Clearside Biomedical, Inc.

Good day, and thank you for standing by. Welcome to the ClearSide Biomedical fourth quarter 2022 financial results and corporate update conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Jenny Coleman, Investor Relations. Please go ahead.

Good afternoon, everyone, and thank you for joining us on the call today. Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements, various remarks that we make during this call, and about the company's future expectations, plans, and prospects today. constitute forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our annual report on Form 10-K for the year ended December 31st, 2021, our quarterly report on Form 10-Q for the quarter ended September 30, 2022, and our other SEC filings available on our website. We expect that our 10-K for the year ended December 31, 2022 will be filed tomorrow. In addition, any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change. On today's call, we have George Blazeski, our Chief Executive Officer, and Charlie Degnan, our Chief Financial Officer. After formal remarks, we will open the call for your questions. I would now like to turn the call over to George.

Thank you, Jenny. Over the past year, we have reinforced ClearSight's leadership position in the delivery of therapeutics into the supracoroidal space. We've successfully executed on our strategic plans with the launch and commercialization of the first FDA-approved supracoroidal product, Zypyr, by our partner, Bausch & Lomb. And we completed and announced positive data from our Phase I-IIa OASIS trial of CLSA-X in wet AMD. We have also seen promising data presented by partners utilizing our proprietary STS microinjector to administer gene therapy and oncology agents to treat a variety of retinal diseases. On today's call, I will cover key highlights from the past year and provide a snapshot of our plans for 2023. I will begin with our development programs, both internal and with our partners. Last month, we reported exciting data from our lead internal program, CLSAX, that combines our proprietary small molecule suspension of Excedinib with delivery by our SCS microinjector. Excedinib is a highly potent tyrosine kinase inhibitor, or TKI, that achieves pan-VEGF blockade, directly inhibiting VEGF receptors 1, 2, and 3 with high potency and specificity. We believe this broad VEGF blockade may have advantages over existing retinal therapies by acting at a different level of the angiogenesis cascade. We reported positive data from OASIS, our open-label Phase I-IIa trial in wet AMD. The trial consisted of four cohorts with escalating doses that monitored participants for three months. This was followed by a three-month extension study in the higher-dose cohorts. for a total of six-month follow-up. Participants enrolled in OASIS were heavily anti-VEGF treatment experienced patients with active disease at screening, which was confirmed by an independent reading center. In OASIS, we assessed three components. Primary endpoint evaluated safety and tolerability of CLS-AX, and we also looked at durability and biological effect. First, safety. We were very pleased with the safety results we saw with CLSA-X. In all participants in the trial, CLSA-X was well tolerated and demonstrated an excellent safety profile. There were no adverse effects, no dose-limiting toxicities, and because we are injecting behind the retina, we did not have any instances of vitreous floaters or dispersion of drug into the vitreous. We anticipated this favorable safety profile as Excedinib is a well-characterized small molecule with less propensity for inflammation compared to a biological agent or gene therapy. In addition, the safety of the suprachoroidal injection procedure with our SCS microinjector has already been assessed through the approval of Zypyr. Second, durability. OASIS demonstrated that two-thirds of patients may be able to go at least six months without additional treatment, which is a really important element for patients and caregivers managing this disease. For those participants in the extension study that received higher doses in cohorts three and four, 67% went at least six months without additional treatment, and 50% of participants went beyond six months. This translates to a 77% to 85% reduction in treatment burden. That's calculated by comparing the number of monthly injections participants had six months before CLSAX to the monthly injections they received after CLSAX. We believe that reduction in treatment burden is the current unmet medical need in the wet AMD space. Finally, biological effect. In OASIS, our six-month data was encouraging as we observed anatomic signs of biological effect on the OCT scans. We also saw stable mean best corrected visual acuity and stable mean central subretinal thickness in the extension study participants. These strong results in all three areas are supportive of excedinib's potency and panVEGF blockade. Furthermore, delivery via our SCS microinjector into the suprachoroidal space specifically targets the affected choreoretinal tissues for potential efficacy benefits and compartmentalizes drugs away from the front of the eye for potential safety benefits. OASIS reinforces our belief that CLSAX has the potential to reduce treatment burden in patients with wet AMD while maintaining stable visual acuity. gives us confidence as we advance into our next clinical trial. Given this favorable OASIS data, we intend to conduct a randomized, controlled, double-masked Phase IIb clinical trial called Odyssey with CLS-AX and wet AMD participants. On February 24th, the FDA issued draft guidance for the industry on developing drugs for the treatment of wet