Mesoblast Limited · ASX:MSB

Mesoblast — 2021 Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases

27 slides from Mesoblast's conference presentation, Jul 16, 2021

1. Slide 1: Top-line Results for Remestemcel-L in COVID-19 ARDS

   For personal use only mesoblast the regenerative medicine company Top-line Results for Remestemcel-L in COVID-19 ARDS 2021 Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases JULY 2021 ASX: MSB; Nasdaq: MESO

2. Slide 2: Cautionary Note Regarding Forward-Looking Statements

   For personal use only CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This presentation includes forward-looking statements that relate to future events or our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, le

3. Slide 3: Our Mission

   For personal use only Our Mission Mesoblast is committed to bringing to market innovative cellular medicines to treat serious and life-threatening illnesses

4. Slide 4: Platform Technology – Mechanism of Action (MOA)

   Platform Technology – Mechanism of Action (MOA) Our mesenchymal stromal cells respond to and are activated by multiple inflammatory cytokines through surface receptors, resulting in For personal use only orchestration of an anti-inflammatory cascade IL-10 Breg TH1 Proliferation Mesenchymal Cytokine

5. Slide 5: Acute GVHD: A Prototypic Disease Driven by Cytokine Storm

   Acute Graft versus Host Disease (GVHD): A Prototypic Disease Driven by Cytokine Storm For personal use only PHASE 1 PHASE 2 PHASE 3 Host Tissue Damage Immune Cell Activation Inflammation and End Organ by BMT Conditioning & Cytokine Storm Damage Conditioning Activation of Macrophage regimen, Tissue C

6. Slide 6: Remestemcel-L in Steroid Refractory Acute GVHD: Clinical Evidence for a MOA

   Remestemcel-L in Steroid Refractory Acute GVHD: Clinical Evidence for a MOA Applicable to Various Inflammatory Conditions For personal use only Consistent efficacy and safety outcomes in a total of 309 children from three studies:  Remestemcel-L was used as first-line therapy in a randomized contro

7. Slide 7: Cytokine Storm in COVID-19 ARDS Resembles Secondary HLH

   Cytokine Storm in COVID-19 ARDS Closely Resembles Secondary Hemophagocytic Lymphohistiocytosis (sHLH): A T Cell Driven Disease For personal use only  Secondary (or acquired) hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening disease characterized by lymphocyte and macrophage hyperinfla

8. Slide 8: Robust Adaptive Naïve T Cell Response in COVID-19 is Critical for Viral Clearance

   Robust Adaptive Naïve T Cell Response in COVID-19 is Critical for Viral Clearance Lack of Adequate T Cell Response Results in Increased Viral Load and Severe Disease Average SARS2 infection Severe SARS2 infection For personal use only  Analysis of SARS-CoV-2-specific adaptive immune responses durin

9. Slide 9: Severe COVID-19 Associated with Depletion of Naïve T Cells

   Severe COVID-19 Disease is Associated with Progressive Depletion of Naïve T Cells, and Aberrant Activation of Non-Naïve CD4 and CD8 T Cells For personal use only Naïve T Cells Non-Naïve Activated T Cells HLA-DR+ HLA-DR+ KI67+ CD38+ KI67+ CD38+ 80 100 ** * * ** % of Non-naïve CD8 T cells % of Non-naï

10. Slide 10: Severity of COVID-19 Associated with Increased Activated T Cells Producing IFN-γ and GM-CSF

    Severity of COVID-19 Infection is Associated with Increased Activated T Cells Producing IFN-𝛾𝛾 and GM-CSF For personal use only Figure: Pathogenic Th1 cells with high expression of GM-CSF in COVID-19 patients. (B) Representative density plots showing an analysis of co-expression of GM-CSF and…

11. Slide 11: Age Associated with Reduced Naïve T Cell Response and Greater Severity

    Age > 65 years is Associated with Reduced Naïve T Cell Response to SARS-CoV-2, Delayed Viral Clearance and Greater Disease Severity For personal use only Naïve CD4 and CD8 T Cells reduced in Age > 65 associated with greater age > 65 COVID-19 peak disease severity Median duration to negative status l

12. Slide 12: Meta-Analysis of Case Fatality Rates for COVID-19 Patients on Mechanical Ventilation

    Meta-Analysis of Case Fatality Rates (CFR) for COVID-19 Patients on Invasive Mechanical Ventilation (IMV): Mortality Significantly Increases with Age For personal use only 100% IMV and CFR Stratified by Age Alive Dead Unknown Age n (%, 95% CI) n (%, 95% CI) n (%, 95% CI) 90% 84.40% ≤40* (N=4,145) 1,

13. Slide 13: Objectives of Immunomodulation with Remestemcel-L in COVID ARDS

    Objectives of Immunomodulation with Remestemcel-L in COVID ARDS For personal use only MSCs have the potential to:  Reduce activated non-naïve CD4 and CD8 T cells  Reduce inflammatory cytokines produced by non-naive T cells to reduce macrophage and neutrophil influx, activation and cytokine storm 

14. Slide 14: Clinical Experience with Remestemcel-L in COVID-19 ARDS

    Clinical Experience with Remestemcel-L in COVID-19 ARDS For personal use only Emergency IND in Ventilator-Dependent COVID-19 ARDS  11 patients (10/11 were < 65 years) with moderate or severe ARDS on ventilators, received two infusions of remestemcel-L 2 million cells/kg within five days at Mt. Sina

