Slide 1: Angiogenesis Highlights 2021 Roche Analyst Webcast
Angiogenesis Highlights 2021 Roche Analyst Webcast South San Francisco, 16 Feb 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: Welcome
Welcome Karl Mahler Head of Investor Relations and Group Planning
Slide 4: Agenda
Welcome Karl Mahler, Head of Investor Relations and Group Planning Ophthalmology Strategy Update Atul Dandekar, Vice President and Global Franchise Head, Ophthalmology Ophthalmology Pipeline Update Chris Brittain, Vice President and Global Head of Ophthalmology Product Development Faricimab in DME a
Slide 5: Strong short- and mid-term news flow
Strong short- and mid-term news flow Diversifying the late stage pipeline and setting new standards of care Product Indication Filing/Data Product Indication Filing/Data tominersen Huntington’s 2022 Adj SCCHN 2021 gantenerumab Alzheimer’s 2022 (Neo)Adj NSCLC 2021/22 Tecentriq SRP-9001 DMD latest 202
Slide 6: Roche Ophthalmology Franchise: Addressing key unmet medical needs
Roche Ophthalmology Franchise Addressing key unmet medical needs Offering substantially improved patient benefits PDS and faricimab have the potential to improve outcomes with longer durability % of patients maintained • Port Delivery System (PDS): permanent, refillable intraocular implant. One-time
Slide 7: Agenda
Welcome Karl Mahler, Head of Investor Relations and Group Planning Ophthalmology Strategy Update Atul Dandekar, Vice President and Global Franchise Head, Ophthalmology Ophthalmology Pipeline Update Chris Brittain, Vice President and Global Head of Ophthalmology Product Development Faricimab in DME a
Slide 8: Retinal diseases are the fastest growing segment of the Ophthalmology market
Retinal diseases are the fastest growing segment of the Ophthalmology market Ophthalmology market Global Retinal Disease Landscape Retinal vascular diseases remain leading causes of vision loss Market growth driven by aging population and product innovation Total Market (2020) - $20.7 Billion 16,000
Slide 9: Reduction in treatment burden is a key unmet medical need
Reduction in treatment burden is a key unmet medical need Real world vision outcomes are suboptimal Adherence to IVT therapies is low and infrequent Lower frequency of injections associated with worse dosing in the real world correlates with vision loss outcomes Germany (n=420) 8,000 France (n=398)
Slide 10: Improved durability will help improve real world outcomes
Improved durability will help improve real world outcomes Faricimab and PDS are potential new standards of care % of patients maintained Durability of response Comparisons meant for illustrative purposes only 10 Lucentis USPI, Eylea USPI and Beovu USPI; Faricimab data presented at Angiogenesis 2021
Slide 11: Roche's industry leading retina pipeline
Roche’s industry leading retina pipeline Focus on nAMD, DME/DR and GA Indication Phase I Phase II Phase III Approved RG7921 faricimab Neovascular AMD Lucentis 0.5 mg PFS RG6120 PDS w ranibizumab1 Diabetic Macular faricimab RG6179 Lucentis 0.3 mg PFS Edema PDS w ranibizumab Diabetic RG7774 PDS w rani
Slide 12: Ophthalmology Personalized Healthcare
Ophthalmology Personalized Healthcare Remote monitoring & advanced analytics to help treat vision loss early 3 core areas to deliver value across the Ophthalmology franchise Personalized Health Care (how we can enhance patient experience and outcomes) Remote Retinal Imaging Data Monitoring and Algor
Slide 13: Roche Ophthalmology strategy execution is on track
Roche Ophthalmology strategy execution is on track Faricimab nAMD / DME joint filing planned for H1 2021 • Positive faricimab nAMD and DME Ph3 data – 1st therapy with Q4M dosing in Ph3 • Positive PDS nAMD Ph3 study – US approval anticipated in Q4 21, additional ex-US studies planned • PDS DME & DR P
