Slide 1: Hepatitis Investor Event at AASLD
Hepatitis Investor Event at AASLD November 19, 2024 Confidential © 2024 Vir Biotechnology, Inc.™ 1
Slide 2: Legal Disclaimer
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 chronic hepatitis Delta (CHD) or chronic hepatitis B virus (CHB
Slide 3: Agenda
Agenda Speaker Topic Marianne De Backer, M.Sc., Ph.D., MBA Opening Remarks, Addressing Significant Unmet Medical Need in Hepatitis Delta Chief Executive Officer and Director (HDV) & Chronic Hepatitis B (CHB) Mark Eisner, M.D., M.P.H. Phase 2 SOLSTICE Data update at AASLD & Next Steps for Clinical De
Slide 4: Opening Remarks
Opening Remarks Marianne De Backer © 2024 Vir Biotechnology, Inc. 4
Slide 5: Vir's Mission: Powering the Immune System to Transform Lives
VIR’S MISSION: POWERING THE IMMUNE SYSTEM TO TRANSFORM LIVES © 2024 Vir Biotechnology, Inc. 5
Slide 6: Strategic Pillars Driving Our Mission Forward
Strategic Pillars Driving Our Mission Forward 5 clinical-stage assets in infectious disease and oncology with near term catalysts Focused investments in areas of high unmet need Industry-leading and AI-driven antibody discovery, protein engineering and masking technology © 2024 Vir Biotechnology, In
Slide 7: Vir Today: Advancing Infectious Disease and Oncology Programs to Drive Growth
Vir Today: Advancing Infectious Disease and Oncology Programs to Drive Growth Leveraging Immune-Targeted Approaches to Transform Patient Care Infectious Disease Oncology – Solid Tumors Hepatitis Delta Chronic Hepatitis B HER2 PSMA EGFR (Phase 2) (Phase 2) (Phase 1) (Phase 1) (Initiating Phase 1) Goa
Slide 8: Transformational Data in Hepatitis Delta
Transformational Data in Hepatitis Delta (HDV) Hepatitis Delta (HDV) Next Steps Transformative Data HDV Registrational Study (combo Q4W de novo) • FDA Type C Meeting • Large proportion of patients achieving undetectable Held HDV RNA <LLOQ, TND • ECLIPSE will be a Ph 3 • Decreasing ALT for the majori
Slide 9: Promising End of Treatment Seroclearance in Chronic Hepatitis B
Promising End of Treatment Seroclearance in Chronic Hepatitis B (CHB) Chronic Hepatitis B (CHB) Next Steps Promising EOT Seroclearance CHB Functional Cure (HBsAg <1,000 IU/mL) Data • ~39% for tobevibart + elebsiran • 24w-off treatment, functional cure data in • ~46% for tobevibart + elebsiran + PEG-
Slide 10: Hepatitis Delta: Occurs Exclusively in Patients with HBV Infection
Hepatitis Delta: Occurs Exclusively in Patients with HBV Infection and Dramatically Increases Risk of Death, Cancer and Cirrhosis Liver-Related >50% Death in 10 Years1 3x Risk of Liver-Related Death vs. HBV4 Average Progression to Risk of Liver Cancer (HCC) 5 year Cirrhosis and Liver Failure2 3x vs.
Slide 11: Hepatitis Delta: A Threat to Adults in Their Prime Years
Hepatitis Delta: A Threat to Adults in Their Prime Years across all ethnicities © 2024 Vir Biotechnology, Inc. 11 © 2024 Vir Biotechnology, Inc. 11 11
Slide 12: Hepatitis Delta: Current Patient Challenges
Hepatitis Delta: Current Patient Challenges The most 1 No approved treatments in the US, limited severe form of options outside of the US viral hepatitis 2 Underdiagnosis and no reflex testing1 in AASLD guidelines 3 Severe clinical outcomes drive significant financial burden 4 Limited physician and
Slide 13: Geographic Concentration of US Patients
Hepatitis Delta: Geographic Concentration of US Patients will allow for Lean, Targeted Vir Commercialization Effort Implications: % of total diagnosed US population1 ✓ Concentrated in urban centers ✓ Relatively few HDV specialists ✓ Activation through targeted awareness / testing drives resource eff
Slide 14: Key Patient Challenges and Vir Priorities
Key Patient Challenges Vir Priorities 1 No US approved treatments, Advancing a transformative efficacious limited options outside of the treatment US Understanding who Delta patients are, 2 Underdiagnosis and no reflex to bridge testing to treatment testing1 in AASLD guidelines Ensuring the earliest
