```markdown [Corporate and Pipeline Highlights](index=1&type=section&id=Corporate%20and%20Pipeline%20Highlights) Vir initiated a Phase 3 trial for chronic hepatitis delta, advanced oncology T-cell engagers, and holds $1.0 billion in cash - Initiated the Phase 3 registrational ECLIPSE program for chronic hepatitis delta (CHD), which has received U.S. FDA Breakthrough and Fast Track designations, as well as EMA PRIME and Orphan Drug designations[1](index=1&type=chunk) - Dose escalation is ongoing for two PRO-XTEN™ dual-masked T-cell engagers: VIR-5818 (HER2-targeting) and VIR-5500 (PSMA-targeting)[1](index=1&type=chunk)[2](index=2&type=chunk) - A Phase 1 study of VIR-5525, an EGFR-targeting T-cell engager, is on track to begin in the second quarter of 2025[1](index=1&type=chunk)[2](index=2&type=chunk) - The company holds a strong financial position with approximately **$1.0 billion** in cash and investments, providing an operational runway into mid-2027[1](index=1&type=chunk) [Pipeline Programs](index=1&type=section&id=Pipeline%20Programs) The company advances its clinical pipeline, highlighted by a Phase 3 CHD program, oncology TCEs, and CHB partnership efforts [Chronic Hepatitis Delta (CHD)](index=1&type=section&id=Chronic%20Hepatitis%20Delta%20(CHD)) - The first Phase 3 trial, ECLIPSE 1, enrolled its first patient in March 2025 to assess the efficacy and safety of tobevibart and elebsiran[3](index=3&type=chunk) - A second Phase 3 trial, ECLIPSE 2, is planned to evaluate switching to tobevibart and elebsiran in patients who have not achieved viral suppression with existing therapy[3](index=3&type=chunk) - The combination therapy is supported by multiple key regulatory designations, including FDA Breakthrough Therapy, FDA Fast Track, EMA PRIME, and EMA Orphan Drug designations, highlighting the significant unmet need[4](index=4&type=chunk) [Solid Tumors](index=2&type=section&id=Solid%20Tumors) - VIR-5818 (HER2-targeting TCE) and VIR-5500 (PSMA-targeting TCE) are advancing through dose escalation[6](index=6&type=chunk) - Early Phase 1 data for VIR-5818 showed tumor shrinkage in **50% (10/20)** of participants at doses ≥400 µg/kg[6](index=6&type=chunk) - Early Phase 1 data for VIR-5500 showed PSA reductions in **100% (12/12)** of mCRPC patients after an initial dose ≥120 µg/kg[6](index=6&type=chunk) - A Phase 1 study of VIR-5525, an EGFR-targeting TCE, is planned to initiate in Q2 2025[6](index=6&type=chunk) [Chronic Hepatitis B (CHB)](index=2&type=section&id=Chronic%20Hepatitis%20B%20(CHB)) - Functional cure data from the 24-week follow-up of the Phase 2 MARCH study will be presented at the EASL Congress on May 9, 2025[6](index=6&type=chunk) - Future advancement of the CHB program is contingent on securing a worldwide development and commercialization partner[6](index=6&type=chunk) [Preclinical Pipeline Candidates](index=3&type=section&id=Preclinical%20Pipeline%20Candidates) - The company is progressing multiple undisclosed PRO-XTEN™ dual-masked TCEs against clinically validated targets for various solid tumors[14](index=14&type=chunk) - In collaboration with the Gates Foundation, a broadly neutralizing antibody has been advanced to development candidate status in the HIV cure program[14](index=14&type=chunk) [Corporate Update](index=3&type=section&id=Corporate%20Update) Vir amended its Alnylam collaboration, assuming sole responsibility for elebsiran development and commercialization - Vir and Alnylam amended their collaboration agreement after Alnylam elected not to opt-in to its profit-sharing option for elebsiran in CHB and CHD[14](index=14&type=chunk) - Vir is now solely responsible for all development, manufacturing, and commercialization activities for elebsiran[12](index=12&type=chunk) [First Quarter 2025 Financial Results](index=3&type=section&id=First%20Quarter%202025%20Financial%20Results) Vir reported Q1 2025 revenues of $3.0 million, a sharp decrease, and a net loss of $121.0 million, maintaining $1.02 billion cash | Financial Metric | Q1 2025 | Q1 2024 | Change (YoY) | | :--- | :--- | :--- | :--- | | Total Revenues | $3.0M | $56.4M | -94.6% | | R&D Expenses | $118.6M | $100.1M | +18.5% | | SG&A Expenses | $23.9M | $36.3M | -34.2% | | Net Loss | $121.0M | $65.3M | +85.3% | | Net Loss Per Share | $(0.88) | $(0.48) | +83.3% | - Cash, cash equivalents, and investments totaled approximately **$1.02 billion** as of March 31, 2025[9](index=9&type=chunk) - The decrease in revenue was primarily due to **$51.7 million** of deferred revenue recognized in Q1 2024 from the expiration of a GSK agreement option[10](index=10&type=chunk) - The increase in R&D expenses was mainly driven by a **$30.0 million** expense to Alnylam and costs to initiate the ECLIPSE Phase 3 program[11](index=11&type=chunk) [2025 Financial Guidance](index=4&type=section&id=2025%20Financial%20Guidance) Vir