Sign Maryland Assignment of Partnership Interest Mobile

Document type sign assignment of partnership interest maryland mobile

so welcome everybody to sight and sound technology's very special evening webinar where we're absolutely delighted to be welcoming brian culley from lineage cell therapeutics we'll be talking about brian and introducing him properly in just a moment my name is stuart lawler i'm from sight and sound technology and my colleague glenn tukey who's our chief executive is here with us as well and glenn will be speaking in just a second you're very welcome as i said to this session that we've been planning for uh quite a while and we're very excited to do talk about this because it's always interesting to hear what's happening in the field of research and clinical trials and where things might be looking in the future and we're looking forward to brian's presentation and indeed to your questions and answers or rather to your questions and to brian's comments as well as and speaking of questions you can get in touch on zoom this evening by either raising your hand so you can click the raise hand button or you can type in the chat window which is also available to you during the presentation and uh glenn and myself will be keeping an eye on your comments and questions and where there will be um an opportunity at the end for a q a with brian now before we do anything else i'm going to introduce ed len tukey who's the chief exec of sight and sound technology to say a couple of words glenn yeah thank you stuart and welcome brian we're very pleased to have you here with us this evening um i'm the chief exec of sight and sound and i've been in this uh fantastic industry for 13 years um those of you who haven't heard of us at sight and sound 42 years now um i have to hasten to add that i haven't been at the helm for all 42 years although i feel like i've been sometimes for 142 years we're the leading supplier of technology for blind low vision in the uk we're best known for that for sure many don't know that we're also in the world of uh literacy and behavioural and a wider range of disabilities as well so we're very proud and pleased to be working with probably anyone's time 40 000 or so um people who use technology to uh help them level up the world and i'm sure brian's going to tell us how he's going to make us all redundant in coming years but uh right now we uh use that tech and the support and the training we give to uh to help people with uh any form of disability um for those of you in the uk you can find us in northampton glasgow and the wed stewart is in almost sunny dublin where we uh where we have centers um but you can find us off wedging all over the uk so we've got about 40 people we're 15 million to another business so we're well established and if after this you feel that you can benefit from many supporting technology training or knowledge around some of the technologies that support low vision then just please do get in touch with us um but before that um you can you can hear everything that brian's got to say because i too am right at the front of the audience ready to uh listen to tonight's events um so uh over to you stuart and uh to introduce brian uh thanks very much glenn and just add to what glenn said if you want to know more you want to have a look at what we do and we're doing lots of stuff as leon has just mentioned you can see us on the web at site and sound dot co dot uk or of course we're also available on social media so you can find us there if you want to keep up to date with what we're doing now brian culley is the chief executive of lineage lineage and joined in september 2018 um he's an experienced public biopharm pharmaceutical ceo having served in that position with a number of companies and his broad experiences included the clinical development of pharmaceutical sorry of pharmaceutical products from development through phase three we're really looking forward to hearing brian's presentation this evening it's just gone 10 30 in the morning where brian is on the west coast of the us so brian thank you very much for joining us and uh the floor is is yours well thank you stuart and thank you glenn it's it's really nice to be partnering with you guys on this presentation today and uh good evening to uh all of those who are rejoining from the uk um i'm going to share this slide deck which should be present now for everyone and just move this over here and i'll be ready to go so thanks i'm gonna spend about about 15 minutes talking about principally about one of our three programs in cell therapy to try to improve outcomes for people suffering with dry amd lineage cell therapeutics is a listed company and so i refer everyone first to our safe harbor clauses i will be making some forward-looking statements my background was covered you know this is the third time i've i've run a biotech company and i have extensive experience including in in difficult areas i ran one of the largest clinical studies that's ever been done in sickle cell disease it's the almost 400 patient clinical trial and i i really get tremendous enjoyment out of managing clinical studies and trying to develop therapies that drive positive clinical outcomes so an overview of the business before i really dive into our lead program um the way that lineage cell therapeutics operates is that we transplant cells into patients and and we use what we call off-the-shelf cells so we're manufacturing cell types that may be lost by your body due to disease or injury or accident and so we're replacing them so our approach is really like transplant medicine there's a lot of noise and confusion around what cell therapy is our form of that is that we manufacture specific cell types we do control our own manufacturing we have two facilities where we can manufacture clinical trial material and we have three programs that are currently in the clinic we have today's topic which is a program in dry amd but we also manufacture a special kind of cell for spinal cord injury and we manufacture a special immune cell to treat cancer and it's been very exciting because we have seen some early evidence which supports our belief that cell therapy can drive successful outcomes in in areas where traditional approaches haven't been able to provide solutions we are a for-profit uh drug development or therapeutic development business and so we are aware that there are um you know commercial attributes that are of great interest to our investors and and their investments help us move our programs forward and uh we have been quite successful recently moving those programs forward and we we have announcements coming and in fact even this quarter we have announcements pertaining to data that