Welcome to the Lineage Cell Therapeutics Third Quarter 2021 conference call. At this time, all participants are in a listen-only mode. An audio webcast of this call is available on the Investors section of Lineage website at www.lineagecell.com. This call is subject to copyright and is the property of Lineage. And recordings, reproductions, or transmissions of this call without the express written consent of Lineage are strictly prohibited. As a reminder, today's call is being recorded. I would now like to introduce your host for today's conference, Ioana Hone Director of Investor Relations at Lineage. Ms. Hone, please go ahead.

Thanks you Kris. Good afternoon, and thank you for joining us. A press release reporting our third quarter 2021 financial results, was issued earlier today, November 10th, 2021 and can be found on the investors section of our website. Please note that today's discussion will contain forward-looking statements, within the meaning of federal securities laws. Including statements regarding our strategy, goals, product candidates, clinical trials, data announcements and updates, anticipated regulatory meetings and interaction, planned manufacturing improvements, financing, cash management, and runway, anticipated collaboration opportunities and benefits, and commercial potential. Statements made during this discussion that are not statements of historical fact should be considered forward-looking statements, which are subject to significant risks and uncertainties. Actual results or performance may differ materially from the expectations indicated by our forward-looking statements due to known and unknown risks and uncertainties. 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 in our filings with the SEC, including in our quarterly report on Form 10-Q, filed today, November 10th, and our annual report on Form 10-K for the year ended December 31, 2020. With us today are Brian Culley, our Chief Executive Officer, Kevin Cook, our Chief Financial Officer, and Gary Ho, our Senior Vice President of Clinical and Medical Affairs. Brian and Kevin will provide some prepared remarks and then all of the executives will be available for questions from analysts. With that, I would like to turn the call over to Brian.

