Uveitic Macular Edema

- CLS-AX Phase 3 Ready Based on Positive Phase 2b Topline Data in Wet AMD - - Differentiated Profile for CLS-AX Targeting Flexible Dosing Similar to a Biologic with the Potential Extended Duration of a Tyrosine Kinase Inhibitor (TKI) - - Versatility of SCS Microinjector® Featured in Multiple Presentations - ALPHARETTA, Ga., Oct. 22, 2024 (GLOBE NEWSWIRE) -- Clearside Biomedical, Inc. (Nasdaq: CLSD), a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS®), announced today that multiple presentations were delivered at the 2024 Annual Meeting of the American Academy of Ophthalmology (AAO) and preceding events that highlighted encouraging safety and efficacy data from clinical trials of therapies utilizing Clearside’s SCS Microinjector® to deliver drugs into the suprachoroidal space to treat a variety of retinal diseases. “During this year’s AAO meeting, physicians indicated significant interest in the target product profile for CLS-AX, which we believe could provide a differentiated option in wet AMD with flexible dosing and extended duration,” said Victor Chong, M.D., MBA, Chief Medical Officer of Clearside. “The positive topline data from our recent ODYSSEY trial was presented in several sessions and was well received. CLS-AX demonstrated extended duration and stable vision and anatomic measures throughout the trial in a patient population with active disease confirmed by an independent reading center. ODYSSEY supports the ability to administer multiple doses of CLS-AX from 12 weeks up to 36 weeks with a well-tolerated safety profile. These results strongly support advancing our CLS-AX wet AMD program into Phase 3 development. Our ultimate objective for CLS-AX is to maintain visual acuity and reduce the number of injections, therefore reducing the number of office visits, which can benefit patients, caregivers and payors with improved outcomes, while also fitting into existing physician practice.” Glenn Yiu, M.D., Ph.D., Professor of Ophthalmology, University of California, Davis, highlighted, “Suprachoroidal delivery is a proven way to deliver medication for sight-threatening retinal disease directly to the back of the eye. Clearside’s SCS Microinjector is being used to deliver a wide variety of drug candidates into the suprachoroidal space, providing targeted delivery to potentially improve duration, efficacy and safety with the compartmentalization of medication to reduce toxic effects on non-diseased cells. In the recent ODYSSEY Phase 2b trial, there was an 84% reduction in the frequency of injections after the initial dose of CLS-AX, with approximately 90% of CLS-AX participants not requiring any additional treatment up to 4 months, 81% up to 5 months and 67% up to 6 months. This encouraging data is consistent with recent real-world outcomes on the use and durability of Clearside’s first approved suprachoroidal treatment, XIPERE® (triamcinolone acetonide injectable suspension) for uveitic macular edema, in which more than 75% of eyes did not require retreatment for 6 months after a single dose of XIPERE.” Sessions on Suprachoroidal Drug Delivery Utilizing Clearside’s SCS Microinjector: AAO: Suprachoroidal Drug Delivery in the Real WorldPresented by: Glenn Yiu, M.D., Ph.D. AAO: A Phase 2 Dose-Escalation Study Evaluating Suprachoroidal Delivery of Investigational ABBV-RGX-314 Gene Therapy for DR (abstract 30078795)Presented by: Arshad Khanani M.D., M.A. Sessions on TKIs Including CLS-AX in Retinal Diseases: AAO: Tyrosine Kinase Inhibitors and Retinal Diseases: Clinical StudiesPresented by: Rishi Singh, M.D. Eyecelerator: AAO 2024 Retina Showcase – Clearside BiomedicalPresented by: Victor Chong, M.D., MBA Innovate Retina: Tyrosine Kinase Inhibitors: A Suprachoroidal Perspective Presented by: Roger Goldberg, M.D., MBA Innovate Retina: Tyrosine Kinase (TKIs) - Directed Treatments: The Promise of New Targets Presented by: Arshad Khanani M.D., M.A. About Clearside’s Suprachoroidal Space (SCS®) Injection Platform and SCS Microinjector® Clearside’s patent protected, proprietary suprachoroidal space (SCS®) injection treatment approach offers unprecedented access to the back of the eye, where sight-threatening disease often occurs. The Company’s unique platform is inherently flexible and intended to work with established and new formulations of medications. Clearside’s patented SCS Microinjector® can deliver a wide variety of drug candidates into the suprachoroidal space, providing targeted delivery to potentially improve efficacy and compartmentalization of medication to reduce or eliminate toxic effects on non-diseased cells. The SCS Microinjector system comprises a syringe, a custom-designed hub, and two 30-gauge hollow microneedles of varying lengths, each approximately one millimeter, optimizing insertion and suprachoroidal administration of drugs. About ODYSSEY Phase 2b Clinical Trial ODYSSEY was a