Ocular Therapeutix, Inc.

Dr. Question and Answer session. To ask a question, please press star one. As a reminder, this conference call is being recorded and will be available for replay on the Investor Relations section of the Ocular Therapeutics website. I would now like to turn the call over to Ocular's Vice President of Investor Relations, Bill Slattery, Jr. Please go ahead, Mr. Slattery.

Good morning, everyone, and thank you for joining us today. Earlier this morning, we issued a press release outlining our financial results and business updates for the third quarter 2024. Mindful of everyone's time, Ocular's Executive Chairman, President, and CEO, Dr. Praveen Dougal, will briefly provide a summary of recent business highlights so we can quickly get to your questions. Joining Dr. Dougal for the Q&A portion of the call will be Donald Notman, Chief Financial Officer and Chief Operating Officer Sanjay Nayak, Chief Strategy Officer, and Steve Myers, Chief Commercial Officer. We refer everyone to this morning's press release and our Form 10-Q for a comprehensive update of third quarter financial and business results. During today's call, certain statements we will be making constitute forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially as a result of a variety of factors, including risks and uncertainties identified in the risk factors section of our annual report on Form 10-K and our other SEC filings. With that, I'd like to hand the call over to Dr. Praveen Dougal to review our recent updates.

Praveen? Thank you, Bill, and thank you to everyone for joining us today. When I joined Ocular, our number one priority was bringing Xpaxly to market for wet age-related macular degeneration. Wet AMD affects about 1.65 million people in the United States, which translates to approximately one in every 160 adults. That means many of us are likely to know someone who is affected by this disease. And it reminds us that this market is large, and underserved, with up to 40% of patients discontinuing treatment within the first year alone. Just before AAO in mid-October, we reported that recruitment has progressed rapidly for SOLE1, allowing us to project full randomization by year-end 2024, which is well ahead of our prior guidance. We are thrilled to share that following this outstanding SOL1 recruitment success, our active study sites can now enroll new patients directly into SOL-R, our second registrational trial for ex-paxley in wet AMD. Let me repeat, SOL1 has reached a key enrollment milestone and we have turned the switch allowing clinical sites to directly enroll patients into SOLAR. This is a significant milestone, and we expect this adjustment to further accelerate the pace of SOLAR enrollment. As we reflect on the start of this year, there were widespread concerns that enrolling SOL1 would be challenging. The consensus was that The trial's unique superiority design, which we believe is directly in line with the FDA's draft guidance and validated with a special protocol agreement would lead to significant recruitment hurdles. In fact, some investors projected it would take us as long as 18 months to two years to complete randomization. In response, We assembled a world-class team who went beyond simply activating clinical trial sites. The team leaned on decades of experience and relationships to actively engage and communicate with the retina community in a way that resonated deeply. This extraordinary level of engagement sparked a remarkable level of enthusiasm and commitment from investigators and study coordinators for both our sole studies. Our approach has transformed what was expected to be a difficult enrollment process into one marked by rapid and enthusiastic participation. Accelerating the enrollment timelines for SOLE 1 has positioned us for an impactful year in 2025, setting the stage for a significant milestone with clinical data expected in the fourth quarter. By reaching enrollment targets ahead of schedule, we are advancing more rapidly toward the top line data that will provide pivotal insights into Xpaxley's potential in treating wet AMD. This acceleration brings us one step closer to potentially delivering a much needed therapeutic option to patients who deserve a more sustainable treatment and better long-term outcomes. But enrolling SOL1 is just the beginning. SOL1 is the first of two registrational studies for Xpaxly and wet AMD. Our second registrational trial, SOLAR, is a repeat dosing non-inferiority study. These two studies were meticulously crafted to work in harmony strategically designed to enhance each other's enrollment while providing a broad evaluation of Xpaxley's durability, repeatability, and flexibility. Goal one focuses on highlighting Xpaxley's durability. The goal here is to establish superiority in durability over two milligram Aflibrocept. SOLAR, on the other hand, is a more familiar repeat dosing non-inferiority trial that is designed to ensure our findings are robust and applicable in real-world settings. Both studies were thoughtfully aligned with regulatory guidance. SOLAR 1 supported by a special protocol agreement and SOLAR supported by a type C written response from the FDA earlier this year. Importantly, neither of these trials require sham for masking. The FDA has repeatedly stated, including most recently on a podium at AAO, that they do not recommend sham for masking because sham can elicit bias. In addition to taking important steps to reduce our regulatory risk, we've focused just as much attention on taking steps to de-risk the clinical outcomes and reduce variability between subjects. In SOL1, we are administering two loading doses of the Fliverset and require subjects to gain at least 10 ETDRS letters in BCVA or to reach approximately 20-20 vision prior to randomization. This ensures that we are only selecting subjects that have been responsive to anti-VEGF therapy and allows us to focus on durability of each treatment arm. Meanwhile, in SOLAR, we've gone a step further by incorporating five loading doses and two observation periods to carefully screen out subjects who are