Slide 14: Agenda
Welcome Karl Mahler, Head of Investor Relations and Group Planning Ophthalmology Strategy Update Atul Dandekar, Vice President and Global Franchise Head, Ophthalmology Ophthalmology Pipeline Update Chris Brittain, Vice President and Global Head of Ophthalmology Product Development Faricimab in DME a
Slide 15: Archway phase 3 trial design
Archway phase 3 trial design Evaluate the efficacy and safety of the PDS Q24W for nAMD The Port Delivery System with Ranibizumab Archway • Innovative, investigational drug delivery Innovative, •Patients investigational with nAMD responsive to drug delivery any anti-VEG system treatmenta system • Per
Slide 16: Archway phase 3: PDS maintained vision through week 72
Archway phase 3: PDS maintained vision through week 72 Observed mean BCVA change from baseline Subset of patients who 15 completed study visits All patients completed study visitsa (data collection ongoing) Observed Mean BCVA Change From Baseline, ETDRS Letters 10 • Innovative, investigational drug
Slide 17: PDS controlled retinal thickness through week 72
PDS controlled retinal thickness through week 72 Observedmean Observed mean CPT CPT change change from frombaseline baseline 100 Subset of patients who completed study visits AllAll patients completed patients study completed visits study a visitsa (data collection ongoing) • Innovative, investigati
Slide 18: Treatment burden and supplemental treatment
Treatment burden and supplemental treatment ~5x fewer treatments in PDS patients over a mean duration of 80 weeks Total mean number of > 90% of patients did not receive supplemental treatment before each refill- Ranibizumab treatmentsa,b exchange procedure • 24Innovative, • Innovative, investigation
Slide 19: PDS insertion and refill procedures generally well tolerated
PDS insertion and refill procedures generally well tolerated PDS with Intravitreal Ranibizumab 100 mg/mL Q24W Ranibizumab 0.5 mg Q4W (n = 248) (n = 167) MedDRA Preferred Term, n (%)b Onset After Week 40 Overallc Onset After Week 40 Overallc Cataractd 11 (4.4%) 20 (8.1%) 2 (1.2%) 8 (4.8%) Conjunctiva
Slide 20: Patient preference: 93% preferred PDS over intravitreal injections
Patient preference: 93% preferred PDS over intravitreal injections PDS Patient Preference Questionnaire (PPPQ) Next for PDS with Ranibizumab • Innovative, investigational drug delivery system • Innovative, investigational drug delivery Permanent, •The refillable ocular PPPQ was administered to allim
Slide 21: Port Delivery System is a Platform Technology
Port Delivery System is a Platform Technology DutaFabs* are next generation bispecifics designed for increased efficacy & durability New bispecific format (DutaFabs) Further improving the standard of care Monospecific Bispecific mAb Fab fragment (Crossmab) Bispecific Fab fragment e.g. Lucentis e.g.
Slide 22: Higher molar doses of anti-VEGF do not lead to greater efficacy or durability
Higher molar doses of anti-VEGF do not lead to greater efficacy or durability 0.5mg ranibizumab at top of dose-response curve Mean change in BCVA at month 12 in HARBOR 10.1 9.2 8.6 -45 0.6 8.2 -44 1.1 -3.4 1.3 *Pre-specified in HARBOR SAP Injection frequency similar in 0.5mg and 2mg prn arms †Adjust
Slide 23: Ang-2 and VEGF-A are key drivers of angiogenesis
Ang-2 and VEGF-A are key drivers of angiogenesis, inflammation, vascular instability, and leakage Healthy vasculature Pathogenic Pathogenicstate State Pericyte Basement membrane Angiogenic switcha Angiogenic growth Ang-2 levels increase, competitively inhibiting Ang-1 and Endothelial cell preventing
Slide 24: Faricimab - Beyond anti-VEGF monotherapy