Biotechnology expects its existing cash and investments to fund operations into mid-2027 based on current plans - The Company expects its cash, cash equivalents and investments to fund its operations into mid-2027[18](index=18&type=chunk) [About Key Programs](index=4&type=section&id=About%20Key%20Programs) Key programs include PRO-XTEN™ T-cell engagers for solid tumors and a tobevibart/elebsiran combination for chronic hepatitis [About PRO-XTEN™ T-cell Engagers (VIR-5818, VIR-5500, VIR-5525)](index=4&type=section&id=About%20VIR-5818,%20VIR-5500,%20VIR-5525) - These are investigational T-cell engagers (TCEs) targeting HER2, PSMA, and EGFR, respectively, for the treatment of solid tumors[20](index=20&type=chunk) - The PRO-XTEN™ masking technology is designed to keep the TCEs inactive until they reach the tumor microenvironment, where they are activated to kill cancer cells. This aims to minimize systemic toxicity and expand the therapeutic index[21](index=21&type=chunk) [About Tobevibart and Elebsiran](index=4&type=section&id=About%20Tobevibart%20and%20Elebsiran) - Tobevibart is an investigational monoclonal antibody designed to inhibit hepatitis B and delta virus entry into liver cells and reduce the level of circulating viral particles[22](index=22&type=chunk) - Elebsiran is an investigational siRNA designed to degrade hepatitis B virus RNA, thereby limiting the production of hepatitis B surface antigen (HBsAg)[23](index=23&type=chunk) [Financial Statements](index=7&type=section&id=Financial%20Statements) Condensed Q1 2025 financial statements show total assets of $1.31 billion, liabilities of $263.9 million, and a $121.0 million net loss [Condensed Consolidated Balance Sheets](index=7&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) | Balance Sheet (in thousands) | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | **Cash, cash equivalents & investments** | $1,024,078 | $1,151,391 | | **Total Assets** | **$1,307,727** | **$1,398,813** | | Total Current Liabilities | $137,286 | $119,662 | | **Total Liabilities** | **$263,908** | **$248,428** | | **Total Stockholders' Equity** | **$1,043,819** | **$1,150,385** | [Condensed Consolidated Statements of Operations](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) | Statement of Operations (in thousands) | Three Months Ended March 31, 2025 | Three Months Ended March 31, 2024 | | :--- | :--- | :--- | | Total Revenues | $3,032 | $56,376 | | Total Operating Expenses | $142,579 | $136,457 | | Loss from Operations | $(139,547) | $(80,081) | | **Net Loss** | **$(120,965)** | **$(65,276)** | | **Net Loss Per Share** | **$(0.88)** | **$(0.48)** | ```

Financial Data and Key Metrics Changes - R&D expenses for 2024 were $507 million, down from $580 million in 2023, reflecting a 12.59% decrease despite absorbing approximately $103 million in Sanofi transaction expenses [49] - G&A expenses decreased to $119 million in 2024 from $174 million in the prior year, marking a 31.61% reduction year-over-year [50] - The net loss for 2024 was $522 million compared to $615 million in 2023, a decline of approximately 15.08% [51] - The company ended 2024 with $1.1 billion in cash, cash equivalents, and investments, providing a runway into mid-2027 [53] Business Line Data and Key Metrics Changes - The hepatitis delta program is set to initiate the ECLIPSE Phase III program in the first half of 2025, with promising results from the SOLSTICE Phase II data showing 41% of patients achieving HDV RNA levels below the target not detected threshold at 24 weeks [20][22] - In oncology, the T-cell engager programs, including VIR-5818 and VIR-5500, have shown early signs of clinical activity, with a 33% confirmed partial response rate in colorectal cancer for VIR-5818 and 100% PSA declines in prostate cancer for VIR-5500 [31][38] Market Data and Key Metrics Changes - The market for hepatitis delta therapies is characterized by a lack of efficacious treatment options, severe clinical outcomes, and potential for value-based pricing [10] - The company has received significant regulatory support for its hepatitis delta program, including breakthrough therapy designation and Fast Track designation from the FDA, as well as PRIME designation and Orphan Drug status from the EMA [25] Company Strategy and Development Direction - The strategic focus on T-cell engagers and hepatitis has positioned the company for future growth and value creation, allowing for efficient resource allocation across its pipeline [8] - The company aims to maximize the value of its broader pipeline through active exploration of partnership opportunities [17] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's strategy for long-term success and value creation, emphasizing the strong financial position and the potential impact of their innovative therapies [18][53] - The company is committed