randomized, double-masked, parallel-group, active-controlled, multicenter, 36-week, Phase 2b clinical trial in participants with wet AMD previously treated with intravitreal anti-vascular endothelial growth factor (VEGF) standard of care therapy. A total of 60 participants were treated for 36 weeks and randomized to either CLS-AX (1 mg) or aflibercept (2 mg) with a 2:1 randomization schedule (40 participants in CLS-AX arm and 20 participants in aflibercept arm). CLS-AX was administered via suprachoroidal injection using Clearside’s SCS Microinjector, and aflibercept was administered via intravitreal injection. Participants in the trial were determined to have active disease with a median duration of wet AMD diagnosis of 9.9 months. The ODYSSEY trial achieved its objectives, including primary outcomes in mean change from baseline in best corrected visual acuity and safety and tolerability of CLS-AX, and secondary outcomes in visual function and ocular anatomy, the need for supplemental treatment, and treatment burden as measured by total injections over the trial duration. CLS-AX demonstrated compelling intervention-free rates with 100% of CLS-AX participants not requiring any additional treatment up to 3 months, 90% up to 4 months, 81% up to 5 months, and 67% up to 6 months after the initial CLS-AX dose. In the CLS-AX group, the injection frequency was reduced by approximately 84% compared to the average monthly injections in the 24 weeks prior to screening. About CLS-AX (axitinib injectable suspension) Clearside is developing CLS-AX as a longer-acting therapy for the treatment of retinal diseases. CLS-AX (axitinib injectable suspension) is a proprietary suspension of axitinib for suprachoroidal injection. Axitinib is a tyrosine kinase inhibitor (TKI), currently approved as an oral tablet formulation to treat advanced renal cell carcinoma, that achieves pan-VEGF blockade, directly inhibiting VEGF receptors-1, -2, and -3 with high potency and specificity. Clearside believes this broad VEGF blockade may have efficacy advantages over existing retinal therapies by acting at a different level of the angiogenesis cascade and may benefit patients who sub-optimally respond to current, more narrowly focused anti-VEGF therapies. Suprachoroidal injection of this proprietary suspension of axitinib has demonstrated meaningful potential in Phase 1/2a and Phase 2b wet AMD clinical trials in which CLS-AX was well tolerated and demonstrated a positive safety profile. With suprachoroidal administration of axitinib, there is the potential to achieve prolonged duration and targeted delivery to affected tissue layers by compartmentalizing axitinib behind the retina, thereby limiting drug exposure to the front of the eye. About Age-Related Macular Degeneration (AMD) Age-related macular degeneration causes a progressive loss of central vision and is the most common cause of legal blindness in individuals over age 55. Neovascular AMD (wet AMD) is generally caused by abnormal blood vessels that leak fluid or blood into the macula, the part of the retina responsible for central vision, and accounts for the majority of vision loss in patients with this disorder. Approximately 11 million patients in the U.S. are living with AMD1, and about 10% of all patients with AMD have the wet form2. Current treatments require life-long, frequent injections to maintain efficacy. This treatment regimen tends to cause a treatment burden for patients resulting in reduced compliance and under-treatment leading to potentially limited outcomes. In the U.S., the total economic impact of late-stage AMD is estimated to be approximately $49 billion, with the majority of costs attributed to lower productivity related to job loss or job reduction due to the condition3. Sources1 Pennington, Katie L and DeAngelis, Margaret M, Eye and Vision, Epidemiology of age-related macular degeneration (AMD): associations with cardiovascular disease phenotypes and lipid factors, Dec 22, 2016.2 Prall, F Ryan and Ciulla, Thomas A, Medscape: Exudative (Wet) Age-Related Macular Degeneration (AMD), June 16, 2022.3 Retina International, The Socio-economic Impact of Age-related Macular Degeneration (AMD) in Bulgaria, Germany, and USA, Oct 12, 2022. About XIPERE® (triamcinolone acetonide injectable suspension) for suprachoroidal use XIPERE® (triamcinolone acetonide injectable suspension) for suprachoroidal use is a proprietary suspension of the corticosteroid triamcinolone acetonide for administration to the suprachoroidal space for the treatment of macular edema associated with uveitis. XIPERE is approved by the U.S. Food and Drug Administration and is commercially available in the United States. Bausch + Lomb, a leading global eye health company dedicated to helping people see better to live better, has the exclusive license for the commercialization and development of XIPERE in the U.S. and Canada. Arctic