we've collected in dry amd so that's quite exciting and the company has uh managed to be well funded throughout this period and um you know it's it's very variable i think this last point about the the value of the company is a little old uh we've continued to grow and make some real progress and i think we're probably now around 400 million u.s in terms of market value so now turning to our basic approach we are working to bring forward this this essentially new branch of medicine where we transplant these cell types into the body we start with undifferentiated stem cells so these are these are incredibly powerful cells for a couple of reasons one is that undifferentiated stem cells have within them the ability to become any of the cell types in in the body they haven't decided what they're going to be to grow up right like a small child with a lot of promise might become a police officer or a politician these undifferentiated stem cells have not yet decided to become liver cells or heart cells but we know what the information is we know the men the recipe rather to convert them into specific cell types and only those cell types so we have the recipe if you will to manufacture retina cells from undifferentiated stem cells and we do it completely we never put a stem cell inside of a patient we only turn those stem cells into retina cells and then we transplant retina cells into the patient we don't manipulate the dna there are some technologies out there which involve manipulating the dna the genome of the of the cells we don't do that um it's more exposure as i say it's like a recipe we sort of coax the cells into becoming retina cells and only retina cells and we're able to do this from a single vial of cells a cell line was established more than 20 years ago and the incredible thing about these undifferentiated stem cells if you need more of them you can simply plate them out provide them with the nutrients that they need and they'll divide like like many cell types they'll divide and so we have essentially an endless supply of those cells and at some point after growing huge numbers of them we convert them into retina cells and then freeze them down so we have the ability to um through this self-renewing uh attribute of these cells we can manufacture tremendous numbers billions upon billions of retina cells this is our facility we have about 30 employees there many hundreds of patents that are associated with our work and protect our technologies and this is a summary of our three clinical stage programs and the one at top there is the one i'll talk about today operation rpe cells so operogen is our code name for it rpe cells is the identifier the retinal pigment of the epithelial cells to treat dry md with geographic atrophy and one of the notable things about this program is that we have received 16 million u.s from the israeli innovation authority this is technology that was first established in israel and we've since moved it over to the united states enrollment is complete in this clinical trial uh late last year we finished enrolling all 24 patients so the the patients all had dry amd with ga um this audience needs no explanation about what dry amd with ga means uh on a very serious level and so um but but there may be some others who have joined who aren't as familiar so um this is a panel of images that shows the progression of the disease this is a progressive disease which only gets worse with time and its attribute primary attribute is the death of specialized retina cells in the back of the eye and these uh images here showing an increasing area of the black smudge there that is the area where the cells are dying off and you can see in this individual between 2012 and 2015 they went from having normal 20 20 vision to being legally blind a us definition of legal blindness and then continued to deteriorate after a couple more years all the way to 2640. so this is what happens this isn't a reversible condition things only get worse with time it's enormous unmet need the other form of amd called wet amd there are tremendously successful therapeutics for that condition but there's nothing yet to treat dry amd despite the fact that far more people have the dry form of age-related macular degeneration than people have the wet form so there's a huge unmet need and opportunity here so how do we do it what's a solution what do we do with lineage that's different well these cartoons here show how we envision a before and after so beforehand those orange cells those are the rpe cells they are sandwiched between photoreceptors and and some of the other layers of the retina and as they become sick and die off and degenerate waste accumulates that's called drusen that's just the accumulation of of lipids and fats from the vision cycle and ordinarily those are cleared by the rpe cells that's one of their jobs but when those rpe cells die off that drusen can accumulate in the eye and you can just look right in and see it it's quite quite easy to find what we are looking to do is manufacture brand new rpe cells now moving to the right here shaded blue we have these new rpe cells we manufactured them we injected them into the patient we place them very carefully into the sub-retinal space and they are taking over the job of the retina cells that are that are sick or or have died off and in doing so they're they're acting to recover uh or rescue the photoreceptors that are so important to your vision uh and clearing out that jerusalem material so this is what we are trying to accomplish in the patient's eye the clinical trial had multiple components but i like to break it into two sections i like to break it into cohorts one through three and there were 12 people in the in that in that group those 12 patients were all legally blind so they had very severe disease um everyone was worse than 2200 and they were essentially a safety cohort we didn't expect to be able to to see a lot of benefit because they had very advanced progressive disease but then after seeing some encouraging signs we moved into another group called cohort four and these individuals had had better baseline vision some of them were as high as 20 65 and this is where we're really looking to see if we could provide some sort of evidence benefit or looking for evidence of a benefit in those patients and this is just a single injection about 50 to 100 microliters of cells are administered right to the sub-retinal space in these patients and we completed the enrollment in this study in november of last year so what have we seen 24 people's treatment what have we seen well we're quite excited that no one rejected the cells there was no acute or even delayed rejection of our cells they were retained in the eye and