Hello. Welcome to Vir Biotechnology’s Second Quarter 2024 Financial Results and Business Update Call. This conference call is being recorded. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. I will now turn the call over to Richard Lepke, Senior Director of Investor Relations. You may begin, Mr. Lepke.

Thank you, operator, and hello everyone. I am Richard Lepke, Senior Director of Investor Relations at Vir Biotechnology. Joining me on the call are Dr. Marianne De Backer, our Chief Executive Officer; Dr. Jennifer Towne, our Chief Scientific Officer; Dr. Mark Eisner, our Chief Medical Officer; and Brent Sabatini, our Chief Accounting Officer. Before we begin, I would like to remind everyone that some of the statements we are making today are forward-looking statements under applicable securities laws. These forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements, to differ significantly from those expressed or implied by such forward-looking statements. These risks and uncertainties and risks associated with our business are described in today's press releases and the company's reports filed with the Securities and Exchange Commission, including Forms 10-K, 10-Q and 8-K. With that, I will turn the call over to Marianne. Please go ahead.

Good afternoon, everyone, and thank you for joining us today. At Vir, our mission is powering the immune system to transform lives. During today's earnings call, we will discuss two significant announcements that mark critical milestones on our journey to realize this vision. Before we dive into these announcements, let me quickly highlight some key achievements from the second quarter. We presented promising Phase 2 SOLSTICE data in chronic hepatitis delta at the EASL Congress, which generated significant interest from both the scientific and medical community. These preliminary data underscore the potential of our combination therapy with tobevibart and elebsiran to revolutionize the treatment landscape for people living with hepatitis delta. We are now preparing to engage with regulatory authorities to discuss the registrational path forward. We also recently received FDA IND clearance and fast track designation for this combination therapy. In parallel, we remain focused on advancing our functional cure program for chronic hepatitis B, and we eagerly anticipate reporting 48-week end of treatment data from the Phase 2 MARCH Part B study at the major medical congress in the fourth quarter. Now let me turn to the two significant announcements that will be the main focus of today's call. First, I'm excited to announce that Vir has entered into an exclusive worldwide license agreement with Sanofi for three clinical-stage masked T-cell engagers and the exclusive use of the PRO-XTEN protease-cleavable masking platform for oncology and infectious diseases. This license agreement is subject to HSR review and clearance, which we expect will take about 30 days from signing. Second, we will be providing a corporate update on our strategic restructuring. To provide you with a comprehensive overview of these announcements and their impact on our company, we have structured today's call as follows. First, I will summarize the strategic rationale behind the Sanofi license agreement and the corporate restructuring. Then, Jen will provide details on the masking platform and its potential applications. Mark will discuss the clinical stage assets we have licensed. Brent will provide a financial overview, including the terms of the agreement and our capital allocation priorities in light of the restructuring. And finally, I will offer some closing remarks before we open the call for questions. Let me now provide more details on our exclusive worldwide license agreement with Sanofi and the strategic measures we have announced today. First, the agreement adds three potentially best-in-class clinical stage assets: SAR446309 or AMX-818, a dual-masked HER2-targeted T-cell engager in Phase 1 development; SAR446329 or AMX-500, a dual-masked PSMA-targeted T-cell engager in Phase 1 clinical development; and SAR446368 or AMX-525, a dual-masked EGFR-targeted T-cell engager with a cleared IND scheduled to begin Phase 1 in early 2025. For the duration of the call, we will refer to these assets by the last four digits of their drug candidate code: 6309, 6329, and 6368, respectively. Looking ahead, these assets have multiple near-term key catalysts expected in the next nine to 18 months. Second, we obtained the exclusive license to Sanofi's PRO-XTEN protease-cleavable masking platform for oncology and infectious diseases. T-cell engagers are, in essence, engineered by specific monoclonal antibodies. Given our deep antibody protein engineering and T-cell biology expertise, we believe that we can unlock meaningful synergies and create new best-in-class therapies. Upon closing, we are also excited to strengthen Vir's capabilities by welcoming the team of key Sanofi employees with extensive scientific and oncology development expertise. Finally, we are strategically reprioritizing our pipeline, which has led to a restructuring of our organization. To better understand the potential impact of the licensed assets, let's first discuss the current landscape of cancer therapeutics and the unmet needs that still exist. Despite advances in cancer research, the global burden of cancer remains high with 10 million deaths annually and a five-year survival rate of just 5% for some cancers. T-cell engagers have shown promise as a potent therapeutic modality, but they often have lower tolerability because of off-tumor on-target toxicity in healthy tissue, systemic toxicity, such as cytokine release syndrome, and the inability to achieve therapeutically active doses in the tumor microenvironment. These limitations have hindered the widespread adoption of T-cell engagers to date. Our solution to addressing these challenges is the potential best-in-class to extend protease activating masking technology. This proprietary platform allows T-cell engagers, cytokines, and auto molecules to be selectively activated in the tumor microenvironment. By masking the T-cell engagers, this technology aims to minimize off-tumor toxicities and systemic side effects while enabling the achievement of therapeutically active doses directly in the tumor tissue. This technology has the potential to significantly improve the safety and efficacy profile of future treatments. Now this strategic transaction not only enhances our clinical pipeline but also augments our core R&D capabilities and, upon closing, will bring a complementary platform to the company. At Vir, we have always prided ourselves on our world-class immunology and biology expertise, which has enabled us to uniquely discover and engineer monoclonal antibodies to address serious infectious diseases. With the anticipated addition of the PRO-XTEN masking platform, we will be even better positioned to develop innovative therapies that selectively target disease-causing cells while sparing healthy tissue. An important component of the agreement is that we are adding a team of key employees who offer extensive expertise in oncology clinical development, in-depth knowledge of the proprietary masking platform, and valuable expertise in manufacturing dual mask molecules. By combining our existing strengths with this new expertise, we will create a powerful synergy to drive innovation, and we look forward to working together to advance our mission following the closing of the transaction. As we anticipate integrating the licensed assets into our pipeline, we are taking decisive steps to focus on the highest value near-term opportunities. First, we are focusing our resources on our core programs in hepatitis delta, hepatitis B, and, upon closing, the newly licensed masked T-cell engager clinical portfolio. Second, we are phasing out programs in influenza and COVID-19 as well as our T-cell-based viral vector platform and programs. Where appropriate, these programs will be made available for partnering. Third, we are implementing a workforce restructuring that will result in a reduction of approximately 25% of our employees. These actions are expected to yield significant cost savings while allowing us to effectively utilize our strong balance sheet to advance our strategic priorities. By streamlining our operations and allocating our capital efficiently, we are positioning Vir for long-term success and sustainable growth. In addition, we are revising our 2024 expense guidance lower. Brent will summarize the details later on the call. I do want to take a moment to express my deepest gratitude to all our employees, including those who will be leaving the company for their dedication and their significant contributions to our mission. These decisions, while difficult, are necessary to ensure that we are allocating our capital and our talent in the most effective way possible to bring transformative therapies to patients. We believe that this strategic restructuring will enable us to deliver on that promise more effectively than ever before. With that, I would now like to turn the call over to Jen, who will provide more details on the masking platform and its potential applications in oncology and in infectious diseases.