Slide 15: SOLSTICE Data Update at AASLD
PHASE 2 SOLSTICE Data Update at AASLD: Potentially Transformative Treatment for Chronic Hepatitis Delta Mark Eisner © 2024 Vir Biotechnology, Inc. 15
Slide 16: Our Ambition in HDV: Chronic Viral Suppression
Our Ambition in HDV: Chronic Viral Suppression to undetectable levels with Monthly Dosing HBsAg is the key viral protein responsible for recognition, binding, and entry of HBV and Inhibition of viral entry HDV virions to hepatocytes (tobevibart) Complementary mechanisms of action: Degradation of HBV
Slide 17: SOLSTICE Phase 2 Trial Design
In the SOLSTICE Phase 2 trial, Vir is Evaluating Tobevibart and Elebsiran with the Goal of Achieving Transformational HDV Virologic Suppression Tobevibart Q2W Tobevibart 300 mg SC Q2W HDV RNA >500 IU/mL (Overall N = 33 including N = 15 cirrhotic) ALT >ULN; ALT <5 × ULN 1:1 Non-cirrhotica Combo Q4W d
Slide 18: Demographic and Baseline Characteristics
Demographic and Baseline Characteristics were Generally Balanced Across the Treatment Groups Tobevibart Q2W Combo Q4W de novo Combo Q4W rollovera N = 33 N = 32 N = 13 Age, y, mean SD 44.8 9.2 41.5 8.0 42.5 8.8 Male, n (%) 16 (48.5) 18 (56.3) 9 (69.2) Race, n (%) White 28 (84.8) 25 (78.1) 12
Slide 19: High Rates of Undetectable HDV Viremia
High Rates of Undetectable HDV Viremia were Achieved and Maintained in Participants Receiving the Tobevibart + Elebsiran Combination HDV RNA 2 log10 decrease or HDV RNA <LOD HDV RNA <LLOQ, TND Protocol defined endpoint Tobevibart Q2W Combo Q4W de novo High proportions of virologic suppression as me
Slide 20: ALT Decreased in the Majority of Participants
ALT Decreased in the Majority of Participants Between Day 1 and Week 24 ALT Normalization Change in ALT Change in ALT (Tobevibart Q2W Cohort) (Combo Q4W de novo Cohort) 100 350 200 175 80 76 76 74 74 300 % participants 200 150 ALT (IU/L) 125 ALT (IU/L) 60 56 Grade 2 47 47 50 50 50 150 Grade 2 100 40
Slide 21: Majority of Patients Achieved the Protocol Defined Endpoint
Majority of Patients Achieved the Protocol Defined Endpoint, Over Half had Undetectable HDV Viremia in the Combination Cohort HDV RNA ≥2 log10 decrease or HDV RNA <LOD HDV RNA <LLOQ, TND + ALT Normalization + ALT Normalization Protocol defined endpoint Tobevibart Q2W Combo Q4W de novo HDV RNA <LLOQ,
Slide 22: Virologic Efficacy & ALT Normalization Similar in Non-Cirrhotic and Cirrhotic
Virologic Efficacy & ALT Normalization were Similar Between Non-Cirrhotic and Cirrhotic Participants Receiving Tobevibart + Elebsiran Mean HDV RNA HDV RNA <LLOQ, TND ALT Normalization 100 100 83 Mean HDV RNA (log10 IU/mL), 80 80 73 75 % participants 67 % participants 60 60 40 Mean ± SD 40 33 40 27 2
Slide 23: High Rates of Virologic Suppression in Rollover Cohort
High Rates of Virologic Suppression were Achieved and Maintained in Participants in Combination Rollover Cohort HDV RNA 2 log10 decrease or HDV RNA <LOD HDV RNA <LLOQ, TND 100 100 100 100 100 100 100 100 82 83 80 78 80 80 75 % participants % participants 64 60 60 44 41 40 40 30 30 20 20 27/33 32/32
Slide 24: HDV RNA & ALT Normalization Rates Increased Over Time
HDV RNA <LLOQ, TND + ALT Normalization Rates Increased Over Time for the Combination Rollover Cohort HDV RNA ≥2 log10 decrease or HDV RNA <LOD HDV RNA <LLOQ, TND + ALT Normalization + ALT Normalization 100 100 80 80 % participants % participants 70 70 60 56 60 47 50 50 50 50 40 40 40 40 33 26 27 25
Slide 25: Rapid and Sustained HDV RNA Suppression
Rapid and Sustained HDV RNA Suppression with Tobevibart + Elebsiran Combination Mean HDV RNA (log10 IU/mL) by Visit Combo Q4W rollover Combo Q4W de novo HDV RNA levels decreased rapidly in the tobevibart + elebsiran combination Q4W cohorts and these decreases were maintained over time HDV, hepatitis
Slide 26: SOLSTICE Results Show Substantial Response (Cross Trial Comparison)