Thank you, Ioana, and good afternoon, everyone. We appreciate you joining us on the call today. As you well have seen in today's press release, the Lineage team had another productive quarter. Most notably, we delivered additional positive clinical data from our lead asset OpRegen, which is intended to treat dry age-related macular degeneration with geographic atrophy. We also took important strides to advance our OPC1 program to treat spinal cord injury. And we continue to grow our executive team with the appointment of Mr. George Samuel as our General Counsel. Lastly, we continue to generate awareness for the Company, our data and our mission through various investor and medical events, presentations, and other engagements. As I say each call, Lineage is pioneering a new branch of medicine. Our approach for each of our product candidates is to manufacture, differentiates in cell types, with all batches for ever produced from a single-cell line, and transplant those differentiated cells into the body. in order to restore and improve function, which has been lost due to aging, injury, or disease. Simply put, we believe that if a certain type of cell in your body is dying or dysfunctional, you need to replace that specific type of cell. And as a reminder, our approach does not require any gene editing or reprogramming of the cells original DNA. It's impossible to perfectly control those edits And there are unanswered questions about how often they will lead to clinical complications. Any safety concerns are not theoretical as you've probably seen recently, in reports from companies which employ them. We are involved in the debate over which editing approach or platform is best because we avoid these risks entirely. When we manufacture ourselves, we harness the natural developmental programming contained within each of our single-source cell lines. This regenerative medicine platform, which we own is broad and powerful. Not only for the value of our 3 current indications, but also because our cell transplant approach might someday be applicable to a large number of additional cell types and address many different unmet needs. We view our approach as the path to reaching our long-term goal of becoming the leading cell therapy Company. With that, I will turn to a brief review of our recent accomplishments in set some expectations for the remainder of this year and early 2022. I will as usual, begin with OpRegen our lead product candidate intended to treat dry AMD with GA, a disease with no FDA-approved treatments. Our approach to treating this disease is the transplant healthy new retina cells to replace or support the ones that have died or are dysfunctional. Replacing the entire cell, avoids risks and limitations inherent in approaches that target just a single pathway, which may be insufficient to drive a clear clinical benefit, or gene therapy approaches which target a certain mutation, which might only be relevant to a small subset of patients. Importantly, we now have evidence that our approach can not only slow the disease process, which is the objective of the leading companies in this space. But also even Holt or reverse an area of atrophy, which obviously would have a far greater impact on disease progression. We feel evidence of this reversal of GA in 3 patients so far, particularly in those who received a fulsome covering of our OpRegen cells across their atrophic area. This phenomenon is something we refer to as retinal restoration and is identifiable by the new appearance of critical layers of retina, and specifically, the presence of new areas of RPE model layer with overlying ellipsoid zone, external limiting membrane and outer loop nuclear layer, all of which were not present in previously confirmed atrophic areas at the time of baseline assessment. This is a remarkable clinical observation, which is achievable with just a 1-time administration of RPE cells performed at about 30 minutes under local anesthesia. We believe our approach may have an enormous advantage in terms of compliance, convenience, and benefit over traditional drugs being developed by competitors that require monthly or semi-monthly injections. We also have seen Phase 3 data from 1 of the leading complement inhibition companies, and is unclear whether that data will support approval. But if we assume that it does, given that that product's clinical benefit was somewhat modest, it clearly leaves abundant room for improvement and opportunity. That and the restoration data, which we have previously presented, is something which has never been shown with any complement inhibitors or Oxidative Stress Reducers. But in addition to that anatomical observation, we have reported, we also have seen functional improvement in the majority of our patient's treated eyes. In contrast, visual acuity declines in the majority of our patients untreated eyes. Now seeing these benefits, even though small population is exciting, but visual acuity can be a difficult assessment to rely on in clinical trials because the size and location of atrophy only broadly correlates with vision. For this reason, we expect our primary efficacy endpoint in a registrational trial will be the change in the rate of growth of atrophy over time, which is similar to what is being pursued by companies like Apellis and Iveric. Overall, the data set we are collecting includes both functional and anatomical evidence, which further reinforces our belief that the suspension of OpRegen RPE cells can generate clinically meaningful outcomes in patients with dry AMD with GA and particularly in those with earlier-stage atrophic disease. Looking ahead, we will be providing an important clinical update at the 2021 Academy of Ophthalmology annual meeting, which takes place this week and through this coming weekend. Dr. Michael Ip, who is a retinal imaging experts from UCLA's Doheny Eye Institute, will present new imaging data, which He, and Dr. Srivastava, have generated from our cohort 4 patients. You're already aware that we have recorded retinal restoration using high resolution OCT imaging, which is necessary because of the inability of older FAF technology to detect our healthy RPE cells. But we more recently have performed a sub-study analysis of that same data using a separate technology known as 3D Okta. 3D Okta is a validated Part 11 compliant, imaged grading software, which can provide quantitative information on the thickness in area of key layers of the retina. Using this approach, we can interrogate not just the boundary of GA as defined by the formation of new layers, but now we're able to report on the individual measurements of thickness and volume of areas such as the outer nuclear layer or the RPE-drusen complex. also will provide a general clinical study update. But what we're most excited about in the coming days, is being able to provide a second separate method of measuring retinal restoration. And for that data to again come from an independent and highly respected group of experts. And because this presentation will be made at the largest ophthalmology meeting in the world, we are hopeful that these data will foster greater professional awareness of our program. In addition, we also are working with our advisors to prepare for multiple engagements with FDA to discuss aspects of OpRegen designation, our manufacturing plans, and the design of a late-stage clinical trial. We anticipate the first of these events will occur in this quarter and will continue into the first quarter of 2022. Throughout this year, we have provided a cascade of positive event updates from the use of OpRegen, with increasing evidence of benefit and the durability of those benefits has risen as more and more time has lapsed from the date of treatment. With our minimum 12 months