 Okay, so let's get started. Good morning everybody. I'm very happy to be here today and with the retinal rounds and we talk about age-related macular degeneration. I'm not sure if this was clear on the invite that we are talking about optimizing outcomes in this very common disease. So I'm very happy to give an introduction on the topic and then we will have our three retinal fellows to address specific new therapeutic options which are partially already available or and some of them are hopefully upcoming soon to our patients. As it is closer, I will discuss some of these new therapeutic options from pharmaceutical companies and maybe also there also some imaging device manufacturers involved, which I'm linked to in terms of research funding, consultancy, contracted research and honoria, mainly as part of my reading center activities. So as an introduction, AMD, as we all know, is a common cause of irreversible visual loss and almost 10% of the worldwide populations are affected. Alone in the US, we have 11 million people with this devastating disease, and if you look into the future, the numbers are even expect to double by 2050. So why are we here today? This is to share with you the current state that we are actually entering a new era in AMD management. So if you think about, that's all about anti-vegif and every four, every six, every eight weeks injection, though this is almost now history. And there are several developments to report. The point is that the patterns for runnabismap and beversismap have expired in the US last year and are set to expire this year in the middle of this year in Europe, while Flippersap, we still have some time to go. We also have very exciting news of new, two new approvals. This is a poor delivery system, approved end of last year and Flippersap approved last month, and this will be addressed in detail by our two senior retina fellows and the following. And also, there are more breaking news. If we go beyond Neovascular AMD, probably the most prominent news is that Pecasetoplan, that's the palace, drug has reported promising early phase, the three results last year. And this, there are many, many, as I said, there are many, many other current therapeutic strategy tested in clinical trials. Some of them already in phase three, and some of them are expected to report actually in 2022, so until the end of this year. It's kind of challenging to keep track on this topic right now because there's so many developments, and as you may imagine, it's not all in peer review journals, most of this information you can get is on the internet on press releases or on stockmark information. So what opportunities exist in principle to optimize outcome of our AMD patients and I think there are two different approaches. One is for the Neovascular form that we increase the treatment durability, reduce the treatment burden and improve the real world outcomes. And the other one, and this is probably, or this is obviously much more challenging is to address the multifactual nature of the disease other than the antibody treatment. So this is a list, and I'm not saying that this is complete but this is a list of treatment strategies to leave the burden of the frequent four weeks, six weeks, eight week monitoring and treatment of Neovascular AMD. And the first three on the list will be addressed by our retinal fellows. These include a new molecular targets, the continuous drug delivery device combination with reservoir and gene therapy. But there are others just to be complete, including a degradable implant, a slow clearing, large molecule, and an old successful treatment option to a flipper set to use it at a high dose. And just to give you some ideas about the benchmark, this degradable implants or the slow clearing large molecules are currently tested to be given every six months. So twice a year and not in this four week or eight week schedule. Before I will leave the floor for the retinal fellows, I will like to briefly touch on biosimilars, which are low cost alternatives for anti-vegetable therapy, and they're just entering the market or the access to our patients right now. So what are biosimilars? Biosimilars are almost identical copies of an original biological medical product that can be introduced after the patents expire. They have a similar molecular structure as the originator. But it's not a generic drug because it's not a chemical, it's not synthetic manufactured, it's a biologic with a high molecular complexity, and it's produced in living systems. And as of such, the manufacturing process is reported to be quite complex and various on different factors. It's indeed an extensive review and approval process in place as defined by our agencies, including the FDA. And if we look beyond ophthalmology biosimilars have largely changed the world in oncology and other disciplines. In terms of economics, I'm sorry I have to talk again about economics, but this is always in the discussion with these new developments, and we see it's projected to save over $100 million in healthcare in the next five years to biosimilars. So these are biosimilars in ophthalmology for neovascular AMD, and this is more than one as you can see, and two of them are already approved. And I can skip this maybe, but if you look beyond the US in India, there's already an approved biosimilars has been used and there have been some reports about ocular inflammation. In terms of the terminology, you may have seen this already on TV that that several spots outside of themology again where they have these antibody names followed by a four letter random appearing suffix, and this is the way how biosimilars are are labeled. So you have the originator and then you have a random four letter suffix to keep track about the actual agent. And they're no currently approved. I'm a Flippers biosimilars in the US, and you may have heard that