Roche Holding Ltd · SIX:RO
Roche — Investor Presentation (February 2025)
41 slides from Roche's investor presentation, Feb 7, 2025
Slide 1: Immunology/WCN 2025 Virtual IR Event
Immunology/WCN 2025 Virtual IR Event Feb 7th 2025
Slide 2: Welcome
Welcome Bruno Eschli Head of Investor Relations
Slide 3: Agenda
Agenda Welcome Bruno Eschli, Head of Investor Relations Immunology kidney pipeline Larry Tsai, SVP and Global Head of Product Development Immunology Gazyva in Lupus Nephritis (REGENCY) – WCN data presentation Brad H. Rovin, MD, FASN, FACP Q&A 3
Slide 4: 2025 Pharma pipeline
2025 Pharma pipeline 12 key pivotal readouts including 4 NMEs expected New Molecular Entities (NME) 2 giredestrant Ph III persevERA 2 fenebrutinib Ph III FENhance 1/2 1 vamikibart Ph III HR+ BC Ph III evERA RMS, PPMS Ph III FENtrepid DME/UME SANDCAT/MEERKAT Itovebi (inavolisib) Elevidys CT-388 Pi3Km
Slide 5: IR events currently planned for 2025
IR events currently planned for 2025 Additional events driven by readouts Immunology/WCN Update on NGS Neurology Update Diagnostics Day Pharma Day 7 Feb 20 Feb 4 Apr 27 May 22 Sep 16:30 – 17:30 CET 20:30 - 21:30 CET 16:00 – 17:30 CEST 14:00 - 16:30 CEST tbd Virtual event Virtual event Virtual event
Slide 6: Immunology kidney pipeline
Immunology kidney pipeline Larry Tsai SVP and Global Head of Product Development Immunology
Slide 7: Well positioned for a strong future in immunological kidney and related diseases
Immunology Well positioned for a strong future in immunological kidney and related diseases Chronic kidney disease is predicted to become Immunology kidney development program the 5th leading cause of death globally by 20401 Molecule Indication Ph1 Ph2 Ph3 Status Years of life loss due to CKD predic
Slide 8: Gazyva: Deeper B-cell depletion key to improved clinical response
Immunology Gazyva: Deeper B-cell depletion key to improved clinical response Ph III (ALLEGORY) in SLE readout expected 2025 Gazyva is designed for enhanced B-cell depletion Gazyva immunology development program B cell depletion: Gazyva vs Rituxan4 Ph III (ALLEGORY) in SLE trial design Experimental P
Slide 9: Multiple B cell depletion approaches for SLE/LN in development
Immunology Multiple B cell depletion approaches for SLE/LN in development Initiating Ph II study for Lunsumio and Ph I study for P-CD19CD20-ALLO1 Bispecifics: Allogeneic CAR-T: Lunsumio (CD20 x CD3) & CD19 x CD3 P-CD19CD20-ALLO1 Minimal B cells detected in spleen at Day 211 Transposon-based CAR in
Slide 10: Sefaxersen (antisense oligonucleotide Factor B) in IgAN
Immunology Sefaxersen (antisense oligonucleotide Factor B) in IgAN Positive Ph II UPCR results at 6 months; Ph III (IMAGINATION) ongoing Sefaxersen (ASO Factor B) Clinical development program in IgA nephropathy Alternative complement pathway Early Ph II results3 Ph III (IMAGINATION) trial design ASO
Slide 11: Gazyva LN data presentation at WCN
Gazyva LN data presentation at WCN Brad H. Rovin MD, FASN, FACP
Slide 12: Results from the REGENCY trial assessing efficacy and safety of obinutuzumab in active lupus nephritis
RESULTS FROM THE REGENCY TRIAL ASSESSING EFFICACY AND SAFETY OF OBINUTUZUMAB IN ACTIVE LUPUS NEPHRITIS Brad H. Rovin,1 Richard A. Furie,2 Jay P. Garg,3 Mittermayer B. Santiago,4 Gustavo Aroca-Martínez,5 Adolfina Elizabeth Zuta Santillán,6 Harini Raghu,3 Imran Hassan,7 Bongin Yoo,3 Elsa Martins,8 Him
