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Edited Transcript of ADVM earnings conference call or presentation 12-Mar-20 8:30pm GMT

·27 min read

Q4 2019 Adverum Biotechnologies Inc Earnings Call MENLO PARK Apr 1, 2020 (Thomson StreetEvents) -- Edited Transcript of Adverum Biotechnologies Inc earnings conference call or presentation Thursday, March 12, 2020 at 8:30:00pm GMT TEXT version of Transcript ================================================================================ Corporate Participants ================================================================================ * Aaron Osborne Adverum Biotechnologies, Inc. - Chief Medical Officer * Leone D. Patterson Adverum Biotechnologies, Inc. - President, CEO & Director * Myesha Lacy Adverum Biotechnologies, Inc. - VP of IR & Corporate Communications ================================================================================ Conference Call Participants ================================================================================ * Alethia Rene Young Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research * Patrick Edward Dolezal LifeSci Capital, LLC, Research Division - Senior Analyst * Philip M. Nadeau Cowen and Company, LLC, Research Division - MD & Senior Research Analyst * Tara A. Bancroft Piper Sandler & Co., Research Division - Research Analyst ================================================================================ Presentation -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- Good afternoon, and welcome to the Adverum Biotechnologies' Fourth Quarter and Year-end 2019 Corporate Update Conference Call. (Operator Instructions) As a reminder, this conference call is being recorded. I would now like to hand the call over to Myesha Lacy, Vice President of Investor Relations and Corporate Communications of Adverum. Please go ahead. -------------------------------------------------------------------------------- Myesha Lacy, Adverum Biotechnologies, Inc. - VP of IR & Corporate Communications [2] -------------------------------------------------------------------------------- Thank you, operator, and welcome, everyone. Today, we issued a press release reporting our financial results for the fourth quarter of 2019. A copy of this release is available on the press releases page of the Investor Relations section of our corporate website at www.adverum.com. Please note that a replay of today's call also will be available on the Events and Presentation section of our website. Joining me for the prepared remarks portion of the call today is Leone Patterson, President and Chief Executive Officer; and Dr. Aaron Osborne, Chief Medical Officer. Then Leone, Aaron and our Chief Financial Officer, Thomas Leung, will be available for the Q&A portion of the call. As a reminder, we will be making forward-looking statements regarding our product development plans, research activities and operations as well as our financial outlook. These statements are subject to risks and uncertainties that may cause actual results to differ materially from those forecasted. A description of these risks can be found in our 10-K, which was filed this afternoon. I would now like to turn the call over to our President and CEO, Leone Patterson. -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [3] -------------------------------------------------------------------------------- Thank you, Myesha. Good afternoon, everyone, and thank you for joining us today. Before we dive into our business progress, I'd just like to acknowledge the fluid situation as it relates to coronavirus and the broader community. Like many companies, we are taking necessary precautions to support our employees and our business, and we will continue to monitor the situation closely. During this call, we will review the significant momentum in advancing our lead gene therapy candidate, ADVM-022 and also provide a corporate update. Aaron will then review the significant clinical progress with ADVM-022, targeting with AMD, including recent data presentations and our plans for advancing our second indication diabetic retinopathy or DR. We will then open the call for questions. This is an exciting time to be working in gene therapy and to be part of what many considered to be a gene therapy revolution in treating serious diseases. At Adverum, we are focused on delivering what we believe can be transformative therapies for patients living with serious ocular and rare diseases. We believe our lead gene therapy program, ADVM-022 has the potential to be a onetime intravitreal injection gene therapy approach for our lead indication with AMD. This past year, we have gained significant momentum with our clinical progress in the development of 022 and the OPTIC Phase I dose-ranging study. As a reminder, we have been exploring 2 doses in the OPTIC trial at 6E11 and a threefold lower dose of 2E11. We have presented data from our first 2 cohorts, and I'm excited to announce that we recently completed dosing all 9 patients in our third cohort. We are now focused on completing enrollment in cohort 4 and screening of patients has begun. The clinical