in one case the earliest treated patient has now been out more than five years with this transplant being engrafted into the eye the early patients went on to immunosuppressive drugs for as long as a year but as time has gone by and we've gained experience and comfort with the treatment we shortened that exposure to immunosuppressive drugs first down to three months and and then even more recently we treated a patient without um without any tacrolimus that's one of the stronger immunosuppressive drugs the patient's still getting local immunosuppression but we removed the tacrolimus entirely for a patient to see how they would tolerate it and we look forward to reporting on how that patient has done uh soon and so it's it's been quite encouraging the fears around rejection of cells have not come to be we also have seen improvements in vision especially in the cohort four patients that i described we've seen a reduction in the growth rate of the atrophy and we've seen some interesting things in things like reading speed and the clearance of that jerusalem material but the one thing that stood out more than anything that we're really excited about is one of our patients actually showed a restoration of their retinal tissue so i said previously that this area of ga only gets larger well in this one patient the area of ga actually got smaller we first noticed it at nine months and it has been persistently smaller out to our last check which was 23 months and the patient also has benefited with improved vision so this was quite extraordinary because human beings lack the ability to regenerate retinal tissue if you suffer a cut on your skin your body has the information the programming to be able to repair that tissue but you don't have that that capability in your eye so this is the first known report of retinal tissue restoration in a human being and it's very exciting and we think that um being able to reproduce this if we if we are able to reproduce this and demonstrate that it can happen again uh is is really incredibly promising and what may be uh ultimately one of the more notable findings to ever occur in the field of dry amd research so this is a look at how those 12 patients in cohort 4 have performed with respect to their visual acuity so these are these are values off of an etdrs eye chart and what you can see is the treated eye which is shown in the green line over time those treated eyes are doing better than the orange lines the orange lines is the untreated eye and you can see that on average patients are doing uh seeing about 10 letters more with their treated eye now these are somewhat small numbers you can see at the top of the figure where it says n equals 7 and n equals five um that's the number of patients uh but but now those numbers are n equals twelve so we uh we intend to report this quarter on how the data have uh evolved sinc we last reported it in november so there's an update that people will be able to look forward to to see if we're continuing to see these sorts of improvements in visual acuity this is again an audience that needs no explanation but one of our standard explanatory slides is showing what 10 or 15 letters of improvement might look like to an individual who's reading an eye chart and so this is moving from the um the letter k and the gray circle how does 10 or 15 letters of improvement look uh that it's it's quite notable you it's not subtle this is an improvement for these individuals and we have had individuals who have had uh 20 or even more letters at some of their recorded time points so those are those are fairly significant improvements in their visual acuity another important metric in the patient population is the growth of their geographic atrophy or ga over time and in this slide same same patients same time frame but you see that the curves are now inverted the orange or untreated eye is now above the green line and that's because the area of atrophy and the untreated eye is growing more rapidly than the treated eye so this is what we would expect we want the lines to be inverted compared to vision where you want to see an improvement here you want to see a reduction so we're quite happy to see this the lines the the collection of data and geographic atrophy takes longer it's slower because these are slow growing areas of atrophy so it can take a year or so to be able to detect differences but we are encouraged that we do seem to see some separation of the curves and we hope that as we go from five six four patients to eight nine twelve patients that these lines will further separate this is a bit of a complicated slide but this is what i was talking about before with the retinal restoration the color coding here is is time and the images are essentially aerial photos of an area of atrophy so back in may of 2017 um colored in orange we've essentially traced the area of atrophy so this isn't let's think of it as like an aerial map of the atrophy and you can see it changing from orange to red it has grown going from orange to red over the course of about a year so we confirmed that this patient had a rapidly growing area of atrophy and then at red baseline that's where they received a treatment and then we looked again at month nine and that's colored in blue and you can see now in the center panel the blue area is smaller than the red area and and that was the extraordinary finding where we had a reduction in the area of atrophy that continued looking at month 15 in green you can't even see it it's entirely covered and then all the way out to month 23 in yellow we couldn't we couldn't wait to month 24 we had had to look early so we looked at month 23 and continued to see that this patient's area of atrophy was still smaller than it was recorded at baseline so that is really extraordinary and again this patient has also benefited from an improvement in visual acuity now we we of course ask the question why did this happen what was different about this patient and we think that the answer is that this patient received a more aggressive uh coverage of their area of atrophy the cells were pushed further across the area of atrophy so they got more complete coverage and we think that that led to this benefit and so after we saw and understood this we actually told our surgeons to please be more aggressive to plea please try and reproduce this and so we have now a number of patients uh that that we are hopeful will be able to show that this phenomenon can be repeated and that is the result of some surgical technique and not not something exclusive to this patient i i don't actually know of any reason why this patient would have been genetically different we think it was more of a procedural difference and we we hope to be able