Vision, a specialty ophthalmology company based in China, has the exclusive license for the commercialization and development of XIPERE, which they refer to as Arcatus®, in Greater China, South Korea, Australia, New Zealand, India and the ASEAN Countries. A link to the full prescribing information is available at https://www.xipere.com/hcp/#isi. About Clearside Biomedical, Inc. Clearside Biomedical, Inc. is a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS®) to improve patient outcomes. Clearside’s SCS injection platform, utilizing the Company’s patented SCS Microinjector®, enables an in-office, repeatable, non-surgical procedure for the targeted and compartmentalized delivery of a wide variety of therapies to the macula, retina, or choroid to potentially preserve and improve vision in patients with sight-threatening eye diseases. Clearside is developing its own pipeline of small molecule product candidates for administration via its SCS Microinjector. The Company’s lead program, CLS-AX (axitinib injectable suspension), for the treatment of neovascular age-related macular degeneration (wet AMD), recently completed a Phase 2b clinical trial, and planning for a Phase 3 program is underway. Clearside developed and gained approval for its first product, XIPERE® (triamcinolone acetonide injectable suspension) for suprachoroidal use, which is available in the U.S. through a commercial partner. Clearside also strategically partners its SCS injection platform with companies utilizing other ophthalmic therapeutic innovations. For more information, please visit clearsidebio.com or follow us on LinkedIn. Cautionary Note Regarding Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “believe”, “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Clearside’s current beliefs and expectations. These forward-looking statements include statements regarding the clinical development of CLS-AX (including any future clinical trials), and the potential benefits of CLS-AX, Clearside’s suprachoroidal delivery technology and Clearside’s SCS Microinjector®. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Clearside’s reliance on third parties over which it may not always have full control and other risks and uncertainties that are described in Clearside’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission (SEC) on March 12, 2024, Clearside’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC on August 12, 2024, and Clearside’s other periodic reports filed with the SEC. Any forward-looking statements speak only as of the date of this press release and are based on information available to Clearside as of the date of this release, and Clearside assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. Source: Clearside Biomedical, Inc.

The ELEVATUM study showed clinically meaningful improvement in vision and reduction in retinal fluid in people with diabetic macular edema (DME) treated with Vabysmo who identify as African American, Black, Hispanic and Latino1 Efficacy and safety from this phase IV study were consistent with data from the Vabysmo phase III DME studies1These racial and ethnic groups are disproportionately affected by diabetes and at higher risk of developing DME, a leading cause of vision loss2-3 Basel, 18 October 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today positive topline one-year results from the open-label, single-arm phase IV ELEVATUM study evaluating Vabysmo® (faricimab) for the treatment of diabetic macular edema (DME) in people from racial and ethnic groups that are often underrepresented in clinical trials.4 Initial data from 124 participants in the United States (US) showed that after one year of treatment with Vabysmo, administered every eight weeks, participants could read an additional 12.3 letters on average – equivalent to about two and a half lines on an eye chart. Results among major racial and ethnic groups represented in this study were similar. Hispanic and Latino participants started the study with the most severe disease and had an average vision gain of 14.1 letters from baseline at one year, equivalent to nearly three lines on an eye chart. African American and Black participants gained an average of 11.3 letters from baseline at one year. Vabysmo was well tolerated, with no new safety events identified.1 These data were presented in a late-breaking oral presentation at the American Academy of Ophthalmology (AAO) 2024 Annual Meeting in Chicago, Illinois, on 18 October.1 The study is the first retina trial for historically underrepresented populations. “Vabysmo has been shown to be an effective first-line treatment for diabetic macular edema, and for the first time, we have data specifically demonstrating its ability to improve vision in Black, African American, Hispanic and Latino patients who are disproportionately impacted by this condition,” said investigator Jeremiah Brown, M.D., of