there was a shortage about on the racism up last year, and some people or health insurance companies suggested to use the racism up biosimilars a license for oncology to apply in the eye and there were there was a red flag that this should not be done. Okay, so I'm talking about to address the multi factor disease of AMD of obviously this is a much more complex questions and we will not answer this today. But to summarize, there are different pathways into the into discussion and there are huge different ways of application, how to apply new therapeutical agents. And just to address some of them today. One attempt one target is neuro protection. This is, I'm, this is that have been several attempts in the past but no major breakthrough. In this context I think it's always important to know that the error supplementation didn't show an effect on progression of the traffic lesion size. As you know that you can reduce the risk for conversion to late stage disease but once you have atrophy. It doesn't doesn't do much to the further expansion of lesions. The next topic which is currently under discussion is what is summarized here as rejuvenate repair and generate damaged cells. This includes photo by by a modulation and sub threshold nano laser second intervention still in phase two on the edge of phase three. There are, and this is a list of current stem cell approaches ongoing. I'm getting longer and longer and my impression. Now to very advanced AMD probably also looking. I'm published last year as early phase street. There was a trend, often positive effect on lesion size expansion. Again is the audio for you as well. Sorry. Just seems like the audio may have been cutting out on game was it cutting out for you as well. Stefan would you mind just turning your camera off that might help it was just in the past probably 20 seconds that it was cutting out. Yes, it was put off of me as well. Sorry. No worries at all. And conclude, and there's an increasing number of activities and so targets beyond that Jeff, which we will not discuss into detail today. As an outlook. I think there will be more and more treatments options coming up and we will. Who will talk about the PDS and implant. Please. Great. Thanks. Let me try to share my screen. Do you guys just see the slider DC the full. We see the presenter view so. Okay, let me try to switch it. How about now. Still presenter view in the top left you might be able to click the use slide show sometimes that. Let me see one more try. There we got it. You got it. Okay. Well great so obviously a lot in the pipeline and a few things newly available. So I'm going to talk about one of those things that can potentially help us achieve continuous delivery of intraocular that Jeff. This is my wife enjoying some Utah powder upon little water peak. Okay. So this is the brand new port delivery system, which has been named sas Vimo. It looks like a little Appendorf tube. And this is a surgically placed refillable implants that sits in the vitreous cavity that can slowly and continuously diffuse anti VGF. That's specifically ran invisible into the vitreous cavity for exodative AMD patients. And this is what it looks like in the eyes is, I believe this is that about a post one month visit that's been published in one of their more recent papers that shows it externally where we can refill it. So as it sits in the vitreous cavity, and we'll get to some short surgical videos a little bit later as well. And then the refill happens just in clinic with a kind of a bi directional exchange needle that removes the old fluid and replaces it with new high concentration of randomism. So let's talk a little bit about the data and the trials that led to the now recent FDA approval of the pds. The phase two or ladder trial happened a few years ago this looked at different concentrations of renovatives about in the pds as well as comparison to monthly intervitural injections their primary outcome. The phase two study was not vision but time to first refill, which had to meet both specific vision and OCT based criteria, and at the highest dose of randomism. This was 15.8 months from implants to time to mean first refill. This also helped determine the appropriate dose. And as we'll see in a bit improve some surgical steps within the protocol. And then more recently we have the phase three archway trial so this was a randomized open label trial conducted at 78 different sites across the US. Here the primary outcome was change and best corrected visual acuity, unlike the ladder trial in archway they had a planned and mandatory refill for all patients with pds at six months. And kind of their their ultimate outcome was that the pds implant was found, both non inferior and equivalent to monthly randomism. So let's dive a little more into this phase three trial that came out not too long ago in ophthalmology. So some some specific inclusion exclusion criteria, not comprehensive but I think some of the key ones. So patients had to be diagnosed with wet AMD within nine months prior to enrollment and really importantly they had to demonstrate structural response on OCT and show either stable or improved vision. After three or more anti that Jeff injections prior to enrollments in the trial so you had to prove that they were anti that Jeff responsive. Also importantly this wasn't necessarily a randomism that could have been any of the available anti that Jeff agents. Exclusion criteria, they can't have really severe sub foveal pathology so no no fibrosis or atrophy. The treatment could only consist of anti that Jeff therapy so no PT steroids, focal laser, other things like that. And then importantly, as we'll see today also could not have had any like glaucoma surgeries or other super temporal quadrant surgeries in the study I have seen at the results of the enrolled 418 patients randomized three to two to pds to individual