10 IU/mL in Cohorts 4 and 5, respectively.

Overall, 10 participants achieved HBsAg seroclearance by Week 48 across all cohorts with the majority occurring in Cohorts 4 and 5.

Importantly, nine out of these 10 participants, including all four in Cohort 5, also achieved seroconversion defined as anti-HBsAb > 10 mIU/mL, which suggests the potential for durability of response after stopping therapy.

Participants in Cohorts 4 and 5 were able to maintain HBsAg seroclearance 24 weeks after end of treatment at 16.7% (3/18) and 15.4% (2/13), respectively.

Among participants who had HBsAg seroclearance by end of treatment, 4/4 had anti-HBs levels >500 mIU/mL at end of treatment had sustained HBsAg seroclearance 24 weeks post end of treatment.

All participants (3/3) who had anti-HBs levels <100 mIU/mL at end of treatment experienced rebound in HBsAg.

Three participants had anti-HBs between 100-500 mIU/mL;

2 experienced a rebound and 1 sustained HBsAg seroclearance through 24 weeks post end of treatment.

The treatment regimens were generally well tolerated and resulted in no new safety signals.

We believe the data from this study provides us proof of concept of our approach to achieving a functional cure in HBV and that anti-HBs titers >500 mIU/mL at end of treatment were associated with sustained HBsAg seroclearance at 24 weeks post end of treatment.

Participants with HBsAg seroclearance, n (%) Cohort 1

(n=15) Cohort 2

(n=15) Cohort 3

(n=18) Cohort 4

VIR-2218 x6 VIR-2218 x 6 lead-

in + PEG-IFN∝ x 12 VIR-2218 x 6 +

PEG-IFN∝ x 24 VIR-2218 x 6 +

PEG-IFN∝ x ≤48 VIR-2218 x 13 +

PEG-IFN∝ x ≤44

At any time up to Week 48

0 (0%) 1 (6.7%) 1 (5.6%) 4 (22.2%) 4 (30.8%)

At Week 48 0 (0%) 1 (6.7%) 0 (0%) 3 (16.7%) 4 (30.8%)

With Anti-HBs (>10mIU/mL) at Week 48

0 (0%) 1 (6.7%) 0 (0%) 3 (16.7%) 4 (30.8%)

At 24 weeks post-EOT 0 (0%) 1 (6.7%) 0 (0%) 3 (16.7%) 2 (15.4%)

Preliminary 48-week safety and efficacy data from novel investigative cohorts of elebsiran alone and in combination with IFN-α in participants with chronic HBV infection.

All participants are virally suppressed on NRTIs .

1 Two participants withdrew from study prior to Week 16;

1 participant had HBsAg seroclearance at Week 32, stopped PEG-IFN per protocol, and had a rebound in HBsAg by Week 48.

Phase 2 Trial of tobevibart and elebsiran with and without IFN-α (MARCH).

In July 2021, we initiated the Phase 2 MARCH trial to evaluate the combination of tobevibart and elebsiran as a functional cure regimen for chronic HBV infection.

Tobevibart and elebsiran have the potential to act in concert by inhibiting virion production, removing potentially tolerogenic HBV proteins, and stimulating new HBV specific T cells.

All patients were virally suppressed on NRTIs.

The MARCH trial is being conducted in two parts.

Part A is the first evaluation of the combination of tobevibart and elebsiran and is primarily assessing the safety of the combination as well as efficacy.

Part B of the trial is evaluating 24- and 48-week regimens of the tobevibart and elebsiran combination with and without IFN-α.

Q4W = every 4 weeks

* Not exhaustive – does not include monotherapy arms for tobevibart.

Additional cohorts may be added.

Part A of the MARCH trial evaluated the safety of the combination of tobevibart and elebsiran.

Cohort 1 was a lead-in with elebsiran followed by coadministration of tobevibart from Week 16-20.

Cohort 2 and 3 evaluated the concomitant administration of tobevibart and elebsiran and from Day 1 through Week 12, evaluating 18 mg and 75 mg tobevibart administered weekly.

Cohort 1 demonstrated a mean 3.1 log10 decline in HBsAg at end of treatment while Cohorts 2 and 3 demonstrated a 2.7 log10 decline in HBsAg.

Although no participants achieved HBsAg <LLOQ, most participants achieved HBsAg <10 IU/mL.

Tobevibart in combination with elebsiran was generally well tolerated with most adverse events being mild.

Follow-up data showed rebound of HBsAg after end of therapy but HBsAg levels remained -0.8 to -0.9 log10 IU/mL below baseline 48 weeks post end of treatment.

Preliminary data from the ongoing open-label Phase 2 MARCH trial evaluating the safety, tolerability and antiviral activity of tobevibart in combination with elebsiran in virally suppressed participants with chronic HBV infection who received continuous NRTI therapy for two months or more.

All participants are virally suppressed on NRTIs.

Part B of the MARCH trial is evaluating the combination of tobevibart and elebsiran with and without IFN-α for 24 and 48 weeks.

Initial 24-week data from Part B demonstrated that tobevibart+elebsiran and tobevibart+elebsiran+IFN-α achieved HBsAg seroclearance in 15.0% (3/20) and 14.3% (3/21) of participants, respectively.

All participants who received tobevibart+elebsiran and achieved HBsAg seroclearance had rebound in HBsAg.

Of the three participants who received tobevibart+elebsiran+IFN-α and achieved HBsAg seroclearance, only one had rebound in HBsAg.

Participants who had sustained HBsAg seroclearance had higher anti-HBs antibodies levels compared to those who did not.

All treatment emergent adverse events in the tobevibart+elebsiran cohort were Grade 1-2 in severity.

Of those treated with tobevibart+elebsiran+IFN-α, treatment-emergent adverse events were generally consistent with those expected for IFN-α with Grade 3 treatment-emergent adverse events reported in five participants.

48 week cohorts of tobevibart+elebsiran and tobevibart+ elebsiran+IFN-α are ongoing with end of treatment data expected in the fourth quarter of 2024.

*Denotes participants who sustained HBsAg loss at 12 weeks post-EOT

Anti-HBs concentrations in the VIR-2218-1001 and VIR-2218-1006 studies were determined using the Anti-HBs2 Assay IVD Kit on the Siemens ADVIA Centaur instrument and the Elecsys Anti-HBs II assay on the Roche Cobas instrument, respectively.

The laboratory developed test using the Elecsys Anti-HBs II assay incorporated the addition of a VIR-3434 binding blocker (anti-idiotype Fab fragment) to the samples prior to analysis, preventing assay interference by VIR-3434.

Values <LLOQ were imputed as 1 mIU/mL

Summary of Phase 2 Combination Trials.

Data from VIR-2218-1001 and the MARCH trial support our approach to achieving functional cure in HBV.

In the VIR-2218-1001 trial, we were able to demonstrate that the combination of elebsiran+IFN-α was able to increase HBsAg seroclearance rates to 25.8% compared to what has been observed with siRNAs (0%) and IFN-α as monotherapy (3-7%) at end of treatment.

In addition, we were able to observe an approximate 5-fold increase in HBsAg seroclearance rates between Week 24 and 48.

From MARCH Part B, 24 weeks of tobevibart+elebsiran and tobevibart+elebsiran+IFN-α resulted in HBsAg seroclearance rates about 3-fold higher compared to elebsiran+IFN-α alone demonstrating the additional activity of tobevibart.

Data expected in the fourth quarter of 2024 should inform whether a similar increase in HBsAg seroclearance rates will be observed between Week 24 and Week 48 as was observed in VIR-2218-1001.

2 HBsAg > 10 mIU/mL;

Tx = Treatment

Other Collaborators.

In April 2021, Brii Bio initiated a Phase 2 trial of elebsiran in combination with BRII-179, an investigational therapeutic vaccine, for the treatment of chronic HBV infection.

Treatment has been completed in this trial.

Treatment of elebsiran alone or in combination with BRII-179 with and without coadjuvant IFN-α was generally well tolerated.

Although the combination of elebsiran and BRII-179 had greater anti-HBs responses and improved HBsAg-specific T cell responses, comparable HBsAg reduction was observed in all cohorts at EOT (-1.7-1.8 log10 IU/mL).

In December 2021, we and Gilead initiated a multi-center, open-label Phase 2 clinical trial designed to evaluate the safety, tolerability and efficacy of various combinations of elebsiran, GS-9688 (selgantolimod), Gilead’s investigational TLR-8 agonist, nivolumab and TAF in adults with chronic HBV.

The trial enrolled approximately 120 patients ages 18 to 65 who were either viremic or are NRTI-suppressed.

Patients who were HBeAg-positive (an indicator of acute viral replication), as well as those who were HBeAg-negative, were enrolled.

The primary efficacy endpoint is the proportion of patients who achieve a functional cure (defined as HBsAg loss and HBV DNA <20 IU/mL at follow-up week 24).

The Phase 2 PREVAIL platform trial and its THRIVE/STRIVE sub-protocols of tobevibart and/or elebsiran and/or IFN-α in viremic patients with chronic HBV infection was initiated in the first half of 2023.

The THRIVE sub-protocol is evaluating the safety and efficacy of regimens containing combinations of an NRTI with tobevibart and/or elebsiran in inactive carriers defined as adults with chronic HBV that are HBeAg negative with HBV DNA ≤2000 IU/mL and ALT ≤ upper limit normal (ULN).

The STRIVE sub-protocol is evaluating the safety and efficacy of regimens containing combinations of an NRTI with tobevibart and/or elebsiran and/or IFN-α in adults with chronic HBV infection who have not received prior NRTI or IFN-α treatment.

Participants will be HBeAg positive or negative with HBV DNA >2000 IU/mL, ALT>ULN and ≤ 5× ULN.

Forty years after the start of the epidemic, HIV remains one of the world’s most serious public health challenges.

With approximately 1.5 million new cases of HIV worldwide each year, there remains a strong need for prophylactic vaccine.

We are taking a different immunologic approach to HIV prevention using human cytomegalovirus (HCMV) as a vector designed to maximize T cell immunity.

Based on in vivo data, we hypothesize an HCMV-based vaccine may be able to “program” unique T cell responses against HIV, which is different from other vaccine approaches.

HCMV as a vector is a weakened version of the virus designed to deliver the HIV vaccine material to the immune system without itself causing disease in the trial participants.

HCMV has been present in much of the global population for centuries.

Most people living with HCMV experience no symptoms and are unaware that they are living with the virus.

HCMV remains detectable in the body for life, which suggests it has the potential to deliver and then safely help the body retain HIV vaccine material for a long period of time, potentially overcoming the waning immunity observed with more short-lived vaccine vectors.

VIR-1111, a prototype HIV vaccine, was evaluated in a Phase 1 first-in-human study that demonstrated no safety signals and no vector shedding or viremia.

No sustained HIV-insert-specific T cell responses were observed.

VIR-1388 has incorporated modifications that have the potential to enhance HIV-specific immunogenicity compared to VIR-1111 and provide broader coverage against circulating strains of HIV.

The VIR-1388 Phase 1 study was initiated in 2023.

Disease Overview and Limitations of the Current Standard of Care

According to the Joint United Nations Programme on HIV/AIDS (UNAIDS), each year there are approximately 700,000 HIV-related deaths globally.

Unless treated, infection with HIV results in an almost universally fatal disease, acquired immune deficiency syndrome, or AIDS.

According to the World Health Organization (WHO), almost 36 million people have died from HIV-related illnesses globally since cases were first reported in 1981.

Highly effective HIV treatments are now available, but these medicines only suppress HIV and are not curative.

They require life-long administration and carry the risk for viral breakthrough and resistance.

Furthermore, while HIV prevention programs based on behavioral modification, pharmacological intervention, use of barrier devices and other methods continue to be developed, such approaches have had at most a modest effect on HIV transmission globally in high-risk populations.

Although pre-exposure prohylaxis (PrEP) with antiretroviral therapy has been available for several years, it requires daily administration to be effective.

Long-acting antiretroviral PrEP has recently been approved but still requires injections every 2 months to be effective.

Therefore, we believe the most effective means of curbing the worldwide HIV epidemic would be a safe and effective vaccine for individuals who are or may become sexually active.

VIR-1111 and VIR-1388 for HIV

While the role of HER2 in breast and gastric cancer has been well established for many years, only recently has there been a recognition of the importance of HER2 in other disease types, in particular as a resistance biomarker to other signaling pathways such as EGFR.

With more patients undergoing biopsies after progression from prior therapies, and the advance of more routine molecular genotyping, numerous aberrations in HER2 have been discovered.

Collectively, HER2+ tumors (IHC 3+ or in situ hybridization [ISH]+) and solid tumors with activating HER2 mutations represent a large unmet need.

VIR-5818, with its novel mode of action and potential for large safety margins due to masking, may be an important treatment option that can extend survival and provide cancer immunity to these tumors.

VIR-5818 is a HER2-targeted, conditionally activated masked TCE designed to exploit dysregulated protease activity in tumors while sparing healthy tissues in which there is minimal protease activity, thus broadening the safety margin and therapeutic index.

The core consists of two, tandem, single-chain variable fragments (scFvs) targeting CD3 and HER2 that are flanked by two unstructured polypeptide masks (XTEN ™ ) that sterically reduce target engagement in normal tissues and extend half-life.

Protease cleavage sites at the base of the XTEN ™ masks enable proteolytic activation of fully masked TCE in the tumor microenvironment, unleashing a small, highly potent, unmasked TCE, which is able to redirect cytotoxic T-cells to kill target-expressing tumor cells.

The potent, unmasked form (uTCE) of VIR-5818, also has a much shorter half-life to potentially increase the therapeutic index if the activated form should leak back into circulation.

In healthy tissues, in which protease activity is tightly regulated, VIR-5818 should remain predominantly masked and as an intact prodrug.

Additional information is available in “Our Technology Platforms” section.

In preclinical ( in vitro ) studies, binding affinities of VIR-5818 were found to be similar between human and cynomolgus monkey HER2 and CD3, thus cynomolgus monkeys are a relevant species for toxicology studies.

GLP NHP toxicology studies have demonstrated minimal toxicities with a NOAEL at the top dose evaluated of 6mg/kg.

Unmasked VIR-5818 had single digit pM potent cytotoxicity to HER-2 expressing tumor cells, but significantly less cytotoxic to HER-2 expressing cardiomyocytes, requiring >1uM, thus demonstrating the potential wide therapeutic index compared to normal tissue and showing the need for dysregulated proteases (only found in tumor cells) for unmasking and eventual cell killing.

Phase 1 Trial of VIR-5818 ± pembrolizumab.

VIR-5818 is being evaluated in a Phase 1 clinical trial designed to study its safety and pharmacokinetics alone, and in combination with pembrolizumab, in participants with a variety of HER2-expressing cancers, including breast and colorectal cancer (CRC).

As of November 2024, the study had enrolled 79 heterogeneous and heavily pretreated participants in monotherapy cohorts, and we presented early safety and efficacy data from the monotherapy cohort at an investor event on January 8, 2025.

Early efficacy data showed that 50% (10/20) of participants receiving VIR-5818 doses ≥400 µg/kg experienced dose-dependent tumor shrinkage across multiple HER2-positive tumor types at either QW or Q3W dosing schedule after an initial step-up dosing in Cycle 1.

This includes participants who had received up to 9 prior lines of therapy.

Strong anti-tumor activity was observed in a subset of participants with HER2-positive CRC who have exhausted standard of care.

In this subset, confirmed partial responses (cPRs) were seen in 33% (2/6) of participants at early doses, and one patient continued in cPR for more than 18 months as of the data cut-off in November 2024.

All the HER2-positive CRC tumors were also MSS (Microsatellite Stable) which traditionally are unresponsive to immunotherapies..

Preliminary safety data demonstrated that VIR-5818 was generally well-tolerated, with minimal grade 1 or 2 CRS (20% and 10%, respectively) and no grade 3 or greater CRS observed in any of the 79 participants across doses up to 1 mg/kg.

Most TEAEs were low grade, reversible and manageable.

The maximum tolerated dose (MTD) has not yet been reached.

Preliminary pharmacokinetics and safety data indicate low systemic unmasking of the TCE, suggesting tumor-specific activation.

Dual masking results in a half-life of approximately 6 days, which may enable a less frequent dosing regimen.

As a result, VirBio is currently evaluating a Q3W dosing regimen.

Dose escalation is ongoing, and the MTD has of VIR-5818 has not yet been reached.

VIR-5500 for the treatment of metastatic castration-resistant prostate cancer

Molecular Characteristics and Preclinical Data .

VIR-1111 is a prototype T cell vaccine using an engineered HCMV vector designed to elicit T cells that recognize HIV epitopes different from those recognized by prior HIV vaccines, to exploit the capacity of HCMV to induce persistently high frequencies of T cells pre-programmed to migrate into tissues, and to stimulate a different type of immune response to HIV, known as an human leukocyte antigen E (HLA-E ) restricted cluster of differentiation (CD) 8 T cell response.

VIR-1388 contains a novel immunogen intended to provide broader coverage against circulating strains of HIV compared to the clade A Gag immunogen in VIR-1111.

Genetic modifications of the HCMV vector used for VIR-1388 recapitulate those of rhesus CMV vectors that elicited an HLA-E restricted immune response and protected more than 50% of nonhuman primates (NHPs) from repeated exposure to simian immunodeficiency viruses (SIV).

Phase 1 Trial of VIR-1111.

The trial was a multiple ascending dose clinical trial designed to evaluate the safety, tolerability, reactogenicity and immunogenicity of VIR-1111 in CMV-positive healthy adult volunteers, initiated in December 2020 and completed in December 2022.

The immunogenicity evaluation included an assessment of the breadth and nature of the T cell response to the vaccine.

In November 2022, we announced that safety and immunology data from the initial two cohorts of the trial showed no safety signals and no vector shedding or viremia reported to date.

In addition, no sustained HIV insert-specific T cell responses were observed in the first two cohorts.

Safety and immunology data reported in 2023 from the highest dose cohort 3 were consistent with the data from cohorts 1 and 2.

The manufacture and early clinical development of VIR-1111 was funded by the Bill & Melinda Gates Foundation.

Similar to VIR-5818, VIR-5500 is a protease-activated, bispecific dual-masked TCE, designed to exploit the dysregulated protease activity in tumors relative to healthy tissues, thus expanding the safety margin and therapeutic index.

The VIR-5500 core consists of a VHH (single-variable domain on a heavy chain) domain targeting PSMA and an scFv-targeting CD3.

The core is flanked by 2 unstructured polypeptide masks (XTEN ™ masks) that sterically reduce target engagement in healthy tissue and extend the half-life of the protein.

Protease cleavage sites at the base of the XTEN ™ masks enable proteolytic activation of unmasked protein in the tumor microenvironment, unleashing a small, highly potent unmasked TCE, designed to redirect cytotoxic T-cells to kill PSMA-expressing tumor cells.

In healthy tissues, in which protease activity is minimal due to tight regulation, VIR-5500 should remain predominantly inactive.

Phase 1 Trial of VIR-5500 .

Learnings from VIR-1111 have informed the vector and trial design of VIR-1388.

We initiated a Phase 1 trial of VIR-1388 in September 2023.

The trial is a multiple ascending dose clinical trial designed to evaluate the safety, tolerability, reactogenicity and immunogenicity of VIR-1388 in CMV-positive healthy adult volunteers.

VIR-1388 is a subcutaneously administered HIV T cell vaccine using HCMV as a vector.

Like VIR-1111, VIR-1388 has been designed to elicit T cells that recognize HIV epitopes that are different from those recognized by prior HIV vaccines and to stimulate a different and specific type of T cell immune response to HIV, known as an HLA-E restricted immune response.

VIR-1388 has additional modifications that have the potential to enhance immunogenicity compared to VIR-1111.

This trial is supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation, and is being conducted by the HIV Vaccine Trials Network.

Initial data from the trial is expected in the second half of 2024.

In response to the COVID-19 pandemic, we moved rapidly to address this global health challenge.

Our focus has been on treating and preventing COVID-19, as well as potential future coronavirus outbreaks.

To do so, together with our collaborator GSK, we developed the mAb sotrovimab for the treatment and prophylaxis of COVID-19.

Sotrovimab is based on a parent antibody, S309, which was derived from samples previously gathered for research on pan-coronavirus-neutralizing mAbs.

Data suggest that sotrovimab has the potential for ‘dual-action’, or the ability to block viral entry into healthy cells and an enhanced ability to clear infected cells.

In May 2021, the FDA granted an emergency use authorization (EUA) to sotrovimab for the early treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and at high risk for progression to severe COVID-19, including hospitalization or death.

In December 2021, the European Commission granted marketing authorization to Xevudy® (sotrovimab) in the EU for the treatment of adults and adolescents at increased risk of progressing to severe COVID-19.

In March 2022, the FDA de-authorized sotrovimab’s use in all U.S.

regions due to increases in the proportion of COVID-19 cases caused by non-susceptible new variants.

Sotrovimab has obtained emergency authorization, temporary authorization or marketing approval (under the brand name Xevudy ® ) for early treatment of COVID-19 in more than 30 countries.

Over 2.1 million doses of sotrovimab have been delivered as of December 31, 2022.

We continue to conduct in vitro testing of sotrovimab against new variants and subvariants as they emerge, and to collect and evaluate real-world evidence, both of which are being shared with regulatory authorities.

Sotrovimab is also being evaluated in two additional indications:

(1) to determine if sotrovimab can prevent symptomatic COVID-19 infection in uninfected immunocompromised adults, and (2) to evaluate if sotrovimab treatment can improve clinical outcomes in patients hospitalized with COVID-19.