to demonstrate that later this year there are many many comes um you know we we do often present not just the science but you know an investment perspective and so there are many companies that are working in this area although i would say that it's actually quite a small number compared to the commercial opportunity um but most of those companies are focused on complement they're interested in and how the inflammatory uh role that uh that is involved with the death of these retina cells and so a number of companies are looking at ways that they could reduce inflammation or affect inflammation cascades um the cell therapy companies they're they're not a large number of us or they're really just a handful which is curious to us because only cell therapy has the ability to uh restore tissue with infrequent dosing we all are aware of therapies that require an injection in the eye every month or every other month cell therapy proposes at the worst to be delivered every couple of years and potentially just a one-time one-time treatment for your entire life so uh so cell therapy to us is a modality that has some real advantages within cell therapy only lineage has ever shown this phenomenon of retinal restoration and we're also the only company that has access to a a delivery device that was established by a company called gyroscope it's quite a quite an interesting way of delivering the cells on the left here is a traditional way of delivering cells you you actually push the needle into the eye you remove the vitreous and insert the needle below the retina um so far so good you can deliver your cells you can deliver your material beneath the retina but then when you remove the needle a lot of that material can flow out of a hole that you made and that can lead to adverse events and complications and it doesn't give you control over your dose so this relationship that we have with gyroscope gives us access to a device in which the needle comes around the outside of the eye and up underneath the retina and in doing so you never puncture the retina so you have better dose control and you avoid the adverse events that are associated with cells leaking out of that hole so this has been an exciting new way that we've tried to improve not just the cells but how we deliver those cells assuming that we have some success and that this is something that many many people are going to want to have access to we've worked very hard on our manufacturing we make about 99 pure rpe cells we do extensive analytics to make sure that they are functionally active that they're the correct type of cells and again we don't genetically modify these cells we just expand them and instruct them to become retina cells we also have a thon inject formulation so the surgeon is able to thaw these cells just a few minutes before administering them uh and it the surgery itself only takes about 30 minutes so it's not unlike a glaucoma surgery the patient's awake um and there's a small incision performed in the in the sclera the needle is slid down and around and in most cases in less than a half of an hour the patient is is up and and leaving with their new transplant and we've been able to scale our manufacturing tremendously in a container about the size of a milk jug we're able to manufacture 5 billion rpe cells which gives us thousands of clinical doses so the commercial or the cost implications of being able to manufacture thousands and thousands of clinical doses from a single cell line it's always the same cell line it'll be the same cell line for 30 years um being able to manufacture you know upwards you know innumerable amounts of material from our process provides us with some real advantages so operation is i think really well positioned to disrupt what's been going on in the dry amd uh market there are some regulatory advantages or some commercial advantages but more important than all of that are what we see are the clinical advantages we think that the single use uh the potential to restore tissue um the benefits that we that we are trying to ensure can occur in connection with the changes in visual acuity all of these really give us a lot of excitement about what we're seeing and we sort of are unique it's a different approach but i think that uh it's quite compelling and you know i hope that some of the questions that we get are going to allow us to talk more about how we view this being used in the future i didn't want to say without talking about the other programs i do want to say for the opportune program we do have additional data that we will announce this quarter and then again next quarter um and this is from those patients in in october november there's six patients that we haven't reported yet so they're to have at least three months of follow-up uh that will report this quarter and then at least six months of follow-up that will report at the next quarter um and and these are a cohort of patients that came to us following the covid slowdown it was really hard to enroll patients for a few months but we've got it all in the fall and it's really exciting and from here we're going to want to go talk to fda about next steps so lineage is is really a different cell therapy company um we have three clinical stage programs we control our own manufacturing we have hundreds and hundreds of patents related to cell therapy the company is well funded and we're a growing leader in regenerative medicine but most importantly here at the bottom of the slide we're really working hard to see what we can do about helping the millions suffering with dry amd be able to you know slow their disease perhaps stop the disease or even it has hoped reverse the disease so with that i will um stop sharing the slides and uh invite us to head into a q a session uh thank you very much brian a really fascinating presentation and really interesting just to get a glimpse of what's going on right now and i guess more excitingly what might happen in the future really really great and powerful presentation thank you very much i'm going to go across to glenn to have a look at some of the comments that have been coming in on the chat during the presentation yeah thanks stuart um i've got a couple actually uh not necessarily highly related to the center of what you've been talking about but around the edges maybe in october lineage received a patent extending the op regen cells to other eye diseases how soon until some of those applications end up in clinical trials and how soon would other eye cells other than rpe cells rods cones get into the clinic yeah that's a that's a very nice question so um i really don't think of this as a treatment for dry amd with ga this is a an rpe replacement therapy so i don't think we should be