Polypoidal choroidal vasculopathy

Researchers have developed a light-activatable prodrug nanomedicine for age-related macular degeneration (AMD) therapy. Through the intravenous injection of the nanomedicine and application of light irradiation to diseased eyes, anti-angiogenic and photodynamic combination therapy can be activated, offering a minimally invasive alternative for the treatment of AMD and other ocular disorders characterized by abnormal blood vessel growth. Researchers at the LKS Faculty of Medicine of the University of Hong Kong (HKUMed), and collaborators from the Zhongshan Ophthalmic Centre of Sun Yat-sen University, Guangzhou, have developed a light-activatable prodrug nanomedicine for age-related macular degeneration (AMD) therapy. Through the intravenous injection of the nanomedicine and application of light irradiation to diseased eyes, anti-angiogenic and photodynamic combination therapy can be activated, offering a minimally invasive alternative for the treatment of AMD and other ocular disorders characterised by abnormal blood vessel growth. The research has been published in Advanced Science and a Patent Cooperation Treaty application was filed based on the research. According to the Hong Kong Eye Survey data published in 2019, the prevalence of early AMD among individuals aged 70 and older has reached 7.5% in Hong Kong1, making AMD the second most common cause of visual impairment and blindness in the adult population of Hong Kong. Currently, intravitreal injections of antibodies against vascular endothelial growth factor are the first-line treatment for wet AMD. However, this invasive procedure is uncomfortable for patients, and carries the risk of serious ocular complications, such as endophthalmitis and retinal detachment. Therefore, there is an urgent need for novel formulations that enable the delivery of anti-angiogenic agents into the eye without an intravitreal injection, such as intravenous injection. Additionally, anti-angiogenic agents have limited efficacy in regressing existing neovascularisation. Photodynamic therapy (PDT) offers a clinical solution by utilising non-toxic photosensitisers activated by specific wavelengths of light to generate reactive oxygen species (ROS), which can damage and obliterate neovascularisation. PDT is widely used for the treatment of polypoidal choroidal vasculopathy, a common subtype of wet AMD in Asia. Therefore, combining anti-angiogenesis therapy with PDT may offer a more effective approach to treating wet AMD, thus helping slow down the progression of the disease and improve the vision outcome for patients. Research methods and findings The research team designed a novel photoactivatable prodrug nanosystem. After a single intravenous injection of the nanoparticles into a choroidal neovascularisation mouse model, red-light irradiation of the mouse's eye activated the nanoparticles to generate ROS, which not only causes the regression of abnormal neovascularisation, but also triggers the release of anti-angiogenic drugs from the nanoparticles to inhibit the growth of new blood vessels. This combinational therapy demonstrated excellent therapeutic efficacy without any noticeable systemic or ocular side effects. Research significance The study represents the first attempt at integrating a photoactivatable anti-angiogenic agent with a photosensitiser into a single nanoformulation for AMD treatment. The treatment procedure is simple and safe, as the therapeutic effect of the anti-angiogenic agent and photosensitiser in ocular lesions can be achieved through the intravenous administration of nanoparticles and light irradiation to the eye. This pioneering research may open up new avenues for the development of minimally-invasive therapeutics for AMD and other neovascular ocular disorders. The formulation uses US FDA-approved therapeutic agents and excipients, making it promising for future clinical translation. The study was led by Dr Wang Weiping, Associate Professor of Dr Li Dak-Sum Research Centre and Department of Pharmacology and Pharmacy, HKUMed, and Principal Investigator of the State Key Laboratory of Pharmaceutical Biotechnology, HKU. The other corresponding author was Professor Liang Xiaoling, Department of Ophthalmology, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, State Key Laboratory of Ophthalmology, Sun Yat-Sen University, and Zhongshan Ophthalmic Centre, Sun Yat-sen University; the co-first authors were Xu Shuting, PhD candidate, Department of Pharmacology and Pharmacy, HKUMed, and Dr Cui Kaixuan, Postdoctoral fellow, Department of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University. Other researchers included Long Kaiqi, PhD candidate, Department of Pharmacology and Pharmacy, HKUMed; Dr Li Jia and Dr Fan Ni, Postdoctoral fellows, Department of Pharmacology and Pharmacy; and Professor Lam Wai-ching, Head and Clinical Professor of the Department of Ophthalmology, Vancouver General Hospital and University of British Columbia, Canada, and Honorary Clinical Professor, Department of Ophthalmology, School of Clinical Medicine, HKUMed. This work was supported by the National Natural Science Foundation of China Excellent Young Scientists Fund (No. 82222903) and the National Natural Science Foundation of China (No. 82271099).