In addition, Vir is preparing for future pandemics by developing coronavirus mAbs that we believe have the potential to have even broader application and be more potent than sotrovimab.

Disease Overview and Limitations of Current Standard of Care

The FDA has granted either EUAs or marketing approvals to multiple vaccines, drugs and/or antibodies to prevent or treat COVID-19 in the U.S.

For prophylaxis, despite the high efficacy of the COVID-19 vaccines, there are still populations in whom vaccine immunogenicity is suboptimal, such as the elderly with comorbidities, immunocompromised persons, or those who may not want or be able to tolerate vaccines.

For early treatment, both mAbs and small molecules have shown strong efficacy data and have pros and cons around convenience and compliance.

For example, for some patients and their physicians, intramuscular, or IM, or IV mAbs may be preferred to small molecules due to administration in a single treatment visit (“one and done”), concerns about compliance with small molecules (multiple pills, multiple times per day, over multiple days), and concerns about oral treatment initiation requirements.

For hospitalized patients, there is still significant unmet need.

Data suggest that COVID-19 mAbs may have a role in improving clinical outcomes such as decreasing intensive care unit stays and/or mortality in hospitalized patients who have severe or critical COVID-19.

Importantly, the ongoing durability of current vaccines, small molecules, and mAbs in the setting of the continued emergence of variants is uncertain.

Sotrovimab for COVID-19

Molecular Characteristics

Sotrovimab is an engineered human immunoglobulin 1 (IgG1) neutralizing anti-SARS-CoV-2 monoclonal antibody that has Fc modifications designed to improve bioavailability in the respiratory mucosa and increase half-life, and incorporates Xencor’s Xtend TM technology.

Sotrovimab binds with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein.

It is designed to have dual-actions of neutralizing the virus by blocking viral entry into healthy cells, while also enhancing the ability to clear infected cells.

Sotrovimab potently neutralizes live SARS-CoV-2 in vitro and in vivo, and binds to a highly conserved epitope that is shared with SARS-CoV-1.

Early Treatment

In August 2020, we initiated the lead-in phase of our Phase 2/3 trial COVID-19 Monoclonal antibody Efficacy Trial - Intent to Care Early, or COMET-ICE, for the treatment of adults at high risk of hospitalization or death from COVID-19 via IV administration.

This trial was a Phase 2/3, randomized, double-blind, multi-center, placebo-controlled trial investigating IV infusion of 500 mg of sotrovimab in adults with mild to moderate COVID-19 at high-risk of progression to severe disease, who were not hospitalized and did not require oxygen.

The trial included a lead-in phase to evaluate the safety and tolerability of sotrovimab, followed by an expansion phase with 1:1 randomization of sotrovimab and placebo.

The final COMET-ICE trial results in the full trial population of 1,057 participants demonstrated an adjusted relative risk reduction of 79% (p<0.001) in all-cause hospitalization for more than 24 hours or death due to any cause by day 29 compared to placebo, meeting the primary endpoint of the trial.

In May 2021, the FDA granted an EUA to sotrovimab for the early treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and at high risk for progression to severe COVID-19, including hospitalization or death.

In December 2021, the European Commission granted marketing authorization to Xevudy® (sotrovimab) in the European Union (EU) for the treatment of adults and adolescents at increased risk of progressing to severe COVID-19.

In March 2022, the FDA de-authorized sotrovimab’s use in all U.S.

regions due to increases in the proportion of COVID-19 cases caused by the Omicron BA.2 subvariant.

Sotrovimab has obtained emergency authorization, temporary authorization or marketing approval (under the brand name Xevudy®) for early treatment of COVID-19, supplying more than 30 countries.

We continue to conduct in vitro testing of sotrovimab’s ability to neutralize new variants and subvariants as they emerge, and to collect and evaluate real-world evidence, both of which are being shared with regulatory authorities.

In August 2022, sotrovimab entered the Phase 3 PROphylaxis for paTiEnts at risk of COVID-19 infecTion, or PROTECT-V, platform trial sponsored by Cambridge University Hospitals National Health Service, or NHS, Foundation Trust assessing the use of a 2 g dose of sotrovimab administered IV in uninfected, high-risk immunocompromised individuals.

This is a randomized, double-blinded, placebo-controlled trial that is currently enrolling participants.

The primary endpoint is PCR-confirmed symptomatic COVID-19 infection at three months.

Key secondary endpoints include PCR-confirmed symptomatic COVID-19 infection at subsequent timepoints, time to confirmed SARS-CoV2 infection, safety, mortality and disease severity.

Due to significant uncertainty in the anticipated infection rate, the sample size will be monitored and reviewed regularly by the independent Data Monitoring Committee (IDMC).

Timing of initial data will depend on continued rate of enrollment.

Hospitalized treatment

In December 2021, sotrovimab entered the Randomized Evaluation of COVID-19 Therapy, or RECOVERY, trial, a Phase 3 trial in the UK evaluating standard of care alone versus usual standard of care plus a single 1 g dose of sotrovimab given IV.

This is a randomized, controlled, open-label, platform trial assessing several possible treatments in patients hospitalized with COVID-19 in the UK.

Trial participants who are hospitalized with COVID-19 are eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus a single dose of sotrovimab given IV.

Timing of initial data will depend on continued rate of enrollment.

There remains medical need for prevention of serious influenza illness.

The variability in the efficacy of influenza vaccines could be due to incomplete coverage against seasonal strains and the lack of an effective immune response in many individuals after receiving the vaccine.

We are developing influenza mAbs as a universal prophylactic for influenza to address the limitations of flu vaccines.

In May 2021, we signed a definitive collaboration agreement, or the 2021 GSK Agreement, with Glaxo Wellcome UK Limited to expand our existing collaboration to include the research and development of new therapies for influenza and other respiratory viruses.

See the section titled “Our Collaboration, License and Grant Agreements—Collaboration Agreements with GSK” for a description of the 2021 GSK Agreement.

Disease Overview and Limitation of Current Standard of Care

According to the WHO, on average, each year the influenza virus is estimated to infect one billion individuals and to result in 290,000 to 650,000 deaths globally.

According to the Centers for Disease Control and Prevention (CDC), in the 2018-2019 flu season, despite the availability of the flu vaccine, approximately 36 million people were diagnosed with influenza, 500,000 people were hospitalized, and 34,000 people died from influenza in the U.S.

Influenza vaccines have historically had limited success, with an average efficacy of 40% overall, across all populations.

This limited efficacy results from incomplete coverage against seasonal strains and the lack of an effective immune response in many individuals after receiving the vaccine.

We are developing influenza mAbs as a universal prophylactic for influenza to address the limitations of existing flu vaccines, which we believe will lead to meaningfully higher levels of protection against seasonal and pandemic strains of influenza.

VIR-2482 for Influenza A

Molecular Characteristics

VIR-2482 is an investigational mAb targeting a functionally conserved epitope on the influenza A hemagglutinin protein located within the stem region.

In preclinical studies, we demonstrated that in vitro VIR-2482 covers all the major strains of influenza A that have arisen since 1918.

In addition, in prophylactic lethal challenge studies of influenza A in mice, VIR-2482 was able to protect mice from death at VIR-2482 exposures we believe to be clinically relevant.

We engineered the parent form of VIR-2482 to extend its half-life to create VIR-2482, which incorporates Xencor’s Xtend TM technology.

Phase 1 and 2 Clinical Studies

VIR-2482-3001 was a Phase 1 first-in-human, randomized, double-blinded, placebo-controlled single ascending dose trial in healthy adult volunteers with endpoints of safety, tolerability, and pharmacokinetics, or PK, when VIR-2482 is administered intramuscular (IM) in four different doses:

60 mg, 300 mg, 1200 mg, and 1800 mg.

This trial was initiated in August 2019 and is now complete.

The trial showed VIR-2482 was well-tolerated up to 1800 mg and is estimated to have a half-life of 58 days based on preliminary clinical data.

In October 2022, we initiated PENINSULA (PrevENtIoN of illnesS dUe to InfLuenza A), a Phase 2 randomized, double-blind, placebo-controlled, dose-ranging trial in healthy adult volunteers aged 18 to 64 to evaluate the safety, tolerability and efficacy of two different intramuscularly administered doses of VIR-2482 in preventing illness due to influenza A.

The primary efficacy endpoint is the proportion of trial participants with protocol-defined influenza illness 1 , requiring one systemic symptom and one respiratory symptom with polymerase chain reaction (PCR) confirmed influenza A infection, compared to placebo.

Secondary endpoints included the proportion of participants with CDC-defined influenza-like-illness with PCR-confirmed influenza A infection 2 , and the proportion of participants with WHO-defined influenza-like-illness with PCR-confirmed influenza A infection 3 .

This study enrolled ~3,000 healthy adults aged 18-64 randomized 1:1:1 into placebo, 450 mg, and 1200 mg of VIR-2482 arms.

The results showed that the primary and secondary efficacy endpoints were not met.

Specifically, there was a non-statistically significant reduction in influenza illness of approximately 16% at 1,200 mg using the primary endpoint.

In this same group, an approximate 57% reduction in influenza A illness was observed when illness was defined according to CDC criteria.

Post-hoc analyses showed that the relative risk reduction in CDC-defined criteria increases further to 65% when excluding the confirmed flu cases that occurred within a few days of dosing.

VIR-2482 was generally well tolerated and no safety signals were identified.

The PENINSULA trial was funded in part with federal funds from the Department of Human Services (HHS);

the Administration for Strategic Preparedness (ASPR);

and the BARDA, under OT number 75A50122C00081.

Efficacy Analyses

Occurrence of Influenza-Like-Illness (ILI) with PCR-Confirmed Influenza A

# of Participants with Endpoint/

Placebo Placebo

n (%) VIR-2482

Primary Endpoint Number of Participants Protocol-Defined ILI 1

25 (2.54%) 24 (2.45%) 21 (2.12%)

Relative Risk Reduction (%) - 3.78% 15.85%

95% CI (%) - -67.23, 44.63 -49.27, 52.56

p-value - 0.89 0.56

Secondary Endpoints Number of Participants with CDC-Defined ILI 2

17 (1.73%) 15 (1.53%) 7 (0.71%)

Relative Risk Reduction (%) - 11.45% 57.23%

95% CI (%) - -76.25, 55.51 -2.51, 82.15

Number of Participants with WHO-Defined ILI 3

11 (1.12%) 12 (1.22%) 6 (0.60%)

Relative Risk Reduction (%) - -9.80% 44.13%

95% CI (%) - -147.41, 51.27 -50.49, 79.26

Percentages are calculated relative to the number of participants in the full analysis set.

1 Protocol-defined ILI is defined as PCR-confirmed influenza A infection with at least one respiratory symptom:

sore throat, cough, sputum production, wheezing, or difficulty breathing and at least one systemic symptom:

fever (temperature >37.8°C), chills, weakness, or myalgias.

2 CDC-ILI is defined as fever (temperature >37.8°C) and cough and/or sore throat.

3 WHO-ILI is defined as fever (temperature >38°C) and cough.

We are continuing to develop next generation antibodies that we believe have the potential to have even broader applications in treating both influenza A and B.

Our Preclinical Programs

We continue to advance next-generation mAbs based on our proprietary platform and enabled by AI and machine learning to deliver high-quality drug candidates more efficiently.

We expect to file multiple investigational new drug applications (INDs) in the next 12-24 months, including:

• VIR-1949 , an investigational therapeutic T cell vaccine based on our HCMV vector platform that is designed to treat precancerous lesions caused by human papillomavirus;

• VIR-7229 , an investigational mAb against COVID with exceptional breadth and potency against SARS-CoV variants and related animal coronaviruses;

• VIR-2981 , an investigational neuraminidase-targeting mAb against both influenza A and B viruses;

• VIR-8190 , an investigational mAb with dual specificity against RSV and MPV;

potential cocktail of broadly neutralizing antibodies with Fc modifications to control viral load and achieve a functional cure of HIV.

HPVs cause primary infections acquired in childhood or by sexual transmission.

Persistent HPV infections may result in cervical or anal dysplasia that can progress to cancer.

HPV also causes head and neck and other less common cancers.

Most pre-cancerous cervical and anal dysplasia and HPV-related cancers are due to HPV 16 and 18 types.

Cancer is caused by the viral oncogenes, E6 and E7.

Licensed vaccines are protective, but the HPV disease burden is expected to remain for decades due to pre-existing infections and poor vaccine uptake.

Building upon our CMV vectored vaccine platform, Vir’s CMV-HPV vaccine candidate (VIR-1949) offers a novel approach to therapy for HPV-associated diseases because the CMV vector has the potential to stimulate high frequencies of HPV-specific CD4+ and CD8+ T cells that are predominantly effector memory T cells pre-programmed to traffic into tissues.

Proof of biology studies using rhesus CMV vaccines demonstrate T cell homing to tissues, clearance of simian immunodeficiency virus and TB and long-term persistence of immunity.

The CMV-HPV immunogen is a multi-component fusion protein designed for breadth against HPV 16 and 18, and other cancer causing HPV types.

CMV-HPV is anticipated to generate high frequencies of HPV-specific T cells with the potential to eliminate pre-cancerous disease and limit HPV tumor progression.

Notably, cervical high-grade squamous intra-epithelial lesion (HSIL) regression has been associated with a local CD8+ T cell response.

The benefits of an HPV therapeutic vaccine are as an alternative to the risks of surgery for dysplasia and to improve often poor outcomes of HPV cancer.

VIR-1949 is our first oncology program that expands our pipeline beyond infectious disease into viral-associated cancer.

COVID-19 continues to be a disease area with high unmet medical need and currently there are no FDA approved or authorized products for Pre-exposure Prohylaxis (PREP) for immunocompromised individuals who may not respond sufficiently to vaccines.

We have leveraged our mAb platform 2.0 to develop VIR-7229, an investigational, pre-clinical COVID mAb, which was optimized using data AI structure and antibody (dAIsY TM ), our proprietary AI-driven design of fragment antigen binding (Fab) and FC mAb variants, to improve potency, breadth, and resistance to viral escape.

In vitro data show that VIR-7229 can neutralize all historical and current variants of SARS-CoV-2 as well as related animal coronaviruses with potency compatible with intramuscular injection.

Our goal for VIR-7229 is to provide a next-gen COVID mAb with exceptional breadth against future variants for prophylaxis in individuals who do not mount an adequate response to vaccines.

We have validated that this potentially prophylactic mAb continues to be efficacious even as the virus evolves and is potent enough for intramuscular administration.

In September 2023, we received approximately $50 million in new BARDA funding, including $40 million in Project NextGen funding, which supports the development of VIR-7229 through Phase 1 in the context of developing alternative mAb delivery technologies.

VIR-2981, is an investigational neuraminidase-targeting mAb that has been shown in in vitro and in vivo models to neutralize both flu A and flu B, including seasonal and zoonotic strains with pandemic potential.

Because it inhibits the neuraminidase enzyme – similar to flu antivirals currently used to prevent or treat influenza symptoms – VIR-2981’s mechanism of action has been clinically validated.

Vir-2891 is being developed as a single administration for season-long prophylaxis of influenza in individuals at risk of severe disease.

The passive immunization approach planned for VIR-2981 has been effective in other acute viral respiratory diseases such as RSV and COVID-19.

Compared to Vir’s previous candidate for influenza A prophylaxis, Vir-2482, Vir 2981 has been shown to have higher potency in in vivo studies, in addition to extended breadth.

We are identifying and refining human antibodies with antiviral activity against RSV alone and those that also have dual specificity against RSV and MPV.

Both RSV and MPV cause significant medical burden in young children and individuals with a variety of immune deficits.

The passive immunization concept of using antibodies to prevent respiratory viral infections, and/or reduce disease associated with infection, has been successfully demonstrated for RSV (nirsevimab) and other respiratory viruses such as COVID-19.

mAb combination (cure)

Despite recent advances in the availability of antivirals to control HIV, treatments still require frequent, if not daily administration over a lifetime.

Notably, there is precedent indicating that in a subset of patients, the administration of bNAbs subsequent to antiretroviral interruption can mediate sustained suppression of HIV-1 replication.

This effect may result from the elicitation of enduring HIV-specific T cell responses, offering a rationale for exploring bNAbs as a candidate for enduring HIV-1 functional cure.

With the support of the Bill and Melinda Gates Foundation, we are selecting and engineering bNAbs to optimize their breadth, potency, half-life, effector functions and manufacturability.

This aims to develop a unique and innovative HIV-1 therapy approach for both long-acting therapy and functional cure of HIV-1 infected individuals.

VIR-5500 is being evaluated in a Phase 1 clinical trial designed to assess its safety, pharmacokinetics, and preliminary efficacy in participants with mCRPC.

As of November 2024, the study had enrolled 18 participants with significant disease burden who have received 3 to 6 prior lines of therapy, and we presented early safety and efficacy data from the ongoing dose escalation trial at an investor event on January 8, 2025.

PSA reductions were observed in 100% (12/12) of participants after an initial dose ≥120 µg/kg.

PSA50 response was confirmed in 58% (7/12) of participants receiving a first dose ≥120 µg/kg.

Preliminary data show no dose-limiting toxicities observed up to 1000 µg/kg without the use of prophylactic corticosteroids or anti-IL6 antibodies.

Safety findings showed minimal grade 1 or 2 CRS (17% and 11%, respectively) and no grade 3 or greater CRS at any dose.

Most TEAEs were low grade.

No hearing loss has been reported, suggesting safety benefits of dual masking in preventing on-target, off-tumor toxicities.

Dose escalation is ongoing, and the MTD for VIR-5500 has not yet been reached.

Preliminary pharmacokinetics and safety data indicate tumor-specific activation with minimal unmasking outside the tumor.

The dual-masked TCE shows a preliminary half-life of 8-10 days, potentially enabling a Q3W dosing regimen, which is currently being evaluated.

The safety and tolerability profile observed for VIR-5500 in ongoing dose escalation, together with the observed signs of early anti-tumor activity at low doses, may enable a wide therapeutic index.

The Epidermal Growth Factor Receptor (EGFR) is a clinically validated target, well-known to play a key role in cancer.

This molecule is over-expressed in a variety of solid tumors, such as colorectal, squamous cell carcinoma of the head and neck, non-small cell lung cancer, and renal cell carcinoma, making it an attractive target for targeted cancer therapy.

We are advancing VIR-5525, an investigational dual-masked TCE that combines a bispecific EGFR and CD3 binding TCE with the PRO-XTEN ™ masking technology.

This technology is designed to keep the TCEs inactive until they reach the tumor microenvironment, where tumor-specific proteases can cleave off the mask and activate the TCEs leading to killing of cancer cells.

By driving the activity exclusively tin the tumor microenvironment, we aim to increase efficacy and tolerability while limiting toxicity.

The FDA has cleared the IND for VIR-5525, and a Phase 1 clinical study is expected to begin enrollment in the first half of 2025.

Undisclosed PRO-XTEN ™ TCE Targets:

We are advancing multiple undisclosed dual-masked TCEs targeting clinically validated targets with potential applications across a variety of solid tumors.

These preclinical candidates leverage the PRO-XTEN ™ masking technology with novel TCE fragments discovered and engineered using our antibody discovery platform.

Despite major advances in HIV treatment, most persons living with HIV must take daily antiretroviral medications for viral control.

HIV bnAbs are a novel modality that have shown promise for controlling virus without daily antiretroviral medications.

Furthermore, in rare individuals, HIV bnAb treatment has induced a state of sustained viral control off all therapy, effectively achieving a functional cure.

With the support of the Gates Foundation, we are developing a unique and innovative HIV bnAb therapeutic.

We are selecting and engineering HIV bnAbs (including using dAIsY ™ ) for exceptional breadth and potency to combat both the diversity of HIV strains worldwide and the ability of the virus to escape from therapeutic intervention.

In addition, we are modifying these bnAbs with our Fc engineering technology to enhance their half-life, effector functions, and engagement with the patient’s immune system.

We believe the resulting therapeutic can make an important impact on the lives of people living with HIV.

Our Technology Platforms

Our technology platforms are designed to modulate the immune system by exploiting critical observations of natural immune processes.

We are using our platforms to advance our current product candidates and generate additional product candidates for multiple indications.

Vir Biotechnology, Inc.

has built a strong foundation based on cutting-edge core scientific capabilities and a team of experts who bring deep knowledge and experience to our R&D efforts.

This has enabled us to make significant strides in infectious disease, and strategically expand our focus to address critical unmet needs in oncology.

Platforms for the Creation of Transformative Medicines

We have purposefully assembled a portfolio of technology platforms that we believe will, individually or in combination, allow us to modulate the immune system in innovative ways and to exploit the vulnerabilities of pathogens.

Our current platforms are focused on antibodies and T cells.

We have assembled these platforms through internal development, collaborations and acquisitions.

We are using our platforms, and continue to evaluate others, to advance our current product candidates and generate additional product candidates for multiple indications.

We follow the science to select the modality, or combination of modalities, that gives us the highest chance of success for a specific pathology in a given patient population.

The diversity of our different platforms allows us to select the best modality or modalities for a given clinical need.

Millions of people suffer from infectious diseases and cancer, both of which result in chronic disease by evading the immune system.We have purposefully assembled a portfolio of technology platforms that we believe will, individually or in combination, allow us to modulate the immune system in innovative ways, harnessing its power to combat viruses and fight cancer.

Our R&D engine is propelled by two core technology platforms:

Antibody Platform:

We have established robust methods for identifying rare antibodies with unique breadth/potency/resistance profile and development potential.

