Roche Holding Ltd · SIX:RO
Roche — American Society of Hematology 63rd Annual Meeting 2021
44 slides from Roche's conference presentation, Dec 15, 2021
Slide 1: 2021 ASH 63rd Annual Meeting Roche Analyst Audio Webcast
2021 American Society of Hematology’s 63rd Annual Meeting Roche Analyst Audio Webcast 15 December, 2021
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: Agenda
Agenda Welcome Karl Mahler - Head of Investor Relations Roche hematology strategy Peter Ahnesorg - Franchise Head Hematology, Global Product Strategy Key data presented at ASH: Hemlibra, mosunetuzumab, glofitamab, cevostamab, Venclexta Charles Fuchs, MD, MPH - SVP, Global Head of Oncology and Hemato
Slide 4: Welcome
Welcome Karl Mahler | Head of Investor Relations
Slide 5: 2021: Key late-stage news flow
2021: Key late-stage news flow Compound Indication Milestone Xofluza Healthy patients; High risk patients; Post exposure EU approval Evrysdi SMA type 1/2/3 EU approval faricimab DME/nAMD US/EU joint filing (DME+AMD) Regulatory Tecentriq 1L PDL1+ NSCLC EU approval Venclexta + azacitidine 1L unfit AML
Slide 6: Roche hematology strategy
Roche hematology strategy Peter Ahnesorg | Franchise Head Hematology, Global Product Strategy
Slide 7: Roche's approach to Hematology
Roche’s approach to Hematology Pharma Vision 2030: Providing more patient benefit at less cost to society Building on our key areas Venture to new frontiers Innovate of strength • Leading developer of • Polivy as potential new SOC in 1L • Serious efforts to establish bispecific antibodies DLBCL foot
Slide 8: Broadest portfolio in hematology
Broadest portfolio in hematology Small Gene Recombinan mAb Molecule ADC Bispecific Therapy t Protein CLL mosunetuzumab mosunetuzumab iNHL/FL glofitamab mosunetuzumab DLBCL/MCL glofitamab cevostamab MM GPRC5d x CD3 AML MDS Myelofibrosi rhPTX-2 s SPK-801 Non-Maligna crovalimab 1 nt SPK-801 = approved
Slide 9: Roche's scientific expertise in hematology runs deep
Roche’s scientific expertise in hematology runs deep Breaking boundaries in hematology • 11 Breakthrough Therapy Designation by the FDA in hematology medicines • RTOR for Venclexta in 1L CLL and 1L AML and AA for Polivy R/R DLBCL • POLARIX PRIME designation in EU Investing in early disease, presenti
Slide 10: 1L DLBCL can be curative, but high unmet need remains
1L DLBCL can be curative, but high unmet need remains ~40% of patients are not cured with R-CHOP PFS is an appropriate primary end point in 1L DLBCL Trial-level correlation between treatment effects on PFS and OS in RCTs • PFS is a valid endpoint to demonstrate efficacy benefit in 1L DLBCL • For new
Slide 11: Polivy in DLBCL
Polivy in DLBCL First positive trial (POLARIX) in 1L DLBCL in >20 years Polivy program Multibillion CHF market opportunity in 1L DLBCL Anti-CD79b ADC • No new 1L therapies approved since R-CHOP • 3x more drug treated patients in 1L than 2L DLBCL • No novel treatments expected in 1L DLBCL for >3.5 ye
Slide 12: Mosunetuzumab and glofitamab (CD20 x CD3 bispecifics)
Mosunetuzumab and glofitamab (CD20 x CD3 bispecifics) Can be tailored to address diverse patient and customer needs with the potential to offer CAR-T like efficacy “off the shelf” • FL/DLBCL/MCL/other Patient histologies Mosunetuzumab s • 1L or R/R disease + • First-in-class bispecific in iNHL • Pat
Slide 13: Mosunetuzumab and glofitamab development plans