to advancing its key programs while maintaining financial flexibility, with a focus on accelerating clinical enrollment and initiating activities toward registration for its lead programs [54][56] Other Important Information - The company has implemented significant cost-saving initiatives, resulting in a 30% reduction in R&D spending year-over-year [49][50] - The PRO-XTEN platform has shown promising early results across multiple solid tumor types, with plans to initiate a Phase I study for VIR-5525 in the first half of 2025 [41][42] Q&A Session Summary Question: Can you elaborate on the mechanism for the cleavage and how efficient it is in the tumor microenvironment? - Management indicated that efficient cleavage is observed in both HER2 and PSMA programs, with minimal toxicity in peripheral tissues, suggesting tumor-specific cleavage [63][64] Question: What additional steps are needed to start the ECLIPSE trial? - Management confirmed that they are on track to initiate the ECLIPSE program in the first half of the year, with a focus on efficient patient recruitment due to high unmet need [70] Question: What sort of patients are envisioned for the Phase I study of 5525? - The Phase I study will include patients who have exhausted all current standard of care, allowing for prior experimental drug treatments [78] Question: What are the go/no-go criteria for the hepatitis B program? - Management is looking for a 30% functional cure in the triplet and 20% in the doublet, based on prior interactions with key opinion leaders [76] Question: Will you approach the need for steroid prophylaxis similarly for 5525? - Management confirmed that they will not use prophylactic steroids for 5525, similar to the approach taken with the other two assets [115]

Group 1 - Vir Biotechnology reported a quarterly loss of $0.76 per share, better than the Zacks Consensus Estimate of a loss of $0.85, and an improvement from a loss of $0.86 per share a year ago, resulting in an earnings surprise of 10.59% [1] - The company posted revenues of $12.37 million for the quarter ended December 2024, missing the Zacks Consensus Estimate by 15.22%, and down from $16.79 million in the same quarter last year [2] - Over the last four quarters, Vir Biotechnology has surpassed consensus EPS estimates two times and topped consensus revenue estimates just once [2] Group 2 - The stock has gained approximately 24% since the beginning of the year, significantly outperforming the S&P 500's gain of 1.3% [3] - The company's earnings outlook, including current consensus earnings expectations for upcoming quarters, will be crucial for future stock performance [4] - The current consensus EPS estimate for the upcoming quarter is -$0.92 on revenues of $21.56 million, and for the current fiscal year, it is -$3.55 on revenues of $59.08 million [7] Group 3 - The Zacks Industry Rank for Medical - Biomedical and Genetics is in the top 24% of over 250 Zacks industries, indicating a favorable outlook for the industry [8] - Empirical research shows a strong correlation between near-term stock movements and trends in earnings estimate revisions, which can be tracked by investors [5] - The estimate revisions trend for Vir Biotechnology is currently mixed, resulting in a Zacks Rank 3 (Hold) for the stock, suggesting it is expected to perform in line with the market in the near future [6]

Growth and Operations - The company has experienced significant growth in operations, particularly in research, development, and regulatory affairs, necessitating improvements in managerial and operational systems[360]. - The company must manage growth effectively to avoid delays in executing business plans and potential disruptions in operations[360]. Acquisitions and Integration - The company has previously acquired numerous biotechnology companies between 2016 and 2018, with the success of these acquisitions dependent on effective integration into existing product candidates[358]. Financial Risks and Fluctuations - The company faces risks related to market fluctuations and potential impairments of acquired goodwill and intangible assets, which could adversely affect financial results[359]. - The company's financial condition and results of operations are expected to fluctuate from quarter to quarter and year to year due to various uncontrollable factors[377]. - The company is exposed to foreign currency exchange rate fluctuations, which may unpredictably affect its operating results[378]. - The market price of the company's common stock has been volatile, influenced by external economic conditions and investor concerns, potentially leading to substantial losses for shareholders[379]. Compliance and Regulatory Risks - The company is subject to stringent privacy laws and regulations, which, if not complied with, could result in significant fines and reputational