Welcome to the Lineage Cell Therapeutics Third Quarter 2022 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's website at www.lineagecell.com. This call is subject to copyright and is property of Lineage. 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 you to the host for today's call, Ioana Hone, Head of Investor Relations at Lineage. Ms. Hone, please go ahead.

Thank you, Jack. Good afternoon and thank you for joining us. A press release reporting our third quarter 2022 financial results was issued earlier today, November 10, 2022, and can be found on the Investors section of our website. Please note that today's remarks and responses to your questions reflect management's views as of today only, and will contain forward-looking statements within the meaning of federal securities laws. 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. 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 performance to differ, we refer you to the forward-looking statement sections in today's press release and in the company's SEC filings, including its most recent annual report on Form 10-K and its subsequent quarterly reports on Form 10-Q. 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 Culley, our Chief Executive Officer and Interim Chief Financial Officer; and Gary Hogge, our Senior Vice President of Clinical and Medical Affairs. Brian will provide some prepared remarks and then he and Gary will be available for questions from analysts. With that, I'd like to turn the call over to Brian.

Thanks, Ioana, and good afternoon, everyone. We appreciate you joining us on the call today. I'd like to begin by welcoming Jill Howe as our new CFO. Jill is an experienced executive with a long track record of successful execution in capital raising, strategic financial management, corporate operations and many other areas of finance and accounting. And we are fortunate to have someone with Jill's extensive background joining us at this time in the evolution of our company. Jill's first day will be November 14th, and you can expect her to join me on future earnings calls. Next, I want to begin with a few comments about the evolving landscape in dry AMD. As everyone on this call is aware, the most advanced program in our pipeline OpRegen is in RPE cell transplant designed to treat dry AMD with GA. Dry AMD is a disease which has attracted a lot of attention lately, because there are currently no FDA approved therapies for it but several large trials have read out with potentially approvable results. One competitor in particular is expected to maintain its late February PDUFA date for its complement inhibitor to treat dry AMD. There has been abundant speculation about whether their data will support approval. While much of the discussion around dry AMD is currently focused on complements, we believe OpRegen’s proposed product profile and the data we have collected to-date are superior to that of any complement inhibitors. For this reason, I want to take some time today to discuss the possible approval or rejection of a complement inhibitor and the impact that, that decision might have on the value of the OpRegen program. I wouldn't ordinarily speak so directly about competitor data. But I've been receiving a lot of questions about complement inhibition lately and if…

[Operator Instructions] Jack Allen with Baird.

This is Ben on for Jack Allen. We have a few questions. First off, where are you in the regulatory process as it relates to getting approval for the use of the novel delivery device for OPC1 program in spinal cord injury? And then moving forward, what are the plans as it relates to advancing this program? How quickly do you expect to enroll patients? And then how quickly do you think you could move this into a pivotal study?

I think we'll both answer that question. Ben, thank you for that. Gary, can you start with the regulatory process for the device?

Sure. So what we've done is we've interacted with the agency on a number of preclinical animal testing and proof of the device and intended safety and use. So we've initially provided our responses to their questions. They in turn, have asked us additional questions. And we've gone about to complete those additional experiments and answers to their questions. And we'll again, as Brian said, submit those shortly.

