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January 2026 Corporate Overview Presentation 2026 Vir Biotechnology, Inc. 1
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Legal disclaimer Forward-Looking Statements Statements in this presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding: the therapeutic and commercial potential of Vir Biotechnology's CHD program, as well as Vir Biotechnology's strategy, plans and expectations related thereto; the therapeutic and commercial potential of Vir Biotechnology's oncology solid tumor portfolio, preclinical pipeline and the PRO-XTEN® masking technology, as well as Vir Biotechnology's strategy, plans and expectations related thereto; the potential of and Vir Biotechnology's expectations for its other pipeline programs; Vir Biotechnology's anticipated cash runway; Vir Biotechnology's plans and expectations for its clinical development programs, including protocols for and enrollment into ongoing and planned clinical studies, potential partnering opportunities, and data readouts and presentations, as well as anticipated timelines; the potential benefits, safety and efficacy of Vir Biotechnology's investigational therapies; and any assumptions underlying any of the foregoing. Words such as “aim,” “anticipate,” “believe,” “could,” “expect,” “goal,” “intend,” “may,” “plan,” “potential,” “promising,” “will,” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. These forward-looking statements are based on the beliefs of the management of Vir Biotechnology, as well as assumptions made by and information currently available to management. Such statements reflect the current views of Vir Biotechnology with respect to future events and are subject to known and unknown risks, including, without limitation: unexpected safety or efficacy data or results observed during clinical studies or in data readouts, including the occurrence of adverse safety events; risks of unexpected costs, delays or other unexpected hurdles; the timing and amount of Vir Biotechnology's actual operating expenses, as determined in accordance with U.S. Generally Accepted Accounting Principles; difficulties in collaborating with other companies, some of whom may be competitors of Vir Biotechnology or otherwise have divergent interests, and uncertainty as to whether the benefits of Vir Biotechnology's various collaborations can ultimately be achieved; challenges in accessing manufacturing capacity; clinical site activation rates or clinical enrollment rates that are lower than expected; the timing and outcome of Vir Biotechnology's planned interactions with regulatory authorities, as well as general difficulties in obtaining any necessary regulatory approvals; successful development and/or commercialization of alternative product candidates by Vir Biotechnology's competitors, as well as changes in expected or existing competition; Vir Biotechnology's use of AI and machine learning in its efforts to engineer next-generation proteins and in other research and development efforts; geopolitical changes or other external factors; and unexpected litigation or other disputes. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. The actual results may vary from the anticipated results and the variations may be material. Other factors that may cause the Company’s actual results to differ from current expectations are discussed in the Company’s filings with the U.S. Securities and Exchange Commission, including the section titled “Risk Factors” contained therein. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in this presentation. You are cautioned not to place undue reliance on any scientific data presented or these forward-looking statements, which speak only as of the date of this presentation. Except as required by law, Vir Biotechnology undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. Vir Biotechnology claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995 for all forward-looking statements. Product candidates included in this presentation are investigational and have not been approved by the US Food and Drug Administration or other regulatory authorities. No representation is made or intended regarding their safety or efficacy or that of other investigational agents mentioned herein. Any comparative data presented are based on cross-trial comparisons and not head-to-head clinical studies; therefore, caution should be exercised in interpreting these data. PRO-XTEN® is a trademark of Amunix Pharmaceuticals, Inc., a Sanofi company 22026 Vir Biotechnology, Inc.
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3 POWERING THE IMMUNE SYSTEM TO TRANSFORM LIVES 2026 Vir Biotechnology, Inc.
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Our path to delivering transformational therapies to people living with devastating diseases Commercializing our chronic hepatitis delta (CHD) combination therapy will drive near-term revenue sustainability Aiming Vir Bio's discovery engine at developing a robust pipeline of cancer immunotherapies creates sustainable long-term growth 2026 Vir Biotechnology, Inc. 4 Accelerating our masked T-cell engager (TCE) immunotherapy portfolio offers key value inflection points Financial Highlights ~$781M cash and investments1 with cash runway into Q4 2027 Strategic Collaborations Selectively partner drug candidates to focus internal resources, unlock the value of our pipeline and maximize benefit to patients 1 We estimate our cash, cash equivalents, and investments to be approximately $781 million as of December 31, 2025. This is a preliminary, estimated, and unaudited financial result. Actual results may differ from this estimate.
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World class protein engineering, antibody discovery dAIsY AI/ML for antibody optimization Exclusive PRO-XTEN® universal masking technology We’ve developed a powerful Vir Bio discovery engine to fuel the next generation of therapeutics World class protein engineering, antibody / TCE discovery dAIsY AI/ML for antibody / TCE optimization Exclusive PRO-XTEN® universal masking technology Building on legacy of infectious disease innovation to deliver next generation of powerful medicines, including cancer immunotherapies with better therapeutic index EbangaTM (ansuvimab-zykl) for the treatment of ebola virus Xevudy® (sotrovimab) for the treatment of SARS-COVID 19 2026 Vir Biotechnology, Inc. 5 Our distinctive capabilities dAIsY : (dataAI structure and antibodY) AI engine; TCE: T-cell engager Ebanga is a trademark of Ridgeback Bio. Xevudy is a registered trademark of GSK
