Roche Holding Ltd · SIX:RO
Roche — ASH Annual Meeting 2022 Virtual IR event
53 slides from Roche's conference presentation, Dec 14, 2022
Slide 1: Slide 1
Slide 2: ASH Annual Meeting 2022 Virtual IR event
ASH Annual Meeting 2022 Virtual IR event 14 December 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 | Head of Investor Relations
Slide 5: Agenda
Agenda Welcome Bruno Eschli, Head of Investor Relations Roche hematology strategy Peter Ahnesorg, Franchise Head Hematology, Global Product Strategy Key data presented at ASH Charles Fuchs, Global Head of Oncology and Hematology, Product Development Spark Therapeutics SPK-8011 data presentation Gall
Slide 6: Key late-stage pipeline readouts 2023
Key late-stage pipeline readouts 2023 * Compound Indication Data readout Tecentriq + chemo Neoadjuvant / adjuvant NSCLC Ph III IMpower030 Tecentriq + Avastin Adjuvant HCC Ph III Imbrave050 Tecentriq + chemo Neoadjuvant / adjuvant TNBC Ph III GeparDouze/NSABP B-59 Tecentriq Adjuvant SCCHN Ph III IMvo
Slide 7: Roche hematology strategy
Roche hematology strategy Peter Ahnesorg | Franchise Head Hematology, Global Product Strategy
Slide 8: Roche being a leader in hematology
Roche being a leader in hematology Investing across Broad portfolio enables Exploring diversified Improving patient / growing indications novel combinations modalities provider experience and new disease areas Moving into multiple Polivy + CD20 x CD3 Bispecifics Fixed duration myeloma, MDS
Slide 9: Hematology market expected to grow strongly
Hematology market expected to grow strongly Roche has one of the broadest hematology portfolios with ~20 agents in 10+ diseases Roche’s hematology portfolio is well positioned in a growing market 109 † glofitamab (CD20 x CD3), 18 DLBCL CD19 x 4-1BBL, CD19 x CD28 9 FL +85% 14 CLL * 59 5 cevostamab (F
Slide 10: Tailoring powerful therapeutics with bispecifics across hematology
Tailoring powerful therapeutics with 9 bispecifics across hematology Building on successful launches of Hemlibra and Lunsumio Advanced antibody engineering drives best in class potential • 2:1 format for improved efficacy (glofitamab, GPRC5D, HLA-A2-WT1) DLBCL glofitamab CD19 x 4-1BBL • Highly engin
Slide 11: Non-Hodgkin's Lymphoma (NHL)
Non-Hodgkin’s Lymphoma (NHL)
Slide 12: Polivy + R-CHP is the first new treatment in >20 years in 1L DLBCL
Polivy + R-CHP is the first new treatment in >20 years in 1L DLBCL 27% PFS improvement vs. R-CHOP with comparable safety Improvement in PFS has significant positive impacts on patients and treatment cost Treatment effects on PFS strongly predicts for treatment effects Cost of disease progression is
Slide 13: Polivy + R-CHP expected to become the SOC in 1L DLBCL
Polivy + R-CHP expected to become the SOC in 1L DLBCL Approved in >50 countries including EU, UK, Japan, Canada; Strong uptake in early launch countries: Germany1 & Japan US filing accepted (PDUFA date April 2nd) CHFm QoQ CER growth 80 +40% 60 +14% 29 40 25 22 20 41 22 25 0 Q1 22 Q2 22 Q3 22 Europe
Slide 14: Lunsumio vs. glofitamab: Tailored to address diverse needs
Lunsumio vs. glofitamab: Tailored to address diverse needs Off-the-shelf, fixed duration therapies with durable responses and manageable safety • High CR rate and durable responses • Favorable tolerability profile with low grade, infrequent CRS Tailored to address diverse patient • No required hospi
Slide 15: Lunsumio: Outpatient treatment for indolent lymphoma and unfit patients
Lunsumio: Outpatient treatment for indolent lymphoma and unfit patients Ph III combination trials in 2L+ DLBCL/FL reading out in 2023/24 Approved (EU) 3L+ FL Lunsumio • Approved in EU in 3L+ FL; filed with FDA with approval expected end of this year Ph III data 2023/24 • Ph III combination trials re
Slide 16: Glofitamab: Fixed duration treatment for aggressive lymphoma
Glofitamab: Fixed duration treatment for aggressive lymphoma Ph III (STARGLO) glofitamab + GemOx reading out in 2023/24 Filed 2022 3L+ DLBCL • Positive pivotal data in 3L+ DLBCL submitted to EMA and FDA glofitamab Ph III data 2023/24 • Ph III combination trials reading out in 2023/24: glofitamab + G
