Slide 1: Roche
Slide 2: Angiogenesis 2022 Virtual IR event
Angiogenesis 2022 Virtual IR event Basel, 14 February 2022 2
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 4
Slide 5: Agenda
Agenda Welcome Bruno Eschli, Head of Investor Relations Ophthalmology franchise strategy Nilesh Metha, Global Franchise Head, Ophthalmology Ophthalmology clinical development Gams Brittain, Vice President and Global Head of Ophthalmology Product Development Angiogenesis 2022 highlights * 2-Year data
Slide 6: 2022: Key late-stage newsflow and upcoming IR events
2022: Key late-stage newsflow* and upcoming IR events Virtual event Virtual event Roche ESG Day Virtual/live event Roche Pharma Day Angiogenesis MDA Virtual Event Access Virtual Eventto Healthcare ASCO ASCO IR Event Roche Pharma Day Monday, 14 February AANWednesday, 16 March Digitalisation Monday, 1
Slide 7: Unmet needs in wAMD and DME
Unmet needs in wAMD and DME Dosing frequency and efficacy are key unmet needs named by ophthalmologists Source: Deutsche Bank research, Proprietary market research survey of 41 US ophthalmologists, published Oct 4, 2021 7
Slide 8: Vabysmo US approval: Positive initial feedback from ophthalmologists
Vabysmo US approval: Positive initial feedback from ophthalmologists* on clinical use in nAMD and DME Proportion of patients who would gain Percentage of patients who would switch meaningful benefit from fewer to Vabysmo from other therapies or would eye injections consider as initial therapy 28% Ne
Slide 9: Ophthalmology franchise strategy
Ophthalmology franchise strategy Nilesh Mehta | Global Franchise Head, Ophthalmology 9
Slide 10: Significant unmet need remains in retinal disease
Significant unmet need remains in retinal disease Suboptimal visual outcomes and epidemiology underpin the market Despite significant Real-word data show patients receive Incidence and prevalence of improvements, many people as few as three to seven treatments in common retinal diseases are do not a
Slide 11: 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 (2021) - $21.8 Billion 16'000
Slide 12: Reducing treatment burden without compromising visual outcomes is a key unmet need
Reducing treatment burden without compromising visual outcomes is a key unmet need Adherence to IVT therapies is low and infrequent Improved durability will help improve dosing in the real world correlates with vision loss real world outcomes 8'000 <25% received 7'000 10+ injections 6'000 Real world
Slide 13: Vabysmo nAMD and DME 1-year data published in the Lancet
Vabysmo nAMD and DME 1-year data published in the Lancet 2 publications highlighting 4 pivotal phase 3 studiesa: YOSEMITE and RHINE (DME)1 TENAYA and LUCERNE (nAMD)2 • 3220 patients were enrolled across 4 trials • Primary endpoint met in all 4 studies: Patients treated with faricimab up to Q16W achi
Slide 14: Vabysmo (faricimab): US approval January 2022
Vabysmo (faricimab): US approval January 2022 T&E label allowing flexible dosing up to q16w (every four months) Vabysmo improves vascular stability Positive results over four studies in nAMD/DME via neutralization of both Ang-2 and VEGF-A Indication Ph1 Ph2 Ph3 Data DME YOSEMITE/RHINE Anti–Ang-2 Fab
Slide 15: Susvimo in nAMD: US approval in Q4 2021