Thank you, Marianne, and hello, everyone. As you can see on the slide, the PRO-XTEN technology consists of a protease releasable XTEN mask that can be universally applied to various protein therapeutic modalities. The PRO-XTEN technology has two key features. First, it employs a universal mask, which in the case of a T-cell engager is applied to both arms, masking both the part of the molecule that targets the tumor-associated antigen and the part that activates the T-cell, the CD3 arm. Second, the technology utilizes a protease-cleavable linker, which enables preferential masking and drug activation specifically in the tumor microenvironment. This is possible because the tumor microenvironment is known to have high levels of specific proteases that cleave the linker, releasing the active drug from the XTEN mask. The PRO-XTEN technology can be applied to T-cell engagers, cytokines, and likely other modalities. This masking technology allows for the selective activation of potent immune modulators at the site of the tumor while minimizing their activity in healthy tissues. The XTEN mask has been clinically proven with ALTUVIIIO, an approved drug, to provide half-life extension to the masked molecule. Now let's take a closer look at how this technology can overcome the historical limitations of T-cell engagers and unlock new opportunities in cancer treatment. In blood circulation, the molecule remains fully masked with all of its components, including the XTEN mask, the linker, and the tumor targeting and T-cell engaging components, all intact and connected. This mask configuration allows for a long half-life in the blood, which is essential for effective drug delivery to the tumor site. As the masked T-cell engager reaches healthy tissue, the dual masking of both the tumor-associated antigen and the CD3 arms limits binding to healthy cells and T-cells. This unique feature reduces T-cell mediated cytotoxicity, thereby improving the tolerability of the treatment. However, when the masked T-cell engager enters the tumor microenvironment, a critical transformation occurs. The tumor microenvironment is characterized by high levels of tumor-associated proteases. These proteases recognize and cleave the protease-cleavable linkers on the PRO-XTEN masked T-cell engager and therefore, unmask and activate the molecule specifically in the tumor tissue. The selective unmasking and activation in the tumor microenvironment allows for higher concentration of active drug where it's needed most, while minimizing exposure and toxicity in the healthy tissues. Once unmasked, the active T-cell engager can engage T-cells and tumor cells promoting potent antitumor activity resulting in the killing of the tumor cells. Importantly, any unmasked molecules that exit the tumor microenvironment are rapidly eliminated from the body due to a short half-life once unmasked, further reducing the risk of off-tumor toxicity. We believe that this approach has the potential to revolutionize the field of T-cell engagers and other immunotherapies. Now I'd like to share some compelling preclinical proof-of-concept data that demonstrate the ability of the PRO-XTEN masked HER2 T-cell engager to be conditionally activated in the tumor microenvironment. Let's start with the graph on the left, which shows the in vitro T-cell-dependent killing of HER2-positive tumor cells in the presence of PRO-XTEN masked and unmasked T-cell engagers. As you can see, the masked HER2 T-cell engager leads to a 10,000-fold shift in cytotoxicity compared to the unmasked HER2 T-cell engager in vitro. In other words, the masked T-cell engager is essentially ineffective in the absence of the proteases found in the tumor microenvironment, which is exactly what we want to minimize off-target toxicity. Looking to the middle graph, we see the in vivo antitumor efficacy in a HER2-positive tumor model following treatment with masked or unmasked HER2 T-cell engagers. The masked HER2 T-cell engager induces robust tumor regression, demonstrating equivalent efficacy to the unmasked molecule. This provides strong evidence that the unmasking process is occurring as intended in the tumor tissue. Finally, the graph on the right shows the relative levels of masked and unmasked T-cell engager present in tumors versus healthy tissues, 48 hours after treatment with the masked HER2 T-cell engager. As predicted, the only site where we see an accumulation of unmasked active T-cell engager is in the tumor. In contrast, the masked inactive molecule is present across many tissue types. This preferential unmasking at the disease site with minimal to no exposure of the active molecule in normal tissue is critical to reduce off-tumor toxicity. Now, let's explore how this technology can also maximize the therapeutic index. Starting with the graph on the left, we see that the masked HER2 T-cell engager demonstrates extended pharmacokinetics compared to the unmasked molecule. The prolonged circulation time of the masked molecule allows the drug to reach the tumor tissue while the rapid clearance of any unmasked molecule in the periphery helps to minimize off-target toxicity. Moving to the middle graph, we observe minimal cytokine release with the masked T-cell engager as indicated by the low levels of IL-6. Cytokine-release syndrome has been a major limitation for the current T-cell engagers, and this evidence is highly encouraging for the platform. Finally, the box on the right showcases the improvement in therapeutic index achieved. In nonhuman primate studies, the maximum tolerated dose of the masked HER2 T-cell engager was 43 milligrams per kilogram compared to just 0.2 milligrams per kilogram for the unmasked HER2 molecule. This represents a greater than 100-fold improvement in therapeutic index. Notably, the unmasked HER2 T-cell engager was lethal due to cytokine release syndrome at a dose of 0.3 milligrams per kilogram, highlighting the significant safety challenges associated with conventional T-cell engagers. As we anticipate integrating the PRO-XTEN masking platform and the talented team from Sanofi and Vir, I'd like to highlight the synergistic capabilities and expertise that this deal brings together. First, at Vir, we have a deep understanding of T-cell biology and how to optimize their activity to kill cells in infectious diseases. This expertise can be directly applied to maximizing the ability of the masked T-cell engagers to eliminate tumor cells. Second, our monoclonal antibody platform enables the rapid generation of novel antibodies for identified tumor targets. By combining our antibody discovery capabilities with the PRO-XTEN masking technology, we can rapidly create a new generation of masked T-cell engagers that can address a broad range of tumor antigens, expanding the potential impact of this modality. Third, our next-generation protein engineering capabilities, which leverage proprietary AI and machine learning tools and high-throughput wet lab selection, enable us to optimize multiple protein characteristics simultaneously. We can potentially create masked molecules with optimized stability, pharmacokinetics, and tumor-specific activations, further improving their therapeutic potential. Now let's discuss how the unique combination of properties offered by this proprietary platform sets it apart from other masking technologies. First, the PRO-XTEN platform employs a dual masking approach, where both the tumor-associated antigen and CD3 binding domains are masked. This feature maximizes the therapeutic index by decreasing both the off-tumor activity and the systemic immune activation. Second, the platform is designed to provide a short half-life for the active drug while maintaining a long half-life for the masked drug. This allows the masked drug to reach the site of action before being cleared, enhancing its associated potential. Once activated, the short half-life of the active drug provides a safety advantage by limiting systemic exposure. Third, the platform features universal tunable masks that can be applied to any T-cell engager. This innovative plug-and-play format allows us to use the same mask across multiple therapeutic candidates, saving time and resources compared to developing new masks for each antibody and expediting the development process. Fourth, the platform has broad applicability as it can be used to mask not only T-cell engagers, but also cytokines and other therapeutic modalities. This versatility expands the potential impact of the technology and allows us to explore a wide range of immune targeting approaches. Finally, the masking technology has been validated in human clinical studies, providing a strong foundation for its use in our pipeline. We believe that with the unique properties of the platform and our combined expertise, we are uniquely positioned to develop a next-generation of masked T-cell engagers and cytokines. This powerful combination will set Vir apart and strengthen our position as a leader in the development of transformative immunotherapies.