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Delivering a differentiated pipeline in oncology and infectious disease Driving near-term and long-term value creation 62026 Vir Biotechnology, Inc. 1 Masked TCEs licensed from Sanofi 2 In collaboration with the Gates Foundation ARPIs: androgen receptor pathway inhibitors; EGFR: epidermal growth factor receptor; HER2: human epidermal growth factor receptor 2; HIV: human immunodeficiency virus; PSMA: prostate-specific membrane antigen; siRNA: small interfering RNA; TCE: T-cell engager Tobevibart incorporates Xencor’s XtendTM and other Fc technologies Norgine holds exclusive license for the commercial rights to the combination of tobevibart and elebsiran in Europe, Australia and New Zealand Brii Biosciences retains rights to the combination of tobevibart and elebsiran in the Greater China Territory (People’s Republic of China, Hong Kong, Taiwan and Macau) Disease Area Product Candidate Goal Pre-clinical Phase 1 Phase 2 Phase 3 Approval CLINICAL PROGRAMS Chronic Hepatitis Delta tobevibart + elebsiran Treatment Solid Tumors VIR-5500 (PSMA)1 ± ARPIs Treatment Solid Tumors VIR-5818 (HER2)1 ± pembrolizumab Treatment Solid Tumors VIR-5525 (EGFR)1 ± pembrolizumab Treatment PRE -CLINICAL PROGRAMS HIV Treatment / Cure 2 Preclinical antibody candidates Treatment Solid Tumors 7 PRO-XTEN® TCE programs including lung, colorectal, and bladder cancers Treatment AntibodysiRNA Masked TCE
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Upcoming clinical milestones PROGRAM DRUG CANDIDATES REGIMEN CATALYST TIMING Hepatitis Delta tobevibart (mAb) + elebsiran (siRNA) SOLSTICE: 72 & (partial) 96-week data ECLIPSE 1: topline data ECLIPSE 2: topline data ECLIPSE 3: topline data Jan’26 4Q’26 1Q’27 1Q’27 PSMA-Expressing Prostate Cancer VIR-5500 dual-masked PSMAxCD3 TCE Phase 1 dose escalation response data Feb’26 ASCO GU HER2-Expressing Solid Tumors VIR-5818 dual-masked HER2xCD3 TCE Phase 1 dose escalation response data 2H'26 EGFR-Expressing Solid Tumors VIR-5525 dual-masked EGFRxCD3 TCE Phase 1 initial dose escalation clinical data TBA CD3: cluster of differentiation 3; EGFR, epidermal growth factor receptor; HER2: human epidermal growth factor receptor 2; PSMA: prostate-specific membrane antigen; siRNA: small interfering RNA; TBA, to be announced; TCE: T-cell engager; mAb, monoclonal antibody 2026 Vir Biotechnology, Inc. 7
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Our clinical programs address large and growing unmet needs Infectious Disease Oncology – Solid Tumors 2032 prevalence estimate for U.S., EU4 and UK EGFR VIR-5525 Phase 1 Drug-Treated Patients3 431K mNSCLC 69K mHNSCC 271K mCRC HER2 VIR-5818 Phase 1 Drug-Treated Patients3 27K HER2+ mUC 11K HER2+ mCRC PSMA VIR-5500 Phase 1 Drug-Treated Patients3 100K mCRPC 60K mHSPC CHD Tobevibart + elebsiran Phase 3 Active Viremic Patients 174K U.S.1 + UK + EU2 (all 27 member states) 1 U.S. sources include Wong 2024, Polaris 2024, Stockdale 2020, Gish 2024; 2 EU sources include Polaris 2024, Delmas 2014, Wong 2024, Heidrich 2009, Reinheimer 2012, Stockdale 2020, Stroffolini 2020, Brancaccio 2019, Annual England Sentinel System 2020, Tseneva-Damyanova 2023, Papatheodoridis 2023, Parames 2016, Genne 2011, Hirzel 2015; 3 Clarivate DRG, projected drug treated patients, 2032 CHD: chronic hepatitis delta; EGFR: epidermal growth factor receptor; EU4: France, Germany, Italy and Spain; HER2: human epidermal growth factor receptor 2; mCRC: metastatic colorectal cancer; mCRPC: metastatic castrate-resistant prostate cancer; mHNSCC: metastatic head and neck squamous cell carcinoma; mHSPC: metastatic hormone-sensitive prostate cancer; mNSCLC: metastatic non-small cell lung cancer; mUC: metastatic urothelial carcinoma; PSMA: prostate-specific membrane antigen 2026 Vir Biotechnology, Inc. 8
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Our path to delivering transformational therapies to people living with devastating diseases: Chronic Hepatitis Delta (CHD) Commercializing our chronic hepatitis delta (CHD) combination therapy will drive near-term revenue sustainability Accelerating our masked T-cell engager (TCE) immunotherapy portfolio offers key value inflection points Aiming Vir Bio's discovery engine at developing a robust pipeline of cancer immunotherapies creates sustainable long-term growth 2026 Vir Biotechnology, Inc. 9 Financial Highlights ~$781M cash and investments1 with cash runway into Q4 2027 Strategic Collaborations Selectively partner drug candidates to focus internal resources, unlock the value of our pipeline and maximize benefit to patients 1 We estimate our cash, cash equivalents, and investments to be approximately $781 million as of December 31, 2025. This is a preliminary, estimated, and unaudited financial result. Actual results may differ from this estimate.
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CHD: devastating liver disease, significantly underserved with high mortality 102026 Vir Biotechnology, Inc. 5 years Average progression to cirrhosis and liver failure2 >50% Liver-related death in 10 years1 Risk of liver cancer (HCC) vs. HBV3 3X 1 Negro F. (2023). Hepatitis D: A Review. JAMA. 330(24):2376–2387; 2 Pan C, (2023). Diagnosis and Management of Hepatitis Delta Virus Infection. Dig Dis Sci. Aug;68(8):3237-3248; 3 Sagnelli C, et al. (2021) HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges. Life,11(2):169. https://doi.org/10.3390/life11020169; 4 U.S. sources include Wong 2024, Polaris 2024, Stockdale 2020, Gish 2024; 5 EU sources include Polaris 2024, Delmas 2014, Wong 2024, Heidrich 2009, Reinheimer 2012, Stockdale 2020, Stroffolini 2020, Brancaccio 2019, Annual England Sentinel System 2020, Tseneva-Damyanova 2023, Papatheodoridis 2023, Parames 2016, Genne 2011, Hirzel 2015; 6 Stockdale A, et al. (2020). The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis. J Hepatol, 73, 523-32 CHD: chronic hepatitis delta; HBV: hepatitis B virus; HCC: hepatocellular carcinoma ~113K in total EU (27 member states) and UK with RNA+ patients5 in U.S. with RNA+ patients4 ~61K worldwide with RNA+ patients6 ~7M CHD