RVO is the third indication for Vabysmo, in addition to neovascular or ‘wet’ age-related macular degeneration and diabetic macular edemaApproval is based on two phase III studies demonstrating early and sustained vision improvements that were non-inferior to aflibercept Vabysmo also demonstrated rapid and robust drying of retinal fluid Additional U.S. label update across indications includes information on rare post-marketing reports of retinal vasculitis and/or retinal vascular occlusion; reporting rate is in line with other broadly used intravitreal treatments Basel, 27 October 2023 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the United States Food and Drug Administration (U.S. FDA) has approved Vabysmo® (faricimab) for the treatment of macular edema following retinal vein occlusion (RVO). RVO is the third indication for Vabysmo, in addition to neovascular or ‘wet’ age-related macular degeneration (nAMD) and diabetic macular edema (DME).1 Together, the three retinal conditions affect around 70 million people worldwide and are among the leading causes of vision loss.2-5 “Vabysmo is a new treatment option for RVO that can help people preserve and improve their vision, with the added benefit of retinal drying,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “The efficacy and safety profile of Vabysmo has been well established in global clinical trials and is reinforced by a growing breadth of real-world evidence, with hundreds of thousands of people treated.” Vabysmo is the first and only bispecific antibody approved for the eye.1,6 Today’s approval in RVO is based on positive results from the global phase III BALATON and COMINO studies that demonstrated monthly treatment with Vabysmo provided early and sustained improvement in vision in people with branch and central RVO, meeting the primary endpoint of non-inferior visual acuity gains at 24 weeks compared to aflibercept. This was further supported by data showing Vabysmo achieved rapid and robust drying of retinal fluid. In BALATON and COMINO, Vabysmo was generally well tolerated and the safety profile was consistent with previous trials. The most common adverse reaction was conjunctival haemorrhage (3%). Safety results were consistent across study arms.7-9 Information has also been added to the Warnings and Precautions section of the U.S. label based on rare post-marketing cases of retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation. The reported rate of retinal vasculitis with vascular occlusion is 0.06 per 10,000 injections, in line with real-world reported frequencies of other broadly used intravitreal treatments for people living with nAMD, DME and RVO.10-12 To date, Vabysmo is approved in more than 80 countries around the world for people living with nAMD and DME, with approximately 2 million doses distributed globally.12 About retinal vein occlusion (RVO)RVO is the second most common cause of vision loss due to retinal vascular conditions. It affects an estimated 28 million adults globally, mainly those aged 60 or older, and can lead to severe and sudden vision loss.2,13 The level of angiopoietin-2 (Ang-2) is elevated in RVO and it is thought that increased Ang-2 expression drives disease progression.14,15 RVO typically results in sudden, painless vision loss in the affected eye because the vein blockage restricts normal blood flow in the affected retina, resulting in ischaemia, bleeding, fluid leakage and retinal swelling called macular edema.13,16,17 Currently, macular edema due to RVO is typically treated with repeated intravitreal injections of anti-vascular endothelial growth factor therapies.16 There are two main types of RVO: branch retinal vein occlusion, which affects more than 23 million people globally and occurs when one of the four smaller ‘branches’ of the main central retinal vein becomes blocked; and central retinal vein occlusion, which is less common, affecting more than four million people worldwide, and occurs when the eye’s central retinal vein becomes blocked.2,17 About the BALATON and COMINO studies8,9BALATON (NCT04740905) and COMINO (NCT04740931) are two randomised, multicentre, double-masked, global phase III studies evaluating the efficacy and safety of Vabysmo®️ (faricimab) compared to aflibercept. For the first 20 weeks, patients were randomised 1:1 to receive monthly injections for six months of either Vabysmo (6.0 mg) or aflibercept (2.0 mg). From weeks 24 to 72, all patients received Vabysmo (6.0 mg) up to every four months, using a treat-and-extend dosing