Slide 17: Glofitamab: Fixed duration and simple dosing schedule
Glofitamab: Fixed duration and simple dosing schedule Treatment burden is important for patient/provider convenience Glofitamab in 3L+ DLBCL requires weekly dosing for only 2 weeks (vs. 12 weeks for epcoritamab) D-7 D1 D8 D1 D1 D1 D1 D1 D1 D1 D1 D1 D1 D1 Glofitamab Cycle 1* Cycle 2 Cycle 3 Cycle 4 C
Slide 18: CD19 x 4-1BBL (RG6076) in R/R NHL
CD19 x 4-1BBL (RG6076) in R/R NHL B cell-targeted costimulatory T cell agonist with first-in-class potential CD19 x 4-1BBL + glofitamab Pharmacodynamic biomarker data support novel MoA • Signal 1: NK or T cell activation delivered by glofitamab • A dose relationship with reversal of PD1+ terminally
Slide 19: CD19 x CD28 (RG6333) in R/R NHL
CD19 x CD28 (RG6333) in R/R NHL B cell-targeted costimulatory T cell agonist with distinct MoA vs 4-1BB CD19 x CD28 + glofitamab Animal data show enhanced and prolonged T cell activity • CD19 x CD28 delivers a strong costimulatory signal to • Strong combination effect of CD19 x CD28 with CD20 x CD3
Slide 20: Myeloid malignancies (MM, AML, MDS)
Myeloid malignancies (MM, AML, MDS)
Slide 21: Emerging pipeline in Multiple Myeloma (MM)
Emerging pipeline in Multiple Myeloma (MM) Four molecules with different modalities in clinical development High unmet need remains in MM Broad pipeline of MM assets Follow up from diagnosis (years) • MM remains incurable despite new treatments with 15% of patients having • Exploring new modalities,
Slide 22: Venclexta development program in MM and MDS
Venclexta development program in MM and MDS Ph III studies reading out in 2023 Developing Venclexta in 1L CLL indications with USD ~60bn market • Ph III (CRISTALLO) Venclexta + Gazyva in 1L fit CLL ongoing size by 2028 • Ph III (CLL14) Ven+G in unfit 1L: 60% of pts remained in remission 4 years afte
Slide 23: FcRH5 x CD3 and GPRC5D x CD3 in R/R MM
FcRH5 x CD3 and GPRC5D x CD3 in R/R MM T cell engaging bispecifics with novel targets for combination development Cevostamab (FcRH5 x CD3) GPRC5D x CD3 T cell Target Activation CD3 CD3 Apoptosis Head-to-tail FcRH5 geometry Synapse Silent Fc MM cell region • FcRH5 protein (FCRL5 gene) is expressed ex
Slide 24: Allogeneic CAR-Ts for hematologic malignancies
Allogeneic CAR-Ts for hematologic malignancies Partnership with Poseida Therapeutics Allogeneic CAR-Ts have the potential to address Poseida has differentiated technology, clinical limitations of first generation cell therapies experience, and complementary programs • Better scaling, off-the-shelf a
Slide 25: HLA-A2 WT1 x CD3 TCB (RG6007) in hematologic and solid tumors
HLA-A2 WT1 x CD3 TCB (RG6007) in hematologic and solid tumors TCR receptor-like T cell bispecific targeting intracellular oncoprotein WT1 Potential tumor targets beyond cell WT1-TCB ex vivo activity on primary AML patient samples1 surface proteins AML lysis in panel of AML Dose-dependent reduction o
Slide 26: Non-malignant hematology
Non-malignant hematology
Slide 27: Hemlibra continuing to grow across all geographies
Hemlibra continuing to grow across all geographies #1 prophylaxis treatment for hemophilia A in the US/EU Continued market share gains in the US/EU • 36% patient share in US/EU; >65% of patients are on ≥2 weeks dosing • Further penetration expected among severe patients who continue to experience an
Slide 28: Hemlibra has set a high bar in hemophilia A
Hemlibra has set a high bar in hemophilia A Hemlibra is a transformational advance for patients Future development will be more incremental as the unmet need has changed Factor VIII • Up to 90% of patients on Hemlibra experience zero treated bleeds per year1, with convenient dosing (low incentive to
Slide 29: Crovalimab in PNH, aHUS and SCD
