Slide 1: Roche
Slide 2: Forward-looking statements
This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’, ‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, str
Slide 3: SABCS 2025 Virtual IR Event
SABCS 2025 Virtual IR Event December 11 2025
Slide 4: Welcome
Welcome Bruno Eschli Head of Investor Relations
Slide 5: Agenda
Agenda Welcome Bruno Eschli, Head of Investor Relations Breast cancer franchise update Maura Dickler, VP, Global Head for Breast & Gynecologic Cancers, Product Development Ph III (lidERA) giredestrant in adjuvant ER+/HER2-negative, early BC Aditya Bardia, MD, MPH, FASCO, Professor of Medicine, Geffe
Slide 6: Significant positive Ph III news in Q4 2025
Significant positive Ph III news in Q4 2025 Gazyva: Positive Ph III results in INS Fenebrutinib: Positive Ph III results in Giredestrant: Positive Ph III results in (INShore) and SLE (ALLEGORY) RMS (FENhance 2) and PPMS (FENtrepid) adjuvant ER+ BC (lidERA) Ind. Ph I Ph II Ph III Ind. vs. Ph I Ph II
Slide 7: Up to 19 NMEs with launch potential by 2030
Up to 19 NMEs with launch potential by 2030 3 NMEs approaching filing; Peak sales assumptions for fenebrutinib in MS raised 0.5-1bn peak sales 1-2bn peak sales afimkibart 2-3bn peak sales >3bn peak sales CT-388 IBD, AtD, RA, MASH Obesity +/- T2D sefaxersen CT-868 IgAN T1D with BMI ≥25 zosurabalpin C
Slide 8: A solid base to deliver long-lasting future growth
A solid base to deliver long-lasting future growth Significant upside potential due to Ph III successes for Gazyva in SLE, fenebrutinib in MS and giredestrant in ER+ BC illustrative Business development ▪ BD to accelerate pipeline rejuvenation ▪ In-house pipeline with upside potential Pharma pipelin
Slide 9: Consensus outlook 2024-29
Consensus outlook 2024-29* Growth driven by our young on-market portfolio; potential pipeline up-side Biosimilar gap (24-29) Consensus sales growth (24-29) Potential up-side 2026+ CHF Vabysmo 2.5bn Itovebi 1.1bn Ronapreve 015 bn Lucentis 0.1bn Polivy 1.0bn Assets with low to no coverage in Columvi 0
Slide 10: 2025 news flow complete: Positive Ph III results for PiaSky in aHUS
2025 news flow complete: Positive Ph III results for PiaSky in aHUS Compound Indication Milestone Itovebi + palbociclib + fulvestrant 1L PIK3CA-mut HR+ BC EU approval Columvi + GemOx 2L+ DLBCL US/EU approval / (US/EU) Lunsumio SC 3L+ FL US/EU approval Elevidys DMD EU approval Regulatory Gazyva Lupus
Slide 11: 2026: Key newsflow outlook
2026: Key newsflow outlook* Compound Indication Milestone Lunsumio + Polivy 2L+ DLBCL US approval giredestrant adjuvant ER+/HER2- early BC US/EU filing giredestrant + everolimus post CDKi ER+/HER2- mBC US/EU filing/ US approval PiaSky aHUS US/EU filing fenebrutinib RMS US/EU filing fenebrutinib PPMS
Slide 12: Breast cancer franchise update
Breast cancer franchise update Maura Dickler VP, Global Head for Breast & Gynecologic Cancers, Product Development
Slide 13: Oncology strategy: Expanding into ER+ breast cancer
Oncology/Hematology Oncology strategy: Expanding into ER+ breast cancer Clear focus on our E2E disease areas to accelerate innovation and strengthen our key franchises End-to-end disease areas Solid tumors: Breast cancer Lung cancer OUR AMBITION Where we play Hematology: Malignant heme1 Hemophilia S
Slide 14: Oncology solid tumor pipeline with combination opportunities in BC
Oncology/Hematology Oncology solid tumor pipeline with combination opportunities in BC Giredestrant has the potential to become a new SoC backbone in ER+ BC Phase I Phase II Phase III RG6114 inavolisib autogene cevumeran giredestrant RG6180 multiple indications RG6171 RG6171 giredestrant multiple ER
Slide 15: ER+ breast cancer represents a significant market opportunity