Faricimab - Beyond anti-VEGF monotherapy The first bispecific antibody designed for intraocular use One molecule - Two targets Anti–Ang-2 Fab Anti–VEGF-A Fab Enhances vascular stability Inhibits vascular leakage Reduces inflammation and and neovascularization vascular leakage Modified Fc Reduces sys
Slide 25: Agenda
Welcome Karl Mahler, Head of Investor Relations and Group Planning Ophthalmology Strategy Update Atul Dandekar, Vice President and Global Franchise Head, Ophthalmology Ophthalmology Pipeline Update Chris Brittain, Vice President and Global Head of Ophthalmology Product Development Faricimab in DME a
Slide 26: Faricimab: global phase III studies for DME and nAMD
Faricimab: 4 global phase III studies for DME and nAMD Diabetic Macular Edema Neovascular Age-Related Macular Degeneration • Innovative, investigational drug delivery • Innovative, investigational drug delivery YOSEMITE and RHINE TENAYA and LUCERNE Phase III, multicenter, randomized, double-masked,
Slide 27: First time pivotal ph3 data released simultaneously for two major retinal diseases
The first time that pivotal ph3 study data has been released simultaneously for two major retinal diseases; nAMD and DME DME nAMD YOSEMITE / RHINE TENAYA / LUCERNE Primary endpoint BCVA change from baseline1 : BCVA change from baseline2: • Non-inferiority achieved for faricimab up to • Non-inferiori
Slide 28: YOSEMITE and RHINE for Diabetic Macular Edema (DME)
YOSEMITE and RHINE for Diabetic Macular Edema (DME) Global studies with ~2000 patients across 353 study sites Study Details • Baseline demographics and ocular characteristics similar between treatment arms and across studies • Baseline DR severity well-balanced across treatment arms • Missed doses d
Slide 29: YOSEMITE and RHINE in DME
YOSEMITE and RHINE in DME Evaluating efficacy and safety of faricimab versus aflibercept Primary endpoint† Change from baseline in BCVA Final averaged over weeks 48, 52, and visit 56 Continue Faricimab dosing 6.0 mg Q8W Continue Long-term R Faricimab dosing extension 1:1:1 6.0 mg PTI* Continue study
Slide 30: Personalized treatment interval (PTI) in DME
Personalized treatment interval (PTI) in DME Based on the treat-and-extend concept to individualize dosing interval Initiation phase Personalized Treatment Interval – automated, standardized & objective ► BCVA and reading center CST was used for standardization and maintaining study masking Minimum
Slide 31: YOSEMITE and RHINE met primary endpoint in DME
YOSEMITE and RHINE met primary endpoint in DME BCVA gains with faricimab Q8W or up to Q16W non-inferior to aflibercept Q8W Favors aflibercept Favors faricimab NI Margin Faricimab Q8W −0.2 (−2.0, +1.6) YOSEMITE vs aflibercept Q8W +1.5 (−0.1, +3.2) RHINE Faricimab PTI vs +0.7 (−1.1, +2.5) YOSEMITE afl
Slide 32: Consistent improvement in BCVA with faricimab in DME
Consistent improvement in BCVA with faricimab in DME YOSEMITE RHINE 14 14 Adjusted mean BCVA change from baseline (ETDRS letters) from baseline (ETDRS letters) Adjusted mean BCVA change 12 12 10 10 8 8 6 Average of weeks 48–56 6 Average of weeks 48–56 +11.6 letters* +11.8 letters* 4 4 +10.9 letters*
Slide 33: In treatment-naïve DME patients, BCVA improvement similar to aflibercept
In treatment-naïve DME patients, improvement in BCVA from baseline with faricimab was similar to aflibercept YOSEMITE RHINE 14 14 Adjusted mean BCVA change from baseline (ETDRS letters) from baseline (ETDRS letters) Adjusted mean BCVA change 12 12 10 10 8 8 Average of weeks 48–56 6 Average of weeks
Slide 34: Change in CST from baseline through week 56 favored faricimab
