Core Insights - Clearside Biomedical is showcasing its SCS Microinjector platform and CLS-AX program at the 25th EURETINA Congress, highlighting its potential for treating multiple retinal diseases [1][3] Group 1: SCS Microinjector Platform - The SCS delivery platform is designed for targeted treatment of retinal diseases such as wet AMD, diabetic retinopathy, and ocular cancer [2] - The SCS Microinjector allows for the delivery of various drug candidates into the suprachoroidal space, aiming to improve efficacy and reduce toxic effects on non-diseased cells [8][9] Group 2: CLS-AX Program - CLS-AX is a proprietary suspension of axitinib for suprachoroidal injection, which may offer advantages over existing retinal therapies by achieving pan-VEGF blockade [6][7] - The program includes a Phase 3 trial for wet AMD and a streamlined Phase 2 trial for non-proliferative diabetic retinopathy [3] Group 3: Upcoming Presentations - Dr. Sobha Sivaprasad will present Phase 2b results from the ODYSSEY trial and updates on the Phase 3 program for neovascular age-related macular degeneration [4] - Victor Chong will discuss the evolution of suprachoroidal drug delivery and participate in a panel at the Ophthalmology Futures Retina Forum [5]

Summary of Clearside Biomedical Conference Call Company Overview - Clearside Biomedical focuses on delivering therapeutic agents to the suprachoroidal space, pioneering a proprietary injection procedure and device for this purpose [4][5] - Established partnerships with Oral Biosciences and REGENXBIO for developing treatments for choroidal melanoma and retinal diseases [5][6] - Commercialization partnerships with Bausch and Lomb and Arctic Vision for their FDA-approved product XIPERE, which delivers triamcinolone to the suprachoroidal space [6] Core Product and Development - XIPERE has shown better performance in terms of duration and effect than predicted by pharmacokinetic models, leading to increased acceptance among physicians [10][14] - Development of CLS AX (axitinib) for wet AMD, with successful completion of phase 2b ODICEY trial, positioning it as a phase 3 ready product [7][8] - The product aims for flexible dosing with a duration comparable to biologics, targeting a market need for variability in patient responses [16][26] Competitive Landscape - CLS AX is positioned against current TKI competitors that offer a six-month duration, with Clearside aiming for a three to six-month duration to accommodate patient variability [15][21] - The company believes its product has a better efficacy profile due to a lower IC50 and a more favorable redosing criteria compared to competitors [19][20] - Emphasis on the absence of ocular serious adverse events (SAEs) in their trials, which contrasts with some competitors [20] Regulatory Strategy - The phase 3 trial is designed to last two years, with a primary endpoint at 52 weeks, allowing for two cycles of treatment [31][32] - The trial design aims to minimize variability by excluding patients with high variability in results, which has been accepted by regulatory agencies [39][42] - The company is focused on a non-inferiority design with good masking to mitigate regulatory risks associated with treatment failures [48][49] Funding and Future Plans - Ongoing outreach to strategic partners and potential investors to fund the advancement of CLS AX into phase 3 trials [50] - The company is exploring various funding options, including combinations of investors and strategic partnerships [50] Additional Insights - The acceptance of suprachoroidal injections is increasing, with over 15,000 injections performed and more than 100 peer-reviewed publications supporting the procedure [14] - The company believes that the flexibility in dosing frequency will be appealing to physicians and align with real-world clinical practices [44][45]

Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash and cash equivalents totaled approximately $20 million, which is expected to fund operations into the fourth quarter of 2025 [38]. Business Line Data and Key Metrics Changes - The company reported positive results from the Odyssey Phase IIb WET-AMD clinical trial, leading to a successful end-of-Phase II meeting with the FDA regarding the planned Phase III activities for CLSAX [8]. - CLSAX is positioned as a leading maintenance treatment for WET-AMD, with plans to enroll treatment-naive patients to potentially expand its commercial value [21][30]. Market Data and Key Metrics Changes - The wet AMD market represents over $12 billion in annual sales, and the company believes that CLSAX's flexible dosing regimen will provide a competitive advantage [32]. Company Strategy and Development Direction - The company is focused on advancing its small molecule superchoroidal pipeline led by CLSAX for the treatment of wet AMD, with increasing interest from retinal specialists and pharmaceutical companies [40]. - The Phase III trial design aims to reduce variability and maximize commercial potential by targeting treatment-naive patients and employing flexible dosing intervals [21][30]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the Phase III program's design and its potential to demonstrate the efficacy of CLSAX, with expectations of minimal to no anti-VEGF rescue needed during the trial [30]. - The company is actively pursuing options to fund the CLSAX Phase III program, including potential partnerships [38]. Other Important Information - The company has made significant progress with its partners in validating the applicability of superchoroidal delivery for various indications, with ongoing or planned Phase III trials in multiple territories [9][10]. Q&A Session Summary Question: How might the amendments to the Phase 3 plan improve results from Phase 2? - Management believes that excluding patients with higher variability will lead to better results in the general population, as those who did not require extra treatment performed well [47][48]. Question: How long is expected to enroll the treatment-naive population? - Enrollment is expected to take around 12 months, based on recent trials [51]. Question: What is the estimated overall cost of the Phase III program? - While specific costs were not disclosed, similar Phase III trials have been around $55 million to $60 million each [58]. Question: What are the powering assumptions in the Phase III trial? - The powering assumptions are based on a 14-letter variability, similar to other studies, with a 4.5% letter margin as suggested by the agency [94]. Question: Can you elaborate on redosing criteria and physician discretion? - Redosing criteria will rely on OCT biomarkers, with a focus on intra-retinal fluid, while rescue criteria will be based on vision loss and worsening anatomy [100][103].

Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash and cash equivalents totaled approximately $20 million, which is expected to fund operations into the fourth quarter of 2025 [27] - The company is actively pursuing options to fund the CLSAX Phase III program, including potential partnerships with third parties [27] Business Line Data and Key Metrics Changes - The SES microinjector has been used for over 15,000 suprachoroidal injections, indicating strong interest from retinal specialists and pharmaceutical companies [6] - Positive results from the Odysee Phase 2b clinical trial have led to a successful end of Phase II meeting with the FDA regarding CLSAX [6][7] Market Data and Key Metrics Changes - The wet AMD market represents over $12 billion in annual sales, highlighting the commercial potential for CLSAX [22] - The company’s partner Arctic Vision has achieved several regulatory milestones in the Asia Pacific region, with products approved in Australia and Singapore [9] Company Strategy and Development Direction - The company aims to position CLSAX as a leading maintenance treatment for wet AMD, focusing on reducing variability in clinical trial outcomes [11][21] - The Phase III trial design includes two pivotal non-inferiority trials, which are expected to maximize commercial opportunities and reduce regulatory risks [14][22] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the Phase III program's design and its potential to demonstrate the drug's efficacy and safety [39][40] - The company is optimistic about the broad applicability of suprachoroidal delivery in treating serious retinal diseases, with ongoing evaluations for additional small molecule treatments [23][25] Other Important Information - The company is preparing for participation in upcoming healthcare conferences to further engage with stakeholders [27] - The management team emphasized the importance of flexible dosing regimens in the competitive landscape of wet AMD treatments [22] Q&A Session Summary Question: How might the amendments to the planned Phase III improve results from Phase II? - Management believes that moving to a more general patient population will yield better results, as the previous Phase II focused on difficult-to-treat patients [35] Question: How long is expected to enroll the treatment-naive population? - Enrollment is expected to take around twelve months, based on recent trials [38] Question: What is the estimated overall cost of the Phase III program? - While specific costs were not disclosed, similar Phase III trials have been estimated around $55 million to $60 million [46] Question: What is the financing strategy for the Phase III study? - The company is pursuing options to fund the clinical part of the study, including potential partnerships [52] Question: Can you elaborate on the redosing criteria? - Redosing will rely on OCT biomarkers, with a focus on intra-retinal fluid, and will be scientifically justified to reduce variability [75][76]