harm[367]. - The company may incur substantial costs to comply with evolving data privacy regulations, which could impact financial condition and operational practices[372]. - The company is actively monitoring changes in data privacy regulations, which may require significant resources to ensure compliance[372]. - The company has incurred and will continue to incur significant costs related to compliance as a public company, impacting its financial condition[385]. Cybersecurity and Data Protection - The company has implemented security measures to protect data, but vulnerabilities remain, and significant breaches could materially affect business operations[363]. - The company has a cybersecurity insurance policy, but it may not cover all potential liabilities from security breaches[364]. Internal Control and Accounting - A material weakness in internal control over financial reporting could impair the accuracy of financial statements and investor confidence, potentially leading to sanctions[387]. - Changes in generally accepted accounting principles may adversely affect the company's reported financial results, causing unexpected fluctuations[389]. Tax Considerations - As of December 31, 2024, the company had net operating loss carryforwards of $645.3 million for federal tax purposes and $450.2 million for state tax purposes, with federal carryforwards beginning to expire in 2036 and state carryforwards in 2031[375]. - The Tax Cuts and Jobs Act of 2017 requires the company to capitalize and amortize research and development expenditures over five or fifteen years, which may reduce anticipated net operating losses in the coming years[376]. Shareholder Considerations - The concentration of ownership among executive officers and principal stockholders may limit new investors' influence over significant corporate decisions[382]. - The company does not anticipate paying cash dividends in the foreseeable future, with capital appreciation being the sole source of gain for investors[384].

Financial Performance - Revenue for Q4 2024 was $12.4 million, down from $16.8 million in Q4 2023, and full-year revenue for 2024 was $74.2 million, compared to $86.2 million in 2023[12]. - Vir Biotechnology reported total revenues of $12,374,000 for Q4 2024, a decrease of 26.5% compared to $16,787,000 in Q4 2023[32]. - The company's net loss for Q4 2024 was $104,589,000, compared to a net loss of $115,973,000 in Q4 2023, reflecting a 3.5% improvement[32]. - Net loss attributable to Vir Biotechnology for Q4 2024 was $(104.6) million, or $(0.76) per share, compared to a net loss of $(116.0) million, or $(0.86) per share, in Q4 2023[19]. - The company reported a 28% year-over-year reduction in operating expenses for 2024, excluding the upfront expense related to the Sanofi licensing agreement[11]. - Research and development expenses for the year ended December 31, 2024, were $506,499,000, down from $579,720,000 in 2023, indicating a reduction of 12.6%[32]. - Total current assets decreased to $1,042,458,000 in 2024 from $1,588,226,000 in 2023, representing a decline of 34.4%[30]. - The company's total liabilities decreased to $248,428,000 in 2024 from $328,824,000 in 2023, a reduction of 24.4%[30]. - As of December 31, 2024, Vir Biotechnology's cash and cash equivalents totaled $222,947,000, a decrease from $241,576,000 at the end of 2023[30]. - The company has approximately $1.10 billion in cash, cash equivalents, and investments as of December 31, 2024, with a cash runway into mid-2027[11]. Clinical Development - The ECLIPSE Phase 3 registrational clinical program in chronic hepatitis delta is on track to begin in the first half of 2025[1]. - The company plans to initiate a Phase 1 study of VIR-5525, its dual-masked EGFR-targeting T-cell engager, in the first half of 2025[1]. - The company anticipates functional cure data from the 24-week follow-up of the MARCH Part B Phase 2 trial in the second quarter of 2025[8]. - The dual-masked T-cell engager VIR-5818 showed tumor shrinkage in 50% of participants receiving doses ≥400 µg/kg[8]. - The dual-masked T-cell engager VIR-5500 demonstrated PSA reductions in 100% of metastatic castration-resistant prostate cancer patients after an initial dose ≥120 µg/kg[8]. - The company is advancing multiple undisclosed dual-masked T-cell engagers against clinically validated targets in solid tumors[12]. Strategic Focus - The company anticipates continued focus on its oncology and hepatitis programs, with ongoing clinical studies and potential partnering opportunities[28]. - Vir Biotechnology's strategy includes leveraging artificial intelligence and machine learning for next-generation protein engineering and other R&D efforts[28]. - The weighted-average shares outstanding for basic calculations increased to 136,808,690 in Q4 2024 from 134,608,811 in Q4 2023[32].