Slide 13: Disclosures
Disclosures • This study was funded by F. Hoffmann-La Roche Ltd. Editorial assistance was provided by Nucleus Global, an Inizio Company, and funded by F. Hoffmann-La Roche Ltd. • B.H. Rovin has received consulting fees from F. Hoffmann-La Roche Ltd/Genentech, Inc. • R.A. Furie has received research
Slide 14: Lupus Nephritis: Unmet Medical Need and Involvement of B Cells
Lupus Nephritis: Unmet Medical Need and Involvement of B Cells • Treatment of lupus nephritis remains sub-optimal, with morbidity and mortality significantly increased in individuals with SLE – The risk of ESKD from lupus nephritis remains high1 • B cells are central to lupus nephritis pathogenesis,
Slide 15: Obinutuzumab: A Type II Anti-CD20 Antibody
Obinutuzumab: A Type II Anti-CD20 Antibody • Obinutuzumab is a humanized type II anti-CD20 approved for the Type II anti-CD20 antibody5,6 treatment of CLL and follicular lymphoma1,2 • Obinutuzumab resulted in enhanced B-cell depletion compared with rituximab or ofatumumab in oncology3-5: – Glycoengi
Slide 16: Phase II NOBILITY Study Efficacy and Safety
Phase II NOBILITY Study (NCT02550652) Efficacy and Safety Week 52 Week 76 Week 104 Δ19%, P=0.03 Safety Event, Δ20%, P=0.01 Obinutuzumab Placebo Δ12%, P=0.11a Patients, n (%) Plus ST Plus ST (Up to Week 104) (n=64) (n=61) Any AE 58 (91) 54 (89) CRR CRR CRR 35% 38% 41% Deaths 1 (2) 4 (7) Serious AE 16
Slide 17: REGENCY Phase III Study Design
REGENCY Phase III Study Design The REGENCY study evaluated the efficacy and safety of obinutuzumab compared with placebo in patients with active lupus nephritis when added to ST consisting of MMF plus glucocorticoids Week 0 2 24 26 50 52 76 80 106 132 158 184 Q6 m Arm 1 Blinded treatment (regimen 2-
Slide 18: Study Inclusion and Exclusion Criteria
Study Inclusion and Exclusion Criteria Key Inclusion Criteria Key Exclusion Criteria • Adults 18-75 years • eGFR <30 mL/min/1.73m2 of body surface area • Classification criteria for SLE according to ACR • UPCR <1 g/g • Active ISN/RPS class III or IV lupus nephritis with or without • ESKD requiring d
Slide 19: Baseline Demographic and Clinical Characteristics
Baseline Demographic and Clinical Characteristics Obinutuzumab Plus STa Placebo Plus STa (n=135) (n=136) Race (stratification factor) Black 15 (11.1%) 17 (12.5%) Other 120 (88.9%) 119 (87.5%) Region (stratification factor) United States and Canada 20 (14.8%) 20 (14.7%) Latin America and the Caribbea
Slide 20: Patients Achieving CRR
Primary Endpoint: CRR at Week 76 Treatment Difference 13.4% (95% CI: 2.0 to 24.8) 60 P=0.0232 Patients Achieving CRR at Week 76 (% ±95% CI) Primary Endpoint: CRR at Week 76 50 Includes all of the following: 40 • UPCR <0.5 g/g • eGFR ≥85% of baseline 30 46.4% • No intercurrent events of rescue therap
Slide 21: Proportion of Patients With B-Cell Depletion Over Time
Proportion of Patients With B-Cell Depletion Over Time Obinutuzumaba Placeboa 99.2 99.2 99.2 100 95.8 94.3 95.1 Proportion of Patients With B-Cell Depletionb (%) 90 80 70 A higher proportion of 60 patients in the obinutuzumab group achieved deep 50 depletion of peripheral 40 CD19+ B cells compared w