highly VEGF dependent. This approach emphasizes patient stability. Again, here we are continuing to focus on reducing risk by taking action to ensure that the enrolled patient population is as homogeneous as reasonably possible. By building in these measures, we're reducing variability, enhancing patient selection, and we believe strengthening the potential for successful clinical trial outcomes. From the onset, we also designed SOL1 and SOLAR to complement each other and boost recruitment for both studies. Initially, all subjects enrolling in SOLAR were required to be loading or randomization failures in SOL1. This approach ensured that SOLAR, which is widely seen as the more attractive trial for physicians to enroll their patients in, did not cannibalize enrollment in SOL1. As I shared at the outset of my comments, today we're announcing that SOL1 has reached a key enrollment milestone, and our trial sites are now enrolling subjects directly into SOLAR. We expect this important update will lead to further acceleration in SOLAR enrollment, which is already well underway. As SOL1 very quickly approaches complete randomization, subjects who are not ultimately randomized can seamlessly transition into SOLAR. This coordinated approach allowed us to avoid the typical slowdown seen toward the end of trial enrollment, creating a streamlined and efficient pathway that capitalizes on recruitment momentum at our clinical sites. We believe that this will provide us with a tremendous advantage as we continue to strengthen our deep history and strong relationships with our clinical trial sites. heading into 2025. The bottom line is that we've seen outstanding demand for participation in our expaxily clinical studies, underscoring the strong enthusiasm and interest within the retina community for a durable treatment option. This level of demand is particularly encouraging as it signals the excitement for Expaxly among both patients and physicians. Based on our historical clinical data generated for Expaxly, combined with actions we have taken to de-risk our SOL studies, we remain confident in the potential success of both SOL1 and SOLR. To date, Expaxly is the only TKI we are aware of to show proof of concept for monotherapy activity in treatment-naive wet AMD patients. To take that a step further, if you look at our prior U.S. wet AMD study, treatment with Xpaxly alone resulted in an impressive 100% ERP protocol rescue free rate at six months. And that was in a trial where no steps were taken to de-risk the patient population or trial design. We believe Xpaxly is the only TKI to show clear signals of efficacy in subjects with non-proliferative diabetic retinopathy, or NPDR. In our Helios trial, the administration of a single Xpaxly hydrogel, literally zero subjects were observed to have developed any vision-threatening complications at 48 weeks, compared to 38% of subjects in the sham control arm, which is in line with natural history data. In other words, not a single patient after just one injection of Axpaxli developed a potentially blinding complication at 48 weeks. Moreover, every subject in the Axpaxli arm with non-center-involved diabetic macular edema experienced disease improvement. It cannot be overstated. These types of results do not occur by accident. We believe the results from SOL1 and SOL-R may set a new standard, emphasizing the strengths of our data and underscoring our advantages in the competitive landscape. As such, it is imperative that we be prepared for a strong commercial launch. should Xpaxly be approved. If clinical demand is a proxy for commercial interest, and we believe it is, then we should plan for strong commercial interest in Xpaxly, potentially ushering in a new era of wet AMD treatment. We benefit greatly from having a remarkable commercial team that is currently achieving excellent results with Dextenza. the first and only drug-eluting intracanalicular insert. Xtensa utilizes the same elutex technology that is used in Xpaxly, and its performance strengthens our market presence and provides a strategic edge that we're committed to maintaining. We have taken several steps over the past few months to build on our existing commercial infrastructure to support the eventual manufacture and distribution of Xpaxly to retina specialists. And we plan to further expand these efforts in 2025. As we continue to execute, our commitment to the investment community is to maintain financial discipline. Based on our current operating plans, we believe our cash and cash equivalents of approximately $427 million on hand at the end of the third quarter provides runway into 2028 and fully funds Sol1 and Solar, the top line results. As we conclude the prepared remarks in today's call, I'd like to leave you with these key messages. Our mission at Ocular is clear. We are dedicated to becoming a leader in the treatment of retinal disease and improving vision in the real world. We are making outstanding progress on the two complementary studies in our registrational program for Xpaxley in wet AMD, Sol1 and SolR. Sol1 has reached a key enrollment milestone and we expect to complete SOL1 randomization by year end with top line data to follow in the fourth quarter of 2025. SOLAR enrollment continues to gain momentum and physicians can now enroll their patients directly into this clinical trial. In type C written responses received this year, the FDA has agreed that the design of these two studies should be sufficient to meet our regulatory requirements. And we believe positive data from these studies will enable us to achieve a differentiated product label, provide commercially relevant data, and meet the real-world need for a sustainable treatment option that improves long-term outcomes for patients with wet AMD. 2024 has been a year of significant change and tremendous execution at Ocular. But this is all in anticipation of what's ahead as we prepare for what we expect will be a milestone year in 2025. We thank you for your ongoing encouragement and support for ocular therapeutics. Operator, I would now like to open the call for questions.