Oncology/Hematology ER+ breast cancer represents a significant market opportunity Adjuvant setting constitutes the largest population Breast cancer by subtype1 ER+ breast cancer epidemiology by line of treatment Unknown TNBC 6% 273k 11% High risk (~20%) Drug-treated, US + EU5 ER-/HER2+ 4% ER+/HER2+
Slide 16: Portfolio of potentially BIC molecules to further improve SoC in BC
Oncology/Hematology Portfolio of potentially BIC molecules to further improve SoC in BC Targeting key signaling nodes that drive etiology and progression of BC Differentiated molecules with a potential to redefine BC treatment paradigm as monotherapy and in combinations Giredestrant: Next generation
Slide 17: Despite advances in treatment, a high unmet need remains in ER+ BC
Oncology/Hematology Despite advances in treatment, a high unmet need remains in ER+ BC ER+ BC treatment landscape Low risk Medium risk High risk (~55%)1 (~25%)1 (~20%)1 Neoadj Remaining unmet need SURGERY ▪ Up to 1/3 pts on adjuvant ET eventually relapse2,3 ▪ Existing ETs come with AEs, e.g., arthra
Slide 18: Giredestrant: Next-gen SERD with potential to become SoC backbone ET
Oncology/Hematology Giredestrant: Next-gen SERD with potential to become SoC backbone ET Robust ER antagonist activity demonstrated in the neoadjuvant setting Preclinical potency1 Efficacy in the neoadjuvant ER+/HER2- BC setting coopERA study results2 EMPRESS study results3 Potency (IC50) across thr
Slide 19: Giredestrant: Positive Ph III (evERA) in ESR1m and ITT in 2L+ mBC
Oncology/Hematology Giredestrant: Positive Ph III (evERA) in ESR1m and ITT in 2L+ mBC Potential to be the first only-oral SERD combination therapy in the post-CDK4/6i setting Ph III (evERA) INV-PFS results1 Interim OS results across subgroups1 ESR1m population ITT population Median, Median, Months M
Slide 20: Giredestrant: Comprehensive clinical program across patient populations
Oncology/Hematology Giredestrant: Comprehensive clinical program across patient populations Upcoming Ph III results in 1L ER+ mBC: persevERA (ET-sensitive) and pionERA (ET-resistant) Giredestrant aims to replace SoC ET across eBC & mBC giredestrant 1L ER+/HER2- mBC Low risk Medium risk High risk 1 R
Slide 21: Itovebi: Defining new SoC in PIK3CAm ER+ BC
Oncology/Hematology Itovebi: Defining new SoC in PIK3CAm ER+ BC Approved in US, EU and China, additional launches ongoing PI3Kα inhibition Ph III (INAVO120) OS results in 1L ER+/HER2- mBC2 Potency/selectivity (inavolisib vs. alpelisib)1 Median, 96.8 months 100 87.0 Inavolisib (n=161) 34.0 Pi3Kα pote
Slide 22: Itovebi: Potential to expand broadly in PIK3CAm BC
Oncology/Hematology Itovebi: Potential to expand broadly in PIK3CAm BC Potential for inavolisib-based regimen in PIK3CAm ER+ BC 1 inavolisib 1L PIK3CAm (INAVO120) ER+/HER2- mBC (AI resistant) Low risk Medium risk High risk inavolisib Post-CDK4/6i PIK3CAm (~55%)1 (~25%)1 (~20%)1 2 Readout 2026 (INAVO
Slide 23: RG6794 (GDC-4198): Next-gen CDKi in ER+ BC
Oncology/Hematology RG6794 (GDC-4198): Next-gen CDKi in ER+ BC Potential to overcome CDK2-driven resistance to CDK4 inhibition CDK4/6i resistance mechanism1,2 Activity against CDK4, CDK23 In vitro potency4 IC50 (nM) CDK4 CDK2 GDC-4198 0.3 4.6 Abemaciclib 0.8 270 Palbociclib 2.3 >103 ▪ CDK4/6i resist
Slide 24: RG6794 (GDC-4198): Early clinical activity in ER+ mBC
Oncology/Hematology RG6794 (GDC-4198): Early clinical activity in ER+ mBC Ongoing Phase Ib/II (MoonROSE) study to investigate RG6794 (GDC-4198) + giredestrant combination Ph I: Preliminary activity in post-CDK4/6i setting1 Phase Ib/II (MoonROSE) study with giredestrant Phase Ib Randomized Efficacy-m
Slide 25: Ph III (lidERA) giredestrant in adjuvant ER+/HER2-negative, early BC