We then improve on their properties with AI-enabled protein engineering.

Our antibody platform capitalizes on successful immune responses occurring in (i) people who have recovered from infectious diseases or (ii) transgenic mice expressing human-IgG following immunization.

In both approaches, we select rare and highly potent antibodies that can be developed to treat and prevent rapidly evolving and/or previously untreatable pathogens or to treat disorders beyond infectious diseases.

We have applied this platform to identify mAbs for a range of pathogens including SARS-CoV-2, HBV, HDV, influenza A and influenza B virus, Ebola, HIV, RSV, MPV, malaria, rabies, clostridium difficile , Staphylococcus aureus , Klebsiella pneumoniae , and Acinetobacter spp .

Examples of the power of this platform are sotrovimab, our anti-SARS-CoV-2 mAb, which has been granted Emergency Use Authorization or marketing authorization under the brand name Xevudy® in multiple regions, and Ebanga TM (ansuvimab), the anti-Ebola virus mAb identified by our scientists in collaboration with the NIH and others and marketed by Ridgeback Biotherapeutics LP.

The fully-human antibodies that we discover may also be modified via our proprietary AI-driven protein engineering technology platform, dAIsY TM , to enhance their therapeutic potential by further improving affinity, resistance profile, PK and/or manufacturability properties.

We are developing antibody-based therapies for the treatment or prevention of infections by rapidly evolving and/or previously untreatable pathogens, as well as of disorders beyond infectious diseases, for which we believe we can make an impact.

mAbs rely on multiple mechanisms of action, including neutralization, killing of target cells (i.e., virus-infected cells, tumor cells, immune cells), as well as modulation of the immune response.

We combine high-throughput, rapid isolation of rare, highly potent, broad-spectrum and fully human antibodies with targeted AI-enhanced engineering to increase their therapeutic potential.

We expect the following benefits from mAb candidates identified using our antibody platform:

• Effective regardless of an individual’s ability to generate their own immune response;

• Diminished likelihood of self-reactivity (e.g., off-target binding) because our mAbs are fully human and purged from autoreactivity by the host immune system;

• For infectious disease mAbs, broad coverage of most or all strains of a pathogen, or even multiple pathogens and high affinity binding to conserved antigen epitopes characterized by structural/functional constraint, resulting in a high barrier to resistance from viral escape;

• Longer half-life than naturally occurring antibodies through Fc engineering;

• Potential to induce a vaccinal effect, i.e.

to elicit endogenous adaptive immune response that may provide durable protection even after the mAb is no longer present;

• Antibody-mediated cell killing affects against infection and tumors;

• Tunable potency/affinity for inhibitory or agonist properties

Sotrovimab, ansuvimab, tobevibart,VIR-2482 as well as other mAbs in early preclinical development such as VIR-7229 were generated using our antibody platform.

We continue to leverage our expertise in antibody discovery and development, enhanced by machine learning and artificial intelligence.

Using strategies such as our dAIsY ™ system, we can engineer our candidates to optimize key biological and biophysical properties, such as half-life and developability.

This discovery platform is utilized to generate antibodies that can be further developed into therapeutic molecules, including the generation of dual-masked TCEs against novel tumor targets.

PRO-XTEN ™ Masking Platform:

Exclusively in-licensed from Sanofi in 2024, this platform enables the development of potentially best-in-class masked TCEs for solid tumors.

The dual-masking approach is designed to enhance tumor specificity while minimizing off-target effects, potentially improving both efficacy and safety.

This technology could make our future medicines more specific, effective, and tolerable by ensuring they act only where needed, reducing damage to healthy cells and tissue.

Initial Phase 1 data has provided clinical proof of concept for this approach across multiple tumor types.

These platforms are complemented by our internal capabilities in process development, analytical development, manufacturing, and quality control.

We also maintain strategic partnerships with contract development and manufacturing organizations (CDMOs) to support our clinical programs.

This combination of cutting-edge technologies, artificial intelligence-driven optimization, and deep immunological expertise positions us to create potentially transformative medicines for some of the more challenging diseases facing humanity today.

monoclonal antibody platform;

protein engineering capabilities;

artificial intelligence

Antibody Platform

We have developed cutting-edge platforms to identify and enhance rare, potent monoclonal antibodies (mAbs) using AI-enabled protein engineering for the treatment of infectious diseases and cancer.

Our platforms leverage the efficient interrogation of memory B cells from two primary sources:

convalescent human patients and transgenic mice expressing human- immunoglobulin G (IgG) following immunization.

This approach enables the selection of highly potent antibodies with unique characteristics that can be further developed into therapeutic molecules, including dual-masked TCEs targeting novel TAA.

Our platform has been successfully applied to identify mAbs for multiple pathogens including SARS-CoV-2, HBV, HDV, Ebola virus, and HIV.

Noteworthy achievements include:

• Sotrovimab (Xevudy ® ):

Anti-SARS-CoV-2 mAb, granted Emergency Use Authorization (EUA) or marketing authorization in multiple regions.

• Ansuvimab (Ebanga ™ ):

Anti-Ebola virus mAb developed in collaboration with the NIH and marketed by Ridgeback Biotherapeutics LP.

MAbs function through various mechanisms including pathogen neutralization, target cell lysis (infected or tumor cells), and immunomodulation.

Our approach combines rapid, high-throughput isolation of rare and highly potent fully human mAbs from cell culture-based libraries of clonal B lymphocytes.

Our proprietary antibody screening technology enables the screening of antibodies from hundreds of millions of B cells derived from either convalescent individuals or human-Ig immunized mice.

This screening identifies rare and potent mAbs capable of binding highly conserved antigens, neutralizing multiple pathogens, or selectively targeting host proteins, including tumor antigens or antigens involved in the modulation of anti-tumor immune responses.

These fully human antibodies can be refined using our proprietary AI-driven protein engineering technology, dAIsY ™ , enhancing their potency, resistance, pharmacokinetics, as well as their manufacturability.

This involves optimizing the antigen-binding fragment (Fab) regions to improve efficacy, potency, and manufacturability, as well as the Fc region to fine-tune the antibody's half-life and to enhance its ability to engage effector functions of the immune system.

In this context, we have developed a set of novel and proprietary Fc mutations that have the potential to enhance the anti-tumor efficacy of antibodies.

Hu-Ig = humanized immunoglobulin

We use a proprietary antibody screening technology that allows us to screen the antibodies produced from hundreds of millions of B cells derived from survivors of an infection or from human-Ig immunized mice to identify those rare mAbs that have the characteristics needed to create an effective medicine.

Rare characteristics include, for example, the ability to bind to a highly conserved antigen within a pathogen, to neutralize multiple different pathogens or to selectively bind host target proteins.

We refer to this technology as High Throughput Isolation since we are able to screen hundreds of millions of B cells to find rare antibodies in just a few weeks.

After identification of top mAb development candidates, our proprietary AI-driven protein engineering technology, dAIsY TM , is used to generate libraries of mAb variants which are further screened using functional assays, as well as screened for favorable pharmacokinetic and manufacturability properties.

Top mAb variants may be recombined as the basis for new libraries, in iterative cycles to identify the lead antibody sequence.

Precision Antibody Engineering to Create the Best Medicines

Our strategy is to optimize both the Fab and Fc domains of mAbs using our proprietary AI-driven engineering approach to generate the best medicine to treat or prevent a broad range of infectious and non-infectious diseases.

Once we isolate a rare, fully human antibody via High Throughput Isolation, we then engineer the Fab and Fc domains, to enhance expected efficacy, potency and manufacturability.

The Fab portion binds to the target antigen of interest.

The Fc portion binds to effector proteins and cells in the body to engage the immune system in killing and clearing targeted cells.

Fab engineering is performed to further increase mAb potency and breadth of coverage.

MAb potency and breadth depend on the epitope targeted, affinity of binding and valency.

In some cases, it may be valuable to create mAbs that bind to more than one epitope, so-called “multi-specific” mAbs, by engineering the Fab region using a wide range of proprietary and non-proprietary formats.

Effector functions can be enhanced or reduced via Fc mutations that alter the binding affinity of the Fc domain of a mAb to the various FcRs, based on a detailed understanding of the role of individual FcRs in immunity.

Fc engineering selects and optimizes the specific ways in which mAbs engage FcRs, which in turn govern properties such as the half-life of the antibody as well as “effector functions,” i.e.

the way that the immune system is recruited by the mAb to fight infection or kill other target cells.

The Fc engineering of our mAbs fine tune the interactions with activating and inhibiting FcRs, which are differentially expressed on immune cells, and takes into account the FcgR polymorphisms in the human population, to generate mAbs tailored for specific indications.

Examples of immunity that can be altered via Fc engineering include the recruitment of serum proteins to infected areas, phagocytosis and destruction of viruses and viral particles, the killing of target cells through a process known as ADCC and the presentation of antigens to elicit potentially long-lasting B and T cell immunity.

Antibodies as T Cell Vaccines

We are using Fc engineering to create antibodies that are designed to not only directly treat or prevent infection but also to elicit an effective adaptive immune response against chronic viral infections, such as HBV or HIV.

We refer to this property as a vaccinal effect, i.e., eliciting continued protection even after the mAb is no longer present.

This technology benefits from the fact that FcRs on specialized antigen-presenting cells, which are called dendritic cells, or DCs, internalize complexes of antibody and antigen.

Our strategy leverages the observation that different FcRs on antigen presenting cells can bind differentially to the Fc portion of the mAb.

By engineering the Fc region, we can therefore select which FcRs preferentially interact with the antibody-antigen complex to generate activated DCs that we believe can mediate an effective and durable T cell immunity.

Specific vaccinal mutations in the Fc domain can enhance immune responses to a pathogen in two ways.

First, the mAb can deliver increased amounts of antigen to DCs.

Second, FcRs deliver signals that activate DCs.

In turn, activated DCs can stimulate T cells specific to the delivered antigen, resulting in T cell immunity.

In this way, an antibody with vaccinal Fc mutations can potentially actively immunize infected patients.

The in vivo data supporting enhancement of the vaccinal effect through Fc mutants has been demonstrated by others, e.g.

in a CD20 positive tumor model, using mice with humanized Fc receptors.

In this experiment, anti-CD20 mAbs and CD20 tumor cells were administered to mice months before being later rechallenged with a lethal dose of CD20 tumor cells.

Most of the mice (80%) who received a mAb with Fc mutants that enhanced binding to activating FcRs IIa and IIIa survived.

Conversely, 70% or more mice who received a mAb without the enhancing Fc mutations died.

This durable protection is believed to be the result of the induction of a protective T-cell response.

We have also generated similarly compelling animal data in the context of influenza infection, in which vaccinal antibodies induced CD8 T cell responses.

We are testing this technology in chronic HBV infection with tobevibart, and if it performs as expected at mediating HBV functional cure, we believe the technology could be used similarly with other mAbs to control other chronic infections, including HIV.

T Cell-Based Viral Vector Platform

We are exploiting the unique immunology of HCMV, a commonly occurring virus in humans, as a vaccine vector to potentially prevent and treat infection by pathogens refractory to current vaccine technologies.

HCMV infects a large proportion of the human population and causes a life-long asymptomatic infection that typically causes no harm.

This is due to millions of years of co-evolution between the virus and host in which the virus evades sterilizing immunity using specialized viral genes, while at the same time allowing the generation of certain T cell responses that prevent HCMV infection from becoming lethal.

We have modified the HCMV genome to express proteins from HIV and HPV.

This approach is based on fundamental observations made in NHPs, with vaccine vectors made from rhesus cytomegalovirus, or RhCMV.

HCMV is the most potent known inducer of T cell responses of any human virus and may induce potent and long-lasting T cell responses to a broader range of epitopes than observed for other viral vaccines.

In addition, we can make proprietary modifications in the HCMV genome that we expect will elicit different types of pathogen-appropriate T cell responses.

We term this approach “immune programming.” We believe this platform may also have applicability beyond infectious diseases, potentially to cancers that can be controlled by T cells that recognize tumor antigens.

We expect the following benefits from using HCMV as a platform:

• Highly potent and long-lived T cell responses throughout the body, targeting the antigens of interest;

• Induction of high numbers of specialized T cells, known as effector memory cells, that are present in tissues and allow control of infection in the first few days;

• Immune responses to three- to four-fold more antigenic epitopes in a target protein than other viral vectors;

• Programmable T cell responses allowing selection of the type of T cells elicited;

• Opportunity for repeated vaccination using the same backbone HCMV vector against different infections;

• Opportunity to use the same HCMV vector to protect against or treat multiple pathogens;

• Potential to induce responses even to proteins that the host is tolerant of, such as self-proteins expressed in a tumor.

VIR-1111, VIR-1388 and VIR-1949 were generated using our T cell platform.

We believe that the type of T cell response elicited by an HCMV-based vaccine vector can be selected by mutating certain genes in HCMV.

We term this approach “immune programming.” We believe that immune programming is critical to combating infections such as HIV and TB that have proven intractable, to date, for other vaccine technologies.

The unique immunology of HCMV depends on the virus’s ability to elicit high frequencies of memory T cells, especially tissue-trafficking T cells and to regulate the normal immune processes of antigen presentation by major histocompatibility complex, or MHC proteins.

The MHC proteins, class I, class II and MHC-E (called HLA proteins in humans) bind small peptide fragments on the surfaces of antigen presenting cells that are detected by T cells.

HCMV contains multiple genes that regulate many of the steps in antigen presenting cells that elicit T cell immunity by altering antigen presenting cell biology, the types of antigen presenting cells infected by the viral vaccine and the mechanisms responsible for the ability of a T cell to recognize antigens together with MHC molecules.

Through manipulation of the HCMV genome, we believe we can program different types of pathogen-appropriate T cell responses.

Immune programming and protection from lethal challenge were observed in NHPs vaccinated with RhCMV vectors against SIV and TB.

An RhCMV vaccine with genome changes favoring T cell detection of peptide fragments bound by MHC-E protected more than half of NHPs from infection when challenged with a highly virulent form of SIV, whereas all animals in the control group became infected.

RhCMV vaccines manipulated to generate T cells that detected peptides bound to MHC-I were not protective, demonstrating the potential value of a programmable T cell vaccine platform.

Protection has also been observed against TB in preclinical studies of NHPs after immunization with either of two RhCMV vaccines.

Modifications to one of the protective vaccines elicited T cells that recognized peptides plus MHC-II and MHC-E responses, while the other was programmed to elicit a T cell response against peptides attached to MHC-I.

This shows the potential significance of being able to specifically program a vaccine to elicit T cells that will be most effective against a given infection, as the programming of a vaccine to protect against SIV can be different from the programming of a vaccine to protect against TB.

These preclinical data supported our use of the HCMV T cell platform to vaccinate against HIV and TB.

The Bill & Melinda Gates Foundation is providing funds for the process development and manufacturing and early clinical development of our HIV vaccine program.

MHC-E as a Near-Universal Target for Medicines that Leverage T Cell Receptors

T cells need to be able to recognize a highly diverse set of pathogen proteins to be effective.

This diversity comes from the use of multiple different host immune response major histocompatibility complex (MHC) proteins to present foreign antigens to T cells.

The genes for HLA class I and to a lesser extent the HLA class II are highly variable between individuals, while HLA-E genes are less variable between individuals.

The immune response MHC genes that are highly variable between individuals are responsible for eliciting most T cell responses.

These MHC molecules enable T cells to recognize foreign proteins through the use of a specific T cell receptor (TCR) on the T cell surface.

The programmed T cell responses elicited by HCMV vectors with certain gene modifications are predicted to use MHC -E, which may have advantages when MHC class I proteins have been blocked on infected cells and tumors.

T cells with TCRs recognizing antigenic peptides together with MHC-E may be functional when typical T cell responses are not functional and potentially allow for the generation of universal TCR-based medicines beyond vaccines, such as off-the-shelf cancer T cell therapy.

PRO-XTEN ™ Masking Platform

The PRO-XTEN ™ masking technology exploits the high protease activity of the tumor microenvironment to specifically release the active form of a drug via release of the mask only in tumor tissues.

It can be applied to a variety of molecules such as TCEs, cytokines, or other molecules to broaden the therapeutic index for patients.

The preferential release of the drug in the tumor microenvironment is designed to minimize on-target, off-tissue toxicity.

The XTEN ™ masks are designed to extend the half-life resulting in more convenient dosing regimens for patients and clinicians.

This masking approach could be key to pursuing validated oncology targets typically associated with therapies of high toxicity, ultimately offering an opportunity to potentially increase the therapeutic index of drug candidates and deliver more efficacious and safer options for patients.

We are currently investigating the PRO-XTEN ™ technology in conjunction with TCEs.

These are powerful anti-tumor agents that direct the immune system, specifically T-cells, to destroy cancer cells.

The PRO-XTEN ™ masking technology is designed to keep the TCEs inactive (or masked) until they reach the tumor microenvironment, where tumor-specific proteases cleave off the masks and activate the TCEs leading to killing of cancer cells.

By driving the activity exclusively to the tumor microenvironment, we aim to circumvent the traditionally high toxicity associated with TCEs and increase their efficacy and tolerability.

T-Cell Engager

Our dual-masked TCEs are single protein polypeptides with three key functions, a bi-specific TCE at their core, two universal PRO-XTEN ™ masks, which are connected to the TCE component by protease-cleavable linkers.

The bi-specific TCE is comprised of two antibody fragments:

a TAA binding domain and a CD3 binding domain.

Upon unmasking, they are designed to simultaneously recruit T-cells to cells expressing the target TAA, preferentially cancer cells, directing the cytotoxic activity of T-cells against the tumor.

Our discovery and antibody engineering capabilities are extendable to optimizing TAA and T-cell engagement component and identifying novel TCE fragments for additional targets, not only in oncology but also in infectious disease.

The protease-activated linkers that are part of PRO-XTEN ™ were discovered by applying a combination of in vitro and in vivo experiments together with a genetic algorithm for sequence optimization.

tumor microenvironment;

T-Cell Engager;

cluster of differentiation 3;

tumor associated antigen;

cytokine release syndrome;

once every 3 weeks

Our Collaboration, License and Grant Agreements

License Agreement with Sanofi

On September 9, 2024, we closed a license agreement with Amunix Pharmaceuticals, a Sanofi company, previously announced on August 1, 2024 (the Sanofi Agreement), pursuant to which we obtained an exclusive (as to Sanofi and its affiliates), worldwide, royalty-bearing, sublicensable (through multiple tiers), transferable license to research, develop, manufacture, commercialize and otherwise exploit:

(i) three clinical-stage masked TCEs of Sanofi, for all therapeutic, prophylactic, palliative, and diagnostic uses, excluding the ophthalmological field, and (ii) the PRO-XTEN ™ universal masking technology for oncology and infectious disease, excluding the ophthalmological field.

As part of the closing of the Sanofi Agreement, we made an upfront payment to Sanofi in the amount of $100.0 million and transferred $75.0 million to an escrow account that is due to former shareholders of Amunix Pharmaceuticals, Inc.

upon VIR-5525 achieving “first in human dosing” by 2026.

Sanofi will also be eligible to receive up to an additional $323.0 million in future development and regulatory milestone payments, up to an additional $1.49 billion in commercial net sales-based milestone payments, and low single-digit to low double-digit tiered royalties on worldwide net sales.

In addition, if, within a two-year period from the execution of the Sanofi Agreement, we execute a transaction that gives rise to VirBio receiving certain sublicense income related to the licenses obtained from the Sanofi Agreement, Sanofi may be eligible to receive a portion of such income.

The Sanofi Agreement will remain in force, on a product-by-product and country-by-country basis, until the expiration of all royalty payment obligations.

We may terminate the Sanofi Agreement in its entirety, or on a target-by-target basis, for convenience upon 120 days’ written notice if there have been no commercial sales of such target or upon 12 months written notice after the first commercial sale of such target as long as such termination is after December 31, 2026.

Collaboration Agreements with GSK

2020 Collaboration Agreement with GSK

In June 2020, we entered into a definitive collaboration agreement with GSK, or the 2020 GSK Agreement, pursuant to which we agreed to collaborate to research, develop and commercialize products for the prevention, treatment and prophylaxis of diseases caused by SARS-CoV-2, the virus that causes COVID-19, and potentially other coronaviruses.

In June 2020, we entered into a definitive collaboration agreement with GSK (the 2020 GSK Agreement), pursuant to which we agreed to collaborate to research, develop and commercialize products for the prevention, treatment and prophylaxis of diseases caused by SARS-CoV-2, the virus that causes COVID-19, and potentially other coronaviruses.

The collaboration initially focused on the development and commercialization of three types of collaboration products under three programs:

(1) antibodies targeting SARS-CoV-2, and potentially other coronaviruses, or the Antibody Program;

(2) vaccines targeting SARS-CoV-2, and potentially other coronaviruses, or the Vaccine Program, and (3) products based on genome-wide CRISPR screening of host targets expressed in connection with exposure to SARS-CoV-2, and potentially other coronaviruses, or the Functional Genomics Program.

The initial antibodies under the Antibody Program are sotrovimab and VIR-7832.

The original 2020 GSK Agreement contained the following key terms.

For a period of four years beginning April 2020, the parties agreed to conduct certain research and development activities under mutually agreed development plans and associated budgets for each of the three programs, and under the oversight of a joint steering committee, or JSC.

During such period, generally, subject to certain rights granted to WuXi Biologics (Hong Kong) Limited, or WuXi Biologics, under then existing agreements between us and WuXi Biologics, the parties would have an exclusive research collaboration with respect to antibody products directed to SARS-CoV-2 or to any other coronavirus, and in connection with functional genomics CRISPR screens for drug discovery and development in connection with SARS-CoV-2 or other coronaviruses.