of data on all patients available later this quarter, we're excited to move this program forward and unlock the potential of this approach. Overall, we believe we are seeing the validation of our cell transplants approach with each passing day, and that the manufacture and delivery of replacement RPE cells eventually will be proven to be the most powerful and effective method of treating this degenerative condition. And next we'll move to OPC1, our cell transplant for treating spinal cord injury patients. OPC1 is a 1-time administration of oligodendrocyte progenitor cells, which are delivered directly into the area of spinal cord injury. As with dry AMD, there currently are no FDA-approved treatments for spinal cord injury despite many attempts. Our view of this indication, is it is very similar to dry AMD in so far as we may be able to demonstrate that transplanting a whole functional cell into a damaged area can accomplish things which are beyond the reach of traditional small molecules or other biologic approaches. Those efforts have not yet led to any approvals, so it's clearly time for some new approaches. Because a clinical effect alone is insufficient for commercial success, we've spent the past 2 years working on a new manufacturing process for OPC1. Our attention to this area, lead to tremendous advances in the purity, scale and reproducibility of our OPC1 batches. This new process was recently moved into our in-house GMP facility at a batch size, which can support a registrational size clinical trial. And we expect to complete GMP production via this new process, and with a new thought and inject formulation in the first quarter of next year. Ensuring ample supplies clinical material for the controlled study, we wish to conduct in this indication. At the same time that we're completing steps to introduce our newly manufactured lots into clinical development. We also plan to initiate an interim clinical safety study, of a new delivery device through our collaboration with Neogame technologies. This new device was developed to help avoid complications and risks, which could occur with an earlier delivery system. Obviously, delivering materials that spinal quarters of delicate procedure. And anything we can do to reduce patient risk is important to us. We also have learned from the OpRegen program that careful placements of cells can be correlated with better outcome. So, it made sense to us to invest in superior delivery options. 2 of the notable advantages of this new device are easier manipulation of the XYZ axis, and the ability to deliver Cells much more slowly because the patient can continue to be connected to a respirator during delivery. This is a huge advancement over the prior method, and we're excited to be pioneering this approach. Over the past quarter, we completed the manufacturer of clinical device prototypes and continue the required verification and validation work based on FDA input, which we received. We expect to complete that evaluation this quarter and immediately thereafter, we intend to initiate human clinical performance and safety testing with the new delivery device and plan to submit an amendment through our open IND in the first quarter of 2022. We also are preparing for an FDA interaction to discuss our cell manufacturing improvements, which we similarly anticipate to occur in the first quarter of 2022. Interestingly, because this performance trial is focused on safety and delivery, we are able to expand the eligible patient criteria beyond the sub-acute population treated to date. And we have feedback from FDA indicating their openness to us, including patients with chronic injuries on this trial. This is notable not only because it's generally easier to identify and enroll patients who have a chronic injury, but also because any hint of improvement in patients who have functionally plateaued for years would be an incredible finding. Now, to be clear, showing an improvement in mobility in chronic injury patients is not the intent of the study. It's just something we want to keep aware of. We didn't expect to see retinal restoration in the OpRegen program. So it's important to collect the data across a large number parameters, and sometimes you find unexpected surprises. Overall, I'm pleased with the progress we've made to get all of these pieces to fall into place in a coordinated manner. We have the GMP clinical material, the new delivery device testing, and some new ideas on regulatory strategy all converging next year to support further testing of OPC1. And I'll conclude the OPC1 section by adding that, the work that we have done on this program reflects our commitment to advancing nascent cell therapy technologies into commercially viable product candidates. I've said many times that cell therapy is on the cusp of a breakout. But that breakout will require a maturation from early or academic programs through manufacturing and delivery enhancements and ultimately to the generation of controlled clinical data. The Lineage model is to serve as that bridge and facilitate the adoption of this new branch of medicine. Now thirdly, I'll move to VAC2, our investigational off-the - shelf dendritic cell cancer vaccine. VAC2, as many of you will recall, is comprised of mature dendritic cells which we manufacture from proprietary established cell banks, which are then loaded with a tumor specific target or antigen to instruct and deploy the body's immune system to attack and eliminate cancer cells. Our partner Cancer Research UK, continues to be responsible for this study, but enrollment has been impacted by COVID restrictions across the UK. CRUK is still working on enrolling the final patients into the study and following completion of enrollment, we anticipate additional clinical data will become available and recorded. Because the trial operationally is out of our hands. We're unable to accurately predict when that final patient will be treated. But I will share that I am increasingly frustrated by the pace of enrollment in this trial. We have initiated steps to address this situation, so that the VAC2 program can advance in a more predictable fashion under our direction and control. Meanwhile, our focus is on making improvements and modernizations to the VAC manufacturing process, which will help prepare VAC2 for future trials, and provide competitive advantages for any future VAC programs we made design in advance. If manufacturing focused investment is similar to what we did successfully for both OpRegen and OPC1, and is core, so many is just competitive advantage in selling gene therapy. As part of the manufacturing enhancement process, we aim to enhance the flexibility of the back platform because one could theoretically answer any antigen into our dendritic cells. And we believe the back platform is therefore capable of producing a tremendous number of product candidates, with each one being distinguished by the specific antigen, which are dendritic cells are presenting to the patient's immune system. This opens up a large number of potential corporate partnerships by allowing us to use our dendritic cells as carriers for other companies antigens, while simultaneously retaining the option to advance our own programs. And these partnerships can diversify our oncology pipeline across more programs and provide new opportunities for success without the financial burden of independent development. As you're aware, we already have the first instance of this with our glioblastoma program, which we have partnered. Overall, I believe we have continued to execute on our plans, and generate valuable progress by advancing all 3 of our clinical programs, and further strengthening the Company's capabilities. With that, I'm happy to turn the financial update over to Kevin.