Ph III (lidERA) giredestrant in adjuvant ER+/HER2-negative, early BC Aditya Bardia MD, MPH, FASCO Professor of Medicine, Geffen School of Medicine, University of California Los Angeles
Slide 26: Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment: lidERA results
Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial Presenting author: Aditya L. Bardia, MD University of California, Los Angeles, Los An
Slide 27: Disclosure information
Disclosure information Aditya L. Bardia. I have the following relevant financial relationships to disclose: • Consultant/advisory board: Alyssum, BMS, Daiichi Pharma/AstraZeneca, Eli Lilly, Genentech, Inc., Gilead, Menarini, Merck, Novartis, Pfizer, Sanofi, and Vyome. • Contracted research/grant (to
Slide 28: Background – adjuvant ET
Background – adjuvant ET • ER+, HER2-negative breast cancer accounts for > 70% of early breast cancers (eBC).1 • Endocrine therapies (tamoxifen or AIs) are a mainstay of treatment of ER+, HER2-negative eBC.1 • The last approvals of new endocrine therapy (ET) in eBC came with the introduction of AIs
Slide 29: Background – adjuvant ET
Background – adjuvant ET • ER+, HER2-negative breast cancer accounts for > 70% of early breast cancers (eBC).1 • Endocrine therapies (tamoxifen or AIs) are a mainstay of treatment of ER+, HER2-negative eBC.1 • The last approvals of new endocrine therapy (ET) in eBC came with the introduction of AIs
Slide 30: Background – giredestrant
Background – giredestrant Giredestrant (GDC-9545) is a potent next-generation oral SERD and full ER antagonist, designed to drive deep and sustained inhibition of ER signaling, both ligand-dependent and ligand-independent.1 Estrogen Full antagonism ER Giredestrant Degradation Genes for proliferation
Slide 31: Background – giredestrant
Background – giredestrant • In cellular viability assays, giredestrant ESR1 WT, coopERA ER-active Breast has been shown to be more potent than cell lines Cancer other SERDs.1–5 in vitro5 primary analysis6 • In eBC, giredestrant demonstrated superior antiproliferative activity in the neoadjuvant sett
Slide 32: lidERA Breast Cancer study design
lidERA Breast Cancer study design A global, randomized, open-label, multicenter Phase III trial At least 5-year treatment duration 5-year follow-up Key eligibility criteria • Participants with ER+, HER2-negative early breast cancer N = 4170 • Stage I–III disease (anatomical) Giredestrant (30 mg PO Q
Slide 33: Statistical design
lidERA Breast Cancer Statistical design • The primary endpoint was IDFS,* defined as the time from randomization to first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence; ipsilateral locoregional invasive breast cancer recurrence; distant recurrence; contralateral in
Slide 34: Patient flow
lidERA Breast Cancer Patient flow 4170 randomized 2084 giredestrant 2086 SOC ET 21 not treated 15 not treated 2060 received study drug 2074 received study drug 326 tamoxifen, 441 anastrozole, Type of ET in the control arm: 1052 letrozole, 256 exemestane 16% tamoxifen and 84% AI 1713 treatment ongoin
Slide 35: Baseline demographics and characteristics
lidERA Breast Cancer Baseline demographics and characteristics Giredestrant SOC ET Giredestrant SOC ET n = 2084 n = 2086 n = 2084 n = 2086 Median age, years (range) 54.0 (22–91) 54.0 (25–89) ER status, n (%)‡ Female sex, n (%) 2073 (99.5) 2075 (99.5) Low-positive (1–10% of cells positive) 45 (2.2) 5
Slide 36: Primary endpoint: IDFS
lidERA Breast Cancer Primary endpoint: IDFS 100 Giredestrant SOC ET + Giredestrant + everolimus SOC ET everolimus 80 100 97.7% n(n= =2084 102) n(n==2086 105) 94.6% Events, n (%) 140 (6.7) 196 (9.4) 96.9% 92.4% 60 Stratified HR 0.70 IDFS (%) 90 92.3% (95% CI) (0.57, 0.87); p = 0.0014* 89.6% 40 80 20
Slide 37: Primary endpoint: IDFS