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Neutralization of HDV & HBV virions (tobevibart) Degradation of HBV RNA & reduction of HBsAg production (elebsiran) tobevibart (mAb) + elebsiran (siRNA) combination therapy key differentiators Our CHD combination regimen is potentially best-in-class Two complementary MOAs & highly differentiated target product profile 112026 Vir Biotechnology, Inc. cccDNA: covalently closed circular DNA; CHD: chronic hepatitis delta; HBsAg: hepatitis B virus surface antigen; HBV: hepatitis B virus; HDV: hepatitis D virus; Int: integrated; MOA: mechanism of action; NRTI: nucleoside/nucleotide reverse transcriptase inhibitor; RNP: ribonucleoprotein; SVP: subviral particle CHD Deep & increasing HDV RNA target not detected (TND) responses over time1 Similar efficacy in cirrhotic and non-cirrhotic patients 4 Monthly dosing (physician or patient administered)2 Rapid & sustained reduction of HBsAg levels, limiting HDV replication 3 Favorable safety profile5 Inhibition of viral entry (tobevibart)
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Ph2 SOLSTICE trial evaluating potential best-in-class therapy for CHD Study design: tobevibart + elebsiran Q4W and tobevibart Q2W Primary Endpoints: • Proportion of participants with HDV RNA <LOD or ≥2 log10 IU/mL reduction (virologic response) and ALT <ULN (ALT response) at Week 24 • TEAEs and serious TEAEs Inclusion criteria: • HDV RNA >500 IU/mL • ALT >ULN; ALT <5 × ULN • Non-cirrhotica or cirrhotic (CTP-A)b • N = 65, randomized 1:1 a Non-cirrhotic: liver biopsy with METAVIR F0 to F3 or liver stiffness <12 kPa within 12 months of screening and platelet count >150 × 103/µL b Compensated cirrhotic participants: liver biopsy with METAVIR F4 or liver stiffness ≥12 kPa within 12 months of screening, a platelet count >90 × 103/µL, and a CTP score of 5 or 6, inclusive at screening and at the start of the study ALT: alanine aminotransferase; CHD: chronic hepatitis delta; CTP: Child-Turcotte-Pugh; EOT: end of treatment; HDV: hepatitis D virus; LOD: limit of detection; Q2W: once every 2 weeks; Q4W: once every 4 weeks; SC: subcutaneous; TEAE: treatment-emergent adverse event; ULN: upper limit of normal SOLSTICE ClinicalTrials.gov Identifier: NCT05461170 Day 1 Week 48 AASLD 2025 New England Journal of Medicine Week 24 AASLD 2024 Week 72 Full cohort data CHD combination Q4W de novo tobevibart 300 mg + elebsiran 200 mg SC Q4W (Overall N = 32, including N = 18 cirrhotic) tobevibart Q2W tobevibart 300 mg SC Q2W (Overall N = 33, including N = 15 cirrhotic) Week 96 Partial cohort data Week 192 EOT 2026 Vir Biotechnology, Inc. 12
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0 24 48 72 96 0 20 40 60 80 100 % of participants with HDV RNA TND N=32 N=33 32 33 32 33 31 32 24 24 Study Week Ph2 SOLSTICE trial evaluating potential best-in-class therapy for CHD Monthly combo therapy achieved undetectable HDV RNA in 88% of patients that reached Week 96 vs. 46% with monotherapy 13 HDV RNA TND 66% 88% 77% 49% 46% 53%41% 30% tobevibart + elebsiran Q4W (N=32) tobevibart Q2W (N=33) Undetectable HDV RNA is a known driver of improved CHD patient outcomes. Data from the ongoing SOLSTICE Phase 2 trial are encouraging, as they continue to show the potential of the tobevibart and elebsiran combination to achieve robust HDV suppression by tackling the viral cycle through multiple mechanisms. Tarik Asselah, M.D., Ph.D. Professor of Hepatology at the Hôpital Beaujon, APHP mAb + siRNA mAb alone CHD CHD: chronic hepatitis delta; HDV, hepatitis D virus; mAb: monoclonal antibodies; Q2W: once every 2 weeks; Q4W: once every 4 weeks; siRNA: small interfering RNA; TND: target not detected HDV RNA TND = undetectable HDV RNA Data are reported for participants who completed the visit with non-missing HDV RNA and ALT or discontinued treatment before the visit By week 96, N=3 participants discontinued tobevibart+elebsiran Q4W and N=7 participants discontinued in tobevibart Q2W and are counted as failures in analysis; n=7 and n=8 Respectively have not yet reached the week 96 visits but remain on treatment; 1 participant receiving tobevibart Q2W is censored after week 52 due to a site protocol deviation Data as of 11/19/25 2026 Vir Biotechnology, Inc.
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Ph2 SOLSTICE trial evaluating potential best-in-class therapy for CHD ~90% of participants receiving tobevibart + elebsiran achieved very low HBsAg values by Week 24 and maintain suppression 142026 Vir Biotechnology, Inc. Hepatitis delta virus (HDV) requires serum HBV surface antigen (HBsAg) to replicate and complete its lifecycle; clearing HBsAg limits HDV replication CHD: chronic hepatitis delta; HDV: hepatitis D virus; mAb: monoclonal antibodies; Q2W: once every 2 weeks; Q4W: once every 4 weeks; siRNA: small interfering RNA Data are reported for participants who completed the visit with non-missing HBsAg measurement or discontinued treatment before the visit By week 96, N=3 participants discontinued tobevibart+elebsiran Q4W and N=7 participants discontinued in tobevibart Q2W and are counted as failures in analysis; n=7 and n=8 respectively have not yet reached the week 96 visits but remain on treatment; 1 participant receiving tobevibart Q2W is censored after week 52 due to a site protocol deviation Data as of 11/19/25 0 24 48 72 96 0 20 40 60 80 100 % of participants with HBsAg <10 IU/mL N=32 N=33 32 33 32 33 31 32 24 24 Study Week HBsAg <10 IU/mL 21% 19% 17% 91% 94% 88% 22% 88% CHD mAb + siRNA mAb alone N=32 32 32 31 24 N=33 32 33 32 24 tobevibart + elebsiran Q4W (N=32) tobevibart Q2W (N=33)