Retina Consultants of Texas, who presented the data at AAO. “As a clinician who serves patients from these communities that are so often underrepresented in clinical trials, I believed it was important to take part in this groundbreaking study, and hope the findings will inform and improve the care we provide to our patients in the clinic daily.” Results were consistent with the phase III YOSEMITE and RHINE DME studies.5 A secondary endpoint showed robust retinal drying with Vabysmo across these racial and ethnic groups, who, on average, achieved a decrease of 206.3 microns in central subfield thickness (CST) from baseline.1 Reducing CST indicates retinal drying, which is an important clinical measure, as swelling from excess fluid in the back of the eye is associated with distorted and blurred vision.6 “We established ELEVATUM to specifically evaluate Vabysmo in underrepresented populations,” said Nilesh Mehta, Roche’s Global Therapeutic Area Head for Ophthalmology. “Including diverse populations and perspectives is part of our broader Roche Diversity, Equity & Inclusion (DE&I) strategy and is essential if we want to improve scientific understanding of diabetic macular edema and ultimately improve standard of care for all people living with this condition.” Among the 124 patients, 45% self-identified as Hispanic or Latino, and 48% as Black or African American.1 The study was designed to facilitate enrolment and promote retention of underrepresented patients. For example, ELEVATUM was conducted at sites that treat a high proportion of these populations in urban, rural and community-based locations. In addition, eligibility criteria allowed participants with a haemoglobin A1c (HbA1c) level up to 12%.4 An HbA1c test measures a person’s average blood sugar levels over the past three months and is used to diagnose diabetes.7 Typically, the threshold for DME trials is an HbA1c level of 10%. However, HbA1c levels can be higher in Black, African American, Hispanic and Latino populations compared with Caucasians, meaning a lower HbA1c threshold can inadvertently lead to the exclusion of patients from various ethnic and racial groups.8-9 To date, Vabysmo is approved in more than 100 countries for DME and neovascular or ‘wet’ age-related macular degeneration, and in over 30 countries for macular edema following retinal vein occlusion (RVO). More than five million doses of Vabysmo have been distributed globally since its initial US approval in 2022.10-15 About ELEVATUM4 ELEVATUM (NCT05224102) is a phase IV, multicentre, open-label, single-arm study designed to evaluate Vabysmo® (faricimab) as a treatment for diabetic macular edema (DME) in patients that have been historically underrepresented in clinical trials, including people who self-identify as Black, African American, Hispanic or Latino. Trial participants have not been treated with an anti‑vascular endothelial growth factor before the study. They receive treatment every four weeks with Vabysmo up to week 20, followed by treatment every eight weeks up to week 52. The primary endpoint is change from baseline in best corrected visual acuity at week 56. Secondary endpoints include safety and change in central subfield thickness from baseline over time. About Diabetic Macular Edema Affecting around 29 million people globally, diabetic macular edema (DME) is a vision-threatening retinal condition associated with blindness and decreased quality of life when left untreated.16-17 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.18-19 The number of people with DME is expected to grow as the prevalence of diabetes increases.20 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).21-22 The POYANG study is evaluating Vabysmo in adult treatment-naive patients with choroidal neovascularisation secondary to pathologic myopia.23 Roche has initiated several phase IV studies, including the ELEVATUM study of Vabysmo in underrepresented patient populations with DME and the SALWEEN study of Vabysmo in a subpopulation of nAMD highly prevalent in Asia.4, 24 Roche has also initiated the VOYAGER study, a global real-world data collection platform, and supports several other independent studies to further understand retinal conditions with a high unmet need.25 About Vabysmo® (faricimab)Vabysmo is the first bispecific antibody approved for the eye.11, 26 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.5, 26 Vabysmo is approved in more than 100 countries around the world, including the United States (US), Japan, the United Kingdom and the European Union (EU) for people living with neovascular or ‘wet’ age-related macular degeneration and diabetic macular edema, and in more than 30 countries, including the US, EU and Japan, for people living with macular edema following retinal vein occlusion. Review by other health authorities is ongoing.10-15 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 innovative treatments across different modalities, such as antibodies, and gene and cell therapies targeting multiple vision-threatening conditions, including retinal vascular and diabetic eye diseases, geographic atrophy, and autoimmune conditions, such as thyroid eye disease and uveitic macular edema. 