Thank you, Brian. And good afternoon, everyone. Let's briefly review our recent financial results. Total revenues for the third quarter were approximately $2.3 million, a $1.7 million increase from the same period in 2020. This increase was due primarily to increased royalty revenue from a certain partner based on an updated communication to us regarding the royalties owed. Total operating expenses for the third quarter of 2021 were approximately $8.1 million, an increase of approximately $900,000 as compared to the same period in 2020. That increase was primarily related to increased litigation expenses related to the hysteria steel, as well as share-based compensation expense. As a result of these items, our loss from operations for the third quarter was approximately $6.8 million, an increase of $100 thousand as compared to the same period in 2020. The net loss attributable to Lineage for the third quarter of 2021 was $7.8 million or $0.05 per share as compared to $7.8 million net loss last year, or $0.05 per share for the same period. Turning to the Balance Sheet, the Company ended the quarter with approximately $65 million in cash, cash equivalents and marketable. securities. That wraps up the financial section. So, I thank you for your time and will now turn the call back over to Brian.

Thanks Kevin. I want to spend the last minute or two here just being really clear about some of the events and milestones that we anticipate. So first, just three days from now, additional interim data from the OpRegen clinical study will be featured at the 2021 American Academy of Ophthalmology Annual Meeting in that presentation I described by Dr. Michael Ip. Before year end, we plan to provide an additional data update, which will be able to include a minimum of 12 months on all treated patients in the OpRegen study. And as a reminder, that was -- that is the primary endpoint for that study, a 12-month observation period. We also have multiple interactions with the FDA plans, where we will discuss OpRegen product designation or manufacturing plans and later stage clinical development. Those steps are anticipated to begin this quarter and continue into the first quarter of next year. For the OPC1 program, we aim to complete the evaluation of the spinal delivery system or the system in non-clinical testing, and that is anticipated in this quarter. We also expect to complete GMP production of OPC1 via our improved and larger scale manufacturing process, using also our new and inject formulation that is anticipated to occur in the first quarter of next year. We have an FDA interaction planned to discuss recent manufacturing improvements we made to OPC1 that's anticipated in the first quarter of next year. And we're looking forward to initiating clinical performance, and safety testing of the new delivery device with an IND amendment and that submission is planned for the first quarter of next year. With respect to the VAC programs, completion of enrollment by Cancer Research UK and the ongoing VAC2 Phase 1 in non-small cell lung cancer is something we hope will occur in the first quarter of 2022. The continued development of the new VAC-based therapeutics with our strategic partner will be ongoing throughout next year. And thirdly, we'll be evaluating opportunities for new VAC product candidates based on internally identified or partnered tumor antigens, which also will be ongoing throughout next year. At Lineage, we believe the field of cell therapy is poised for explosive growth and that scalable allogeneic off-the-shelf approaches, which are prepared in formulation that are optimal for clinical settings, have the ability to provide significant commercial advantages over autologous or patient-derived sources and methods. And our objective is to usher in a new branch of medicine using our proprietary differentiation protocols. And I believe the data we have been generating is supportive of that goal. With that, I would like to thank you very much for joining us this afternoon and Operator, we are ready to respond to any analyst questions that you may have.

Your first question comes from the line of Mayank Mamtani from B. Riley. Your line is open.

This is actually William on for Mayank. I really appreciate you taking our questions today and great overview of your third quarter, really, really a lot of good events that went on. Was just curious in regards to your upcoming FDA interactions for your OpRegen. Curious if you'd be discussing the -- might have the strongly 3D Okta that you said that you'll be highlighting at AAO coming up this weekend. And then the possibility about incorporating this into later studies. And also just kind of at a high level in your discussions with the FDA, will you be communicating to these -- these conversations broadly to the public and what we might be expect overall?

Let's get Gary Ho involved in that question. Gary, are you on track for that?