Crovalimab in PNH, aHUS and SCD Exploring complement-mediated diseases in hematology and beyond Recycling anti-C5 mAb for rapid and Indication Ph I Ph II Ph III sustained complement inhibition 3 COMPOSER 1. High affinity binding COMMODORE 1 (switch) Paroxysmal Nocturnal 2023 PNH Hemoglobinuria 2. Pr
Slide 30: Key data presented at ASH
Key data presented at ASH Charles Fuchs | Global Head of Oncology and Hematology, Product Development
Slide 31: Non-Hodgkin's Lymphoma (NHL)
Non-Hodgkin’s Lymphoma (NHL)
Slide 32: Polivy in 1L DLBCL (POLARIX)
Polivy in 1L DLBCL (POLARIX) Updated PFS demonstrated a sustained benefit, consistent with the primary analysis Ph III (POLARIX) trial design PFS benefit was maintained with longer follow-up • Updated results with median follow-up 39.7 months demonstrated sustained PFS benefit in Pola-R-CHP (HR 0.76
Slide 33: Lunsumio monotherapy in 3L+ FL
Lunsumio monotherapy in 3L+ FL Durable efficacy with a manageable safety profile Pivotal Ph II (GO29781) Majority of responding pts in remission after 2 years; 24-month DoCR = 63% Baseline characteristics N=90 DoR N=90 Median lines of prior therapy, n 3 (2–10) (range) ORR 78% Prior ASCT 21% CR 60% D
Slide 34: Lunsumio monotherapy in 3L+ FL
Lunsumio monotherapy in 3L+ FL Extended DoCR and 12-month improvement in mPFS compared with last prior therapy DoCR PFS 1. Mosunetuzumab (n=54) 1. Mosunetuzumab (N=90) 0 Prior therapy (n=32) 0 Prior therapy (N=90) 0. 0. Probabilit Probabilit 8 8 0. 0. y y 6 6 0. 0. 4 4 0. 0. 2 2 0. 0. 0 0 2 4 6 8 10
Slide 35: Glofitamab monotherapy in 3L+ LBCL
Glofitamab monotherapy in 3L+ LBCL Relapse is uncommon in patients who are in complete remission at end of treatment (EOT) Pivotal Ph II (NP30179) CR remain durable with significant follow up (11.5 months) post-EOT DoCR (N=61)* PFS with landmark at EOT (N=61)† • Heavily pre-treated, high refractory
Slide 36: Glofitamab + R-CHOP in 1L DLBCL
Glofitamab + R-CHOP in 1L DLBCL High response rate and significantly reduced CRS rates suitable for outpatient setting Ph Ib (NP40126) Glofit + R-CHOP treatment showed consistent antitumor activity (N=53) Baseline characteristics , n (%) N=56* Best overall response‡ N=53§ CMR rate 75.5% Ann Arbor st
Slide 37: CD19 x 4-1BBL (RG6076) + glofitamab in R/R NHL
CD19 x 4-1BBL (RG6076) + glofitamab in R/R NHL Promising tumor activity and manageable safety Ph I dose escalation (BP41072) CD19-4-1BBL + glofitamab shows promising antitumor activity (N=45) aNHL iNHL Baseline characteristics N=83 (N=45) (N=24) CR rate 49% 65% Median lines of prior therapy, n (rang
Slide 38: Multiple Myeloma (MM)
Multiple Myeloma (MM)
Slide 39: Cevostamab (FcRH5 x CD3) in R/R MM
Cevostamab (FcRH5 x CD3) in R/R MM Enduring response after 1 year of fixed-duration cevostamab therapy Ph I (GO39775) Duration of response in responders who completed C17 (N=18) • Highly pretreated and highly refractory patients • A VGPR or better was achieved in 17 of the 18 patients by the time of
Slide 40: GPRC5D x CD3 (RG6234) in R/R MM
GPRC5D x CD3 (RG6234) in R/R MM Highly active in patients with R/R MM Ph I IV & SC dose-escalation Response rate across all tested Step-up dosing mitigated the target doses risk of severe CRS Key inclusion criteria • Median follow-up: 11.6 months for IV and 8 • CRS primary observed in C1 months for
Slide 41: Non-malignant hematology
Non-malignant hematology
Slide 42: Hemlibra in infants with severe hemophilia A
Hemlibra in infants with severe hemophilia A Ph III (HAVEN 7) to address unmet needs Ph III (HAVEN7) trial design Multi-center, open-label study of emicizumab in infants aged Unmet need in infants with severe hemophilia A ≤12 months with severe hemophilia A without FVIII inhibitors Many infants do n
Slide 43: Hemlibra in infants with severe hemophilia A
Hemlibra in infants with severe hemophilia A Ph III (HAVEN 7) results show consistent efficacy across bleeding endpoints Model-based ABR† across bleed categories (95% CI) Mean emicizumab trough concentrations by study week Treated Treated muscle Treated bleeds All bleeds spontaneous bleeds bleeds 0.
