Good morning. My name is Mike Connor. On behalf of the JP Morgan Healthcare Investment Banking Team, it's our pleasure to introduce Adverum Biotechnologies. As many of you know, Adverum is advancing the clinical development of its novel gene therapy candidate, ADVM-022, as a one-time intravitreal injection for the treatment of patients with wet AMD and DME. Today from the company, we are joined by Laurent Fischer, Chief Executive Officer, Leone Patterson, the President, and Aaron Osborne, Chief Medical Officer. I'll now turn over to Laurent and the team to walk through the presentation. Laurent? Thank you, Mike. Good morning, everybody. I'd like to first thank JPMorgan for inviting Adverum to present today, and I hope that everybody's doing well and staying safe at home. These are my forward-looking statement on slide two. They're also available in our SEC filing and on the Adverum website. At Adverum, our global mission is to establish ocular gene therapy as a one-time treatment that preserves patients' sight for life. We're gene therapy pioneers with a disruptive platform technology offering a potential one-and-done treatment for patients living with the leading causes of blindness worldwide, wet age-related macular degeneration and diabetic macular edema. On Adverum disruptive technology is based on our AAV.7m8 vector platform that has the potential to provide a functional cure for patients living with wet AMD and DME with a single in-office intravitreal injection. We announced this week that we completed the enrollment in our phase II INFINITY study in DME, the first gene therapy study in DME, and we're planning to initiate our first pivotal trial in wet AMD mid-year after meeting with regulators later this quarter. We focus on execution with the goal of delivering this transformative gene therapy to patients globally as early as possible, and are building out our manufacturing capacity to deliver hundreds of thousands of doses of ADVM-022, which is why we're building our new GMP facility in North Carolina. Our team is experienced in gene therapy, anti-VEGF clinical development, and vector manufacturing, and we continue to expand the team to support the future commercialization of ADVM-022. Beyond these two large ocular market opportunities, we are advancing our gene therapy pipeline in ocular and rare diseases, leveraging the AAV.7m8 platform and our expertise in both vector and cassette engineering. On slide five, you can see that the anti-vascular endothelial growth factors have now become the standard of care for the treatment of wet AMD and DME, resulting in improving visions and preventing severe vision loss. There are about 90 million people worldwide that are treatable with wet AMD and DME. This is a large and growing $11.5 billion market opportunity, the socioeconomic impact in the United States alone is estimated to be about $139 billion. This is due to vision loss, including falls and depression. There are many parts of the world where obesity and diabetes are rapidly growing epidemics, and where one-and-done treatments such as ADVM-022 could have a significant impact in reducing vision loss in working age adults. On slide six, you can see that in clinical studies, anti-VEGFs have transformed the standard of care, and they have demonstrated improvement in vision in clinical studies, as demonstrated on the right-hand side in the MARINA study, where Lucentis is given as a monthly intravitreal injections over two years. Patients who receive a sham injection, a placebo, lose about five letters or one line of vision every six months, while patients who receive 24 injections on a regular monthly basis over two years maintain their vision. However, in the real world, there's a stark contrast, and if you look at real-world evidence, you can see that in Europe with the AURA study, patients actually receive less than the required number of injections necessary to preserve their vision. They range from nine injections over two years in the U.K. to 5.2 in Italy, and as a result, patients start losing vision as early as one year after treatment initiation. Whether the cause is cost, treatment burden, or lack of retina specialists, clearly the less frequent the injection, the worse the outcome. Even in the United States, in the recent SIERRA-AMD study that was based over 79,000 electronic medical records over four years, it shows that patients who receive on average 14.6 injections over two years, despite this high number of injections, also start to lose vision after 12 months. Our own market research on slide eight confirms that a reduction in injection frequency, better efficacy in the real world, ease of administration, and better control of fluid in the macula are the main areas of unmet medical need. What is the solution? A new gene therapy that is easily administered in the office, that is disease-modifying by maintaining dry retinas with a predictable and manageable safety profile that can be deployed globally, even in areas where retina specialists are present in insufficient numbers. Let's look at the treatment landscape today on slide 10. You have a number of approved in-office intravitreal therapies, injectables, that are administered every 4-12 weeks. The most recently approved is Beovu, and several investigational agents that push that treatment interval with novel mechanisms of action, such as KSI-301, at 