Sure. So thanks for the question, William. Yes. So certainly the Dohainee (ph) data would be incorporated in any discussions we have with the agency because they have provided supporting evidence of retinal restoration and treatment effect. And so again, it's done in an independent fashion. They use OCT images which are already had been obtained as part of the study. And they review those independently. And basically, what that does is it looks for thickness in volume, and a layer-by-layer basis. And they compile that over time. Then they produce these heat maps and show the improvement from baseline to the 1-year primary endpoint. So we definitely incorporate that into discussions with the agency about potential designation changes or incorporation into a subsequent clinical study to show again that there's treatment effect not only on the area of geographic atrophy, but throughout the layers of the retinal structure of interest.

And then I guess just high level then -- with those, because there are -- I believe you said there will be multiple FDA. Will you be communicating those findings in an ongoing process?

Sure. really very much, I jumped in . But for part 2. For competitive reasons, we obviously won't be previewing our regulatory strategy or discussions. But after we hold the, the FDA meetings and we have the specific feedback to the plan that we will pursue. that is something that we absolutely would be sharing. Typically for how Lineage does things we would share that in abundant at the tail. I have said several times that there are many designs which might fit well for our particular situation, including various adaptive or continuous phase 2, 3 designs. And the work is currently ongoing to determine the clinical plan that we will present to the FDA as our first and best choice. But as a reminder, we only completed enrollment on November 10th of last year, literally 1 year ago. So those patients have now just finally reached, literally today, the primary endpoint of 1-year post treatment. So I think we're on track and moving quickly. And any discussions on the next study design are going to need to include those data. So they're being collected and analyzed. And that's why we'll expect that interaction in particular to be designed would be something that would occur in Q1 of next year rather than Q4 of this year.

Right. Makes sense. And then one about OPC1, you mentioned that you have a new cell inject formulation. I was wondering if you get extra -- any information on how that might be improved over your current formulation, sorry, maybe a higher level, but also curious, maybe like cell viability or just any extra benefits that the patients might expect.

The key advantages here, what we're really trying to accomplish was a formulation that was ready-to-use. So one of the headaches of most cell therapy approaches is the dose preparation. And in particular for the OPC1, the prior study required the preparation of the cells, had to wash out the medium and place them, and count them. And this work had to begin the day before. So you have tissue culture activities and then eventually you could get that material into the patient the next day. That's a big headache and we have the technology and the experience, the success of doing that with on OpRegen. So we deployed some of the same approaches in order to have a thought and inject formulation which will go from a frozen state right into the delivery needle and be administered to the patient without that long delay. So we're putting those kinds of commercial planning and utility -- anticipation into practice, while we're going through and working on things like scale or -- in all of our programs, whether we're following up on clinical data, etc. Those are some of the key advantages, and I have an estimate of about a 90% reduction in the handling and manipulation costs and complexity. By the way, it also will help vastly reduce the possibility of a dosing error, which did occur in the hands of a prior sponsor at one of the sites. There are a lot of advantages to having a thaw-and-inject formulation. And as you did hear me say in the body of the call that one of the things that we're really excited about is that we will be able to administer ourselves more slowly by using this formulation compatibly with the new device because we will not be -- will not have to take the patient off the respirator during the administration of the cells. And just as an FYI, I was watching some pre -clinical animal work very recently, and the administration of the cells is essentially automated. Everyone's pencils down for 5 minutes while the cells are being administered. It used to be a manual process where you're pushing it in quickly and you had the hurry because there was a clock running because the respirator was not functioning at that time. We think this is a huge and really underappreciated benefit to utilizing this new formulation with this new manufacturing process and this new device, and we think it will facilitate the clinical activity and even open up additional sites that maybe didn't have the capabilities to handle these cells, but they certainly have the ability to just throw them at the bed side in the surgical suite and administer them.

That's fine. I really appreciate that extra color and thank you for answering our questions today. And look forward to everything. Thanks. Bye.

Appreciate that, William. Thank you.

Your next question comes from the line of Joe Pantginis from H.C.W. Your line is open.

Hey everybody. Good afternoon. Thanks for taking the question. Brian, I want to ask a specific question and then I'm going to get a little more macro. So during your prepared comments, you gave us a little bit of a tease with regard to OPC1 saying that you're toying with new ideas with regard to regulatory strategy. I'm just wondering if you could provide a little more color on that comment.