And then with respect to advancing the spinal cord injury program, there's three chunky steps that I think about. We have to get the device clear because it's a better way of delivering the cells. We have a new method of manufacturing the cells which I've shown this data many times. It appears to be significantly superior to the old way. So we have to bridge those new cells in and then we need to conduct the large trials that can support approval. In terms of the three factors that come to mind, and how long things will take, speed, quality and probability of success. I think speed is something that we're going to have a wonderful opportunity to improve upon, compared to the last study. As a reference, I would -- and I hope I get these correct. But in the OpRegen program, I think it took about two years to get the first four patients. But it only took about six weeks to get the last four patients. So that reflects improvements in how this company has been able to conduct and enroll patients in trials. And obviously, a significant improvement. In terms of quality, we will never go fast, so fast that we are sacrificing quality. So sometimes people would like to see us move quicker. But we also want to ensure that our quality is at a very high level. And then with respect to the third item, which would be Phase 3 studies, or whatever comparative study design would be sufficient to gain approval. There is no precedent right now for therapeutic intervention in spinal cord injury, so we don't really know. We have to sit down with the agency after we've crossed some of these earlier steps, and then have a discussion about what they would need to see. And I do think that, that will be a two-way discussion, because I happen to believe that there is a bit of a gap between the assessment tools that people naturally think of in the setting, and what matters really to patients who suffer from these debilitating spinal cord injury. So I don't know that that necessarily means an SPA, but I think there needs to be a real interesting conversation about how best to demonstrate that OPC1 cells can lead to greater mobility after therapy compared to not having received those cells.

And then just a quick follow up on GA. Could you maybe just frame again your thoughts regarding the read through from your competitors' ongoing regulatory discussions to the OpRegen program, please?

Win-win. I won't go through everything but if anatomy is the basis for an approval, I think our anatomical data is better than anyone's. If functional improvement is required, well, we've demonstrated functional improvement. It's in small numbers, but we know that the complement inhibitors have not shown a functional benefit to patients. So I don't intend to be glib, but win-win.

And then just real quick, lastly. Obviously, recognizing that the program is driven by Roche, wonder if you had any updated comments as to their plans to advance the OpRegen asset moving forward?

I am only able to direct you to several quarters now of revenue that we have recognized under the collaboration, which is obviously a reflection of the work that is being performed. Some of that has to do with the manufacturing, but there are other aspects of readiness that are ongoing. So, I'm able to characterize that we're very satisfied, very happy with the progress. But unfortunately, I'm not able to provide you today with any specificity as to when the next study would initiate. But you could expect that, that initiation would appear on the clinicaltrials.gov website. So that would be a good place where you'll be able to get some new information on that study when it becomes available.

Mayank Mamtani with B. Riley Securities.

This is William Wood on from Mayank Mamtani. Nice to see your continued progress here, Brian, just a couple of questions from us. So in regards to the OpRegen discussion that we've -- that you've sort of put forth, I was curious what is your awareness on the FDA stance of thinking about newer, probably much more transformative modalities, especially if they recognize trial conduct could get challenging if these initial pretty marginal drugs are approved? And then additionally, also, could you provide some references of what a control arm could be in a GA study? And should we be looking at sort of more of a gene editing trial to think of it as an appropriate reference?

Thanks, William, for the question. With respect to trial conduct and sort of an appetite for new modalities, I don't have any different insight than most people on this call. What I do is read the same tealeaves around FDAs commitment to guidance around selling gene therapy and their commitment to working with companies. So I think that as modalities change and become more prominent and ultimately become mainstream, if not dominant, that the agency has a history of adapting to that, even going back and looking at the history of somewhat of a transition from small molecules to antibodies. So we see that happening with gene therapy, we see that happening with cell therapy, and I expect that that would continue to occur and would have some pertinence to the ophthalmology setting for dry AMD as well, because clearly there are differences between injections or oral compounds and cellular transplants like ours.

Yes. I mean to add is again, we have Roche and Genentech is addressing the next phase of development for OpRegen but certainly in our discussions with the therapeutic area experts, and other regulatory consultants. We certainly believe that an untreated control arm, when we were considering moving the study forward, would make the most sense was the most ethical and allow them to cross over then to treatment, provide the safety and efficacy profiles. So look the same. But again, that was those were plans that were that we had long ago and Genentech and Roche certainly has their own development pathway.

And then just one more, you've got the newest -- the news, U.S. R&D facility in the -- the expanded facility in Israel, which really should allow you to ramp up both your clinical and preclinical efforts, including potentially the RPE manufacturing for the OpRegen program. I'm just curious if you could add any color on how you're potentially using those facilities, whether it's specifically for the RPE manufacturing or maybe potentially how you plan to capitalize those new facilities going forward in general?