regimen. The BALATON study was conducted in 553 people with branch retinal vein occlusion. The COMINO study was conducted in 729 people with central retinal or hemiretinal vein occlusion. The primary endpoint of each study was the change in best-corrected visual acuity from baseline at 24 weeks. Secondary endpoints (weeks 0-24) included change in central subfield thickness and drying of retinal fluid, from baseline over time up to week 24. Secondary endpoints (weeks 24-72) were treatment durability at 68 weeks and continuation of weeks 0-24 endpoints. About the Vabysmo® (faricimab) clinical development programmeRoche has a robust phase III clinical development programme for Vabysmo. The programme includes AVONELLE-X, an extension study of TENAYA and LUCERNE, evaluating the long-term safety and tolerability of Vabysmo in neovascular or ‘wet’ age-related macular degeneration (nAMD), and RHONE-X, an extension study of YOSEMITE and RHINE, evaluating the long-term safety and tolerability of Vabysmo in diabetic macular edema (DME).18,19 Roche has also initiated several phase IV studies, including the ELEVATUM study of Vabysmo in underrepresented patient populations with DME, the SALWEEN study of Vabysmo in a subpopulation of nAMD highly prevalent in Asia, as well as the VOYAGER study, a global real-world data collection platform.20-22 Roche also supports several other independent studies to further understand retinal conditions with a high unmet need.12 About Vabysmo® (faricimab)Vabysmo is the first bispecific antibody approved for the eye.1,6 It targets and inhibits two signalling pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A). Ang-2 and VEGF-A contribute to vision loss by destabilising blood vessels, causing new leaky blood vessels to form and increasing inflammation. By blocking pathways involving Ang-2 and VEGF-A, Vabysmo is designed to stabilise blood vessels.23,24 Vabysmo is approved in more than 80 countries around the world, including the United States, Japan, the United Kingdom and the European Union for people living with neovascular or ‘wet’ age-related macular degeneration and diabetic macular edema, and in the United States for people living with macular edema following retinal vein occlusion. Review by other regulatory authorities is ongoing.1,6,12,25,26 About Roche in ophthalmologyRoche is focused on saving people’s eyesight from the leading causes of vision loss through pioneering therapies. Through our innovation in the scientific discovery of new potential drug targets, personalised healthcare, molecular engineering, biomarkers and continuous drug delivery, we strive to design the right therapies for the right patients. We have the broadest retina pipeline in ophthalmology, which is led by science and informed by insights from people with eye diseases. Our pipeline includes gene therapies and treatments for geographic atrophy and other vision-threatening diseases, including rare and inherited conditions. Applying our extensive experience, we have already brought breakthrough ophthalmic treatments to people living with vision loss. Susvimo™ (previously called Port Delivery System with ranibizumab) 100 mg/mL for intravitreal use via ocular implant is the first United States Food and Drug Administration-approved refillable eye implant for neovascular or ‘wet’ age-related macular degeneration that continuously delivers a customised formulation of ranibizumab over a period of months.27 Vabysmo® (faricimab) is the first bispecific antibody approved for the eye, which targets and inhibits two signalling pathways linked to a number of vision-threatening retinal conditions.1,6,23,24 Lucentis® (ranibizumab injection)^ is the first treatment approved to improve vision in people with certain retinal conditions.28 About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. ^Lucentis® (ranibizumab injection) was developed by Genentech, a member of the Roche Group. Genentech retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world. All trademarks used or mentioned in this release are protected by law.References[1] U.S. Food and Drug Administration (FDA). Highlights of prescribing information, Vabysmo. 2023. [Internet; cited October 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761235s000lbl.pdf.[2] Song P, et al. Global epidemiology of retinal vein occlusion: a systematic review and meta-analysis of prevalence, incidence, and risk factors. J Glob Health. 2019;9:010427. Song P, et al. Global epidemiology of retinal vein occlusion: a systematic review and meta-analysis of prevalence, incidence, and risk factors. J Glob Health. 2019;9:010427.[3] Yau JWY, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–64.[4] Connolly E, et al. Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population. Br J Ophthalmol. 2018;102:1691–95.[5] Bright Focus Foundation. Age-Related Macular Degeneration: Facts & Figures [Internet; cited October 2023]. Available from: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures.[6] MHRA approves faricimab through international work-sharing initiative [Internet; cited October 2023]. Available from: https://www.gov.uk/government/news/mhra-approves-faricimab-through-international-work-sharing-initiative.[7] Tadayoni R, et al. Faricimab in RVO: Results from the BALATON and COMINO phase 3 studies. Presented at: Angiogenesis, Exudation and Degeneration 2023, 10-11 February 2023; Florida, United States.[8] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to branch retinal vein occlusion (BALATON) [Internet; cited October 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740905.[9] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to central retinal or hemiretinal vein occlusion (COMINO) [Internet; cited October 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740931.[10] Ma P, et al. Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS). Frontiers in Pharmacology. 2022;13:1017889.[11] Food and Drug Administration. FDA AEs reporting system (FAERS) public dashboard. [Internet; cited October 2023]. Available from: https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard. [12] Roche data on file.[13] Moorfields Eye Hospital, United Kingdom National Health Service Foundation Trust. RVO [Internet; cited October 2023]. Available from: https://www.moorfields.nhs.uk/condition/retinal-vein-occlusion.[14] Joussen et al. Angiopoietin/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data. Eye. 2021;35:1305-1316.[15] Regula JT, et al. Targeting key angiogenic pathways with a bispecific CrossMab optimized for neovascular eye diseases. EMBO Molecular Medicine. 2016;8:1265–88.[16] Schmidt-Erfurth U, et al. Guidelines for the Management of Retinal Vein Occlusion by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2019;242:123-162.[17] Campochiaro P. Molecular pathogenesis of retinal and choroidal vascular diseases. Prog Retin Eye Res. 2015;49:67-81.[18] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with nAMD (AVONELLE-X) [Internet; cited October 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04777201.[19] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with DME (Rhone-X) [Internet; cited October 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04432831.[20] Clinical Trials.gov. A study to investigate faricimab treatment response in treatment-naïve, underrepresented patients with DME (ELEVATUM). [Internet; cited October 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT05224102.[21] APVRS. Design and Rationale of the SALWEEN Trial: A Phase 3b/4 Study of Faricimab, a Dual Angiopoietin-2 and Vascular Endothelial Growth Factor-A Inhibitor, in Patients With Polypoidal Choroidal Vasculopathy. [Internet; cited October 2023]. Available from: https://2022.apvrs.org/abstract/?code=200351.[22] Clinical Trials.gov. A Real-World Study to Gain Clinical Insights Into Roche Ophthalmology Products (VOYAGER). [Internet; cited October 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476926.[23] Heier JS, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials. The Lancet. 2022; 399:729-740.[24] Wykoff C, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with DME (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. The Lancet. 2022; 399:741-755.[25] Chugai obtains regulatory approval for Vabysmo, the first bispecific antibody in ophthalmology, for neovascular age-related macular degeneration and diabetic macular edema [Internet; cited October 2023]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20220328160002_909.html.[26] European Medicines Agency. Summary of Product Characteristics, Vabysmo, 2022 [Internet; cited April 2023]. Available from: https://www.ema.europa.eu/en/documents/product-information/vabysmo-epar-product-information_en.pdf.[27] U.S. FDA. Highlights of prescribing information, Susvimo. 2006 [Internet; cited October 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761197s000lbl.pdf.[28] U.S. FDA. Highlights of prescribing information, Lucentis. 2006 [Internet; cited October 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125156s114lbl.pdf. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Nathalie AltermattPhone: +41 79 771 05 25 Simon GoldsboroughPhone: +44 797 32 72 915 Karsten KleinePhone: +41 79 461 86 83 Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262 Rebekka SchnellPhone: +41 79 205 27 03 Sileia UrechPhone: +41 79 935 81 48 Roche Investor Relations Dr. Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.com Dr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.com Dr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.com Dr. Gerard Tobin Phone: +41 61 68-72942 e-mail: gerard.tobin@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 27102023_Vabysmo RVO Approval_en

