But you are still working, in some cases, with academic centers that don’t always have the same expectations around turnaround time because of the volume of activity that they and the number of sites that — excuse me, the number of trials that they may support at one time.
Joe Pantginis: Got it. Thanks, Brian
Brian Culley: You bet. Thank you, Joe.
Operator: The next question comes from the line of Kristen Kluska from Cantor Fitzgerald. Please go ahead. .
Q – Unidentified Analyst: Hi. This is Rick Miller [ph] on for Kristen. Thanks for taking our question. We just have one here. From a big picture market perspective and with the caveat of all the differences between OpRegen and the complement inhibitors, do you have any thoughts on the appellate market penetration stats for SYFOVRE showing around 77,000 injections in the first quarter. Specifically, does this tell you anything about the overall market size and appetite for a therapy in the space and maybe appetite for new therapy options in the space?
Brian Culley: Thank you, Rick. I do think the appellate — I do think the SYFOVRE launch does provide some interesting insights into what’s possible in the setting of dry AMD. And specifically, I think their product profile with the safety concerns that are probably well known to everyone on this call yet they’re seeing some fairly good uptake of that product tells you a lot about demand. It tells you a lot about the opportunity and the eagerness for a new therapy. I concur with your comment and the implication that we have a very different product profile, a onetime therapy that might perhaps be able to restore vision or halt the disease in its tracks. So we don’t know what the ultimate commercial profile of this product will look like, if any.
But I’m encouraged by the fact that even a product that has been clinically shown to have no effect on visual acuity and can only slow the advancement of the disease by approximately 20% a year — and I recognize I’m generalizing with that because there are multiple products and you can have monthly or every out you monthly dosing. But as a general matter, it doesn’t seem to me to have much of a clinical benefit. It does have some now well-known risks associated with it. And yet, I think last quarter, they did pretty well. So I think that tells us that all of the predictions around a multibillion-dollar opportunity in the setting of dry AMD is clear. It tells us something great about the demand for new therapies and the rapid uptake of new therapies by both the provider and the patient.
What we have not seen perhaps is what the level of compliance and commitment to monthly or every other monthly injections in your eye is going to be in the long run. But I don’t care because OpRegen is not administered in that schedule. So we don’t have that as a hurdle for our expected product profile. So I think we continue to stand in a very good place with the added benefit that a theoretical commercial opportunity is turning into an actual commercial opportunity in front of our very eyes. Operator, can we have the
Operator: Yes, he just dropped from the call. The next question comes from the line of Michael Okunewitch from Maxim Group. Please go ahead.
Michael Okunewitch: Hey, guys. Thank you for taking my questions. I guess to start off, I do want to ask about the dose study gearing to start up in the near future, could you just remind us of how many centers you’re targeting and provide any additional color on what you’re expecting in terms of the enrollment rate?
Brian Culley: Yes. Thank you for that question, Michael, and your time today. We only need to enroll or we’re only planning to enroll rather 6 to 10 patients. So it will only be presumably a handful of sites, although we initially reached out to more than 10 when we were doing our initial feasibility discussions and evaluations of site capabilities. The harder question is around enrollment rate. There aren’t many precedents. But I think we benefit from the fact that unlike the first time that this therapy was administered to patients. And in some cases, it was known to be a subclinical dose. So you’re having a conversation with a patient about having an additional surgery, and they are being told they will not benefit from it.
And so that would be, to my mind, a pretty significant hurdle to overcome, but the prior sponsor was able to overcome that and was able to enroll such patients. Today, we have the benefit of 30 individuals who have been exposed to this therapy upwards of 5, 7, even now more than 10 years of safety experience. So I think the conversation with patients might be a little bit easier. And we also are going to include approximately half of the patients on the study with chronic conditions. And unlike the subacute patients where you’re — you need to catch them in your neck because they have a window 3 weeks to 6 weeks after their injury where you want to treat them, chronic patients could have 1, 2, 4, 5 years old injury and so they are probably going to be easier to identify, although there is the confounding factor of maybe someone who’s been living with their injury for 5 years isn’t as interested in clinical trials as they may have been when they’re first coming to grips with their new life being a person lived experience in this condition.
So I’m not able to make projections not because I don’t want to, but because it’s very difficult to know what it’s going to look like with this particular design. What I would offer is that I have been involved in and successfully completed, to my knowledge, the largest ever clinical trial in a hematological disorder, and was running a small company at that time and going head-to-head with Pfizer with a very similar 350-patient study. And my organization and the operational excellence that we brought to bear was able to successfully complete our study faster than Pfizer with all of their resources. So, I think we have a great team here. We have some new hires, and I think that, that’s going to put us in the best possible position to get that enrollment as quickly as possible and get those answers so that we can move on to what we’re more excited about, which is the ultimate question of a controlled study and how much of a benefit do patients get from this treatment.