Thank you, Jen, and hello, everyone. I'll now provide an overview of these programs and our plans for clinical development. Following closing, the licensing agreement would provide us with a robust portfolio of assets targeting clinically validated antigens in oncology. These assets include three dual masked T-cell engagers, each targeting a different antigen: HER2, PSMA, and EGFR. 6309 is a dual masked HER2 CD3 T-cell engager. This asset has the potential to address significant unmet needs in HER2-expressing cancers with initial indications, including third-line or later HER2-positive metastatic colorectal cancer and second to third-line HER2-positive metastatic breast cancer. 6329 is a dual masked PSMA CD3 T-cell engager. This asset is initially being developed for the treatment of third-line or later metastatic castration-resistant prostate cancer, a disease with limited treatment options and poor outcomes. 6368 is a dual masked EGFR CD3 T-cell engager. This asset has the potential to address multiple EGFR-expressing tumors with initial indications, including third-line or later metastatic colorectal cancer, second to third-line metastatic non-small cell lung cancer, and second to third-line metastatic head and neck carcinoma. While we refer to specific lines of therapy and initial indications for these assets, it's important to note that our goal is ultimately to move up to earlier lines over time as the data support. HER2, PSMA, and EGFR are all known to be important targets in a variety of solid tumors and existing therapies against these targets have demonstrated clinical benefit. However, existing therapies often come with significant toxicities, limiting their ability to be dosed high enough to achieve optimal efficacy. In the following slides, I will provide more details on each of these assets, including their current clinical development plans. Now let's dive deeper into 6309, the dual masked HER2 CD3 T-cell engager. As you can see on the left side of this slide, there is a significant disease burden associated with HER2-positive cancers, particularly in metastatic colorectal cancer, breast cancer, and gastroesophageal junction cancer. We estimate that annually, there are tens of thousands of newly diagnosed patients with metastatic HER2-positive cancers in key regions. Despite the availability of HER2-targeting agents, there remains a significant unmet need in the treatment of HER2-positive tumors. While these therapies have improved outcomes for patients, mortality rates remain high due to disease progression. Additionally, there are major safety concerns associated with current HER2-targeted therapies, particularly cardiac dysfunction, interstitial lung disease, and pneumonitis. In the HER2 low segment, which represents the majority of breast cancers, the treatment options are even more limited. There is only one approved HER2-targeted therapy for this population, Enhertu, highlighting the need for additional effective and well-tolerated treatment options. The current Phase 1 study design for 6309 is carefully crafted to optimize the dose, demonstrating proof-of-concept with a dual masking platform and evaluate its potential across multiple HER2-expressing solid tumors. The study began with a single-agent dose escalation phase to optimize the dose of 6309. Patients are enrolling at increasing dose levels until an optimized dose is determined. The study also includes a combination dose escalation phase with pembrolizumab. In addition, there are potential expansion cohorts to evaluate the efficacy and safety of 6309 in specific tumor types, such as HER2-positive metastatic colorectal cancer, HER2-positive breast cancer, and HER2-low breast cancer. The data from these expansion cohorts will inform further development in these indications. We are excited about the potential of 6309 to transform the treatment landscape for patients with HER2-expressing cancers. As the only masked HER2 T-cell engager currently in clinical development, 6309 is designed to offer lower off-tumor and systemic toxicity, allowing for higher doses, potentially improved efficacy, and a better risk-benefit profile compared to existing HER2-targeted therapies. The Phase 1 study is currently being conducted at 10 active sites in Europe and Australia. Monotherapy and combination therapy data is anticipated to be available in the second half of 2025, which will be a key catalyst for the program. Now let's shift our focus to 6329, a dual masked PSMA directed T-cell engager. Metastatic castration-resistant prostate cancer represents a significant disease burden with a large number of patients across lines of therapy. Despite currently available treatments, approximately 50% of patients with non-metastatic castration-resistant prostate cancer experience metastatic recurrence within three years. Furthermore, only 34% of patients with metastatic prostate cancer are alive five years after diagnosis, highlighting the need for more effective therapies. We believe that 6329 is a highly differentiated asset by leveraging the PRO-XTEN masking technology, 6329 targets PSMA, a highly expressed antigen on prostate cancer cells to drive T-cell-mediated intratumor responses in the tumor microenvironment. As the only dual masked PSMA directed T-cell engager currently in clinical development, 6329 is designed to offer lower off-tumor toxicity, allowing for higher doses and potentially improved efficacy compared to existing PSMA-targeted therapies. Consequently, we believe that 6329 can offer patient benefit in third-line metastatic castration-resistant prostate cancer with the potential to move into earlier lines of therapy in combination with antiandrogen therapies, which are the standard-of-care for these patients. The Phase 1 study is ongoing, evaluating 6329 as monotherapy in a dose escalation design with the potential to advance into monotherapy and combination therapy expansion cohorts. A key advantage of the PRO-XTEN technology is universal masking. This allows the use of the safety experience, especially regarding the risk of cytokine release syndrome from the 6309 Phase 1 study. This knowledge enabled 6329 to start at a higher dose and potentially dose titrate faster, accelerating the development timeline. The Phase 1 study is currently being conducted at six active sites in Europe and Australia. Monotherapy data is expected to be available in the second half of 2025. This data readout will be a key catalyst for the program. Now let's turn our attention to 6368, a dual masked EGFR CD3 T-cell engager with IND clearance. EGFR-expressing solid tumors represent a significant disease burden with a large number of newly metastatic patients diagnosed each year. EGFR is broadly expressed across a wide range of tumor types, making it an attractive target for cancer therapy. While the graph on the left highlights some of the most prevalent EGFR-expressing cancers, it's important to note that EGFR is also expressed in many other tumor types. Despite available treatments, the unmet need for patients with EGFR-expressing tumors remains high. The five-year survival rate for metastatic patients ranges from near 3% to 38% in second and third-line settings to these tumor types; the outcomes are dismal. Leveraging the PRO-XTEN masking technology, we believe that 6368 has the potential to provide a safe and tolerable treatment option for patients in the second line and beyond settings for this difficult-to-treat cancer. The preclinical data for 6368 provides similar validation as seen with the previous PRO-XTEN masked T-cell engagers, demonstrating the platform's ability to minimize off-target toxicity while maintaining prudent antitumor activity in the tumor microenvironment. In vitro, the masking of 6368 leads to a 10,000-fold shift in cytotoxicity compared to the unmasked EGFR T-cell engager, highlighting the ability of the PRO-XTEN technology to prevent off-target immune synapse formation. In vivo, the PRO-XTEN masked EGFR T-cell engager demonstrated similar antitumor activity to the unmasked EGFR T-cell engager effectively inhibiting tumor growth compared to the control. This selective activation in the tumor microenvironment is consistent with the preclinical data shown for the other PRO-XTEN masked T-cell engagers. These preclinical findings support the clinical development of 6368. And with IND clearance, this asset is well-positioned to rapidly advance into a Phase 1 clinical study in patients with metastatic head and neck squamous cell carcinoma, non-small cell lung cancer, and colorectal cancer. The Phase 1 clinical study for 6368 is targeted to begin in the first quarter of 2025. Importantly, EGFR expression in healthy tissues poses a significant challenge that potential therapeutics must minimize off-tumor toxicity to be clinically viable. The dual masking technology employed in 6368 can potentially offer a critical advantage over conventional EGFR-targeted approaches. The rapid clearance of 6368 achieved through shortened half-life outside the tumor microenvironment enhances its safety profile and suggests that it could be a transformative treatment option for these patients. To conclude, the PRO-XTEN masking platform and the clinical assets licensed from Sanofi will, following closing, represent a significant step forward in our mission to develop innovative therapies that address the unmet needs of people living with cancer. With that, I would like to hand the presentation over to Brent.