Change in central subfield thickness (CST) from baseline through week 56 consistently favored faricimab YOSEMITE RHINE 0 0 Adjusted mean CST change Adjusted mean CST change -50 -50 from baseline (µm) from baseline (µm) Average of weeks 48–56 Average of weeks 48–56 -100 -100 -150 -150 −170.3 µm* −170
Slide 35: Strong durability with faricimab in PTI arm
Strong durability with faricimab in PTI arm >70% of patients on at least Q12W dosing intervals at Week 52* YOSEMITE (n=286) RHINE (n=308) Q4W Q4W 10.8% 13.3% Q8W 15.4% Q8W Q16W 15.6% Q16W 52.8% 51.0% Q12W Q12W 21.0% 20.1% Q12W + Q16W 73.8% Q12W + Q16W 71.1% ITT population * ITT, intent-to-treat popu
Slide 36: More patients treated with faricimab had absence of DME
More patients treated with faricimab had absence of DME compared with aflibercept through week 56 100% YOSEMITE Proportion of patients with CST <325 µm 80% 60% 40% 20% 0% Aflibercept Q8W 4 8 12 16 20 24 28 32 36 40 44 48 52 56 Faricimab Q8W 100% Faricimab PTI Proportion of patients RHINE with CST <3
Slide 37: More patients with faricimab had absence of intraretinal fluid
More patients treated with faricimab had absence of intraretinal fluid (IRF) versus aflibercept through Week 56 YOSEMITE RHINE 100% 100% Proportion of patients without IRF Proportion of patients without IRF 80% 80% 60% 60% 40% 40% 46% 48% 20% 42% 39% 43% 43% 41% 34% 20% 41% 39% 37% 33% 29% 22% 25% 2
Slide 38: Absence of subretinal fluid high; DR severity improvement similar
Absence of subretinal fluid (SRF) was high and comparable between faricimab and aflibercept; Improvement in DR severity similar Absence of SRFa ≥ 2-step improvement in DRSS at week 52b YOSEMITE 100% 100% 80% 80% YOSEMITE 60% 60% Proportion of patients without SRF % Patients 96% 95% 95% 96% 97% 96% 9
Slide 39: Intraocular inflammation adverse events low in DME studies
Adverse events of intraocular inflammation (IOI) were low and consistent with other DME studies YOSEMITE RHINE Intraocular inflammation through week 56 Faricimab Faricimab Aflibercept Faricimab Faricimab Aflibercept Q8W PTI Q8W Q8W PTI Q8W (N=313) (N=313) (N=311) (N=317) (N=319) (N=314) Patients wit
Slide 40: No cases of retinal vasculitis in either study
No cases of retinal vasculitis in either study YOSEMITE RHINE Faricimab Faricimab Aflibercept Faricimab Faricimab Aflibercept Q8W PTI Q8W Q8W PTI Q8W Retinal vasculitis through week 56 (n = 313) (n = 313) (n = 311) (n = 317) (n = 319) (n = 314) Number of patients with events 0 0 0 0 0 0 YOSEMITE RHI
Slide 41: Other important safety events were infrequent
Other important safety events were infrequent YOSEMITE RHINE Faricimab Faricimab Aflibercept Faricimab Faricimab Aflibercept Q8W PTI Q8W Q8W PTI Q8W Serious AEs (n = 313) (n = 313) (n = 311) (n = 317) (n = 319) (n = 314) Rhegmatogenous retinal detachment, n (%) 1 (0.3%) 0 0 0 0 0 Retinal tear, n (%)
Slide 42: YOSEMITE and RHINE in DME: durability and anatomy
YOSEMITE and RHINE in DME Demonstrating advantages in durability potential and anatomy Faricimab improves vascular stability via simultaneous neutralization of both Ang-2 and VEGF-A YOSEMITE and RHINE BCVA gains from baseline with faricimab 6.0mg dosed at Q8W or up to Q16W were non- met primary endp
Slide 43: TENAYA and LUCERNE for nAMD
TENAYA and LUCERNE for nAMD Global studies that enrolled 1300+ patients in over 270 study sites Study Details • Baseline demographics and ocular characteristics generally well-balanced across treatment arms and studies • Discontinuation rates low with minimal impact from Covid-19 on overall results
Slide 44: TENAYA and LUCERNE in nAMD
TENAYA and LUCERNE in nAMD Evaluating efficacy and safety of faricimab versus aflibercept Disease activity Primary endpoint* Final visit assessment At weeks 20 and 24, based Change in BCVA from baseline on BCVA and CST criteria, averaged over Week 40, 44 and and investigator’s evaluation 48 visits I
