Hi everyone, and thank you for joining the H.C. Wainwright Fifth Annual Ophthalmology Virtual Conference. My name is Vivian, and I'm an analyst on the Corporate Access team. HCW is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts and over 650 companies covered across all sectors. If you would like more information, please visit our website at hcwco.com. From a logistics standpoint, please make sure to reference your virtual conference online portal that provides your individual links to your meetings and all presentations. Now, I'd like to introduce Lloyd Clark, who is SVP of Ophthalmology Strategy and Innovation at Annexon Biosciences. Thank you. Hi everyone, and thank you for joining the H.C. Wainwright Fifth Annual Ophthalmology Virtual Conference. My name is Vivian, and I'm an analyst on the Corporate Access team. HCW is a full-service investment bank dedicated to providing corporate finance. Hi everyone, and thank you for joining the H.C. Wainwright Fifth Annual Ophthalmology Virtual Conference. My name is Vivian, and I'm an analyst on the Corporate Access team. HCW is a full-service investment bank dedicated to providing corporate finance, strategic advisory, and related services to public and private companies across multiple sectors and regions. We have a total of 24 publishing senior analysts in over 650 companies covered across all sectors. If you would like more information, please visit our website at hcwco.com. From a logistics standpoint, please make sure to reference your virtual conference online portal that provides your individual links to your meetings and all presentations. Now, I'd like to introduce Lloyd Clark, who is SVP of Ophthalmology Strategy and Innovation at Annexon Biosciences. Vivian, thank you very much for that kind introduction and for the invitation from you as well as H.C. Wainwright to participate in your annual Ophthalmology Virtual Congress. I'm Lloyd Clark. I'm a practicing retina specialist and clinical trialist for 25 years. I recently joined Annexon in support of the development of an independent business unit as we push our lead candidate for dry AMD forward through phase III and through the potential for a blockbuster treatment option for patients with dry macular degeneration. As always, I'll be including forward-looking statements in my presentation today. For more information, you can consult our website or SEC filings. I've just joined Annexon over the last few months, been in retina for 25 years. This is an extremely exciting time for us at Annexon. We have multiple opportunities to have a positive impact on millions of patients worldwide with complement-mediated diseases of the body, brain, and eye. We'll be talking more specifically about ophthalmology today, but we have a really broad development platform. Annexon is celebrating our 10th annual 10-year anniversary this year in San Francisco. We have a platform of different products, all capitalizing on the classical complement pathway, specifically inhibiting C1q. We have a clinically validated scientific platform across multiple indications. We have a near-term opportunity. Our first candidate drug is a systemic C1q inhibitor designed to treat Guillain-Barré syndrome. We've had excellent positive results in our phase III clinical trial. We're working with regulators now to bring this therapy to the market in hopes of changing the standard of care, the first approved treatment for GBS. This is a severe debilitating neurological disease. We'll talk more about our geographic atrophy candidate drug today, really a tremendous opportunity to affect vision, to preserve vision where we have no vision preservation opportunities in this disease state that's very common. Another incredible blockbuster opportunity. Finally, we have an earlier phase development, an oral complement inhibitor with the opportunity to affect multiple indications. What's our approach? We really have a pioneering scientific approach that's more than 20 years old, based out of Ben Barres' lab at Stanford, blocking the classical complement pathway at the very top, C1q. This is the initiator of neuroinflammation in the brain, body, and eye. By blocking this upstream, we can inhibit many of the downstream effects of neuroinflammation as well as inhibiting the C3-C5 feedback loop. The science is tremendously empowering here as we try to interrupt neuroinflammation at the top of the disease pathway. We now have robust clinical data across multiple programs that really validate this idea and differentiate it from other treatment options. Here's our timetable for our candidate drugs. First, tanruprubart is our Guillain-Barré syndrome systemic C1q inhibitor. We have fully completed our phase III clinical trial program, positive results. We're in discussions with regulators globally to bring this treatment to market. We're going to talk about Vonaprument today, our dry age-related macular degeneration drug that's just completed enrollment for our registration program, a really exciting therapy. Again, our small molecule ANX1502 for a number of autoimmune indications. Next up, we'll be evaluating tanruprubart for a number of other debilitating neurological diseases, including Huntington's disease and ALS. Let's get into Vonaprument. It has been known recently as ANX007, but has recently grown up and has the name Vonaprument. It's the only geographic atrophy program currently