Late-breaking post-hoc data indicate Vabysmo leads to less fibrosis, which may negatively impact vision, than aflibercept in people with diabetic macular edema (DME)Real-world data reinforce that first-line Vabysmo use improves outcomes and extends treatment intervals rapidly during the first four months for people with neovascular or ‘wet’ age-related macular degeneration (nAMD) and DMEClinical data reiterate Vabysmo’s positive anatomical outcomes, including reduced blood vessel leakage in the macula and greater and faster retinal fluid control Vabysmo is currently approved in over 70 countries to treat nAMD and DME, with more than one million doses distributed globally Basel, 20 July - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that data from its ophthalmology portfolio will be highlighted in 25 abstracts at the 2023 American Society of Retina Specialists (ASRS) Annual Meeting, which will be held from 28 July to 1 August in Seattle, United States. The data further advance the depth of clinical and real-world evidence supporting the use of Vabysmo® (faricimab), the first and only bispecific antibody for the eye, for the treatment of neovascular or ‘wet’ age-related macular degeneration (nAMD) and diabetic macular edema (DME).1-14 “The clinical and real-world data at ASRS reinforce the improvement in outcomes brought by Vabysmo in two leading causes of vision loss, particularly new analyses suggesting that Vabysmo is associated with less vision-impacting fibrosis than aflibercept,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “By improving disease control while offering a potentially less frequent treatment regimen, Vabysmo may help people spend less time managing their condition.” Vabysmo is currently approved in over 70 countries to treat nAMD and DME, with public reimbursement in over 20 markets and more than one million doses distributed globally.15 Neovascular AMD and DME are two leading causes of vision loss worldwide, affecting more than 40 million people.16-19 The following key data will be presented at ASRS 2023: Late-breaker: Vabysmo’s effect on epiretinal membrane (ERM) formation in DME compared to aflibercept Two-year post-hoc data from the YOSEMITE and RHINE phase III studies will be presented for the first time on ERM formation in DME patients, indicating Vabysmo leads to less retinal fibrosis than aflibercept.3 ERMs are fibrotic tissues on the surface of the retina, which may negatively impact the anatomy of the eye and compromise vision.20 Vabysmo drying and durability data Data will be presented reiterating positive anatomical outcomes previously seen with Vabysmo treatment, including reduced blood vessel leakage in the macula, and greater and faster retinal fluid control.4,6,7 Blood vessel leakage can cause a build-up of fluid and swelling in the back of the eye, contributing to sight loss.21,22 Data will also further support how increased intervals between doses of Vabysmo to treat nAMD and DME, compared to aflibercept, do not compromise outcomes.4,6,7 Vabysmo real-world data Roche’s expanding programme of real-world studies for Vabysmo includes more than 8,500 participants in almost 30 countries.15 Updates will be presented on real-world data from the FARETINA studies of Vabysmo in nAMD and DME looking at extended dosing intervals and impact on vision, including Vabysmo’s use as a first-line treatment.9,10 Preliminary data on early outcomes and treatment patterns in the United Kingdom FARWIDE studies of Vabysmo in nAMD and DME will be shared for the first time.11,12 In addition, independent investigator studies of Vabysmo are expected to be presented. The TRUCKEE study, which focused on real-world outcomes in people with nAMD across 14 sites in the United States is scheduled for presentation on 31 July during the Wet AMD Symposium 3 (1:38 PM to 1:44 PM PDT).23 Further information on select Roche abstracts that will be presented at ASRS 2023 can be found in the table below. TopicAbstract TitlePresentation DetailsVabysmo An Assessment of the Impact of Disease Activity Criteria on Dosing Interval Assignment in Clinical Trial Patients With nAMD Paper PresentationSession: Wet AMD Symposium 1July 29, 20238:49 AM to 8:53 AM PDTElevatum Study Design and Rationale: A Phase 4 Trial of Faricimab (VABYSMO) in Underrepresented Patients With Diabetic Macular Edema Paper PresentationSession: Diabetic Retinopathy Symposium 2July 30, 20232:04 PM to 2:07 PM PDTImpact of Faricimab vs Aflibercept on Epiretinal Membrane Formation Over 2 Years in Eyes with DME in the YOSEMITE/RHINE Phase 3 Trials Paper PresentationSession: Late Breaking AbstractsJuly 30, 20233:58 PM to 4:03 PM PDTFaricimab Reduces Macular Leakage vs Aflibercept in Patients With DME Paper PresentationSession: Diabetic Retinopathy Symposium 3July 31, 202310:53 AM to 10:57 AM PDTFaricimab Causes Rapid and Sustained Intraocular Suppression of Ang-2 and VEGF-A for Up to 16 Weeks in nAMD and DMEPaper PresentationSession: Diabetic Retinopathy Symposium 3July 31, 202310:57 AM