Clearside Biomedical, Inc.

Good day and thank you for standing by. Welcome to the ClearSci Biomedical Quarter 2023 Financial Results and Corporate Update Call. At this time, all participants are in a listen-only mode. After the speaker presentation, there will be a question and answer session. To ask a question during this session, you will 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 turn the conference over to your speaker today, Jenny Coben, ClearSight Investor Relations.

Good morning, 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, prospects, 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, 2022, and our other SEC filings available on our website. 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 Levesque, our Chief Executive Officer, and Charlie Degnan, our Chief Financial Officer. After our formal remarks, we will open the call for your questions. I would now like to turn the call over to George.

Thank you, Jenny. We delivered a productive start to 2023 as we execute on our near-term plan to advance our lead asset, CLSAX, an investigational proprietary suspension of Excedinib for suprachoroidal injection. Excedinib is a highly potent tyrosine kinase inhibitor 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 therapies for retinal diseases by acting at a different level of the angiogenesis cascade. Suprachoroidal injection of our proprietary CLSAX suspension delivers Excedinib directly to the site of disease and has demonstrated signs of biological effect and the potential for extended duration of therapy in our Phase I-IIa OASIS clinical trial in wet AMD. Results from the OASIS trial and extension study were presented last month at the ARVO annual meeting by Dr. Dennis Marcus. The trial consisted of four cohorts with single escalating doses of CLSA-X administered to participants who were then followed for three months. All participants enrolled in OASIS were heavily anti-VEGF treatment experienced with active disease at screening, which was confirmed by an independent reading center. The three-month trial was followed by an additional three-month extension study in the higher dose cohorts for a total of six months follow-up for those OASIS participants who elected to continue. CLS-AX was administered by our proprietary SCS microinjector, demonstrated an excellent safety and tolerability profile at all doses and in all cohorts. There were no adverse effects, no dose-limiting toxicities, no sign of inflammation, and because we inject behind the retina, we didn't have any instances of vitreous floaters or dispersion of drug into the vitreous. We anticipated this favorable safety profile as exudative is a well-characterized small molecule with much less propensity for ocular inflammation as compared to the administration of biological agents or viral-based gene therapies. In terms of outcomes, the OASIS extension study demonstrated that two-thirds of wet AMD patients in the two higher-dose cohorts were able to go at least six months without additional treatment. Participants experienced a 77% to 85% reduction in treatment burden, as measured by the number of anti-VEGF treatments they received during the six months compared to the six-month period prior to entering the OASIS trial. We observed anatomic signs of biological effect and reported stable mean best corrected visual acuity, or BCVA, and stable mean central subfield thickness, or CST, in the extension study participants in the two higher-dosed cohorts. These promising results are supportive of the potential safety, potency, and pan-VEGF blockade effects of CLSAX delivered via our SCS microinjector into the supracoroidal space. We're excited to further explore the potential of CLSAX in ODYSSEY, our planned randomized double-mass, multi-centered Phase IIb clinical trial in participants with wet AMD. Our primary goals for ODYSSEY are to demonstrate improved duration and reduce treatment burden for the CLSAX arm while maintaining visual acuity. We expect that the results of this trial will provide the necessary data to properly inform the design of a Phase III program for CLSAX in wet AMD. We believe CLSAX has the potential to be a twice-a-year maintenance drug for wet AMD, which, if demonstrated, would compare favorably to on-label maintenance dosing for the currently approved anti-VEGF drugs. The census on-label is 12 times a year, ILEA 2 mg is 6 times a year, and Bovismo is up to 6 times per year. We believe the Odyssey trial is balanced to meet its objectives effectively and efficiently with top-line results expected in Q3 2024. The Odyssey trial will compare CLSAX against a current standard of care, ILEA, or a FlibberSeb. In essence, we are comparing CLSAX maintenance versus a FlibberSeb maintenance with a goal of demonstrating similar visual acuity outcomes with a lower treatment burden for the CLSAX arm. plan to enroll a total of 60 treatment-experienced patients with wet AMD. Patients will be randomized, or participants will be randomized two-to-one. Forty participants will receive CLS-AX administered by suprachoroidal injection via the ClearSide SCS microinjector, and 20 participants in the comparator arm will receive intravitreal aflibrocept. The trial will include participants diagnosed with wet AMD within 36 months of their screening visit and with a history of responding to anti-VEGF treatments for the disease. Participants will have reading center confirmation of persistent active disease. The primary outcome measures for this trial are the mean change in BCVA over 36 weeks, as well as the assessment of safety and tolerability