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152026 Vir Biotechnology, Inc. 0 24 48 72 96 0 20 40 60 80 100 % of participants with ALT normalization Study Week N=32 N=33 32 33 32 33 31 32 24 24 56% 55% 54% 61% 69% 58% 47% 76% ALT: alanine aminotransferase; Q2W: once every 2 weeks; Q4W: once every 4 weeks; ULN: upper limit of normal ALT ULN (male) = 40 IU/mL; ALT ULN (female) = 33 IU/mL. Data are reported for participants who completed the visit with non-missing HDV RNA and ALT or discontinued treatment before the visit. By week 96, N=3 participants discontinued tobevibart+elebsiran Q4W and N=7 participants discontinued in tobevibart Q2W and are counted as failures in analysis; n=7 and n=8 respectively have not yet reached the week 96 visits but remain on treatment; 1 participant receiving tobevibart Q2W is censored after week 52 due to a site protocol deviation Data as of 11/19/25 ALT Normalization 15 tobevibart + elebsiran Q4W (N=32) tobevibart Q2W (N=33) CHD Ph2 SOLSTICE trial evaluating potential best-in-class therapy for CHD ALT normalization was similar between tobevibart + elebsiran and tobevibart monotherapy
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162026 Vir Biotechnology, Inc. Safety or tolerability measure, n (%)a Tobevibart + elebisran Q4W de novo N = 32 Tobevibart Q2W N = 33 Any TEAE 28 (88) 32 (97) Grade 1-2 27 (84) 30 (91) Grade 3 1 (3)b 1 (3)c Grade 4 0 1 (3)d Treatment-related TEAE 23 (72) 26 (79) TEAE leading to study drug interruption 0 1 (3)e TEAE leading to study drug discontinuation 0 3 (9)f Serious TEAE 1 (3)g 1 (3)c Treatment-related serious TEAE 0 0 Q2W: once every 2 weeks; Q4W: once every 4 weeks; SAE: serious adverse event; TEAE: treatment-emergent adverse event. aA participant with multiple events within a category is counted only once in that category. bGrade 3 worsening of diabetes mellitus type 2 deemed unrelated to study drugs by investigator. cGrade 3 hepatocellular carcinoma (SAE) deemed unrelated to study drugs by investigator. dGrade 4 neutropenia on Week 12 and Week 16; recovered to grade 2 or 3 after Week 16 without treatment. eReason for study drug interruption: neutropenia (Preferred term). fReason for discontinuation: 2 cases of influenza-like illness (Preferred term) and 1 case of hepatocellular carcinoma. gOne participants with 2 concurrent SAEs of worsening nasal septum deviation and worsening nasal concha hyperplasia (both Grade 2) who underwent planned admission to the hospital for surgery; both SAEs were deemed unrelated to study drugs by investigator. Ph2 SOLSTICE trial evaluating potential best-in-class therapy for CHD Majority of adverse events were grade 1 or 2 transient through Week 72 Most TEAEs were grade 1 or 2 across treatment groups, and the most common TEAE (influenza- like illness) was generally mild to moderate and transient
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Ph2 SOLSTICE results to-date show monthly tobevibart + elebsiran combo is well tolerated with robust and durable efficacy Summary of available data through Week 96 172026 Vir Biotechnology, Inc. CHD Monthly combination therapy achieves and maintains HDV RNA TND in 88% of participants who reached Week 96 High reductions in serum HBsAg; ~90% of participants on combination therapy achieved HBsAg reductions to <10 IU/mL by Week 24 and maintained suppression ALT normalization at Week 48 was similar between combination and monotherapy cohorts and remained stable No grade 3 or higher treatment-related adverse events (TRAEs) with the combination therapy, and TRAEs were generally mild to moderate and transient ALT: alanine aminotransferase; CHD: chronic hepatitis delta; HBsAg: hepatitis B surface antigen; HDV: hepatitis D virus; TND:target not detected HDV RNA TND = undetectable HDV RNA
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*Defined as failure to achieve HDV RNA < 500 IU/mL with bulevirtide ALT: alanine aminotransferase; HDV: hepatitis D virus; TND: target not detected HDV RNA TND = undetectable HDV RNA ECLIPSE ClinicalTrials.gov Identifiers: ECLIPSE 1 NCT06903338, ECLIPSE 2 NCT07128550,ECLIPSE 3 NCT07142811 Registrational ECLIPSE program progressing ahead of schedule Initial topline data anticipated in Q4 2026 18 ECLIPSE 1 Phase 3 • HDV RNA TND + ALT normalization at Week 48 • Tobevibart + elebsiran vs. deferred treatment (n=120, 2:1) ECLIPSE 2 Phase 3 • HDV RNA TND at Week 24 • Tobevibart + elebsiran vs. bulevirtide switch* (n=150, 2:1) ECLIPSE 3 Phase 2b • HDV RNA TND at Week 48 • Tobevibart + elebsiran vs. bulevirtide naïve (n=100, 2:1) FDA breakthrough designation FDA Fast Track EMA PRIME designation EMA Orphan Drug designation Fully enrolled Fully enrolled Enrollment On Track CHD 2026 Vir Biotechnology, Inc.
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Accelerating access to our CHD regimen to patients in Europe and ANZ through collaboration with Norgine 192026 Vir Biotechnology, Inc. • Norgine is a leading European-focused specialty pharma with market-leading products in hepatology/GI, rare disease and pediatric oncology • Exclusive commercial license in Europe, Australia, New Zealand o €55M initial reimbursement paid at closing o Up to €495M in clinical, regulatory and sales milestones o Tiered mid-teen to high-twenties percent royalties on net sales o ~25% sharing of future ECLIPSE external clinical costs • Vir Biotechnology retains all commercialization rights in the U.S. and all other markets outside of the Greater China Territory1 CHD 1 Brii Biosciences retains rights to the combination of tobevibart and elebsiran in the Greater China Territory (People’s Republic of China, Hong Kong, Taiwan and Macau) Norgine holds exclusive license for the commercial rights to the combination oftobevibart and elebsiran in Europe, Australia and New Zealand CHD: chronic hepatitis delta
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Our path to delivering transformational therapies to people living with devastating diseases: cancer immunotherapy Commercializing our chronic hepatitis delta (CHD) combination therapy will drive near-term revenue sustainability Accelerating our masked T-cell engager (TCE) immunotherapy portfolio offers key value inflection points Aiming Vir Bio's discovery engine at developing a robust pipeline of cancer immunotherapies creates sustainable long-term growth 2026 Vir Biotechnology, Inc. 20 Financial Highlights ~$781M cash and investments1 with cash runway into Q4 2027 Strategic Collaborations Selectively partner drug candidates to focus internal resources, unlock the value of our pipeline and maximize benefit to patients 1 We estimate our cash, cash equivalents, and investments to be approximately $781 million as of December 31, 2025. This is a preliminary, estimated, and unaudited financial result. Actual results may differ from this estimate.