to 11:01 AM PDTTime to Retinal Fluid Control With Faricimab vs Aflibercept in Patients With DME in the Phase 3 YOSEMITE/RHINE TrialsPaper PresentationSession: Diabetic Retinopathy Symposium 3July 31, 202311:01 AM to 11:05 AM PDTFaricimab Rapidly Improves Fluid Parameters in Patients With nAMD Paper PresentationSession: Wet AMD Symposium 3July 31, 20231:30 PM to 1:34 PM PDTEfficacy, Durability, and Safety of Faricimab in DME: 1-year Results from China Subpopulation of Phase 3 RHINE Trial Virtual Paper on Demand PresentationVabysmo Real-World Data Early Treatment Patterns and Outcomes in Patients with Diabetic Macular Edema Treated with Faricimab: the FARETINA-DME Study Paper PresentationSession: Diabetic Retinopathy Symposium 3 July 31, 202311:05 AM to 11:09 AM PDTEarly Treatment Patterns and Outcomes in Patients with Neovascular Age-Related Macular Degeneration Initiating Faricimab: the FARETINA-AMD StudyPaper PresentationSession: Wet AMD Symposium 3July 31, 20231:34 PM to 1:38 PM PDTReal-world Use of Faricimab to Treat nAMD Patients in the UK Virtual Paper on Demand PresentationReal-world Use of Faricimab to Treat DME Patients in the UK Poster PresentationSusvimoPort Delivery System With Ranibizumab (PDS) for Continuous Treatment in DME and DR: Additional Results From the Phase 3 Pagoda and Pavilion TrialsPaper Presentation Session:Late Breaking AbstractsAugust 1, 202310:53 AM to 10:59 AM PTAnti-IL-6 (for Uveitic Macular Edema)A Novel Intravitreal Anti-IL-6 Monoclonal Antibody for Uveitic Macular Edema (UME): Preliminary Results From the Phase 1 DOVETAIL StudyPaper PresentationSession: Inflammatory & Infectious Diseases SymposiumJuly 29, 20234:04 PM to 4:10 PM PDT About neovascular age-related macular degenerationAge-related macular degeneration (AMD) is a condition that affects the part of the eye that provides sharp, central vision needed for activities like reading.16 Neovascular or ‘wet’ AMD (nAMD) is an advanced form of the disease that can cause rapid and severe vision loss if left untreated.24,25 It develops when new and abnormal blood vessels grow uncontrolled under the macula, causing swelling, bleeding and/or fibrosis.24 Worldwide, around 20 million people are living with nAMD – the leading cause of vision loss in people over the age of 60 – and the condition will affect even more people around the world as the global population ages.16-18 About diabetic macular edemaAffecting around 21 million people globally, diabetic macular edema (DME) is a vision-threatening retinal condition associated with blindness and decreased quality of life when left untreated.19 DME occurs when damaged blood vessels leak into and cause swelling in the macula – the central area of the retina responsible for the sharp vision needed for reading and driving.21,26 The number of people with DME is expected to grow as the prevalence of diabetes increases.27 About the Vabysmo® (faricimab) clinical development programmeRoche has a robust phase III clinical development programme for Vabysmo® (faricimab). The programme includes AVONELLE-X, an extension study of TENAYA and LUCERNE evaluating the long-term safety and tolerability of Vabysmo in neovascular or ‘wet’ age-related macular degeneration (nAMD), and Rhone-X, an extension study of YOSEMITE and RHINE evaluating the long-term safety and tolerability of Vabysmo in diabetic macular edema (DME).28,29 In addition, Roche is investigating the efficacy and safety of Vabysmo in people with macular edema following retinal vein occlusion in two phase III studies, BALATON and COMINO.30,31 Roche has also initiated several phase IV studies, including the ELEVATUM study of Vabysmo in underrepresented patient populations with DME, the SALWEEN study of Vabysmo in a subpopulation of nAMD highly prevalent in Asia, as well as the VOYAGER study, a global real-world data collection platform.32-34 Roche also supports several other independent studies to further understand retinal conditions with a high unmet need.15 About Vabysmo® (faricimab)Vabysmo® (faricimab) is the first bispecific antibody approved for the eye.13,14 It targets and inhibits two signalling pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A).35,36 Ang-2 and VEGF-A contribute to vision loss by destabilising blood vessels, causing new leaky blood vessels to form and increasing inflammation.35,36 By blocking pathways involving Ang-2 and VEGF-A, Vabysmo is designed to stabilise blood vessels. Vabysmo is approved in over 70 countries around the world, including the United States, Japan, the United Kingdom and in the European Union for people living with neovascular or ‘wet’ age-related macular degeneration and diabetic macular edema.13-15,37,38 Review by other regulatory authorities is ongoing. About Roche in ophthalmologyRoche is focused on saving people’s eyesight from the leading causes of vision loss through pioneering therapies. Through our innovation in the