Slide 45: TENAYA and LUCERNE met primary endpoint in nAMD
TENAYA and LUCERNE met primary endpoint in nAMD BVCA gains with faricimab dosed up to Q16W non-inferior to aflibercept Q8W Favors aflibercept Favors faricimab NI Margin +0.7 (−1.1, TENAYA Faricimab up to Q16W +2.5) vs aflibercept Q8W 0.0(−1.7, LUCERNE +1.8) -5 0 5 Treatment difference (ETDRS Letters
Slide 46: Initial BCVA gains sustained with majority on faricimab up to Q16W
Initial BCVA gains were sustained with majority of patients in the faricimab arm up to Q16W TENAYA in nAMD LUCERNE in nAMD Aflibercept Q8W Faricimab up to Q16W Aflibercept Q8W Faricimab up to Q16W 10 from baseline (ETDRS letters) from baseline (ETDRS letters) 10 Adjusted mean BCVA change Adjusted me
Slide 47: Comparable proportion of patients gaining or maintaining vision
Comparable proportion of patients gaining or maintaining visiona with faricimab up to Q16W and aflibercept Q8W TENAYA in nAMD LUCERNE in nAMD 100% 100% Aflibercept Q8W (n = 300) Aflibercept Q8W (n = 291) Proportion of patients Proportion of patients 80% Faricimab up to Q16W (n = 292) 94% 95% 80% Far
Slide 48: Meaningful reductions in CST with faricimab up to Q16W
Meaningful reductions in central subfield thickness (CST) with faricimab up to Q16W TENAYA in nAMD LUCERNE in nAMD Aflibercept Q8W Faricimab up to Q16W Aflibercept Q8W Faricimab up to Q16W 0 0 Adjusted mean CST change Adjusted mean CST change from baseline (µm) from baseline (µm) -50 -50 -100 -100 −
Slide 49: Durability with faricimab: ~45% on Q16W, almost 80% on ≥Q12W
Durability with faricimab: ~ 45% of patients on Q16W and almost 80% on ≥ Q12W dosing at Week 48* TENAYA (n=334) LUCERNE (n=331) Median number of injections: Faricimab – 6 Q8W Aflibercept – 8 Q8W 20.3% 22.2% Q16W Q16W 45.7% 44.9% Q12W Q12W 34.0% 32.9% Q12W + Q16W Q12W + Q16W 79.7% 77.8% 49 Percentage
Slide 50: Intraocular inflammation adverse events were low
Adverse events of intraocular inflammation (IOI) were low TENAYA LUCERNE Faricimab up to Q16W Aflibercept Q8W Faricimab up to Q16W Aflibercept Q8W Intraocular Inflammation through week 48 (N=333) (N=336) (N=331) (N=326) Patients with any events of IOI (excluding endophthalmitis) 5 (1.5%) 2 (0.6%) 8
Slide 51: No cases of retinal vasculitis in either study
No cases of retinal vasculitis in either study TENAYA LUCERNE Faricimab up to Q16W Aflibercept Q8W Faricimab up to Q16W Aflibercept Q8W Retinal vasculitis events through week 48 (n = 333) (n = 336) (n = 331) (n = 326) Number of patients with events 0 0 0 0 TENAYA LUCERNE Faricimab up to Q16W Afliber
Slide 52: Other Important Safety Events Were Infrequent
Other Important Safety Events Were Infrequent TENAYA LUCERNE Faricimab up to Q16W Aflibercept Q8W Faricimab up to Q16W Aflibercept Q8W Serious AEs (n = 333) (n = 336) (n = 331) (N=326) Rhegmatogenous retinal detachment, n (%) 0 0 0 0 Retinal tear, n (%) 0 0 0 0 Retinal pigment epithelial tear, n (%)
Slide 53: TENAYA and LUCERNE conclusions
TENAYA and LUCERNE conclusions Faricimab demonstrating >Q12W dosing intervals in ~80% of patients in the first year TENAYA and LUCERNE Non-inferiority in mean change from baseline in BCVA with faricimab dosed up to Q16W to met primary endpoint aflibercept Q8W in patients with nAMD at Week 48 Durabil
Slide 54: Q&A
Welcome Karl Mahler, Head of Investor Relations and Group Planning Ophthalmology Strategy Update Atul Dandekar, Vice President and Global Franchise Head, Ophthalmology Ophthalmology Pipeline Update Chris Brittain, Vice President and Global Head of Ophthalmology Product Development Faricimab in DME a
Slide 55: Doing now what patients need next
Doing now what patients need next 55