Thank you, Mark. I would now like to discuss the financial aspects of this transaction and how it aligns with our strategic priorities. Following closing, our license agreement with Sanofi will provide us with exclusive rights to three clinical-stage dual masked T-cell engagers. In addition to these clinical-stage assets, the agreement will also provide us with exclusive use of Sanofi's protease-cleavable masking platform for oncology and infectious diseases. After HSR clearance, which we expect will take about 30 days from deal signing, Vir will be responsible for and have sole decision-making authority over all development and commercialization activities related to these assets. In exchange for these rights, Sanofi will be eligible for future development, regulatory, and commercial net sales-based milestone payments as well as tiered royalties on worldwide net sales. These payments are structured to allow Sanofi to benefit from Vir's successful advancement and commercialization of these assets. As part of the agreement, at closing, we will make an upfront payment of $100 million as well as a near-term escrow milestone payment of $75 million, which is subject to 6368 achieving first-in-human dosing, totaling $175 million in near-term payments. As we anticipate integrating the newly licensed assets into our pipeline, we are also taking steps to prioritize our R&D portfolio and restructure our workforce to ensure that we are allocating our resources to the opportunities with the highest potential for patient impact. By concentrating our efforts on our key programs, we believe we can maximize value creation. As part of this prioritization, we have made the decision to stop our R&D programs in influenza, COVID-19, and the T-cell-based viral vector platform; where appropriate, we will seek strategic partners to continue the development of these assets. We are also implementing a workforce restructuring that will result in a reduction of approximately 25% or approximately 140 employees. This reduction excludes the onboarding post-closing of approximately 50 key employees from Sanofi. We expect to end 2024 with around 435 employees, a reduction of close to 200 employees versus our peak in 2023. We estimate this workforce restructuring will result in the reduction of our cost structure by approximately $50 million annually, with savings expected to begin to be fully realized in the first quarter of 2025. In addition, we anticipate cost savings of approximately $50 million through the end of 2025 from the phase-out programs. These cost reductions will allow us to allocate more resources to our core programs while maintaining a strong financial position. Combined with the strategic restructuring efforts announced in late 2023, we have successfully streamlined our operations and reduced our annual cost structure by an estimated $90 million in total from our peak, positioning Vir for enhanced financial resilience. We remain committed to identifying additional cost-saving measures as we move forward. I'll now briefly touch on some key financial highlights for the second quarter of 2024. R&D expenses for the second quarter of 2024 were $105.1 million compared to $168.1 million for the same period in 2023. The decrease was primarily driven by lower clinical development costs and manufacturing costs associated with Vir 2482, lower manufacturing costs associated with our hepatitis programs, and lower personnel costs related to cost-saving initiatives implemented in 2023. SG&A expenses for the second quarter of 2024 were $30.3 million compared to $45.5 million for the same period in 2023. The decrease was primarily related to cost-saving initiatives implemented during the second half of 2023. Restructuring, long-lived asset impairment, and related charges for the second quarter of 2024 were $26.3 million compared to $5.4 million for the same period in 2023. The increase was primarily related to impairment charges related to closing our St. Louis, Missouri facility previously announced on December 13, 2023. We ended the second quarter of 2024 with cash, cash equivalents, and investments of $1.43 billion compared to $1.51 billion at the end of the first quarter of 2024, representing a $78 million decline quarter-over-quarter. I'll now summarize our revised financial guidance for 2024, which takes into account the anticipated impact of the licensing agreement and the workforce restructuring. We now expect our 2024 full-year GAAP operating expenses to be in the range of $580 million to $610 million. Our revised expense guidance reflects a $70 million reduction compared to our prior guidance and demonstrates our commitment to financial discipline. When excluding non-cash stock-based compensation and restructuring expenses from the GAAP operating expense range, the resulting range of $450 million to $500 million represents a 26% year-over-year decline at the midpoint. From a cash perspective, our cash utilization in the second half of 2024 is expected to be similar to the first half of 2024. The expense and cash guidance includes anticipated operating expenses associated with the license agreement. However, they exclude the impact of the previously mentioned $100 million upfront payment due to Sanofi at closing and the $75 million escrow payment. We will incorporate any associated impact on our guidance during our third quarter 2024 earnings press release. As we move forward, we remain confident in our ability to execute on our strategic priorities and create long-term value for our shareholders.