injections they had a very high retention rate was completion through the first 40 weeks, and we're looking here at their best corrected visual surgery during those first 40 weeks and you can see that it stays pretty much equivalent except for a small drop in the pds group immediately after surgery which then recovers to their baseline. And this of course looks a little different than the curves were used to looking at because we don't have the initial improvement included in the trial and that's because all of these patients had previously received at least three vitriol and anti that Jeff injections. So within the trial we're not seeing that improvement but retrospectively they looked and saw that there was an average 11 letter improvement prior to trial enrollment with their initial anti that Jeff therapy. So this curve now looks pretty similar to what we've seen in the original anchor and Marina trials. Similarly, they also showed stable and equivalent OCT thickness measurements between the two groups. And they also showed that based on their refill criteria that only 1.6% of the pds patients required any supplemental injections during these first 40 weeks. And, and finally at the end of 40 weeks they send out a questionnaire and fast majority of patients who had the pds implant work happy with it and said that they prefer that over monthly injections. So let's look a little bit at some of these surgical videos this doesn't show all the steps. And I'll talk a little bit about how they changed the surgical procedure bit from kind of the beginning of the latter study to the end of the archway study. So they measure a 3.5 a squirrel 3.5 millimeter square measurement which is four millimeters back from the limb this this is after they've done a careful pertumia in the super temporal quadrant. You'll also notice that they have a 27 gauge infusion line, which they actually don't turn on until the end of the case just to repressurize the eye if it is soft. And the surgeons also use a traction suture, much like for traps or tubes. So let's play here as they do a careful cut down with an nbr blade. And then a new step that they added that they found that reduced vitreous hemorrhages was they use the endo laser to treat kind of that exposed you via to then reduce vitreous hemorrhages that were associated with the pds and with the actual paris planate incision. Here's the implantation of the pds that should fit pretty snugly in that incision, and they can kind of just tap it in there. And then of course, closure is super important, which is a little unusual for retina surgeons and I think we have a lot to learn from glaucoma and at the end of this I'd love to get their feedback about things that are you know tips and things that could potentially be done better. But, but kind of a two layer closure where you're ensuring that Tina and conjugal Tyva is is closed here also selecting patients that that have healthy conjugal Tyva also seems to be important. So really ensuring that there is going to be the lowest risk possible possible of retraction or erosion or exposure of this implant is really key in its surgical success. And then the refill and clinic is really interesting so I have a little animation here. So the shorter needle that enters and then extracts the fluid and replaces it with that high concentration of randomism ab. And this is what it looks like in real life. Some key points where you have to be almost perfectly perpendicular. And you need to target the center stock of that pds implant. You can see that fluid being extracted there as as it's being filled at the same time. So, pretty quick refill procedure that again in the archway study was performed at six months. But the latter study study did show that many patients could go potentially a lot farther with an average out to 15 months for refill. So the most important part of all this thinking about, you know, kind of, if we're going to be using this and in what patients we should be using this is is the safety profile. So let's let's kind of get into that a little bit. So this this is from the phase three are twice we'll kind of go through the ocular adverse events. So a first off was concrete have a bleb or filtering bleb leak so they saw this in about 6.5% of patients. And then a couple pictures of what it looks like so they reported that almost all of these 15 out of 16 was just a focalized localized conjugal bleb or swelling without leak that resolved on its own. And then what we see on the left side of the screen, and almost kind of just like an attempt in encapsulation over the pds. And then they saw they saw one kind of more significant bleb, but actually this apparently did not need surgical intervention and it resolved without treatment. And then on the left side of the Cambridge like I mentioned was actually a lot more common early in the early parts of the phase two ladder study. And it seems to have been improved with addition of that external laser as well as the placement of the infusion line to avoid hypotony at the end of the case of notes, all of these cases which happened, about 5% of cases resolved without the track to me in this archway study. And then was about the same between the pds and intervitual injection patients and a decent number of faked patients were included in both arms. And then the erosion and retract retraction, definitely, you know, a significant complication here that that obviously perfecting that surgical technique will hopefully help minimize. But nine of 11 of these cases did need some type of surgical intervention whether it was just repositioning the tenons and kind of typo, or I think it was somewhere between three and five of these cases required partial thickness over that area to help where they've had that retraction. Endophthalmitis clearly a big concern. It happened in 1.6% of patients, so four cases, which