16-20 weeks, providing an incremental benefit. Beyond these, you have surgical approaches with a PDS that pushes treatment interval to six months, or a subretinal gene therapy requiring a vitrectomy, a surgical procedure that is associated with the development of cataracts in nearly all patients after one year and limits the potential of this intervention. ADVM-022 is the only gene therapy that can be delivered with a simple in-office intravitreal injection and may provide lifelong vision to millions of patients. Our most advanced program with ADVM-022 is in wet age-related macular degeneration on slide 11. On slide 12, you can see that ADVM-022 uses a proprietary 7m8 platform that was designed by directed evolution to allow the viral vector to be administered via IVT, enable it to cross the ILM, the inner limiting membrane, and efficiently transduce retinal cells. The C11 expression cassette has a codon-optimized aflibercept to enhance the cellular expression of the anti-VEGF protein. This results in a biofactory approach where aflibercept, which has been used safely in over 9 million eyes, is constantly produced at the site of the disease. On slide 13, you can see that in our preclinical studies, you see an efficient transduction, in this case of green fluorescent protein, as seen in the NHP retinal flat mount on the left side of the slide. You can see that after a single IVT injection on the right-hand side, our aflibercept levels are roughly similar to what is seen three to five weeks after bolus injection. Importantly, the expression of aflibercept is stable and durable up to 13 months in these post-mitotic cells. Wet or neovascular age-related macular degeneration is the leading cause of blindness in people over the age of 65 and is a late-stage manifestation of age-related macular degeneration. It is characterized by new blood vessel formation in the macula. These blood vessel leak fluid and destroy the anatomy of the retina, leading to sudden onset of vision loss. Wet AMD affects 1.5 million people in the U.S. and 5 million people worldwide and is a growing market with 200,000 new cases in the U.S. per year. They require frequent anti-VEGF treatment for life with a significant cost and significant burden to society and patients. On slide 15, I'll introduce our OPTIC study with ADVM-022, which supports moving forward with a pivotal trial in wet AMD that we plan to initiate mid-year. The goal of this first study with ADVM-022 in anti-VEGF treatment experienced patients was to establish the safety and efficacy of ADVM-022, in particular, the maintenance of vision in this patient population, where any improvement in anatomy and the need for rescue injections over two years. In this patient population, I'd like to note that unlike in treatment-naive patients, the goal here is to preserve vision. We evaluated four cohorts that are followed up to 92 weeks with a single loading dose of anti-VEGF before receiving ADVM-022. This first cohort we evaluated received six times 10 to the 11 copies with a 13-day oral steroid prophylaxis. The second cohort was also evaluated in six patients at two times 10 to the 11 with the same oral 13-day prophylaxis regimen. Cohort 2 and 3 evaluated the low dose, but this time with an eye drop steroid prophylaxis, and Cohort 4 again went back to the high dose. The aflibercept rescue criteria were a loss of 10 letters, an increase in CST by 75 micron, or hemorrhage due to AMD. Patients who have now reached two years have the option to roll over to a five-year study. As you can see on slide 17, OPTIC patients were treatment-experienced and required frequent injection monthly to maintain their vision, up to 109 injection in one subject, and their vision was at 20/50, slightly below what is required to drive. Slide 18 is our swim lanes, where you can see that in the year prior to the administration of ADVM-022, patients received over nine injections of either Lucentis, EYLEA, or Avastin. The fourth cohort received slightly less anti-VEGF as our investigators became more confident with ADVM-022. All patients receive a single dose of EYLEA, followed by ADVM-022. In the first cohort, you can see that all patients were rescue injections free at out to 92 weeks, six out of six. Our sentinel patient has other conditions that put him at risk for COVID-19 and has refused to come back to the study site. He's out here doing well and recently was seen by his regular retina specialist, and he receives regular injections in the other eye. His vision is doing well as well. He was asked how he was doing and if he would actually start again since he was the first patient to receive this transform gene therapy, and he said, "100% yes." A very happy patient who has been able to stay safely at home and not go back to sites on a monthly basis to receive his injections, except for the other eye, unfortunately. Cohort 2, you can see that at the low dose, three out of six patients were injection-free. The low dose Cohort 3, seven out of nine patients were supplemental injection-free. In Cohort 4, we have only one patient who received a top-up injections. You can see that was also the case with a couple of patients in Cohort 2 and 3 that received occasional top-up injections, but much less frequently than what they had received before entering the study. If you look at the overall reduction in the annualized injection frequency