Good afternoon, everyone. Thanks for joining us for Oppenheimer's annual healthcare conference. I'm Justin Kim, one of the senior research analysts at Opco. It's my pleasure to be introducing Dr. Laurent Fischer, President and CEO of Adverum Biotechnologies, to give an update and presentation on the company. Please go ahead, Laurent. Justin, thank you for the introduction, and thank you for inviting us to present at the Oppenheimer Annual Healthcare Conference. My name is Laurent Fischer. I'm the President and CEO of Adverum. I look forward to introducing you to the company. I will be making a forward-looking statement there on this slide. We're developing an investigational gene therapy product called Ixo-vec that is designed to be a one-time injection in the eye to deliver an aflibercept encoding vector that has the potential to actually provide lifelong benefit for the treatment of wet age-related macular degeneration, which is currently treated with lifelong injections in the eye. What is unique about our vector is that it can be injected through a routine outpatient intravitreal injection. It transduces the back of the eye, transforms into a biofactory that actually produces aflibercept, the active product of Eylea, potentially for the life of the patients. On the right lower-hand side corner, you can see patients from our first in-human study, OPTIC, that showed after three years after single injections, this patient had no supplemental injection and had stable vision and no fluid visible in their macula measured by the central subfield thickness. We actually just presented last week at Macular Society the preliminary result from a LUNA trial that evaluated two doses of Ixo-vec, and we're very pleased to report that we show a best-in-class reduction in treatment burden in patients who were high disease activity requiring more than nine annualized anti-VEGF injections, with a 90% reduction overall in anti-VEGF injections and 85% of the patients at 2E11 and 68% at 6E10 dose that were totally free of injections at six months. Patients maintained vision and their fluid anatomic endpoint were stable with stable CST at both doses. Importantly, we defined and identified an improved prophylactic regimen where they go for a prophylactic regimen of Ozurdex and difluprednate drops that led to more than 90% of the patients having no or minimal inflammation defined as zero or trace cells at the time point we're presenting. The inflammation we noticed were actually interior cells that were responsive to local corticosteroids per protocol, and there was no Ixo-vec-related serious adverse events. As you well know, wet AMD is a lifelong disease that requires lifelong injection in the eye. There are about 1.5 million patients in the U.S. with 200,000 new cases every year and 20 million patients worldwide that suffer from wet AMD, which is the leading cause of vision loss. Up to 42% of the patients will develop bilateral disease two to three years after their diagnosis. Our goal is to transform the potential treatment of this disease where currently, despite the injection that patients receive, there's actually a loss of vision, and this requires lifetime injections and a significant cost to patients and the healthcare system. With a one-time individual gene therapy, the potential is to preserve vision for life and result in significant direct and indirect healthcare savings. The difference that we see with the current standard of care is that with these frequent injections in the eye that people try to extend as long as possible, and the fact that these elderly patients often are hospitalized or unable to go to their visits, in the real world we see after initial gain in vision a loss in vision over a period of years. We're hoping to be able to bridge that gap with Ixo-vec by providing stable levels of aflibercept in the eye for life, in contrary to what we see with the current bolus standard of care. This is actually the latest two drugs approved anti-VEGF for the treatment of wet AMD. On the left-hand side is Vabysmo, a bispecific antibody that was approved a couple of years ago. You can see very good vision gains in the early weeks and then a slight drop in vision over a period of two years. On the lower left-hand side in the box, you can see that this is compared to Eylea every eight weeks. Patients often need more frequent injections every six weeks. As a result, in this study, you can see that gray line showing the fluid fluctuations in these patients' population over a period of time, which is known to lead to poor vision outcome. So if you think about where we are today, we see actually with the first generation anti-VEGF on the market, great vision improvements, but frequent injections requiring an injection in the eye every four to eight weeks. Eylea HD Vabysmo can extend that treatment injection to 4-16 weeks per label and the potential for new agents that require injection of anti-VEGF and implants to push that limit to six months. But only gene therapy can really preserve vision long-term, potentially for life. Adverum with Ixo-vec and REGENXBIO with their subretinal approach product have data past three years to date, and we have actually levels of Eylea that we can measure up to 4.5 years in our first in-human study OPTIC. This is the OPTIC data that we recently published in The Lancet Discovery Science in January of this year. You can see that we can, with one injection, not only reduce the treatment burden but preserve vision. We see an 84% reduction in annualized anti-VEGF treatments at 3 years, with 53% of the patients being entirely free of injections. This is the highest three year percentage free that we know in the field, and 2E11 was well tolerated through three years of follow-up. This is the design of our LUNA phase