Slide 44: Crovalimab in PNH
Crovalimab in PNH Ph III (COMMODORE 3): Patient population had high transfusion requirements prior to enrollment Ph III (COMMODORE 3) trial design Baseline characteristics N=51 Key eligibility criteria: Time from PNH diagnosis to enrollment, 24 weeks 7.1 (0.7‒18.2) • Patients with PNH in China media
Slide 45: Crovalimab in PNH
Crovalimab in PNH Ph III met both co-primary endpoints of hemolysis control & transfusion avoidance Ph III (COMMODORE 3) results: Patients experienced rapid and sustained hemolysis control Mean proportion of patients achieving hemolysis control (LDH ≤1.5 ULN) Mean LDH ≤1.5 ULN was reached by Week 3
Slide 46: Spark Therapeutics SPK-8011
Spark Therapeutics SPK-8011 Gallia Levy | Chief Medical and Product Strategy Officer at Spark Therapeutics
Slide 47: SPK-8011 gene therapy in hemophilia A
SPK-8011 gene therapy in hemophilia A Four pillars of for successful gene therapy: safety, efficacy, predictability, and durability The goals of gene therapy, involving the use of a recombinant AAV vector to target hepatocytes, include: Doses studied in hemophilia A gene therapy clinical trials7–9 •
Slide 48: SPK-8011 gene therapy in hemophilia A
SPK-8011 gene therapy in hemophilia A Phase I/II open-label, multicenter, non-randomized trial Ph I/II SPK-8011 trial design Participants were enrolled into four dose cohorts Eligibility Criteria 5 × 1011 vg/kg (n=2) • Males ≥18 years of age with FVIII:C ≤2% • If FVIII:C 1–≤2, baseline treatment: 1
Slide 49: SPK-8011: Durable FVIII activity observed up to 5 years
SPK-8011: Durable FVIII activity observed up to 5 years Majority of participants maintained FVIII expression within mild hemophilia range Measured FVIII activity levels following infusion of SPK-8011 in 16 participants with ≥1 year of follow-up FVIII:C (one-stage assay) Mean FVIII activity OSA • At
Slide 50: SPK-8011: ABRs decreased with sustained FVIII expression
SPK-8011: ABRs decreased with sustained FVIII expression Pre-infusion Post-infusion 50 45 Reduction in ABR: 40 • 82% for participants on prior prophylaxis Annualized Bleeding Rate 35 • 99% for participants on prior on-demand treatment 30 25 20 15 10 5 0 *1 2 3 4 *6 *7 8 *9 10 11 13 14 *15 16 17 18 1
Slide 51: SPK-8011 safety profile
SPK-8011 safety profile No deaths, no FVIII inhibitor development, no thrombotic events reported Median (range) follow-up (n=24): 191 (2–285) weeks AEs related to SPK-8011: • 1 participant with an acute infusion reaction AEs related to IM agents: • 11 participants reported LFT elevations • 8 partici
Slide 52: Conclusions
Conclusions With 5 years of follow up, a single infusion of SPK-8011 resulted in: Durable FVIII Investigations are No major safety ongoing to overcome Evaluation of the expression, with a 82–99% reductions signals; timing of the challenge of AAV- phase I/II study majority of in ABR and transient ALT
Slide 53: Doing now what patients need next
Doing now what patients need next 53