Slide 22: Serologic Results
Serologic Results Adjusted Mean Change in Anti-dsDNA Adjusted Mean Change in C3 Adjusted Mean Change in C4 antibodies (Log Transformed) From Baseline From Baseline From Baseline Obinutuzumab Placebo Obinutuzumab Placebo Obinutuzumab Placebo 0.12 Adjusted Mean Change (g/L) Adjusted Mean Change (g/L)
Slide 23: Key Secondary Endpoints
Key Secondary Endpoints Obinutuzumab Placebo Treatment Difference P Secondary Endpoints Plus STa Plus STa (95% CI) Value (n=135) (n=136) CRR at Week 76 with prednisone taper 42.7 (34.32 to 51.09) 30.9 (23.12 to 38.65) 11.88 (0.57 to 23.18) 0.0421 (≤7.5 mg/day between Weeks 64 and 76), % (95% CI) Pro
Slide 24: Intercurrent Events at Week 76 in ITT Population
Intercurrent Events at Week 76 in ITT Population Patients, n (%) Obinutuzumab Plus STa (n=136) Placebo Plus STa (n=132) ≥1 intercurrent event 15 (11.1) 34 (25.0) Treatment failure 5 (3.7) 24 (17.6) Chronic dialysis 0 1 (0.7) Clinically significant, sustained worsening in UPCR 5 (3.7) 22 (16.2) and/o
Slide 25: Exploratory Analysis: Time to Lupus Nephritis Flare From Weeks 24 Through 76
Exploratory Analysis: Time to Lupus Nephritis Flare From Weeks 24 Through 76 25 Obinutuzumaba (n=135) Placeboa (n=136) 23.5% Proportion of Patients (%) 20 Censored HR, 0.44 Lupus nephritis flare definition 95% CI, 0.24 to 0.82 15 • eGFR decrease >20% compared with Week 24 in P=0.0074b patients with
Slide 26: Exploratory Analysis: Time to an Unfavorable Kidney Outcome Through Week 76
Exploratory Analysis: Time to an Unfavorable Kidney Outcome Through Week 76 40 Obinutuzumaba (n=135) Placeboa (n=136) HR, 0.37 95% CI, 0.18 to 0.75 Proportion of Patients (%) Censored 30 P=0.0039b Unfavourable kidney outcome definition 21.3% 20 First of the following events: • Death • Doubling of se
Slide 27: Change in eGFR From Baseline to Week 76
Change in eGFR From Baseline to Week 76 6 4 Treatment Difference Adjusted Mean Change 3.84 (95% CI, −1.83 to 9.51) (mL/min/1.73m2 ±SE) 2 P=0.1842 2.31 SE, 2.713 0 −1.54 SE, 2.706 -2 -4 Obinutuzumaba Placeboa -6 eGFR, estimated glomerular filtration rate; SE, standard error; ST, standard therapy. a P
Slide 28: Prespecified Subgroup Analyses of CRR at Week 76
Prespecified Subgroup Analyses of CRR at Week 76 Responders Placebo (%) Obinutuzumab (%) Adjusted Difference (95% CI) All patients (placebo, n=136 vs obinutuzumab, n=135) 33.1 46.4 13.4 (2.0 to 24.8) Sex Female (115 vs 114) 27.0 47.1 20.6 (8.4 to 32.7) Male (21 vs 21) 66.7 42.9 −28.2 (−53.3 to 2.3)
Slide 29: Safety Summary: AEs
Safety Summary: AEs Obinutuzumab Placebo Total Patients, n (%) Plus STa (n=136) Plus STa (n=132) (N=268) • Number of patients with ≥1 AE was Patients with ≥1 AE 126 (92.6) 117 (88.6) 243 (90.7) comparable between arms [Total events] [748] [665] [1413] • Number of patients with serious AEs was numeri
Slide 30: Safety Summary: AEs of Special Interest
Safety Summary: AEs of Special Interest Obinutuzumab Plus STa Placebo Plus STa Total Patients, n (%) (n=136) (n=132) (N=268) IRRsb 21 (15.4) 15 (11.4) 36 (13.4) Grade 3-5 infection 21 (15.4) 9 (6.8) 30 (11.2) Treatment-related neutropenia 17 (12.5) 5 (3.8) 22 (8.2) Worsening of pre-existing cardiac
Slide 31: Safety Summary: Treatment-Related Neutropenia
