Lineage Cell Therapeutics, Inc. Price & Performance (LCTX)

The company's actual results or performance may differ materially from the expectations indicated by such forward looking statements. For a discussion of certain factors that could cause the company's results or to differ we refer you to the forward looking statements sections in today's press release, and in the company's SEC filings including its most recent annual report on Form 10 ks.

We caution you not to place undue reliance on any forward looking statements which speak only as of today and are qualified by the cautionary statements and risk factors described in our SEC filings. With us today are Brian Cully, our Chief Executive Officer and Jill Howe, our Chief Financial Officer. I'll now hand the call over to Brian. Thank you, everyone, and good afternoon, everyone. We appreciate you taking the time to join us on the call. There are three topics which I plan to cover today. I'll start with an update on OpRegen and some recent developments in the field of RPE transplants. We think reflects favorably on our program. Then I'll transition to scalable GMP manufacturing, which is a top to the cell therapy field. And then I'll provide a few words on our in house program OPC1, and our recently initiated spinal cord trial and some plans for the future. As most of you know, our lead candidate OpRegen for patients with dry AMD with geographic atrophy is an allogeneic cell transplant comprised of RPE cells. OpRegen's delivered as a suspension to the subretinal space in a one time surgical procedure and is currently in a Phase 2a study called the GALETT study that's being managed by our partners Roche and Genentech.

We believe the ongoing Gillette study is progressing well. This is an open label study with ninety day primary and secondary endpoints. And it has been enrolling for nearly two years. So we believe that a sufficient amount of data should have been collected and reviewed by now from which to make a decision on is relevant because Roche recently underwent a comprehensive review of its pipeline during which they trimmed nearly 30% of their development programs including some partnered cell therapy programs. We were not affected by those pipeline reductions and instead we've observed since that time what appears to be an increase operating activity in the past year.

For example, about a year after the trial began, Roche and Genentech entered into an additional agreement with Lineage to provide services for things like manufacturing training and long term follow-up of our Phase 1a patients. They continue to open clinical sites in the ongoing Gillette study and they recently sought and obtained our MAT designation for OpRegen. I want to be clear that Lineage has not received any interim data from Roche's ongoing Phase 2a trial and we do not know when any such data will be made available. But these actions by our partners appear to us more likely than not to reflect things moving in a positive direction. I will add that our rising confidence is reflected in certain actions that we are taking. Such as structuring warrants around a positive OpRegen clinical milestone which has been occurs would accelerate the maturity date of those warrants. If the share price exceeds the warrant strike price at that time that could provide us with an additional $36,000,000 of capital.

We did this in part to reduce concerns about a post event financing overhang something which is often associated with major clinical announcements. We continue to be unable to guide to the timing of any Phase 2a updates from Genentech and we don't yet know the process by which findings from the GLET study will become available, But I do want to remind everyone that a decision to advance to a next study could happen at any time. There is no regulatory requirement that we are aware of which requires Genentech to complete enrollment in the ongoing study or to announce collect data before launching a controlled study. Even if Genentech wanted to keep the Gilett study highlights confidential from competitors, they still would be required to post a new clinical trial on clinicaltrials.gov which would trigger acceleration of the maturity date of the warrants. While we all eagerly await information from the ongoing Phase 2a trial, there are two things in the meantime, which I'd like to highlight for you today. The first, is that we have learned that Roche and Genentech plan to provide a three year clinical update from the Phase onetwoa trial which Lineage conducted. For those of you who recall the two year update at last year's Retinal Cell and Gene Therapy Innovation Summit, Genentech reported changes to key anatomical structures and more importantly average gains to BCVA of 5% to seven letters, which persisted for two years.

I'm not able to provide the details about the forthcoming three year data, but Genentech have reviewed the anatomical and functional benefits which were reported at two years and I can report today, that those benefits have indeed continued to persist for another consecutive year. To date, five patients from the Lineage Phase IIIa trial have demonstrated durable anti And I will remind everyone that these effects have not been shown to occur spontaneously. Observing vision gains lasting for three years despite dry AMD being a degenerative and irreversible disease is to us indicative of a powerful and durable treatment effect one which may prove in future clinical trials to be superior to currently available therapies because patients on those treatments continue to lose vision. [indiscernible] than the twelve eleven GA patients, who were treated as part of the pecetaglifloin Phase three studies and reported in the Lancet in 2023 where the mean vision change that best available therapy was a loss of eight to nine letters. And the untreated patient control similarly lost seven letters. More recently, a long term study of more than eighteen thousand people with dry AMD and who did not develop neovascular AMD during the observation period, experienced BCBA losses of 12 letters at thirty six months.

