Slide 1: Slide 1
Slide 2: ASCO 2022 Virtual IR event
ASCO 2022 Virtual IR event 6 June 2022
Slide 3: 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 4: Welcome
Welcome Bruno Eschli, Ph.D. | Head of Investor Relations
Slide 5: Agenda
Agenda Welcome Bruno Eschli, Ph.D., Head of Investor Relations Oncology late-stage pipeline update Elena Bernedo-Arzac, SVP, Oncology Therapeutic Area Head Key data at ASCO 2022 • Glofitamab pivotal Ph1b data in 3L+DLBCL • Polivy Asian sub-population data in 1L DLBCL (POLARIX) Ginna Laport, VP, Glob
Slide 6: Significant key news flow remains in 2022
Significant key news flow remains in 2022 Compound Indication Milestone Vabysmo nAMD/DME US/EU approval US Susvimo nAMD EU approval mosunetuzumab 3L+ FL US/EU approval Regulatory Tecentriq Adjuvant NSCLC EU approval Hemlibra Mild to moderate hemophilia A EU approval Polivy + R-CHP 1L DLBCL EU/US app
Slide 7: Oncology late-stage update
Oncology late-stage update Elena Bernedo-Arzac | SVP, Oncology Therapeutic Area Head
Slide 8: Earlier disease presents opportunity for cure
Earlier disease presents opportunity for cure Need for high efficacy treatments that are well tolerated Outcomes by cancer type and stage at diagnosis1 Chance for a cure: development earlier in the course of disease is critically important to improving the cure rate 100% Cost to society: treatment i
Slide 9: Upcoming readouts in early disease
Upcoming readouts in early disease Potential to expand existing indications Lung / H&N GI / GU Molecule Indication Ph 1 Ph 2 Ph 3 Molecule Indication Ph 1 Ph 2 Ph 3 Adjuvant NSCLC IMpower010 Adjuvant RCC IMmotion010 Tecentriq Neoadjuvant NSCLC IMpower030 Adjuvant HCC IMbrave050 Adjuvant SCCHN IMvoke
Slide 10: Tecentriq: First-in-class CIT in adjuvant NSCLC
Tecentriq: First-in-class CIT in adjuvant NSCLC Strong US launch in PD-L1+ disease* CT screening reduces lung-cancer mortality2 Adjuvant NSCLC treatment still evolving Screening: Early detection technologies expected to increase diagnosis at early stage Committed to improving screening rates to su
Slide 11: Tiragolumab (aTIGIT mAb)
Tiragolumab (aTIGIT mAb) Comprehensive development program ongoing Indication Ph 1 Ph 2 Ph 3 Development strategy 1L NSCLC: PD-L1 high SKYSCRAPER-01 Continues to next analysis 1L ES-SCLC SKYSCRAPER-02 1 Build on Tecentriq Lung cancer Stage III unres. NSCLC SKYSCRAPER-03 Neoadj / Adj NSCLC SKYSCRAPER
Slide 12: Broad and diverse breast cancer portfolio
Broad and diverse breast cancer portfolio Expanding beyond HER2+ disease Novel mechanisms and technologies Breast cancer cases by subtype1 HER2 mAb 40% of HR+ patients have 7% PI3K mutation 4% 10% HER2+ HER2 ADC BC 69% 10% HER2 TCB mAb • runimotamab (HER2xCD3) CPI mAb TNBC HR+/HER2− TNBC Small molec
Slide 13: HER2+ franchise: High efficacy and safety bar established in eBC
HER2+ franchise: High efficacy and safety bar established in eBC Perjeta 8-year follow-up data from landmark APHINITY study expected in 2022 Phesgo with strong global launch Continuing to build on existing standard of care Global Perjeta/Phesgo Patients preference Phesgo heredERA (1L HER2+/ER+ mBC)
Slide 14: ER+/HER2– BC: Giredestrant Ph II final neoadjuvant results
ER+/HER2– BC: Giredestrant Ph II final neoadj. results presented Results support on-going Ph III (IidERA) development in the adjuvant setting Ph II (coopERA) final results in neoadjuvant ER+/HER2- breast cancer at ASCO 2022 Baseline to week 2 Baseline to surgery CCCA at week 2 and at surgery Ki67 re
Slide 15: HR+/HER2- BC: High unmet need remains
HR+/HER2- BC: High unmet need remains Large addressable population for SERD and PI3K programs Targeting both early and metastatic disease eBC 1L mBC 2L/3L mBC Endocrine Therapy Giredestrant: Potential for best-in-class SERD Given until resistance • Differentiated MoA: immobilizes on the chromosomal
Slide 16: Broad and diverse portfolio in malignant hematology
