Financial Data and Key Metrics Changes - For the quarter ended September 30, 2025, total net revenue was $1 million compared to $10.5 million for the same quarter in 2024, primarily due to the recognition of deferred revenue related to a prior year agreement [16] - Operating expenses for the quarter totaled $63 million, an increase from $43.3 million in the prior year, driven by clinical trial costs for ongoing phase three trials [17] - The net loss was $59.7 million, or $0.85 per share, compared to a net loss of $29.4 million, or $0.54 per share, in the prior year [17][18] - Cash and investments totaled $204 million as of September 30, 2025, down from $371 million as of December 31, 2024, but expected to fund operations into Q4 2027 [18] Business Line Data and Key Metrics Changes - Duraview is positioned to be the first to file and first to market among investigational sustained delivery programs for wet AMD and DME, with top-line data expected in mid-2026 [5][6] - Enrollment for the Lucia trial, a phase three trial for Duraview in wet AMD, was completed in July, with over 900 patients recruited across two trials [6] - The phase three DME program is set to begin with first patient dosing expected in Q1 2026, leveraging existing clinical trial infrastructure [11] Market Data and Key Metrics Changes - The global market for wet AMD and DME is currently valued at $10 billion and is expected to grow, dominated by monotherapy anti-VEGF biologics [8] - Current treatment options lead to a high burden of frequent injections, with many patients remaining undertreated [8][9] Company Strategy and Development Direction - The company aims to deliver innovation in wet AMD and DME through Duraview, a sustained-release TKI designed to improve treatment efficacy and reduce patient burden [9][10] - The manufacturing capability is being enhanced to support commercialization, with a GMP-compliant facility already producing registration batches [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the differentiated clinical profile of Duraview and its potential to transform treatment paradigms in retinal diseases [5] - The company is well-capitalized to deliver phase three data in 2026 and advance its DME program [19] Other Important Information - The company completed a $172 million follow-on offering in October, enhancing its cash position [7][16] - Recent preclinical data showed Duraview's active ingredient, virolanib, inhibits both VEGF-mediated vascular permeability and IL-6-mediated inflammation, supporting its multi-mechanism of action [7][12] Q&A Session Summary Question: Market sizing for wet AMD population in the U.S. - Approximately 20% of wet AMD patients require monthly treatment, with 50% unable to extend beyond eight weeks even with newer agents [21][22] Question: Enrollment criteria for DME program - The DME program will enroll both treatment-naive and previously treated patients, using aflibercept as a control [25] Question: Use of blended endpoint in trials - The blended endpoint is used to reduce missing data and capture recovery in vision, which is common in clinical trials for wet AMD [27][29] Question: Differentiation in IL-6 inhibition - IL-6 plays a significant role in DME, and blocking both VEGF and IL-6 pathways could lead to improved outcomes compared to anti-VEGF-only approaches [31][34] Question: Statistical analysis plan for superiority testing - The analysis plan allows for testing superiority if non-inferiority is met, which could position Duraview as a premium medication [36][37]

Financial Data and Key Metrics Changes - For Q4 2024, total net revenue was $11.6 million, down from $14 million in Q4 2023. Net product revenue was $0.8 million compared to $0.7 million in the same period last year [33][34] - For the full year 2024, total net revenue was $43.3 million, down from $46 million in 2023. Net product revenue for 2024 was $3.2 million, significantly lower than $14.2 million in 2023 due to the sale of YUTIQ product rights [36][37] - Operating expenses for Q4 2024 totaled $56.8 million, up from $30.4 million in the prior year, primarily due to ongoing Phase 3 trials for DURAVYU [35] - The net loss for Q4 2024 was $41.4 million or $0.64 per share, compared to a net loss of $14.1 million or $0.33 per share in Q4 2023 [36] - The company ended 2024 with $371 million in cash and investments, up from $331 million at the end of 2023, and expects this will fund operations into 2027 and beyond [39] Business Line Data and Key Metrics Changes - The company is focusing on the DURAVYU program, with net product revenue expected to remain at immaterial levels as YUTIQ supply to ANI Pharmaceuticals will cease by May 31, 2025 [33][34] - Net revenue from royalties and collaborations for Q4 2024 was $10.8 million, down from $13.3 million in Q4 2023, primarily due to lower recognition of deferred revenue from YUTIQ [34] Market Data and Key Metrics Changes - DURAVYU is positioned as a leader in ocular sustained drug delivery, with ongoing Phase 3 trials in wet AMD and positive Phase 2 results in DME [11][12] - Enrollment in the LUGANO and Lucia trials for wet AMD is exceeding expectations, with completion anticipated in the second half of 2025 [13][28] Company Strategy and Development Direction - The company aims to be the first to submit a new drug application for a six-month intravitreal wet AMD program, which could capture significant market share [14][27] - The strategic focus is on advancing DURAVYU through clinical trials and preparing for commercial launch, with a strong emphasis on patient-centric trial design [15][30] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical trials and the potential for DURAVYU to transform treatment for retinal diseases, highlighting the strong safety and efficacy data [10][30] - The company plans to engage with regulatory agencies regarding the pivotal trial design for DME, with a meeting expected in the second quarter of 2025 [26][89] Other Important Information - The Northbridge manufacturing facility is operational and ready for registration batch manufacturing to support NDA filing [100][102] - The company has a solid patent protection strategy for DURAVYU, enhancing its competitive position in the market [22] Q&A Session Summary Question: How many clinical sites have been activated for the wet AMD pivotal program? - Most sites are activated in the U.S., with approximately 60 active sites per study. Plans include 60 to 80 sites for ex-U.S. studies [46][51] Question: Can you comment on the subgroup analysis of the 2.7% milligram versus aflibercept? - The analysis shows a strong dose response, with the 2.7% dose demonstrating significant improvements in visual acuity and fluid control compared to the control group [54][56] Question: What is the current status of the razuprotafib program? - Razuprotafib is on a lower priority but continues with preclinical activities. The focus remains on wet AMD execution [130] Question: What are the plans for post-marketing studies for DURAVYU? - Plans include studies comparing DURAVYU against current industry leaders, focusing on supplement-free rates and long-term efficacy [78][81] Question: What is the expected cash runway guidance? - The cash guidance extends into 2027, covering ongoing work for DURAVYU and wet AMD, but does not include the DME study itself [129]