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T-cell engagers (TCEs) are a powerful modality in cancer therapy Our masked TCEs act like Trojan Horses, powered by the PRO-XTEN® platform 21 Clinically validated, used on a blockbuster drug for hemophilia A 2 2026 Vir Biotechnology, Inc. TCE Designed to reduce toxicity, enabling higher dosing and wider therapeutic window The PRO-XTEN® masking platform Our masked TCEs act like Trojan Horses, designed to maximize therapeutic index Universal, plug-and-play platform enables acceleration of next generation of drug candidates Longer drug half-life supports optimization of dosing schedules • 10 TCE breakthrough immunotherapies already on the market1 • Application in solid tumors limited due to toxicity and off- tumor activation • Masking ensures TCEs are only activated in the tumor microenvironment TCEs hold tremendous potential, limited by toxicity 1 Glaser, A., Kochanowski, K., Oh, D., Porritt, R. A., & Kim, H. (2024). T cell engagers emerge as a compelling therapeutic strategy for solid tumors. Journal of Experimental Medicine 2ALTUVIIIO® [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] is marketed for hemophilia A and is a registered trademark of Sanofi Q3W: once every three weeks Masks cleaved off by the proteases in the tumor microenvironment
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Our unique pipeline of TCEs is enabled by the PRO-XTEN® masking platform Allows our TCEs to overcome challenges of unmasked and single-masked TCEs 222026 Vir Biotechnology, Inc. TCE Tumor-binding domain Variable region binds tumor-associated antigen T-cell-binding domain Variable region binds CD3 to recruit T- cells PRO-XTEN® mask XTEN masks off-tumor activity of the TCE and prolongs half-life Cleavable linkers Proteases in the TME selectively cleave linkers to release masks Internal linkers Responsible for connecting the variable regions of the heavy and light chains Shields the core of TCEs, expanding potential in cancer therapy CD3: cluster of differentiation; TCE: T-cell engager; TME: tumor microenvironment
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Our clinical pipeline of masked TCEs reflects the promise of the PRO-XTEN® platform • The only dual-masked PSMA-targeted TCE • Phase 1 study (n=18) oEfficacy: 100% PSA decline, 58% PSA50 responses at early doses2 oSafety: no Gr3 CRS, and very low levels of ≥Gr3 TRAEs • Next steps: continue Q3W monotherapy dose escalation in mCRPC and in first-line taxane-naïve mCRPC in combo with enzalutamide (an ARPI) • The only masked HER2-targeted TCE • Phase 1 study (n=79) oEfficacy: 33% response and 100% biomarker response in mCRC, up to 50% tumor shrinkage across all HER2 tumors evaluated at early doses 4 oSafety: no Gr3 CRS, and very low levels of ≥Gr3 TRAEs • Next steps: continue dose escalation in combo with pembrolizumab; evaluating next steps for dose expansion • Potential to unlock multiple high-value indications • Phase 1 initiated in Q3 2025 • Target indications: NSCLC, CRC, HNSCC, and cSCC • Next steps: continue dose escalation of monotherapy and in combo with pembrolizumab VIR-5500 (PSMAxCD3)1 VIR-5818 (HER2xCD3)3 VIR-5525 (EGFRxCD3)5 2026 Vir Biotechnology, Inc. 23 TCE 1 VIR-5500 ClinicalTrials.gov Identifier: NCT05997615; Data cutoff: November 13, 2024 2 Doses ≥ 120 µg/kg (n=12) 3 VIR-5818 ClinicalTrials.gov Identifier: NCT05356741; Data cutoff: November 11, 2024 4 Doses ≥ 400 µg/kg (n=20; HER2+ mCRC n=6) 5 VIR-5525 ClinicalTrials.gov Identifier: NCT06960395 Note: detailed clinical data shared during Jan. 8, 2025, investor event ARPI: androgen receptor pathway inhibitors; CD3: cluster of differentiation 3; CRC: colorectal cancer; CRS: cytokine release syndrome; cSCC: cutaneous squamous cell carcinoma; EGFR: epidermal growth factor receptor; Gr3: Grade 3; HER2: human epidermal growth factor receptor 2; HNSCC: head and neck squamous cell carcinoma; mCRC: metastatic colorectal cancer; mCRPC: metastatic castrate-resistant prostate cancer; NSCLC: non-small cell lung cancer; PSMA: prostate-specific membrane antigen; PSA: prostate specific antigen; Q3W: once every 3 weeks; TCE: T-cell engager; TRAEs: treatment related adverse events
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VIR-5500 PSMA-targeted masked TCE has shown strong early dose response and promising safety profile in late-line mCRPC 242026 Vir Biotechnology, Inc. Strong PSA50 responses and favorable safety profile at early dose cohorts1 in Phase 1 • 100% (12/12) response across all 12 patients • 58% (7/12) PSA50, 8% PSA90 for 1st dose ≥120 µg/kg (n=12) • Promising early signs of efficacy and tolerable safety profile with no association with Gr ≥3 CRS, no IL-6 elevations, no prophylactic corticosteroids Individual case subject 200/300/400 µg/kgPatient case study1: whole-body MRI and PSMA-PET show tumor cell death • Patient reported significant improvement of pain symptoms • Significant >90% PSA decline • The right humerus shows significant increase in tumor cell necrosis/lysis, and decrease in PSMA-positive tumor cells 1 VIR-5500 ClinicalTrials.gov Identifier: NCT05997615; Data cutoff: November 13, 2024 2 Confirmed by a second evaluation at least three weeks later CRS: cytokine release syndrome; mCRPC: metastatic castrate-resistant prostate cancer; PSA: prostate-specific antigen; PSMA: prostate-specific membrane antigen; QW: once weekly; TCE: T-cell engager PSMA
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VIR-5500 data to be presented at ASCO Genitourinary Cancers Symposium (ASCO-GU) in February 252026 Vir Biotechnology, Inc. Safety • Weekly and Q3W dosing in late-line monotherapy dose escalation • Detailed safety data, including CRS rates and treatment-related adverse events Next steps • Plans for expansion cohorts in late-line mCRPC • Dose selection for expansion cohorts Clinical efficacy • Dose response relationship • RECIST evaluations showing tumor response assessments in evaluable patients • PSA responses observed, including overall PSA, PSA50, and PSA90 • Longitudinal view of PSA response durability TCE CRS: cytokine release syndrome; mCRPC: metastatic castrate-resistant prostate cancer; PSA: prostate-specific antigen; Q3W: once every 3 weeks; RECIST: Response Evaluation Criteria in Solid Tumors
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Our strategic approach creates short and long-term value drivers chronic hepatitis delta ECLIPSE 1 topline data in 4Q26 ECLIPSE 2 & 3 topline data in 1Q27 universal masked TCEs VIR-5500 PSMA data update at ASCO GU in 1Q26 VIR-5818 HER2 data update in 2H26 discovery engine Discovery engine driving future innovation 7 preclinical PRO-XTEN® TCE targets identified Strategic Collaborations Selectively partner drug candidates to focus internal resources, unlock the value of our pipeline and maximize benefit to patients Financial Highlights ~$781M cash and investments1 with cash runway into Q4 2027 2026 Vir Biotechnology, Inc. 26 1 We estimate our cash, cash equivalents, and investments to be approximately $781 million as of December 31, 2025. This is a preliminary, estimated, and unaudited financial result. Actual results may differ from this estimate.
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PATIENTS ARE WAITING 2026 Vir Biotechnology, Inc. 2026 Vir Biotechnology, Inc. 27
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Presented January 2025 Phase 1 Clinical Data: VIR-5500 (PSMA) 282026 Vir Biotechnology, Inc.