limited to a certain definition of disease there are other diseases for which replacing the rpe could be beneficial so stargardt's certainly comes to mind uh the teleform maculopathy comes to mind like there are other places where we might be able to enjoy some sort of benefit for the immediate term we're focusing on dry amd there's certainly enough people out there that um you know it's a fine place to start but i think that longer term in connection with a life cycle management strategy we would definitely be interested in seeing where else the transplant of rpe cells could be beneficial and and you know perhaps in other disease settings you may be able to see better results or i you know it's it's really unknowable it depends on the causal reasons for the disease but if replacing rpe with you know fresh vigorous rpe cells is potentially helpful i think we'd ultimately want to look at that look at going into those areas okay uh thank you for that the another question uh same uh questioner actually was interested in your your team and said you'd had some recent exact changes uh and had you replaced your cfo um so that's an interesting left field one for you i'm happy to i'm happy to answer it no um uh yeah ms roberts was our chief financial officer she helped us tremendously with um with some of the um sort of rebranding and new priorities that we had in place for a couple of years she had an opportunity that was sort of a i can't say no so uh we are actually you know between cfos right now i'm filling the dual role which uh which is okay but we we have a an open position so we are going to be hiring a new cfo so that position will be filled so um yeah that's just professional evolution it happens at all levels so um you know not not anything that i think people need to worry about well back to back in the day job uh what sort of cost per patient uh does your your therapy income where are you with that yeah so the the important thing to keep in mind um there's a distinction between um the terms autologous and allogeneic so um what we do allogeneic is really off the shelf so i talked about the manufacturing scale and when you can produce huge numbers of cells and produce large numbers of treatment courses from a single batch that allows you to be very competitive on price there are some other technologies in the eye and elsewhere where companies or or academics are starting with the patient's own cells and then manipulating and then putting them back in one of the challenges there is that that is a very personalized treatment so so you're basically building a therapy for one person so i don't know how the economics of that really work out how can you really how can you have a profitable business if you are essentially making a personal medicine now it works in cancer because in cancer and some many places you can charge 300 400 500 000 but that's not realistic in the eye you know therapies in the eye might be you know four-digit five-digit therapies low five-digit therapies would be more pragmatic and and acceptable to the payer community and so i think when companies like ours are working on their therapies they're thinking about how they're going to be able to fit into a world where the the payments for these therapies are you know despite how long it may last they're far more realistic in light of the overall value proposition and not some of these crazy six figure charges that you hear about in other disease settings so we don't price the therapy today we we absolutely won't and um you know until and unless it's approved that's a very you know uh downstream question but what i can say is that by using allogeneic cell lines and enhancing our our manufacturing production it means that each specific vial of cells that would go to a patient is going to be very cost effective so i hope that's enough of an answer without actually providing specific pricing information because we don't have it today good one like it so um you mentioned competitors uh center biotech and notch new companies on the horizon um you know where do you fit in against them and where do they play in your marketplace yeah that's a broader question about um allergenic cell therapy more broadly um you know there there's there's a to use a gambling or poker reference and hopefully people get there's there's a buy-in to sit at the cell therapy table and and when people are thinking about lineage and other companies uh what i would say is that the buy-in to sit at the cell therapy table is that you you should be in the clinic you know if you're if you're real how do you assess if a company is really doing well you should be in the clinic you should have human data not animal data you should be able to manufacture your material in an economic way i mean it's one thing to say you can make material for a you know small number of people in a phase one study but you know do you have a clear path to providing a commercial and affordable commercial solution you know these there's a real questions that i don't know if every every company can answer um one has to think about the um the safety um you know i don't know i think it's very unclear at this point how some of the gene editing technologies are going to play out there have been some notable issues in certain places um they may be company specific they may be technology specific but if you want to have a seat at the table and sell therapy and you know be you know really credible you have to be able to make yourselves effectively efficiently reproducibly you have to be able to deliver them well and you have to be able to show people a clear path that y u have a commercial product and that that's been sort of the dna of our company is is working that way so i don't know every detail about you know the notches and the santas and the and the blue rocks and the semas and everything each is each is a little different and what they're emphasizing but i can say quite proudly that that lineage has worked very hard to help mature this field and be able to demonstrate things like you know fears about rejection of cells just haven't been unfounded today at least with our technology so i'm quite encouraged with respect to where we stand against and among all of those other companies that uh that some of which are are getting quite a lot of notoriety and and you know they they still have i don't envy them they still have years to go before they're sort of having multiple clinical programs like we are so i'm excited about where we're positioned and i think we have a lot of upside as well excellent front of the pack with a home uh more of a home question here can you expand on the one patient that resulted in retinol restoration that was not necessarily genetics versus