scientific discovery of new potential drug targets, personalised healthcare, molecular engineering, biomarkers and continuous drug delivery, we strive to design the right therapies for the right patients. We have the broadest retina pipeline in ophthalmology, which is led by science and informed by insights from people with eye diseases. Our pipeline includes gene therapies and treatments for geographic atrophy and other vision-threatening diseases, including rare and inherited conditions. Applying our extensive experience, we have already brought breakthrough ophthalmic treatments to people living with vision loss. Susvimo™ (Port Delivery System with ranibizumab) 100 mg/mL for intravitreal use via ocular implant is the first U.S. Food and Drug Administration-approved refillable eye implant for neovascular or ‘wet’ age-related macular degeneration that continuously delivers a customised formulation of ranibizumab over a period of months.39 Vabysmo® (faricimab) is the first bispecific antibody approved for the eye, which targets and inhibits two signalling pathways linked to a number of vision-threatening retinal conditions by neutralising angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A).13,14,35,36 Lucentis®* (ranibizumab injection) is the first treatment approved to improve vision in people with certain retinal conditions.40 *Lucentis® (ranibizumab injection) was developed by Genentech, a member of the Roche Group. Genentech retains commercial rights in the United States and Novartis has exclusive commercial rights for the rest of the world. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com. All trademarks used or mentioned in this release are protected by law.References[1] Zarbin M, et al. An assessment of the impact of disease activity criteria on dosing interval assignment in clinical trial patients with nAMD. Paper presentation at: American Society of Retina Specialists (ASRS) Annual Meeting; 28 July – 1 August 2023.[2] Coney JM, et al. Elevatum study design and rationale: a phase IIII trial of faricimab (VABYSMO) in underrepresented patients with diabetic macular edema. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[3] Jaffe GJ, et al. Impact of faricimab vs aflibercept on epiretinal membrane formation over two years in eyes with DME in the YOSEMITE/RHINE phase III trials. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[4] Nudleman E, et al. Faricimab reduces macular leakage vs aflibercept in patients with DME. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[5] Muni RH, et al. Faricimab causes rapid and sustained intraocular suppression of Ang-2 and VEGF-A for up to 16 weeks in nAMD and DME. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[6] Rachitskaya AV, et al. Time to retinal fluid control with faricimab vs aflibercept in patients with DME in the phase III YOSEMITE/RHINE trials. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[7] London NJ, et al. Faricimab rapidly improves fluid parameters in patients with nAMD. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023. [8] Sun X, et al. Efficacy, durability, and safety of faricimab in DME: one-year results from China subpopulation of phase III RHINE trial. Virtual Paper on Demand Presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[9] Borkar D, et al. Early treatment patterns and outcomes in patients with diabetic macular edema treated with faricimab: the FARETINA-DME study. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[10] Leng T, et al. Early treatment patterns and outcomes in patients with neovascular age-related macular degeneration initiating faricimab: the FARETINA-AMD study. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023.[11] Patel PJ, et al. Real-world use of faricimab to treat nAMD patients in the UK. Virtual Paper on Demand Presentation at: ASRS Annual Meeting; 28 July – 1 August 2023. [12] Gale RP, et al. Real-world use of faricimab to treat DME patients in the UK. Poster Presentation at: ASRS Annual Meeting; 28 July – 1 August 2023. [13] United States Food and Drug Administration (U.S. FDA). Highlights of prescribing information, Vabysmo. 2022 [Internet; cited July 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761235s000lbl.pdf. [14] Medicines and Healthcare products Regulatory Agency. MHRA approves faricimab through international work-sharing initiative [Internet; cited July 2023]. Available from: https://www.gov.uk/government/news/mhra-approves-faricimab-through-international-work-sharing-initiative. [15] Roche data on file.[16] Bright Focus Foundation. AMD: Facts and figures [Internet; cited July 2023]. Available from: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures. [17] Connolly E, et al. Prevalence of AMD-associated genetic risk factors and four-year progression data in the Irish population. Br J Ophthalmol. 2018;102:1691–5.[18] Wong WL, et al. Global prevalence of AMD and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2:106–16.