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292026 Vir Biotechnology, Inc. Ongoing dose escalation of first dual-masked TCE in prostate cancer VIR-5500 (PSMA) 60 µg/kg 120 180 180 µg/kg 300 600 1000 µg/kg 500 1000 2000 µg/kg 30 µg/kg 200 300 400 µg/kg Continued Dose Escalation QW Highest Potential Dose Eligibility: Documented progressive metastatic CRPC ≥ 1 prior taxane regimen Participants unsuitable for standard of care 0 to 2 ECOG status Life expectancy >6 months 18 patients enrolled up to 1000 µg/kg QW Dose Escalation Q3W Dose Escalation Q3W enrollment ongoing • Starting at 500 1000 2000 µg/kg dose level Cleared DLT Currently Evaluating Planned 500 1000 2000 µg/kg Continued Dose Escalation Q3W Highest Potential Dose CRPC: castration resistant prostate cancer; ECOG: Eastern Cooperative Oncology Group; QW: once weekly; Q3W: once every 3 weeks; TCE: T-cell engager VIR-5500 ClinicalTrials.gov Identifier: NCT05997615; Data cutoff: November 13, 2024
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Minimal systemic unmasking and potential for Q3W dosing 302026 Vir Biotechnology, Inc. VIR-5500 (PSMA) LLOQ: lower limit of quantification; PK: pharmacokinetics; Q3W: once every 3 weeks; TCE: T-cell engager; uTCE: unmasked TCE VIR-5500 ClinicalTrials.gov Identifier: NCT05997615; Data cutoff: November 13, 2024 Minimal unmasked TCE outside the tumor 8-10 Day Half-Life: Supportive of Q3W Dosing VIR-5500 Unmasked uTCE Only one VIR-5500 patient with detectable unmasked TCE (Dose: 200/300/400 µg/kg) 0 1 2 3 4 5 6 7 0.1 1 10 100 1000 Nominal Time, Day VIR-5500 concentration, nM 30 μg/kg 60 μg/kg 120/120/180 μg/kg 200/300/400 μg/kg 300/600/1000 μg/kg VIR-5500 Dose 1 (All Patients, n=18) • For 13 out of 14 evaluable patients, unmasked TCE concentrations were below LLOQ • Single patient with detectable uTCE shown above • Linear, dose proportional PK observed with potential for Q3W dosing
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Well-tolerated without prophylactic corticosteroids or anti-IL-6 premedication in early Phase 1 testing 312026 Vir Biotechnology, Inc. VIR-5500 (PSMA) Potential Best-in-Class Safety No Anti-IL-6, No Corticosteroids, No Gr ≥3 CRS VIR-5500 (n=18) Grade 1 N (%) Grade 2 N (%) Grade ≥ 3 N (%) TEAEs (max grade) in any patients n (%) Any TEAE 18 (100) 17 (94.4) 2 (11.1) Related TEAE 6 (33.3) 4 (22.2) 2 (11.1) TRAEs (max grade) in >10% of pts (n=18) CRS 3 (16.7) 2 (11.1) 0 (0) Fatigue 3 (16.7) 2 (11.1) 0 (0) Decreased appetite 2 (11.1) 0 (0) 0 (0) Anaemia 1 (5.6) 1 (5.6) 0 (0) AST increase 1 (5.6) 0 (0) 1 (5.6) No DLTs reported No ICANS or hearing loss observed 0 1 2 3 4 5 30 µg/kg (n=3) 60 µg/kg (n=3) 120/180/180 µg/kg (n=4) 200/300/400 µg/kg (n=5) 300/600/1000 µg/kg (n=3) Grade 1 Grade 2 Participants with CRS (n) CRS by VIR-5500 Dose Regimen1 1 Note: highest CRS grade per participant shown AE: adverse event; AST: aspartate aminotransferase; CRS: cytokine release syndrome; DLT: dose limiting toxicities; ICANS: immune effector cell-associated neurotoxicity syndrome; IL6: interleukin-6; TEAE: treatment emergent adverse event; TRAEs: treatment related adverse events VIR-5500 ClinicalTrials.gov Identifier: NCT05997615; Data cutoff: November 13, 2024 No corticosteroid or anti-IL-6 premedication requirement • No grade ≥3 CRS events at any dose • No CRS events at highest dose
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Strong PSA50 responses and tolerable safety at early doses in Phase 1 testing 322026 Vir Biotechnology, Inc. VIR-5500 (PSMA) -100 -75 -50 -25 0 25 PSA Best % Change from Baseline 200/300/400 μg/kg QW PSA50 PSA90 300/600/1000 μg/kg QW 120/180/180 μg/kg QW PSA30 PSA Best % Change from Baseline (Any timepoint) 0 1 2 3 4 5CRS Grade Early Phase 1 responses: PSA Responses (1st dose ≥ 120 µg/kg) Any decline 12/12 (100%) PSA50 7/12 (58%) PSA90 1/12 (8%) • Early response across all 12 patients • No association with CRS, no IL-6 elevations • Tolerable safety profile • Significant room to dose escalate; potential for Q3W dosing CRS: cytokine release syndrome; mCRPC: metastatic castration resistant prostate cancer; PSA: prostate-specific antigen; QW: once weekly; Q3W: once every 3 weeks VIR-5500 ClinicalTrials.gov Identifier:NCT05997615; Data cutoff: November 13, 2024 PSA Responses (1st dose ≥ 120 ug/kg) mCRPC patient case study
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Meaningful responses and evidence of durability at early dose cohorts 332026 Vir Biotechnology, Inc. VIR-5500 (PSMA) Longitudinal Responses Detail • 7/12 (58%) subjects demonstrate confirmed PSA 50 response1 • Trend towards increased durability with dose escalation • Anticipate deeper and more durable responses as dose escalates *Note : Participant had dose interruption at Day 20 due to unrelated case of bronchial infection Note: Axis truncated at 0% 1 Confirmed by a second evaluation at least three weeks later PSA: prostate-specific antigen; QW: once weekly VIR-5500 ClinicalTrials.gov Identifier: NCT05997615; Data cutoff: December 3, 2024 0 7 14 21 28 35 42 49 56 63 70 77 84 -100 -75 -50 -25 0 PSA Best % Change from Baseline μg g μg g μg g PSA50 PSA90 Days post 1st infusion * 120/180/180 μg/kg QW 200/300/400 μg/kg QW 300/600/1000 μg/kg QW
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Presented January 2025 Phase 1 Clinical Data: VIR-5818 (HER2) 342026 Vir Biotechnology, Inc.