And among the cohort of the oldest patients with moderate vision loss at base line, or moderate vision rather at baseline the mean loss was 20 letters. Based on the information I shared today, about mean BCVA of those OpRegen patient remaining above baseline at three years The performance to date between OpRegen and anti complement or OpRegen and an untreated control is not just that patient vision is moving in opposite direction. But that that delta is getting wider over time. The second opportunity item I wanted to highlight is some recent news emerging from competing RPE companies which I think is extremely positive for us. First, a small U. S. Based company which uses RPE cells which they source from cadavers, recently reported gains in vision at twelve months. Using their approach.

Second, a different small competitor, this one based outside of The U. S. But using a cell Lineage a source of RPE. Plans to share data from their RPE program at the ARVO Conference in May.

We've seen some of their top line data and it is both positive and consistent with our original findings. And then third, according to a recent news article, Astellas' RPE therapy is very close to proof of concept results. We haven't seen their data, but we assume it will be positive or we don't think this program would be highlighted by their Chief Strategy Officer. If you're surprised, that I would highlight our competitors in such a positive way, It's because we're working a completely new modality and it's normal for people to be unconvinced by a relatively small number of patients especially when we're all making claims about uncommonly positive clinical outcomes. But every time a company independently reports positive data, from an RPE transplant. And those data points get aggregated they can become a powerful endorsement of our mechanism and add conviction to this approach. At this point, there are four and probably soon there will be five independent reports of functional games from an RPE transplant. From among those companies, investors will presumably try to sort out which among us is best positioned win the large addressable market. And given everything that is required to successfully manufacture and commercialize an allogeneic cell therapy product for such a large patient population, I feel confident that the combination of Lineage manufacturing process Genentech's development strategy, and Roche as the commercialization partner provides us with a triumvirate of advantages over these other programs.

And while we wait for the story to play out, these other programs may also provide our shareholders with validating endorsements that we're on the right track. This topic actually leads nicely into my discussion of scalable cell therapy manufacturing. Lineage has been making investments of time and capital into our capability for many years. Which has generated new intellectual property, but perhaps more poignantly, has helped us achieve specific and measurable milestones in that area. I think we're all aware that unlike five years ago, exceptional clinical data is no longer sufficient to drive high valuations. In connection with increased awareness of modern cell therapy investors have learned much from the crowded and that if you don't have a credible path to commercial scale manufacturing, then maybe you really don't have a viable product candidate. And that concern is especially true for allogeneic cell therapy programs because the main reason allogeneic is attractive is because it's supposed to offer affordable production of consistent But that is not the definition of allogeneic. Allogeneic just means the cells are sourced from a donor instead of from the patient. The term allogeneic should not be expanded to assume affordable production or immediate use products In some cases, allogeneic might only mean a donor provides a single source or a single dose of a therapy, such as the case for an organ transplant.

In better instances, companies might be generating ten, one hundred or maybe up to one thousand doses of their therapy from a bag of donated blood. But while those programs are allogeneic by definition, they aren't maximally reducing the cost of production. Our view is that you're not actually delivering on the benefit of an allogeneic therapy unless your production system can deliver millions of doses.

And that's where we're working to establish a leading position in allogeneic process development production and scale. I want to explain why we believe this is a credible path.

Given the large patient population, we've always known that OpRegen would require a commercially viable manufacturing platform. So for years, we've invested heavily in process development and other cell therapy manufacturing capabilities. But those investments do not need to be limited only to OpRegen. In many cases, the methods Trade Secrets insights and know how we have acquired can be and in some cases already has been applied to our other programs. In this way, over time, we are enabling Lineage to develop multiple programs, each possessing the necessary dyad of clinical evidence and commercially viable production.

The main reason I speak on this topic so often is that when I look at the cell therapy landscape especially, at the non cancer allogeneic field, I can only find vague and aspirational statements about stable cell bank or theoretical projections about manufacturing scale, I have not yet found evidence that these companies have produced their drug product by a scalable process in a GMP environment. So while they may be allogeneic by definition, they haven't yet shown a believable line of sight to the primary reason for pursuing an allogeneic approach which is a large scale production capability. And in our view, if you can't deliver on large scale production, you aren't going to be able to affordably address a large patient population. So what we've been working on is to become the first company to reduce to practice a clear and convincing case of a scalable GMP production process. We believe doing this will set a high bar for allogeneic economics and pelp make lineage an attractive company and partner.