data presentations on OPTIC cohorts 1 and 2 have been very promising, where ADVM-022 demonstrated robust efficacy and evidence of a dose response. We look forward to presenting new clinical data from OPTIC in May this year. Additionally, we plan to present data from all 4 cohorts in OPTIC in the second half of this year. We also plan to develop 022 in a second indication, diabetic retinopathy or DR, with an IND submission in the first half of 2020 and a Phase I/II beginning in the second half of the year. We are positioning our company to be a leader in gene therapy. Beyond ADVM-022, we are focused on developing a pipeline of novel gene therapies. Our industry-leading AAV platform provides us with a number of compelling options for expansion, and we look forward to talking about this progress during the course of this year. Also, we are making great strides in other areas of our business. First, at the beginning of the year, we moved to our new headquarters in Redwood City. This move supports our growth plans and enables us to expand our core capabilities, including process development and manufacturing. Next, we appointed Angela Thedinga, as Chief Technology Officer. Angela brings deep and relevant experience in gene therapy as she led AveXis' efforts in developing the early manufacturing strategy, which enabled them to transition to early-stage AAV manufacturing process to a scalable commercial manufacturing process. Angela will focus on leading our manufacturing strategy as we advance towards later-stage clinical trials and prepare for potential commercialization. And finally, we are in a strong financial position with over $300 million in cash. After completing a public follow-on offering last month, raising net proceeds of approximately $141 million, which, together with a year-end cash of $166 million, is expected to fund operations into 2022. Before turning the call over to Aaron, I wanted to just share how excited I am to be leading this company where we are at the cutting-edge of developing a potential onetime treatment for patients with wet AMD and DR. We are committed to our mission to advance these programs in a pipeline of novel gene therapies for patients with serious ocular and rare diseases. I'd now like to turn the call over to Aaron, who will provide further details on our clinical progress for ADVM-022. Aaron? -------------------------------------------------------------------------------- Aaron Osborne, Adverum Biotechnologies, Inc. - Chief Medical Officer [4] -------------------------------------------------------------------------------- Thanks, Leone. Our primary focus as a company is always on the needs of our patient population. In this regard, to date, we are not aware of any specific coronavirus impact on the OPTIC trial. We are continuously monitoring the evolving situation with coronavirus and are in regular communication with our clinical trial sites and our vendors involved in our clinical trials. Our thoughts and wishes are with everyone who has been impacted by COVID-19. Now turning to OPTIC. This has been a truly exciting time for ADVM-022, as we advanced OPTIC for wet AMD and develop plans for a second clinical indication in diabetic retinopathy. OPTIC continues to progress very well. As Leone mentioned, we recently completed patient dosing in cohort 3 and opened screening for cohort 4. There is strong support from the investigators and clinical sites to quickly enroll this cohort to allow us to share data from all 4 cohorts in a total of 30 patients later this year. In January of this year, Dr. Charles Wykoff presented detailed efficacy and safety data from cohort 1 patients. Then in February, Dr. David Boyer presented a further update from OPTIC, including data from patients in cohort 2, who received a threefold lower dose of ADVM-022. To briefly summarize the data from cohorts 1 and 2, ADVM-022 demonstrated a robust efficacy signal and evidence of the dose response, which we measured as follows. In cohort 1, using a dose of 6E11 vector genomes per eye, 6 of 6 patients remained rescue injection free at a median follow-up of 6 weeks, with 3 of those patients out to 50 weeks -- 52 weeks or beyond. In cohort 2, using a threefold lower dose of 2E11, 4 of 6 patients were injection free at 24 weeks. This provides us further evidence of robust efficacy in addition to a dose response. In both cohorts combined, 10 of 12 or 83% of patients remained rescue free -- rescue injection free. For these patients, vision was generally maintained as demonstrated by stable mean best corrected visual acuity compared to baseline. Retinal anatomy improvements were achieved and maintained as demonstrated by mean central subfield thickness compared to baseline. It's important to remember that patients in OPTIC previously required frequent anti-VEGF injections to maintain their vision. In cohorts 1 and 2, patients had received an average of over 9 anti-VEGF injections in the 12 months prior to receiving ADVM-022 in OPTIC. The assessment of safety is a paramount importance in early phase clinical trials, and we are pleased to report ADVM-022 continues