of CLS-AX. The secondary outcome measures are treatment burden, as measured by total injections over trial duration, other changes in visual function and ocular anatomy, such as CST, and the need for supplemental treatment. Participants in both arms will receive three monthly loading doses of Aflibrisib at two milligrams. The second loading dose visit, defined as the baseline visit, participants in the CLSAX arm will also receive one milligram of CLSAX by suprachoroidal injection. Participants in the comparator arm will also receive a sham suprachoroidal injection to ensure masking of the trial. Participants in the CLSAX arm will then receive another CLSAX dose at week 24, unless they require supplemental treatment prior to that visit. Therefore, participants in the CLSAX arm will receive at least two doses of CLSAX during the trial, which will provide valuable multi-dose safety information for an end-of-Phase II meeting with the FDA and the design of a Phase III trial. In the comparator arm, participants will receive additional Aflivirseb injections every eight weeks until week 36, unless they require supplemental treatment prior to the scheduled every eight-week Aflivirseb dose. Disease activity assessments will be conducted in both arms at week 12 and then every four weeks through week 32. This will determine if there is a need for supplemental treatment based on the occurrence of any one of the following four criteria compared to baseline. BCVA reduction of greater than 10 letters, an increase in the central subfield thickness of greater than 100 microns, BCA reduction of greater than five letters, and an increase of CST of greater than 75 microns, or the presence of a new or worsening vision-threatening hemorrhage due to wet AMD. The detailed trial design slides are available on our website in the corporate presentation. We believe this trial design makes sense for two key reasons. First, we are enrolling treatment experience participants with a history of responding to standard anti-VEGF treatments. We believe this will minimize recruitment of anti-VEGF sub and non-responders and may provide a larger population of participants to facilitate our trial enrollment efforts. This trial is more closely aligned with the recent FDA draft guidance for WET-AMD drug development by utilizing Aflibirzeb as a preparator, BCVA as the primary outcome measure, and utilizing a 36-week duration. Together, this will help us most effectively and efficiently prepare for a phase three program in WET-AMD. Our clinical operations team has been working hard to get Odyssey up and running this quarter. I am pleased to announce today that the study will open for enrollment in the next few weeks, and we expect to enroll our first patient shortly thereafter. We are targeting a total of 30 U.S.-based clinical trial sites and expect top-line data from the trial in the third quarter of next year. Moving on to Zypyr. At ARVO, Dr. Peter Chang presented survey data regarding the use of our SCS microinjector from retina uveitis specialists who have completed at least 10 suprachoroidal injections of Zypyr. The findings from the survey of early adopters of Zypyr suggest suprachoroidal injection was easy to learn and patient improvements in vision and macular edema aligned with the findings in clinical registration trials. This broadening use of our suprachoroidal delivery platform is encouraging as multiple clinical trials advance both with us and our development and commercialization partners. Our US and Canadian commercial partner for Zypyr, Bausch & Lomb, continues to expand outreach with Zypyr product education and SES injection awareness and training to healthcare providers. A significant number of physicians have been trained to date in the proper use of our SES microinjector. Fauci has also filed for Zypure regulatory approval in Canada, so we're looking forward to market expansion and additional territory. Our Asia Pacific commercial partner for Zypure, Arctic Vision, is currently enrolling a confirmatory phase three trial in macular edema associated with uveitis, and has completed a phase 1 clinical trial for the treatment of diabetic macular edema. Data from the DME trial is expected to be made public in the near future. Let me now provide a brief update on our SCS microinjector partner programs. Last week, Regenexx Bio announced that they had completed enrollment in the expansion cohorts of phase 2 AV8 and altitude clinical trials. These trials are utilizing supercorrelant delivery of RGX314 in patients with wet AMD and diabetic retinopathy. Regenexx Bio expects to report additional interim trial data from both trials, including initial data from the most recent cohorts in the second half of 2023. Regenexx Bio also announced that IND sponsorship has now been transferred to AbbVie for continued clinical development of the two superchoroidal gene therapy clinical programs using ClearSight's SCS microinjector. AbbVie is a widely recognized global leader in eye care. In the future, RGX314 will be referred to as ABBV-RGX314. Our oncology partner, Aura Biosciences, is utilizing our SCS microinjector to deliver their viral-like drug conjugate, Belsar, for the treatment of choroidal melanoma. Based on promising data presented earlier this year, ORA announced final plans for its global phase three trial utilizing the superchloroidal lute of administration. They expect to begin dosing for the trial in the first half of this year. With that summary of our programs, I'll now turn the call over to our CFO, Charlie Degnan, for a financial update. Charlie?