We are primarily responsible for the development and clinical manufacturing activities for the Antibody Program, and for conducting the initial development activities directed to a vaccine in the Vaccine Program.

GSK is primarily responsible for the commercialization activities for the Antibody Program (except in connection with sales of antibody products licensed to WuXi Biologics in mainland China, Hong Kong, Macau and Taiwan), the later-stage development, manufacturing and commercialization activities for the Vaccine Program and the development, manufacturing and commercialization activities for the Functional Genomics Program.

We and GSK are required to use commercially reasonable efforts to conduct the activities assigned to each party under each development plan and to seek and obtain regulatory approval for collaboration products that arise from such activities in the United States and specified major markets.

Subject to an opt-out mechanism, we and GSK share all development costs, manufacturing costs and costs and expenses for the commercialization of the collaboration products, with us bearing 72.5% of such costs for the antibody products, 27.5% of such costs for the vaccine products, and we and GSK sharing equally all such costs for the functional genomics products, and all profits will be shared in the same ratios.

If we and GSK elect to conduct a technology transfer of manufacturing technology under our agreement with WuXi Biologics (as further described below), we will bear 72.5% of the costs related to such manufacturing technology transfer and for commercial manufacturing of the antibody products under such agreement with WuXi Biologics, and GSK will bear 27.5% of such costs.

The parties will also share the committed costs for the reservation of manufacturing capacity for the drug substance for antibody products in the foregoing ratio under our agreement with Samsung Biologics as well as such costs relating to committed manufacturing capacity for antibody products as are approved by the JSC from time to time.

On a collaboration product-by-collaboration product basis, each party has the one-time right, at specified points in development, to opt out of its co-funding obligations, and the other party may, at its election, either pursue such program unilaterally, or also cease research and development activities and funding of such collaboration product.

If the opt-out provisions are not exercised by either party subject to the terms of the 2020 GSK Agreement, the parties share all profits and losses arising from any collaboration product in the same ratios in which the parties bore development costs for such collaboration program.

For each collaboration product as to which a party exercises its opt-out right, the commercializing party pays to the opt-out party royalties on net sales of the applicable collaboration product at rates based on factors such as the stage of development of such collaboration product at the time the opt-out party exercises such right, and whether the opt-out party is the lead party, or a portion of the sublicense revenue if the commercializing party chooses to sublicense or otherwise divest rights to such collaboration product.

On an antibody product-by-antibody product basis, we have a co-promotion right for such antibody product in the United States, under which we have the right to perform up to 20% of details in connection with such antibody product.

GSK will lead commercialization and book all sales and is required to use commercially reasonable efforts to commercialize each collaboration product following regulatory approval in the United States and specified major markets.

This definitive agreement superseded and replaced the April 2020 preliminary agreement with GSK.

In connection with the 2020 GSK Agreement, we also entered into a stock purchase agreement in April 2020, pursuant to which we issued 6,626,027 shares of our common stock to Glaxo Group Limited, or GGL, an affiliate of GSK, at a price per share of $37.73, for an aggregate purchase price of approximately $250.0 million.

The 2020 GSK Agreement as amended will remain in effect with respect to each collaboration program for as long as there is a collaboration product being developed or commercialized by the lead party, or the non-opt-out party, in such program.

(1) antibodies targeting SARS-CoV-2, and potentially other coronaviruses (the Antibody Program);

(2) vaccines targeting SARS-CoV-2, and potentially other coronaviruses (the Vaccine Program);

and (3) products based on genome-wide CRISPR screening of host targets expressed in connection with exposure to SARS-CoV-2, and potentially other coronaviruses (the Functional Genomics Program).

The antibody under the Antibody Program is sotrovimab, developed and commercialized for the treatment and prophylaxis of COVID-19.

In connection with the 2020 GSK Agreement, we also entered into a stock purchase agreement in April 2020, pursuant to which we issued 6,626,027 shares of our common stock to Glaxo Group Limited, an affiliate of GSK (GGL), at a price per share of $37.73 and an aggregate purchase price of approximately $250.0 million.

In February 2023, we and GSK entered into two amendments to the 2020 GSK Agreement.

Pursuant to the amendments, we and GSK agreed to remove the Vaccine Program from the 2020 GSK Agreement and to wind down and terminate the cost-sharing arrangements and all ongoing activities in relation to the Vaccine Program.

As of the effective date of amendments, the Vaccine Program had not yet advanced to its predefined development candidate stage.

We retained the right to progress development of vaccine products directed to SARS-CoV-2 and other coronaviruses independently (including with or for third parties) outside the scope of the 2020 GSK Agreement, subject to the payment of tiered royalties to GSK on net sales of any vaccine products covered by certain GSK intellectual property rights in the low single digits.

In addition, we and GSK agreed to modify the Antibody Program to remove from the collaboration all coronavirus antibodies other than sotrovimab and VIR-7832, and certain variants thereof, which remained subject to the terms of the 2020 GSK Agreement.

We retained the sole right to progress the development and commercialization of the terminated antibody products independently (including with or for third parties), subject to the payment of tiered royalties to GSK on net sales of such terminated antibody products at percentages ranging from the very low single digits to the mid-single digits, depending on the nature of the antibody product being commercialized.

Subject to an opt-out mechanism, the parties share all development costs, manufacturing costs, and costs and expenses for the commercialization of the collaboration products, with us bearing 72.5% of such costs for sotrovimab, except that GSK has the sole right to develop (including to seek, obtain or maintain regulatory approvals), manufacture and commercialize sotrovimab in and for mainland China, Hong Kong, Macau and Taiwan at GSK’s sole cost and expense.

As the lead party for all manufacturing and commercialization activities, GSK incurs all of the manufacturing, sales and marketing expenses and is the principal on sales transactions with third parties.

The 2020 GSK Agreement will remain in effect with respect to sotrovimab for as long as it is being commercialized by the lead party.

Either party has the right to terminate the 2020 GSK Agreement in the case of the insolvency of the other party, an uncured material breach of the other party with respect to a collaboration program or collaboration product, or as mutually agreed by the parties.

In December 2021, Beecham S.A.

assigned and transferred all its rights, title, interest, and benefit in the 2020 GSK Agreement to GlaxoSmithKline Biologicals S.A., including all its rights to bring claims under such agreement.

On May 27, 2022, we entered into Amendment No.

1 to the 2020 GSK Agreement, or Amendment No.

Pursuant to Amendment No.

1, we and GSK acknowledged that the antibody products that had been licensed to WuXi Biologics in mainland China, Hong Kong, Macau and Taiwan and had reverted to us pursuant to the Termination Agreement (described below) and agreed with GSK that they are now included in and governed by the 2020 GSK Agreement, subject to certain amendments relating to sotrovimab.

Under the terms of Amendment No.

1, GSK has the sole right to develop (including to seek, obtain or maintain regulatory approvals), manufacture and commercialize sotrovimab in and for mainland China, Hong Kong, Macau and Taiwan at GSK’s sole cost and expense (other than certain payments for which we remain responsible under certain of our existing agreements with third parties).

GSK paid us a one-time upfront payment of $7.0 million in consideration for the rights and licenses granted to GSK under Amendment No.

In addition, GSK will be obligated to pay us tiered royalties on net sales of sotrovimab in mainland China, Hong Kong, Macau and Taiwan in percentages ranging from the high teens to the low thirties.

Such royalties are payable to us during the term of the 2020 GSK Agreement applicable to the Antibody Program.

On February 8, 2023, we and GSK entered into Amendment No.

2 and Amendment No.

3 to the 2020 GSK Agreement.

Pursuant to Amendment No.

2 to the 2020 GSK Agreement, effective as of March 31, 2022, or the Effective Date, we and GSK agreed to remove the Vaccine Program from the 2020 GSK Agreement, and to wind down and terminate the cost-sharing arrangements and all ongoing activities in relation to the Vaccine Program.

As of the Effective Date, the Vaccine Program had not yet advanced to its predefined development candidate stage.

We retain the right to progress development of vaccine products directed to SARS-CoV-2 and other coronaviruses independently (including with or for third parties) outside the scope of the 2020 GSK Agreement, subject to the payment of tiered royalties to GSK on net sales of any vaccine products covered by certain GSK intellectual property rights in the low single digits, subject to certain deductions in certain circumstances.

Pursuant to Amendment No.

3 to the 2020 GSK Agreement, we and GSK agreed to modify the Antibody Program to remove from the collaboration all coronavirus antibodies other than sotrovimab and VIR-7832, and certain variants thereof.

Sotrovimab and VIR-7832, and certain variants thereof, remain subject to the terms of the 2020 GSK Agreement, and we retain the sole right to progress the development and commercialization of the terminated antibody products independently (including with or for third parties), subject to the payment of tiered royalties to GSK on net sales of such terminated antibody products at percentages ranging from the very low single digits to the mid-single digits, depending on the nature of the antibody product being commercialized, and subject to certain deductions in certain circumstances.

In May 2021, the FDA granted an EUA in the United States for sotrovimab, for the early treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and at high risk for progression to severe COVID-19, including hospitalization or death.

In December 2021, the EC granted marketing authorization to Xevudy ® (sotrovimab) in the EU for the treatment of adults and adolescents at increased risk of progressing to severe COVID-19.

In April 2022, the FDA excluded the use of sotrovimab in all U.S.

regions due to the continued proportion of COVID-19 cases caused by certain variants, and in December 2024, the FDA revoked EUA granted to sotrovimab.

Going forward, we expect a nominal amount of collaboration revenue, if any, from our 2020 GSK Agreement, and we may incur negative collaboration revenue related to costs for ongoing required support efforts that our partner GSK leads.

2021 Expanded GSK Collaboration

In May 2021, we entered into the 2021 GSK Agreement under which the parties agreed to expand the 2020 GSK Agreement, to include collaboration on three separate programs:

(1) a program to research, develop and commercialize mAbs for the prevention, treatment or prophylaxis of the influenza virus, or the Influenza Program, excluding VIR-2482 unless GSK exercises its exclusive option (the VIR-2482 Option) to co-develop and commercialize after the Company completes a Phase 2 clinical trial;

(2) an expansion of the parties' current Functional Genomics Program to focus on functional genomics screens directed to targets associated with respiratory viruses, or the Expanded Functional Genomics Program;

and (3) additional programs to develop neutralizing mAbs directed to up to three non-influenza target pathogens selected by GSK, or the Selected Pathogens, and such programs, or the Additional Programs.

In 2021, we entered into the 2021 GSK Agreement under which the parties agreed to expand the 2020 GSK Agreement, to include collaboration on three separate programs:

(1) a program to research, develop and commercialize mAbs for the prevention, treatment or prophylaxis of the influenza virus, excluding VIR-2482 unless GSK exercises its exclusive option (the VIR-2482 Option) to co-develop and commercialize after the Company completes a Phase 2 clinical trial (the Influenza Program);

(2) an expansion of the parties’ current Functional Genomics Program to focus on functional genomics screens directed to targets associated with respiratory viruses (the Expanded Functional Genomics Program);

and (3) additional programs to develop neutralizing mAbs directed to up to three non-influenza target pathogens selected by GSK (the Selected Pathogens, and such programs the Additional Programs).

In connection with the 2021 GSK Agreement, we entered into a stock purchase agreement with GGL pursuant to which we issued 1,924,927 shares of our common stock to GGL for an aggregate purchase price of approximately $120.0 million.

The 2021 GSK Agreement superseded and replaced the preliminary agreement entered into with GSK in February 2021, or the 2021 Preliminary Agreement.

On February 21, 2024, the Company and GSK entered into a letter agreement (the Letter Agreement) pursuant to which the Company and GSK agreed to remove the Influenza Program from the 2021 GSK Agreement and to wind down and terminate the cost-sharing arrangements and all ongoing activities in relation to the Influenza Program.

As of the effective date of the Letter Agreement, GSK had not exercised the VIR-2482 Option.

As it relates to the Expanded Functional Genomics Program and Additional Programs, for a period of three years following the effective date of the 2021 GSK Agreement, or the Research Term, the parties will conduct certain research and development activities under mutually agreed development plans and associated budgets for the programs within the expanded collaboration.

Subject to certain exceptions, we will exclusively collaborate with respect to (a) functional genomic screens for targets associated with respiratory viruses during the Research Term, and compounds or products developed through the Expanded Functional Genomics Program directed to a collaboration target for five years following the target selection (unless either party elects to opt-out earlier), and (b) products directed to Selected Pathogens during the Research Term, which ends in 2024.

We will mutually agree upon the allocation of responsibility for the development of products under the Expanded Functional Genomics Program, and for the development and early-stage manufacturing of products under the Additional Programs if and when GSK decides which Selected Pathogens to pursue.

GSK will be primarily responsible for commercial manufacturing and commercialization activities for products under the Expanded Functional Genomics Program and Additional Programs, if and when selected by GSK.

For each collaboration program, upon execution of the definitive agreement, we will grant GSK certain license rights related to the development, manufacturing and commercialization of products arising from the program.

The parties will share 50% of all development costs in accordance with the budget for each of the collaboration programs, with each party having the right (on a target-by-target, or collaboration product-by-collaboration product basis, as applicable) to opt-out of its co-funding obligations at specified points in development.

In such case, the party continuing with the program will pay to the opt-out party a royalty on net sales of products arising from such program at specified rates based on the stage of development at which the opt-out is exercised.

Following the exercise of an opt-out right by a party the other party may, at its election, either pursue development and commercialization of such product or program unilaterally, or also cease the conduct and funding of such collaboration product or program.

In the absence of any opt-out, the parties will also share 50% of all profits and losses arising from any collaboration product.

Each party is required to use commercially reasonable efforts to conduct the activities assigned to it under each development plan and, where applicable, to seek and obtain regulatory approval for collaboration products that arise from such activities in the United States and specified major markets.

GSK will lead commercialization and book all sales, and is required to use commercially reasonable efforts to commercialize each collaboration product following regulatory approval in the United States and specified major markets.

GSK made an upfront payment to us of $225.0 million, 50% became payable at the effective date of the 2021 Preliminary Agreement and 50% of became payable following the execution of the 2021 GSK Agreement.

In September 2022, GSK exercised its first Selected Pathogen Right, selecting RSV as its first pathogen under the Additional Programs of the 2021 GSK Agreement.

GSK agreed to retroactively share the research and development costs that we had incurred under its RSV program since April 2022 in accordance with the applicable provisions of the 2021 GSK Agreement.

GSK can select up to two additional non-influenza target pathogens prior to March 25, 2024.

With respect to each Additional Program, unless earlier terminated, the 2021 GSK Agreement will remain in effect for as long as there is a product from such collaboration program being developed or commercialized by the lead party in the collaboration program or by the non-opt-out party, if applicable.

With respect to the Expanded Functional Genomics Program, unless earlier terminated, the 2021 GSK Agreement will remain in effect (a) until the end of the Research Term, if no targets are selected for the Expanded Functional Genomics Program prior to the end of the Research Term, or (b) if at least one target is selected for the Expanded Functional Genomics Program prior to the end of the Research Term, for as long as there is a product from the Expanded Functional Genomics Program being developed or commercialized by the lead party in the Expanded Functional Genomics Program or by the non-opt-out party, if applicable.

Either party has the right to terminate the 2021 GSK Agreement in the case of the insolvency of the other party, an uncured material breach of the other party with respect to a collaboration program or a collaboration product, or as mutually agreed by the parties.

As of the effective date of the Letter Agreement, GSK’s VIR-2482 Option was terminated.

The Company has no further obligations to GSK with respect to VIR-2482.

In addition, as of the effective date of the Letter Agreement, GSK exercised its opt-out option with respect to VIR-2372 and VIR-2981.

The Company had no further obligations to GSK with respect to VIR-2372 and VIR-2981.

As a result of GSK’s opt-out to VIR-2372 and VIR-2981, the Company may continue to pursue the development and commercialization of those programs unilaterally.

If either of those programs is commercialized, the Company will pay GSK a royalty on net sales in the low single digits.

As it relates to the Expanded Functional Genomics Program, all remaining targets selected were mutually rejected in the first quarter of 2024, with remaining exclusivity to such targets expiring in mid-2025.

No further research activity is expected by either party under the program.

Regarding the Additional Programs, GSK selected RSV as its first pathogen in 2022.

During the first quarter of 2024, we recognized contract revenue of $51.7 million as GSK’s rights to select the remaining up to two additional non-influenza target pathogens expired on March 25, 2024.

We opted-out of the RSV program during the fourth quarter of 2024.

As a result of our opt-out, GSK may continue to pursue the development and commercialization of the RSV program unilaterally.

If the RSV program reaches commercialization, GSK will pay us a royalty on net sales in the low single digits.

Collaboration and License Agreement with Alnylam

In October 2017, we entered into a collaboration and license agreement with Alnylam, or the Alnylam Agreement, for the development of siRNA products for the treatment of HBV and following the exercise of certain program options, the development and commercialization of siRNA products directed to up to four other infectious disease targets selected by us.

The technology licensed under the Alnylam Agreement forms the basis of our siRNA technology platform.

Pursuant to the Alnylam Agreement, we obtained a worldwide, exclusive license to develop, manufacture and commercialize the HBV siRNA product candidates, including elebsiran, for all uses and purposes other than agricultural, horticultural, forestry, aquaculture and other residential applications, such excluded fields, the Excluded Fields.

In addition, Alnylam granted us an exclusive option, for each of the infectious disease siRNA programs directed to our selected targets, to obtain a worldwide, exclusive license to develop, manufacture and commercialize siRNA products directed to the target of each such program for all uses and purposes other than the Excluded Fields.

In October 2017, we and Alnylam Pharmaceuticals (Alnylam) entered into a collaboration and license agreement (the Alnylam Agreement).

Pursuant to the Alnylam Agreement, we obtained a worldwide, exclusive license to develop, manufacture and commercialize the siRNA product candidates directed to HBV, including elebsiran, for all uses and purposes including the treatment of HBV and HDV.

In addition, Alnylam granted us an exclusive option, for each of the infectious disease siRNA programs directed to our four selected targets, to obtain a worldwide, exclusive license to develop, manufacture and commercialize siRNA products directed to the target of each such program for all uses and purposes other than certain excluded fields.

Our options are each exercisable during a specified period following selection of candidates for each program, or two years following the initiation of certain activities under an agreed-upon development plan, if earlier.

On a product-by-product basis for each product arising from the HBV and, following our option exercise, the infectious disease programs, Alnylam has an exclusive option, exercisable during a specified period for each such product, to negotiate and enter into a profit-sharing agreement for such product.

On a product-by-product basis for each siRNA product directed to HBV and, if we exercise our license option, the siRNA products directed to the up to four infectious disease targets, Alnylam has an exclusive option, exercisable during a specified period for each such product, to negotiate and enter into a profit-sharing agreement for such product.

We and Alnylam were jointly responsible for funding the initial research and development activities for elebsiran through completion of proof of concept trials.

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Following our exercise of an option for a program and payment of the program option exercise fee and any outstanding program costs due to Alnylam, we are solely responsible, at our expense, for conducting all development, manufacture and commercialization activities for products arising from each such program unless Alnylam exercises its profit-sharing option.

We are required to use commercially reasonable efforts to develop and commercialize one siRNA product directed to HBV and one siRNA product directed to the target of each other infectious disease program for which we exercise our option, in each of the major markets.

We are required to use commercially reasonable efforts to develop and commercialize one siRNA product directed to HBV, whether for the treatment of HBV or HDV, as well as one siRNA product directed to the target of each other infectious disease program for which we exercise our option, in the United States and certain specified major markets.

If Alnylam exercises a profit-sharing option for a product, such as elebsiran, we will negotiate the terms of such profit-sharing agreement.

We retain final decision-making authority with respect to which infectious disease product candidates we advance and the development programs for the HBV and infectious disease product candidates, subject to certain limitations.

We retain final decision-making authority with respect to which infectious disease product candidates we advance and the development programs for the HBV and HDV, as well as infectious disease product candidates, subject to certain limitations.

During the term of the Alnylam Agreement, neither we nor Alnylam may develop or commercialize any gene-silencing, oligonucleotide-based product directed to the same target as any product candidate under the Alnylam Agreement, other than pursuant to the Alnylam Agreement, subject to certain exceptions.

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Upon the achievement of a certain development milestone, as further discussed below, we were obligated to issue shares of our common stock equal to the lesser of (i) 1,111,111 shares or (ii) a certain number of shares based on our stock price at the time such milestone was achieved.

We will be required to pay Alnylam up to $190.0 million in the aggregate for the achievement of specified development and regulatory milestones by the first siRNA product directed to HBV, and up to $115.0 million for the achievement of specified development and regulatory milestones for the first product directed to the target of each infectious disease siRNA program for which we exercised our option.

Following commercialization, we will be required to pay to Alnylam up to $250.0 million in the aggregate for the achievement of specified levels of net sales by siRNA products directed to HBV and up to $100.0 million for the achievement of specified levels of net sales by products directed to the target of each infectious disease siRNA program for which we exercised our option.

We will also be required to pay Alnylam tiered royalties at percentages ranging from the low double-digits to mid-teens on annual net sales of HBV products, and tiered royalties at percentages ranging from the high single-digits to the sub-teen double-digits on annual net sales of licensed infectious disease products, in each case subject to specified reductions and offsets.