AMD. In this guidance, they recommend that all trials for this disease should use either Aflibirzeb or Ranivizumab in the comparator arm. We spoke with the agency regarding its development of the draft guidance and to clarify our understanding of the recommendations. We were fully prepared and ready to open enrollment this quarter in Odyssey based on our planned trial design. However, Based on our discussion with the agency and in response to this new guidance, we have adjusted the Odyssey trial design to use on-label Aflibirseb dosing in the comparator arm. As part of our planning process, we had considered and evaluated various clinical trial scenarios, including using Aflibirseb as a comparator. As a result, we are able to smoothly and seamlessly transition to an adjusted Odyssey trial design utilizing Aflibirseb. We anticipate this changeover will take a relatively short period of time to complete as we make the necessary paperwork and operational adjustments with our clinical research organization partners. We now plan to open the trial for enrollment next quarter and currently expect data in the second half of next year. Our clinical team is led by our Chief Clinical Officer, Dr. Susan Koltis, who joined us last year as a member of the leadership team with overall operational responsibility for conduct and execution of our clinical trials. She has substantial prior experience in advancing ophthalmic therapies from the early clinical development stages through final approval for commercialization, which is an important and valuable asset for us at this stage. We've had a smooth handoff related to our clinical operations as Dr. Tom Chula has transitioned to the role of Chief Medical Advisor, Retina, and chair of our Scientific Advisory Board. We are pleased that Tom continues to provide his expert advice and counsel on ClearSight's supercorroital development programs, including the ODYSSEY Phase IIb trial. I would also like to highlight the progress being made with Zypyr, ClearSight's first FDA-approved product and the first commercial product used using the supercorroital delivery. Zypyr was launched in the United States almost a year ago by our commercialization partner, Bausch & Lomb. They've done excellent work getting the drug into the hands of physicians, and they continue to expand outreach and training to healthcare providers. We estimate that over 1,000 retinal physicians have been trained to date in the use of the SES microinjector. In addition, Bausch & Lomb recently filed for Zypyr regulatory approval in Canada. so we're looking forward to market expansion in that additional territory. Our Asia-Pacific commercial partner for Zypyr is Arctic Vision, a leading China-based ophthalmic company. Arctic Vision is currently enrolling a confirmatory Phase III trial in macular edema associated with uveitis, and Arctic Vision just completed a Phase I clinical trial for the treatment of diabetic macular edema. Data from this trial is expected to be made public in the near future. and we look forward to their progress in these programs and future data readouts. As part of our corporate strategy, we value partnerships to expand the benefits of supracoital delivery utilizing our STS microinjector outside our core areas of expertise. Our current STS microinjector partners are focused on ocular oncology and gene therapy. Our oncology partner, Oral Biosciences, is utilizing our SES microinjector to deliver their viral-like drug conjugate, Belsar, for the treatment of choroidal melanoma, a serious disease that is the most common intraocular tumor in adults with no approved therapies. At the Macular Society annual meeting last month, ORA presented positive interim efficacy data from their ongoing Phase II study. The data presented showed very favorable safety profile along with an excellent response to the therapy with 89 to 100% tumor control. Based on their promising data, Aura announced final plans for its global phase three trial utilizing the suprachoroidal route of administration. They expect to begin enrollment in that trial this year. Our gene therapy partner, Regenexx Bio, continues to advance two Phase II clinical trials with their asset, RGX314, delivered superchoroidally with our SCS microinjector. These programs are being developed in collaboration with AbbVie. Recently, Regenexx Bio announced cohort expansions in both the AV8 and altitude superchoroidal clinical trials. The ABA clinical trial in wet AMD continues to enroll patients in cohort six at the third dose level. Regenexx has announced new interim data demonstrating that RGX314 was well tolerated with a meaningful reduction in treatment burden at six months observed across all dose levels. The altitude trial in diabetic retinopathy continues to enroll patients in two new cohorts at a higher third dose level. Progenix Bio has announced new data demonstrating that RGX314 was well tolerated and BCVA remained stable through six months. Patients treated with RGX314 demonstrate clinically meaningful improvements in disease severity and less disease worsening versus observational control at six months. Last week, Regenexx Bio reported that both the wet AMD and diabetic retinopathy supercoital clinical trials are on track to be completed in the first half of 2023, with additional interim trial data expected in the second half of 2023. With our Xypher approval, our successful OASIS trial, and the ongoing clinical development programs by our partners in the U.S. and China, Super-choroidal drug delivery via our SCS microinjector is now more widely accepted than ever by retinal communities. I will now turn over the call to our CFO, Charlie Degnan, for a financial update. Charlie?