which was higher than the intervitual injection arm. These all occurred more than one month after surgery so I think kind of like tubes and things like that that there's obviously some persistent risk of endophthalmitis with this foreign body in the eye. And notably three or four of these were associated with contact table retraction. So I think that really emphasizes how important tenons and contact table closure is for this new device and in both help helping avoid exposure erosion but but even more importantly, helping that helping avoid endophthalmitis and then three or four of these cases with treatment some of which included detractomy were able to return to their baseline. There are also two retinal detachments that were repaired with detractomy and one high female. So, so clearly some you know some elevated risk which I think is going to come with any surgical procedure and hopefully able to be minimized with surgeon comfort and kind of continuing to improve that surgical protocol but certainly some elevated risks with with a foreign body there. So kind of thinking about who, who might be, you know, a patient that would benefit from PDS who would be the perfect PDS patient. One I think, you know, it clearly has to be a patient with what AMD who has shown good responsiveness to anti-veget therapy. You don't want to put this into a patient not knowing if they may not be a good responder to anti-veget. They have to have some some decent visual potential I think to to a kind of accept this risk of surgery. They have to have difficulty meeting the current treatment burden I think we see a big spectrum of patients some have no problem coming in every month they're retired it's their number one social activity of the month and they like coming in I think these patients are not the ones who are who are seeking necessarily these these longer term treatments but on the other end of the spectrum we have a lot of patients that hate coming in for injections they hate injections themselves, and they're always asking about more durable treatments or surgical options. So I think there, there are definitely a sizable number of patients who are asking for something like this and, and you know I think you, you don't want to talk patient into this type of surgical procedure. You want a patient who's able to undergo surgery and enthusiastic about it was who's essentially asking for it. I think I think that will kind of be the ideal patient especially as we're starting and becoming more comfortable with this type of procedure. Ideally, you would want them to have no past or future glaucoma surgeries. The future might be a little hard to predict but obviously, you know, patient has moderate glaucoma or maybe any glaucoma maybe maybe we shouldn't be using the super temporal quadrant for this implant. So, you know, healthy congenitiva, which can be a little more difficult in our elderly patients with thin conge, then tenons, scleroplax and things like that so really a close exam of that quadrant I think is going to be really important in increasing our success. And then also, you know, we want to think about whether they're a better candidate for something else we're going to hear about a couple other available or upcoming treatment options. You know, longer lasting injectables, gene therapy, things like that. So thinking about, you know, is kind of which one of these new treatments is best for this patient is something that's going to be I think tricky to figure out and probably involve a long discussion with the patient and kind of our own comfort with the surgical techniques and new treatments. I'd love to try to answer any questions and especially if the glaucoma folks have any advice or concerns about this. I'd love to hear that too. Thank you very much. So this was an excellent overview and really appreciate your approach from the practical approach to the topic. So are there any questions where people are getting sorted. You addressed at the end. Patient selection. So if you think about the patient populations and having anti veg treatment for one year. What would you would be your estimate how many patients what will be the percentage of patients would be, you could offer this pds implant like 10% 50% 80% Yeah, that's a really good question. I think, you know, obviously patients that are successfully extended out, you know, the longer they're successfully extended on the agents we have right now. There's a little bit of diminishing return in those patients in a surgery like this. I think this surgery probably benefits most the patients who are kind of stuck at four to six weeks and don't like it. That being said, you know, I don't know, I think that's probably, that's still a pretty sizable amount probably close to, you know, anywhere from like 20 to 40% of patients, maybe approaching 50% of patients we just can't get past six weeks or so. And, you know, I would say the majority of those don't like it very much and would be very interested in a surgical longer lasting option. So, you know, my ballpark guests would be something like, I think, 25 to 30% of patients would be kind of eligible and be the group of patients that would benefit most from this. And then I think it'll be an individual discussion with each one, making sure they understand, you know, the risks that come along, especially in the post-op period to see if that's something that they're interested in. Very good. And, and what would you say is a good responder so how many anti-vegetarian injections, minimum number of injections for the patient had before moving forward with the implant? Well, I certainly, I definitely wouldn't go less than three because that was what was done in the trial. I think that's in most patients, that's usually enough to, especially if they are, are going to show you a good response, you often know that pretty quickly. You know, the other