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 (US) Food and Drug Administration-approved refillable eye implant for neovascular or ‘wet’ age-related macular degeneration (nAMD) that continuously delivers a customised formulation of ranibizumab over a period of months.27, 28 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 and vascular endothelial growth factor-A.5, 11, 12, 26 Vabysmo is approved around the world for people living with nAMD, diabetic macular edema and macular edema following retinal vein occlusion.10-15 Lucentis® (ranibizumab injection)* was the first treatment approved to improve vision in people with certain retinal conditions.29 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. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. 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] Emanuelli A. ELEVATUM, the First Industry Sponsored Trial Focused on Underrepresented Patients in Retina in the US. Presented at: American Academy of Ophthalmology (AAO) Annual Meeting; 2024, October 18; Chicago, IL, USA.[2] Coney J, Scott A. Racial disparities in the screening and treatment of diabetic retinopathy. Journal of the National Medical Association. 2022;114 (2):171-181.[3] Lee R, et al. Epidemiology of diabetic retinopathy, DME and related vision loss. Eye and Vision. 2015; 2, 17.[4] Clinical Trials.gov. A Study to Investigate Faricimab Treatment Response in Treatment-Naive, Underrepresented Patients With Diabetic Macular Edema (ELEVATUM) [Internet; cited October 2024]. Available from: https://www.clinicaltrials.gov/study/NCT05224102.[5] 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; 399:741-755.[6] US National Institutes of Health - National Eye Institute. Macular edema. 2023. [Internet; cited October 2024]. Available from: https://www-nei-nih-gov.libproxy1.nus.edu.sg/learn-about-eye-health/eye-conditions-and-diseases/macular-edema.[7] Eyth E, Naik R. Hemoglobin A1C. 2023. [Internet; cited October 2024]. Available from: https://www-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/books/NBK549816/.[8] Cavagnolli G, et al. Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis. PloS one. 2017;12 (2).[9] Borkar DS, et al. Understanding the impact of HbA1c thresholds on DME clinical trial eligibility by race. Presented at: AAO 2023; November 3-6, 2023; San Francisco, CA, USA. Poster PO492.[10] European Medicines Agency. Summary of product characteristics, Vabysmo. 2022. [Internet; cited October 2024]. Available from: https://www.ema.europa.eu/en/documents/product-information/vabysmo-epar-product-information_en.pdf.[11] US FDA. Highlights of prescribing information, Vabysmo. 2023 [Internet; cited October 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761235s003lbl.pdf.[12] Medicines and Healthcare products Regulatory Agency approves faricimab through international work-sharing initiative. [Internet; cited October 2024]. Available from: https://www.gov.uk/government/news/mhra-approves-faricimab-through-international-work-sharing-initiative.[13] Chugai obtains regulatory approval for Vabysmo, the only bispecific antibody in the ophthalmology field, for additional indication of macular edema associated with RVO. [Internet; cited October 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20240326160000_1054.html.[14] Chugai obtains regulatory approval for Vabysmo, the first bispecific antibody in ophthalmology, for nAMD and DME. [Internet; cited October 2024]. Available from: https://www.chugai-pharm.co.jp/english/news/detail/20220328160002_909.html.[15] Roche data on file.[16] Im JHB, et al. Prevalence of DME based on optical coherence tomography in people with diabetes: a systematic review and meta-analysis. Survey of Ophthalmology. 2022 Jul-Aug;67(4):1244-1251.[17] The Lancet. Diabetes: A defining disease of the 21st century. Lancet. 2023 24;401 (10394):2087.[18] All About Vision. Macula lutea. [Internet; cited October 2024]. Available from: https://www.allaboutvision.com/resources/macula.[19] National Eye Institute. Diabetic Retinopathy. [Internet; cited October 2024]. Available from: https://www-nei-nih-gov.libproxy1.nus.edu.sg/learn-about-eye-health/eye-conditions-and-diseases/diabetic-retinopathy.[20] Liu E, et al. DME: Clinical risk factors and emerging genetic influences. Clinical and Experimental Optometry. 2017;100:569–76.[21] Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with nAMD (AVONELLE-X). [Internet; cited October 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04777201. [22] Clinical Trials.gov. Clinical Trials.gov. A study to evaluate the long-term safety and tolerability of Vabysmo in participants with diabetic macular edema (DME) (RHONE-X). [Internet; cited October 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT04432831.