Our SOLSTICE phase 2 Results Show Substantial Virologic and Biochemical Response in Hepatitis Delta (Cross Trial Comparison) HDV RNA <LLOQ, TND* ALT Normalization* 100% SOLSTICE 100% MYR 301 100% SOLSTICE 100% MYR 301 Participants (%) Participants (%) 80% 80% 80% 80% 64% 60% 60% 60% 60% 51% 47% 50%
Slide 27: ~90% of Participants Achieved HBsAg <10 IU/mL
~90% of Participants Achieved HBsAg <10 IU/mL with Tobevibart + Elebsiran at Week 24: A Potential Key Milestone Controlling both Viruses HBsAg Level HBsAg (IU/mL) Category at Week 24 6 Mean HBsAg (log10 IU/mL), 100 3 11 4 22 Mean ± SD 80 2 <0.05 60 38 0.05 to <10 0 84 78 10 to <100 40 ≥100 Missing D
Slide 28: Majority of Adverse Events Were Grade 1-2
Majority of Adverse Events were Grade 1-2 & Transient, no Grade 2 or Higher ALT Elevations Have Occurred to Date Combo Q4W Tobevibart Q2W Combo Q4W rollover de novo N = 33 N = 13 Safety or tolerability measure, n (%)a N = 32 Any TEAE 29 (87.9) 25 (78.1) 5 (38.5) Grade 1-2 28 (84.9) 25 (78.1) 5 (38.5
Slide 29: Conclusions: Preliminary Results from the Phase 2 SOLSTICE Trial
Conclusions: Preliminary Results from the Phase 2 SOLSTICE Trial The combination rapidly reduces HDV RNA leading to high rates of undetectable HDV RNA Among patients with data through 36 weeks in the de novo combination cohort, 64% achieved HDV <LLOQ, TND Decreasing ALT for the majority of patients
Slide 30: Development Plan: Registrational Clinical Trials Starting in 1H'25
Development Plan: Registrational Clinical Trials Starting in 1H’25 Phase 2 Supportive Registrational Clinical Program Trial in HDV* Q4 2024 ECLIPSE 1 – Phase 3 HDV RNA LLOQ, TND + ALT normalization at week 48 Pivotal Studies SOLSTICE • tobevibart + elebsiran vs. deferred treatment (n=120, 2:1) Suppo
Slide 31: KOL Perspective on Hepatitis Delta Data
KOL Perspective Perspective on Hepatitis Delta Data and Unmet Medical Need in HDV Nancy Reau. M.D. Richard B. Capps Chair of Hepatology, Associate Director of Solid Organ Transplantation and Section Chief of Hepatology at Rush University Medical Center © 2024 Vir Biotechnology, Inc. 31
Slide 32: Pursuit of a Functional Cure in Chronic Hepatitis B
PHASE 2 MARCH Part B Data Update at AASLD Pursuit of a Functional Cure in Chronic Hepatitis B (CHB) © 2024 Vir Biotechnology, Inc. 32
Slide 33: Chronic Hepatitis B: A Global Challenge with Unmet Needs
Chronic Hepatitis B: A Global Challenge with Unmet Needs Chronic HBV infection is estimated to affect approximately 254 million people globally1 • ~1.6 million in the United States and ~2.8 million in Europe6 Chronic HBV infection has been associated with long-term liver outcomes and complications,
Slide 34: Our Ambition in HBV: Functional Cure Following Finite Treatment
Our Ambition in HBV: Functional Cure Following Finite Treatment Regimen HBsAg is the key viral protein responsible for recognition, binding, and entry of HBV Inhibition of viral entry virions to hepatocytes (tobevibart) Complementary mechanisms of action: Degradation of HBV Tobevibart RNA & reductio
Slide 35: MARCH Part B Trial Design
MARCH Part B Evaluates 3 Regimens with the Goal of Achieving and Maintaining High Rates of HBsAg Loss, Today we are at End of Treatment Current analysis EOT 24 weeks 48 weeks Day 1 Week 44/48b post-treatment post-treatment NRTI therapy N = 121 Tobevibart (N = 20) • On NRTIs ≥6 months • HBV DNA <100
Slide 36: Baseline Characteristics Balanced Across Treatment Groups
Baseline Characteristics were Generally Balanced Across Treatment Groups Tobevibart Tobevibart + elebsiran Tobevibart + elebsiran + PEG-IFNα (44 weeks) (44 weeks) (48 weeks) N = 20 N = 51 N = 27a Age, y, mean SD 45.6 10.8 47.3 8.3 47.6 9.5 Male, n (%) 12 (60.0) 39 (76.5) 14 (51.9) Race, n (%
Slide 37: High Levels of HBsAg Loss at EOT
Combination of Tobevibart + Elebsiran Results in High Levels of HBsAg Loss at EOT Without or With PEG-IFNα in Lower HbsAg Participants Baseline HBsAg Loss by Baseline HBsAg Categorya 50 45* 45 Participants (%) 39 40 30 25 22 20 16 10 0/20 0/12 0/6 0 8/51 6/27 0 8/32 5/11* 0 7/18 5/11 0 Total Populat