patients I think this will become an option in our, some of our long-term patients that will be treated for years and years and just know that they're still dependent on anti-veget. But they're ready for something longer acting like this. So I think, I think three would, would remain my minimum. I see Paul Bernstein and Mike Teschi here. Do one of you would like to give an update where we are with the Moran on this new treatment option? Okay, I'm on. We are, I think already approved for the PDS and we're going to be having training on this in the next few weeks and towards the end of March. So we're having a special training session. But it should be available. I don't know about, you know, insurance approval will be a challenge. I hear yesterday that I think nationwide 45 of these have been implanted commercially in the last few, in the last month or so. So it's just starting. But I think, you know, there's going to be, there is definitely a learning curve and we don't want to have a bunch of complications right at the beginning. That's, that's not going to be good for anyone. So your question about, you know, kind of conch closure, you know, something we do in small zone and cataract surgery, I'd really, you know, again, really advise you to make sure people do have robust tenons. There's just no replacement for that. And then just make sure that, you know, that you're really down to bear sclera and you're not, you know, leaving any tenons on the base as well. Those would be the only two tips. It's like, you know, the archway trial they did use this partial thickness cornea graphs to cover that's been done with, with success, you know, actually over the years for various things like glaucoma and that's something that I think, you know, over time, you know, could be used really effectively. Great, thanks. And, and we move on and I would like to introduce Hongam, Dr Lee, who will talk now about the biospecific antibody. Can you guys hear me and see my screen appropriately. Okay, great. Good morning everyone. My name is Hongam Lee and I am a second year and a fellow at the Moran Eye Center. And today we'll be talking about a new play on the field as Dr Flakenstein has called it. But, but by small, and these, these has just been recently approved last month, January 2022. In this business wire press release. So FDA approved, and it's marketed as the first by specific antibody, designed for intraocular use. And it actually has been approved not only just for a new vascular AMD but also for DME but today we'll focus on its indication and use for wet AMD. So, you caught me stumbling on the pronunciation of the name of this, the brand name of these drugs, the generic name is the scientific name is for recent map. And the brand name is, I bet a lot of you probably when you see this word pronounced as barbismo, the correct pronunciation as I learned yesterday at the dinner was is by small. And the anatomy of the name actually tell you a lot about what this molecule is about. So the V in the bias mode stand for the V in anti that chef a and the a stand for anti inch two. And these are the two pathway that these by specific molecules aim to target. So the bias here stand for by specific and the why is meant to resemble the shape of the molecule. So why shape and the MO stand for molecule. So just from you know understanding the anatomy of the name itself you can have an overall understanding of what this of the design of this molecule and what it aim to do. So, so, for specific antibody is often up to use one molecule to target, and the two target are anti inch to an anti version of a intervention as well know is the target of alia. Okay. So this is a quick basic sign review into inhibition of to the time to pathway and that chef R2 pathway of the two pathway involved in new vascular AMD and the inhibition of these two by as to drive vascular instability. And with vascular stability, we have fast for leakage, new visualization and inflammation. The first two is what we can visibly see in patient with AMD on OCT and on exam and the elevated level of both and to invest together, synergistically increased the vascular stability is ability. And that leads to what we see as what AMD or new as AMD, as we know that both of these levels are elevated or upregulated in patient with an AMD. Okay, so. So that's, that's how my advice more work is that it independently minds and neutralize both as to invest a thereby enable doing inhibition of two distinct pathway involved in what AMD this is the first time that we have a medication that is designed and has been demonstrated to this. And this is a screenshot from the bar by small prescription information that you can get online via this link. So the indication is as I mentioned for what AMD and also diabetic magadema. And if you follow the instruction of the prescription information. Then you would do a for a monthly a Q4 week. Dosing for the first four months. And then you would evaluate the patient after the first four months, you value the patient at eight weeks later and 12 weeks later. So essentially week 20 with 24 to inform you if you are able to extend the patient to 12 weeks and then they are to 16 weeks or to 12 weeks. So, it's a little bit different from how what we do be doing in clinical practice with Aliyah where you do. I'm around you do like three monthly, a series of three, so loading those, and then you extend by one to two weeks. Here, they extend by up to four weeks so you have like either eight weeks interval, or 12 weeks interval treatment or 16 weeks interval treatment, but nothing really in between. And contraindication are just like any other interval to injection. No ocular or prior infection inflammation or hepatitis to the drugs. And just a quick note that, you know, this has not been studied in pregnancy or children. And it's clearly most of our patients and will