on slide 19, you can see an impressive 99% reduction at the high dose, and an 85% reduction in annualized anti-VEGF following ADVM-022 at the low dose. ADVM-022 was well-tolerated after a single IVT injections. Overall, you can see that the related ocular adverse events were mild to moderate. There was no ADVM-022 related non-ocular adverse events, and when observed, inflammation has been responsive to and managed with steroid eye drops only. Importantly, there's been no clinical or fluorescein evidence of posterior inflammation, no vasculitis, no retinitis, no choroiditis, vascular occlusion, or endophthalmitis. On the right-hand side, you can see that as expected with gene therapy, where there's billions of copies you inject in the eye, there's minimal inflammation. This inflammation, which results in a few aqueous and vitreous cells, very low levels, goes down over time, as does the need for steroid eye drop prophylaxis. On slide 21, you can see that in Cohort 1, we had stable vision and anatomy with 100% of patients being rescue-free out to 92 weeks. The anti- VEGF levels that we measured in this first cohort, 18 months after receiving a single injection of 022 were robust and in the range of what you would expect approximately three weeks after a single bolus injection of EYLEA. On slide 22, you can see that the low dose Cohort 2 and 3 out to 68 weeks, 67% of the patients are rescue-free, and those rescue-free patients have improved vision by 3.2 letters and an impressive reduction in fluid of 100 micron. The current treatment paradigm falls short of providing long-term durability. The challenge, as you can see in slide 23, is that there's a recurrence of fluid and fluctuation in the retinal thickness as you extend the treatment from monthly to bimonthly injections. Recent data published this past week show that in patients with AMD, where the most retinal fluid fluctuations, they will tend to lose about 9.4 letters over two years. That's clearly a problem with current treatments. I'd like to show a case study from our own OPTIC study. Clearly the goal is to keep patients' eyes dry. As you can see in slide 24, we had one patient that before coming to study, received an IVT injection every five weeks. Before their injection, every time they came, they had this OCT that shows significant amount of fluid in the macula and the retina. Two weeks after the injection of aflibercept, before they received ADVM-022, you can see that the fluid is significantly reduced but not entirely gone. After one injection, that patient has completely dry maculas up to 48 weeks. This is one patient who see these every time they come, have seen these frequent injections before treatment with 022, ask their patients whether they're cured or not. I would say this is probably equivalent of a functional cure. In fact, well-known retina specialist, Dr. Wykoff, from a clinician perspective, believes that the data we see here is what matters more than anything else because it shows that disease-modifying effect. We've seen incredible benefits of the VEGF suppression in these patients with 022. On slide 26, if you think about a patient perspective, this is what a TPP could look like with a single IVT injection of ADVM-022. You can see that 022 is well-tolerated with related ocular events that were mild to moderate. No evidence of retinitis, choroiditis, vasculitis, or vascular occlusion. When observed, ocular inflammation has been mild and responsive to steroid eye drops. You can see that patients have been entirely rescue injection-free up to 92 weeks, and 93% of the patients have the high dose and in 67% the low dose with stable vision and improved anatomical outcomes. We've also seen for the first time recently presented the robust anti-VEGF protein levels at 18 months after a single injection. From the free injection frequency, we've seen a very impressive 99% reduction in annualized anti-VEGF in the high dose and 85% in the low dose. We're also evaluating ADVM-022 in DME, diabetic macular edema. DME is actually a type of diabetic retinopathy that is the leading cause of vision loss in working age adults, impacting 30 million people with diabetes, 400 million worldwide, and about 5% of these patients have DME. What's different here is that they require more frequent anti-VEGF injections up front. There are many parts of the world where diabetes and obesity are most prevalent, where retina specialists are in short supply. On slide 29, you can see our INFINITY phase II study design, which was designed to show superiority to EYLEA. Comparing two doses of ADVM-022, two and six times 10 to 11, with a primary endpoint at 24 weeks. This is compared to a single injection of aflibercept. The primary endpoint here will be time to worsening of disease activity, and the secondary endpoints will include visual acuity, retinal anatomy using OCT, and Diabetic Retinopathy Severity Scale. Of note is that this is the first gene therapy trial in DME. I'm very proud to say that our team did a fantastic job in over-enroll the study in less than six months during the COVID pandemic, all virtually, and will be presenting data in the second half of this year. If this data is positive, this would warrant pursuing either DME or DR as an indication. 