Core Insights - Vir Biotechnology, Inc. announced promising initial data from a phase I study for its investigational candidates VIR-5818 and VIR-5500 targeting solid tumors [1][2] - The company's shares surged by 58.2% following the announcement, with a 21.1% increase over the past year compared to a 14.3% decline in the industry [2] Group 1: VIR-5818 for HER2-Expressing Cancers - VIR-5818 targets HER2-expressing solid tumors and is being evaluated both as a monotherapy and in combination with Merck's Keytruda [4] - Early efficacy data indicated that 50% of patients receiving doses ≥400 µg/kg experienced tumor shrinkage across multiple HER2-positive tumor types [5] - A confirmed partial response of 33% was observed in a subset of participants with HER2-positive colorectal cancer who had exhausted standard care [5] - Treatment with VIR-5818 was reported to be generally safe and well tolerated [6] Group 2: VIR-5500 for PSMA-Targeting Cancers - VIR-5500 is designed to target PSMA in metastatic castration-resistant prostate cancer (mCRPC) and is currently undergoing a phase I study [9] - All 12 patients treated with an initial dose of VIR-5500 ≥120 µg/kg experienced reductions in prostate-specific antigen (PSA), with a 58% PSA 50 response rate confirmed [9] - The treatment was also generally safe and well tolerated, with no dose-limiting cytokine release syndrome observed [9] Group 3: Technology and Mechanism - Both VIR-5818 and VIR-5500 utilize PRO-XTEN masking technology, allowing selective activation of T-cell engagers in the tumor microenvironment, which minimizes damage to healthy cells [3]

Core Insights - Vir Biotechnology is primarily focused on developing novel agents for managing hepatitis, and there has been a significant rally in its share price recently [1] Company Overview - Vir Biotechnology is a biotech company listed on NASDAQ under the ticker VIR [1] Market Activity - The recent rally in Vir Biotechnology's share price indicates increased investor interest and potential market momentum [1]

Core Insights - Vir Biotechnology (NASDAQ: VIR) is developing treatments for hepatitis B (HB) and hepatitis delta (HD) and is expected to report data in the oncology space that may positively impact its stock performance [1] Company Developments - The company has been focusing on trading around significant events such as trial results and NDA/BLA approvals, indicating a strategic approach to market movements [1]

Core Insights - Vir Biotechnology has significantly transformed its strategic focus and technological platforms since July, phasing out its vaccines and viral immunotherapy programs while maintaining the development of chronic hepatitis treatment [1] Group 1 - The company has shifted its focus away from vaccines and viral immunotherapy [1] - Development efforts are now concentrated on chronic hepatitis treatment [1]

Financial Performance - Total revenues for the three months ended September 30, 2024, were $2,380,000, a decrease from $2,639,000 in the same period of 2023[14] - The net loss for the three months ended September 30, 2024, was $213,717,000, compared to a net loss of $163,413,000 for the same period in 2023, representing an increase of approximately 30%[14] - The company reported a net loss per share attributable to Vir of $(1.56) for the three months ended September 30, 2024, compared to $(1.22) for the same period in 2023[14] - As of September 30, 2023, the company reported a net loss of $499.1 million, compared to a net loss of $417.4 million for the nine months ended September 30, 2024[21][23] - Total revenues for the nine months ended September 30, 2024, were $61,831 thousand, down from $69,393 thousand in the same period of 2023, a decrease of $7,562 thousand[125] - Net loss for Q3 2024 was $(213,717) thousand compared to $(163,413) thousand in Q3 2023, an increase in loss of $50,304 thousand[125] Expenses - Research and development expenses for the nine months ended September 30, 2024, were $400,416,000, compared to $470,754,000 for the same period in 2023, reflecting a decrease