15. Slide 15: Baseline Summary Data: Intent to Treat Patients Pre-Specified Age

    Baseline Summary Data: Intent to Treat Patients Pre-Specified Age < 65 & ≥ 65 For personal use only ITT Patients < 65 years ITT Patients ≥ 65 years Category REM Mean Control Mean REM Mean Control Mean n=58 n=67 n=54 n=43 Sex (%) Male 76% 70% 65% 65% Female 24% 30% 35% 35% Age (Yrs) 52 (9.9) 51 (9.8)

16. Slide 16: Baseline Summary Data: Increased Co-Morbid Conditions in Patients ≥ 65

    Baseline Summary Data: Increased Co-Morbid Conditions in Patients ≥ 65 For personal use only ITT Patients < 65 years ITT Patients ≥ 65 years < 65 vs ≥ 65 All Patients - ITT REM Mean Control Mean REM Mean Control Mean Chi-Squared n=58 n=67 n=54 n=43 P-Value Medical History COPD 2% 1% 13% 12% 0.0004 A

17. Slide 17: Greater Mortality in Control Patients Older than 65

    Greater Mortality through Day 60 in Control Patients Older than 65, Consistent with Other Trials For personal use only Controls Age < 65 vs ≥ 65 (n=110) Absence of All Cause Death at Day 60 Mortality Through 60 Days 42% (28/67) <65 vs 70% (30/43) ≥65 HR: 2.098; 95% CI (1.251, 3.519), p=0.005 Log Ran

18. Slide 18: Remestemcel-L vs Controls: Mortality through 60 Days

    Remestemcel-L vs Controls with COVID-19 ARDS: Mortality through 60 Days in Treated Patients For personal use only All Modified Intent to Treat Patients (n=217), Remestemcel-L vs Control Absence of All Cause Death at Day 60 Mortality Through 60 Days REM 48.2% (53/110) vs Control 53.3% (57/107) HR: 0.

19. Slide 19: Pre-Specified Mortality Analysis through 60 Days by Age

    Remestemcel-L vs Controls: Pre-Specified Mortality Analysis through 60 Days < or ≥ 65 Years Old For personal use only Modified Intent to Treat Patients < 65 years old (n=123) Modified Intent to Treat Patients ≥ 65 years old (n=94) REM vs Control REM vs Control Absence of All Cause Death at Day 60 Ab

20. Slide 20: Analysis of Respiratory Function Improvement

    Remestemcel-L vs Controls: Analysis of Respiratory Function Improvement* For personal use only Treated Patients (mITT) < 65 years old (n=123) Treated Patients (mITT) ≥ 65 years old (n=94) Remestemcel-L vs Control Remestemcel-L vs Control Respiratory Function Improvement: Patients < 65 years Respirat

21. Slide 21: Dynamic Changes in the Treatment Regimes During the Trial

    Dynamic Changes in the Treatment Regimes During the Trial For personal use only Source: Noel A. et al. Epic Health Research Network. Nov 2020 | 21

22. Slide 22: Dexamethasone did not Reduce Mortality in Controls on Ventilation

    Dexamethasone did not Reduce Mortality in Controls on Invasive Mechanical Ventilation with Moderate/Severe COVID-19 ARDS For personal use only Controls < 65 years old +/- Dexamethasone (ITT n=67) Controls ≥ 65 years old +/- Dexamethasone (ITT n=43) Absence of All Cause Death at Day 60 Absence of All

23. Slide 23: Remestemcel-L plus Dexamethasone: Synergistic in Reducing Mortality

    Remestemcel-L plus Dexamethasone: Synergistic in Reducing Mortality in Exploratory Population < 65 years old For personal use only All Treated Patients < 65 years old on Dexamethasone (n=73) Absence of All Cause Death at Day 60 Mortality Through 60 Days REM + Dex 14% (4/29) vs Dex 45% (20/44) HR: 0.

24. Slide 24: Remestemcel-L Increases Ventilator-Free Days Alive in Patients < 65

    Remestemcel-L Increases Ventilator-Free Days Alive through 60 Days in Patients < 65 years old For personal use only All Treated Patients < 65 years old All Treated Patients < 65 years old (n=123) on Dexamethasone (n=73) Ventilator-Free Days Alive Through Day 60 Ventilator-Free Days Alive Through Day

25. Slide 25: Remestemcel-L plus Dexamethasone: Respiratory Function and Clinical Improvement

    Remestemcel-L plus Dexamethasone: Analysis of Respiratory Function and Clinical Improvement* in Exploratory Population < 65 years old Treated Patients (mITT) < 65 years old Treated Patients (mITT) < 65 years old For personal use only on Dexamethasone (n=73) on Dexamethasone (n=73) Respiratory Functi

26. Slide 26: Conclusions and Next Steps for Remestemcel-L in ARDS Due to COVID-19

    Conclusions and Next Steps for Remestemcel-L in ARDS Due to COVID-19 For personal use only  Remestemcel-L did not significantly reduce overall mortality  Remestemcel-L reduced mortality and increased ventilator-free days through 60 Days in pre-specified patient population < 65 years old  Addition

27. Slide 27: Mesoblast – the regenerative medicine company

    For personal use only mesoblast the regenerative medicine company

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