Mosunetuzumab and glofitamab development plans Moving into earlier lines of therapy in combination with SOC Mosunetuzumab program Glofitamab program Late line monotherapy • Mosun in 3L+ FL filed in EU, FDA filing in coming weeks • Glofit in 3L+ DLBCL, data readout. Results to be shared with health a
Slide 14: Cevostamab (FcRH5 x CD3) in R/R MM
Cevostamab (FcRH5 x CD3) in R/R MM Promising activity in heavily pretreated patients FcRH5 x CD3 bispecific antibody Fc receptor-homolog 5 (FcRH5) • Expressed exclusively in B-cell lineage (myeloma cells > normal B cells) Anti-CD3 Anti-FcRH5 1 Fab region Fab region • Near ubiquitous expression on my
Slide 15: Venclexta in CLL, AML, MM, MDS
Venclexta in CLL, AML, MM, MDS 6th BTD for Venclexta in MDS obtained Venclexta progam Bcl-2 inhibitor CLL • Venclexta + Gazyva approved in 1L CLL: fixed dose, chemo free regimen • Ph III (CristaLLo) in 1L fit CLL initiated in Q2’20; primary endpoint: MRD-negativity AML • US: Full approval in 1L unfi
Slide 16: Hemlibra
Hemlibra Transformational advance for Hemophilia A patients Continuing to gain market share in US and globally ~85% 5 Hemlibra target • ~13,000 active patients on commercial Hemlibra 155 % population • Non-inhibitor approval in 98 countries, %% • 32% patient share in the reimbursement in 42 countrie
Slide 17: SPK-8011 in hem A: efficacy and safety data up to 4 years
Non-malignant hematology: SPK-8011 in hem A Efficacy and safety data up to 4 years Hemophilia A gene therapy Ph I/II results (SPK-8011-101) ABR post vector administration of participants Durable Factor VIII activity up to 4 years with sustained expression (n=16)* AAV-Spark2 00 • Bio-engineered adeno
Slide 18: Crovalimab in PNH, aHUS, SCD
Crovalimab in PNH, aHUS, SCD Recycling anti-C5 mAb for maximal complement inhibitionAnti-C5 mAb Paroxysmal Nocturnal Hemoglobinuria (PNH) 1. High affinity binding • Ph III COMMODORE 1/2 (switch & naïve, non-inferiority to eculizumab) achieved first-patient-in in H2 2020 2. Preferential Ab uptake of
Slide 19: Key data presented at ASH
Key data presented at ASH: Hemlibra HAVEN6, mosunetuzumab, glofitamab, cevostamab, Venclexta Charles Fuchs, MD, MPH | SVP - Global Head of Oncology and Hematology Product Development
Slide 20: Hemlibra HAVEN6: moderate to mild hemophilia A patients
Hemlibra HAVEN6: moderate to mild hemophilia A patients HAVEN6 study design Unmet need in moderate and mild hemophlia A Key inclusion criteria • Deficiency in FVIII levels may result in spontaneous • Mild or moderate HA* bleeding, in particular into joints1 • Without FVIII inhibitors 1.5 mg/kg QW or
Slide 21: Hemlibra was efficacious for preventing bleeding events
Hemlibra was efficacious for preventing bleeding events Efficacy data consistent across all bleeding EPs and with other Haven studies Model-based ABR* (95% CI) Treated participants with zero bleeds Treated Treated Treated Treated joint All bleeds spontaneous target joint bleeds bleeds bleeds bleeds
Slide 22: Mosunetuzumab monotherapy in R/R FL
Mosunetuzumab monotherapy in R/R FL Primary endpoint met: CR rate greater than historical control Pivotal phase II study (GO29781) Best percentage change from baseline in • Single-arm, pivotal Ph II expansion in patients with R/R FL tumor SPD* and ≥2 prior therapies • Q3IV dosing; C1 step-up dosing
Slide 23: Mosunetuzumab achieved deep and durable responses
Mosunetuzumab achieved deep and durable responses with favorable tolerability profile Progression-free survival Managable CRS and saftey N (%) N=90 mPFS: 17.9 months (95% CI: 10.1, NE) CRS (any Grade)* 40 (44.4%) Grade 1 23 (25.6%) Grade 2 15 (16.7%) Grade 3 1 (1.1%) Grade 4 1 (1.1%)† AE leading to