Broad and diverse portfolio in malignant hematology Novel mechanisms and technologies TCB mAb mosunetuzumab cevostamab DLBCL 1 : 1 format glofitamab Build on key areas of strength GPRC5DxCD3 HLA-A2-WT1xCD3 FL • POLIVY as potential new SOC in 1L DLBCL 2 : 1 format CD19 x CD28 • Introducing CD20xCD3 b
Slide 17: 1L DLBCL: Polivy + R-CHP approved in EU
1L DLBCL: Polivy + R-CHP approved in EU First new treatment in >20 years with clinically meaningful PFS improvement High unmet need in 1L DLBCL remains Multibillion market opportunity in 1L DLBCL ~52k 1L DLBCL: R-CHOP Number of patients ~16k EU5 ~9k “Cured” R/R DLBCL US (~60%) (~40%) 1L 2L 3L+ • ~40
Slide 18: Mosunetuzumab and glofitamab (CD20 x CD3 bispecifics)
Mosunetuzumab and glofitamab (CD20 x CD3 bispecifics) Potential to be first-in-class and best-in-class in FL and DLBCL Tailored to address diverse patient and Most advanced clinical development plan healthcare system needs DLBCL FL 1L R/R 3L+ 1L 2L+ 3L+ Polivy + Polivy + glofitamab G + chemo G + ben
Slide 19: Glofitamab clinical data
Glofitamab clinical data Ginna Laport | VP Global Head of Hematology NHL CLL, Product Development
Slide 20: Glofitamab in R/R DLBCL: pivotal Phase II expansion results
Glofitamab in patients with R/R diffuse large B-cell lymphoma (DLBCL) and ≥2 prior therapies: pivotal Phase II expansion results Single-arm pivotal Phase II expansion cohort in patients with R/R DLBCL and ≥2 prior therapies Key inclusion criteria Glofitamab IV administration • DLBCL NOS, HGBCL, Fixe
Slide 21: Baseline characteristics
Baseline characteristics Heavily pre-treated, highly refractory population Clinical cut-off date: March 14, 2022; *unless otherwise specified; †safety-evaluable population (all treated patients); ‡ECOG PS 2, n=1 (0.6%); Ab, antibody; ASCT, autologous stem cell transplant; trFL, transformed 21 follic
Slide 22: Response rates – primary endpoint met
Response rates – primary endpoint met High CR/ORR rate at recommended phase II dose (RP2D) Glofitamab 2.5/10/30mg Efficacy endpoint1 (n=155) 61 (39.4%) CR rate* [95% CI: 31.6%, 47.5%] 80 (51.6%) ORR* [95% CI: 43.5%, 59.7%] • Median duration of follow-up: 12.6 months (range: 0–22) • Responses were ac
Slide 23: Complete response rates by IRC in pre-specified subgroups
Complete response rates by IRC in pre-specified subgroups Consistent CR rates in patients with prior CAR-T therapy; CR rates higher in relapsed patients 23
Slide 24: Durable responses maintained after cessation of therapy
Durable responses maintained after cessation of therapy Duration of overall response by IRC Duration of complete response by IRC N=80 N=61 Median DoR follow-up, mo (range) 10.6 (0–21) Median DoCR follow-up, mo (range) 10.6 (0–21) 12-months DoR, % (95% CI) 63.6 (51.1, 76.2) 12-months DoCR, % (95% CI)
Slide 25: DoCR in earlier cohorts shows durable responses beyond 24 months
DoCR in earlier cohorts show durable responses beyond 24 months Supporting cohort Duration of complete response by IRC • Patients in earlier cohorts have extended follow up for duration of response • patients with R/R DLBCL, HGBCL, trFL and PMBCL with ≥2 prior lines of therapy (n=101) • patients tre
Slide 26: Time-to-event endpoints
Time-to-event endpoints Early trend for plateau observed in PFS and OS curves Progression-free survival by IRC Overall survival* N=155 N=155 Median PFS follow-up, mo (range) 12.6 (0–22) Median OS, months (95% CI)† 11.5 (7.9, 15.7) Median PFS, months (95% CI)† 4.9 (3.4, 8.1) 12-month OS rate, % (95%
Slide 27: Glofitamab safety profile
Glofitamab safety profile Well tolerated, with a favorable safety profile n (%)* N=154 AEs (≥15%) by grade and relationship with glofitamab Median no. of cycles received (range) 5 (1–13) Median relative dose intensity, % (range) 100 (94–100) AE 152 (98.7) Related AE 140 (90.9) Grade 3–4 AE 87 (56.5)
Slide 28: Cytokine release syndrome