Susvimo in nAMD: US approval in Q4 2021 First & only eye implant with continuous drug delivery over 6 months Susvimo nAMD Update Clinical development program Indication Ph1 Ph2 Ph3 Data • Purposeful launch in nAMD ensuring surgical excellence and optimal customer & patient DME fixed Q6M PAGODA 2022
Slide 16: Susvimo and Vabysmo: Achieving and maintaining vision gains with fewer treatments
Susvimo and Vabysmo: Achieving and maintaining vision gains with fewer treatments for leading causes of vision loss Unmet need Susvimo Vabysmo High treatment burden due to frequent 3 / year ~50%2 eye injections 2 / year1 Manageable treatment schedule 4 / year ~75% Sub-optimal vision outcomes due to
Slide 17: Four strategic levers in Roche ophthalmology
Four strategic levers in Roche ophthalmology Internal innovation Improved outcomes Long-acting Personalised complemented by via novel MoAs delivery methods healthcare external partnering Internal innovation • pRED • gRED External partnering • Anti-VEGF/Ang-2 • The Port Delivery • Clinical decision •
Slide 18: Ophthalmology clinical development
Opthalmology clinical development Christopher Brittain | Vice President and Global Head of Ophthalmology Product Development 18
Slide 19: Roche ophthalmology: Strong momentum with promising launches in nAMD & DME
Roche ophthalmology: Strong momentum with promising launches in nAMD & DME Phase 3 Phase 2 + Phase 1 NMEs First and only intravitreal injection targeting two distinct biological pathways, approved simultaneously in nAMD & DME that can be used as infrequently as every 4-months Comino NME NME Vabysmo
Slide 20: Vabysmo, the first intraocular bispecific antibody
Vabysmo, the first intraocular bispecific antibody: 1 molecule, 2 disease pathway targets for durable efficacy Anti–Ang-2 Fab1 Anti–VEGF-A Fab1 Stabilizes vessels Reduces vascular leakage Reduces vascular leakage Inhibits neovascularization Reduces inflammation Dual inhibition of Ang-2 and VEGF-A Mu
Slide 21: Broadening the portfolio with platform technologies and new indications
Broadening the portfolio with platform technologies and new indications Fab DutaFab platform Port delivery platform Geographic Atrophy • Monotherapeutic approach • DutaFab technology enables • Safety and efficacy • Progressive and irreversible • DME, nAMD, RVO creation of a novel bispecific establis
Slide 22: DutaFabs are the next generation of bispecific molecules
DutaFabs are the next generation of bispecific molecules, designed for increased efficacy and durability Target 1 Monospecific Fab eg, ranibizumab Bispecific binding allows targeting of 2 pathways 1,2 Lucentis Highly potent, extremely stable molecules, enabling prolonged CrossMAb intraocular target
Slide 23: The Port Delivery (PD) Platform
The Port Delivery (PD) Platform The PD is designed to continuously deliver specifically engineered or The PD is compatible with different molecules formulated drugs Higher concentration Port Delivery System in implant with ranibizumab Passive diffusion Lower PortDelivery Port DeliverySystem System c
Slide 24: Geographic Atrophy: Multifactorial and irreversible disease with no approved treatments
Geographic Atrophy: Multifactorial and irreversible disease with currently no approved treatments >5 million people globally affected Pathogenesis of GA remains unclear, key risk factors identified by GA AMD=age-related macular degeneration; GA=geographic atrophy; CFB=complement factor B.; 1. van Lo
Slide 25: Three different therapeutics in development for GA