We are required to pay Alnylam up to $190.0 million in the aggregate for the achievement of specified development and regulatory milestones for the first siRNA product directed to HBV, whether for the treatment of HBV or HDV, and up to $115.0 million for the achievement of specified development and regulatory milestones for the first product directed to the target of each infectious disease siRNA program for which we exercised our option.

In March 2020, we achieved one of the specified development milestones relating to elebsiran pursuant to the Alnylam Agreement.

As such, we paid Alnylam $15.0 million in April 2020, thereby reducing the $190.0 million referenced above to $175.0 million of potential development and regulatory milestones remaining to be paid related to elebsiran.

Following commercialization, we will be required to pay to Alnylam up to $250.0 million in the aggregate for the first achievement of specified levels of net sales by siRNA products directed to HBV, whether for the treatment of HBV or HDV related to elebsiran, and up to $100.0 million for the achievement of specified levels of net sales by products directed to the target of each infectious disease siRNA program for which we exercised our option.

We will also be required to pay Alnylam tiered royalties at percentages ranging from the low double-digits to mid-teens on annual net sales of siRNA products directed to HBV, such as elebsiran, whether for the treatment of HBV or HDV, and tiered royalties at percentages ranging from the high single-digits to the sub-teen double-digits on annual net sales of licensed infectious disease products, in each case subject to specified reductions and offsets.

The royalties are payable on a product-by-product and country-by-country basis until the later of the expiration of all valid claims of specified patents covering such product in such country and 10 years after the first commercial sale of such product in such country.

Alnylam is also entitled to receive a portion of any consideration we receive as a result of granting a sublicense under the licenses granted to us by Alnylam under the Alnylam Agreement or an option to acquire such a sublicense, determined based on the timing of the grant of such sublicense.

In November 2018, in connection with the inclusion of the HBV siRNA program as the subject of a potential grant of a sublicense to Brii Bio under the Brii Agreement, as defined under the section titled “Collaboration, Option and License Agreement with Brii Bio,” which triggered certain payment obligations under the Alnylam Agreement, we entered into a letter agreement with Alnylam, or the Alnylam Letter, making certain modifications to the payments due to Alnylam as a result of the grant of the option and potential payments that would result from Brii Bio’s exercise of rights under such sublicense.

In November 2018, in connection with the inclusion of the HBV siRNA program as the subject of a potential grant of a sublicense to Brii Bio under the Brii Agreement, as defined below), which triggered certain payment obligations under the Alnylam Agreement, we entered into a letter agreement with Alnylam (the Alnylam Letter), making certain modifications to the payments due to Alnylam as a result of the grant of the option and potential payments that would result from Brii Bio’s exercise of rights under such sublicense.

As a result of the rights granted under the Brii Agreement and pursuant to the Alnylam Letter, in February 2020 we transferred to Alnylam a specified percentage of the equity consideration allocable to the HBV siRNA program that we received from Brii Bio and its affiliated companies in connection with the entry into the Brii Agreement.

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Either party may terminate the agreement for cause for the other party’s uncured material breach on 60 days’ written notice (or 30 days’ notice for payment breach), or if the other party challenges the validity or enforceability of any patent licensed to it under the Alnylam Agreement on 30 days’ notice.

In March 2020, we achieved one of the specified development milestones relating to elebsiran pursuant to the Alnylam Agreement, as amended.

As such, we paid Alnylam $15.0 million in April 2020, and issued Alnylam 1,111,111 shares of our common stock in May 2020.

In March and April 2020, we entered into two further amendments to the Alnylam Agreement, or the Amended Alnylam Agreement, to expand our existing collaboration to include the development and commercialization of siRNA products targeting SARS-CoV-2 and potentially other coronaviruses, and up to three targeting human host factors for SARS-CoV-2, or collectively, the COVID Collaboration Targets.

In December 2020, we and Alnylam entered into a letter amendment, or the Letter Agreement, further amending the Amended Alnylam Agreement to modify certain funding and governance provisions in connection with the siRNA products directed to the COVID Collaboration Targets, including VIR-2703, or the COV Target, and to modify certain rights of each party with respect to products arising from such programs.

Pursuant to the Letter Agreement, Alnylam was responsible for conducting pre-clinical research activities set forth in the existing workplan for the COV Target, or the COV Workplan, at its discretion and sole expense, and we were no longer obligated to reimburse Alnylam for any share of costs incurred by Alnylam in conducting activities under the COV Workplan after July 1, 2020.

In July 2021, Alnylam elected to discontinue the development of the COV Target, and all other related research and development activities in accordance with their rights under the Letter Agreement.

As a result, the COV Target and the siRNA program related thereto are no longer included within the Amended Alnylam Agreement and all rights to the siRNA program directed to the COV Target reverted to Alnylam.

License Agreements with MedImmune

2012 Sub-License and Collaboration Agreement with MedImmune

In March 2012, our subsidiary Humabs entered into a sub-license and collaboration agreement with MedImmune, LLC, or MedImmune, as amended, or the 2012 MedImmune Agreement, pursuant to which Humabs conducted certain activities under a mutually agreed research plan for the development of therapeutic antibodies directed to influenza viruses (including influenza A and influenza B) and to Klebsiella bacteria.

The 2012 MedImmune Agreement was amended in April 2013, April 2015, December 2015, August 2016, July 2017, and September 2018 to designate Klebsiella as an extra target, to extend the term of the research program and provide for related payments, and to incorporate certain research activities funded by MedImmune under a specified government grant.

Under the 2012 MedImmune Agreement, as amended, MedImmune obtained a worldwide exclusive license from Humabs to develop and commercialize products directed to such targets for all uses in humans and animals except for active vaccination.

In consideration for the grant of the license, MedImmune made certain upfront payments to Humabs.

MedImmune is obligated to pay Humabs development, regulatory and commercial milestone payments of up to $96.5 million in the aggregate for the first product directed to influenza viruses to achieve the applicable milestones, and up to $12.0 million for the first product directed to Klebsiella to achieve the applicable milestones.

MedImmune will also be obligated to pay royalties based on net sales of products directed to influenza viruses or Klebsiella at certain fixed percentages in the low to mid-single-digits, with the rate determined based on the specific target to which the product is directed, in each case subject to specified reductions and a royalty floor.

The royalties are payable, on a product-by-product and country-by-country basis, until the later of the last to expire valid claim that would, but for the licenses granted under the 2012 MedImmune Agreement, be infringed by the sale of such product in such country, and 10 years from the first commercial sale of the first product in such country.

MedImmune also made certain payments to Humabs in consideration for Humabs’ conduct of the research program.

We will be obligated to pass through the milestone payments and royalty payments that we receive under the 2012 MedImmune Agreement, following deduction of certain expenses incurred by us or Humabs thereunder, to Humabs’ securities holders pursuant to the Humabs SPA, as defined under the section titled “—Securities Purchase Agreement with Humabs.”

The 2012 MedImmune Agreement will remain in force until MedImmune has fulfilled all of its obligations to make milestone and royalty payments.

MedImmune may terminate the 2012 MedImmune Agreement in its entirety, or on a product-by-product, license-by-license or country-by-country basis, for convenience, upon 90 days’ notice.

Either MedImmune or Humabs may terminate the 2012 MedImmune Agreement for the other party’s uncured material breach or in the event of bankruptcy of the other party.

2018 License Agreement with MedImmune

In September 2018, we entered into a license agreement with MedImmune, or the 2018 MedImmune Agreement, pursuant to which we obtained a worldwide, exclusive license to develop and commercialize half-life extended versions of two specified antibodies under development by MedImmune that target influenza A and influenza B, respectively, for all uses in humans and animals.

The license from MedImmune includes the grant of a sublicense under MedImmune’s license to certain intellectual property controlled by Humabs that was granted to MedImmune pursuant to the 2012 MedImmune Agreement.

Under certain circumstances and during certain periods of time we have the right to nominate up to two variants of each of these antibodies for inclusion under the license.

MedImmune retained the rights to continue to develop and to commercialize the two specified antibodies that target influenza A and influenza B, in each case that are not the half-life extended versions that are licensed to us.

Additionally, we obtained a worldwide, exclusive license under MedImmune’s antibody half-life extension technology to develop and commercialize half-life extended antibodies directed to up to two additional targets selected by us for all uses in humans or animals for the prevention, treatment or diagnosis of infectious diseases and had the right to nominate such additional targets during a specified period following the effective date of the 2018 MedImmune Agreement.

We are solely responsible, at our sole cost, for the development of products containing half-life extended versions of antibodies directed to the influenza targets and any additional selected targets, and are obligated to use commercially reasonable efforts to develop and obtain regulatory approval for at least one product containing half-life extended versions of antibodies directed to each of influenza A, influenza B and any additional targets, if applicable, in the United States and specified markets in Europe and Asia.

We are also obligated to use commercially reasonable efforts to commercialize products containing half-life extended versions of antibodies directed to such targets in such markets.

In consideration for the grant of the licenses under the 2018 MedImmune Agreement, we made an upfront payment to MedImmune of $10.0 million.

We will be obligated to make development and regulatory milestone payments to MedImmune of up to $92.0 million, of which $5.0 million was paid in the third quarter of 2019, in the aggregate for products containing half-life extended versions of antibodies directed to influenza A that we licensed, up to an additional $39.2 million in the aggregate for such products directed to influenza B that we licensed, and up to $250,000 in the aggregate for certain specified products directed to the additional selected targets, if applicable.

We will also be required to make sales-related milestone payments to MedImmune following commercialization up to an aggregate of $200.0 million for the achievement of specified levels of aggregate annual net sales of products containing half-life extended versions of antibodies directed to influenza A and/or influenza B.

MedImmune will also be entitled to receive tiered royalties based on net sales of products containing half-life extended versions of antibodies directed to influenza A and/or influenza B at percentages ranging from the mid-single-digits to sub-teen double-digits and a royalty based on net sales of products containing half-life extended versions of antibodies directed to any additional selected targets, if applicable, at a percentage in the low single-digits, in each case subject to specified reductions.

These royalties are payable, on a product-by-product and country-by-country basis, until the latest to occur of expiration of the last to expire valid claim covering such product in such country, expiration of regulatory exclusivity for such product in such country, and 12 years after the first commercial sale of such product in such country.

Additionally, we are responsible for paying any royalties due under the 2012 MedImmune Agreement as a result of our commercialization of products under the 2018 MedImmune Agreement.

The 2018 MedImmune Agreement will remain in force until the expiration on a country-by-country and product-by-product basis of all of our obligations to pay royalties to MedImmune.

We may terminate the 2018 MedImmune Agreement in its entirety or on a product-by-product basis, for convenience, upon 120 days’ notice.

Either party may terminate the 2018 MedImmune Agreement for cause for the other party’s uncured material breach on 60 days’ notice or immediately in the event of bankruptcy of the other party.

Additionally, MedImmune may terminate the 2018 MedImmune Agreement for cause on 30 days’ written notice if we challenge the validity or enforceability of the patents to which we have obtained a license under the 2018 MedImmune Agreement.

Master Exclusive License Agreement with OHSU

In June 2012, our subsidiary TomegaVax, Inc., or TomegaVax, entered into a master exclusive license agreement, or the OHSU Agreement, with Oregon Health & Science University, or OHSU.

The OHSU Agreement was revised and restated in August 2014 and again in August 2019, at which time we assumed TomegaVax’s rights and obligations as licensee under the OHSU Agreement.

Under the OHSU Agreement, we obtained a worldwide exclusive license under certain patent rights and a non-exclusive license under certain know-how to make, have made, use, offer to sell, sell, have sold and import certain products relating to CMV vectors in all fields of use.

The OHSU Agreement provides for us to include within the license grant additional patent or know-how rights covering certain inventions arising at OHSU and relating to the use of CMV vaccine vectors through the execution of technology addenda, each such addendum, a Technology Addendum.

Each Technology Addendum relates to one or more invention disclosures and their corresponding patent family or know-how rights.

During the term of the OHSU Agreement to date, we have entered into 17 such Technology Addenda.

We must use reasonably diligent efforts to develop and commercialize the CMV vector products consistent with its reasonable business practices and judgment, including by achieving certain specified development and regulatory milestones within certain periods.

We use technology licensed under the OHSU Agreement in our T cell platform and in our product candidate VIR-1111.

Pursuant to the initial entry into the OHSU Agreement and certain of the Technology Addenda, TomegaVax issued a specified percentage of its then outstanding common stock to OHSU, which was subsequently exchanged for shares of our common stock as a result of our acquisition of TomegaVax in September 2016.

In connection with the second revision and restatement of the OHSU Agreement in August 2019, we issued an additional specified number of shares of our common stock to OHSU.

We are obligated to pay OHSU up to $1.3 million upon the achievement of certain development and regulatory milestones for each CMV vector product, and up to $2.0 million upon the achievement of certain aggregate annual net sales milestones for all CMV vector products.

We will also be required to pay OHSU a royalty in the low single-digits on net sales of licensed products on a product-by-product basis, subject to specified reductions and offsets, and specified minimum annual royalty payments.

The royalties are payable, on a product-by-product and country-by-country basis, until the later of (a) the expiration of all valid claims in the licensed patents covering such product in the country of sale or country of manufacture, as applicable, and (b) 10 years after the first commercial sale of such product in the country of sale.

OHSU is also entitled to receive a specified percentage of any consideration received by us as a result of the grant of a sublicense under the rights granted under the OHSU Agreement, with the applicable percentage based on the development stage of the applicable program at the time of the grant of the sublicense.

The OHSU Agreement will remain in force until the expiration of all licensed patent rights or 10 years after the effective date of the last Technology Addendum, whichever is the later.

Each individual Technology Addendum remains in force until the expiration of the patent rights to which it applies, or 10 years after the effective date of such Technology Addendum, whichever is later.

Either party may terminate the OHSU Agreement, or any individual Technology Addendum, for the other party’s uncured material breach on 60 days’ written notice, which may be extended by an additional 120 days under certain conditions.

The OHSU Agreement and each Technology Addendum also terminate in the event of bankruptcy of either party.

We may also terminate the OHSU Agreement in its entirety, or any Technology Addendum individually, upon 60 days’ notice.

OHSU may immediately terminate the OHSU Agreement if we or our sublicensees bring any action or proceeding against OHSU, subject to certain exceptions.

Exclusive License Agreement with the Institute for Research in Biomedicine

In December 2011, Humabs Holdings GmbH, or Humabs Holdings, the former parent company of our subsidiary Humabs, entered into an exclusive license agreement, or the IRB Agreement, with the Institute for Research in Biomedicine, or IRB.

Prior to our acquisition of Humabs BioMed SA (referred to herein as Humabs) in August 2017, the former parent company of Humabs (later consolidated into Humabs) entered into an exclusive license agreement in December 2011 with the Institute for Research in Biomedicine (IRB, and the agreement, the IRB Agreement).

The IRB Agreement amended and restated an original 2004 exclusive license agreement between the parties in connection with IRB’s proprietary technologies relating to human monoclonal antibodies and the discovery of unique epitopes recognized by such antibodies.

In May 2008, Humabs entered into an exclusive license agreement with IRB, or the Humabs IRB Agreement, and together with the IRB Agreement, the Current IRB License Agreements.

In May 2008, Humabs entered into an exclusive license agreement with IRB (the Humabs IRB Agreement, and together with the IRB Agreement, the Current IRB License Agreements).

Pursuant to the Humabs IRB Agreement, IRB granted to Humabs an exclusive license under certain intellectual property rights for the development of certain monoclonal antibodies.

Following the entry into the Humabs IRB Agreement, in February 2012, Humabs and IRB entered into a research agreement, or the IRB Research Agreement, concurrently with the termination of an original research agreement dated July 2004 between Humabs Holdings and IRB, to provide for a continuing research collaboration between Humabs and IRB, and to coordinate the exploitation of intellectual property rights arising from the IRB Research Agreement with the rights granted under the Current IRB License Agreements.

In February 2012, Humabs and IRB entered into a research agreement, or the IRB Research Agreement, to provide for a continuing research collaboration between Humabs and IRB, and to coordinate the exploitation of intellectual property rights arising from the IRB Research Agreement with the rights granted under the Current IRB License Agreements.

Under the terms of the IRB Research Agreement, IRB performs certain research activities for Humabs, and all intellectual property rights arising under the IRB Research Agreement are either owned by Humabs, or included in and licensed to Humabs pursuant to the terms of the Current IRB License Agreements.

In August 2017, we acquired all of the share capital of Humabs as described further below.

Prior to the closing of such acquisition, Humabs Holdings was consolidated into Humabs, such that Humabs Holdings ceased to exist as a separate legal entity, and Humabs became the successor-in-interest to Humabs Holdings’ rights under the IRB Agreement.

As a result, Humabs is the licensee under each of the Current IRB License Agreements.

We use technology licensed under the Current IRB License Agreements in our antibody platform and in our product candidates VIR-2482 and tobevibart.

We use technology licensed under the Current IRB License Agreements in our antibody platform and in our product candidate tobevibart.

Pursuant to the Current IRB License Agreements, IRB granted to Humabs an exclusive, worldwide, royalty-bearing, sublicensable license under patent and know-how rights covering or associated with IRB’s proprietary technology platform relating to antibody discovery, as well as rights in certain antibodies, including as a result of activities under the IRB Research Agreement, in each case for all purposes, including to practice the licensed technology platform, and to develop, manufacture and commercialize any drug, vaccine or diagnostic product containing such licensed antibodies.

Humabs is required to use commercially reasonable efforts to develop and commercialize licensed products, and must maintain an active program to commercialize licensed products.

Humabs is required to use commercially reasonable efforts to develop and commercialize licensed products, as well as maintain an active program to commercialize licensed products.

Humabs is required to pay to IRB a flat royalty on net sales of licensed products approved for non-diagnostic use in the low single-digits, and a flat royalty on licensed products for diagnostic use at 50% of the non-diagnostic product rate, in each case subject to standard reductions and offsets.

A single royalty stream is payable on products that include the licensed antibodies (including antibodies that are owned by Humabs, but developed using the licensed technology), irrespective of whether a given product is covered by patents under both of the Current IRB License Agreements.

Humabs’ obligation to pay royalties to IRB, on a country-by-country basis, is reduced upon the expiration of the relevant patents in such country, and expires 10 years after the date of first commercialization of a licensed product in such country.

Humabs is also required to pay to IRB a specified percentage in the sub-teen double-digits of consideration received in connection with the grant of a sublicense to a non-affiliate third party, subject to a specified maximum dollar amount for the first up front or milestone payment received under such sublicense for each licensed product, and a lower specified maximum dollar amount for subsequent up front or milestone payments for such licensed product.

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Pursuant to the Rockefeller Agreement, we are required to use commercially reasonable efforts to develop and commercialize infectious disease products as soon as reasonably practicable, including by achieving certain specified development milestone events within specified time periods for products arising from our HBV and influenza programs.

We use technology licensed under the Rockefeller Agreement in our antibody platform and in our product candidates tobevibart.

We paid Rockefeller an upfront fee of $0.3 million for entry into the Rockefeller Agreement, and are required to pay annual license maintenance fees of $1.0 million, which will be creditable against royalties following commercialization.

In addition, for the achievement of specified development, regulatory and commercial success milestone events, we will be required to pay up to $80.3 million, in the aggregate, for up to six infectious disease products.

We use technology licensed under the Rockefeller Agreement in our antibody platform and in our product candidate tobevibart.

Under the agreement we are required to pay annual license maintenance fees of $1.0 million, which will be creditable against royalties following commercialization.

In addition, for the future achievement of specified development, regulatory and commercial success milestone events, we will be required to pay up to $80.3 million, in the aggregate, for up to six infectious disease products.

Any follow-on products beyond six products may result in additional milestone event payments.

We will also be required to pay to Rockefeller a tiered royalty at a low single-digit percentage rate on net sales of licensed products, subject to certain adjustments.

We will also be required to pay Rockefeller a tiered royalty at a low single-digit percentage rate on net sales of licensed products, subject to certain adjustments.

Our obligation to pay royalties to Rockefeller will terminate, on a product-by-product and jurisdiction-by-jurisdiction basis, upon the latest of the expiration of the last valid claim of a licensed patent in such jurisdiction, the expiration of all regulatory exclusivity in such jurisdiction or 12 years following the first commercial sale of the applicable licensed product in such jurisdiction.

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Collaboration, Option and License Agreement with Brii Bio

In May 2018, we entered into a collaboration, option and license agreement with Brii Biosciences Limited (previously named BiiG Therapeutics Limited), or Brii Bio Parent, and Brii Bio, and such agreement, the Brii Agreement, pursuant to which we granted to Brii Bio, with respect to up to four of our programs (excluding mAbs in Vir’s active research and development program against coronaviruses), an exclusive option to obtain exclusive rights to develop and commercialize compounds and products arising from such programs in China, Taiwan, Hong Kong and Macau, or collectively the China Territory, for the treatment, palliation, diagnosis, prevention or cure of acute and chronic diseases of infectious pathogen origin or hosted by pathogen infection, or the Field of Use.

Our HBV siRNA program being developed under the Amended Alnylam Agreement (described above) is included within the Brii Agreement as a program for which Brii Bio may exercise one of its options.

In May 2018, we entered into a collaboration, option and license agreement with Brii Biosciences Limited (Brii Bio Parent) (formerly known as BiiG Therapeutics Limited), and Brii Bio (and such agreement, the Brii Agreement), pursuant to which we granted to Brii Bio, with respect to up to four of our programs, an exclusive option to obtain exclusive rights to develop and commercialize compounds and products arising from such programs in the China Territory (People’s Republic of China, Taiwan, Hong Kong and Macau), for the treatment, palliation, diagnosis, prevention or cure of acute and chronic diseases of infectious pathogen origin or hosted by pathogen infection, or the Field of Use.