Cytokine release syndrome Mostly low grade, time of onset was predictable, and mostly occurred during cycle 1 n (%) N=154 CRS by cycle and grade† CRS (any grade)* 97 (63.0) Grade 1 (fever) 73 (47.4) Grade 2 18 (11.7) Grade 3 4 (2.6) Grade 4 2 (1.3) Median time to CRS onset from C1D8 dose, 13.6 (6.2–
Slide 29: Other adverse events of interest
Other adverse events of interest Low rate of treatment discontinuations due to AEs and low rate of ICANS events n (%) N=154 n (%) N=154 Infections (all grades) 59 (38.3) AE leading to treatment discontinuation 14 (9.1) Grade ≥3 23 (14.9) Infections and infestations¶ 6 (3.9) Neutropenia* (all grades)
Slide 30: Glofitamab conclusions
Glofitamab conclusions • Primary efficacy endpoint met; CR: 39.4% in heavily pre-treated, highly refractory patients with DLBCL • Consistent CR rate in patients with prior CAR-T; higher CR rate in relapsed vs refractory patients • CRs achieved early and were durable after the fixed treatment duratio
Slide 31: Asia subpopulation analysis from the Phase III POLARIX trial
Asia subpopulation analysis from the Phase III POLARIX trial Results consistent with the global POLARIX study The Asia subpopulation (n=281) included patients from mainland China, Japan, South Korea, and Taiwan (enrolled during the global phase), and from the China extension cohort PFS for Pola-R-CH
Slide 32: Early pipeline programs in focus (pRED)
Early pipeline programs in focus Johanna Bendell, M.D. | Global Head Oncology, Roche Pharma Research & Early Development (pRED)
Slide 33: pRED oncology strategy
pRED oncology strategy Covering a range of modalities in line with state of the art cancer biology Cancer Immunotherapy (CIT) Cancer Cell Targeted Therapy (CTT) T cell redirection Immunomodulation T cell generation Oncogenic drivers Synthetic lethality APC MHC- Gene Gene peptide Normal A B Viable ce
Slide 34: pRED oncology development pipeline
pRED oncology development pipeline Phase 0 Phase 1/2 NME Cibisatamab (CEA x CD3) HLA-A2-WT1 x CD3 T cell HLA-A2-MAGE-A4 x CD3 2 : 1 format TCBs redirection GPRC5D x CD3 EGFRvIII x CD3 Small molecules NME FAP 4-1BBL Bispecifics Co-stimulators CD19 4-1BBL Fusion proteins CIT Immuno- CD19-CD28 mAbs mod
Slide 35: GPRC5D x CD3 TCB (RG6234) in r/r multiple myeloma
GPRC5D x CD3 TCB (RG6234) in r/r multiple myeloma Novel 2:1 format T cell bispecific with best-in-class potential • GPRC5D is the most TIL activation and tumor cell lysis in bone marrow aspirates from MM patients1 Target specific target yet known CD3 Head-to- tail in MM TIL activation and tumor cell
Slide 36: GPRC5D x CD3 TCB (RG6234) in r/r multiple myeloma
GPRC5D x CD3 TCB (RG6234) in r/r multiple myeloma Novel 2:1 format T cell bispecific with best-in-class potential Compelling emerging clinical activity in heavily pretreated pts with r/r MM1 Patient characteristics Early efficacy data n=41 patients n=34 efficacy-evaluable patients Median age 63 year
Slide 37: CD19 4-1BBL (RG6076) in r/r NHL
CD19 4-1BBL (RG6076) in r/r NHL B cell-targeted costimulatory T cell agonist with first-in-class potential CD19 4-1BBL + CD20xCD3 TCB Potential for off-the-shelf alternative to 2nd generation CD19-CAR-T cell Change in tumor volume over time1 Combination of CD20-TCB and CD19 4-1BBL induces intratumor
Slide 38: CD19-CD28 (RG6333) in r/r NHL
CD19-CD28 (RG6333) in r/r NHL B cell-targeted costimulatory T cell agonist with distinct MoA vs 4-1BB CD19-CD28 MoA CD19-CD28 synergizes with CD20-TCB - boosting and prolonging T cell activity Radiance CD20-TCB CD20-TCB + CD19-CD28 [p/sec/cm2/sr] 5000 D3 3000 1000 80000000 D17 60000000 20000000 • 2n
Slide 39: PD1-LAG3 (RG6139) in solid tumors
PD1-LAG3 (RG6139) in solid tumors Bispecific checkpoint inhibitor that preferentially targets TILs PD1-LAG3 has the potential to replace current CPI therapies in inflamed tumor types PD1-LAG3 structure and MoA Improved tumor growth inhibition in preclinical models1 PD-1 • In preclinical models, PD1-