to demonstrate a favorable safety profile with no drug-related or procedure-related serious adverse events, no drug-related systemic adverse events and no adverse events meeting the criteria for dose-limiting toxicities. Low-grade inflammation that is responsive to steroid eye drop treatment has been commonly reported. Importantly, we have seen no evidence of vasculitis, retinitis or choroiditis following intravitreal ADVM-022 administration. In cohorts 3 and 4 of OPTIC, we're administering prophylactic steroid eye drops instead of prophylactic oral steroids as were used in cohorts 1 and 2. We believe that the use of steroid eye drops will decrease the systemic exposure to steroids and allow for a longer period of steroid coverage, potentially reducing the occurrence of the generally mild inflammatory events that have been reported after cessation of oral steroids in cohorts 1 and 2. We look forward to sharing the data from cohorts 3 and 4 later this year. Given the promising data on ADVM-022 presented today, we are excited to move forward with our plans to explore a second indication, diabetic retinopathy. Diabetic retinopathy represents another large and underserved market that may benefit from a onetime long-lasting intravitreal anti-VEGF gene therapy. Of the estimated 8 million people with diabetic retinopathy in the U.S., only 2 million are diagnosed and only 1 million are treated. Retina specialists are very excited by the potential that a onetime intravitreal anti-VEGF therapy could offer. Currently, most patients with diabetic retinopathy do not receive anti-VEGF therapies due to concerns around that short duration of effect and subsequent risk of diabetic retinopathy progression and sight loss. Diabetic retinopathy is the leading cause of vision impairment and blindness amongst working age adults. As the prevalence of diabetes continues to grow, the prevalence of diabetic retinopathy is expected to increase. There are significant unmet needs for more effective and more durable anti-VEGF therapies that can reduce the incidence of sight threatening complications and improve outcomes. We believe maintaining consistent levels of VEGF suppression with ADVM-022 could be particularly important for this rapidly progressing disease, potentially improving treatment outcomes over currently available therapies and allowing for an earlier time point of intervention. I will now turn the call back over to Leone. -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [5] -------------------------------------------------------------------------------- Thanks, Aaron. We will now open the call to questions. Operator? ================================================================================ Questions and Answers -------------------------------------------------------------------------------- Operator [1] -------------------------------------------------------------------------------- (Operator Instructions) Our first question comes from Alethia Young with Cantor. -------------------------------------------------------------------------------- Alethia Rene Young, Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research [2] -------------------------------------------------------------------------------- Congrats on the progress from angiogenesis. So maybe 2 for me. I just wanted to maybe talk a little bit about, kind of, the potential state of enrollment in cohort 4. I don't know, I think, there was probably good demand in cohort 3. So just wanted to see if there was any kind of perspective you could give on how fast that could enroll? Or do you kind of already have the people staked out? And my second question is on diabetic retinopathy. Can you talk about any kind of potential readthroughs that we might be able to start making from the AMD data that we've seen and when we start thinking about potential efficacy there? And then maybe just can you touch upon how you think this therapy might be potentially more impactful and competitive than like, perhaps, let's say, like a monthly dosing drug like an Eylea or something like that versus kind of the standard of care, which still remains pretty prevalent in that population? -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [3] -------------------------------------------------------------------------------- Sure. This is Leone. So in terms of state of enrollment, I'll start and obviously, if Aaron has anything to add. But we're currently screening patients. Obviously, we're focused fairly heavily on getting those patients enrolled as soon as possible, and it's very much part of what we're focused on, primarily, is to get that enrollment done. And 6E11, as you may recall, the efficacy we had with the first cohort, which is the same dose as cohort 4, is that we are still really showing robust efficacy, durability out to the longest time point now, 50-week median. So we believe that there is a lot of interest, and we continue to hear that from investigators to enroll patients in that cohort, 6E11. So Aaron, see, if you have anything to add on that so we can go to the other 2 points as