Boy, you're really putting me on the spot. Not -- that's good. Not yet. Here's what I can say, or I here's what I'm comfortable saying, is that there are clinical settings -- there are disease settings where the endpoints are difficult, and dry AMD is one of them. We all love to think that visual acuity is easy to rely on, but it's challenging. Which is why the world shifted to more of an anatomical endpoint than growth. So similar, -- a similar situation exists in the setting of spinal cord injury. It's very difficult to demonstrate improvements in mobility, because the tools and assessments that are generally collected, are favorably crude 3-point scales and so forth. And there are other assessments that have been in development and other companies or an academic centers for many years that are maturing and are probably more useful. And the way that I would try to put a finer point on this is that I talked to a patient who is on this study who received OPC1 Cells and he told me, I didn't score as high on 1 of the scales, because the particular mobility -- the particular movement which I had gained didn't register. And so he said "but it was useful for me, I could curl a finger and hold on to a mug or a cup. " And so it was useful for him for independence and his ability to keep himself hydrated. But it never showed up as a benefit clinically because there was a disconnect between his gain of function and the score, or the scale that was being used. So without going into specific details, there are other tools that are available. And I'm very interested in how we might re-approach some of that in order to increase our probability of success by narrowing the gap between what the cells and the therapy can provide and what is being measured. And I have some experience with this previously in my career, and I think that there are -- I'm looking forward to hopefully getting some more information and being able to share more of a conceptually that's what I'm talking about, trying to make sure that what we're measuring is not just clinically important, but it's also more closely tied to the benefits that we believe this therapy can provide.

No, that's really helpful. Thanks. And I look forward to FDA visibility on their feedback. So going to the more macro front as I alluded to, you have a lot of logistical things going on at the Company. Manufacturing of yourselves first and foremost, as well as your device initiatives with OPC1. I guess I'll ask the question this way, based on all those logistics that you have to deal with and are dealing with, do you have any impacts or have you had to change your plans with regard to all of the global supply chain issues that everyone is experiencing right now.

That is a very clever question. I'm proud that the manufacturing folks in particular were concerned about supply chain issues and brought it to our attention. So we have done a lot of pre -purchasing of critical materials, and we have had the benefit of being an international Company, right? We have approximately half of our staff located in Israel and half of our staff located in the U.S.. There have been times where we have acquired or purchased equipment or materials in one country and shifted to the other. And by the way, sometimes you can find cost savings. But it's more important for us to have availability of those materials. So I have heard stories about lack of availability of things as simple as tips and plastic. I'm a little bit more concerned with reagents, key reagents, because if you are running a 2-month long manufacturing campaign and you get to day 40 and you're supposed to add secret ingredient number 7 and it's not available, you're done. So the manufacturing team, which is the same team working on all 3 programs. That's one of our efficiencies and tangible efficiencies about how we run the business has been very good about advanced purchasing and basically stockpiling in particular things, materials or reagents that don't have expiration dates and so forth. So I hope that every Company is able to avoid those challenges. But one easy way to solve them is to just order from multiple suppliers and know that you will eventually be using that stuff.

That's really helpful. Thanks for that. And it's obviously an ongoing issue, and it's nice to hear that you planned ahead, and are dealing with it. I guess my other -- my last question is also somewhat macro-focused, but on the VAC program. Beyond the non-small cell -- VAC2 and the lung cancer program, I guess, how would you characterize your ongoing BD discussions for additional antigens that people might be interested in?

How would I characterize those discussions?

Scope of discussions, and how advanced or immature they might be.

Almost as a rule -- Joe it's a very good question. It's a very fair question, but almost as a rule l try not to comment on business development activity or try to put any sort of potential or anticipation behind it, because I have experienced huge global partnerships that fell apart 24-hours before they were signed for almost unrelated reasons. So, what I would say is we maintain a high level of interest and engaging with different entities. Actually a very broad array of entities, form and type of those entities with respect to partnering. But I'm far more comfortable letting something gets signed and announced than to say, for example, I want to have 3 of these this year or 1 big one this year or any kind of guidance at all on partnering. I think we'll just let the surprises happen when they happen during the year and on any of our programs.

And you know what Brian, that's a very fair answer. And I had to ask it anyway, because of the potential around beyond lung cancer of the platform potential of the VAC Cell. So but thank you for all the color. Thanks a lot.

Great stuff, Joe. Thank you.

Your next question is from the line of Kristen Kluska or from Kantar Fitzgerald, your line is open.