enroll in the trial that led to the FDA approval, early patient. The approval, you know, stand from the data that we've got from the two phase three clinical studies. Tanya and certain this were the patient will enroll and in 2019 with analysis done 48 weeks after analysis. So these are non inferior trials they are not meant to be had to have comparisons. And the study was conduct over 271 site across the world but mostly in the United States and in Europe. And maybe a few in Australia and in Asia. So, who are the patient I wouldn't want to study they are patient with new vascular AMD age above 50 treatment naive. And they have like macular CNVM, and they will randomly assigned to one to one ratio to either the study on the control on the study arm is by by smoke recent maps 6.0 milligram up to every 16 weeks after forwarding loading those versus the control arm is a flipper smart. Aliyah to point milligram every eight weeks after three loading those and the analysis is conducted at 48 weeks so roughly one year. The primary end point outcome measure is mean change in best corrective visual QT from baseline at, and they take the average at week 40 with 44 with 48 to give you the average here. So in a vibe by this is the tenure tenure trial patient with a bias will gain about 5.8 letters versus 5.1 in the flipper set arms. Similarly in the lucid trial six point six letter versus so it's the same in both the bias more and the flipper set arms. It's just the summary here, five to six letters improvement, and this figure here got to just show you the favorability of the bias more versus idea. I would say this is close to equivalent is not in fear is what I'm trying to tell you it's not in fear, whether whether it is superior is not demonstrated here. And this chart graph here tell you, at 48 weeks, how many of these patients are we able to extend to every 16 weeks. And the answer in both tries a roughly 45%. But if you also count those who they were able to send to 12 weeks, then you get up to 80%. And another easy way to look at this is at week 48. We have 45 so roughly 50% of patient that able to extend to 16 weeks. What does that mean that mean they get follow the following those and plus two injection and with 28 and 44. So they get a total of sick injection at 48 weeks so in one year they get about six injection. And then 33 of them get seven injection and the rest got nine injection. So on average, you can say that patient. If you follow the vibrational clinical try protocol will end up getting between six to nine injection with most of them, 80% of patient getting either six or seven injection. This is comparing to at least in this study, our patient in a famous arm receive a total of eight injection because they get three loading those. And then after that they get fixed QA injection. That means three plus five so eight injection. So, if you take the average, on average patient in the vibrational arm get one less injection per year. And we care about common adverse reaction. So very similar safety profile compared to earlier. The most common is conjugal hemorrhage which to us is not detrimental so that's the very acceptable adverse reaction. So we care about our property, you know, giving the recent history of the failure of the overview with the concern for random vasculitis. These two phase three trial demonstrate no case of random vasculitis report at least in this two phase three clinical trial. In terms of our P.T. is something that we were about is 3% for the bismuth versus 1% for a fever set. I don't have here the data for end of the Midas but it's less essentially less than 1%. So that's the price tax so a little bit more expensive than alia $2191 for one dose of abysmal versus $1850 for alia. So that's a difference of $340 per dose. So it is potentially a cheaper treatment option. If you are able just to get one less injection per year and I mentioned earlier that at least from this clinical trial on average this patient, most patients get one less injection so the price tax different of $340 is, I would say well, it would be acceptable. Can you try to come to an end please. Here's some key point here. Thank you. Thank you very much. I think this is a piece of you something very easy to implement in our in our patients. Is there any any quick question please raise up your hand. And not not the case why Chris tried to use that already to show your screen where we'll ask one more question to, to Dr. Lee. So, do you think that we need another trial to compare directly a flavor set on this regimen before we can really say that this is long acting or do we have any stronger data to suggest that this will make a big difference. I feel that at this point we can always say that it's not inferior, but we can say that is superior. But if they are both the same. If this Q 16 week release. I can say that it is definitely durable because if you think about it 48 in 48 weeks after the first four loading those that's already like 16 week right, then you have 32 weeks left, because 48 minus 16 weeks. That is 32 weeks right and 32 weeks you only have you can you're only able to say that you can you can maintain the Q 16 with two time with this one year follow up. But if you are able to do this just for one year, the price that you actually save about $1,000. If you let's really try to be any picky about you, you potentially can save $1,000. I think I think we're all very motivated to try this out and I would also reckon that from patients from the patient perspective, there will be much interest in in this new option. Okay, thank you very much because we are running out of time a little bit I would like to pass on to Dr bear, who will talk about an even more innovative approach about gene therapy and Amy to stick it away. Thanks Dr. Can you all hear me and see my screen okay. Excellent. And so yeah, for those who don't know