Three different therapeutics in development for GA Anti-HtrA1 (RG6147) Fab antibody fragment neutralises HtrA1: Targets proteolysis of retinal matrix proteins • Serine protease that may potentially disrupt stability & survival of extracellular matrix protein, preventing GA progression • Intravitreal
Slide 26: Roche ophthalmology: Strong momentum with promising launches in nAMD & DME
Roche ophthalmology: Strong momentum with promising launches in nAMD & DME Phase 3 Phase 2 + Phase 1 NMEs First and only intravitreal injection targeting two distinct biological pathways, approved simultaneously in nAMD & DME that can be used as infrequently as every 4-months Comino NME NME Vabysmo
Slide 27: Vabysmo DME 2-Year Data and Susvimo nAMD 2-Year Data
Vabysmo DME 2-Year Data (Ph III YOSEMITE & RHINE) Susvimo nAMD 2-Year Data (Ph III Archway) Nancy Holekamp | M.D., Retina Specialist 27
Slide 28: Faricimab in Diabetic Macular Edema: Two-Year Results From YOSEMITE and RHINE
Faricimab in Diabetic Macular Edema: Two-Year Results From the Phase 3 YOSEMITE and RHINE Trials John A. Wells, MD1 Kemal Asik, PhD2; Zdenka Haskova, MD, PhD2; Jane Ives, MSc3; David Silverman, MSc, MBChB, MRCOphth, FFPM3; Yannan Tang, PhD2; and Hugh Lin, MD, MBA, 2 On behalf of the YOSEMITE and RHI
Slide 29: YOSEMITE and RHINE investigated faricimab Q8W or PTI dosing up to Q16W
YOSEMITE and RHINE investigated faricimab Q8W or treat-and-extend–based PTI dosing with up to Q16W intervals YOSEMITE & RHINE Phase 3, randomized, double-masked, active comparator–controlled trials Patients with center-involving DME (CST ≥ 325 µm)a BCVA 25–73 ETDRS letters (Snellen BCVA ~20/320–20/4
Slide 30: The PTI algorithm is a protocol-driven treat-and-extend regimen
The PTI algorithm is a protocol-driven treat-and-extend regimen, with decisions based on changes in CST and BCVA Initiation Phase PTI Phase Change in CST from reference CST, %c ► 4 initial Q4W doses through week 12 Change in BCVA from reference BCVA, Improved CST Stable CST Worsened CST +5 ► Q4W dos
Slide 31: Baseline patient characteristics were well balanced across treatment arms
Baseline patient characteristics were well balanced across treatment arms Faricimab Aflibercept Faricimab Faricimab Aflibercept Faricimab Q8W PTI Q8W Q8W PTI Q8W (n = 315) (n = 313) (n = 312) (n = 317) (n = 319) (n = 315) Age, years, mean (SD)a 61.6 (9.5) 62.8 (10.0) 62.2 (9.6) 62.5 (10.1) 61.6 (10.
Slide 32: Vision gains with faricimab were noninferior to aflibercept at 1 year
Vision gains with faricimab Q8W and PTI up to Q16W were noninferior to aflibercept Q8W at 1 year 14 14 12 12 Adjusted mean BCVA change from baseline, ETDRS letters 10 10 8 8 6 6 Average of weeks 48–56a Average of weeks 48–56a 4 Faricimab Q8W: +10.7 ETDRS letters 4 Faricimab Q8W: +11.8 ETDRS letters
Slide 33: Vision gains maintained through year 2
Vision gains with faricimab Q8W and PTI up to Q16W were noninferior to aflibercept Q8W at 1 year and maintained through year 2 14 14 Adjusted mean BCVA change 12 from baseline, ETDRS letters 12 10 10 8 8 6 6 Average of weeks 92–100a Average of weeks 92–100a 4 Faricimab Q8W: +10.7 ETDRS letters 4 Far
Slide 34: More than 50% of PTI patients achieved Q16W dosing at week 52
More than 50% of patients in the faricimab PTI arms achieved Q16W dosing at week 52 Week 52a Week 52a 62% of patients completed one full Q12W dosing cycle and Q4W maintained Q12W or Q16W 10.8% Q4W dosing without an interval 13.3% reduction below Q12W through week 56b Q8W 15.4% Q8W 15.6% Q16W Q16W 52