II trial that we presented at Macular Society last week, evaluating two doses of Ixo-vec, 2E11 and 6E10, and several prophylactic regimens. The prophylactic regimen we evaluated was either steroid eye drops, difluprednate for 22 weeks, with or without oral steroids for 10 weeks, or an Ozurdex intravitreal dexamethasone implant with steroid eye drops added after week four, with or without oral steroids. These were randomized in a 2-to-1 fashion. Supplemental injection criteria were an increase in CST by 75 microns from baseline, confirmed by a central reading center, or loss of greater than 10 letters from baseline, or new vision-threatening hemorrhages due to wet AMD. You can see the study disposition as of November 15th. Most of the patients obviously had passed week 14, and about half of the patients were at week 26. Two patients discontinued, one patient passed away for unrelated causes, and one patient had dementia and could no longer be followed. You can also see that these patients actually received multiple anti-VEGF, including Vabysmo, bevacizumab, for 10 patients. We will be reporting a pre-specified interim analysis when all patients have achieved the 26-week visit mid-year. These are the baseline characteristics. You can see on the right-hand side in OPTIC and in LUNA the total of the patients, the totality of the population, that these patients were high treatment burden patients with active disease requiring nearly 10 annualized injections per year prior to entering the study. The vision was slightly improved in LUNA compared to OPTIC with 72 letters versus 65, and there was slightly better control with less fluid at CST of 350 microns versus 397, and about 40% of the patients still had their lens, so they still had not had a cataract surgery. This is the reduction in treatment burden in LUNA 6E10 on the left-hand side, 2E11 in the middle compared to OPTIC. You can see a 90%-94% reduction in annualized treatment burden at week 26, comparing well to the 86% we saw in OPTIC 2E11 at similar time points. Now, looking at the injection-free rates for 6E10, 2E11 in OPTIC, you can see 68% of the patients at 6E10 entirely free of injection at week 26 versus 85% at 2E11 and 73% at OPTIC 2E11 at week 26. Now, looking at the totality of the patient population, this is still a small study across both doses. You can see in the swim lane plots on the left-hand side the multiple colored dots representing injections with the different anti-VEGF, after the line patients being followed with open dots being the visits and the orange dots being the need for rescue or supplemental injections. So you can see that overall 75% of the subjects are free of injections, with a 93% reduction in annualized anti-VEGF, nine subjects only required one injection, and six more than one injection. Now, looking at the vision and anatomic outcomes in LUNA, you can see that in both doses we see stable vision out to week 26. And as I mentioned earlier, vision was slightly better in LUNA compared to OPTIC, and you can see the dotted line is OPTIC at the same time points with also vision being preserved throughout the duration of the study. The lower part of this graph shows you the CST, the central subfield thickness, a measure of the amount of fluid in the macula. You can see that nice drop that occurs early on and perfectly stable CST throughout week 26 at two doses of Ixo-vec in LUNA 6E10, 2E11, comparing well to the 2E11 we saw in OPTIC. Now, looking only at the patients that received zero supplemental injections, so a majority of them, you can see that similarly to what you saw earlier, we preserve vision out to week 26 at both doses, and we see a nice drop in central subfield thickness that is fully maintained out to week 26. We also measured levels of aflibercept protein expression in the aqueous humor in these patients, both in LUNA and in OPTIC. And in OPTIC, we know that every single patient in whom we measure those protein levels are completely stable out to 4.5 years, as measured by these lines. In the two purple dots that you see, the two colored purple dots on the left-hand side are the two doses evaluated in LUNA, and you can see a very nice overlap of these two doses, all within what we believe are therapeutic levels. Of note is that there's no minimum levels of aflibercept that are predictive of a therapeutic threshold, as a few subjects had undetected levels and had 0 injections. two had actually one or two injections, and that was across both doses. The preliminary safety summary shows that Ixo-vec was well tolerated with inflammation that was responsive to protocol-defined local corticosteroids. We had no Ixo-vec-related SAEs. All AEs were mild to moderate. We saw no episcleritis, vasculitis, retinitis, choroiditis, vascular occlusion, or hypotony. The most common AEs were dose-related anterior inflammation, primarily anterior chamber cells, and anterior pigmentary changes that were consistent with OPTIC 2E11 and what we published in January in the Lancet Discovery Science. The local prophylactic regimens are promising, with the Ozurdex plus difluprednate resulting in more than 90% of patients having no or minimal inflammation, zero trace cells, and that optimized prophylactic resulted in an improved safety profile compared to OPTIC 2E11 that was all manageable with local steroids. We found out that Ozurdex alone did not provide adequate prophylaxis or prophylaxis of sufficient duration, and that oral corticosteroids showed no incremental benefit, which is a plus in this patient population. This is the heat map from the Ozurdex plus difluprednate on the left-hand side, anterior chamber cells on the right-hand side, vitreous cells. You can see that there are only a couple of trace cells, a couple of time points with that optimized