To explain in detail what this looks like, if you were to generate 100 vials of a master cell bank in a GMP lab and randomly select one of those vials to manufacture another 100 vials of a working cell bank and then you randomly select one of those vials to make 100 vials of your product, you will have credibly demonstrated that you have reduced to practicing production capability of 1,000,000 files. We don't believe any of the Alginia companies we monitor has achieved this milestone.

Yet we believe it is a necessary component to commercial success in a market indication. So we are focusing on this goal as a way to capitalize further on our investments in Oprichan and help differentiate us from our peers in this area. Next and thirdly, I'll briefly comment on our second clinical stage allogeneic program, OPC, one. You might have seen this program highlighted on CNN back in January, and if not, interview we did with Sanjay Gupta still available on our website.

OPC1 is designed to help increase recovery and mobility It is comprised of a population of the myelin generating cells of the spinal cord and these cells help control the messages between your brain and your muscles. Our approach to addressing paralysis due to spinal cord injury is to manufacture replacement cells of the spinal cord and deliver them right to the site of injury which is basically the same approach that produced successful outcomes to date.

In dry AFD. OPC1 has been tested in 30 individuals with severe spinal cord injuries and while the long term safety and efficacy data we have collected so far is promising, and merits further investigation This was an acquired program and we have two areas of improvement we'd like to complete. Before we would feel ready to move OPC1 into a later stage trial. The first area of improvement is delivery. We recently began a small clinical study called the dosed study to test the safety and performance of a novel delivery device. We believe the device we are testing in this study will be superior to the original delivery system in two ways. First, it's easier to use and deploy to clinical sites. And more importantly, the new device allows a dose of cells to be administered to patients over four to five minutes without stopping the patient's respiration. Previously, it was necessary to stop ventilation you delivered the cells. This is a significant enhancement to the procedure. In addition to the safety and the performance of the new device, we also will be collecting functional assessments on all patients which gives us the opportunity investigate any signals of efficacy that may arise.

That is important because this study will be the first time OBC1 is administered patients with a chronic spinal cord injury. Which represents an additional and larger patient population for this experimental therapy. The first site for this clinical study is just down the road at UC San Diego Health and patient enrollment is expected to commence next quarter. The second area of improvement is our new manufacturing process, which actually has two subparts, We first applied lessons from our OpRegen program to increase the scale, purity and control of the cells we make. And second, we developed a new immediate use formulation which eliminates the lengthy dose preparation steps that were required in prior studies. Subject to obtaining clearance from FDA, we plan to introduce the cells we make from this improved process and the new formulation into the dose of the trial. In parallel with these two ongoing enhancements to the OPC1 program, we also are working on the design of a larger trial with a focus on collecting more sensitive and clinically relevant endpoints which we think will help overcome the complexity of data capture in this patient population. When all three of these necessary activities have been concluded, the design, the device and the cells we believe we, neither alone or with a future partner, will be in a position to conduct a larger clinical trial of OPC1.

And I should add that we still plan to apply for a certain clinical grant as soon as they begin accepting applications which CERM has indicated will occur this spring. Last comment, I want to make before we review our financials is that we don't often highlight individual patent issuances, but just so that you are aware, we have continued to add value to our patent portfolio. For example, earlier this year, two additional OpRegen patents issued, which included claims covering certain aspects of how we manufacture ourselves, Some of the discoveries we make, we patent. While others we intentionally retain as trade secrets. But overall, we aim to increase our proprietary position for OpRegen in all of our development programs in the best possible way. And with that, I will turn things over to Jill for a review of our Thanks, Brian, and good afternoon, everyone.