Slide 35: Proportion achieving Q16W dosing increased to ≥60% at week 96
Proportion of patients who achieved faricimab Q16W dosing increased to ≥ 60% at week 96 Median number of injections Week 96a Week 96a in year 2 (weeks 60–96)c Faricimab PTI: 3 injections Faricimab Q8W: 5 injections Q4W Aflibercept Q8W: 5 injections 7.0% Q4W 10.1% Q8W Q8W 14.8% 11.8% 79% of patients
Slide 36: Comparable proportion of patients gained or avoided vision loss at 2 years
Comparable proportion of patients gained or avoided loss of vision with faricimab Q8W and PTI up to Q16W vs aflibercept Q8W at 2 years 100% 100% 80% 80% ≥ 15 ETDRS letters at 2 years, %a ≥ 15 ETDRS letters at 2 years, %a Patients who avoided a loss of Patients who gained 60% 60% 98% 98% 98% 98% 97%
Slide 37: Greater reductions in CST at 1 year
Greater reductions in CST with faricimab Q8W and PTI up to Q16W vs aflibercept Q8W at 1 year 0 0 Average of weeks 48–56a Average of weeks 48–56a Adjusted mean CST change -50 -50 Faricimab Q8W: −206.6 µm* Faricimab Q8W: −195.8 µm* Faricimab PTI: −196.5 µm* Faricimab PTI: −187.6 µm* from baseline, µm
Slide 38: Greater CST reductions maintained through year 2
Greater reductions in CST with faricimab Q8W and PTI up to Q16W vs aflibercept Q8W at 1 year were maintained through year 2 0 0 Average of weeks 92-100a Average of weeks 92-100a Adjusted mean CST change -50 -50 Faricimab Q8W: −216.0 µm* Faricimab Q8W: −202.6 µm* Faricimab PTI: −204.5 µm* Faricimab P
Slide 39: More patients achieved absence of DME through year 2
More patients achieved absence of DME with faricimab Q8W and PTI up to Q16W vs aflibercept QW8 through year 2 100% * ** * * * * ** ** * ** ** ** * * * * * * * * * * * ** * * * 80% * * * 60% * Patients with absence of DME, %a 40% Proportion at weeks 92–100 77.3–81.0% 20% 86.5–91.8% 78.2–85.9% 0% 0 4
Slide 40: More patients achieved absence of IRF through year 2
More patients achieved absence of IRF with faricimab Q8W and PTI up to Q16W vs aflibercept through year 2 100% 80% * * * 60% * * * * * * * * Patients with absence of IRF, %a 40% * 59% 63% 61% 46% 42% 39% 49% 43% 43% 48% 45% 20% 33% 33% 35% 38% 26% 24% 1% 1% 2% 13% 16% 22% 22% 0% 0 16 48 52 56 92 96
Slide 41: Rates of absence of SRF were high and comparable
Rates of absence of SRF through year 2 were high and comparable with faricimab Q8W and PTI up to Q16W vs aflibercept Q8W 100% 80% 60% 96% 95% 95% 96% 97% 96% 98% 96% 95% 97% 97% 97% 97% 95% 95% 97% 97% 94% 97% 94% 97% Patients with absence of SRF, % 40% 62% 63% 61% 20% 0% 0 16 48 52 56 92 96 100 * 1
Slide 42: Proportion with ≥2-step DRSS improvement consistent across arms
Proportion of patients with ≥ 2-step DRSS improvement was consistent across studies and treatment arms 100% 100% Patients with ≥ 2-step ETDRS-DRSS 80% 80% improvement from baseline, % 60% 60% 40% 40% 51% 54% 46% 43% 42% 43% 47% 44% 44% 44% 44% 20% 36% 20% n = 229 n = 237 n = 242 n = 221 n = 220 n =
Slide 43: Faricimab was well tolerated through study end
Faricimab was well tolerated through study end YOSEMITE/RHINE Pooled Exposure-Adjusted Incidence Rates Through Study End, Events Per Faricimab Q8W Faricimab PTI Aflibercept Q8W 100 Patient-Years (95% CI)a (n = 630) (n = 632) (n = 625) Total patient-years at riskb 1138.9 1157.2 1138.2 58.65 55.13 43.
