Roche Holding Ltd · SIX:RO
Roche — CureSMA Annual Meeting 2021
32 slides from Roche's conference presentation, Jun 14, 2021
Slide 1: CureSMA Annual meeting 2021 Roche Analyst Audio Webcast
CureSMA Annual meeting 2021 Roche Analyst Audio Webcast Basel, 14 June 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 and Group Business Planning JEWELFISH: Safety, pharmacodynamic and exploratory efficacy data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam RAINBOWFISH: A study of risdiplam in infants with presymptom
Slide 4: Welcome Karl Mahler
Welcome Karl Mahler Head of Investor Relations and Group Business Planning
Slide 5: 2021: Key late-stage news flow
2021: Key late-stage news flow* Compound Indication Milestone Status Filing on track for H1 in nAMD faricimab nAMD Ph III TENAYA/LUCERNE and DME casirivimab/imdevimab SARS-CoV-2 Outpatient Ph III Study 2067 EAU in US, filed in EU casirivimab/imdevimab SARS-CoV-2 Post-exposure prophylaxis Ph III Stud
Slide 6: Roche: Broad pipeline in neuroscience and rare diseases
Roche: Broad pipeline leading the way to first/best in class medicines in neuroscience and rare diseases NeuroImmunology NeuroDegeneration NeuroMuscular NeuroDevelopment & Psychiatry Multiple Sclerosis Alzheimer disease SMA Angelman syndrome Ocrevus gantenerumab Evrysdi UBE3A LNA First B-cell target
Slide 7: Evrysdi: Meaningful evidence being generated across a broad program
Evrysdi: Meaningful evidence being generated across a broad program Overview of the risdiplam development program • Spanning types 1, 2, & 3 SMA; naïve and pre-treated • Newborns to 60 years old; randomized, placebo-controlled data in 2 – 25 years old • Including real-world spectrum of SMA – scolios
Slide 8: Kathryn Wagner, M.D. Ph.D.
JEWELFISH: Safety, pharmacodynamic and exploratory efficacy data in non- naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam RAINBOWFISH: A study of risdiplam in infants with presymptomatic spinal muscular atrophy (SMA) Kathryn Wagner, M.D. Ph.D. Vice President of Ne
Slide 9: JEWELFISH: Safety, pharmacodynamic and exploratory efficacy data
JEWELFISH: Safety, pharmacodynamic and exploratory efficacy data in non-naïve patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam Claudia A Chiriboga,1* Claudio Bruno,2 Tina Duong,3 Dirk Fischer,4 Janbernd Kirschner,5,6 Eugenio Mercuri,7 Marianne Gerber,8 Ksenija Gorni,9 H
Slide 10: Introduction
Introduction • Risdiplam is a centrally and peripherally distributed oral SMN2 pre-mRNA splicing modifier that increases the levels of functional SMN protein1,2 • Studies are limited for patients with SMA who are more advanced in age, have more severe disease, and who have been previously exposed to
Slide 11: Study design
Study design A multicenter, open-label study of once-daily oral administration of risdiplam in non‐treatment‐naïve patients with SMA1 12-month interim 24 months analysis Primary analysis Risdiplam OLE Inclusion criteria n=174 Confirmed genetic Primary endpoint: diagnosis of 5q SMA • Safety • PK Aged
Slide 12: The JEWELFISH population is broad and heterogeneous
The JEWELFISH population is broad and heterogeneous with a high degree of motor impairment at baseline Previous treatment RG7800 Onasemnogene (MOONFISH) Nusinersen Olesoxime abeparvovec All patients (n=13) (n=76)* (n=71) (n=14)† (N=174) Age at enrollment, years, median (range) 30.0 (16–58) 12.0 (1–6
Slide 13: Reasons patients began treatment with risdiplam
Patient- and caregiver-reported reasons why patients began treatment with risdiplam following previous treatments* Patients previously treated with Primary reasons to enroll in JEWELFISH nusinersen† (n=77) n (%) Treatment-related tolerability concerns‡ 24 (31) Treatment response: Lack of efficacy 14
Slide 14: Low rates of discontinuation in the JEWELFISH study
Low rates of discontinuation (5% [9/174]) were observed in the JEWELFISH study* Enrolled (N=174) Previous Onasemnogene RG7800 (n=13) Nusinersen (n=76) Olesoxime (n=71) treatment abeparvovec (n=14) • Withdrawal by subject (n=1) • Withdrawal due to • Withdrawal by subject • Withdrawal by (n=2) unrelat
Slide 15: No treatment-related safety findings led to withdrawal
No treatment-related safety findings have led to withdrawal in any JEWELFISH patients Previous treatment All patients RG7800 Onasemnogene Nusinersen Olesoxime (N=173)* (MOONFISH) abeparvovec (n=76) (n=70) (n=13) (n=14) Patients with at least one AE, n (%) 12 (92) 71 (93) 63 (90) 13 (93) 159 (92) Tot
Slide 16: AEs and SAEs were reflective of underlying disease
AEs and SAEs were reflective of underlying disease Previous treatment RG7800 Onasemnogene All patients Nusinersen Olesoxime (N=173)* (MOONFISH) abeparvovec (n=76) (n=70) (n=13) (n=14) URTI 0 14 (18) 14 (20) 2 (14) 30 (17) Pyrexia 1 (8) 17 (22) 8 (11) 4 (29) 30 (17) Headache 1 (8) 15 (20) 12 (17) 0 2
Slide 17: Risdiplam led to rapid and sustained increases in SMN protein