[23] Clinical Trials.gov. A study to evaluate the efficacy and safety of faricimab in patients with choroidal neovascularization secondary to pathologic myopia (POYANG). [Internet; cited October 2024]. Available from: https://www.clinicaltrials.gov/study/NCT06176352.[24] APVRS. Design and rationale of the SALWEEN trial: A phase IIIb/IV study of faricimab, a dual angiopoietin-2 and vascular endothelial growth factor-a inhibitor, in patients with polypoidal choroidal vasculopathy. [Internet; cited October 2024]. Available from: https://2022.apvrs.org/abstract/?code=200351.[25] Clinical Trials.gov. A real-world study to gain clinical insights into Roche ophthalmology products (VOYAGER). [Internet; cited October 2024]. Available from: https://clinicaltrials.gov/ct2/show/NCT05476926.[26] 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.[27] US FDA. Highlights of prescribing information, Susvimo. 2021. [Internet; cited October 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761197s000lbl.pdf.[28] Holekamp N, et al. Archway randomised phase III trial of the Port Delivery System with ranibizumab for neovascular age-related macular degeneration (nAMD). Ophthalmology. 2021.[29] US FDA. Highlights of prescribing information, Lucentis. 2014. [Internet; cited October 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/125156s0069s0076lbl.pdf. Roche Global Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com Hans Trees, PhDPhone: +41 79 407 72 58 Sileia UrechPhone: +41 79 935 81 48 Nathalie AltermattPhone: +41 79 771 05 25 Lorena CorfasPhone: +41 79 568 24 95 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 Yvette PetillonPhone: +41 79 961 92 50 Dr. Rebekka SchnellPhone: +41 79 205 27 03 Attachment 18102024_MR_Vabysmo ELEVATUM study _en

- Phase 2b ODYSSEY Trial in Wet AMD Remains on Track with Topline Data Expected in Late Q3 2024 - - ODYSSEY Safety Review Committee Recommends Trial Continue as Planned with no Serious Adverse Events Observed - - Recent Key Opinion Leader Webinar Highlighted the Broad Applicability and Real-World Experience of Suprachoroidal Drug Delivery - ALPHARETTA, Ga., Aug. 12, 2024 (GLOBE NEWSWIRE) -- Clearside Biomedical, Inc. (Nasdaq: CLSD), a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS®), today reported financial results for the second quarter ended June 30, 2024, and provided a corporate update. “Our Phase 2b ODYSSEY clinical trial utilizing CLS-AX (axitinib injectable suspension) in patients with wet AMD continues to advance on track and on time with topline data expected in late Q3 2024,” said George Lasezkay, PharmD, JD, President and Chief Executive Officer. “In July, the Safety Review Committee reviewed masked safety data and noted that there have been no drug-related Serious Adverse Events (SAEs), including no endophthalmitis or retinal vasculitis, and recommended the trial continue as planned without modifying the protocol. Both arms of the ODYSSEY trial have completed six months of treatment, with CLS-AX being re-dosed per protocol in the CLS-AX arm. Re-dosing with CLS-AX is an important and differentiating feature of the ODYSSEY trial, and the re-dosing data will be valuable as we evaluate the effects of CLS-AX in this chronic disease and plan our Phase 3 clinical development program.” Dr. Lasezkay continued, “Several noteworthy events have also occurred featuring our commercial product, XIPERE®1, for the treatment of patients with macular edema associated with uveitis. Most importantly, our Asia-Pacific partner, Arctic Vision, reported positive results from their Phase 3 trial for XIPERE, known as ARCATUS in China, and announced that new drug applications (NDAs) for ARCATUS have been accepted for review in Australia and Singapore. In addition, data presented on the real-world use of XIPERE in the United States has shown the product has excellent durability as 87.7% of eyes did not require an injected or implanted corticosteroid for 6 months after a single dose of XIPERE2.” “In May 2024, consensus guidelines for drug delivery by suprachoroidal administration, co-authored by 16 practicing retinal physicians, were published in the prominent journal, RETINA®. The article describes the physicians’ best practices for injection into the suprachoroidal space. These valuable guidelines, combined with our progress with CLS-AX and the promising real-world and Phase 3 data from XIPERE continue to demonstrate the advantages of suprachoroidal administration utilizing our proprietary SCS Microinjector® to deliver therapies to the back of the eye for the treatment of a variety of retinal diseases,” concluded, Dr. Lasezkay, Key Highlights Topline data expected in late third quarter of 2024 from Phase 2b ODYSSEY clinical