surgical procedures yeah so it's it's always difficult when you have an n of one right because the immediate question is well why was that patient different so um we can't say because we have not been able to go back in time and you know treat that patient in different ways and you know kind of do that experiment so you have to start making assumptions so one of the things that we know is different about that patient was that they got essentially complete coverage so it when when you're thinking about an area of atrophy you know you want to be very careful when you're delivering cells you don't want to disrupt the macula you don't want to end up with a patient being worse off than they went in right so it's it's tricky to get your cells delivered fully across an area of atrophy now this patient in particular had as you saw in the pictures had sort of like these lobes or domains with their area of ga was multi-multi-focal so it may be that that area of atrophy it was easier to kind of lift it or separate it from the underlying and in doing so we were able to get almost complete coverage of our cells across the area of ga now if you go and compare that with a patient that's got say you know a 14 millimeter square ga it's really hard to get total coverage you've got very little to work with there but if you have these little pockets and islands you might be able to to get very nice coverage so we think of it we assume right now until proven otherwise that that patient had an extraordinary result because they got such comprehensive exposure to our cells across the whole area of ga it is much easier to ascribe their outcome to the process than it is to think that they had something genetic because our cells are indiscriminate about the reason why someone has ga so if you think of it this way the analogy here is is my car i need to get my car and go somewhere but it won't it won't take me there why well maybe the tires are all flat maybe the engine's missing maybe it's out of gas maybe i don't have the key there's a million reasons why i might not be able to get from a to b and all these other approaches are trying to say oh well i supply tires or i supply gas or i supply an engine we supply a new car right so i don't really care the reason why somebody has dry amd with ga which pathway is broken doesn't matter to us because we're providing new cells so we think that we cover everything so that's why we feel that the genetic profile of that individual is unlikely to explain why they had such an extraordinary outcome you know applying occam's razor it's far more likely that they did well because they got very aggressive treatment and we're hoping to demonstrate that right now because we went back to the investigators and said in the patients that are treated in your in your in your clinic going forward we would like to have you be more aggressive push those cells really work hard to get those cells across the ga and we also were looking for patients at smaller areas of ga or more of this island profile rather than a big giant circle in doing so we think that increases the probability that we'll be able to demonstrate that it was not a single phenomenon that it's actually something that's reproducible and ultimately where we want to go is we want people to be diagnosed early and and you can imagine that we've gone from these huge areas of ga to smaller and smaller i want to get to the point where somebody's having impaired vision they go to the doctor they get referred to a specialist they're diagnosed with dry md they've got early stage ga there's a little spot in there and we go in and we drop ourselves in there and that's it they're good for the rest of their lives that is where i think this technology is ultimately headed well that's uh interesting because it sort of is quite neatly positions the next question which is well could the infrequency of the treatment be a factor why fewer companies are looking at cell therapy less product needed therefore less profit you know if you're if you uh cue them with one shot then uh they're never going to come back um i so i don't think so and that's because there are so many people that have dry amd so so it it there's there's sort of like this almost like you know criticism or reputation that pharmaceutical companies don't want cures because it's not profitable i've never in 30 years met anyone who really has that view but i've met innumerable people who want to do good before you know their day is over so i i think that very it you know if that were the case then there would be no gene therapy companies but we have huge uh influx of capital pouring into gene therapy companies over the last few years and those are companies that are trying to cure people um you know bubble boy syndrome sickle cell disease i mean it's it's a it's a one-time treatment um but yet those companies are backed by very serious investors so i don't think it is the case i have a different view i think the reason why we don't have a lot of companies working in dry md is because it's really difficult it is difficult to use a small molecule or an antibody to treat a condition for which the hallmark is the death of the cell so in in some cases you've got you know one thing broken in a in a cellular pathway and you can go in there and you can increase signaling or decrease signaling with a small molecule you can block receptors and things like that but when the cell has gotten to the point that it is that it is uh dying there are so many things that have gone wrong to that cell i find it difficult to believe that you can use a single molecule to affect a single or a few pathways and have that turn into a clinical outcome when the disease condition is is so far advanced so you know i think that those small molecules or antibodies maybe if they're used super early and and constantly i think that would be more likely to show up in a clinical trial but you know we've we've had a number of companies we've had some very large failures in the space and i think it's because it just doesn't fit with much of the pharmaceutical armamentarium and that we need new approaches and in this case the transplant approach is i think where it's gonna where it's gonna fit i i feel the same with our spinal cord program just to go to the side for a moment there are molecules that can help grow axons but axons that don't wire together and fire at the same time don't work very well but using whole cells implanting whole cells and providing the insulation and the connectivity you know that's another place where i think that cell therapy is far more likely to be successful compared to traditional approaches many of which have failed okay um as your plots had large standard deviations did some