As of the date of this filing, our overall cash position is expected to support our current planned operations into Q1 of twenty twenty seven. Our runway has been meaningfully extended following our November 2024 registered direct offering and as of 12/31/2024, we are reporting year end cash, cash equivalents and marketable securities of $47,800,000 Together with the approximately $5,500,000 in net proceeds which we received from the second closing of this offering that occurred in January, this supports our current runway guidance of approximately two years from now. Importantly, the November financing incorporated a milestone milestone warrant a mechanism to accelerate maturity which means Lineage may be able to access an additional 30 if the clinical milestone is achieved and the stock is above $0.91 We implemented this financing strategy because we believe a go no go decision by Roche to publicly disclose their intent to run a controlled clinical trial of OpRegen would be a major event for Lineage and for OpRegen's probability of success. Our strategy was to not only secure immediate capital, but to also create an opportunity for future capital. Which again is contingent part upon the success the successful advancement of OpRegen. Alongside this recent financing activity, we will continue to balance between our cost and investment of capital as we work towards other potential sources of funding such as milestone payments we are eligible for under the Roche Genentech collaboration program grants and or additional business development transactions.

Next, I will review our fourth quarter operating results. Our revenue is generated primarily from collaboration revenue, royalties and other revenues. Total revenues for the fourth quarter were dollars a net increase of $800,000 from dollars as compared to $2,100,000 for the same period in 2023. The increase was primarily driven by more revenue recognized from deferred revenues under the collaboration and license agreement with Roche. Operating expenses are comprised of research and development expenses, and general and administrative expenses. Total operating expenses for the fourth quarter were $7,800,000 a decrease of $400,000 as compared to $8,200,000 for the same period 2023. R and D expenses for the fourth quarter were $3,400,000 a decrease of $500,000 as compared to $3,900,000 for the same period in 2023. The net decrease was primarily driven by a decrease of $1,200,000 for our OPC1 program expenses and $200,000 for other research and development programs. Partially offset by an increase in $400,000 for our OpRegen program expenses and $500,000 for our preclinical program. G and A expenses for the fourth quarter of $4,400,000 were primarily in line with same period in 2023. Loss from operations for the fourth quarter was $5,100,000 a decrease of $1,300,000 as compared to $6,400,000 for the same period in 2023.

Other income expenses for the fourth quarter reflected other income of $1.89 compared to other income of $1,600,000 for the same period in 2023. The net increase was primarily driven by changes in fair value of warrant liability, largely offset by exchange rate fluctuations related to Lineage's international subsidiaries and certain warrant related transaction costs incurred as The net loss attributable to Lineage for the fourth quarter was $3,300,000 or $0.02 per share compared to a net loss of $4,800,000 or $0.03 per share for the same period in 2023. Next, I will review our full year operating results Total revenues for the year were $5,900,000 a net increase of $600,000 as compared to 8,900,000.0 for the same period in 2023. The increase was primarily driven by more collaboration revenue recognized from agreement with Roche. Total operating expenses were 31,000,000 a decrease of $2,700,000 as compared to 33,700,000.0 for the same period in 2023. R and D expenses were 12,500,000.0 a decrease of $3,200,000 as compared to $15,700,000 for the same period in 2023. The decrease is primarily driven by $2,700,000 for our OPC1 program [indiscernible] dollars $1,100,000 for our preclinical and other research and development programs, These decreases were primarily offset by $600,000 for our OpRegen program.

G and A expenses were $18,200,000 dollars an increase of approximately $900,000 as compared to $17,300,000 for the same period in 2023. The net increase was primarily driven by $600,000 for stock based compensation and $400,000 for personnel costs, partially offset by an overall decrease decrease in costs incurred for services provided by third parties. Loss from operations were $21,500,000 a decrease of $3,200,000 as compared to $24,700,000 for the same period in 2023. Other income and expenses reflected other income of $2,900,000 dollars compared to other income of $1,500,000 for the same period in 2023. The net increase of $1,400,000 was primarily driven by changes in the fair value warrant liability exchange rate fluctuations related to Lineage's international subsidiaries, and fair market value changes in marketable equity securities. This increase in other income was partially offset by certain warrant related transaction costs incurred as part of the November 2024 financing as well as the non recurring prior year employee retention credit.

The net loss attributable to Lineage was $18,600,000 or $0.09 per share compared to a net loss of $21,500,000 or $0.12 per share for 2023. And with that, I'll hand the call back to Brian.

Great. Thanks, Jill. So I will summarize by saying first that we remain confident in the potential for OpRegen to drive positive clinical outcomes in dry AMD and we feel the independent evidence generated from other RPE transplant trials supports and elevates that belief. Second, we are planning for success by seeking to capitalize on our historic investments in cell manufacturing and use those investments as a foundation from which additional programs can be advanced into and through clinical trials. And third, we are steadily advancing OBC1 toward a larger trial in spinal cord injury while ensuring first that the necessary attributes for that program to be successful.