Our elebsiran program being developed under the Amended Alnylam Agreement (described above) is included within the Brii Agreement as a program for which Brii Bio has exercised one of its options that is further discussed below.

Brii Bio may exercise each of its options following the achievement by us of proof of concept for the first product in such program.

In partial consideration for the options granted by us to Brii Bio, Brii Bio Parent and Brii Bio granted us, with respect to up to four of Brii Bio Parent’s or Brii Bio’s programs, an exclusive option to be granted exclusive rights to develop and commercialize compounds and products arising from such Brii Bio programs in the United States for the Field of Use.

The number of options that we may exercise for a Brii Bio program is limited to the corresponding number of options that Brii Bio exercises for a Vir program.

All options granted to Brii Bio under the Brii Agreement that are not exercised will expire no later than seven years following the effective date, or two years earlier than such date if Brii Bio has not undergone an initial public offering within such shorter period.

The number of options that we may exercise for a Brii Bio program is limited to the corresponding number of options that Brii Bio exercises for a VirBio program.

All options granted to Brii Bio under the Brii Agreement that are not exercised will expire no later than seven years following the effective date.

All options granted to us under the Brii Agreement that are not exercised will expire no later than two years following the expiration of all options granted to Brii Bio.

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If Brii Bio exercises its option with respect to our development program being conducted under the Amended Alnylam Agreement, Brii Bio’s rights will be subject to the terms of such amended agreement.

Under the terms of the Brii Agreement, following our option exercise, we are obligated to use commercially reasonable efforts to develop at least one licensed product arising from each optioned Brii Bio program, and to commercialize each such product in the United States following regulatory approval, and following Brii Bio’s option exercise, Brii Bio is obligated to use commercially reasonable efforts to develop at least one licensed product arising from each optioned Vir program and to commercialize each such product in the China Territory following regulatory approval.

With respect to programs for which Brii Bio exercises its options, Brii Bio will be required to pay us an option exercise fee for each such Vir program ranging from the mid-single-digit millions up to $20.0 million, determined based on the commercial potential of the licensed program.

Under the terms of the Brii Agreement, following our option exercise, we are obligated to use commercially reasonable efforts to develop at least one licensed product arising from each optioned Brii Bio program, and to commercialize each such product in the United States following regulatory approval, and following Brii Bio’s option exercise, Brii Bio is obligated to use commercially reasonable efforts to develop at least one licensed product arising from each optioned VirBio program and to commercialize each such product in the China Territory following regulatory approval.

With respect to programs for which Brii Bio exercises its options, Brii Bio will be required to pay us an option exercise fee for each such VirBio program ranging from the mid-single-digit millions up to $20.0 million, determined based on the commercial potential of the licensed program.

Brii Bio will also be required to pay regulatory milestone payments on a licensed product-by-licensed product basis ranging from the mid-single-digit millions up to $30.0 million, also determined based on the commercial potential of such program.

Following commercialization, Brii Bio will be required to make sales milestone payments based on certain specified levels of aggregate annual net sales of products arising from each licensed program in the China Territory, up to an aggregate of $175.0 million per licensed program.

Brii Bio also will pay us royalties that range from the mid-teens to the high-twenties, as described below.

Brii Bio also will pay us royalties that range from the mid-teens to the high-twenties.

On June 12, 2020, Brii Bio notified us of the exercise of its option to obtain exclusive rights to develop and commercialize compounds and products arising from elebsiran in the China Territory.

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Brii Bio paid us a $20.0 million option exercise fee in connection with the option exercise.

We are also eligible to receive the following payments related to tobevibart in the China Territory:

a $30.0 million regulatory milestone payment, up to $175.0 million in sales-based milestone payments, and royalties on net sales ranging from mid-teens to mid-twenties.

As partial consideration for our entry into the Brii Agreement, upon closing of Brii Bio Parent’s Series A preferred stock financing, we received Class A ordinary shares equal to 9.9% of the outstanding shares in Brii Bio Parent.

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Upon completion of the Brii Bio Parent IPO, our Class A ordinary shares held at Brii Bio Parent converted into the same single class of ordinary shares issued in the Brii Bio Parent IPO.

Upon exercise of each option for a Brii Bio program, we will be required to pay to Brii Bio an option exercise fee ranging from the low tens of millions to up to $50.0 million, determined based on the commercial potential of the licensed program.

In the event that we exercise an option for a Brii Bio program, we will be required to pay to Brii Bio an option exercise fee ranging from the low tens of millions to up to $50.0 million, determined based on the commercial potential of the licensed program.

We will be required to make regulatory milestone payments to Brii Bio on a licensed product-by-licensed product basis ranging from the low tens of millions up to $100.0 million, also determined based on the commercial potential of such program.

We will also be required to make sales milestone payments based on certain specified levels of aggregate annual net sales of products in the United States arising from each licensed program, up to an aggregate of $175.0 million per licensed program.

In addition, we are obligated under the Brii Agreement to pay Brii Bio tiered royalties based on net sales of products arising from the licensed programs in the United States, and Brii Bio is obligated to pay us tiered royalties based on net sales of products arising from the licensed programs in the China Territory.

In addition, we are obligated under the Brii Agreement to pay Brii Bio tiered royalties based on net sales of products arising from the programs licensed to VirBio in the United States, and Brii Bio is obligated to pay us tiered royalties based on net sales of products arising from the programs licensed to Brii Bioin the China Territory.

The rates of royalties payable by us to Brii Bio, and by Brii Bio to us on net sales range from mid-teens to high-twenties.

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We are obligated to use commercially reasonable efforts to develop and commercialize an antibody product that incorporates Xencor’s licensed technologies, for each of the influenza A and HBV research programs.

These technologies are used in our VIR-2482, incorporating Xencor’s Xtend technology, and tobevibart, incorporating Xencor’s Xtend and other Fc technologies.

These technologies are used in tobevibart, incorporating Xencor’s Xtend.

In consideration for the grant of the license, we paid Xencor an upfront fee.

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We are obligated to use commercially reasonable efforts to develop and commercialize an antibody product that incorporates Xencor’s licensed technologies, for each of the coronavirus research programs.

These technologies are used in sotrovimab, incorporating Xencor’s Xtend technology, and VIR-7832, incorporating Xencor’s Xtend and other Fc technologies.

These technologies are used in sotrovimab, incorporating Xencor’s Xtend technology.

In consideration for the grant of the license, we are obligated to pay royalties based on net sales of licensed products at the mid-single-digits.

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Xencor may terminate each agreement immediately upon written notice if we challenge, or upon 30 days’ written notice if any of our sublicensees challenge, the validity or enforceability of any patent licensed to us under each respective agreement.

Amended and Restated Letter Agreement with the Bill & Melinda Gates Foundation

In January 2022, we entered into an amended and restated letter agreement with the Bill & Melinda Gates Foundation, or the Gates Agreement, which amended and restated the letter agreement with the Bill & Melinda Gates Foundation that we entered into in December 2016.

In connection with the Gates Agreement, the Bill & Melinda Gates Foundation purchased $10.0 million of shares of our Series A-1 convertible preferred stock in December 2016, $10.0 million of shares of our Series B convertible preferred stock in January 2019 and $40.0 million of shares of our common stock in January 2022.

We were obligated to use the proceeds of the Bill & Melinda Gates Foundation’s December 2016 and January 2019 investments in furtherance of its charitable purposes to (i) conduct our programs to develop products to treat or prevent infectious disease caused by HIV and TB, respectively, with at least 50% of the funds to be used for such programs and (ii) develop our HCMV-based vaccine technology platform in a manner reasonably expected to result in the generation of products for the treatment or prevention of other specified infectious diseases, and we are obligated to use the proceeds of the Bill & Melinda Gates Foundation’s January 2022 investment in furtherance of its charitable purposes to develop our vaccinal antibody program, in each case for use in specified developing countries.

We agreed to use reasonable efforts to achieve specified research and development milestones with respect to our HIV program, TB program and vaccinal antibody program, and, if requested by the Bill & Melinda Gates Foundation, to work with the Bill & Melinda Gates Foundation on an additional mutually agreeable infectious disease program.

Additionally, we are bound by specified global access commitments including a commitment to provide any products developed using the proceeds of the Bill & Melinda Gates Foundation’s investment at an affordable price to the people most in need within the specified developing countries, not to exceed a specified percentage over our fully burdened manufacturing and sales costs.

If we fail to comply with (i) our obligations to use the proceeds of the Bill & Melinda Gates Foundation’s investment for the purposes described in the paragraph above and to not use such proceeds for specified prohibited uses, (ii) specified reporting requirements or (iii) specified applicable laws, or if we materially breach our specified global access commitments (any such failure or material breach, a Specified Default), we will be obligated to redeem or arrange for a third party to purchase all of our stock purchased by the Bill & Melinda Gates Foundation under the Gates Agreement at the Bill & Melinda Gates Foundation’s request, at a price equal to the greater of (a) the original purchase price or (b) the fair market value, such redemption or sale, a Gates Foundation Redemption.

Following a Gates Foundation Redemption, if a sale of the company or all of our material assets relating to the Gates Agreement occurs prior to the six month anniversary of the first redemption or sale of any stock in such Gates Foundation Redemption, then the Bill & Melinda Gates Foundation will receive compensation equal to the excess of what it would have received in such transaction if it still held the stock redeemed or sold at the time of such sale transaction over what it actually received in the Gates Foundation Redemption.

Additionally, if a specified default occurs, if we are unable or unwilling to continue the HIV program, TB program, vaccinal antibody program or, if applicable, the mutually agreed additional program (except for scientific or technical reasons), or if we institute bankruptcy or insolvency proceedings, then the Bill & Melinda Gates Foundation will have the right to exercise a non-exclusive, fully-paid license (with the right to sublicense) under our intellectual property to the extent necessary to use, make and sell products arising from such programs, in each case solely to the extent necessary to benefit people in the developing countries in furtherance of the Bill & Melinda Gates Foundation’s charitable purpose.

In the event that we sell, exclusively license or transfer to a third party all or substantially all of our assets, the technology platform, or products arising from programs that are funded using the proceeds of the Bill & Melinda Gates Foundation’s investment, such third party is required to assume our specified global access commitments on terms that are reasonably acceptable to the Bill & Melinda Gates Foundation.

Additionally, we will not grant to any third party any rights or enter into any agreement with any third party that would restrict the Bill & Melinda Gates Foundation’s rights with respect to our specified global access commitments unless such third party expressly assumes such commitments to the reasonable satisfaction of the Bill & Melinda Gates Foundation.

Consistent with the foregoing restriction, we also specifically will not enter into any such agreement negotiated in connection with a decision by us not to pursue the technology platform controlled by us as a result of our acquisition of TomegaVax.

The global access commitments will continue for as long as the Bill & Melinda Gates Foundation continues to be a charitable entity.

In connection with the purchase of $40.0 million of shares of our common stock in January 2022, we entered into a stock purchase agreement, or the Gates Stock Purchase Agreement, with the Bill & Melinda Gates Foundation.

The Bill & Melinda Gates Foundation purchased the shares of our common stock at $45.38 price per share, which is the average of the volume weighted average price of a share of our common stock for the 30 trading day period prior to the date of the Gates Stock Purchase Agreement.

We have agreed to register the shares for resale following expiration of the one-year lock-up period if Rule 144 under the Securities Act of 1933, as amended, is not available for such resale without any volume or manner of sale restrictions.

Separately, in January 2018, March 2018 and January 2022, we entered into three grant agreements with the Bill & Melinda Gates Foundation, pursuant to which the Bill & Melinda Gates Foundation agreed to grant additional funding to us for our HIV, TB and vaccinal antibody programs, respectively, through the award of three research grants totaling in the aggregate up to $12.2 million with respect to the HIV program, up to $14.9 million with respect to the TB program, and up to $10.0 million with respect to the vaccinal antibody program if we achieve all the specified research and development milestones or reporting deliverables under the grants.

In February 2020, we amended the HIV grant agreement pursuant to which we were awarded with a supplemental grant of $8.6 million.

In addition, the term of the HIV grant agreement was extended through October 31, 2022, and we entered another amendment in September 2022 to further extend the term through September 2023.

The TB grant agreement remained in effect until March 31, 2022 and was amended to extend the term through December 31, 2023 and we entered another amendment in January 1, 2024 to further extend the term through September 30, 2024.

As of December 31, 2023, we had received all funding with respect to the HIV, TB and vaccinal antibody programs.

In November 2021, we entered into a grant agreement with the Bill & Melinda Gates Foundation under which we were awarded a grant totaling up to $10.0 million to support the manufacturing and clinical activities of our HIV and TB vaccine programs.

The grant agreement remained in effect until August 30, 2023 and was amended to extend the term through December 31, 2023 and we entered another amendment on January 1, 2024 to further extend the term through June 30, 2024.

As of December 31, 2023, we had received all funding under this grant agreement.

In March 2023, we entered into a grant agreement with the Bill & Melinda Gates Foundation under which we were awarded a grant totaling up to $10.0 million to support the clinical activities of our HIV vaccine program.

This grant agreement will remain in effect until June 30, 2027.

As of December 31, 2023, we had received $3.5 million under this grant agreement.

In September 2023, we entered into a grant agreement with the Bill & Melinda Gates Foundation under which we were awarded a grant totaling up to $5.0 million to support the manufacturing activities of our HIV vaccine program.

This grant agreement will remain in effect until December 31, 2025.

As of December 31, 2023, we had received $1.9 million under this grant agreement.

The grant agreements may be terminated early by the Bill & Melinda Gates Foundation for our breach, failure to progress the applicable funded projects, in the event of our change of control, change in our tax status, or significant changes in our leadership that the Bill & Melinda Gates Foundation reasonably believes may threaten the success of the applicable project.

Amended and Restated Letter Agreement with the Gates Foundation

In January 2022, we entered into an amended and restated letter agreement with the Gates Foundation (formerly known as the Bill & Melinda Gates Foundation, and the agreement, the Gates Agreement), which amended and restated the original letter agreement with the Gates Foundation that we entered into in December 2016.

In connection with the Gates Agreement, the Gates Foundation purchased $10.0 million of shares of our Series A-1 convertible preferred stock in December 2016, $10.0 million of shares of our Series B convertible preferred stock in January 2019 and $40.0 million of shares of our common stock in January 2022.

We were obligated to use the proceeds of the Gates Foundation’s December 2016 and January 2019 investments in furtherance of its charitable purposes to (i) conduct our programs to develop products to treat or prevent infectious disease caused by HIV and tuberculosis, or TB, respectively, with at least 50% of the funds to be used for such programs and (ii) develop our HCMV-based vaccine technology platform in a manner reasonably expected to result in the generation of products for the treatment or prevention of other specified infectious diseases, and we were obligated to use the proceeds of the Gates Foundation’s January 2022 investment in furtherance of its charitable purposes to develop our vaccinal antibody program, in each case for use in specified developing countries.

Additionally, we are bound by specified global access commitments including a commitment to provide any products developed using the proceeds of the Gates Foundation’s investment at an affordable price to the people most in need within the specified developing countries, not to exceed a specified percentage over our fully burdened manufacturing and sales costs.

If we fail to comply with (i) our obligations to use the proceeds of the Gates Foundation’s investment for the purposes described in the paragraph above and to not use such proceeds for specified prohibited uses, (ii) specified reporting requirements or (iii) specified applicable laws, or if we materially breach our specified global access commitments (any such failure or material breach, a Specified Default), we will be obligated to redeem or arrange for a third party to purchase all of our stock purchased by the Gates Foundation under the Gates Agreement at the Gates Foundation’s request, at a price equal to the greater of (a) the original purchase price or (b) the fair market value, such redemption or sale, a Gates Foundation Redemption.

Following a Gates Foundation Redemption, if a sale of the company or all of our material assets relating to the Gates Agreement occurs prior to the six month anniversary of the first redemption or sale of any stock in such Gates Foundation Redemption, then the Gates Foundation will receive compensation equal to the excess of what it would have received in such transaction if it still held the stock redeemed or sold at the time of such sale transaction over what it actually received in the Gates Foundation Redemption.

Additionally, if a specified default occurs, if we are unable or unwilling to continue the HIV program, TB program, vaccinal antibody program or, if applicable, the mutually agreed additional program (except for scientific or technical reasons), or if we institute bankruptcy or insolvency proceedings, then the Gates Foundation will have the right to exercise a non-exclusive, fully-paid license (with the right to sublicense) under our intellectual property to the extent necessary to use, make and sell products arising from such programs, in each case solely to the extent necessary to benefit people in the developing countries in furtherance of the Gates Foundation’s charitable purpose.

In the event that we sell, exclusively license or transfer to a third party all or substantially all of our assets, the technology platform, or products arising from programs that are funded using the proceeds of the Gates Foundation’s investment, such third party is required to assume our specified global access commitments on terms that are reasonably acceptable to the Gates Foundation.

Additionally, we will not grant to any third party any rights or enter into any agreement with any third party that would restrict the Gates Foundation’s rights with respect to our specified global access commitments unless such third party expressly assumes such commitments to the reasonable satisfaction of the Gates Foundation..

The global access commitments will continue for as long as the Gates Foundation continues to be a charitable entity.

The Gates Foundation purchased the shares of our common stock at $45.38 price per share.

In relation to the agreements discussed above, we have entered into various grant agreements with the Gates Foundation, to support our HIV vaccine program, TB vaccine program, HIV vaccinal antibody program and malaria vaccinal antibody program.

The term of the grant agreements will expire at various dates through June 2027.

The grant agreements may be terminated early by the Gates Foundation for our breach, failure to progress the applicable funded projects, in the event of our change of control, change in our tax status, or significant changes in our leadership that the Gates Foundation reasonably believes may threaten the success of the applicable project.

As of December 31, 2024, the Company had deferred revenue of $11.1 million, related to the grants with the Gates Foundation and $11.6 million within accrued and other liabilities, which may need to be refunded to the Gates Foundation.

In August 2024, we announced a strategic realignment that included phasing out certain research programs which include programs associated with the grant agreements for the HCMV-based vaccine technology platform, which includes the HIV vaccine program and the TB vaccine program, but excludes the HIV vaccinal antibody program.

Biomedical Advanced Research and Development Authority

On September 28, 2022, Vir entered into a multi-year agreement under Other Transaction Authority (OTA) with the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S.

Department of Health and Human Services’ (HHS) Administration for Strategic Preparedness and Response (ASPR), with the potential for up to $1.0 billion to advance the development of a full portfolio of innovative solutions to address influenza and potentially other infectious disease threats.

BARDA initially invested $55.0 million for the development of VIR-2482, an investigational prophylactic monoclonal antibody (mAb) designed to protect against seasonal and pandemic influenza, with the balance of the award subject to BARDA exercising up to 12 options in further support of the development of pre-exposure prophylactic antibodies including and beyond VIR-2482 for the prevention of influenza illness or possibly supporting medical countermeasures for other pathogens of pandemic potential.

The BARDA agreement also outlines potential support for Vir’s clinical development of additional future pandemic influenza mAbs, as well as the potential development of up to 10 emerging infectious disease or Chemical, Biological, Radiological, and Nuclear medical countermeasure candidates.

On September 28, 2023, BARDA awarded Vir approximately $50.1 million in new funding to advance the development of novel monoclonal antibody (mAb) candidates and delivery solutions to widen the applicability of mAbs in COVID-19 and in pandemic preparedness and response.

On September 28, 2022, VirBio entered into a multi-year agreement under Other Transaction Authority (OTA) with the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S.

Department of Health and Human Services’ (HHS) Administration for Strategic Preparedness and Response, with the potential for up to $1.0 billion to advance the development of a full portfolio of innovative solutions to address influenza and potentially other infectious disease threats.

BARDA initially invested $55.0 million for the development of VIR-2482, an investigational prophylactic mAb designed to protect against seasonal and pandemic influenza, with the balance of the award subject to BARDA exercising up to 12 options in further support of the development of pre-exposure prophylactic antibodies including and beyond VIR-2482 for the prevention of influenza illness or possibly supporting medical countermeasures for other pathogens of pandemic potential.

The BARDA agreement also outlines potential support for VirBio’s clinical development of additional future pandemic influenza mAbs, as well as the potential development of up to 10 emerging infectious disease or Chemical, Biological, Radiological, and Nuclear medical countermeasure candidates.

On September 28, 2023, BARDA awarded VirBio approximately $50.1 million in new funding to advance the development of novel mAb candidates and delivery solutions to widen the applicability of mAbs in COVID-19 and in pandemic preparedness and response.

The new funding will support research and development of novel alternative mAb delivery technologies that have the potential to revolutionize mAb delivery by increasing expression relative to existing technologies.

Such delivery could widen the breadth of administration options and shorten development and manufacturing timelines.

This new investment falls under Vir’s existing OTA.

This new investment falls under VirBio’s existing OTA.

The balance of the potential remaining funding is subject to BARDA exercising up to 12 options in further support of the development of pre-exposure prophylactic antibodies for the prevention of influenza illness or supporting medical countermeasures for other pathogens of pandemic potential.

$40 million of the total funds is part of ‘Project NextGen,’ an initiative by the HHS to advance a pipeline of new, innovative vaccines and therapeutics for COVID-19 and will support the development of VIR-7229 through Phase 1 in the context of developing alternative mAb delivery technologies.

The Phase 1 trial is expected to be completed in the second half of 2025.