people respond better than others if so what differentiates between them yeah uh absolutely um not everyone i you know when i first joined the company about two and a half years ago i thought it was curious that there was sort of this reputation that cell therapy was going to work 100 of the time in 100 percent of people um and maybe that's just there was so much excitement and there has been so much excitement in the field but the reality is there there's very few therapies out there that work in essentially everyone um personally i don't get much benefit from aspirin which is weird but it's probably got to do with my genetic makeup um so i i think that the it is unsurprising that we have both outliers um in terms of benefits and and not everyone is responding um that doesn't surprise me at all uh but i also think that this is a new technology that has not just the cellular component but also the delivery component and like any new technology there will be improvements over time the cells will get better the delivery of get better the patient's selection will get better and i think what we will see over time is an increase in the benefits so something like as simple as lasik surgery when lasik first came out people were scared to do it it sounded kind of daunting now you know i don't know that people really think twice they're happy to go you know have that kind of procedure done so i definitely think that with an early technology where you're still kind of you know fumbling around trying to figure out how best to deploy it and in whom and when that definitely gives us a lot of opportunity for improvement but i can also mention for that person asking the question that we have previously provided patient-level data so if you go back to some of our earlier i showed summaries today but if you go back to some of our earlier presentations uh that all file publicly you can actually see individual lines with patients and so you can see someone who's gotten 24 letters of improvement at four and a half months and you can see someone who had you know one letter of improvement which is basically meaningless so yeah there's there's definitely variability but over time as we add more data we will start to get a clearer picture of what the percent response really looks like and i think it'll improve over time for the reasons that i that i just stated well are there plans to treat the other eye of the participants uh eventually yes um so we won't be doing any sort of crossover in this study um it would not surprise me talking to a woman just a couple of weeks ago who has had a really wonderful outcome she called it life-changing would she like her other eye to be treated i'm sure she would but in the context of ethical management of clinical studies there won't be any crossovers in these patients the next study that we do will much more likely have a cohort of patients that are not treated and are compared with the ones that are treated so that we can really get a clear picture of what the magnitude of benefit looks like in an average patient okay will your phase three trials move to earlier treatments um i i think we will have and so i can't know until we sit with fda and have a conversation about it but i think that we will have enough safety data that the agency will be comfortable permitting us to go even earlier in our patient characteristics so right now we have inclusion criteria with our clinical trial that select for a certain uh minimum size of of atrophy and and certain um level of vision you have to have a certain level of impairment before you would be eligible for one of our clinical trials i would hope that as we go forward into later stage trials that we would be able to loosen those criteria somewhat on the on the good end on the earlier stage end because that would help us get more patients on study we get more evidence to to you know inform us uh going forward and uh and that would allow us to enroll faster and and i frankly think that that's where it's where this is headed is to earlier stage treatment um as i as i described previously i want to nip this thing in the bud before it before it gets to the point where you you've got um you know a 16 millimeter ga in the back your eye outside of amd and stem cell you mentioned other cells to treat disease can the same process lead to other treatments what comes to mind uh are there partners you think of yeah so um i'm a big believer that that cell therapy is is going to eventually deliver on many of the promises that it offered 10 or 15 years ago but i think cell therapy was a little too ambitious people were talking about you know a decade more ago talking about curing parkinson's and and autism and all of these very ambitious things um we almost as an industry forgot to get some some wins you know get some points on the board and so i like that we are working in the eye and the spinal cord um i like what we're doing in cancer i think that i mean there's been a lot of successes in cell therapy and cancer so i think that um the answer is that yes we we have some places like the eye and the spinal cord which i think are great places to to start longer term for lineage and for others yeah i think there's some other opportunities that people like to go into i know companies that have recently filed inds which will allow them to go into the clinic um i believe this month in areas like parkinson's and uh and and other um you know important and notable conditions so there's an evolution um would i like lineage to to capitalize on that expand what we're doing absolutely do i want to be the amazon of cell therapy yeah you know we the cells that we use can become anything so we just need the instructions and we need the the capital and we could go into other areas and you know obviously we keep a punch list of ideas and and we actually have data in some other ideas that we don't necessarily talk about publicly but yeah i think ultimately this as i talk about ushering in a new branch of medicine there's going to be a whole field of medicine around cell therapy based on where it works better than other approaches and it won't go away it'll it'll become routine and that's part of the life cycle of a technology answer actually like that how do you examine or determine rejection within the eye and what does that look like i guess my joke answer is i i don't know what it looks like because we haven't had it um i i think there are some uh i think there's some some um some things that we would be able to um rely on that would make us suspicious about whether someone was rejecting their cells um but again we haven't seen that i mean the beautiful thing about the eye is you know it's it's it's it's a it's a window right you just look right