well. -------------------------------------------------------------------------------- Aaron Osborne, Adverum Biotechnologies, Inc. - Chief Medical Officer [4] -------------------------------------------------------------------------------- Now just to add that. We're in sort of in daily contact with the investigators. We've got sites in the U.S., we know these investigators really well, and they're truly excited about cohort 4. And we're actively screening patients. We have many lined up and hope to rapidly enroll cohort 4. -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [5] -------------------------------------------------------------------------------- Great. And then in terms of DR and the potential read-through, I think, first of all, obviously, from a safety perspective, the Phase I for OPTIC is a Phase I safety study, and so therefore, the first and foremost thing in terms of the safety profile. And that's why, I think, cohorts 3 and 4 are important because we're using prophylactic steroid eye drops, which will hopefully manage the steroids -- sorry, the inflammation that may have been seen earlier on in cohorts 1 and 2. So we do believe that there are some read-through that will be apparent from even the data we presented when it comes to safety, along with what we'll see in cohorts 3 and 4 and using steroid eye drops as a prophylactic measure. And as it relates to efficacy, yes, I think, there can be some read-through, and I'll have Aaron speak to the disease -- difference in the disease between wet AMD and DR because there is obviously some differences and whether the doses that we would use in DR would be the same as what we would use in wet AMD, I think, it would be useful to talk about the levels of VEGF and compare to the 2 in the patient profile. -------------------------------------------------------------------------------- Aaron Osborne, Adverum Biotechnologies, Inc. - Chief Medical Officer [6] -------------------------------------------------------------------------------- Yes. Thanks, Leone. Yes. So the anti-VEGF agents that are approved at the moment, most of them are approved for use in diabetic macular edema as well as in wet AMD, and those doses have generally been the same. So drugs -- the dose of anti-VEGF is effective, and wet AMD will generally be effective in treating diabetic macular edema and also in improving diabetic retinopathy. And there's a lot of evidence around that, that exists already. So the efficacy that we're seeing in OPTIC is really exciting in terms of its possible applicability to diabetic retinopathy and diabetic macular edema. And I think, just the second part of the question, which was on the difference between 022 and currently available anti-VEGFs, which are approved for diabetic retinopathy, but are not currently used to any great extent, I think this really comes back to the durability. And diabetic retinopathy is a disease that lasts for several years. And what can happen with the anti-VEGF therapies that are available is that they can superficially give the appearance to have improved the disease, but because of their short duration of action, then the patient can actually experience a complication if they do not come back to the clinic. And I think this is the premise of a sustained delivery approach in diabetic retinopathy that you can provide long-lasting, sustained anti-VEGF, which can hopefully tie that patient through the most active period of their diabetic retinopathy and could reduce the risk of those sight-threatening complications. And importantly, it's something that lasts for several months or years rather than something that lasts for just a few weeks. So therefore, when it starts to wear off, if it does start to wear off, this would happen much further down the line, and the patient would be much less likely to experience the sight-threatening complication. And I think that's why the retina community is really excited about the potential of intravitreal gene therapy to make a big difference in diabetic retinopathy. -------------------------------------------------------------------------------- Operator [7] -------------------------------------------------------------------------------- Our next question comes from Tara Bancroft with Piper Sandler. -------------------------------------------------------------------------------- Tara A. Bancroft, Piper Sandler & Co., Research Division - Research Analyst [8] -------------------------------------------------------------------------------- It's great to hear your progress so far, and it's also really promising to hear that you guys don't seem to be experiencing any delays with OPTIC due to COVID. That's great. So I was just wondering if maybe I can get your thoughts on the recent safety signals that we're seeing with BEOVU? And what it was about the product that you think may have led to that? And do you think there's any read-through to intravitreal therapy, in general, and how this may affect sentiment towards a longer-lasting therapy like 022 could be? -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [9] -------------------------------------------------------------------------------- Yes, great