It will evolve and be slightly different for each of them. So starting up a new laboratory is typically a slow process. So initially, you're just cleaning it and then you're equipping it and then you're staffing it before you can finally actually start to generate meaningful data from different programs in there. So you can expect that, that process, that normal process is one that we will be following in a stepwise manner. For RPE, which you specifically asked about the base case is technology transfer to Roche and Genentech for them to be able to conduct the manufacturing. So, that is an area of considerable effort at this time, because that is the intended outcome from the program that Roche and Genentech will be able to internalize the capabilities of manufacturing the cells from the line which we utilize, and to do so in a commercial manner. And then more broadly, internalizing some R&D and being less reliant on vendors, I think is now more important than ever, this can not only help with obvious things like reducing costs, and being able to have greater control, but you can find yourself availed of new intellectual property that maybe a vendor would not have come across, you can find yourself with greater flexibility around your timelines. And in this environment, it still is the case that supply chains are unpredictable. And in some of the aspects of what we do, you really can't hoard some of these reagents. Media has got a expiration date, growth factors and enzymes and proteins, they have expiration dates. You don't want mRNA sitting around for too long, even at very cold temperatures. So internalizing that gives us additional flexibility in order to control our supply chain and make sure that we are neither over-equipped and finding wastage of our inventory, nor having a situation where we are underprepared and can't initiate work, because we don't have the right equipment or reagents in place. So three really big aspects of internalizing some of our R&D at this time.

Just a follow-up on that, it's my understanding, obviously, please correct me if I'm wrong, that Lineage will supply the OpRegen material through the end of Phase 2. And so I was curious if potentially this sort of scale out in R&D had potentially a correlation with a scale up for RPE and/or if I'm just reading too much sort of into the tealeaves there?

No, I can understand how that those dots could appear to be connected. But the facility that we've established in San Diego is more intended to support internal programs than the partner program with Roche and Genentech. And the expansion in Israel is something that we had considered for a while. As you do know, we have five programs now that we've disclosed. So we -- I do not -- I would not want you to think that the additional space that we acquired in Israel, connected to our existing facility is connected in a meaningful way. It simply provides some additional space for us to utilize across all of our programs, but it's not directly involved and not indicative of anything in particular with the OpRegen program.

Kristen Kluska with Cantor Fitzgerald.

Hi, everyone. This is Rick on for Kristen. Thank you for taking our questions. Now that you are undertaking preclinical work for the photoreceptors program, how has the previous experience with preclinical characterization for OpRegen help to expedite this process? And do you have anything you can say about when we may see preclinical data from the photoreceptor program?

I would say it is incredibly valuable to -- incredibly valuable but difficult to describe or measure the benefits of the prior experience with the RPE program. So the knowhow that is established for being process development experts in directed differentiation spills over into other programs, not even limiting that to ophthalmology programs, i.e., photoreceptors, but directed differentiation and control of cellular fate more broadly, and additionally, the development of the analytical methods to support the characterization of your cells. So when I said at the end of my prepared remarks that we are investigating ways to accelerate timelines in cell therapy, you knowingly or unintentionally have actually picked up on one of those, which is the experience that the team gets with these methods allows us to go faster because we retain those learnings and lessons and can apply them to other programs. The second question around preclinical data, I think we provided just a teaser of some engraftment data, when we first revealed that we were also working on photoreceptors. I do not have an additional timeline for when additional data would be provided. But the company has historically been quite open about that. Photoreceptors are difficult to work with. And I'm sure that if we have something that we're comfortable sharing on a non-competitive basis, and publicly, we will be willing and excited to do so.

Michael Okunewitch with Maxim.

So I guess first off, I'd like to see if you could expand a bit on the broader opportunities for the auditory neuronal cells. I guess which condition actually involves the loss of those [steps]? For context, one of the reasons I'm asking is because of some of the activity we've seen in the auditory disease space, in particular, with really picking up its preclinical OTOF-targeting gene therapy company for, I think, $0.5 billion.