Are in place. We very much appreciate your support and belief in our vision. And with that operator, we are ready to take some analyst questions.

Would like to remind everyone that in order to ask a question, Your first question comes from the line of Jack Allen with Baird. Please go ahead.

Great. Thank you so much for taking the guess the first one I wanted to ask on OpRegen was around the competitive landscape. It seems like there are a lot of players that are making advances in the field. You mentioned on the call a few different pieces of differentiation as it relates to Oportun, but [indiscernible] what are you doing as a team to protect your market leadership here as it relates to [indiscernible] And then a quick follow-up on OpRegen. When do you see the updated three year data that was alluded to on the call? And then I just have one follow-up after that as well. Thank you so much.

Thank you, Jack.

Ultimately, product development is intended to be a means by which revenues are captured. So I think what I said in my opening remarks is really the crux of it Whether there's one company working on RPE trans is not as important as whether you are putting in place all of the right and necessary attributes for success. So I use the word triumvirate and I really think that the triumvirate of the lineage manufacturing the Genentech product development capabilities and then Roche as a leader in ophthalmology as a commercialization partner puts us far and ahead in a better position than anyone else. I think it's an open question in the field still. As to how differentiated different programs ultimately can be and that differentiation would presumably need to be demonstrated clinical setting I find that to be a fascinating question, but there is no answer. We have seen cases where [indiscernible] the companies have failed to to advance but it's sometimes unclear why they have left left the area. So find a lot more to be happy about when we see these independent examples validating a novel mechanism like the one that we have But I really don't lose any sleep worrying that these other organizations are going to be more well prepared than Lineage is, to be able to make and sell this product through the various alliances and relationships we have in place.

Got it. And then just very briefly, do you have any additional timeline as it relates to the three year opportune data then I wanted to ask bigger picture. How do you think about the positive early results from not only OpRegen as an RPE replacement therapy, now we're seeing I think you quoted four to five companies in the RPE cell place. Space. EVS is an active modality for cell replacements. How do you see that leading leading across with a broader lineage story? And what do you think of as RPE sell as a proof of concept for OPC1 and potential other programs I want?

Thanks, Jack. Yes. So for the three year data, those inquiries could be directed to Genentech. They get to decide which events and conferences and they've selected a lot of different ones over the years that we've been involved with them. So we don't have today announcement or a disclosure about where they would be announcing that, information only that they intend to. However, I hope it does not go unnoticed that I did say that the effects continued to persist. So we'll be sure to make sure that everyone is aware that if we or Genentech make an announcement, which is the normal course of events, that you would be and everyone would be aware of that. The second one with respect to modality, I think that there's a conflation in the minds of many people that cell therapy is synonymous with CAR T. And while CAR T has certainly revolutionized the therapies in oncology, there are almost countless numbers of programs that are in our view sometimes poorly differentiated And we really think that the growth opportunity is not in oncology, but in all of the other areas that you might call noncology. So these would be the most obvious places where cell transplantation kind of lends itself.

So RPE transplants four or five companies, there's probably a bunch of academic initiatives out there as well. Spinal cord injury has long been one of the premier choices in terms of suitability between the mechanism and the condition And we're very proud to have have the most advanced cell transplant program in that indication. Some of the others that you might find going out into this growth area would be Parkinson's, Bayer just announced that they were going to move from a Phase one to a Phase three. Type one diabetes attracted a great amount of attention for our neighbors at Sona, We also and there are other companies have initiatives in auditory neurons There are hundreds of different types of cells in the human body, clearly not all of them. Is suitable as a cell transplant medicine, so to speak. But the ones that I've mentioned here on the call today certainly are I think they're getting a lot of attention for the companies that are working in this space. So we see it as the real exciting side of cell therapy versus CAR T. For us, CAR T has been wonderful validation of what is possible And now companies like Lineage and others are looking at some of these large fields where small molecules and antibodies have left some opportunity on the table, And I think that there is increasingly going to be excitement and a higher belief system in the use of complex cells as solutions for diseases and conditions which have not been fully solved by small molecules or antibodies. [indiscernible] great to see the growing proof of concept and congratulations again on all the progress.

Thanks so much. [indiscernible] comes from the line of Joel Pantginis with H. C. Wainwright. Please go ahead.