question, Tara. Thank you. So I think I'll start, but then Aaron will, obviously, with his experience as an ophthalmologist and having worked on a number of the other anti-VEGFs, I think, he could answer more specifically. But what I can say is it's very different, the type of inflammation that we're experiencing, which, as you know, is low-grade, manageable with topical steroids. It's very different than the type of inflammation that has been experienced with those patients, who are on BEOVU. So with that, I'll turn it over to Aaron to talk about some of the hypothesis on what's happening. But I think it will be really important to emphasize the difference of where we're incurring -- the type of inflammation we have versus BEOVU, but also where the inflammation is occurring. So I'll hand it over to you, Aaron. -------------------------------------------------------------------------------- Aaron Osborne, Adverum Biotechnologies, Inc. - Chief Medical Officer [10] -------------------------------------------------------------------------------- Thanks, Leone. Yes, obviously, we're concerned to hear those reports. And the inflammation with BEOVU, which has been associated with sight loss has been reported to be a posterior inflammation. So an inflammation in the back part of the vitreous body, but most worryingly, there's been a vasculitis. So that means an inflammation affecting certain retinal vessels which has resulted in the blood not being able to get to the retina and patients losing vision, and that could potentially be permanent, and that's called a vasculitis. So this is what really concerns, I think the retina community, and there was a lot of discussion about that at recent ophthalmology meeting. So in terms of what that potential root cause could be -- we're focused on 022, but some of the things that come up are potentially something around -- this is -- let's remember that BEOVU is a novel therapy, which is a different class with a single chain antibody fragment and those are not used that wisely. So it's conceivable that there could be an issue with the production, and there could be some contaminant there or it could be related to that. Another thought is that it could be related specifically to it being a single chain fragment, which may penetrate deeper into the retina and may be causing some problems in certain patients. And I think the third theory that people discuss is the fact that it's a very high dose of anti-VEGF, it's around 24x the dose of ranibizumab or 12x the dose of an Eylea intravitreal injection. So those are sort of 3 areas that people are looking at to potentially explain what is happening here. I think, importantly, with 022, we have not seen any evidence of retinal vasculitis. We've not seen any evidence of any sort of retinal inflammation. We do commonly see a low-grade inflammation, which affects the front part of the eye following intravitreal injection of 022, and this is expected. We're injecting viral material, and we expect some degree of immune response. But that inflammation is very low grade. It predominantly affects the front part of the eye, and it's something that lasts over a longer period of time, and it's manageable with topical steroid. So a very different type of inflammation, and we have not seen any evidence of that type of information with ADVM-022. -------------------------------------------------------------------------------- Operator [11] -------------------------------------------------------------------------------- Our next question comes from Phil Nadeau with Cowen and Company. -------------------------------------------------------------------------------- Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [12] -------------------------------------------------------------------------------- Maybe a couple on that inflammation that you've seen. Have you decided on the steroid regimen that you're going to use in the DR trial now or does that await data from cohorts 3 and 4? -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [13] -------------------------------------------------------------------------------- So basically, I think -- thank you for bringing that up. So a couple of things. One, as I just mentioned earlier, we've -- cohort 3, we've completed dosing. Obviously, this is an open-label study. And we have rolled -- drive into our cohort 4 using the same protocol, steroid eye drops over a 6-week -- prophylactic steroid eye drops over a 6-week tapering. So that gives you a sense of our level of confidence and comfort to move forward with that approach in that cohort 4, which is at 6E11. The second part in terms of the -- what we'll be using going forward for DR, DME, obviously, we haven't submitted. We're still in the process of submitting our IND and which, we said, we would get that done in the first half of this year. And then we would have -- be able to share a little bit more about the protocol design. But it's safe to say that given this is a patient population that would benefit from using topical steroids as opposed to oral, that we'll be clearly