$10.1 million of the total funds falls under support from the Division of Chemical, Biological, Radiological and Nuclear (CBRN) medical countermeasures of BARDA which will support the discovery of new mAbs against a second pathogen of pandemic potential in the context of further advancing alternative mAb delivery technologies.

Vir was also awarded approximately $11.0 million in additional BARDA funding that will be applied to wind down activities for the BARDA-supported Phase 2 PENINSULA trial evaluating the investigational prophylactic mAb VIR-2482 for the prevention of symptomatic influenza A illness.

As of December 31, 2023, we have utilized a total of $59.8 million under this grant agreement.

VirBio was also awarded approximately $11.0 million in additional BARDA funding that was applied to wind down activities for the BARDA-supported Phase 2 pre-exposure prophylaxis trial of VIR-2482.

In September 2024, we and BARDA entered into Amendment No.

P00003 to the BARDA Agreement, pursuant to which the parties agree to partially de-obligate certain funds from two of the exercised options related to the development of VIR-7229.

Under this Amendment the current BARDA commitment was decreased by $42.1 million.

On October 25, 2024, we notified BARDA of intent to terminate the OTA on December 31, 2024.

All remaining funds were de-obligated upon the date of termination.

Sales and Marketing

Given our stage of development, we have not yet established a commercial organization or distribution capabilities.

We intend to build a commercial infrastructure to support sales of our product candidates.

Given our stage of development, we have not yet established a meaningful commercial (sales or marketing) organization, nor distribution capabilities.

We intend to build a commercial infrastructure to support the sales and marketing of our product candidates.

We expect to manage sales, marketing and distribution through internal resources and third-party relationships.

While we may commit significant financial and management resources to commercial activities, we will also consider collaborating with one or more pharmaceutical companies to enhance our commercial capabilities.

While we may commit significant financial and management resources to commercial activities, we will also consider collaborating with one or more biopharmaceutical companies to enhance our commercial capabilities.

Manufacturing

We manufacture product candidates for three therapeutic modalities:

mAbs, T cells and siRNA.

We have established our own internal process development, manufacturing, supply chain and quality capabilities organizations that work with our selected contract development and manufacturing organizations, or CDMOs, to develop, manufacture, test and supply our early- and late-stage product candidates developed with our proprietary and external technology platforms.

Contract development and manufacturing of our antibody product candidates is supported by our San Francisco, California, laboratory for cell line development, process, analytical and formulation development, small-scale non-GMP manufacturing for preclinical studies and selected quality control testing.

For our human cytomegalovirus (HCMV) product candidates, our in-house capabilities for early-stage process development and HCMV research viral seed stock production will be transferred to a CDMO upon closure of our Portland, Oregon laboratory in 2024.

mAbs, masked TCEs and siRNA.

We have established our own internal process, analytical and pharmaceutical development, manufacturing, supply chain and quality organizations that work with our selected CDMOs, to develop, manufacture, test and supply our early- and late-stage product candidates developed with our proprietary and external technology platforms.

Contract development and manufacturing of our antibody, TCE and siRNA product candidates is supported at our San Francisco, California, corporate headquarters for process, analytical and formulation development, small-scale non-GMP manufacturing for preclinical studies and selected quality control testing.

Our headquarters also conducts cell line development for our antibody and TCE product candidates.

We have established relationships with multiple CDMOs and have produced material to support preclinical studies and Phase 1, Phase 2 and Phase 3 clinical trials.

Material for any Phase 3 clinical trials and commercial supply will generally require large-volume, low-cost-of-goods production.

For example, for our COVID-19 product sotrovimab, we and our collaborator GSK executed manufacturing agreements with CDMOs having large-scale capacity to support future production and product supply, particularly for commercialization.

However, there are no assurances that our manufacturing and supply chain infrastructure will remain uninterrupted and reliable, or that the third parties we rely on to manufacture our products will be able to satisfy demand in a timely manner or not have supply chain disruptions due to future COVID-19 or other pandemic-related shutdowns, stock-outs due to raw material shortages, extended lead times, and/or greater than anticipated demand or quality issues given the operational challenges and raw material shortages that had been experienced during the COVID-19 pandemic.

Manufacturing Technology Platforms

We currently rely on the antibody process platforms and manufacturing facilities of our CDMOs and strategic collaborators for development, manufacturing and supply of all of our preclinical, clinical and future commercial mAb product candidates.

We currently leverage the antibody process platforms and manufacturing facilities of our CDMOs and strategic collaborators for development, manufacturing and supply of our preclinical, clinical and future commercial mAb product candidates.

These manufacturing platforms are based on mAb technology and industrial processes that have been optimized, standardized and well-established across the biopharmaceutical industry over the last 30 years to enable process portability between biomanufacturing facilities and manufacturing with high success rates at most biologic CDMOs, as well as the partnered use of excess capacity with other biopharmaceutical companies.

Contract development and manufacturing of our antibody product candidates is supported by our San Francisco, California laboratory for analytical and formulation development, and selected quality control testing.

In 2023, we completed the build-out of additional in-house capabilities in our San Francisco laboratory for mAb cell line development, Phase 1/2 process development, and small-scale drug substance and drug product manufacturing to produce non-GMP material for preclinical studies.

Start-up of our new process development laboratory is anticipated in 2024.

T Cell Viral Vector

Our T cell based viral vector manufacturing platform is based on genetically engineered HCMV.

We have attenuated the HCMV for the purpose of patient safety, but this attenuation also reduces its yield in production.

We have established a reproducible current Good Manufacturing Practices, or cGMP, manufacturing process in support of Phase 1 and Phase 2 clinical trials with the support of the Bill & Melinda Gates Foundation that has been successfully transferred to and executed at CDMOs specializing viral vector-based manufacturing.

We will rely on these CDMOs for manufacturing and supply of all clinical and future commercial HCMV product candidates.

To further improve manufacturing efficiency and scale-up, we continue to make significant investments in process development, largely funded by the Bill & Melinda Gates Foundation.

Our in-house capabilities for HCMV early-stage process development and research viral seed stock (RSS) production will be transferred to a CDMO upon closure of our Portland, Oregon laboratory expected in the third quarter of 2024.

In 2023, we completed the build-out of additional in-house capabilities in our San Francisco headquarters for mAb cell line development, Phase 1/2 process development, and small-scale drug substance and drug product manufacturing to produce non-GMP material for preclinical studies.

Our new process development laboratory was successfully brought on line in 2024.

T-Cell Engager - PRO-XTEN ™

We have also established process, analytical and formulation development capabilities for our E.

coli -derived TCEs in our San Francisco facility.

Similar to our antibody programs, we leverage on the E.coli process platforms and manufacturing facilities of our CDMOs and strategic collaborators for further development and optimization, manufacturing and supply of our preclinical, clinical and future E.coli TCE product candidates.

The manufacturing processes for TCE drug substances (DS) and drug products (DP) have been developed by our scientists based on established E.

coli manufacturing technology and pharmaceutical industrial processes that have been optimized, standardized and well-established across the biopharmaceutical industry for other biologics.

VirBio licensed and conducted a technology transfer of the siRNA DS and DP process for Elebsiran.

Similarly, we rely on the siRNA process platforms and manufacturing facilities of our CDMOs and strategic collaborators for further development, optimization, manufacturing and supply of our siRNA product candidate.

Manufacturing Agreements

We have entered into the following manufacturing agreements to date in support of our COVID-19 and clinical programs:

COVID-19 - Letter Agreement, Assignment and Master Services Agreement with Samsung Biologics

In April 2020, we entered into a binding letter agreement with Samsung Biologics Co., Ltd.

(“Samsung Biologics”) pursuant to which Samsung Biologics will perform process development and manufacturing services for our SARS-CoV-2 mAbs.

Under the terms of the letter agreement, we had committed to purchase a firm and binding capacity reservation for a specified number of drug substance manufacturing slots in 2021 and 2022.

Samsung Biologics will reserve such manufacturing slots on a non-cancellable, non-adjustable basis and will not offer such manufacturing slots under our capacity reservation to third parties.

We were obligated to pay a total of approximately $362.0 million for such capacity reservation on a take-or-pay basis regardless of whether such manufacturing slots are utilized by us, subject to annual adjustment based on the Korean Consumer Price Index.

The amounts were to be payable during 2021 and 2022 and invoiced on a per-batch basis, with shortfalls invoiced at the end of the year in which such shortfall occurs.

In August 2020, we entered into an Assignment and Novation Agreement with GlaxoSmithKline Trading Services Limited, or GSKTSL, and Samsung Biologics effective as of July 31, 2020 pursuant to which we assigned and transferred to GSKTSL all of our right, title, and interest in, to and under the letter agreement, and GSKTSL became our successor in interest in and to all of our rights, duties, and obligations in, to and under the letter agreement.

On August 4, 2020, GSKTSL entered into a Master Services Agreement with Samsung Biologics effective as of July 31, 2020, or the Samsung Biologics MSA, thereby superseding the letter agreement, and pursuant to which, among other things, Samsung Biologics will perform technology transfer, development, and manufacturing services for clinical and commercial supply of antibody products under our SARS-CoV-2 antibody program.

GSKTSL entered into the Samsung Biologics MSA in connection with the performance of GSK and our obligations pursuant to the 2020 GSK Agreement.

In accordance with the terms of the 2020 GSK Agreement, we will continue to be responsible for 72.5% of the costs under the Samsung Biologics MSA, and GSK will bear 27.5% of such costs under the Samsung Biologics MSA, subject to certain conditions and exceptions.

All outstanding amounts related to these agreements between Vir and GSK were settled and paid during 2023.

As of August 8, 2022, Samsung Biologics has completed all planned technology transfer, development, and manufacturing services for clinical and commercial supply of the SARS-CoV-2 antibody under the terms of the Samsung Biologics MSA and GSKTSL.

COVID-19 - Development and Manufacturing Collaboration Agreement with WuXi Biologics

In February 2020, we entered into a development and manufacturing collaboration agreement with WuXi Biologics (Hong Kong) Limited (“WuXi Biologics”), or the WuXi Biologics Collaboration Agreement, for the clinical development, manufacturing, and commercialization of our proprietary antibodies developed for SARS-CoV-2.

Under the WuXi Biologics Collaboration Agreement, WuXi Biologics conducted cell-line development, process and formulation development, and initial manufacturing for clinical development.

WuXi Biologics had the right to commercialize products incorporating such SARS-CoV-2 antibodies in mainland China, Hong Kong, Macau and Taiwan pursuant to an exclusive license granted for the selected SARS-CoV-2 antibodies that were developed.

We had the right to commercialize such products in all other markets worldwide.

On May 16, 2022, we and WuXi Biologics entered into a Termination Agreement, or the Termination Agreement, pursuant to which we and WuXi Biologics terminated the WuXi Biologics Collaboration Agreement.

Other existing agreements between us and WuXi Biologics remain in effect.

Under the terms of the Termination Agreement, all licenses granted under the WuXi Biologics Collaboration Agreement were terminated and all rights to the SARS-CoV-2 antibody products in mainland China, Hong Kong, Macau and Taiwan reverted to us.

We made a one-time termination payment to WuXi Biologics of $7.0 million in consideration for WuXi Biologics’ development activities under the WuXi Biologics Collaboration Agreement.

Under the terms of the Termination Agreement, we are obligated to pay WuXi Biologics tiered royalties on net sales of sotrovimab in mainland China, Hong Kong, Macau and Taiwan ranging from low single digits to low double digits.

Royalties are payable to WuXi Biologics for a specified royalty term and are subject to reduction in certain circumstances.

COVID-19 - Letter Agreement, Assignment and Master Services Agreement with WuXi Biologics

In June 2020, we entered into a binding letter of intent with WuXi Biologics, or WuXi Biologics Letter of Intent, pursuant to which WuXi Biologics performs certain development and manufacturing services for our SARS-CoV-2 antibody program.

Under the terms of the WuXi Biologics Letter of Intent, we had committed to purchase a firm and binding capacity reservation for the manufacture of a specified number of batches of drug substance of our SARS-CoV-2 antibody in 2020 and 2021.

In addition, we had the right to order an additional specified number of batches of drug substance, provided we make such election by a specified date in the fourth calendar quarter in 2020.

WuXi Biologics is obligated to reserve such manufacturing slots on a non-cancellable basis, and will manufacture the agreed number of batches of drug substance in accordance with an agreed manufacturing schedule.

We were obligated to pay a total of approximately $130.0 million for such capacity reservation, if all batches are manufactured, inclusive of estimated raw material costs, with between 70% and 80% of the batch production fees owed to WuXi Biologics on a take-or-pay basis regardless of whether we utilize such manufacturing slots.

The amounts were to be payable during 2020 and 2021 and invoiced on a per-batch basis.

The SARS-CoV-2 antibody drug substance contemplated to be manufactured in accordance with the terms of the WuXi Biologics Letter of Intent will be utilized in connection with progressing the development and commercialization of the SARS-CoV-2 antibody product under our collaboration with GSK.

In August 2020, we entered into an Assignment and Novation Agreement with GSKTSL and WuXi Biologics effective as of July 29, 2020 pursuant to which we assigned and transferred to GSKTSL all of our right, title, and interest in, to and under the WuXi Biologics Letter of Intent, and GSKTSL became our successor in interest in and to all of our rights, duties, and obligations in, to and under the WuXi Biologics Letter of Intent.

On August 4, 2020, GSKTSL entered into a non-exclusive Master Services Agreement for Commercial Manufacture of Drug Substance with WuXi Biologics effective as of July 29, 2020, or the WuXi Biologics MSA, thereby superseding the WuXi Biologics Letter of Intent, and pursuant to which, among other things, WuXi Biologics will perform development and manufacturing services for clinical and commercial supply of antibody products under our SARS-CoV-2 antibody program.

GSKTSL entered into the WuXi Biologics MSA in connection with the performance of GSK and our obligations pursuant to the 2020 GSK Agreement.

In accordance with the terms of the 2020 GSK Agreement, we will continue to be responsible for 72.5% of the costs under the WuXi Biologics MSA, and GSK will bear 27.5% of such costs under the WuXi Biologics MSA, subject to certain conditions and exceptions.

All material outstanding amounts related to these agreements between Vir and GSK were settled and paid during 2023.

As of January 5, 2023, WuXi completed all planned manufacturing of the SARS-CoV-2 antibody.

In first quarter of 2024, we and a large CDMO entered into various scopes of work and continue to do so with the respect to process performance qualification (PPQ) for Tobevibart drug substance (the Tobevibart agreements).

Under the terms of these agreements, the CDMO is obligated to reserve these manufacturing slots and will manufacture the agreed upon number of batches in accordance with an agreed upon manufacturing schedule to successfully complete PPQ.

As of December 31, 2024, we had unaccrued unpaid commitments of approximately $23 million under the Tobevibart Agreements.

Future commercial supply will be subject to finalizing a commercial supply agreement and relevant terms at the appropriate time.

In the third and fourth quarter of 2024, we entered into binding commitments with a large CDMO for process characterization and manufacture through completion of PPQ of Elebsiran DS (the Elebsiran agreements).

As of December 31, 2024, we had unaccrued unpaid commitments of approximately $9 million under the Elebsiran Agreements.

Future commercial supply will be subject to finalizing a commercial supply agreement and relevant terms at the appropriate time.

For TCEs, we have agreements with CDMOs to manufacture our drug substance and drug products for clinical trials on a yearly basis with no long-term commitments.

The pharmaceutical industry is characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products.

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Gilead’s bulevirtide is approved for use by the EMA.

Gilead received a Complete Response Letter for bulevirtide from the FDA in October 2022 and has indicated that it remains in active discussions with the FDA to work toward FDA approval.

We understand that Gilead received a Complete Response Letter (CRL) for bulevirtide from the FDA in October 2022 and has indicated that it remains in active discussions with the FDA to work toward FDA approval.

Bulevirtide has not been shown to lead to HDV clearance, and requires daily injections to maintain viral suppression.

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GSK is currently developing their lead asset, bepirovirsen, in a Phase 3 program.

Companies with RNAi agents in clinical development include GSK, Roche and Arbutus Biopharma.

In addition, several companies are developing antibodies against surface antigen including Roche, Bluejay Therapeutics & Huahui Health.

Several companies, including Gilead, GSK, and Vaccitech plc have therapeutic vaccines in early clinical development.

No FDA-approved vaccine is currently available for the prevention of HIV.

Moderna Inc is actively engaged in vaccine research and development in this area.

There are also not for profit entities developing vaccines using viral vectors, nanoparticles, DNA, RNA, or formulations, with the goal of stimulating T cell-mediated and/or neutralizing antibody responses against HIV.

To our knowledge, none are using a CMV-based vector.

Clinical trials of these vaccines are ongoing with support from the NIH Vaccine Research Center, the Bill & Melinda Gates Foundation, the U.S.

military, the International AIDS Vaccine Initiative, the European Vaccine Initiative, the South African AIDS Initiative, and their academic and industry partners.

We may also compete with oral or long-acting antiretroviral therapies for pre-exposure prophylaxis of HIV.

Truvada and Descovy, marketed by Gilead, are once-daily therapies approved for this indication.

ViiV recently received FDA approval for long-acting antiretroviral therapy, cabotegravir for pre-exposure prophylaxis of HIV.

Gilead, Merck and ViiV have additional long-acting formulations in development.

There are limited treatments and prophylactic vaccines available for COVID-19 in the U.S.

Currently there are two oral antiviral therapies including LAGEVRIO (molnupiravir) from Merck & Co, Inc., or Merck, and PAXLOVID (nirmatrelvir/ritonavir) from Pfizer Inc., or Pfizer, which are available under EUA and NDA respectively, in the mild to moderate early treatment setting.

In terms of prevention, there are two vaccines available including Pfizer’s COVID-19 vaccine, COMIRNATY® and Moderna, Inc.’s COVID-19 vaccine, SPIKEVAX®.

There are currently no mAbs available in the U.S.

for the treatment of COVID-19, as many have lost their activity against circulating variants and have been deauthorized, therefore there remains a significant unmet need for preventing and treating infection in immunocompromised patients.

Companies with antibodies in clinical development include Invivyd, Inc., or Invivyd, AstraZeneca and Regeneron Pharmaceuticals, Inc, and companies with new oral antivirals in clinical development include Shionogi Inc., Gilead, among others.

The market however remains very dynamic and changes in epidemiology and the emergence of new variants may render current treatments, including sotrovimab, inferior or obsolete in the future.

Companies with RNAi agents in clinical development include GSK, and Arbutus Biopharma.

In addition, several companies are developing antibodies against surface antigen including Bluejay Therapeutics & Huahui Health.

Several companies, including Gilead, Brii, and Virion have therapeutic vaccines in early clinical development.

HER2-associated Breast Cancer and Colorectal Cancer

There are several HER2 therapies currently approved and in development for HER2 associated cancers.

For HER2 positive breast cancer, there are a number of approved drugs including antibody drug conjugates (ADCs) (e.g.

ENHERTU from AstraZeneca and KADCYLA from Roche);

monoclonal antibodies (e.g.

HERCEPTIN & PERJETA from ROCHE);

and inhibitors (e.g.

Pfizer's TUKYSA).

Roche recently discontinued their non-masked HER2 TCE, and we are unaware of other compounds currently in clinical development.

While there are fewer HER2 therapies approved for HER2 positive CRC (ENHERTU from AstraZeneca and TUKYSA from Pfizer), the overall CRC space is highly competitive with standard of care agents (e.g.

Roche’s AVASTIN and Lilly’s ERBITUX) as well as pipeline agents across a number of modalities.

Prostate Cancer

While there are many currently approved options in mCRPC, there are limited options available to patients in later lines that have additional therapeutic benefits with manageable safety profiles as patients relapse.

There are several companies with ongoing efforts in development of later lines that are PSMA-targeting clinical-stage therapeutics.

These include, but are not limited to:

Amgen’s xaluritamig and Janux’s JANX007);

radioligand therapies (e.g.

Novartis’ PLUVICTO) and ADCs (e.g.

Johnson & Johnson’s ARX517).

Competition can also vary by line of therapy for metastatic disease, and many pipeline agents are also being evaluate with standard of care regimens such as anti-androgens (e.g.

Pfizer’s XTANDI).

Intellectual Property

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We require our employees, consultants and advisors to enter into confidentiality agreements prohibiting the disclosure of confidential information and requiring disclosure and assignment to us of the ideas, developments, discoveries and inventions important to our business.

Our patent portfolio includes patents and patent applications that are licensed from a number of collaborators and other third parties, including Alnylam, OHSU, MedImmune, the Institute for Research in Biomedicine, or IRB, Rockefeller and Xencor, and patents and patent applications that are owned by us.

Our patent portfolio includes patents and patent applications that cover our product candidates sotrovimab (previously VIR-7831), VIR-7229, elebsiran, tobevibart, VIR-2482, VIR-1111 and VIR-1388, and the use of these candidates for therapeutic purposes.

Our proprietary technology has been developed primarily through acquisitions, relationships with academic research centers and contract research organizations.

Our patent portfolio includes patents and patent applications that are licensed from a number of collaborators and other third parties, including Sanofi, Alnylam, the Institute for Research in Biomedicine, or IRB, Rockefeller and Xencor, and patents and patent applications that are owned by us.

Our patent portfolio includes patents and patent applications that cover our product candidates sotrovimab, elebsiran, tobevibart, VIR-5818, VIR-5500, and VIR-5525, and the use of these candidates for therapeutic purposes.

Our proprietary technology has been developed primarily through acquisitions, relationships with academic research centers and contract research organizations (CROs).