in the pipeline that has showed vision preservation in these patients, which is really an incredible potential advancement for this unmet medical need. Let's talk about Vonaprument and dry AMD in general. Dry AMD is a very common disease state with at least 8 million people affected worldwide. It's the precursor for wet macular degeneration. There are no current therapies approved by regulatory bodies outside the U.S., and there are no vision-protecting therapies available worldwide. This really clearly is an unmet need in patients with a severe blinding eye disease. We're clearly differentiated compared to other candidate drugs in the pipeline. Our effect is on vision preservation. There's a significant effect in phase II. It's consistent. It's both time-dependent as well as dose-dependent. Very exciting visual acuity signals that we'll go through shortly. Anatomically, we've seen preservation of the central photoreceptors, which is critical for visual acuity. Safe drug, and our results as well as our mechanism align with the emerging idea that geographic atrophy lesion size is really not a clinically meaningful indicator of disease control. We really are attacking this from a different strategy. We have a well-designed global registration path, both in the United States as well as Europe. Of note, we have established PRIME designation for approval in the European Union, the first dry age-related macular degeneration to receive that designation. Our ARCHER II phase III clinical trial program reached an important milestone three weeks ago with complete enrollment of over 630 patients. We should be able to report top-line data in the second half of 2026. Here's a slide to understand geographic atrophy as well as the mechanism of our drug. This is retinal histology. This is two slides looking at the cross-sectional anatomy of the retina. On the top is the normal retina. I want to draw your attention to two bands. The green band on the bottom is the retinal pigment epithelium, and the red band in the middle is photoreceptor cell synapses. In the normal eye, the RPE and the synapse layers are both regular and have bright signals on this histology slide. Now, let's move down to the bottom. This is a patient with geographic atrophy. If you'll notice on the far right, the green band, the retinal pigment epithelium is completely absent. That's due to geographic atrophy. This is what we see in this advanced disease state, complete loss of the underlying nourishing cells of the retina. This is an end-stage finding, and you'll notice not only over top of the loss of the green band, we see no red staining either. There's no synapses over the geographic atrophy. That means the retina is dead, it's non-functional. There's no visual function in the bed of the geographic atrophy lesion itself. As we move to the left, we begin to see more red staining in the area of photoreceptor cell synapses. This is sick retina, retina that has some function but has lost the ability to transmit images to the brain because the synapses have been lost due to a number of insults that are related to aging. Our drug binds to C1q, C1q binds to sick photoreceptors and then eliminates them by recruiting inflammatory cells. Our drug works way upstream to the left and is able to preserve vision by inhibiting the loss of these important synapses. It's not surprising that we're not terribly interested in RPE lesion size because our drug works far to the left, upstream anatomically, as well as upstream in terms of a mechanism of action. We're trying to get to this disease before the complete loss of photoreceptors as well as RPE. Our phase III trial is informed by the ARCHER study, which was our phase II study evaluating Vonaprument. As a reminder, we enrolled 270 patients into one of three arms. The sham group was a sham injection with no treatment versus two doses of Vonaprument, either monthly or every other month. Our primary endpoint was the change in GA lesion size measured at month 12, and there were a number of pre-specified functional analyses, including best-corrected visual acuity, 15-letter loss events, as well as low luminance visual acuity. We followed these patients on treatment for 12 months and then followed them off treatment for six months. Here's the visual acuity data that has informed our design of the [ARCHER III] study. On the top left, we see protection of 15-letter loss in the sham group compared to the treatment groups. Overall, 21.3% of patients lost 15 letters during the first 12 months of ARCHER compared to only 5.6% of patients that were treated monthly with Vonaprument. This informs the Kaplan-Meier curves on the top right of the slide, which demonstrates a 73% risk reduction in 15-letter loss in patients treated monthly compared to the sham arm. At the bottom right, we see the off-treatment analysis. Patients treated with Vonaprument have a significant reduction in the 15-letter loss events compared to the sham group. Off-treatment, there is an immediate increase in the treatment events, underscoring the importance of consistent treatment with Vonaprument for protection of visual acuity loss. Finally, on your bottom left, we see a fellow eye analysis, and this fellow eye analysis demonstrates there was vision protection in the study eye compared to the fellow eye in patients with geographic atrophy. Overall, in the monthly group, we see a 57% reduction