looking at that as our potential way of managing any inflammation that we would see in that study. But we would -- in terms to hear that definitively, we will need to wait until we actually get to the protocol design and willing to share that. -------------------------------------------------------------------------------- Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [14] -------------------------------------------------------------------------------- Got it. And just to follow-up on your comments about the open-label nature of cohort 3. Could you talk to that maybe in a bit more detail? What are you seeing there? And I guess, in particular, how many patients are past the 6-week end of the prophylactic steroid regimen today so you can see what the long-term efficacy of the 6-week cohort, I mean, the 6-week dosing paradigm? -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [15] -------------------------------------------------------------------------------- I think what I can say is that, obviously, at some point, we'll release the real data, Phil. But I think what we can say is, just to remind people, there were 9 patients that were enrolled. We enrolled our first patient in November. We announced the enrollment in November. So you can -- it's fair to say that we have a number of those patients out beyond that 6 weeks. And I think the only thing I can say to that since we haven't presented data is to say that we feel confident with what we're seeing to proceed with our dosing up back to 6E11 using that same steroid regimen of topical steroids over 6 weeks. -------------------------------------------------------------------------------- Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [16] -------------------------------------------------------------------------------- And can you remind us the dose of the topical steroids? Would it be possible to increase the dose for cohort 4, if that was necessary? -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [17] -------------------------------------------------------------------------------- I'll have Aaron answer that question. Go ahead, Aaron. -------------------------------------------------------------------------------- Aaron Osborne, Adverum Biotechnologies, Inc. - Chief Medical Officer [18] -------------------------------------------------------------------------------- Yes. So we're giving 4 times a day drops for 3 weeks and then 3 times a day for a week, twice a day for a week, once a day for a week and then stop. But the maximum frequency is 4 times a day and eye drops can potentially be given more frequently than that. So that certainly would be one option if we needed to increase the amount of steroids being given. But based on the experience in cohorts 1 and 2, the inflammation that we've seen has been manageable with those topical steroids. So obviously, we're now doing that experiment in cohorts 3 and 4 and look forward to getting the data as quickly as possible. -------------------------------------------------------------------------------- Operator [19] -------------------------------------------------------------------------------- (Operator Instructions) Our next question comes from Patrick Dolezal with LifeSci Capital. -------------------------------------------------------------------------------- Patrick Edward Dolezal, LifeSci Capital, LLC, Research Division - Senior Analyst [20] -------------------------------------------------------------------------------- I was just hoping you could guide expectations at the ARVO data update? -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [21] -------------------------------------------------------------------------------- Sure. So as you may probably have heard today that ARVO officially -- the in-person meeting has -- was canceled today. However, you will also see that we wrote in our press release and what we said today in our remarks that we do still plan to present data on the OPTIC trial in May. In terms of the way that we'll do that, obviously, we're waiting to hear back from ARVO. They are offering different ways to present data as still part of -- under ARVO. But without saying that we would still present data -- we still plan to present data on OPTIC in May, as we've said. And either it will be as part of the ARVO umbrella and whatever way they plan to allow presentations to still occur virtually or whatever way that happens. Or it will be -- and/or it will be some form of a webcast that we would do to support that as we have done previously and -- when we've done presentations of data. -------------------------------------------------------------------------------- Patrick Edward Dolezal, LifeSci Capital, LLC, Research Division - Senior Analyst [22] -------------------------------------------------------------------------------- Great. And then, I guess, kind of playing off of Phil's question. If possible, could you provide any additional color on the status of the tapering of steroid use in cohorts 1 and 2? -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [23] -------------------------------------------------------------------------------- So