Hey, guys. Good afternoon. Thanks for taking the question. So couple of questions on OPC1, please. So first, I guess they're all logistics questions. I'm assuming you're using the same centers that you used in Phase IIIa. I'm just curious, is there a certain percentage of new centers where the surgeons have gone through the updated training?

Thank you, Joe. We will have at peak a combination of new sites and experienced sites. The first site at UC San Diego is attractive to us because we do have some dose prep work that needs to get done and they have the right facilities for that. As additional sites come on, those will turn up on our clinicaltrials.gov posting which is already available. And so you'll be able to see the sites as they come aboard.

No, that's great. And just as a side to that, how far ahead say of even appearing on clinicaltrials.gov would the training have occurred? And then my second question was, from the time of the Phase IIIa, which was a while ago, can you describe any changes in the logistics and being able to get patients to the surgical suite faster or any other components that have improved?

Yes. Thank you. With respect to training, there are a lot of different kinds of training. There's protocol training for the labs, the CRO, there's surgical training, for the surgeons, there's even training for transportation and management of the drug. When all that work is complete, then you have a site initiation visit, then you're actively enrolling patients.

So what you find is there is a long continuum from beginning to end as sites go through all of these stage gates And you may have multiple sites in different points along that continuum. And any one time. With respect to the prior study, we absolutely saw opportunities to learn from the prior trial and to look for best practices And in fact, that was one of the reasons why we wanted to develop a immediate use formulation because the original use of this therapy included literally hours of preparing the cells, washing them, plating them, etcetera. Rather than the formulation which we developed which is immediate use.

So there are places that we think will ease the burden for both the patient the caregiver, the provider even the study coordinators and also us as sponsor But at the end of the day, there certainly are some unavoidable activities of getting everyone in for all of their assessments within the appropriate windows and all the other things that are required to execute a high quality clinical trial.

Got it. Thank you, Brian.

Thank you. Your next question comes from the line of Michael Oconulis with Maxim Group. Please go ahead.

Hey, guys. Thank you so much for taking my questions today. [indiscernible] for the dose study, does it will FDA want you to prove the device safe in either of the settings first and kind of like a safety run-in portion for the study before you can open it up to fully enroll across all the planned sites? Or can you just start off pretty much from the get go?

Thank you, Michael. There is it's a great question.

And there is a staging process. So FDA really did us a favor by encouraging us to enroll chronic patients in this study. But they did also want to put some appropriate safety measures in place. So the first several patients in the study will have thoracic injuries. So they would be from T1 to to T10, that's your thoracic range. And there's a hierarchy of if you're familiar with the Asian Spinal Injury Association or Asia, there's international standard for how you classify neurological spinal cord injuries.

And the shorthand of that is [indiscernible] Is AISA, AISB. So AISA would be you've got a no function or sensation below the level of injury.

So you have the least amount to lose in that situation. So we would start with a thoracic patient of ACE A and then we would work our way up into open enrollment, I think around patient four.

All right. Thanks for that. And then just in terms of your capital plans, right, you have strengthened your balance sheet a bit. Are there any plans to accelerate the work on respondents at all? Or do you find it more prudent to maintain more of a steady approach given that we still face some market uncertainty?

I've noticed the market uncertainty for certain.

So resonance absolutely is still an important program for us. We continue to work the University of Michigan as well as internally on that program. It didn't get a lot of airtime in my prepared remarks. Only for the sake of time.

Not because there's anything new or different with it.

I think the organization's management prides itself on being extremely prudent and insisting upon a return on the capital which we invest into our programs. So I think that it is the case that this is not and has not been for years the kind of environment where companies can go as fast as they possibly can And I think we're seeing a lot of penalties being paid for companies that did that. Instead, we are very careful about the investment decisions that we make And we also are aware that we might have a much more attractive cost of capital in the future when OpRegen is a little bit more advanced, and that will make our ability to accelerate development of other programs a little more attractive to our investors. So we really tried to strike an appropriate balance considering macro, micro sector, internal and all the other factors that one might imagine in order to try to maximize the investment opportunity for our share All right.

Thank you very much, Brian. Appreciate your color on the matter.

Thank you, Mike.

Your next question comes from the line of Mayank Mamtani with Ralu Securities. Please go ahead.