Thank you, Brent. As we have shared previously, our goal is to become a sustainable, fully integrated commercial company, and we have committed to utilizing our strong cash position to invest in complementary attractive clinical-stage assets. We have committed to leverage our scientific expertise, proprietary antibody platform, and our capabilities to broaden our aperture beyond infectious diseases. We have committed to increase our financial discipline and build a more fit-for-purpose organization, and we have committed to sharpen our investment focus on areas where we can make the greatest impact on patients as value creation. Starting with the close of the license agreement with Sanofi and coupled with our strategic restructuring, we will have successfully delivered on all of these commitments. Looking ahead, we will be positioned well with a focused set of development priorities to accelerate near-term value creation. Our development priorities include promising programs in hepatitis delta, hepatitis B, and the newly licensed T-cell engagers. We are looking forward to sharing more with you on these programs as well as our earlier stage programs during our R&D Day in late November. As we look to the future, we are excited about the multiple value-driving catalysts anticipated across our pipeline in the next four to 18 months. We expect to report additional clinical data from our hepatitis delta and our hepatitis B program later this year, as well as share updates, subject to closing on the progress of our newly licensed T-cell engagers during the course of 2025 and 2026. These milestones highlight the potential of our pipeline to deliver meaningful near-term value. In conclusion, today marks a pivotal moment for Vir as we embark on a new chapter in our journey of powering the immune system to transform lives. With a strengthened pipeline, our talented team, and a clear vision for the future, we are well-positioned to deliver on our mission and create long-term value for all our stakeholders. Thank you for your continued support and your interest in Vir. We look forward to keeping you updated on our progress. And with that, I'll turn the call back to Rich to begin the Q&A session.