Slide 44: Inflammation and retinal occlusive events were low and comparable
Inflammation & retinal occlusive events through study end were low and comparable across treatment arms Inflammation events YOSEMITE/RHINE Pooled Exposure-Adjusted Incidence Rates Through Study End, Events Per 100 Faricimab Q8W Faricimab PTI Aflibercept Q8W Patient-Years (95% CI)a (n = 630) (n = 632
Slide 45: Over 2 years, faricimab demonstrated durable efficacy with up to Q16W dosing
Over 2 years, faricimab demonstrated durable efficacy through disease control with up to Q16W dosing Faricimab targets 2 distinct disease pathways to promote vascular stability, which may lead to a more Faricimab durable therapy while maintaining long-term vision gains Durable efficacy with faricima
Slide 46: 2-Year Outcomes From the Phase 3 Archway Trial
2-Year Outcomes From the Phase 3 Archway Trial: Management of Neovascular Age-Related Macular Degeneration Using the Port Delivery System With Ranibizumab (PDS) Presented at Bascom Palmer Eye Institute Angiogenesis, Exudation, and Degeneration 2022 – Virtual Edition Charles C. Wykoff, MD, PhD,1 on b
Slide 47: Archway: Designed to evaluate continuous drug delivery with PDS
Archway: Designed to evaluate the efficacy and safety of continuous drug delivery with PDS Q24W Week Day RD/ –21 D1 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 PDS 100 mg/mL Q24W (n = 248) Intravitreal ranibizumab 0.5 mg Q4W (n = 167) Screening Primary endpoint Roll over to
Slide 48: Archway: Designed to evaluate continuous drug delivery with PDS
Archway: Designed to evaluate the efficacy and safety of continuous drug delivery with PDS Q24W Week Day RD/ –21 D1 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88 92 96 PDS 100 mg/mL Q24W (n = 248) Intravitreal ranibizumab 0.5 mg Q4W (n = 167) Screening Primary endpoint Roll over to
Slide 49: Baseline demographics and ocular characteristics were well balanced
Baseline demographics and ocular characteristics were well balanced across treatment arms1 PDS 100 mg/mL Intravitreal Ranibizumab Q24W 0.5 mg Q4W Characteristic (n = 248) (n = 167) Age, years Mean (SD) 75.2 (8.1) 74.8 (7.6) Range 51–96 54–89 Sex, n (%) Male 103 (41.5%) 67 (40.1%) Baseline BCVA, ETDR
Slide 50: PDS Q24W maintained vision through week 40
PDS Q24W maintained vision through week 96 Adjusted mean BCVA change from baseline, efficacy population 15 PDS 100 mg/mL Q24W (n = 248) Adjusted mean BCVA change from baseline, Mean of 5.0 previous anti-VEGF injections before baseline1 Intravitreal ranibizumab 0.5 mg Q4W (n = 167) 10 Refill-exchange
Slide 51: PDS Q24W maintained vision through week 96
PDS Q24W maintained vision through week 96 Adjusted mean BCVA change from baseline, efficacy population 15 PDS 100 mg/mL Q24W (n = 248) Adjusted mean BCVA change from baseline, Mean of 5.0 previous anti-VEGF injections before baseline1 Intravitreal ranibizumab 0.5 mg Q4W (n = 167) 10 Refill-exchange
Slide 52: PDS Q24W was noninferior to monthly ranibizumab
PDS Q24W was noninferior to monthly ranibizumab Difference in adjusted means, 95% CI Change from NI baseline in lower BCVA score, Averaged over Averaged over bound, ETDRS letters weeks weeks −3.9 (95% CI) 60 and 64 88 and 92 Averaged over weeks 60 and 64 PDS 100 mg/mL Q24W −0.4 (−1.5, 0.7) −1.1 (−2.