Slide 40: PD1-LAG3 (RG6139) in metastatic melanoma
PD1-LAG3 (RG6139) in metastatic melanoma Patient case report Confirmed partial response following 3L treatment with PD1-LAG3 64 year-old Caucasian male with CT - Cycle 31 metastatic melanoma: CT - Baseline Day 1 Prior treatment: • 1L pembrolizumab best overall response: PD • 2L pembrolizumab plus
Slide 41: PD1-IL2v (RG6279) in solid tumors
PD1-IL2v (RG6279) in solid tumors Targeting IL-2v to PD-1+ T cells to exploit pre-existing endogenous immunity PD1-IL2v MoA PD1-IL2v: Superior efficacy vs aPD-1 and aPD-1 + FAP-IL2v in preclinical models Panc02 mouse tumor model1 Better effectors Exhausted Collaboration with R. Ahmed & M. Hashimoto,
Slide 42: PD1-IL2v (RG6279) in metastatic melanoma
PD1-IL2v (RG6279) in metastatic melanoma Patient case report Preliminary signs of clinical activity following 3L treatment with PD1-IL2v CT - Baseline CT - Week 6 40 year-old male with metastatic melanoma: Prior treatment • 1L pembrolizumab best overall response: PD • 2L ipilimumab best overall
Slide 43: HLA-A2 WT1 x CD3 TCB (RG6007) in hematologic tumors
HLA-A2 WT1 x CD3 TCB (RG6007) in hematologic tumors TCR receptor-like T cell bispecific targeting intracellular oncoprotein WT1 Potential tumor targets beyond cell surface proteins WT1-TCB ex vivo activity on primary AML patient samples1 AML lysis in panel of AML donor Dose-dependent reduction of tu
Slide 44: FAP-CD40 (RG6189) in solid tumors
FAP-CD40 (RG6189) in solid tumors Tumor stroma targeted activator of antigen presenting cells Targeted myeloid cell activation High affinity binding Preclinically, a high dose of FAP-CD40 did not result in the typical side effects Imaging sub-study2 to FAP in tumor observed with systemic CD40 agonis
Slide 45: Roche pRED - building for the future in oncology
Roche pRED - building for the future in oncology Managed R&D diversification over time Opportunistic areas Committed areas • T cell redirection • Immunomodulation • T cell generation • Oncogenic drivers • Synthetic lethality Exploratory areas Partnerships to explore innovative new modalities E.g. li
Slide 46: Early pipeline programs in focus (gRED)
Early pipeline programs in focus Andrew Chan, M.D., Ph.D. | Senior Vice President, Research Biology, Genentech Research & Early Development (gRED)
Slide 47: Integrated Oncology Strategy
Integrated Oncology Strategy Diverse approaches to cancer therapeutics to provide the best options for patients Oncogenic Adaptive & Innate Tumor Lineage Synthetic Immunity Microenvironment Dependencies Pathways Immunity Great Ape Adenovirus Cloning capacity >9 Kb Maximum antigen length tested: 2,20
Slide 48: Oncogenic pathways
Oncogenic pathways Oncogenic Adaptive & innate Tumor Lineage Synthetic immunity microenvironment dependencies pathways immunity Immune cell engagers and Augment productive T- and Target immune suppression Target specific tumor cell Target mutant oncoproteins engineered cells dendritic cell functions
Slide 49: RAS-MAPK pathway
RAS-MAPK pathway Drugging “undruggable” targets and opening new combinations Optimal clinical effectiveness requires combination strategies to target cross-talk, feedback and resistance mechanisms. gRED portfolio Late stage portfolio / marketed 49
Slide 50: GDC-6036 (KRAS G12C inhibitor)
GDC-6036 (KRAS G12C inhibitor) KRAS is the most frequently mutated oncogene, occurring in more than 25% of all cancers KRAS G12C inhibitor Ph 1b clinical development program GDC-6036 Monotherapy GDC-6036 + Tecentriq (anti-PD-L1) GDC-6036 + cetuximab (anti-EGFR) GDC-6036 + erlotinib (EGFRi) GDC-6036
Slide 51: GDC-1971 (SHP2 inhibitor)
GDC-1971 (SHP2 inhibitor) Highly potent; potential for differentiation from other SHP2i GDC-1971 SHP2 inhibitor Synergy with KRAS G12Ci and SHP2i Combination of GDC-1971 and GDC-6036 results in tumor regressions in vivo Vehicle control GDC-6036 (KRAS G12Ci) 25mg/kg, PO QD GDC-1971 (SHP2i) 60mg/kg, P