Good afternoon. This is Rick on for Kristen. Thank you for taking our questions. To follow-up on an earlier question on the multiple guided FDA interactions in upcoming quarters around OpRegen, how are you thinking about priorities in the potential cadence of regulatory discussions as you're thinking about moving the program forward?

Yeah. I'm going to invite Gary to respond to that and provide a little bit more detail than we have in the past. Sure.

Sure. Rick, as we've announced previously, so we've already got fast-track designation which affords a certain interactions with the agency, on some ability to have them help us guide the program. There are other designations that we can seek that we think we've put enough to fulfill the obligations to. One of them is RMAT, so that's a Regenerative Medicine Advanced Therapy designation. And as the FDA review data, they can also suggest that they think that your data meet their expectations. You can also be -- consider submitting therapy. So in addition to our fast-track, we're considering those 2 options as well. Taken with our data, which again we were 1 year post, our last patient being treated. Those data are being analyzed and collected right now. The study reports are being written and we will review in the studying meeting with the agency to discuss the profile endpoints, size, and scope of the next study. That would occur, following the designation meeting.

Thank you for that answer, and 1 more perhaps. For OPC1 you've guided that you could move from non-clinical testing with the PSD system in 4Q this year, to potential clinical and safety testing with OPC1 with potential IND amendment in first quarter of next year. Could you please discuss how rapidly you believe you could move from the IND amendment stage into clinical testing? Thanks.

Gary, do you have some thoughts on the gap between -- I mean, I know there's a 30-day waiting period, but any further color on that, our readiness there?

Yes. So the agency will review a number of our supporting documents behind that, we'll work on the protocol is Brian speaks to that there's the 30-day created no comments, but the hope would be to, obviously get a first date in hand as quickly as possible. So we haven't yet set a date on that yet, but as quickly as the agency would allow us basically.

Okay. Thank you very much.

Your next question comes from the line of Jason McCarthy from Maxim Group. Your line is open.

Hey Brian, this is Michael Okunewitch on the line for Jason. Thanks for taking my question.

Hi, Michael.

I'd like to look -- Could you talk a bit about the importance of now having achieved typical significance after the 9-month data on OpRegen study? And if this gives you a clear idea of the expected effect size and what kind of trial size you'd need for later stage studies. And are there any comparable trials you can look at to get an idea?

I think it's probably worth being clear that the statistical difference exists, which is wonderful. But we're talking about a difference of treated and untreated eyes, so the population of data points over time. The size of the study details around the endpoint, all the things that everyone including us would like to know more about really are part of the output from our FDA engagement. But I think I can add that there are some precedents out there that are informative. I don't think that if you keep in mind that the size of the study is a function of the end required for a statistical plan to give you evidence based upon some benefit or some Delta. That there's a zone of reasonableness. So if you, for example, ask on one end, where do you start getting sort of ridiculous as far as your benefit? And what I mean by that is, if the bar that exists out there is slowing growth of GA, and we're reversing it. Obviously we have a whopping clinical, excuse me, a whopping effect that can be observed in a very small number of patients. However, when you're doing registrational studies, there's also a realistic floor as to how many patients the agency is going to self-exposures the patient is going -- that FDA is going to want to see in order to feel comfortable with branching and marketing authorization. We have a scenario where there's we can't become overly optimistic, or overly aggressive because we run into the reality of needing to have enough exposures that we're satisfying the agency. That's one side. The other side is that if you I guess study so large that you start to detect with statistical significance, even a small effect, that becomes a very silly, and that's where 1000-patient study or something like that, that's where you're showing statistical significance of some tiny little benefit. That's not our objective. In fact, we've benefited tremendously from the data, which showed a cross different studies, what 12% to 29%, 27%, I don't remember range. That's a floor. That's the comparison, setting aside frequency of treatments, safety profile. Just saying clinical benefit. That's the comparable floor that we're working with. And I think that that's well supported by the future user community of saying we'd like to see 20, 25% slow reduction in the growth of GA. So all of that is to say that there are some reasonable boundary conditions. But I could shorten it to be like, look, I think it's going to be fewer than 300. I don't know, we haven't gone in. But if you're looking for give me an order of magnitude reality check, the precedence which are out there, and the size of the clinical benefit and the reference points from complement inhibition, and the need to have enough exposures, you start closing down the range of what's possible. So somewhere between 200 and 300 patients seems most likely to me, but we won't have the final number and we won't make any further clarity on that until we actually have the output from that meeting with FDA.