Slide 24: Mosun + Pola in R/R B-NHL
Mosun + Pola in R/R B-NHL dose-escalation and expansion High response rates and manageable safety profile M-Pola phase II expansion (GO40516) Responses in all DLBCL patients at RP2D (N=46) Cytokine release syndrome (n=63) Mosunetuzumab CRS (any Grade)* 11 (17.5) • Q3W IV infusions at RP2D up to 17 c
Slide 25: Glofitamab step-up dosing in R/R MCL
Glofitamab step-up dosing in R/R MCL High responses rates and manageable safety Duration of response in efficacy-evaluable patients¤ Ph I Dose Escalation in MCL (NP30179) Glofitamab fixed Key baseline Characteristics N=29* dose +100mg Gpt Prior lines of therapy, median (range) 3 (1-6) Glofitamab SUD
Slide 26: Cevostamab Ph I dose escalation in R/R MM
Cevostamab Ph 1 dose escalation in R/R MM Patients were highly pretreated and highly refractory Baseline characteristics N (%) of patients unless stated N=161 Number of lines of prior therapy, median (range) 6 (2–18) Prior anti-CD38 antibody 142 (88.2) Prior anti-BCMA 54 (33.5) Prior CAR-T 28 (17.4)
Slide 27: Cevostamab monotherapy activity and safety
Cevostamab monotherapy has clinically meaningful activity and manageable safety in heavily pre-treated R/R MM Response rate CRS profile with C1 step-up dosing and C1 double step-up dosing • C1 step-up dosing provided effective CRS mitigation. ORR: 56.7% • CRS was generally confined to C1 and was Pat
Slide 28: Venclexta + Azacitidine in higher-risk MDS
Venclexta + Azacitidine in treatment-naive higher-risk MDS Response rate (n=51) Molecular responses in patients who recieved RP2D and achieved a clinical repsonse (n=33)* Data cutoff: Dec 15, 2020 • 84% of patients who received RP2D Ven+Aza (N=51) responded to treatment • Median time to response: 0.
Slide 29: Key data presented at ASH: POLARIX
Key data presented at ASH: POLARIX Franck Morschhauser | MD, PhD, Professor of Hematology, University of Lille; President of LYSA, LYSARC
Slide 30: The POLARIX Study: Pola-R-CHP versus R-CHOP
LBA-1 The POLARIX Study: Polatuzumab Vedotin with Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (Pola-R-CHP) Versus Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (R-CHOP) Therapy in Patients with Previously Untreated Diffuse Large B-Cell Lymphoma Hervé Tilly,1 Franc
Slide 31: R-CHOP has been the standard of care for over 20 years
R-CHOP has been the standard of care in first-line DLBCL for over 20 years PFS in patients with DLBCL 1.0 receiving R-CHOP in the GOYA trial2 Probability PFS 0.8 0.6 0.4 0.2 R-CHOP (N=712) 0 0 6 12 18 24 30 36 42 48 54 60 Time (months) • Only 60–70% of patients are cured with R-CHOP1,2 • An unmet ne
Slide 32: Polatuzumab vedotin is an ADC targeting CD79b
Polatuzumab vedotin is an ADC targeting CD79b CD79b is ubiquitously expressed on DLBCL cells1–3 Pola+R/G-CHP demonstrated activity in first-line DLBCL4 11% 12% Polatuzumab vedotin Binds to CD79b and is 77% then internalized 100 80 Pola+R/G-CHP (N=66) PFS (%) 60 40 20 Apoptosis 0 Microtubule 0 3 6 9
Slide 33: POLARIX: A randomized double-blinded study
POLARIX: A randomized double-blinded study Pola-R-CHP Polatuzumab vedotin (1.8mg/kg)* R-CHP + vincristine placebo Patients • Previously untreated DLBCL R Cycles 1–6 Rituximab • Age 18–80 years 1:1 (1 cycle=21 days) 375mg/m2 • IPI 2–5 • ECOG PS 0–2 Cycles 7 & 8 Stratification factors R-CHOP • IPI sco
Slide 34: POLARIX: Key endpoints and analysis timing