Michael Okunewitch: On that, just given you have the free — basically a free look now at the thoracic and the chronic patients, which you haven’t really previously been exploring. Do you have any idea of what sort of improvement you would want to see to consider developing those indications further?
Brian Culley: Yes. And I think the right answer and the answer which is informed by many conversations with people with spinal cord injury is anything. I think that the non-lived experience community has this idea in its head that therapies should allow people to throw away wheel chairs and run marathons. And it is unfortunate because when you spend time with people who have spinal cord injuries, you learn that very often they want just the next little thing. And whether that is because a little bit more mobility can provide independence or they can creatively use it to achieve some goal that they have, doesn’t matter, the consistent message that we hear is that, boy, wouldn’t I give anything to have just a little bit blank.
And that might be bladder control. It might be upper extremity mobility. So, I think that if we saw essentially anything in someone who had confirmed plateaued and that we felt that there wasn’t conflating information from, for example, re-vigor — becoming vigorous again on a physical therapy routine that they had previously abandoned. As long as we thought that it was attributable to the cells, I think that, at a minimum, would drive some new investigation into some animal models and perhaps a small pilot study of that larger patient population.
Michael Okunewitch: All right. Thank you very much.
Brian Culley: Thank you, Michael.
Operator: The next question comes from the line of Sean McCutcheon from Raymond James. Please go ahead.
Sean McCutcheon: Hi guys. Thanks for taking the questions. Can you speak to the two patients that you don’t have 24-month data follow-up for within the limited lab coverage subgroup in the Phase 1/2?. And can you give some balance for the variability on the coverage within that subgroup and how much of the target lesion was covered? And then additionally, what’s your commentary on the trajectory of the BCVA and the extensive live coverage group from month 12 to 14. It looks like you are starting to see a decrement there may be in parallel with the LOI group. Thanks.
Brian Culley: Thanks, Sean. I appreciate those questions. Those two individuals simply elected not to continue in the study, personal reasons, I suppose, but they were not part of some serious adverse event or something like that. And neither of them was among the five “specials” that we have widely discussed. With respect to the BCVA trajectory, I wouldn’t put a whole lot of emphasis or analysis behind the movement from 7.6% to 5.5%, although it may reflect a light erosion of treatment effect. And if it does, I actually think that’s great because that means that 36 months, they’re going to be plus three and at 48 months, they’re going to be plus one, right? It kind of suggest that it’s a very slow tail of change in visual acuity.
But I think two letters probably more accurately reflects noise in the system in a relatively small patient population. I would point similarly to the contralateral eye, which, of course, as I stated before, isn’t going to follow a perfect trajectory. But the fact that it was two letters under at 24 months, it could just as easily have been one letter above or five letters below. I think within a small number of letters, you can really fairly say, it’s noise or not conclusive. So I would not have been entirely surprised if at 24 months, it were nine letters instead of five letters. I also wouldn’t have been surprised if it were two letters instead of five letters. I think the important takeaway that we’re seeing is that 24 months is a pretty long amount of time, trying to read into it just what happens between 12 and 24 reminds me of some of our peers that now have approved therapies that were very cute with some of their subgroup analyses.
I’m really trying to take more of a generalized view of what we’re seeing compared to the natural course of the disease and say, look, we know that sham-treated or untreated patients essentially are losing a lot more than this. So maybe we lost two letters going from 12 to 24. But the patients that we think are the best match have lost seven, eight or nine letters over those 24 months. And we think that, that’s a 13, 14, 15 letter difference compared to where we are. Now you’re starting to look at numbers that you think probably are not a chance, but rather attributable to the intervention that we provided.
Sean McCutcheon: Got you. And just one quick follow-up on that. You said that the patients at baseline had foveal involvement within the treatment group and tied patients in the fellow eye or the fellow eye, I should say, had better vision. Do you know the proportion of patients — of fellow eye that had foveal involvement?
Brian Culley: I do not. I don’t know if the fellow eye was required to have full vial involvement. I know that the treated eye in all cases did have foveal involvement, but we would have to circle back with you and provide that, which we’re willing to do. I just don’t know it off the top of my head.
Sean McCutcheon: Got it. Thank you.
Brian Culley: Appreciate that question, Sean. Thank you.
Operator: At this time, I will hand the call back to Brian Culley.
Brian Culley: Excellent. Well, thanks, everyone. We’ve done a little more than an hour, so we’ll wrap up. I appreciate your time, and thanks for your continued interest and exciting work. We look forward to our next call.
Operator: Ladies and gentlemen, this concludes today’s conference. Thank you for your participation. You may now disconnect.