Slide 38: Large Number of Patients Developed Protective Anti-HBs Antibodies
A Large Number of Patients Developed Protective Levels of Anti-HBs Antibodies (≥10 mIU/mL) at End of Treatment, and Indicator of Immune Response Strong anti-HBs development across all regimens studied Tobevibart + elebsiran + PEG-IFNα is ssoci t d with th high st ntibod l v ls EOT, end of treatment;
Slide 39: HBsAg Loss at EOT Strongly Associated with Anti-HBs Antibody
HBsAg loss at EOT is Strongly Associated with Development of Anti-HBs Antibody Anti-HBs ≥ mIU/mL t EOT mong participants with HBsAg loss at EOTa-c 100 100 100 100 Participants (%) 80 60 50 50 40 20 4/8 6/6 4/8 5/5 0 1/1 0 Overall Baseline HBsAg Baseline HBsAg 3,000 IU/mL 3,000 IU/mL Tobevibart + e
Slide 40: Adverse Events Were Generally Mild to Moderate and Transient
Adverse Events were Generally Mild to Moderate and Transient Tobevibart + Tobevibart + Tobevibart elebsiran elebsiran + PEG-IFNα The most common tobevibart- or (44 weeks) (44 weeks) (48 weeks) elebsiran-related AEs (headache and Safety or tolerability measure, n (%)a N = 20 N = 51 N = 27b influenza-
Slide 41: Preliminary Conclusions from the Phase 2 MARCH Part B Trial
Preliminary Conclusions from the Phase 2 MARCH Part B Trial Compelling HBsAg loss and anti-HBs development at end of treatment with 48 weeks of tobevibart + elebsiran, without or with PEG-IFN ~39% HBsAg loss for the tobevibart + elebsiran regimen, in participants with baseline HBsAg<1,000 IU/mL ~46%
Slide 42: CHB: MARCH Functional Cure Data in Q2 2025
CHB: MARCH Phase 2 Functional Cure Data in Q2 2025 ‘ 5 24w Off Treatment Data Completion of Enrollment (48w Post-Treatment) • ~50 tobevibart + elebsiran participants • ~50 tobevibart + elebsiran participants • ~30 tobevibart + elebsiran + • ~30 tobevibart + elebsiran + PEG-IFN- participants PEG-IF
Slide 43: KOL Perspective on MARCH Part B Data & Chronic Hepatitis B
KOL Perspective KOL Perspective on MARCH Part B Data & Chronic Hepatitis B Nancy Reau. M.D. Richard B. Capps Chair of Hepatology, Associate Director of Solid Organ Transplantation and Section Chief of Hepatology at Rush University Medical Center © 2024 Vir Biotechnology, Inc. 43
Slide 44: Closing Remarks: Poised to Achieve Our Near- and Long-term Goals
Closing Remarks: Poised to Achieve Our Near- and Long-term Goals © 2024 Vir Biotechnology, Inc. 44
Slide 45: Breakthrough Results: Transformational HDV Data and Promising CHB Seroclearance
Breakthrough Results: Transformational HDV Data and Promising CHB Seroclearance Hepatitis Delta (HDV) Chronic Hepatitis B (CHB) Next Steps Transformative Data Promising EOT Seroclearance HDV Registrational (combo Q4W de novo) (HBsAg <1,000 IU/mL) Study Starting 1H 2025 • Large proportion of patients
Slide 46: Vir HDV Priorities: Path to Success in HDV
Vir HDV Priorities Path to Success in HDV • Bring forward a transformative efficacious treatment • Understanding who Delta patients are, to bridge testing to treatment • Ensuring the earliest possible access through payor engagement • Accelerating treatment rates through patient and provider educati
Slide 47: Our Development Priorities Are Poised to Accelerate Near-Term Value
siRNA Antibody Masked TCE Our Development Priorities are Poised to Accelerate Near-Term Value Tr e a t m e n t / Disease Area Product Candidate Preclinical Phase 1 Phase 2 Phase 3 A u t h o r i ze d Collaborator P r e ve n t i o n Chronic tobevibart ± elebsiran Treatment Alnylam Hepatitis Delta Note
Slide 48: We Anticipate Important Near-Term Catalysts
We Anticipate Important Near-Term Catalysts Program Drug Candidates/Regimen Catalyst Timing Hepatitis Delta tobevibart (mAb) +/- elebsiran (siRNA) SOLSTICE Phase 2: additional clinical data ✓ 4’24 Chronic MARCH-B Phase 2: 48-week end of treatment Hepatitis B tobevibart (mAb) + elebsiran (siRNA) +/-
Slide 49: Thank you!
Thank you! © 2024 Vir Biotechnology, Inc. 49