of approximately 15%[14] - The company reported a total operating expense of $233,684,000 for the three months ended September 30, 2024, an increase from $189,371,000 in the same period of 2023[14] - Research and development expenses for Q3 2024 increased to $195,178 thousand from $145,028 thousand in Q3 2023, an increase of $50,150 thousand[129] - Selling, general and administrative expenses for Q3 2024 decreased to $25,744 thousand from $40,933 thousand in Q3 2023, a decrease of $15,189 thousand[125] - Total operating expenses for the nine months ended September 30, 2024, were $531,846 thousand, down from $614,682 thousand in the same period of 2023, a decrease of $82,836 thousand[125] - The company incurred restructuring expenses of approximately $10.4 million in Q3 2024, with $8.2 million classified as research and development expenses[82] Equity and Liabilities - Total stockholders' equity as of September 30, 2024, was $1,240,727,000, down from $1,590,236,000 as of December 31, 2023[11] - The accumulated deficit as of September 30, 2024, was $(655,195,000), compared to $(237,824,000) as of December 31, 2023[11] - The total liabilities and stockholders' equity as of September 30, 2024, were $1,498,356,000, down from $1,919,060,000 as of December 31, 2023[11] - The company had no debt outstanding as of September 30, 2024, indicating a strong liquidity position[149] Cash Flow - The company had $1.19 billion in cash, cash equivalents, and investments as of September 30, 2024, which is expected to fund operations for at least the next twelve months[26] - The company reported net cash used in operating activities of $358.7 million for the nine months ended September 30, 2024, a decrease from $670.9 million for the same period in the previous year[23] - Cash, cash equivalents, and investments totaled $1.19 billion as of September 30, 2024, with an accumulated deficit of $655.2 million[137] - Cash provided by investing activities increased to $358.6 million for the nine months ended September 30, 2024, compared to $269.4 million in 2023[143] Research and Development - The company has a clinical development pipeline targeting hepatitis delta virus (HDV) and hepatitis B virus (HBV), along with multiple oncology programs[25] - Research and development expenses primarily relate to discovery efforts and clinical development, with costs recognized as incurred[43] - The company recognized additional net research and development expenses of $1 million and $6.1 million during the three months ended September 30, 2024 and 2023, respectively, under the 2020 GSK Agreement[76] Grants and Collaborations - The Company has been awarded grants totaling up to $49.9 million from the Bill & Melinda Gates Foundation to support various vaccine programs[64] - Under the BARDA Agreement, the Company may receive up to $1.0 billion, with $55.0 million allocated for the development of VIR-2482[65] - The Company recognized grant revenue related to BARDA of $0.5 million and $2.9 million for the three months ended September 30, 2024 and 2023, respectively[67] Strategic Initiatives - The company entered into a sales agreement to offer and sell shares of its common stock for an aggregate offering price of up to $300 million[26] - The company announced a workforce reduction of approximately 25%, equating to about 140 employees, as part of a strategic shift[108] - The company expects to recognize restructuring expenses of approximately $11 million to $13 million primarily related to employee severance cash payouts in the second half of 2024[82] Future Outlook - The company does not expect significant revenue from product candidates until regulatory approvals are obtained, with a nominal amount of collaboration revenue anticipated in 2024[111] - The FDA has excluded the use of sotrovimab in all U.S. regions, leading to uncertainty regarding future collaboration revenue from this product[112] - The company plans to present additional data from the Phase 2 chronic hepatitis delta SOLSTICE trial in November 2024, involving approximately 60 patients[105]