Yes. Good afternoon, team. Congrats on the progress. And thanks for taking our question. So Brian, appreciate you mapping the development stage progress of some of the peer RPE programs. It looks like a couple are coming at ARVO. Some incremental data. Could you touch on where we are with maybe some of these programs in terms of manufacturing the source material cell line process development scale of GMT grade materials that you might be aware to the best of your knowledge Is there any direct comparison on what number of cells that are needed across the programs to kind of get to that therapeutic effect which we're starting to see with some of these programs? And then I do have a follow-up.

Thank you, Mayank. Respect to the number of cells, I think most companies are operating anywhere from maybe 25 or 50,000 up to 200,000 And I think that has to do with a surface area calculation. These cells tend to they're adherent and they tend to form very organized structures. As they are administered to the subretinal space. With respect to the manufacturing by other companies, I very much wish that I had some specific information about their capabilities because I would probably aim to contrast it with our own capabilities in that regard.

I have said before that we are on a feeder free system. Other than the fill finish, it's a closed system. Thousands of doses per batch I don't know where other companies are other than one company that sources their material from cadavers So I don't know that that is necessarily a commercially viable source. Because passaging mature cells is not something that one can do endlessly. The way that a pluripotent stem cell can be passaged endlessly. I also look at the Astellas program. Obviously, that is a very well funded global organization. However, I think their IND opened in 2010. So they have been working for a very long time. We do get the impression that they will have some results announced soon, so perhaps they'll be opportunity to get some insights into their manufacturing capabilities But I think that even at current process scale and current non optimized capabilities, that Lineage is probably setting the bar I hope to be able to not only say more about our capabilities in the near future, but also find some insights about the competitors' capabilities which perhaps will only highlight that we believe we have the most promising opportunity in this particular approach.

Super helpful. [indiscernible] yes, thank you, Brian. And just to follow-up on that comment you made about the controlled study, which could theoretically be run-in parallel to the GALLETT study. Is there any insight you may have on the kind of patient exposure and what efficacy endpoints could make sense given obviously the very large BCVA treatment effect you get to this modality. And not sure again if there's anything to with other programs, believe there's one more that has RMAD designation like yours. But I assume you're in the lead and we'll whatever we learn about the next step from Roche is going to be what others will follow. That is kind of my question. Thanks again for taking my question.

Yes.

Thank you for that, Mayank. I do note that some of the reports I've seen from others indicate pretty significant improvements in BCVA. One hypothesis is that those companies have in fact learned from our experience and are taking great care to deliver the cells right across the GA. That of course was one of our important findings.

So it is possible that that they are seeing absolute values at clinically relevant time points that are even greater than the ones that we have reported study simply attributable to learning from our experience and delivering the cells in exactly ideal location. Which is terrific.

Because it would suggest to me that the ongoing surgical optimization study which Genentech is conducting, holds the promise of potentially having even better results than we have already reported in our Phase one. I have no specific knowledge of that happening at this time, However, it would seem to be plausible given what others have reported with their own approaches. So I do think that there are opportunities here for this treatment, especially because it is novel to improve, which is quite frankly a normal storyline for a new technology that it gets better over time. So I would be hopeful that that would be the case here. But again, Genentech is specifically [indiscernible] to explore various ways, methods, equipment to deliver cells to the subretinal space But because the clinical effects which Lineage have reported do not ever happen spontaneously, one would reasonably assume that Genentech would be able to see signals of efficacy in the ongoing study and thereby make some decisions about how important this program is or is not to them. With respect to the size of the study, I don't know that surgical optimization ever truly ends There are probably people still trying to make LASIK surgery better even today.

So I would imagine that as this technology continues, some version of surgical optimization might continue forever. So I don't know that there necessarily is a discrete and statistically powered endpoint associated [indiscernible] point that a decision to advance into a controlled study could occur at any time and doesn't necessarily have to be tied to the conclusion or any particular follow-up period, of the ongoing GALAPP study And in fact, we intentionally designed the warrants in the financing to be tied to that milestone for exactly that reason.

Makes sense. Thank you, Brian.

Thank you very much.

Our next question comes from the line of Albert Louie with Craig Hallum. Please go ahead.

Hi, Brian.

I was interested in your comment about the potential for Roche to start a new controlled study.

And I guess at any time in the absence of the data disclosure. I was wondering, would there be anything on your end required to prepare for that possibility perhaps on the manufacturing side of things or anything else?