2021 is a year of execution at Adverum. On slide 31, you can see that we recently announced that we're building our own GMP facility in North Carolina. It's a 174,000 sq ft facility that will be production ready by the end of 2023. We have all process development, assay development, and quality control in-house. We're partnering with CMOs to manufacture clinical and additional commercial supply. We use a highly scalable baculo/Sf9 suspension process that we already scaled up from 50 L to 200 L and are now in the process of scaling up to 1,000 L. Our team has broad anti-VEGF, gene therapy, and commercial expertise. We're rapidly growing. We look forward to executing to commercialize this first mass market gene therapy and look forward to updating the investor community on the progress of our ADVM-022 program in wet AMD after we meet with regulators later this quarter, and to initiate our first pivotal trial mid-year. We'll present data from our DME INFINITY study in the second half of the year. We'll be also unveiling our pipeline later this year. With that, I would like to thank you. Thanks to my team and all our investigators and patients who participated in these studies to support the development of ADVM-022. Great. Well, now I'll open it up for any questions at this time. Okay, the first question here is, could you talk a little bit more about your new manufacturing facility? I believe it includes four 1,000 L bioreactors. How many injections will that allow you to produce annually, and when do you expect this facility to be fully ramped up by? Yeah. Let me ask Leone Patterson, our President, to answer this question. Great. Hi, everybody. Super excited about us having our own GMP facility for our commercial supply. It will be, as you said, 174,000 sq ft. We'll be hiring over 200 people in North Carolina. This is a very strategic initiative for us because you need to control your own commercial supply, especially in gene therapy. If you look across the landscape, that this is something that's very important when you are going after a large mass market like we are because you need to control your own commercial supply and especially in gene therapy with our own capabilities from a process development perspective. As mentioned earlier in Laurent's presentation, it'll put supply hundreds of thousands of doses. We will also use a dual process where we will use our own GMP manufacturing but have the flexibility to also use a CMO if needed in terms of demand. We will have that facility up and running by end of 2023, which is super exciting when you think how close that is as we begin to get ready for commercial supply. Great. Thanks, Leone. Our next question here is, you provided a number of clinical updates throughout 2020. Could you lay out sort of what clinical updates we should expect in 2021? Yeah. Thank you. I have to say that 2020 has been particularly challenging with the COVID pandemic and the inability to actually present live presentations like we do here today at JPMorgan. As a result, we've had to work around these challenges, and we expect that will continue. We'll plan to regularly update our clinical trials, and we'll have some data coming out in the first quarter. We're working with society to see if we can present new data. I don't expect this will be the case, unfortunately, given the challenges we've had last year with last-minute changes in plans. Great. The next question here is, with this $80 million manufacturing investment, what is your current cash runway and what are kind of the key milestones you would achieve over that time period? Yeah. Our cash runway, as we announced previously, is to mid-2022. The most significant milestone we talked about is obviously the ability to initiate our first pivotal trial mid-year. The DME data second half, that will be a catalyst to potentially initiate another pivotal trial for a second indication for ADVM-022. We'll have additional milestone as we present our pipeline. Obviously, for us, a key and important meeting will be with regulators this quarter so we can confirm the plans. We're very pleased to see that recently, another gene therapy focusing on anti-VEGF indication showed similar type of design that's required for anti-VEGF approval. Roughly a two phase III trial with non-inferiority after one year of treatment in about 700 patients. We expect that something similar will be announced, but obviously, there are various options we're considering, and we'll be discussing those with regulators and come back to the investment community once we have clarity. The next question here, kind of following off that, is based on those conversations, when do you expect sort of the earliest ADVM-022 could be approved for wet AMD? I think that's a great question. It's a little premature until we've had those conversations. Obviously, we think we can be competitive with other programs given that ADVM-022 does not require surgery. It's a simple in-office IVT injection. We expect that enrollment will be fairly swift as we've seen with INFINITY. There's a lot of excitement around this potential one and done treatment. Our goal is to make it available to patients globally as quickly as possible. Great. There are no more questions in the Q&A at this time. Thanks, Laurent, Leone, and Aaron for presenting today. Thanks to all the investors for joining, and hope everyone has a great rest of their conference. Great. Thank you very much, Mike. Thanks, everybody. Take care, everybody. Thank you. Bye-bye.