For our product candidates, we will, in general, initially pursue patent protection covering compositions of matter and methods of use.

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In total, our patent portfolio, including patents licensed from our collaborators and other third parties, comprises over 100 different patent families as of December 31, 2024, filed in various jurisdictions worldwide.

Our patent portfolio includes issued patents and patent applications in the United States and in many international countries.

Our patent portfolio includes over 1700 active cases with over 850 issued patents in the United States and abroad.

Our patent portfolio for our product candidates and technology platforms is outlined below.

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Key Product Candidates Patent Expiration

Sotrovimab (VIR-7831) 2041 2041

VIR-7229 (2044) (2044)

elebsiran (VIR-2218) 2035 2035

tobevibart (VIR-3434) 2036 2036

VIR-1388 2036 (2035)

VIR-8190 (2044) (2044)

VIR-2981 (2043) (2043)

VIR-1949 (2044) (2044)

(2044) (2044)

Patent Portfolio by Technology Platform

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We have exclusively licensed from IRB two patent families that relate to our antibody platform technology.

The 20-year term of the issued patents and any patent issuing from the pending patent applications in these families is presently estimated to expire between 2024 and 2038, absent any available patent term adjustments or extensions.

The 20-year term of the first of these families expired in 2024.

The US patent in this family is, however, still in force as its term was extend until 2027 due to patent office delay.

The 20-year term of the issued patents and any patent issuing from the pending patent applications in the second patent family is estimated to expire in 2038, absent any available patent term adjustments or extensions.

In addition, we have non-exclusively licensed a group of patents and applications from Xencor.

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Patents Owned by Us

We also own, with our subsidiary Humabs, one patent family that includes, as of December 31, 2023, one pending PCT application and one patent application in Taiwan.

We also own, with our subsidiary Humabs, one patent family that includes, as of December 31, 2024, 34 pending applications in both the US and abroad.

These applications include composition of matter claims, pharmaceutical composition claims, method of treatment claims and composition for use in treatment claims.

The 20-year term of any patents issuing from patent applications in this family is presently estimated to expire in 2042, absent any available patent term adjustments or extensions.

T Cell Platform

PRO-XTEN ™ Platform

Licensed Patents

We have exclusively licensed from OHSU 10 different patent families related to our T cell portfolio.

We have exclusively licensed from Sanofi 13 different patent families related to our PRO-XTEN ™ portfolio.

The 20-year term of the issued patents in these families is presently estimated to expire between 2036 and 2041, absent any available patent term adjustments or extensions.

Patents Owned by Us

We own two patent families that include, as of December 31, 2023, two pending PCT applications and three patent applications in Argentina and Taiwan directed to composition of matter claims, pharmaceutical composition claims, method of treatment claims, composition for use in treating claims and process (method of producing) claims.

The 20-year term of any patent issuing in these families is presently estimated to expire in 2042, absent any available patent term adjustments or extensions.

Patent Term and Term Extensions

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In addition, in certain instances, the term of a U.S.

patent can be extended to recapture a portion of the U.S.

Patent and Trademark Office’s, or the USPTO, delay in issuing the patent as well as a portion of the term effectively lost as a result of the FDA regulatory review period.

patent can be extended to recapture a portion of the delay from the U.S.

Patent and Trademark Office (USPTO) in issuing the patent, as well as a portion of the term effectively lost as a result of the FDA regulatory review period.

However, as to the FDA component, the restoration period cannot be longer than five years and the restoration period cannot extend the patent term beyond 14 years from FDA approval.

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Competitors may have filed patent applications or received patents and proprietary rights that block or compete with our products.

In addition, if competitors file patent applications covering our technology, we may have to participate in litigation, post-grant proceedings before the U.S.

Patent and Trademark Office or other proceedings to determine the right to a patent or validity of any patent granted.

In addition, if competitors file patent applications covering our technology, we may have to participate in litigation, post-grant proceedings before the USPTO or other proceedings to determine the right to a patent or validity of any patent granted.

Future litigation or other proceedings regarding the enforcement or validity of our existing patents or any future patents could result in the invalidation of our patents or substantially reduce their protection.

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The FDA and other regulatory authorities at federal, state and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, approval, advertising, promotion, marketing, post-approval monitoring and post-approval reporting of drugs and biologics such as those we are developing.

In the United States, the FDA approves and regulates drugs under the Federal Food, Drug, and Cosmetic Act, or the FDCA.

Biological products, or biologics, are licensed for marketing under the Public Health Service Act, or the PHSA, and regulated under the FDCA.

In the United States, the FDA approves and regulates drugs under the Federal Food, Drug, and Cosmetic Act (FDCA).

Biological products, or biologics, are licensed for marketing under the Public Health Service Act (PHSA) and regulated under the FDCA.

A company, institution or organization which takes responsibility for the initiation and management of a clinical development program for such products is typically referred to as a sponsor.

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The process required by the FDA before drug and biologic product candidates may be marketed in the United States generally involves the following:

• completion of extensive preclinical laboratory tests and animal trials performed in accordance with applicable regulations, including the FDA’s Good Laboratory Practice, or GLP, regulations;

• completion of extensive preclinical laboratory tests and animal trials performed in accordance with applicable regulations, including the FDA’s Good Laboratory Practice (GLP), regulations;

• design of a clinical protocol and submission to the FDA of an IND application which must become effective before clinical trials may begin;

• approval by an independent institutional review board or ethics committee at each clinical site before the trial is commenced;

• performance of adequate and well-controlled human clinical trials in accordance with FDA’s Good Clinical Practice, or GCP, regulations to establish the safety and efficacy of a drug candidate, and compliance with cGMP to establish safety, purity and potency of a proposed biologic product candidate for its intended purpose;

• preparation of and submission to the FDA of a new drug application, or NDA, or biologics licensing application, or BLA, as applicable, after completion of all pivotal clinical trials;

• performance of adequate and well-controlled human clinical trials in accordance with FDA’s Good Clinical Practice (GCP) regulations to establish the safety and efficacy of a drug candidate, and compliance with GMP to establish safety, purity and potency of a proposed biologic product candidate for its intended purpose;

• preparation of and submission to the FDA of a new drug application (NDA) or biologics licensing application (BLA), as applicable, after completion of all pivotal clinical trials;

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

• a determination by the FDA within 60 days of its receipt of an 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 cGMPs and of selected clinical investigation sites to assess compliance with GCPs;

• 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 GMP and of selected clinical investigation sites to assess compliance with GCP;

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

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

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study.

Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCP, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

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The FDA will not approve an application 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.

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

An approval letter authorizes commercial marketing of the product with specific prescribing information for specific indications.

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Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Emergency Use Authorization

In emergency situations, such as a pandemic, and with a declaration of a public health emergency by the Secretary of the U.S.

Department of Health and Human Services, or HHS, the FDA has the authority to allow unapproved medical products or unapproved uses of cleared or approved medical products to be used to diagnose, treat or prevent serious or life-threatening diseases or conditions caused by chemical, biological, radiological or nuclear warfare threat agents when there are no adequate, approved, and available alternatives.

Under this authority, the FDA may issue an EUA that allows the product to be distributed to patients prior to its formal approval.

Once granted, an EUA will remain in effect and generally terminate on the earlier of (1) the determination by the Secretary of HHS that the public health emergency has ceased or (2) a change in the approval status of the product such that the authorized use(s) of the product are no longer unapproved.

The FDA also may revise or revoke an EUA if the circumstances justifying its issuance no longer exist, the criteria for its issuance are no longer met, or other circumstances make a revision or revocation appropriate to protect public health or safety.

Orphan Drug Designation

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Biosimilars and Regulatory Exclusivity

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product.

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the ACA), signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009 (BPCIA), which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product.

The FDA has since approved a number of biosimilars products.

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Section 505 of the FDCA provides a pathway for generic manufacturers to rely, in part, on the FDA’s prior findings of safety and efficacy for an existing product, or published literature, in support of its application.

Section 505(j) establishes an abbreviated approval process for a generic version of approved drug products through the submission of an Abbreviated New Drug Application, or ANDA.

Section 505(j) establishes an abbreviated approval process for a generic version of approved drug products through the submission of an Abbreviated New Drug Application (ANDA).

An ANDA provides for marketing of a generic drug product that has the same active ingredients, dosage form, strength, route of administration, labeling, performance characteristics and intended use, among other things, to a previously approved product.

The generic version must deliver the same amount of active ingredient(s) in the same amount of time as the innovator drug and can often be substituted by pharmacists under prescriptions written for the reference listed drug.

Upon submission of an ANDA, an applicant must certify to the FDA that (1) no patent information on the drug product that is the subject of the application has been submitted to the FDA;

Upon submission of an ANDA, an applicant must certify to the FDA that:

(1) no patent information on the drug product that is the subject of the application has been submitted to the FDA;

(2) such patent has expired;

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Other companies have been prosecuted for causing false claims to be submitted because of the companies’ marketing of products for unapproved, and thus non-reimbursable, uses.

The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, created additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

The federal Health Insurance Portability and Accountability Act of 1996 (HIPAA) created additional federal criminal statutes that prohibit, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

Also, many states have similar fraud and abuse statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS, information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.

The federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services (CMS) information related to payments or other transfers of value made to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), and teaching hospitals, and applicable manufacturers and applicable group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate family members.

As of January 2022, applicable manufacturers are also required to report such information regarding its payments and other transfers of value to physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified registered nurse anesthetists and certified nurse midwives during the previous year.

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The future commercial success of our product candidates, if approved, will depend in part on the extent to which third-party payors, such as governmental payor programs at the federal and state levels, including Medicare and Medicaid, private health insurers and other third-party payors, provide coverage of and establish adequate reimbursement levels for our product candidates.

Third-party payors generally decide which products they will pay for and establish reimbursement levels for those products.

Third-party payors decide which therapies they will pay for and establish reimbursement levels.

In particular, in the United States, no uniform policy for coverage and reimbursement exists.

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In the United States, the biopharmaceutical industry has been a particular focus of these efforts, which include major legislative initiatives to reduce the cost of care through changes in the healthcare system, including limits on the pricing, coverage, and reimbursement of biopharmaceutical products, especially under government-funded healthcare programs, and increased governmental control of drug pricing.

It is unclear whether the new Trump Administration will reverse or modify any existing regulatory requirements, pursue new reform initiatives or otherwise influence the overall healthcare regulatory environment, and even if proposed, whether such changes or modifications would be implemented or withstand potential litigation.

Pharmaceutical Prices

On August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law by President Biden.

In August 2022, the Inflation Reduction Act of 2022 (IRA) was signed into law.

The new legislation has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

Among other things, the IRA:

requires manufacturers of certain drugs to engage in price negotiations with Medicare (to go into effect in 2026), with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023);

and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).

and replaces the Part D coverage gap discount program with a new discounting program (to go into effect in 2025).

The IRA permits the Secretary of HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

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Among other things, the IRA contains many provisions aimed at reducing this financial burden on individuals by reducing the co-insurance and co-payment costs, expanding eligibility for lower income subsidy plans, and price caps on annual out-of-pocket expenses, each of which could have potential pricing and reporting implications.

Accordingly, while it is currently unclear how the IRA will be effectuated, we cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our activities or result in reduced reimbursement for our products, any of which could adversely affect our business, results of operations and financial condition.

While it is currently unclear certain new measures, including the drug pricing provisions of the IRA, will ultimately be effectuated, we cannot predict with certainty what impact any federal or state health reforms will have on us, but such changes could impose new or more stringent regulatory requirements on our activities or result in reduced reimbursement for our products, any of which could adversely affect our business, results of operations and financial condition.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control biopharmaceutical and biological 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.

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Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others.

Similar to the United States, other countries offer pathways for expedited review, such as the EMA’s PRIME designation, which is granted to investigational medicines that target conditions with unmet medical needs for which no treatment option exists, or where they can offer a major therapeutic advantage over existing treatments.

Orphan drug designation is also available in the EU for medicines intended to treat rare, life-threatening or chronically debilitating conditions where no other satisfactory treatment option is available, or where the medicine can be of significant benefit to those affected by a specific condition, and the benefits include access to specific scientific advice, fee reductions and 10 years of market exclusivity once the medicine is approved.

In addition, in most foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed.

The requirements governing drug pricing and reimbursement vary widely from country to country.

The EU provides options for its member states to restrict the range of medicinal products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

A member state may approve a specific price for the medicinal product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the medicinal product on the market.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products.

Historically, products launched in the EU do not follow price structures of the United States and generally prices tend to be significantly lower.

We, and our service providers, receive, process, store and use personal information and other data about our clinical trial participants, employees, collaborators and others.

We are subject to numerous domestic and foreign laws and regulations regarding privacy and data security, the scope of which is changing, subject to differing applications and interpretations, and may be inconsistent among countries, or conflict with other rules.

Thus we are subject to local, state, federal and international privacy and data protection laws and regulations, which among other things, impose certain requirements related to the privacy, security and transmission of personal information, including comprehensive regulatory systems in the United States, EU and the U.K.

The legislative and regulatory landscape for privacy and data protection continues to evolve in jurisdictions worldwide, subject to differing applications and interpretations, and in some cases inconsistencies or conflicts with other rules.

At the federal level, HIPAA, imposes specific requirements on certain types of individuals and entities relating to the privacy, security and transmission of individually identifiable health information.

Penalties for failure to comply with these requirements vary significantly, and include significant civil monetary penalties and, in certain circumstances, criminal penalties and/or imprisonment.

Various states, such as California, Colorado, Texas, Utah and Virginia have adopted privacy laws, including laws and regulations similar to HIPAA, that impose restrictive requirements regulating the use and disclosure of health information and other types of personal information.

Various states, such as California, Colorado, Oregon, Texas, Utah and Virginia, among others, have adopted privacy laws, including laws and regulations similar to HIPAA, that impose restrictive requirements regulating the use and disclosure of health information and other types of personal information.

Where state laws are more protective, we have to comply with the stricter provisions.

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Regulation of privacy, data protection and data security has also become more stringent in foreign jurisdictions.

For example, the EU adopted the GDPR, which imposes onerous and comprehensive privacy, data protection, and data security obligations onto data controllers and processors, including, as applicable, contractual privacy, data protection, and data security commitments, expanded disclosures to data subjects about how their personal information is used, honoring individuals’ data protection rights, limitations on retention of personal information, additional requirements pertaining to sensitive information (such as health data) and pseudonymized (i.e., key-coded) data, data breach notification requirements, and higher standards for obtaining consent from data subjects.

For example, the EU General Data Protection Regulation 2016/679 (GDPR) imposes onerous and comprehensive privacy, data protection,and data security obligations onto data controllers and processors, including, as applicable, contractual privacy, data protection and data security commitments, expanded disclosures to data subjects about how their personal information is used, honoring individuals’ data protection rights, limitations on retention of personal information, additional requirements pertaining to sensitive information (such as health data) and pseudonymized (i.e., key-coded) data, data breach notification requirements, and higher standards for obtaining consent from data subjects.

Penalties for non-compliance with the GDPR can be significant.

Assisting parties with whom we exchange personal data in complying with the GDPR, or complying with the GDPR ourselves, may cause us to incur substantial operational costs or require us to change our business practices.

Furthermore, European privacy, data protection, and data security laws, including the GDPR, generally restrict the transfer of personal information from the U.K., European Economic Area, or EEA, and Switzerland to the United States and most other countries unless the parties to the transfer have implemented specific safeguards to protect the transferred personal information.

There is uncertainty as to how to implement such safeguards and how to conduct such transfers in compliance with the GDPR, and certain safeguards may not be available or applicable with respect to some or all the personal information processing activities necessary to research, develop and market our products and services.

EU regulators have recently adopted a new set of Standard Contractual Clauses, which impose additional obligations and requirements with respect to the transfer of EU personal data to other jurisdictions and may increase the legal risks and liabilities under the GDPR and local EU laws associated with cross-border data transfers, and result in material increased compliance and operational costs.

If we are unable to implement a valid mechanism for personal information transfers to the United States and other countries, we may face increased exposure to regulatory actions, substantial fines, and injunctions against processing or transferring personal information from Europe, and we may be required to increase our data processing capabilities in Europe at significant expense.

Inability to import personal information from Europe to the United States or other countries may limit our ability to conduct clinical trials in Europe and collaborate with other entities subject to European data protection laws.

At present, there are few, if any, viable alternatives to the Standard Contractual Clauses.

Other countries outside of Europe have enacted or are considering enacting similar cross-border data transfer restrictions and laws requiring local data residency, which could increase the cost and complexity of delivering our services and operating our business.

Furthermore, European privacy, data protection, and data security laws, including the GDPR and the EU’s Standard Contractual Clauses adopted in 2021, generally restrict the transfer of personal information to other countries unless the parties to the transfer have implemented specific safeguards to protect the transferred personal information.

Approximately 50 countries worldwide have modeled their data privacy regulations after the GDPR or adopted similar laws, and other countries outside of Europe have enacted or are considering enacting cross-border data transfer restrictions and laws requiring local data residency.

There is uncertainty as to how to implement such safeguards and how to conduct such transfers in compliance with the GDPR or similar laws, and certain safeguards may not be available or applicable with respect to some or all the personal information processing activities necessary to research, develop and market our products and services.

Assisting parties with whom we exchange personal data in complying with these laws and regulations, or complying with these laws and regulations ourselves, may cause us to incur substantial operational costs or require us to change our business practices.

We may rely on others, such as health care providers, to obtain valid and appropriate consents from data subjects whose data we process.

The failure of third parties to obtain consents that are valid under applicable law could result in our own non-compliance with privacy laws.

Such failure to comply with U.S.

and foreign privacy, data protection, and data security laws and regulations could result in government enforcement actions (which could include civil or criminal penalties), private litigation and/or adverse publicity and could negatively affect our operating results and business.

Claims that we have violated individuals’ privacy rights, failed to comply with privacy, data protection, and data security laws, or breached our contractual obligations, even if we are not found liable, could be expensive and time consuming to defend, could result in adverse publicity and could have a material adverse effect on our business, financial condition, and results of operations.

Such failure would expose us to risk of enforcement actions from data protection authorities in the United States, EU and elsewhere, with the potential for significant financial penalties and/or orders requiring us to change our practices if we are found to be non-compliant, as well as private lawsuits or adverse publicity, all of which could negatively affect our operating results and business.

Human Capital Management

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Our human capital programs are aimed at fostering engagement, innovation and community.

As of December 31, 2023, we had 587 full-time employees, 435 of whom were primarily engaged in research and development activities.

As a result of the COVID-19 pandemic, in March 2020, we implemented work-from-home policies for most of our employees.

To the extent possible, we offer our employees the choice of working full-time in the office, a hybrid approach, or full-time remote.

Our employees who work full-time in the office are predominantly located in San Francisco, California;

Louis, Missouri;

Portland, Oregon;

and Bellinzona, Switzerland.

Louis, Missouri, and Portland Oregon offices will be closing in 2024.

As of December 31, 2024, we had 408 employees, 312 of whom were primarily engaged in research and development activities.

Our employees who work full-time in the office are predominantly located in San Francisco, California and Bellinzona, Switzerland, and employees not within commuting distance of our office locations work remotely.

None of our employees are represented by a labor union and we consider our employee relations to be good.

The principal purpose of our equity incentive plan is to attract, retain, and motivate our employees, non-employee directors, and consultants through the granting of stock-based compensation and performance cash awards.

In addition to highly competitive base compensation, bonus structure and awards granted pursuant to our equity incentive plan, we offer numerous benefits to employees on a country-by-country basis, including a 401(k) plan with matching, health (medical, dental and vision) insurance, life insurance, paid time off, paid parental leave and short-term and long-term disability.

To drive further engagement and individual ownership of the Company, we also maintain an employee stock purchase plan, which provides eligible employees an opportunity to purchase additional VIR stock at a discounted price.

The principal purpose of our annual incentive plan is to attract, retain, and motivate our employees through cash bonuses based on the achievement of the most significant drivers of our near-term goals.

The principal purpose of our equity incentive plan is to encourage long-term, sustainable performance and ongoing retention of our employees, non-employee directors, and consultants with stock-based compensation as well as to align their interests with those of our stockholders.

In addition to highly competitive base compensation, cash bonuses granted pursuant to our annual incentive plan and stock-based awards granted pursuant to our equity incentive plan, we offer numerous benefits to employees on a country-by-country basis, including a 401(k) plan with matching, health (medical, dental and vision) insurance, life insurance, paid time off, paid parental leave and short-term and long-term disability.

Equity, Inclusion and Development

Vir takes a proactive approach to promoting equity and inclusion.

We take a proactive approach to promoting equity and inclusion.

In addition to being an equal opportunity employer, we proactively use a specialized software tool to reduce bias in our job postings to ensure that we utilize inclusive language to reach the broadest range of applicants.

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To ensure pay equity at all levels, we use a leading independent third party pay equity firm to perform an annual independent audit of our pay practices.

Vir offers ongoing, targeted inclusive developmental training for employees and leaders.

We offer ongoing, targeted inclusive developmental training for employees and leaders.

We cultivate an environment where all employees can develop personally and professionally.

Within this, we focus on individual opportunities for growth, developing people managers’ skills and cultivating our leaders’ capabilities to align the organization in service of our mission.

Additionally , Vir values the diversity of its leaders, with female and minority directors comprising over 45% of our current board of directors and women comprising 70% of Vir’s management team.

Additionally , we value the diversity of our leaders, with women and minorities comprising 36% and 60% of our board of directors and executive management team, respectively, as of December 31, 2024.

Our Corporate Information

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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