trial of CLS-AX using suprachoroidal delivery in neovascular age-related macular degeneration (wet AMD).Clearside’s Asia-Pacific partner, Arctic Vision, reported positive topline results from its Phase 3 clinical trial of ARCATUS® for the treatment of uveitic macular edema in China and announced that NDAs for ARCATUS have been officially accepted in Australia and Singapore.Clearside hosted its Suprachoroidal Delivery Key Opinion Leader webinar highlighting broad applicability and real-world experience with suprachoroidal drug delivery and SCS development opportunities, including wet AMD and geographic atrophy. The replay of this event is available on the Clearside website under the Investors section: Events and Presentations.Ophthalmology Science published an article summarizing safety and tolerability data from OASIS, Clearside’s Phase 1/2a Open-Label, Dose-Escalation trial of CLS-AX (axitinib injectable suspension) in wet AMD. The full publication can be accessed here.RETINA®, The Journal of Retinal and Vitreous Diseases published consensus guidelines for drug delivery via Suprachoroidal Space (SCS®) injection. The full publication can be accessed here.Clearside’s gene therapy partner, REGENXBIO, reported progress on their ABBV-RGX-314 programs delivered via suprachoroidal injection with Clearside’s SCS Microinjector®. REGENEXBIO announced that they expect to initiate a global pivotal trial in the first half of 2025 for the treatment of diabetic retinopathy, and that their Phase 2 ALTITUDE® trial is now enrolling a new cohort of patients with center-involved diabetic macular edema (DME). In addition, REGENEXBIO announced their AAVIATE® Phase 2 trial in wet AMD is initiating enrollment in a new cohort at dose level 4.3Multiple data presentations on the use of Clearside’s suprachoroidal delivery platform were featured at prominent medical meetings, including the Association for Research in Vision and Ophthalmology (ARVO), Clinical Trials at the Summit and Retinal Imaging Biomarkers and Endpoints Summit.Glenn Yiu, MD, PhD, Professor of Ophthalmology at the University of California, Davis, was appointed to Clearside’s Scientific Advisory Board (SAB) in July 2024. Dr. Yiu, a board-certified vitreoretinal surgeon, leads the translational research program at UC Davis studying AMD and other retinal diseases, with focus on ocular imaging technologies, gene editing and delivery, and animal models of retinal disease.Tony Gibney was appointed to Clearside’s Board of Directors in April 2024. Mr. Gibney is an experienced biotechnology executive and former investment banker who brings over 25 years of experience dedicated to advising biotechnology companies on business strategy, collaborations, financings, and mergers and acquisitions. Second Quarter 2024 Financial Results License and other revenue for the second quarter of 2024 was $90,000, compared to $1.0 million for the second quarter of 2023. The revenue primarily related to payments pursuant to Clearside’s license agreements and revenue for services and the sales of SCS Microinjector kits to licensees.Research and development expenses for the second quarter of 2024 were $4.6 million, compared to $4.9 million for the second quarter of 2023. The decrease was primarily related to the CLS-AX program ($0.2 million), development of the SCS Microinjector ($0.2 million), and preclinical work ($0.1 million). This was partially offset by a $0.2 million increase in employee related costs.General and administrative expenses remained constant at $3.1 million in the second quarter of 2024 and 2023.Interest income for the second quarter of 2024 was $0.4 million compared to $0.5 million for the second quarter of 2023. The decrease was due to the lower balance of cash, cash equivalents and short-term investments.Other income for the second quarter of 2024 was $1.9 million, compared to $0 for the second quarter of 2023. Other income for the second quarter of 2024 was due to the change in fair value of the warrant liabilities from the prior March 31, 2024 valuation date.Non-cash interest expense remained constant at $2.3 million in the second quarter of 2024 and 2023. Non-cash interest expense was comprised of imputed interest on the liability related to the sales of future royalties and the amortization of the associated issuance costs.Net loss for the second quarter of 2024 was $7.6 million, or $0.10 per share of common stock, compared to net loss of $9.1 million, or $0.15 per share of common stock, for the second quarter of 2023.As of June 30, 2024, Clearside’s cash, cash equivalents and short-term investments totaled $29.4 million. The Company believes it will have sufficient resources to fund its planned operations into the third quarter of 2025. Additional Information In lieu of a second quarter 2024 conference call, the Company hosted a Suprachoroidal Delivery Key Opinion Leader Webinar on Wednesday, July 