me my name is Chris bear on the first year retina fellow here at Moran and we're going to talk about a potential one time treatment with new gene therapy really excited to be able to present this to you. I have no financial disclosures to talk about. So just to quickly start and we're going to move through this pretty quickly in the interest of time but as a representative patient we have an 80 year old woman with exedative magnitude generation. This is her fund is photo showing macular Druzen retinal pigmentary changes, a little bit of treatment history. Her right I started receiving introvertual injections in May of 2020 you can see her presenting OCT here with subretinal fluid. She was stable at four weeks with resolve fluid until September of this past year which had recurrent subretinal fluid. We continue to read four week injections and presently she's doing well with no residual fluid vision is stable at 2025. And I was sort of receiving injections in December of 2019 initially received injections every four weeks, transition to every eight weeks you can see you're presenting OCT here with again a little bit of subretinal fluid and kind of this classic double hump sign. She had recurrent fluid and subjective vision changes in September of 2021 with, you can see intro retina assist here on our OCT. Despite receiving injections every four weeks she's has persistent intratenal and subretinal fluid you can see here vision decreased from about 2030 to 2060 at this OCT here. So we tightened her to every two weeks alternating idea and a vast and injections, and you can see she's had resolution of her subretinal and intratenal fluid with stabilization revision down to about 2030 which is kind of close to her base. So in a patient like this what would you do, you can continue injections at frequent basis every two or four weeks. That becomes problematic. Every two weeks with insurance companies not wanting to reimburse that or do that every two weeks and then injections every four weeks you know can be a little bit burdensome for patients and we'll talk about that in a minute. Photodynamic therapy is always an option although it's not our first line treatment and there are risks and side effects associated with that or is there something else we can do we've heard about a couple things already today. We probably know about the burden of anti-vegeta treatments I'm just going to kind of skip over this. I want to get to the kind of highlights here which is the new gene therapy trial that Miranda is going to be participating in this is called the atmosphere study for patients with neovascular AMD and this is a partnership with Regenex bio offering a potential one time treatment for patients with neovascular AMD. The purpose of this study is to take this AAV8 viral vector with a gene encoding for an anti-vegeta monoclonal antibody and with a sub-retinal approach induce and transfect retinal RPE cells to produce this anti-vegeta molecules designed to sequester and neutralize vegeta molecules produced in these pathologic states. This vector particularly has been studied and it's been shown to have reducing genicity with this pathogenicity and it's been shown to have increased levels in the retina making it I think an ideal candidate for sub-retinal gene therapy like we're seeing here. This is a high level overview of the study so walking you through what this slide shows. The study is going to be looking at taking place at about 60 sites trying to enroll 300 subjects there's going to be three arms patients are going to be randomized equally to these three different arms the first arm is a control group you can see my mouse down here. These patients are going to be randomized to receive monthly ran a busy map injections. The other two groups are going to be the study medications of the treatment groups and they're going to receive different doses of the study medication these doses have been determined based on efficacy and safety data from the earlier phase one and phase two a data. All patients will receive preoperative or ran a busy map injections at four week intervals. You can see here the patients randomized to the treatment group will then undergo surgery and we'll talk about what that looks like here in a minute. All patients will receive a postoperative ran a busy map injection and then patients who are in the control group will continue to receive monthly ran a busy map injections through the duration of the study. All patients who are in the treatment group will receive injections on a PRN basis and that PRN basis is determined by the investigators. If they're receiving if they see new CNVM activity new fluid on a CT. If they have reduction in vision or if they have new hemorrhage on exam. All are going to need to be pseudophagic. And all patients works these studies excludes patients with severe sub phobia pathology similar to the pds studies, severe sub phobia atrophy or fibrosis. So the way this is delivered is through a standard vitrectomy so patient has a standard three port vitrectomy. So using the med one micro dose injector which you can see here attached to the dork 41 gauge sub retinal extendable canula. It allows the surgeon and a very safe and controlled way to inject a sub retinal to eject the medication and create a sub retinal bleb in the inferior retina. We're aiming for about a 200 micro liter bled patients have received their standard postoperative care with standard postoperative drop regimens. As special position requirements you can see a bright positioning for patients with discharge. So we're excited about this for a few different reasons. Number one, this is data from the earlier phase one and phase two aid studies, and this gene therapy is shown to be number one, very safe and well tolerated. You can see that the common adverse effects here are similar to what's been presented already today. We