prophylactic go-forward regimen. With the local steroid eye drops, you can see a few trace and one plus cells at a couple of times, two plus cells. All of these were responsive to local steroids at the latest time point. We identified early on with the first 6 patients who received Ozurdex alone or with oral steroids that there were some breakthroughs around week 8-12. As a result, we amended the protocol to add difluprednate eye drops after week 4, resulting in over 90% of the patients having zero cells or trace cells. We also identified no benefit of oral prednisone in addition to the local corticosteroids, and that, again, is a very positive outcome and something we were the first to try to understand as we continue to explore and advance in the field of ocular gene therapy. Compared to OPTIC, you can see that Ozurdex plus difluprednate, which resulted in 90% of patients having no or trace cells, was superior to what we saw in the OPTIC trial and very pleased with our ability to improve the benefit-risk profile. We looked at ocular pressure, which was stable at both doses of Ixo-vec compared to the fellow eye. If you look at the overall annualized reduction in treatment burden comparing the two doses of Ixo-vec in LUNA and OPTIC in purple and blue compared to 4E10, 3E10 and 1E10 in gray, and the suprachoroidal approach of RGX-314 at 1E12 and 5E11 and 2E11, you can see that Ixo-vec has the highest percentage of reduction in treatment burden. We also have that reduction long-term, both at year one, year two, and year three. More importantly, with the one-time gene therapy, the potential is to be free of injection for life. You can see that here again, Ixo-vec performs very well, with 68%-85% of the patients being free at six months of injection. But more importantly, long-term, at year one, year two, and year three, 60% and 53% of patients being entirely free of injections. If we look at the hardest-to-treat patients, patients with a high baseline above 300 microns, in fact, with means of 417, 429 in LUNA and OPTIC, LUNA in green and OPTIC in blue, you can see a very nice reduction in fluid, and that reduction being completely stable out to week 26 in LUNA, and we know for many years, at least we presented the three-year data in OPTIC last year at AAO, so very encouraging to see that Ixo-vec really has best-in-class ability to keep patients' eyes dry. I showed you this data of the swim lane plots. We're very interested to see that patients who receive bevacizumab were actually enrolled in the study, showing the clear unmet medical need remaining in the field. Looking specifically at these patients that had actually a very high treatment burden with the latest and greatest anti-VEGF, you can see that all of these patients were free of injections, five at the 6E10 and five at the 2E11 dose. So we're very pleased with the palpable benefit profile that we see emerging from LUNA with the potential best-in-class activity. We have a go-forward prophylactic regimen for phase III at two doses and a well-tolerated durability up to 4.5 years from OPTIC. We showed that best-in-class reduction in treatment burden in OPTIC with 90% reduction in anti-VEGF, 85% of patients 2E11 and 60% at 6E10 entirely free of injection at 6 months, and confirmed activity based on visual acuity and anatomic endpoints. We're very pleased with the go-forward regimen of Ozurdex plus difluprednate with an improved safety profile versus OPTIC. Our next steps are to advance toward phase III, with the 26-week interim analysis being presented mid-2024. We plan to have continued FDA and EMA formal and informal interactions to finalize the phase III study design and plan to initiate our phase III in the first half of 2025. With that, thank you very much. Great. Thanks, Laurent. You know, maybe just to touch on one of those analyses that you had done on those sort of on the latest regimens and treatment options. You know, how do you view that population in terms of, you know, what Ixo-vec could provide? I mean, is it just small numbers that they all seem to do well, or do you think that those folks who are able to transition to these longer sort of intervals are probably the maybe best candidates and would maybe potentially do the best on a, you know, infinite sort of injection frequency interval with Ixo-vec? So I think, you know, what you see in this kind of graph is that all of these patients that go into gene therapy trials are the ones that actually require the most frequent injection, hardest to treat, also the ones that, you know, switch around to all the different anti-VEGF to see there's actually a way to improve the efficacy. And we're actually very pleased to see that a vast majority of these patients are doing very, very well, right? Even the ones that required an occasional rescue, those nine participants only had one injection here. And you can see the year prior, most of them had actually nine injections. Also interesting, you know, we have a few patients that actually only had been recently diagnosed and received only a few injections of bevacizumab, and these patients are doing great. So I think what this tells me is that, you know, as you'd expect with a gene therapy product, first in human, you get the hardest-to-treat patients that have, you know, very high treatment burden. And as we start looking forward, we see that even patients who have less need for injections are doing very well, potentially even better, right? Because they don't have that high treatment burden. So for me, it's very encouraging that we have two doses that look like they have best-in-class efficacy with a very manageable safety profile. And with, you know, with gene therapy, you only have one shot at getting your, you know, the best efficacy you can. And it's really managing that