in visual acuity loss events in the treatment eye compared to the fellow eye that was not treated. There's emerging evidence to suggest that there is an anatomic correlation with the ellipsoid zone in the retina with functional benefit in terms of visual acuity. The ellipsoid zone is an area we see on optical coherence tomography that's important as an important metabolic marker in the retina. Our data suggests that our drug dramatically protects from the loss of the ellipsoid zone in the central 1 mm, 1.5 mm group. There's a 59% decrease in ellipsoid zone loss in the treatment group compared to sham. This treatment effect is seen as we move farther out, although less impressive. This finding of ellipsoid zone correlation is consistent with other groups' observations as we move forward in the dry AMD space. In terms of safety data in the ARCHER study, Vonaprument appears to be a safe drug. We had minimal safety events, only one case of endophthalmitis, no cases of occlusive vasculitis, and of importance, there was no evidence of an increased risk of choroidal neovascularization in patients treated with Vonaprument compared to sham in the ARCHER study. This data has informed our ARCHER II phase III clinical trial program. This is our registration study. It is now fully enrolled. Our last patient was enrolled approximately three weeks ago. It's important to remember that we looked at patients that are very similar to the ARCHER population, including patients with both foveal and non-foveal atrophy lesions, but it has been enriched for best-corrected visual acuity to exclude patients with poor vision. One of our observations, as well as some of our colleagues in the geographic atrophy areas, is that patients with vision less than 45 letters really have minimal opportunity for change in their vision. These patients have been excluded from the ARCHER II program to concentrate on patients that have an opportunity for vision preservation. Our study is quite simple. Patients are randomized to either monthly Vonaprument, 5 mg, versus sham. We've enrolled over 630 patients in a two-to-one enrollment scheme in North America, Europe, as well as Australia and New Zealand. Our primary analysis will be after 12 months from dosing, but we'll follow these patients for safety out for 24 months. Our primary endpoint is persistent 15-letter loss through the primary endpoint. That means they have to have two consecutive visits of 15-letter loss. We have a number of secondary endpoints as well that are both functional as well as anatomic. Again, it's important to recognize that we have a global registration path in place, both with the FDA in the U.S. as well as in the EU, and we've achieved PRIME designation within the European Union, the first drug with dry AMD to have that designation. In summary, Vonaprument is a novel neuroprotective agent demonstrating significant benefit in terms of visual acuity signals and photoreceptor structures in geographic atrophy, an incredibly common disease state affecting millions of patients worldwide. Our mechanism blocks C1q for neuroprotection. It's a common mechanism of action across a number of neurodegenerative diseases. We see commonality in our mechanism in the neural tissues of the retina compared to both central as well as peripheral nerves. There's significant validation of this science, not just in the eye, but also in the brain and the body. The key finding from our phase II study and what has informed phase III is preserved visual function. We are the first candidate drug in this pipeline that has demonstrated a functional preservation as opposed to only an anatomic benefit. We see this consistently across multiple different measures. It's a time-dependent protection in terms of loss of vision off treatment, as well as dose-dependent. We see a significant effect with monthly patients compared to every other month. One of the important things that we can see that correlates function with anatomy is protected retinal structure. We do this looking at the ellipsoid zone, an important anatomic feature in the neurosensory retina. This is a marker of photoreceptor protection, and we see significant protection of photoreceptors, particularly in the central subzones, which are most critical for vision. Our drug in phase II appears well tolerated. There were no increased incidents of inflammatory disease, and importantly, there was no evidence of increased choroidal neovascularization or progression to wet macular degeneration. We are really excited to complete enrollment of our phase III ARCHER II program. This is a large global study of over 630 patients. We completed enrollment six weeks ahead of a very aggressive schedule with robust interest worldwide. It is a very exciting time for us here at Annexon. We should have top-line data available to the public in the second half of 2026 with an existing cash runway. It is really exciting times for us here at Annexon. We think we're sort of poised to really make some breakthroughs here in ophthalmology, as well as some very common neuroinflammatory diseases worldwide. Thank you very much for the opportunity to present. Great. Thank you so much, Lloyd, for leading a productive and informative presentation on behalf of Annexon. We appreciate the time and effort that went into putting this together, and are grateful for the team's presence at our conference this year.