have contactable hemorrhage. Importantly, postoperative inflammation was mild and resolved on its own. There are patients the most common was retinal pigmentary changes again most were mild. The two that were severe were observed with were more significant when patients had blubs made in the superior retina which has been changed now to have blood done in the inferior retina in our ongoing studies. And again, no patients had permanent reductions in visual acuity. And there were no evidence or no incidences of endocrinitis or retinal detachments or issues like that. And we're excited because this seems to be effective. So this graph shows you reductions, rejection rates in patients pre and post intervention here and what you can see, I've highlighted these cohorts here because these are the concentrations of the medication that we're going to be giving in this upcoming study. And you can see that there is a pretty significant and sustained reduction in injections. So a 60% reduction extending all the way up to two years in these patients and about a third of these patients have not needed any into VGF injections during the course of the trial. So these are all things that you know we're excited and we're going to be offering here at Moran in the near future moving forward. So if you're interested in more information, so the clinical trials.gov registry for the studies listed here, and then Regenex bio had a nice press release about their phase one and phase two a data at this link right here. So in the interest of time, I'll cut it short there. A special thanks to a few folks here so Dr. Bernstein for, you know, getting us in on the study here and then Lillian Chen and Gina, of course, Kurt says who are our contacts at Regenex bio and have been really helpful. We're sending some of the slides you see here and forward in a lot of the data and information that we've seen. So I'll wrap it up there but if you have any questions happy to take them. But like I said we're excited about this and looking forward to getting patients on this treatment moving forward. Thank you very, very much, Dr. Bear this was was this was wonderful. And so I think there are good reasons to be excited. Please raise your hand if you have any questions. I'm not sure if Dr. Bernstein would like to add something. Before he is getting online and Chris, what could be in the long term I think one concern might be in the long term that you constantly suppress VEGF, and you'll be all aware about the discussions on atrophy development. So, any thoughts on this. That's a great question and that's, you know, that's a really good point and I think that this is where the, the long term studies are going to be beneficial and seeing, you know the developments of atrophy, moving forward so Regenex bio is currently, you know, having long term follow up. So these patients in the initial phase one or phase two a studies are being followed out to five years. I don't have that data yet, but I think those will be really helpful and you know determining the rates of atrophy and, you know, moving forward, but you're right that is a concern and you know something that we have to consider patients moving forward. So, I'm online now I just wanted to add that we are today actually is our site visit site initiation visits so we are approved and ready to go on this. So, at least one patient and in fact it's the patient that Chris presented who seems very interested. Her, her husband is a is a as a retired surgeon so they've already gone online and gone through the risks and benefits I actually offered them the various options of, you know, having the court versus new drugs and they seem very interested in going ahead with this so. It's a very good candidate for this because we really have to do a lot of injections on her. Another thing I don't think you mentioned on this that is that this study in the past I think still going forward is really looking at biomarkers with this to because we there are Paris and TC is done to show that this drug is being made essentially in the eye and is detectable in the anterior chamber so it's, it does, and they'll be able to see if it's really a sustainable effect. So you're the fellow unmuted I'll ask you this question. You know, if you were betting on any one of these, do you feel like that there's a pathway toward one becoming dominant in the market, or is there not really a holy grail and it's going to perhaps be a little bit more like mix that just an abundance of options. Great question. You know, I think that this is really important to, you know, consider patient factors and patient selection and what you're treating what what treatment recommendations you're offering. You know, I think that the easiest one is going to be, you know, for us a map. It's an injection we already doing clinic patients are already used to that and so, you know, I think that's going to be the low hanging fruit, you know, as to say any easiest thing to get patients on board with. I think that have recalcitrant disease like another patient I showed here. You know, first amount might be a good option for that patient but for maybe more long term, or more sustained treatment for those patients gene therapy or the port delivery system might be better for those patients so that's kind of a I know kind of an unsatisfying answer to your question but I think it kind of comes down to. The patient factors that come into play the easiest one to do with the first map because it's on the page is already used to but these other treatments and you know the other things that Dr. mentioned down the line. I think we're going to play a role, a big role moving forward. I think it's a wonderful situation for us right now to actually investigate what is the best best option for patients and so we will have longer discussions with patients and I'm sure about it and we will find out.