Thank you, Marianne. We will now start the Q&A session. Please limit questions to two per person so we get to all of our covering analysts. I'll turn it over to you, operator.

Thank you, Rich. We will now begin our analyst Q&A session. Our first question comes from Phil Nadeau with TD Cowen. Please proceed.

Good afternoon. Thank you for taking our questions and congratulations on the deal. I have two questions regarding the new molecules. First, concerning 6309 and 6329, can you clarify if the ongoing dose escalation phases are involving unselected patient populations of all-comer refractory patients, or are HER2 and PSMA specific patients being enrolled in those trials? That's my first question. Secondly, could you provide some insight into the framework by which you'll assess all three of the TCEs for continued investment and progression? This seems very intriguing. However, there are other agents already on the market or in development that target PSMA, HER, and EGFR. What do you hope to achieve overall? Are you aiming for best-in-class, competitive enough, or do you expect to identify specific populations where these treatments are effective and others are not? Thank you.

Thank you, Phil. I appreciate the question. So maybe I'll ask Mark, our CMO, to address your first question.

I appreciate the question. It’s a really good one. For both 6309 and 6329, we are enrolling heavily pretreated tumor types. For 6309, we're including both HER2-positive patients, whether they are HER2-high or HER2-low. In the PSMA program, there isn’t a strict requirement for PSMA positivity, but it will definitely be considered. Regarding how the assets will be evaluated, the Phase 1 studies will allow us to escalate doses to test the hypothesis that we can achieve a better therapeutic index with improved safety and efficacy compared to unmasked TCEs. Additionally, this approach will permit potential expansion cohorts across different diseases, in both monotherapy and combination therapy. As we gather data, we’ll be able to identify the most promising tumor types and combinations compared to monotherapy. I will need to follow up on any specific hurdles or criteria on a future call. However, I would like to emphasize that the current design of the program enables a thorough exploration of both monotherapy and combination therapy across various tumor types, and specifically for PSMA in prostate cancer.

That’s very helpful.

Yeah. The only thing I would add there, Phil, is as we discussed, I mean, the unmet medical need is still incredibly high in each of these areas for two cancers and PSMA cancers. And there is no TCEs approved in either of the areas that we are discussing today.

That's very helpful. Congrats on the deal and thanks for taking our questions.

Thank you.

Our next question comes from Roanna Ruiz with Leerink. Please go ahead.

Hey, good afternoon. This is Nick Gasic on for Roanna. Thanks for taking our questions. Maybe first from us on the new deal with Sanofi. I guess what are the three T-cell engager programs you are most excited about? I'm curious what your thoughts are on their competitive positioning across the three? And I have a follow-up on HDV.

Thank you for the question. I'll begin and then ask Mark to add his thoughts. To reiterate, for HER2, PSMA, and EGFR, while these are biologically validated targets with considerable ongoing activity, the current landscape still shows a significant unmet medical need and high mortality rates for those with HER2 cancers. We noted that only 34% of patients diagnosed with PSMA prostate cancer survive five years, and the survival rates for EGFR-related cancers are alarmingly low, ranging from 3% to 38%. Despite existing approvals and developments, the need remains critical. There are currently no approved T-cell engagers for any of these targets, and even with other modalities available, particularly for HER2 and PSMA, patients still face high mortality rates and many difficult side effects. Therefore, we see a significant opportunity for our therapeutic agents to make a real difference for patients. Mark, would you like to add anything?

Sure. Thanks, Marianne. I want to emphasize that these targets have all been clinically validated, and we are very enthusiastic about each of them. They are at various stages of development. The HER2 program is the most advanced in clinical trials, and we are obtaining preliminary efficacy and safety data in patients with various tumor types. I believe we have the chance to be the first to achieve clinical proof-of-concept within a TCE. The PSMA program is also in Phase 1, and GenX serves as a strong validation for this approach, which is another asset in Phase 1. Additionally, due to universal masking, we can expedite dose escalation in the PSMA program by utilizing insights from the 6309 HER2 program. Regarding EGFR, as previously mentioned, we expect to enter Phase 1 in early Q1 next year, and it represents a potential high-risk, high-reward opportunity. There are several competitors in clinical trials, but multiple tumor types are EGFR positive. Here, the potential impact of the masking is significant, as this marker is widely expressed, and we need to establish a therapeutic index that can effectively treat the cancers with acceptable safety. This aspect of the EGFR program is particularly exciting.