POLARIX: Key endpoints and analysis timing Key endpoints Primary endpoint Progression-free survival (Investigator-assessed) Event-free survival Complete response rate at end of treatment (PET/CT, IRC-assessed) Secondary endpoints Disease-free survival Overall survival Safety endpoints Incidence, nat
Slide 35: Baseline characteristics
Baseline characteristics ITT population Pola-R-CHP (N=440) R-CHOP (N=439) Age Median (range), years 65.0 (19–80) 66.0 (19–80) Sex, n (%) Male 239 (54) 234 (53) 0–1 374 (85) 363 (83) ECOG PS, n (%) 2 66 (15) 75 (17) Bulky disease (≥7.5cm), n (%) Present 193 (44) 192 (44) Elevated LDH, n (%) Yes 291 (
Slide 36: Primary endpoint: Progression-free survival
Primary endpoint: Progression-free survival Pola-R-CHP significantly improved PFS versus R-CHOP 100 Pola-R-CHP (N=440) R-CHOP (N=439) Censored 80 HR 0.73 (P<0.02) 95% CI: 0.57, 0.95 60 PFS (%) • Pola-R-CHP demonstrated a 27% 40 reduction in the relative risk of disease progression, relapse, or death
Slide 37: Event-free survival
Event-free survival 100 Pola-R-CHP (N=440) R-CHOP (N=439) Censored 80 HR 0.75 (P=0.02) 95% CI: 0.58, 0.96 60 EFS (%) 40 20 0 0 6 12 18 24 30 36 42 Time (months) No. of patients at risk Pola-R-CHP 440 402 348 323 243 78 NE NE R-CHOP 439 386 327 294 218 78 3 NE ITT population. Data cut-off: June 28, 2
Slide 38: Response rates and disease-free survival
Response rates and disease-free survival Best overall response Disease-free survival 100 80 Patients (%) DFS (%) 60 40 Pola-R-CHP (N=381) R-CHOP (N=363) Censored 20 HR (95% CI): 0.70 (0.50, 0.98) 0 Pola-R-CHP R-CHOP 0 6 12 18 24 30 36 42 (N=440) (N=439) No. of patients at risk Time (months) Pola-R-C
Slide 39: Overall survival
Overall survival 100 80 Pola-R-CHP (N=440) 60 OS (%) R-CHOP (N=439) Censored 40 20 HR 0.94 (95% CI 0.65, 1.37); P=0.75 0 0 6 12 18 24 30 36 42 Time (months) No. of patients at risk Pola-R-CHP 440 423 397 384 362 140 15 1 R-CHOP 439 414 401 376 355 132 20 1 ITT population. Data cut-off: June 28, 2021
Slide 40: Patients receiving subsequent treatments
Patients receiving subsequent treatments n=99 n=133 n=41 n=57 n=75 n=103 n=17 n=31 n=9 n=16 † Data cut-off: June 28, 2021. *Subsequent lymphoma treatment was defined as non-protocol anti-lymphoma therapy; †Includes any monotherapy, multi-drug, or cell-based regimen. CAR-T, chimeric antigen receptor
Slide 41: Safety summary
Safety summary Safety profiles were similar with Pola-R-CHP and R-CHOP Pola-R-CHP R-CHOP n (%) (N=435) (N=438) Any-grade adverse events 426 (97.9) 431 (98.4) Grade 3–4 251 (57.7) 252 (57.5) Grade 5 13 (3.0) 10 (2.3) Serious adverse events 148 (34.0) 134 (30.6) Adverse events leading to: Discontinuat
Slide 42: Common adverse events
Common adverse events Pola-R-CHP R-CHOP Peripheral neuropathy* Grade Nausea 1 Diarrhea 2 Neutropenia 3 Anemia 4 Constipation Fatigue Alopecia Decreased appetite Pyrexia Vomiting Febrile neutropenia Cough Headache Decreased weight Asthenia Dysgeusia Frequency (%) Data cut-off: June 28, 2021. Adverse
Slide 43: Conclusions
Conclusions Pola-R-CHP The safety profiles of Exploratory analyses These results significantly prolongs Pola-R-CHP and are ongoing with support the use of PFS compared with R-CHOP were regards to various Pola-R-CHP R-CHOP (HR 0.73) comparable subgroups and in the initial in patients with other progn
Slide 44: Doing now what patients need next
Doing now what patients need next
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