trade-off and that balance between efficacy and safety. I guess, you know, just given what we've seen so far out of LUNA, you know, do you think that there's a real clear efficacy benefit between the two doses? I mean, you know, they both are compelling and, you know, it looks like the safety doesn't seem to be differentiated between the two, at least so far. So just how should we be thinking about what a late-stage study could look like? What are the considerations? You know, is it sort of just speaking with regulators? Just can you walk us through those dynamics? Yeah, of course. I mean, excellent question. So I think so far we may see a real early trend of a dose response based on the percent of patients that are totally free of injections. But, you know, I think that it's too early to tell whether there's one dose that is likely to be superior to the other. We'll see probably mid-year at the 26-week interim analysis with a better read. Same thing for safety. We certainly see that, you know, go-forward prophylactic regimen. There's no difference across doses. If you look at the drops only, there may be a trend. So we may be, you know, able to identify a profile that gives you optimal coverage that can allow for both doses to move forward. It's all about benefit risk. As I mentioned, with gene therapy, you have one-time opportunity to actually be free of injection if you can increase that by 10%-20%. But that means you need to have longer eye drops, maybe for a few weeks or months. Is that a trade-off that is worth for patient and physician? If you ask the patient and the retina specialist, I think they would say yes. But we know that based on, you know, recent safety signals for drugs that need to be injected in the eye very frequently, there's, you know, a trade-off that needs to be balanced. And so for us, you know, the next step is really having conversation about the type of phase III design. There are two designs that have emerged with new guidelines and companies going different directions. We think that the non-inferiority design, which is the way drugs have been approved today, including Vabysmo, Eylea HD, is probably the preferred one. There's been some changes and details of the study that are not trivial, like basically no longer accepting sham injection, requiring to inject saline in the eye to mask the IVT every eight weeks. That's a challenge that retina specialists are concerned with. We have actually stopped doing aqueous taps because we had one case of endophthalmitis. So putting a needle in the eye is not necessarily trivial. And we know that in Europe, it's very unlikely to be acceptable. So those are the ranges of things we want to discuss with regulators as we move forward to finalize the design. By the time we have the mid-year data, we can have an end-of-phase II. We'll actually finalize the dose or doses because there's a potential to bring two doses into phase III. That's also a possibility. And the prophylactic regimen. But I think we're in really great shape to start having those conversations and start making plans to initiate phase III, you know, the first half of next year. And that recent financing enables us to keep the pedal to the metal and make sure that we can start planning for these phase III studies. Understood. In terms of the prophylactic measures, I mean, would those also be sort of placebo-controlled or... It's a good question. You can obviously placebo... you can control for drops with, you know, putting saline. We haven't had conversation yet about Ozurdex. But, you know, importantly, if you think about the several implants, long-acting implants that TKIs that are being evaluated, you can't really mask two implants you're going to put in the eye. So I'm not sure how that's masked. But, you know, masking is really trying to, you know, avoid bias, right, and placebo effect. And so I think, you know, every company has to do the best they can to mask everything they can, but you can't mask everything. You could have, like, different, you know, investigators inject one or the other and do the evaluation. There are ways to mitigate for that. But I think almost pretty much every single product that is in development, including, you know, the one required is subretinal, you know, injection and a vitrectomy, you can't mask for that, right? So, you know, it's all about the balance and doing your best to make sure the study is properly masked. And we're doing that in this study by not showing individual patient data until we get later on to avoid any kind of bias. Okay. Yeah, I mean, I think, you know, having that sort of regimen might be sort of maybe the solution also, right, for the saline endophthalmitis potential risk as well, minus, I guess, a bacterial or viral introduction. Yeah, no, I mean, and again, you know, we had a Staph epidermidis confirmed, you know, endophthalmitis after an injection at week 14. And that can happen. So I think just the injecting saline every eight weeks to mask a potential control arm where people receive Eylea every eight weeks is probably not optimal. But we're very encouraged with the conversation we're having. We have, you know, PRIME designation in Europe that allows us to have, you know, a number of, you know, very repeated interactions both on the CMC side, which is obviously important in gene therapy. And as a reminder, we had the green light to go into phase III by the FDA several years ago. We think we're in good shape and look forward to updating you and the street as we continue to move forward, make progress, and start planning these phase III studies for the first half of next year. Great. We'll look forward to the progress and sort of the, you know, the next steps for Ixo-vec. Very exciting times. Great. Thank you so much, Justin. Thanks, everyone.