Got it. Thanks for that color. Maybe second question just on HDV. Curious how your interactions with the FDA have been going after the recent HDV data at EASL. And maybe curious what your latest outlook is on a potentially accelerated approval pathway here. Thanks.

Yeah. So good question. So we already announced that we have fast track designation from the FDA, which I think speaks to the high unmet medical need and the very compelling clinical data. We are pursuing other accelerated clinical development pathways such as breakthrough therapy designation, and we are pursuing an engagement with the FDA starting this quarter, Q3, to talk about the registrational program. So we're very excited about the Delta program. We're moving quickly to fit into registrational studies.

That’s helpful. Thanks.

Our next question comes from Paul Choi with Goldman Sachs. Please go ahead.

Hi. Thank you. Good afternoon, and let me also offer my congratulations on the deal. My first question, either for Jennifer or for Mark, is can you maybe share any additional insights regarding the safety profile of the T-cell engagers that you just in-licensed from Sanofi, particularly regarding anything in healthy volunteers that would suggest that you can avoid some of the issues with cytokine release syndrome that have been a hallmark of the class, and just any other evidence you can share with regard to the safety profile? And then my second question, more for Mark probably, is as you think about prosecuting the next stage of clinical trials after the dose escalation studies, can you comment on your ability and the company's ability to pursue multiple drugs here, I guess, in the clinic at the same time? Or will you prioritize one over the other depending on the dose escalation data?

Go ahead, Mark.

Sure. Thanks, Paul, for the questions. In terms of the safety data, the first thing I would mention is the preclinical data that Jen described in detail that shows the fact that there's a 10,000-fold reduction in potency in the masked state as opposed to in the tumor microenvironment where the molecules are activated and form immune synapses with the tumor cells. We have had the opportunity during the diligence to look at preliminary clinical data, including safety data. It's been very valuable to be able to see that. We're not able to comment on that today, but I can say that we gained some valuable insights that gave us confidence to move into prosecuting the deal. In terms of the next stage clinical trials, it's a great question about that. In terms of our development capabilities, I think Vir has demonstrated that we can run large trials at scale, including the peninsula trial of influenza prevention, 3,000 or so patients, and multiple Phase 1 and 2 studies subcutaneously in Delta. And bringing on the Sanofi employees, I think we see a lot of synergies between what we can provide in terms of clinical operations, regulatory and other infrastructure and their knowledge and in-depth experience with these assets and their deep relationships with the KOLs and the sites. I feel confident that we'll be able to prosecute multiple trials simultaneously. That, of course, we'll follow the data. We'll prioritize programs that have the most compelling clinical data as those data evolve.

Okay. Great. Thank you for taking our questions.

Our next question comes from Eric Joseph with J.P. Morgan. Please go ahead.

Hi. Thanks for taking the question. Maybe just one or two on 6309. As the trial is designed, it contemplates a combination with PD-1 pembrolizumab. Maybe you can shed some light on the biological rationale behind that combination. Are PD-1 thought to be potentiators of T-cell engagers and any visibility that you might have at this stage on the safety of that combination so far?

Hi. This is Jen. I can start with that. So maybe I'll start and then hand it over to Mark along the ideas of the safety. So I think fundamentally, what a T-cell engager requires is both targeting the tumor with the tumor-associated antigen and activation of the T-cells through the CD3 arm. This informs the immune synapse and allows the T-cells to directly kill the tumor cells. This requires that you have T-cells there that can be activated. And so there's where I think you have real synergy with something like a PD-1, which really removes a break on a T-cell and allows them to be active. So that's really the fundamental concept behind us of a checkpoint inhibitor with a T-cell engager.

Yeah. In terms of the safety of dose escalation in combination with pembro, I'll just refer to my prior statement, which is we have had the opportunity to see preliminary clinical data, including safety data and preliminary efficacy data. And we found this information really valuable. We're not really able to comment in detail on that at this point, but this is information we'll be providing as a subsequent interaction.

Okay. Great. Well, thanks for the great color and congrats on the deal.

Thanks, Eric.

Our next question comes from Mike Ulz with Morgan Stanley. Please go ahead.

Yep. Hey guys, thanks for taking the question. Maybe just now that you have this PRO-XTEN masking platform, you mentioned the potential to leverage it with your own monoclonal antibody platform. Can you maybe just give us a sense where you initially think you might go with your next-generation antibodies that could be masked now or any particular targets you might be interested in? Thanks.

Jen, do you want to take that?

Thank you for the question. I believe there are significant synergies at play. T-cell engagers are fundamentally based on antibodies, utilizing single-chain variable regions that serve as the binding part of the antibody. Our antibody discovery engine greatly enhances the development of the next generation of T-cell engagers. As demonstrated by our first three molecules, we are concentrating on those with biological proof-of-concept as genuine tumor-associated antigens, while there are several others worth exploring as well. This is just the beginning. The platform shows extensive potential, as evidenced by the initial use of XTEN with the molecule ALTUVIIIO to extend its half-life. It has been proven applicable not only to T-cell engagers but also to other biologics, including cytokines and likely antibodies. Thus, there is considerable potential here, starting with those with biological proof-of-concept and expanding from that point.

Got it. Thank you.