Slide 52: Belvarafenib is a potent and selective RAF dimer inhibitor
Belvarafenib is a potent and selective RAF dimer inhibitor Selective inhibition of mutant RAF dimers Efficacy in CPI-experienced NRASmt melanoma Belvarafenib + Cobimetinib: Ph 1b expansion in NRAS melanoma belvarafenib N=15 • Belvarafenib in combination with cobimetinib exhibits encouraging anti-tum
Slide 53: Synthetic immunity
Synthetic immunity Oncogenic Adaptive & innate Tumor Lineage Synthetic immunity microenvironment dependencies pathways immunity Immune cell engagers and Augment productive T- and Target immune suppression Target specific tumor cell Target mutant oncoproteins engineered cells dendritic cell functions
Slide 54: T-cell bispecifics
T-cell bispecifics Strong clinical POC for platform in hematologic indications, advancing in solid tumors MAGE-A4 x CD3 (ovarian, NSCLC, gastric, head & neck) T-cell bispecific pipeline Ovarian carcinoma Ph 1 Ph 2 Ph 3 mosunetuzumab (CD20 x CD3) HLA-A2 *Approval in 3L+ FL anticipated 2022 NHL, CLL M
Slide 55: Adaptive immunity
Adaptive immunity Oncogenic Adaptive immunity & innate Tumor Lineage Synthetic immunity Adaptive microenvironment dependencies pathways immunity Great Ape Adenovirus Cloning capacity >9 Kb Maximum antigen length tested: 2,200amino acids (>80neo-antigens of 25 aa) Augment productive T- and Target mut
Slide 56: Neoantigen specific therapies require individualized approaches
Neoantigen specific therapies require individualized approaches Blood and Mutation Neoantigen Vaccine tumor biopsy identification prediction manufacturing • Autogene cevumeran: Individualized mRNA vaccine directed against patients’ unique tumor neoantigens • VB10.NEO: Individualized DNA vaccine targ
Slide 57: Autogene cevumeran, individualized neoantigen mRNA vaccine
Autogene cevumeran, individualized neoantigen mRNA vaccine Substantially and durably expand T-cells, correlating with delayed recurrence Vaccine induced T-cell response is associated Phase I study in surgically resectable PDAC (target n=20) with longer RFS Investigator-initiated single-center trial
Slide 58: Machine learning improves neoantigen prediction
Machine learning improves neoantigen prediction Peptide-MHC prediction derived from ML of Testing of GRAF algorithm on mass spectroscopy data from cell lines Phase 1 clinical data set (N=44) • Success of individualized immunotherapy requires accurate NetMHC prediction of immunogenic neoantigens for
Slide 59: Tumor microenvironment
Tumor microenvironment Oncogenic Adaptive & innate Tumor Lineage Synthetic immunity microenvironment dependencies pathways immunity Immune cell engagers and Augment productive T- and Target immune suppression Target specific tumor cell Target mutant oncoproteins engineered cells dendritic cell funct
Slide 60: Tumors exhibit one of three basic immune phenotypes
Tumors exhibit one of three basic immune phenotypes Prioritizes immune profiles that represent the greatest unmet need and opportunity Targets for T cell signature TGFβ Signature neuroendocrine signature immunomodulation Immune Inflamed Immune Excluded Immune Desert CD8+ T cells infiltrated, but CD8
Slide 61: SOF10 / RG6440 (anti-latent TGFβ1)
SOF10 / RG6440 (anti-latent TGFβ1) SOF10 selectively binds to TGFβ1 Anti-TGFβ and PD-L1 increases T-cell infiltration into tumors Latent TGFβ1 is activated by protease or via integrin • TGFβ1 is known as a key regulator of tumor microenvironment which forms a “physical barrier” for T-cell infiltrati
Slide 62: gRED oncology portfolio
gRED oncology portfolio 12 molecules in early development (Ph 1 / 2) Phase I Phase II Phase III giredestrant (SERD) inavolisib (mPI3Ka inh) Oncogenic ipatasertib (AKT inh) pathway belvarafenib (pan RAF inh)1 GDC-6036 (KRAS G12C inh) GDC-1971 (SHP2 inh)2 mosunetuzumab (CD20 x CD3) cevostamab (FcRH5 x
Slide 63: Doing now what patients need next
Doing now what patients need next