24, 2024. The replay of this event is available on the Clearside website under the Investors section: Events and Presentations. Quarterly earnings conference calls are expected to resume with the third quarter 2024 financial results. About Clearside Biomedical, Inc. Clearside Biomedical, Inc. is a biopharmaceutical company revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space (SCS®). Clearside’s SCS injection platform, utilizing the Company’s patented SCS Microinjector®, enables an in-office, repeatable, non-surgical procedure for the targeted and compartmentalized delivery of a wide variety of therapies to the macula, retina, or choroid to potentially preserve and improve vision in patients with sight-threatening eye diseases. Clearside is developing its own pipeline of small molecule product candidates for administration via its SCS Microinjector. The Company’s lead program, CLS-AX (axitinib injectable suspension), for the treatment of neovascular age-related macular degeneration (wet AMD), is in Phase 2b clinical testing. Clearside developed and gained approval for its first product, XIPERE® (triamcinolone acetonide injectable suspension) for suprachoroidal use, which is available in the U.S. through a commercial partner. Clearside also strategically partners its SCS injection platform with companies utilizing other ophthalmic therapeutic innovations. For more information, please visit clearsidebio.com and follow us on LinkedIn and X. Cautionary Note Regarding Forward-Looking Statements Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “believe”, “expect”, “may”, “plan”, “potential”, “will”, and similar expressions, and are based on Clearside’s current beliefs and expectations. These forward-looking statements include statements regarding the clinical development of CLS-AX, the expected timing of topline results from the ODYSSEY clinical trial, the potential benefits of CLS-AX, Clearside’s suprachoroidal delivery technology and Clearside’s SCS Microinjector® and Clearside’s ability to fund its operations into the third quarter of 2025. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Clearside’s reliance on third parties over which it may not always have full control and other risks and uncertainties that are described in Clearside’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the U.S. Securities and Exchange Commission (SEC) on March 12, 2024 and Clearside’s other Periodic Reports filed with the SEC. Any forward-looking statements speak only as of the date of this press release and are based on information available to Clearside as of the date of this release, and Clearside assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise. 1XIPERE® (triamcinolone acetonide injectable suspension) for suprachoroidal use is being commercialized by Bausch + Lomb who has the exclusive license for the commercialization and development of XIPERE in the United States and Canada. Arctic Vision has the exclusive license for the commercialization and development of XIPERE, in Greater China, South Korea, Australia, New Zealand, India and the ASEAN Countries. XIPERE was approved by the U.S. Food and Drug Administration in October 2021 and is commercially available in the U.S. A link to the full prescribing information is available at https://www.xipere.com/hcp/#isi. 2Yiu, Glen, “Suprachoroidal Drug Delivery in the Real World”, Clinical Trials at the Summit Meeting, June 2024 3ALTITUDE® and AAVIATE® are registered trademarks of REGENXBIO, Inc. Investor and Media Contacts: Jenny Kobin Remy Bernarda ir@clearsidebio.com(678) 430-8206 -Financial Tables Follow- CLEARSIDE BIOMEDICAL, INC.̶Selected Financial Data (in thousands, except share and per share data)(unaudited) Statements of Operations Data Three Months EndedJune 30, Six Months EndedJune 30, 2024 2023 2024 2023 License and other revenue $90 $1,018 $320 $1,022 Operating expenses: Cost of goods sold — 213 — 213 Research and development 4,603 4,948 10,218 9,399 General and administrative 3,077 3,127 5,901 6,285 Total operating expenses 7,680 8,288 16,119 15,897 Loss from operations (7,590) (7,270) (15,799) (14,875)Interest income 419 458 767 950 Other income, net 1,917 — 418 — Non-cash interest expense on liability related to the sales of future royalties (2,340) (2,294) (4,743) (4,461)Net loss $(7,594) $(9,106) $(19,357) $(18,386)Net loss per share of common stock — basic and diluted $(0.10) $(0.15) $(0.27) $(0.30)Weighted average shares outstanding — basic and diluted 74,731,139 61,654,520 72,292,183 61,413,343 Balance Sheet DataJune 30, December 31, 2024 2023 Cash and cash equivalents$18,238 $28,920 Short-term investments 11,122 — Total assets 33,934 34,018 Liabilities related to the sales of future royalties, net 46,731 41,988 Warrant liabilities 9,121 — Total liabilities 62,219 49,930 Total stockholders’ deficit (28,285) (15,912) Source: Clearside Biomedical, Inc.