Thank you, Michael for the question on our auditory neuron program. I think it's premature of me to define a clear patient population at this time. There are many causes of loss of hearing, aging, of course, is a factor. Sometimes the stimulus loud sounds, concussive forces, certain kinds of medicine in particular, certain types of chemo can cause hearing loss. What I expect that we will be doing is investigating multiple forms of hearing loss in preclinical studies in order to gain some insights into how we would select the correct patient population. I am aware of the Akouos acquisition by Lilly, I thought that was tremendously positive for the field that the valuation of that company, given its stage of development seemed to be remarkable. And I think that's a positive for us to be working in this space. And I think more broadly, cell therapy can be, if not indifferent, at least more encompassing around patient selection, because unlike certain theories which exist or hypotheses which exist in the hearing loss world around how impaired different neurons may be, and whether they need to be rescued or replaced, most of the gene therapy approaches -- not all, but most of them are challenged by providing perhaps one gene product or trying to address one deficiency. Our approach, of course is to replace the entire cell which may give us greater breadth with respect to patient selection, or ultimately patients who get treated with this therapy. But again, I do want to stress that it would be premature and purely speculative for me to try to define a clear patient population at this time. But I am hopeful that some of the preclinical studies will throw some light on that question and direct us down a more a path which is more likely to be successful.

And then I guess, one more like to follow-up on OpRegen. In particular, how you could see OpRegen being applied in a market where there are approved complement inhibitors? Could it be thought of as complements being used as almost a bridge to cell therapy because it might be viewed as a bit of a surgical procedure because it is a cell transplant? Or because it is that one time injection, would you expect OpRegen could be the first thing that doctors will go for, and then possibly use complements as a maintenance therapy to prevent any further progression?

Thanks, Michael, it's a great question. My preference, of course, is for OpRegen to just be a permanent solution and to sit alone in the absence, basically taking people off of complement inhibitors if they're on them, or giving people a better option, rather -- the onetime surgery rather than a monthly or every other month injection. The reality of the dynamics of commercial marketplaces is more likely than not, there would be a constellation of different ways that people would use different therapies. If we were to presume a stabilization or improvement in visual acuity with the utilization of OpRegen, and that that exists in a package insert, and a sales rep can speak to and detail off of that information and that information is not present in competitor therapies, I think this is a quite a compelling argument to be made that could get stronger over time, as we follow these patients for longer, that OpRegen ends up being really the only practical choice or the greatly preferred choice. But there's also the factor of conducting clinical trials in an environment where there may be some changing in the landscape of therapies, i.e. from no therapy to one or more complement inhibitors. So, you didn't ask this, but I'm going to invite Gary to comment on his thoughts on how we might be able to still -- or Roche and Genentech could still conduct large trials, if there's a changing background of complement inhibition, either coming into or coming into and having high adoption or low adoption, or not being present at all.

Yes, so we definitely need to consider a complement. Again, it is efficient, good thing for patients. But it's not necessarily a bad thing for OpRegen. You can look at it as physicians might use it in initial stages to decrease any type of inflammatory effects that are ongoing and then treat with OpRegen after that and give OpRegen a greater chance of success. Alternatively, it might be used -- OpRegen might be used in earlier stage patients since we've shown a benefit when the area of atrophy is less than what we did in the earlier cohorts. So you can consider a scenario where OpRegen used early and complements perhaps used in later stage patients. And the fact is, it may be used in potential trial patients. Again that ultimately is up to Genentech and Roche, but I don't think that, that would necessarily limit the pool of potential available patients to enter the study.

There are no further questions at this time. I would now like to turn the call back to Brian Culley for final remarks.

Wonderful. Thanks, everyone, for joining us today. I hope this was helpful to you and we look forward to following up and continue to make some great progress here at Lineage. Have a great afternoon.

This concludes today's call. We thank you for your participation. You may now disconnect.