lidERA Breast Cancer Primary endpoint: IDFS 100 Giredestrant SOC ET + Giredestrant + everolimus SOC ET everolimus 80 100 97.7% n(n= =2084 102) n(n==2086 105) 94.6% Events, n (%) 140 (6.7) 196 (9.4) 96.9% 92.4% 60 Stratified HR 0.70 IDFS (%) 90 92.3% (95% CI) (0.57, 0.87); p = 0.0014* 89.6% 40 Explor
Slide 38: IDFS in key subgroups
lidERA Breast Cancer IDFS in key subgroups Patients, n Total, n Giredestrant SOC ET HR (95% CI) All patients 4170 2084 2086 0.70 (0.57, 0.87) Age group, years ≤ 45 906 472 434 0.81 (0.50, 1.33) > 45 to ≤ 55 1355 660 695 0.54 (0.36, 0.80) > 55 to ≤ 65 1118 567 551 0.77 (0.53, 1.13) > 65 791 385 406 0
Slide 39: IDFS in key subgroups
lidERA Breast Cancer IDFS in key subgroups Patients, n Total, n Giredestrant SOC ET HR (95% CI) All patients 4170 2084 2086 0.70 (0.57, 0.87) Age group, years ≤ 45 906 472 434 0.81 (0.50, 1.33) > 45 to ≤ 55 1355 660 695 0.54 (0.36, 0.80) > 55 to ≤ 65 1118 567 551 0.77 (0.53, 1.13) > 65 791 385 406 0
Slide 40: Distant recurrence-free interval
lidERA Breast Cancer Distant recurrence-free interval 100 80 100 98.5% 96.1% 97.7% 94.4% Giredestrant SOC ET + 94.2% +Giredestrant everolimus SOC ET everolimus 60 n== 2084 n== 2086 DRFI (%) 90 92.1% (n 102) (n 105) Events, n (%) 102 (4.9) 145 (7.0) 40 Stratified HR 0.69 80 (95% CI) (0.54, 0.89) 20 7
Slide 41: Interim overall survival
lidERA Breast Cancer Interim overall survival 100 80 99.5% 100 98.2% 99.4% 97.0% 97.5% Giredestrant SOC ET + 95.9% +Giredestrant everolimus SOC ET everolimus 60 n= (n = 2084 102) n= (n = 2086 105) OS (%) Events, n (%) 57 (2.7) 71 (3.4) 90 40 Stratified HR 0.79 (95% CI) (0.56, 1.12); p = 0.1863* 20 8
Slide 42: Safety overview (safety-evaluable population)
lidERA Breast Cancer Safety overview (safety-evaluable population) Giredestrant SOC ET n = 2060 n = 2074 Median treatment duration, months (range) 31.64 (0.03–46.36) 30.88 (0.03–46.26) Mean dose intensity, % (SD) 98.77 (3.07) 98.68 (3.73) Patients with ≥ 1 AE, n (%) AEs (all grades) 1955 (94.9) 1957
Slide 43: AE overview (safety-evaluable population)
lidERA Breast Cancer AE overview (safety-evaluable population) Common TEAEs (≥ 7.5% of patients in either arm at any grade) Selected AEs Giredestrant SOC ET Giredestrant n = 2060 SOC ET n = 2074 n = 2060 n = 2074 Arthralgia 1.5 / 46.5 45.3 / 1.8 Patients, n (%) with treatment discontinuations due to
Slide 44: Conclusions
lidERA Breast Cancer Conclusions • Since approval of AIs in the 2000s, lidERA Breast Cancer is the first trial to demonstrate benefit with a novel ET in early breast cancer (eBC). AI, aromatase inhibitor; CI, confidence interval; DRFI, distant recurrence-free interval; ER+, estrogen receptor-positiv
Slide 45: Conclusions
lidERA Breast Cancer Conclusions • Since approval of AIs in the 2000s, lidERA Breast Cancer is the first trial to demonstrate benefit with a novel ET in early breast cancer (eBC). • With a median follow-up of 32.3 months, the lidERA trial demonstrated a statistically significant and clinically meani
Slide 46: Conclusions
lidERA Breast Cancer Conclusions • Since approval of AIs in the 2000s, lidERA Breast Cancer is the first trial to demonstrate benefit with a novel ET in early breast cancer (eBC). • With a median follow-up of 32.3 months, the lidERA trial demonstrated a statistically significant and clinically meani
Slide 47: Acknowledgments
Acknowledgments • We thank the patients who participated in the trial, as well as their families, the research staff, and the Independent Data Monitoring Committee members involved in the trial. • This study was performed with valuable contributions from its global Steering Committee and in collabor
Slide 48: Doing now what patients need next
Doing now what patients need next