we -- I think when I do -- what we can talk about is what to be presented at ANGO. I think in terms of any updates, we'd be providing that at a later time point. But I think it's fair to say that as we continue forward with the protocol in cohorts 3 and 4, that does give some level of insight that we are comfortable with using steroid eye drops as a measure of prophylactically managing any inflammation that we see. But I hope to see if Aaron has anything more to add there on the tapering. And I think a reminder of what the investigators can do beyond the tapering period might be useful as well. -------------------------------------------------------------------------------- Aaron Osborne, Adverum Biotechnologies, Inc. - Chief Medical Officer [24] -------------------------------------------------------------------------------- Sure. So if you remember in cohort 1, we had all patients were treated with prophylactic oral steroids. And there was really a learning process. And after that, the different types of topical steroids were given and some patients even got some more oral steroids. And the timing of that was kind of variable amongst the group. But through December 1, which was the last time point that we analyzed the data, we had one patient who had had an unrelated serious adverse event of a retinal detachment and was post-surgery. And actually, that one patient who remains on the follow-up in OPTIC, that was the only patient that had any cellular inflammation, which potentially was postsurgical, you would expect some cellular inflammation post-retinal detachment surgery. The 5 others, none of those had any cellular inflammation at that time point. And we had two other patients -- 2 of those 5 patients were on a tapering amounts of steroid, which was 2 drops a day each. And the other 3 were no longer on any topical steroids. So certainly, the cellular inflammation was resolving or resolved and we had 2 patients remaining of those -- outside the one who was postsurgical, we had 2 patients who are taking topical steroids. So that's cohort 1. And the other data point that we have is cohort 2, which was at the lower dose, a threefold lower dose, as you remember. And we had -- there, we had out of the 6 patients through 24 weeks follow-up, 2 of the patients have not required any steroid eye drops after their initial oral course and that had 0 or next to 0 inflammation. And we had 2 other patients who have had absolutely minimal inflammation of a maximum of half plus, and those had had short courses of topical steroids and the inflammation had resolved. And then we had another 2 patients who have had more significant inflammation, but that had -- was improving or resolved and they were on tapering eye drops. So we had 2 patients in cohort 2 who were on drops at week 24. So cohort 3 obviously comes next. And there, we have all of the patients getting the 6 weeks of topical eye drops. And we're hoping that those 6 weeks of topical eye drops can reduce the occurrence of having any adverse events or spikes in inflammation early on and can hopefully put the patients on a better course. But it's important to remember this inflammation has been low grade. The vast majority of it has been asymptomatic, nothing affecting the back of the eye. So it's a predictable inflammation that seems to be very manageable with the topical steroid approach. -------------------------------------------------------------------------------- Operator [25] -------------------------------------------------------------------------------- Thank you. I will now turn the call back to Adverum's President and CEO, Leone Patterson. -------------------------------------------------------------------------------- Leone D. Patterson, Adverum Biotechnologies, Inc. - President, CEO & Director [26] -------------------------------------------------------------------------------- All right. Thank you, again, for joining our call today. We have made significant progress this past year. Looking ahead, key catalysts for Adverum this year are: Presenting new data from OPTIC in May; submitting an IND in diabetic retinopathy in the first half of this year; initiating our Phase I/II clinical trial on DR in the second half of the year; and finally, presenting data for all 4 cohorts of OPTIC in the second half. We look forward to further sharing our clinical progress and continued execution as we advance the development of our novel gene therapy, ADVM-022 for the treatment of serious ocular diseases. In closing, I'd like to thank the patients, caregivers and retinal specialists who are participating in the OPTIC trial. And last, but certainly not least, I want to thank the Adverum employees for their tireless efforts. Our achievements at Adverum wouldn't be possible if it weren't for the dedication of this team. Thank you for your time. And this concludes our call. -------------------------------------------------------------------------------- Operator [27] -------------------------------------------------------------------------------- Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.