Slide 53: PDS Q24W controlled retinal thickness (CPT) through week 96
PDS Q24W controlled retinal thickness (CPT; measured ILM-RPE) through week 96 Adjusted mean CPT change from baseline, efficacy population 100 Refill-exchange in patients who rolled over Adjusted mean CPT change from Refill-exchange Refill-exchange Refill-exchange to Portal 50 baseline, µm 0 -50 PDS
Slide 54: Retinal thickness (CST) through week 96
Retinal thickness (CST; measured ILM-Bruch’s membrane) through week 96 Adjusted mean CST change from baseline, efficacy population 100 Refill-exchange in patients who rolled over Adjusted mean CST change from to Portal Refill-exchange Refill-exchange Refill-exchange 50 baseline, µm 0 -50 PDS 100 mg/
Slide 55: ~95% of patients did not receive supplemental treatment
~95% of patients did not receive supplemental treatment before each refill-exchange procedure Received supplemental PDS treatment interval treatment 1 (n = 246) 2 (n = 241) 3 (n = 231) 4 (n = 225) Yes No 1.6% 5.4% 5.2% 5.3% 100 Supplemental treatment criteria Decrease of ≥ 15 letters from the 75 PDS
Slide 56: Systemic safety of PDS Q24W was generally comparable with monthly ranibizumab
Systemic safety of PDS Q24W was generally comparable with monthly ranibizumab PDS 100 mg/mL Intravitreal Ranibizumab Q24W 0.5 mg Q4W System organ class event incidence ≥ 2 events in either arm, MedDRA preferred term (n = 248), n (%) (n = 167), n (%) Total number of patients with ≥ 1 serious AE 61 (2
Slide 57: Ocular AESIs in the study eye through week 96
Ocular AESIsa in the study eye through week 96, safety population Ocular AEs in the PDS Q24W arm were manageable & well characterized in the clinical trial setting PDS 100 mg/mL Intravitreal Ranibizumab Endophthalmitis occurred in 4 (1.6%) PDS patients, and 1 Q24W 0.5 mg Q4W (0,6%) monthly ranibizum
Slide 58: PDS Q24W maintained vision and anatomic outcomes through 2-year follow-up
PDS Q24W maintained vision and anatomic outcomes comparable with monthly ranibizumab through 2-year follow-up in the Phase 3 Archway trial Comparable vision, • PDS Q24W was noninferior to monthly ranibizumab for BCVA change at multiple points during the study controlled retinal thickness • Long-term
Slide 59: Doing now what patients need next
Doing now what patients need next
Slide 60: 2021 estimates for number of patients: AMD
Vabysmo, Susvimo, Lucentis, VEGF/Ang2 DutaFab, RG7921 Age-related Macular Degeneration (AMD) (thousands) ~4.2M 2021 estimates for number of patients 4'500 4'000 ~3.7M 3'500 1'907 3'000 1'776 2'500 2'000 ~1.3M 1'500 2'342 1'000 1'944 751 500 526 0 wAMD population Presenting / diagnosed population Tre
Slide 61: 2021 estimates for number of patients: DME
Vabysmo, Susvimo, Lucentis, RG6179 Diabetic Macular Edema (DME) (thousands) 7'000 ~6.1M 2021 estimates for number of patients 6'000 5'000 ~4.4M 4'000 4'225 3'000 3'433 2'000 ~1M 1'000 1'859 458 929 575 0 DME population Presenting / diagnosed Treated population Source: Roche/Genentech 61
Slide 62: 2021 estimates for number of patients: RVO
Vabysmo, Lucentis Retinal Vein Occlusion (RVO) (thousands) 3000 2021 estimates for number of patients ~2.4M 2500 258 ~1.8M 2000 1500 693 2'194 1000 ~0.7M 500 1'097 272 424 0 RVO population Presenting / diagnosed population Treated population Source: Roche/Genentech 62
Slide 63: 2021 estimates for number of patients: GA
Anti-HtrA1 Fab, ASO factor B*, RG6312, RG6501** Geographic Atrophy (GA) (thousands) 2021 estimates for number of patients 5'000 4'500 4'000 476 3'500 3'000 1'620 2'500 2'000 138 1'500 648 2'276 404 1'000 36 102 93 143 350 220 1'151 298 500 871 611 540 748 0 Prevalence Diagnosed Diagnosed Diagnosed D