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The first clinical stage masked HER2 TCE in ongoing Phase 1 352026 Vir Biotechnology, Inc. VIR-5818 (HER2) Part 1: Monotherapy Dose Escalation - Completed Part 2: Pembrolizumab Combination 200 µg/kg 100 200 400 µg/kg 100 300 800 µg/kg1 100 300 1000 µg/kg 1 µg/kg 100 250 600 µg/kg Recommended expansion dose and schedule Eligibility: HER2 IHC2-3+, ISH+, or mutant Exhausted all SOC 79 patients enrolled Evaluating QW and Q3W Demonstrates wide safety margin Cleared DLT Currently Evaluating VIR-5818 QW and Q3W Currently enrolling Analysis ongoing Pembrolizumab Q3W 200 mg + 1 Evaluating 800 µg/kg Q3W maintenance dose (cycle ≥ 2) in parallel HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry; ISH: in situ hybridization;QW: once weekly; Q3W: once every 3 weeks; SOC: standard of care; TCE: T-cell engager VIR-5818 ClinicalTrials.gov Identifier: NCT05356741; Data cutoff: November 11, 2024
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Minimal unmasked TCE in circulation and potential for Q3W Dosing 362026 Vir Biotechnology, Inc. VIR-5818 (HER2) 0 7 14 21 0.01 0.1 1 10 100 1000 Nominal Time, Days Plasma Concentration, nM VIR-5818 PK, First DoseVIR-5818 and uTCE PK, First Cycle* Minimal unmasked TCE outside the tumor Low levels of uTCE in circulation, consistent with minimal CRS Linear and dose proportional PK * All patients with PK data in step-up cohorts with 100 µg/kg starting dose CRS: cytokine release syndrome; PK: pharmacokinetic; Q3W: once every 3 weeks; QW: once weekly; TCE: T-cell engager; uTCE: unmasked T cell engager Half-life of ~ 6 days unlocks potential Q3W dosing
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Preliminary safety data indicates VIR-5818 is not dose-limited by CRS 372026 Vir Biotechnology, Inc. VIR-5818 (HER2) Highly Tolerable Safety VIR-5818 N = 79 Grade 1 N (%) Grade 2 N (%) Grade ≥ 3 N (%) Any TRAE 15 (19.0) 35 (44.3) 13 (16.5) Pneumonitis* 16 (20.3) 9 (11.4) 2 (2.5)* CRS 16 (20.3) 8 (10.1) 0 Nausea 12 (15.2) 8 (10.1) 0 Asthenia 12 (15.2) 6 (7.6) 1 (1.3) Diarrhoea 14 (17.7) 5 (6.3) 0 Pruritus 13 (16.5) 1 (1.3) 0 Vomiting 8 (10.1) 6 (7.6) 0 TRAE (max grade) in >15% of pts Low Cytokine Levels, Even at Higher Doses Peaks of IL-6 Secretion Post VIR-5818 Dosing IL-6 release significantly lower than for unmasked TCEs, despite higher VIR-5818 dose 100 μg/kg IL-6 peaks for unmasked TCE 400 μg/kg 600 μg/kg 800 μg/kg 1000 μg/kg Third Dose (final step-up)First Dose Peak IL-6 with GBR1302 (unmasked HER2 TCE)1 1 Wermke et al., ASCO-SITC 2018 *Two cases of G3 pneumonitis include one event reversible with treatment and one confounded by rapid progression of pulmonary disease CRS: cytokine release syndrome; IL-6: interleukin-6; TCE: T-cell engager; TRAE, treatment-related adverse event VIR-5818 ClinicalTrials.gov Identifier: NCT05356741; Data cutoff: November 11, 2024
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Notable tumor shrinkage observed during dose escalation 382026 Vir Biotechnology, Inc. VIR-5818 (HER2) HER2+ Solid Tumors (Doses ≥ 400 µg/kg) Breast cancer patient case study 7 No of prior lines 3 7 3 4 4 4 2 3 6 5 1 3 3 1 1 4 1 4 6 9 Liver metastases Efficacy detail: • ≥ 400 µg/kg drive significant RECIST responses o Dose escalation continues in QW and Q3W regimens • 50% observed tumor shrinkage (10/20 patients), with a DCR of 65% o 4/20 responses to date* o Responses in patients with up to 9 prior lines o 14/20 with prior HER2 treatment *Includes cPR, uPR, and mixed responses Note: HER2+ defined as IHC3+ or ISH+ BC: breast cancer; CCA: cholangiocarcinoma; cPR: confirmed partial response; CRC: colorectal cancer; DCR: disease control rate; GEJ: gastroesophageal junction; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry; ISH: in situ hybridization; OC: ovarian cancer; PAAD: pancreatic adenocarcinoma; QW: once weekly; Q3W: once every 3 weeks; RECIST: Response evaluation criteria in solid tumors; SCCAC: squamous cell carcinoma of the anal canal; SLD: sum of longest diameters; uPR: unconfirmed partial response VIR-5818 ClinicalTrials.gov Identifier: NCT05356741; Data cutoff: November 11, 2024
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A patient’s journey: dramatic response in advanced HER2+ breast cancer 392026 Vir Biotechnology, Inc. VIR-5818 (HER2) VIR-5818 Case Study Cycle 2 Day 8 Cycle 3 Day 8 Cycle 4 Day 1 Day 1 Baseline Cycle 1 Day 8 Cycle 2 Day 1 Tumor pain, inflammation HER2: human epidermal growth factor receptor 2 VIR-5818 ClinicalTrials.gov Identifier:NCT05356741; Data cutoff: November 11, 2024 Compelling activity in breast cancer patient by Cycle 1 with transformative clearance of tumor 9 prior lines of therapy, including Enhertu Dose: 100/300/1000 µg/kg Well-tolerated 52% tumor shrinkage from baseline
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HER2+ Colorectal Cancer (All Patients Shown are MSS) Deep responses at early doses in MSS colorectal cancer, a tumor type traditionally resistant to immunotherapy 402026 Vir Biotechnology, Inc. VIR-5818 (HER2) Early Phase 1 efficacy No. of Prior Lines 1 3 4 6 3 4 6 4 6 Case to be discussed by Dr.Tabernero Activity HER2+ CRC ≥400 µg/kg cPR 2/6 (33%) CEA Response* 3/3 (100%) DCR1 5/6 (83%) • 33% response and 100% biomarker response in mCRC • Up to 18.1 months duration of response (pt remains on study) • Significant room to dose escalate; potential for Q3W dosing Note: HER2+ defined as IHC3+ or ISH+ * CEA response defined as >50% decrease in CEA post-treatment. Denominator includes all pts with longitudinal data 1 DCR defined as stable disease or better CEA: carcinoembryonic antigen; cPR: confirmed partial response; CRC: colorectal cancer; DCR: disease control rate; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry; ISH: in situ hybridization; MSS: microsatellite stability; SLD: sum of longest diameters VIR-5818 ClinicalTrials.gov Identifier:NCT05356741; Data cutoff: November 11, 2024 Dose Levels 400 µg/kg 600 µg/kg 800 µg/kg 1000 µg/kg 100-300 µg/kg * CEA Response CRC patient case study