Risdiplam treatment led to rapid and sustained increases in SMN protein levels in patients previously treated with nusinersen or onasemnogene abeparvovec 8 Baseline median SMN protein in whole blood* (range): • Nusinersen: 3.26 ng/mL (1.01–6.91) Median-fold change from baseline • Onasemnogene abepar
Slide 18: Interim exploratory efficacy: stabilization in motor function at Month 12
Interim exploratory efficacy data demonstrated overall stabilization in motor function at Month 12 in patients who began treatment with risdiplam following previous treatments JEWELFISH MFM32 in patients aged 2–60 years* 3 The JEWELFISH population is broad and Mean change from baseline heterogeneous
Slide 19: Conclusions
Conclusions The JEWELFISH population is Risdiplam treatment has broad and heterogeneous, shown a sustained, AEs and SAEs were reflective with a high degree of motor >2-fold increase in median of underlying disease impairment at baseline, SMN protein levels versus reflecting the real-world baseline,
Slide 20: RAINBOWFISH: A study of risdiplam in infants with presymptomatic SMA
RAINBOWFISH: A study of risdiplam in infants with presymptomatic spinal muscular atrophy (SMA) Richard S Finkel,1* Mohammad Al-Muhaizea,2 Michelle A Farrar,3 Leslie Nelson,4 Alexandra Prufer,5 Laurent Servais,6–8 Yi Wang,9 Edmar Zanoteli,10 Muna El-Khairi,11 Marianne Gerber,12 Ksenija Gorni,13 Heide
Slide 21: Introduction
Introduction • In patients with SMA, motor neuron degeneration begins before the onset of symptoms 1 • In clinical studies of SMA, the time from symptom onset to treatment initiation has been established as a predictive factor with regards to efficacy of treatment2 – A shorter disease duration resul
Slide 22: A multicenter, open-label, single-arm study of risdiplam in infants
A multicenter, open-label, single-arm study of risdiplam in infants with genetically diagnosed and presymptomatic SMA PRIMARY ENDPOINT 12 months Screening Risdiplam OLE (≥3 years) SECONDARY ENDPOINTS 24 months Genetic diagnosis of Primary endpoint (n≥5*): Secondary endpoints (all infants; n~25 †): 5
Slide 23: Baseline characteristics for infants enrolled in RAINBOWFISH
Baseline characteristics for 12 infants currently enrolled in RAINBOWFISH Target enrollment ~25 infants (recruitment will close when either at least 25 patients, including a minimum of 5 patients with two SMN2 copies and a baseline CMAP amplitude of ≥1.5 mV are enrolled, OR when a total of 10 patien
Slide 24: Infants treated for at least 12 months achieved HINE-2 motor milestones
Infants treated with risdiplam for at least 12 months (n=5) achieved HINE-2 motor milestones Maintained upright all the time Head control Increasing difficulty (total 2 items) 100% Pivots (rotates) Sitting (total 4 items) 100% At the data cut-off:† • At 80% Month 12: (4/5) scored the of infants Supi
Slide 25: Infants achieved motor milestones within WHO windows
Most of the infants treated for at least 12 months achieved motor milestones within the WHO windows for healthy children Not yet Achieved † achieved Sitting without support* 2 SMN2 copies (n=2) >2 SMN2 copies (n=3) WHO window of Crawling on hands achievement in and knees healthy infants§1 ‡ Standing
Slide 26: Infants reached near maximum CHOP-INTEND scores by 4-5 months
Infants treated with risdiplam for at least 12 months (n=5) reached near maximum CHOP-INTEND scores by 4–5 months of age Maximum score = 64 60 At 4 months of treatment: • 4/5 infants (80%) scored ≥60 50 CHOP-INTEND total score • 1/5 infants (20%) scored 58 40 At 12 months of treatment: • 5/5 infants
Slide 27: No treatment-related SAEs in presymptomatic infants
No treatment-related SAEs were reported in presymptomatic infants treated with risdiplam 2 SMN2 copies >2 SMN2 copies Total risdiplam • One SAE of gastroenteritis norovirus was (n=5) (n=7) (n=12) reported – this was considered Infants with at least one AE, n (%) 4 (80) 6 (86) 10 (83) unrelated to ri
Slide 28: AEs reflective of the age of the infants
AEs were more reflective of the age of the infants rather than the underlying SMA 2 SMN2 copies >2 SMN2 copies Total risdiplam (n=5) (n=7) (n=12) Nasal congestion 1 (20) 3 (43) 4 (33) Cough 0 3 (43) 3 (25) Teething 1 (20) 2 (29) 3 (25) Vomiting 1 (20) 2 (29) 3 (25) Most common AEs, n (%) Eczema 1 (2
Slide 29: RAINBOWFISH summary
RAINBOWFISH summary Most of the infants As of the data cut-off,* No treatment- treated for ≥12 months all 5 infants who had related SAEs were achieved motor received risdiplam for reported in milestones within the ≥12 months reached presymptomatic WHO windows for the maximum score of infants treated
Slide 30: Summary of Roche data at CureSMA
Summary of Roche data at CureSMA JEWELFISH • The first trial in a diverse SMA population aged from 1 to 60 years who received prior treatment, which has showed a consistent safety profile and >2-fold increase in SMN protein levels and stabilization in motor function RAINBOWFISH • Pre-symptomatic bab
Slide 31: Q&A
Q&A
Slide 32: Doing now what patients need next
Doing now what patients need next