[19] Yau JWY, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35:556–64.[20] Moorfields Eye Hospital NHS Foundation Trust. Epiretinal membrane [Internet; cited July 2023]. Available from: https://www.moorfields.nhs.uk/condition/epiretinal-membrane#:~:text=An%20epiretinal%20membrane%20is%20a,cause%20problems%20with%20central%20vision. [21] All About Vision. Macula lutea [Internet; cited July 2023]. Available from: https://www.allaboutvision.com/resources/macula.[22] Kaiser PK, et al. Retinal fluid and thickness as measures of disease activity in neovascular age-related macular degeneration. Retina. 2021;41:1579-86.[23] Chang EY, et al. Real-world efficacy and safety of faricimab in neovascular age-related macular degeneration: the TRUCKEE study. Paper presentation at: ASRS Annual Meeting; 28 July – 1 August 2023 Presentation.[24] Pennington KL, DeAngelis MM. Epidemiology of AMD: associations with cardiovascular disease phenotypes and lipid factors. Eye and Vision. 2016;3:34.[25] Little K, et al. Myofibroblasts in macular fibrosis secondary to nAMD - the potential sources and molecular cues for their recruitment and activation. EBioMedicine. 2018;38:283-91.[26] National Eye Institute. Diabetic retinopathy [Internet; cited July 2023]. Available from: https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy. [27] Liu E, et al. DME: clinical risk factors and emerging genetic influences. Clin Exp Optom. 2017;100:569–76.[28] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with nAMD (AVONELLE-X) [Internet; cited July 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04777201. [29] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with DME (Rhone-X) [Internet; cited July 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04432831.[30] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to branch retinal vein occlusion (BALATON) [Internet; cited July 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740905.[31] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in participants with macular edema secondary to central retinal or hemiretinal vein occlusion (COMINO) [Internet; cited July 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT04740931. [32] Clinical Trials.gov. A study to investigate faricimab treatment response in treatment-naïve, underrepresented patients with DME (ELEVATUM) [Internet; cited July 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT05224102. [33] APVRS. Design and rationale of the SALWEEN trial: a phase IIIb/IIII study of faricimab, a dual angiopoietin-2 and vascular endothelial growth factor-A inhibitor, in patients with polypoidal choroidal vasculopathy [Internet; cited July 2023]. Available from: https://2022.apvrs.org/abstract/?code=200351. [34] Clinical Trials.gov. A real-world study to gain clinical insights into Roche ophthalmology products (VOYAGER) [Internet; cited July 2023]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476926. [35] Heier JS, et al. Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for nAMD (TENAYA and LUCERNE): two randomised, double-masked, phase III, non-inferiority trials. The Lancet. 2022; 399:729-40.[36] Wykoff C, et al. Efficacy, durability and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with DME (YOSEMITE and RHINE): two randomised, double-masked, phase III trials. The Lancet. 2022; 399:741-55.[37] Chugai Pharmaceutical Co. Ltd. Chugai obtains regulatory approval for Vabysmo, the first bispecific antibody in ophthalmology, for nAMD and DME [Internet; cited July 2023]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20220328160002_909.html. [38] European Medicines Agency. Summary of Product Characteristics, Vabysmo, 2022 [Internet; cited July 2023]. Available from: https://www.ema.europa.eu/en/documents/product-information/vabysmo-epar-product-information_en.pdf. [39] U.S. FDA. Highlights of prescribing information, Susvimo. 2006 [Internet; cited July 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761197s000lbl.pdf. [40] U.S. FDA. Highlights of prescribing information, Lucentis. 2006 [Internet; cited July 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125156s114lbl.pdf. Roche Group Media Relations Phone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58Nathalie AltermattPhone: +41 79 771 05 25Karsten KleinePhone: +41 79 461 86 83Nina MählitzPhone: +41 79 327 54 74 Kirti PandeyPhone: +49 172 6367262Sileia UrechPhone: +41 79 935 81 48 Roche Investor Relations Dr. Bruno Eschli Phone: +41 61 68-75284 e-mail: bruno.eschli@roche.comDr. Sabine BorngräberPhone: +41 61 68-88027 e-mail: sabine.borngraeber@roche.comDr. Birgit MasjostPhone: +41 61 68-84814e-mail: birgit.masjost@roche.comDr. Gerard Tobin Phone: +41 61 68-72942 e-mail: gerard.tobin@roche.com Investor Relations North America Loren KalmPhone: +1 650 225 3217 e-mail: kalm.loren@gene.com Attachment 20072023_MR_ASRS Global Curtain Raiser_en