Yeah. The only thing I would add is if you think about these as T-cell engagers and the components of it, as Jen was saying, I mean, on the T-cell engagement side itself, the therapeutic modality, I think we can contribute tremendously with our antibody engineering expertise. And then what is also, I think, very encouraging is that both on the masked side, as Jen said, there's a considerable amount of derisking that has happened given that there's a drug on the market that has been using this month. And also on the cleavable linker side, I think you have seen what Jen presented on the preclinical data, which is very convincingly showing, of course, preclinically in vitro and in vivo that this actually works. So I think there's a lot of derisking that has been on the platform. And as it relates to then really going for new targets, I think we can add a really unique capability.

Our next question comes from Joseph Stringer with Needham & Company.

Hi. Thanks for taking our questions. You mentioned the broad potential of the platform and the in-licensed assets. Just curious if you could provide some additional color behind the decision for the in-licensing, and with the move into oncology intentional, were there other assets and other therapeutic areas that were considered? And then lastly, does the corporate update here affect any of the timelines or any of the resources that you can devote to the HBV or HDV programs? Thank you.

Thank you for your question, Joe. The corporate update does not affect our timelines for the hepatitis delta and hepatitis B studies. Our priority remains on clinical execution for these hepatitis programs, and after the transaction closes, we'll also focus on the newly licensed T-cell engagers. Regarding the decision-making process, over the past year, we have been strategic about utilizing our cash balance, which was $1.43 billion at the end of the second quarter. We aimed to potentially acquire clinical stage assets that align with our existing expertise for strong synergies. We have evaluated many opportunities, but believe this particular fit is unique for various reasons. It addresses a significant unmet need, and our thorough due diligence confirmed the value of both the clinical assets and the underlying science. The biological targets of the three clinical assets are de-risked, and we have solid preclinical data supporting the efficacy of the masking and cleavable linkers. Additionally, this is highly synergistic with our established capabilities, including our antibody expertise, robust clinical development organization, and deep immunology knowledge related to B and T-cells. Finally, this deal will lead to several near-term catalysts and value inflection points for the company, with data on the clinical stage T-cell engagers anticipated within the next nine to 18 months. Overall, we are very excited about this moment for us at Vir.

Our final call for today comes from Alec Stranahan with Bank of America. Please go ahead.

Thanks, and appreciate you taking more questions. Two from us. First, just on the new TC assets. Just trying to understand the competitive positioning a bit more. Anything unique that you could point us to in terms of the design of the mask versus, say, a GenX or CytomX? Or is it more due to the fact that you're using a mask on both the antitumor and the anti-CD3 arms versus the structure of the mask itself? And then I've got a follow-up.

Jen, do you want to take that?

Yes, sure, happy to. So really, I think that the uniqueness is actually in the combination of attributes for this platform. And so I spoke about this, but it was at a fairly high level. So let me elaborate a little bit more. So I think there are some major components. One you hit upon. One is the dual masking. So I think it provides a real advantage to masking both the tumor-associated antigen as well as the CD3 arm, and both arms can be masked because of safety issues. Importantly, this is also a different design, and it's a universal mask. So that's where it comes with this like plug-and-play concept, and that the same mask can be used across multiple different therapeutics. So essentially, the same mask is on all three of the T-cell engagers that are in or close to the clinic. And this allows for rapid execution, both preclinically and also rapid execution in the clinic. As Mark highlighted, this does make a quicker path towards dose escalation for PSMA because the mask itself has been derisked. And ALTUVIIIO itself does also derisk the mask. So there has been an approved product for which this mask is used, providing additional concept around its safety as well as lack of immunogenicity. And then finally, I think the other component that we've hit on that I think is also quite exciting is this broader applicability of the masks, not only for T-cell engagers but also potentially for other molecules like cytokines or potentially other protein therapeutics like antibodies.

Okay.

Alec, I would just add that from a competitive landscape perspective, for HER2, there's no other masked T-cell engagers in development. For PSMA, there is one masked T-cell engager in development and for EGFR, there are three. So I mean, in the broader context of things here, where TCEs, as we discussed, have a lot of shortcomings and a lot of toxicity and really challenging profiles for patients. We have an opportunity here through these masked TCEs to really drive the difference, and the competitive landscape is really not that intense.

Okay. Thanks. That's clear. And then maybe one quick one, just putting a finer point on the applications in immunology. Would this mostly be through half-life extension for, say, cytokines? Or are there any targets or indications you think could be the most apt initial avenues for development? Thanks.

Yeah. So we can extend the half-life, but I think actually, there are two attributes. So the way that the mask is used in ALTUVIIIO is purely fixed on the half-life. The way the mask is used for the T-cell engagers is that it does extend the half-life and allows them to get to the site of action. However, once they are cleaved, they don't have a very short half-life, which then allows them to act in that tumor microenvironment, because they're right there with their target antigen. It activates the T-cells, which then have a longer list and activation profile. But that active molecule once it circulates, then has a very short half-life, and that provides an avid safety benefit. You can envision the same type of thing being applied to a cytokine, having it be activated only at the site where you want it to be activated and then having that short half-life be an attribute, because we all know that these cytokines will be incredibly potent and beneficial for activating immune cells; they often have very high associated toxicity themselves. So while they have a short half-life, you don't want them to have too long at half-life or you're going to have greater toxicity. So I think those both are true. Thank you for the question.

Thank you.

All right. This concludes the Q&A session of the call. Thank you for participating, and I'll turn the call back over to Marianne.

Yes, apologies. Thanks everyone for your interest in listening to our earnings call today, and people will put that close call. Thank you.