in so we can put a scope up and we can look in and the p in rpe cells stands for pigment so we can look and see that our pigmented cells are sitting there right where we deposit them and the imaging technologies are quite remarkable nowadays so we actually see the the bleb which which is where the cells get delivered we see it become formed we watch our material get administered to the eye we check on those patients uh regulate their physician checks on them regularly and is able to see how that transplant is is doing and the anatomy of the eye doesn't change you're always looking in the same place you just follow the vessels you can see exactly what you need to see and where you need to go and so if i don't have this particular set of slides in our in our deck today but if i were to show you the durability the the five-year durability of a treatment you would essentially be looking at the same image like nothing has changed over five years so um so it's it's fun i mean i kind of joke that i don't know what rejection looks like but um i i think you know whether through direct observation or um you know hallmarks of of rejection in the in the body we would be able to detect it if it if it were occurring um but thankfully it hasn't yet this uh this last question here is one that i had actually i should i would have asked if you hadn't because how do you direct the cannula to the required area of the cell level of the retina you know how do you get that around the edge that's uh yeah yeah um well i sure don't do it uh you get to have steady hands so so the retinal surgeons um you know they're very they're very good at orking in sort of mirror images so so there's a there's a video i could i could share glenn and direct people to a link if they want to follow up and it's it's actually really cool to watch i've watched a couple of live surgeries and it's just remarkable um but to describe it you know in basic terms um the sclera the white the white portion of your eye um there's an incision made right into the sclera and um in this very thin cannula um let's just call it a pipe cleaner it's it's a lot more flexible than that but um you just slide it into that incision and there's essentially a separation of the of the tissues just under the sclera you're able to kind of glide along around the back of the eye you know sort of like you know sliding along inside of a globe and as you advance the cannula forward from outside of the patient's eye it is navigating its path underneath the retina and you can actually see the end of this flexible cannula as you're looking in the front of the eye so the camera is positioned in front of the eye and you can actually see it begin to enter the field of vision the the vision of the of the surgeon and you can see it enter the field of vision and then you there's a step under which you extend a micro needle from the end of the cannula and that micro needle has a just the perfect angle to be able to come up and uh be positioned just below the retina and then a little bit of uh what's called buffer is administered to establish the space and then there's a changeover of the line the cells are then administered into that space and then you remove the needle and it just comes out and then a couple of sutures are placed right there on the sclera and the feedback that we've had from the surgeons who have performed this has been has been wonderful they really like it i think they think it's neat right it's a new toy for them they do have to be trained on it it's about a half day of training they they work on animal eyes and a cadaver eye and they're able to be um you know ready to go it's it's it's actually sort of natural for them and so it's been it's been wonderful to see you know this new device it only just got approved i think about a year and a half ago for use um to be able to see it we've we've now used it in our hands seven times and in all seven cases cells were successfully delivered so you know you know baton a thousand at this point yeah very high degree of uh you know probability this is gonna gonna work it's absolutely fascinating actually um let's reach the end of my little list of questions stuart i've run out of things to talk about that's okay glenn we had one more that came in via email uh today um from somebody in spain actually which i had shared with brian um and can patients treat their disease with operation um i'm not exactly sure if that's referring to or what sort of treatment that's referring to but that came in earlier today um there was a question that you had shared someone had uh had asked about um other inherited retinal diseases and if that is that if that's the same question um i partly answered it already you know i think the answer is yes so stargardt's for example would be a you know juvenile retinal disease um there's a cone and rod disease so i i think anything for which the hallmark is the loss of rpe cells could fit into a potential therapeutic opportunity for our operation treatment so uh so yeah i don't i don't think of this uh right now we're testing it narrowly in dry amd with ga but i think longer term there's there's a broader application for the replacement of rpe cells and you know there may be other places where these cells have functions that that could be beneficial to patients and i look forward to being able to explore those as well very good i just had a quick check and there's nobody with hands raised in the audience so i take it glenn that that's all our questions from your end as well um thank you thank you very much uh brian for for a fascinating presentation and some really thorough uh answers to our questions it's been really interesting just as i said earlier to get a glimpse into just what's going on and to get an understanding of where we're going with this really groundbreaking research and work so thank you for taking the time to join us today for a really great session we definitely hope to stay in touch and to everybody who's come along this evening i hope you have um i hope you've gotten as much out of it as we have i know glenn and i have been very interesting and when we spoke to brian originally before christmas we were very um we were really i suppose um interested to share all this stuff with us as wide an audience as we could so thank you very much uh that's it from us thanks for joining us and stay safe and stay well and brian again thank you sincerely yeah absolutely david martin says thank you thank you thank you thank you and he he was asking some questions as well so i think you have to hit them there and then thank uh we've all enjoyed it brian thank you very much i really appreciate you coming on with us tonight i've enjoyed it thank you so much gentlemen thank you