Summary of Surrozen Conference Call Company Overview - **Company**: Surrozen - **Founded**: 2016 - **Focus**: Wnt biology and its therapeutic applications, particularly in ophthalmology [3][4] Industry Context - **Therapeutic Area**: Ophthalmology, specifically targeting retinal diseases such as diabetic macular edema (DME) and age-related macular degeneration (AMD) [4][16] - **Key Competitors**: Merck and Roche, both involved in Wnt biology and retinal disease treatments [9][16] Core Insights and Arguments - **Wnt Pathway**: - Critical for tissue regeneration, stem cell renewal, and response to injury [3][4] - Activation of the Wnt pathway has shown significant clinical benefits, comparable to VEGF inhibition [4][5] - Surrozen's approach involves multispecific antibodies that activate Wnt while inhibiting other pathways like VEGF and IL-6 [5][19] - **Clinical Proof of Concept**: - Merck's acquisition of a competitor's molecule demonstrated compelling clinical proof of concept in diabetic macular edema [4][5] - Surrozen's preclinical models show that their approach can normalize retinal vessels and prevent leakage, which is a significant advancement over existing therapies [9][10][12] - **Safety and Efficacy**: - Current Wnt agonists, such as Amgen's Evenity, have shown to be safe, with no notable safety issues reported in clinical trials [8] - Surrozen aims to leverage intravitreal injections to minimize systemic liabilities [8] - **Differentiation from Competitors**: - Surrozen's molecule 8141 combines Wnt activation with VEGF inhibition, showing greater potency than Merck's RESTRA molecule [18][19] - The company is also developing a trifunctional molecule (8143) that targets Wnt, VEGF, and IL-6 [26] Development Pipeline - **Current Assets**: - 8141: Expected IND filing in 2026, combining Wnt activation and VEGF inhibition [29] - 8143: Trifunctional molecule in development, behind 8141 in the pipeline [28][29] - **Clinical Strategy**: - Plans to target both DME and wet AMD in upcoming studies, with a focus on treatment-naive patients for clearer data interpretation [30][32] Financial Position - **Funding**: - Completed a $175 million PIPE financing, with the first tranche of $75 million supporting operations post-IND clearance [48] - The second tranche of $100 million will provide a cushion for data reporting from phase one studies [48] Intellectual Property - **Patents**: - Surrozen holds a broad patent for multivalent antibodies targeting Frizzled LRP5 or 6, which could infringe on competitors like Merck and Roche [47] Market Expectations - **Upcoming Data**: - Anticipation for results from Merck's studies (Brunello and Barolo) in Q3 next year, which may influence the Wnt biology space [50][52] Additional Considerations - **Expertise in Wnt Biology**: - Surrozen emphasizes its scientific credibility, founded by leading scientists in Wnt biology, to educate the market on the pathway's role in retinal health [41][42] - **Clinical Feedback**: - Retinal specialists express a need for improved retinal drying and visual acuity benefits, which Surrozen aims to address through its innovative mechanisms [41][42]

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 - The company ended Q3 2025 with approximately $345 million in cash, not including about $445 million in net proceeds from an October equity financing [26] - The company has an expected cash runway into 2028, providing financial flexibility for ongoing clinical programs and potential commercialization [27] Business Line Data and Key Metrics Changes - The registrational programs for XPAXLY in Wet AMD and diabetic retinopathy are progressing well, with SOL1 on track for top-line data in Q1 2026 and SOLar reaching its target randomization of 555 subjects [28][29] - The SOL1 trial has over 95% patient retention, indicating strong engagement and compliance [15] Market Data and Key Metrics Changes - The global annual anti-VEGF market is estimated at approximately $15 billion, with significant opportunities for expansion due to high treatment discontinuation rates in Wet AMD and low treatment rates in diabetic retinopathy [9][10] - The company aims to capture a larger addressable market by reducing treatment burden and improving adherence, potentially reaching millions of untreated patients [11][28] Company Strategy and Development Direction - The company is focused on achieving a superiority label for XPAXLY, which could differentiate it from existing anti-VEGF therapies and insulate it from pricing pressures [7][8] - The strategy includes a triad approach: potential superiority, market expansion, and immediate adoptability, aiming to redefine the retina treatment landscape [27][28] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical strategy and market potential for XPAXLY, reinforced by positive feedback from payers and investors [26][27] - The company is committed to delivering long-lasting, clinically impactful therapies for retinal diseases, with a focus on early treatment to improve long-term outcomes [5][19] Other Important Information - The Helios program for diabetic retinopathy aims to pursue a broad label that encompasses both NPDR and DME, addressing a significant unmet need in the market [20][25] - The company has engaged with payers representing a large portion of U.S. commercial lives, receiving positive feedback on the potential of XPAXLY [14] Q&A Session Summary Question: What will the initial label for Wet AMD look like? - Management expects a superiority label based on SOL1, with flexibility for dosing intervals and repeat dosing [33][34] Question: What percentage of enrolled patients in Helios trials will have non-center-involved DME? - Management indicated confidence in achieving a broad label that includes all diabetic eye diseases based on previous study data [36][39] Question: What is the progress of NPDR studies? - Management confirmed that the process for NPDR studies began immediately after the recent financing, leveraging existing site relationships for efficient enrollment [56][59] Question: Are there risks associated with the ordinal two-step DRSS endpoint? - Management expressed great confidence in the ordinal endpoint, citing strong data from previous studies to support its validity [61][63] Question: How long will it take to complete enrollment for Helios 2? - Management believes there will be no issues in completing the trials efficiently due to high demand and enthusiasm from both patients and investigators [66]

Financial Data and Key Metrics Changes - The company ended Q3 2025 with approximately $345 million in cash, not including around $445 million in net proceeds from an October equity financing [25] - The financial strength provides the company with a cash runway into 2028, allowing for flexibility in pursuing clinical programs and preparing for commercialization [26] Business Line Data and Key Metrics Changes - The registrational programs for XPAXLY in Wet AMD and diabetic retinopathy are progressing well, with SOL1 on track for top-line data in Q1 2026 and SOLAR reaching its target randomization of 555 subjects [27][28] - The Helios program for diabetic retinopathy is designed to capture a broad label, addressing both NPDR and DME, with a focus on early treatment to prevent disease progression [19][24] Market Data and Key Metrics Changes - The global annual anti-VEGF market is estimated at approximately $15 billion, with significant opportunities for expansion as many patients remain untreated [8] - In Wet AMD, up to 40% of patients discontinue therapy within the first year, highlighting a substantial market opportunity for XPAXLY to improve adherence and reduce treatment burden [9] Company Strategy and Development Direction - The company aims to redefine the retina experience through a strategic triad: potential superiority label, market expansion, and immediate adoptability of XPAXLY [5][27] - The focus is on achieving a superiority label that distinguishes XPAXLY from existing anti-VEGF therapies, potentially insulating it from pricing pressures and enhancing market dynamics [6][7] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical strategy and market potential of XPAXLY, reinforced by positive feedback from payers and investors [25][26] - The company is committed to delivering long-lasting, clinically impactful therapies for retinal diseases, with a focus on reducing treatment burden and improving patient outcomes [4][12] Other Important Information - The company has engaged with payers representing over 75% of U.S. commercial lives, receiving positive feedback on the potential of XPAXLY to deliver meaningful clinical differentiation [13] - The SOL1 trial has achieved over 95% patient retention, indicating strong engagement and compliance within the study [14] Q&A Session Summary Question: How is the initial label for Wet AMD expected to look? - Management anticipates a superiority label based on SOL1, with flexibility for dosing intervals and repeat dosing [32][33] Question: What percentage of enrolled patients in Helios trials will have non-center-involved DME? - Management indicated that they do not have specific percentages yet but expressed confidence in obtaining a broad label that includes all diabetic eye disease [35][38] Question: What is the progress of the SOLar study? - Management reported that SOLar has reached its target randomization of 555 patients, with a focus on thoughtful patient selection to ensure stability [40][43] Question: What details will be shared in the SOL1 top line? - Management stated that the primary goal of SOL1 is to achieve a superiority label, and they will provide data that supports confidence in the success of SOLar [47][49] Question: How will the NPDR studies be accelerated? - Management noted that they are leveraging existing site relationships and expertise to ensure efficient enrollment and execution of the NPDR studies [51][52] Question: Are there risks associated with the ordinal two-step DRSS endpoint? - Management expressed great confidence in the ordinal endpoint, citing strong data from previous studies to support its validity [57][59]