We maintain a very clear wall between public information and the information that Lineage may come into possession of So I really don't have any particular item to point to And in fact, I struggle to sort of hypothesize what one might look at I suppose in some cell therapy applications, having sufficient material might be an indicator of what a partner is aiming to do But as I've shared a couple of times, our production levels are already so high that we do not have a shortage. We don't need to do anything in particular with respect to our product scale, our process scale. In order to adequately supply even the largest of clinical trials. So I think all those decisions will ultimately be up to our partners in our partners' hands and we will just collaborate and cooperate with them at any point that is in the furtherance of the OpRegen program.

Okay, all right. Got it. Sounds like you have plenty of RPE sales on hand. Maybe just one more question. I was interested in the impairment that you mentioned earlier of the Great Asia Great A or B or complete or incomplete injuries I was wondering if there are any differences between the responses in these type of acute patients in the prior studies?

And if there are any other features that you think might make chronic patients good candidates for OPC?

Thank you for that question. The prior work included only five patients with thoracic injury but twenty five patients with cervical injuries. So the comparisons that we will be making are probably more likely to be interesting on the cervical [indiscernible] But at the same time, this study is intended to be a safety and performance study of a device and delivery And the follow-up periods in spinal cord injury can be quite long. So given the size of the study, the period of follow-up and the objective, the primary endpoint objective of the study we don't really know what meta analysis or what sort of predictive outcomes we might be anticipating But to the extent that chronic patients have never been treated, with OPC1 There certainly are many people in the field who are not intimidated by the presence of the scar and old injuries in these individuals and we would be among them. Believe that the plasticity and the regenerative capability of the spinal cord even after many years can be reengaged and restored perhaps not completely. But I believe even partially could be extremely clinically relevant to individuals who have lost their motor [indiscernible] So we are very excited to see OPC1 go into chronic patients for the first time because unlike sub acute patients where you really don't know what the recovery journey for any individual patient is likely to be, although I will say that the field is getting better at predicting that.

But a chronic patient who has plateaued for many years might be more easy to provide a signal after therapy if they in fact have some sort of change in their performance status So I think what's attractive about chronic is not just that there are larger numbers of patients who perhaps might be easier to enroll because they have already been stable and are not coming off of a very acute injury but also because of their baseline should be stable. And so changes to baseline might be more easily attributed to our intervention.

Okay.

I see. All right. Thank you for taking my questions today.

Thank you, Oliver.

Verify your question comes from the line of Sean McCuschen with Raymond James. Please go ahead.

Hey, Brian.

Can you provide some additional thoughts on the ability to use dosed as a bridge to the new formulation of OPC1 and maybe what comparability studies remain for the new production process, maybe speak to your your confidence in being able to include the new formulation in that current ID? Thanks.

Excellent question and thoughtful question, Sean. We have manufactured OPC1 with our improved process and we have conducted substantially all of the comparability testing that we intend to do So which includes in vivo efficacy studies Importantly for everyone listening, it's very important that the process does not change the potency or efficacy of these cells. And so the comparability testing would include all of the customary features of identity and other characterizations of the cells, potency of the cells, including in vivo study, bioinformatics analysis of the cells, We are substantially complete but we did strategically prefer to have the IND process for dosed be completed as it has been so that we could get the study up and going And then as a second phase, introduce all of the data for the new cells to FDA for their review and append it into the dose study that way. We didn't want to give them both a new device and new cell process to think about. We thought that would be more efficient In hindsight, it still took a long time to review. But I think that's okay. I think staging it in the way that we have makes sense.

I cannot say today whether the new cell process will be introduced into the scope of the six to ten dosed patients or if we will append a small number of patients to the end of dose, But our current thought is that we would use the forthcoming sites and the currently activated site to be the sites that are also utilizing the new formulation of the cells. So I think one of the things that we would like to do is actually get some of that information out perhaps that can aid with some investor comfort by seeing how the new process compares to the old process because we do think that it is much better way of making the cells and we've gotten much better control and that it is going to be deemed by us initially as comparable and we expect the FDA will find that same conclusion.

Understood. Thank you.

Thank you very much, Sean.

That ends our Q and A session. I will now turn the call over to Brian Cooley for closing remarks. Mr. Cooley, please go ahead.

Great. Thank you, everyone. We hope this was helpful and we'll look forward to having you back soon for our Q1 twenty twenty five call with Nick.

Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect. [indiscernible] [indiscernible]