Safety Summary: Treatment-Related Neutropenia Obinutuzumab Placebo Total Patients, n (%) Plus STa (n=136) Plus STa (n=132) (N=268) ≥1 treatment-related AE, 17 (12.5) 5 (3.8) 22 (8.2) patients, n (%) [total events] [24] [7] [31] Neutropenia 15 (11.0) 4 (3.0) 19 (7.1) Leukopenia 2 (1.5) 0 2 (0.7) Febr
Slide 32: Conclusions
Conclusions • REGENCY met its primary endpoint of CRR at Week 76 • Statistically significant and clinically meaningful differences were observed in: – CRR with prednisone ≤7.5 mg/day between Weeks 64 and 76 – Proteinuric response (UPCR <0.8 g/g and no intercurrent events) • No unexpected safety sign
Slide 33: REGENCY New England Journal of Medicine Publication
REGENCY New England Journal of Medicine Publication
Slide 34: Doing now what patients need next
Doing now what patients need next
Slide 35: Hierarchical Statistical Testing
Hierarchical Statistical Testing CRR CRR OCS Alpha=0.04 Alpha=0.01 To maintain the overall type I error rate at 5%, Proteinuric eGFR fixed sequence testing with an adaptation of a fallback procedure1 was used Renal events ORR FACIT-F CRR, complete renal response; eGFR, estimated glomerular filtratio
Slide 36: Additional Baseline Demographic and Clinical Characteristics
Additional Baseline Demographic and Clinical Characteristics Obinutuzumab Plus STa Placebo Plus STa (n=135) (n=136) Serum creatinine (mg/dL) Mean (SD) 0.83 (0.39) 0.88 (0.48) Median (range) 0.79 (0.34 to 3.75) 0.74 (0.27 to 4.39) Anti-dsDNA positive (>120 IU/mL), no. (%) 57 (42.2) 61 (44.9) C3 compl
Slide 37: CRR at Week 76 by Obinutuzumab Dosing Schedule
CRR at Week 76 by Obinutuzumab Dosing Schedule Obinutuzumab Plus ST Obinutuzumab Plus ST Arm 1 Arm 2 (2-2-2 Regimen) (2-2-1 Regimen) (n=69) (n=66) CRR, patients % (95% CI)b 46.9 (35.0 to 58.8) 45.5 (33.4 to 57.5) There was no meaningful difference in CRR between the two obinutuzumab dosing schedules
Slide 38: Change in eGFR Levels From Baseline to Week 76
Change in eGFR Levels From Baseline to Week 76 5 Obinutuzumaba (n=135) Treatment Difference 4 Placeboa (n=136) 3.84 (95% CI, −1.83 to 9.51) 3 P=0.1842 Adjusted Mean Change 2.31 (mL/min/1.73m2 ±SE) 2 SE, 2.713 1 0 -1 −1.54 -2 SE, 2.706 -3 -4 -5 Baseline Week 76 a Plus ST of mycophenolate mofetil plus
Slide 39: B-Cell and IgG Levels by Visit
B-Cell and IgG Levels by Visit CD19+ B-Cell Levels IgG Levels Baseline is the patient’s last observation prior to initiation of study drug. Includes laboratory values through 76-week blinded treatment period. Includes laboratory values until the point of rescue for patients who received rescue thera
Slide 40: Consort Diagram
Consort Diagram Assessed for eligibility (N=513) Excluded (n=242) Randomized (n=271) Allocated to obinutuzumab Safety population Allocated to placebo Safety population ITT population (n=135) n=136a ITT population n=136 n=132a Received obinutuzumab Received placebo Discontinued treatment (n=29) Withd
Slide 41: Detailed Information on Deaths (n=4)
Detailed Information on Deaths (n=4) Date and Age/Sex/Country Study Treatment IgG (g/L) SARS-CoV-2 Vaccination Status Cause of Death 20s Obinutuzumab June 2021 Female Not applicable Not applicable Day 1 dose only Nephrotic syndrome Peru 50s Day 1: 8.71 g/L Placebo February 2022 Pfizer vaccine x3 dos
Roche Holding — Investor Presentation (February 2025) on 6ix