All right, thank you. And then can you just provide a bit more granularity on when you're expecting to hear the output from those upcoming meeting. Both of them for OpRegen as well for OPC1.

There's a whole series of events right in, and I've covered them in the call, the most notable one around design of an OpRegen clinical study that's a meeting that we expect to have in Q1 next year. OpRegen has several engagements. We've got completion of certain activities and then, at least 2 engagements with FDA in Q1. So there's actually a very heavy amount of FDA engagement that we anticipate in Q1. But I will be clear that those engagements can vary. You don't always have an in-person sit-down meeting. Sometimes big questions can be addressed through written correspondence, sometimes it's a call, we don't have everything determined. We leave it to the agency to direct us as their what they are looking for in terms of the form of meeting and et cetera. So Q1 is going to be somewhat of an incredible quarter for us because the number and substance of those regulatory interactions is so high. And that's going to inform so much around, how long it will take them on these to run these studies -- whatever we studies, probability of success, that people ascribe to these studies, when they can initiate enrollment, etc. etc. So it's a really important start to the year for us.

Right. Thank you very much. And then 1 more if you don't mind, just like to touch on your talking earlier about the ability to do 3D measurement of the geographic atrophy. And is there a possibility that you could detect additional signs of retinal restoration beyond those original 3 patients where you've already determined it because you would just -- didn't previously have the tools to measure it?

Yeah. I mean, I'm going to say yes because I didn't expect to see the retinal restoration to begin with. So is it possible? Absolutely. But perhaps Gary, you could add something to how that technology works and what we might be able to learn from it.

Sure. Yes. So the thing about it is this is being done independently and in blinded fashion. I think everyone knows they were treated, but they, , that's doing the analysis don't know in advanced who is or is not a retinal restoration patient. And so independently as they've identified these areas of iRORA or incomplete retinal atrophy, as well as cRORA repair. And so, yes, there's a good possibility that there may be additional patients that they will identify that are retinal restorations. We look to them to validate and which they've done is all right, the 3 that we've identified, potentially, identify additional patients that show a clear benefit.

Thank you very much.

You're welcome.

Your next question comes from the line of Dane Leone from Raymond James. Your line is open.

Thanks for taking the questions. Just one from me. When you meet with FDA, what is the primary endpoint that you would hope to establish for running a pivotal study with OpRegen? Thank you.

Dane, we're going to erase what all the leading companies are doing, which is the same form of change in GA area over time with three separate assessments. I think there's been some misconception in the past in some places. Not your place, but I think there has been some misconception because we've had this visual acuity data, which is so compelling that that would be what we would elect to pursue. But I think that we view that as subordinate to being able to reverse the size of the GA. So we would be monitoring the change of GA over time. We've -- we presume we will be proposing that just like the leading companies in this space. The key difference is that we'd like to rely on OCT as the assessment tool because FAF is incapable of seeing our selves. So the deck is rather stacked against us with FAF, because our selves are invisible using FAF. So it'd be kind of ridiculous, it would be inappropriate. It's not a matter of utility, it's why would you use the wrong tool to try to assess it. I don't think there's a particular level of risk. I don't think that the FDA is going to say no, FAF is the only imaging tool we would ever accept. That seems ridiculous when the field -- the experts in the field, I think are very well aligned. The OCT is a more powerful and informative imaging tool. I think people are going to be delighted that we would be embracing a better camera -- a better imaging technology to measure, essentially the same sort of anatomical changes over time. Gary, is there anything I left out there that I should add about that?

No, I think you captured it. Again, everyone acknowledges that OCT is a superior way. And taken together the microperimetry, visual acuity, and the other functional data in addition to the structural data that the agencies already considered as an approvable endpoint. We think makes a compelling story for OpRegen to utilize that endpoint and show true benefit to the patients.

Got it. Thanks.

Sure.

Great.

I am showing no further questions at this time. I would now like to turn the conference back to Mr. Brian Culley for his concluding remarks.

Well, thank you, everyone. As always, we appreciate your support as we positioned Lineage to become a leader in cell therapy and cell transplant medicine, we obviously still have more we expect to accomplish this year, but I think 2022 and even 2023 are going to be even better as we continue to deliver. And as awareness of our accomplishments continue to grow. Thank you very much, and have a great afternoon or evening.

This concludes today's conference call. Thank you for your participation and have a wonderful day. You may now disconnect.