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Patient Case Study: 2 years on treatment, exceptional durability 412026 Vir Biotechnology, Inc. VIR-5818 (HER2) Rapid and Sustained Decrease Over Time Rapid and sustained CEA decrease with deeper tumor shrinkage when dose escalates CEA: carcinoembryonic antigen; cPR: confirmed partial response; IHC: immunohistochemistry; MSS: microsatellite stability; QW: weekly; SLD: sum of longest diameters; TMB: tumor mutational burden VIR-5818 ClinicalTrials.gov Identifier: NCT05356741; Data cutoff: November 11, 2024 -50 0 -20 -30 -40 -10 0 100 200 500 600 700300 400 Time from first dose (day) Change in SLD from Baseline (%) Dose Levels 200 µg/kg 300 µg/kg 600 µg/kg 60 µg/kg 120 µg/kg Change in Target Tumors Size from Baseline 0 100 200 600 700 800400300 500 Time from first dose (day) 100 200 300 400 500 600 700 800 900 0 Plasma CEA (ng/mL) 400 µg/kg 600 µg/kg 300 µg/kg 200 µg/kg 120 µg/kg 60 µg/kg Dose LevelsCEA 899 ng/mL CEA 112 ng/mL Rapid tumor marker decrease; tumor shrinkage seen 6-12 wks later cPR wk 64 @ 600 µg/kg Dose-Dependent Tumor Shrinkage • 57-Year-old male w/ colorectal cancer (MSS/TMB Low) • Status: remains on study (current dose: 600 µg/kg QW) • HER2 status: IHC 3+ • 6 prior lines including trastuzumab / tucatinib • Significant improvement on quality of life • 114 doses as of data cutoff, patient remains on study
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Molecular evidence of anti-tumor activity across multiple cancer types 422026 Vir Biotechnology, Inc. VIR-5818 (HER2) Molecular Responses: ctDNA (Step-up doses only)Percent Change from Baseline (%) CRC NSCLC BC Salivary CRC Rectum BC CRC BC CRC GEJ NSCLC GEJ -100 -50 0 50 100 Dose (µg/kg) 100 60 100 100 60 60 100 100 100 100 60 60 100 200 120 250 300 120 120 300 300 250 200 120 120 300 400 120 600 1000 300 200 800 1000 600 400 200 200 800 Detail: • High value of biomarkers for immunologics • RECIST responses may be confounded by tumor inflammation • With on-treatment ctDNA collection, VIR-5818 has molecular response for 54% subjects 1 • Now universally collecting ctDNA 1 Molecular response defined as >50% decline in overall ctDNA BC: breast cancer; CRC: colorectal cancer; ctDNA: circulating tumor DNA; GEJ: gastroesophageal junction; NSCLC: non-small-cell lung cancer; RECIST: Response evaluation criteria in solid tumors VIR-5818 ClinicalTrials.gov Identifier: NCT05356741; ctDNA data cutoff: November 19th, 2024; EDC data cutoff: November 11, 2024
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A potential first-in-class HER2 TCE designed to clinically validate the PRO-XTEN® platform 432026 Vir Biotechnology, Inc. VIR-5818 (HER2) Clear activity based on early Phase 1 data with potential for long-term durable responses Emerging activity: wide TI in heavily pretreated population • Unprecedented tolerability: no Gr3+ CRS, 16% all Gr3+ TRAEs • 33% response in heavily pre-treated CRC patients (≥400 µg/kg) • ctDNA Molecular response in 54% of subjects Proof of concept for PRO-XTEN® platform • Clear evidence of unmasking with antitumor activity Universal masks: mechanism designed to apply across platform • Potential rapid dose escalation for VIR-5500 (PSMA) and other targets CRC: colorectal cancer; CRS: cytokine release syndrome; ctDNA: circulating tumor DNA;Gr3: Grade 3; HER2: human epidermal growth factor receptor 2; PSMA: prostate-specific membrane antigen; TCE: T-cell engager; TI: therapeutic index; TRAE: treatment-related adverse event VIR-5818 ClinicalTrials.gov Identifier: NCT05356741; Data cutoff: November 11, 2024
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Phase 1 Clinical Program: VIR-5525 (EGFR) 442026 Vir Biotechnology, Inc.
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VIR-5525 Phase 1 study design: dose escalation and expansion 452026 Vir Biotechnology, Inc. VIR-5525 (EGFR) Part 1 & 2: Monotherapy Dose Escalation & Expansion Part 3 & 4: Pembrolizumab Combination Dose Escalation & Expansion Dose Escalation Continued Dose Escalation Continued Dose Escalation 3 µg/kg Continued Dose Escalation Highest Potential Dose Indications: NSCLC (nonsquamous or squamous histology), CRC, HNSCC, cSCC or have a solid tumor with EGFR amplification Eligibility Criteria: • ≥18 years old • Histological, pathological, or cytological confirmation of disease type that is unresectable, locally advanced, or metastatic • Progressed or was intolerant to all available therapies known to confer clinical benefit appropriate for the tumor type • At least 1 measurable lesion per RECIST 1.1 • ECOG 0-1 Objectives: Primary: safety, tolerability, RP2D Secondary: • PK, PD, ADA • Radiographic response Cleared DLT Currently Evaluating VIR-5525 Planned Pembrolizumab+ ADA: anti-drug antibody; CRC: colorectal cancer; cSCC: cutaneous squamous cell carcinoma; ECOG: Eastern Cooperative Oncology Group; EGFR: epidermal growth factor receptor; HNSCC: head and neck squamous cell carcinoma; NSCLC: non-small cell lung cancer; PD: pharmacodynamics; PK: pharmacokinetics; Rp2D: recommended phase 2 dose; RECIST: Response Evaluation Criteria In Solid Tumors; TCE: T- cell engager Note: Step up dosing and additional schedules may be evaluated based on emerging clinical and PK data
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Preclinical data demonstrate potent activity and substantial safety margin with PRO-XTEN® masking 462026 Vir Biotechnology, Inc. Anti-tumor activity in vitro Tumor growth inhibition in vivo Source: Adapted from Cattaruzza, F., Nazeer, A., Lange, Z., Hammond, M., Koski, C., Henkensiefken, A., & Schellenberger, V. (2020). HER2-XPAT and EGFR-XPAT: Pro-drug T-cell engagers (TCEs) engineered to address on-target, off-tumor toxicity with potent efficacy in vitro and in vivo and large safety margins in NHP. Cancer Research, 80(16_Supplement), 3376-3376. Cattaruzza, F., Nazeer, A., To, M. et al. Precision-activated T-cell engagers targeting HER2 or EGFR and CD3 mitigate on-target, off-tumor toxicity for immunotherapy in solid tumors. Nat Cancer 4, 485–501 (2023). https://doi.org/10.1038/s43018-023-00536-9. ~250-fold safety margin data from IND filing analysis (>200-fold reported in Nature paper). EGFR: epidermal growth factor receptor; EGFR uTCE: EGFR-targeted unmasked T-cell engager; mpk: milligrams per kilogram; TCE: T-cell engager Outside Tumor: masking is maintained, leading to ~10,000-fold shift in cytotoxicity In Tumor: similar anti-tumor activity in PRO-XTEN® masked vs. unmasked EGFR TCE PRO-XTEN® masked EGFR TCE enabled ~250-fold higher tolerated exposure in NHPs vs. unmasked TCE EGFR uTCE EGFR Masked TCE EGFR Masked TCE 1 mpk EGFR Masked TCE 2.5 mpk VIR-5525 (EGFR)