ReNeuron Group plc (RENE) Earnings Call Transcript & Summary

Good morning, everyone, and a very happy new year to everyone. Thanks for attending this analyst meeting. I'm Olav Hellebo, CEO; and as mentioned, Michael Hunt, our Chief Financial Officer, is on the call as well. Before we begin the presentation, just want to make sure everyone either has today's slides in front of them or know how to get them. A copy has been e-mailed to you. If you haven't received it, then you can go to the Investors section of our website and pick them down there. So let's, with that, jump into the presentation that I hope you're looking at. Page 2 has the disclaimer. So I'll leave that for your perusal. On Page 3, we can go to the Board members and some selected members of the management team. What I wanted to focus on, on that page actually is the worldwide experts in cell and gene therapy for ophthalmology that we're working with. We have the best of the best when it comes to getting advice in our program here. Dr. Jason Comander is at Mass Eye and Ear, which is part of Harvard. And he has treated -- he is the surgeon that's treated most of the patients so far in the program. And yes, he's absolutely an excellent person to work with. Professor Robert MacLaren has joined the program more recently. He's very well-known in the field, probably the #1 worldwide when it comes to subretinal therapy of cell and gene therapy. He is at the University of Oxford. He was the founder of Nightstar Therapeutics, which many of you might know. And we are in the process of opening up a site with him at Oxford University. Professor MacLaren was part of our Scientific Advisory Board. And then when he saw the data emerging from the program and the technology behind it, he asked to join the study, which we were obviously very happy to accommodate. Found at Page 4 of the highlights, we have teams working in the U.K. and the U.S. We have a unique allogeneic retinal and neural stem cell therapy platform that's sitting behind everything we do here. The lead program that we're working on is an open drug treatment with FDA Fast Track designation for retinitis pigmentosa. We have positive early Phase II clinical data on that program, and you'll see that later. The Phase II data will be gathered, completed this year. We expect them to have a Phase III study starting next year with a readout 2 years after the start. So -- and we're talking here a single Phase III is what we expect to be needed. On exosomes, this is a very hot field in research, and we've been working on this for several years. We have our own exosome program, and we have ongoing collaborations with pharma and biotech partners. We had an oversubscribed funding round last month. So that means that we are well funded and we have multiple value inflection points on news flow points that's coming over the next 12 months that gives us a lot of opportunity to really make big gains. On the next page, Page 5, is the platform technologies. And on the left, you see the human retinal progenitor cell program. So these are stem cells that are delivered subretinally. We think subretinal delivery is important because that enables engraftment. You bond it all to photoreceptors you'll ever have. So if you lose them, they're not going to come back naturally. Subretinal delivery of these retinal progenitor cells gives an opportunity to create new photoreceptors and actually regain vision. So it is important to put them in the right place. We've been able to create a cryopreserved formulation, which is difficult to do but it's also important to do because it allows global ship-and-store. So not important only for clinical trials, but also commercially. The data we have so far is very positive in RP, and we'll speak about that later. In terms of partnering, we are partnered with Fosun Pharma for China. And other than that, we are unencumbered. The second program, the exosomes. Now we have a high-yielding GMP platform for exosomes, producing exosomes from our neural stem cells. We've proven that these exosomes are able to load, be loaded with siRNAs, miRNAs and proteins. We also discovered that they have a favorable distribution across the blood brain barrier, but can also go to other tissues in a targeted fashion. So they -- although exosomes have multiple different potential uses, what we're focusing on is using them as a delivery vehicle for gene therapy, and we have 3 pharma collaborations ongoing right now on that. The third platform here is iPSCs. So induced pluripotent stem cells, a very hot area for research as well. We've been able to take our neural stem cells and engineer them back into becoming iPSCs while preserving the immortalization. And that means that we're able to create large volumes of these iPSC cells. And this is the biggest issue in the field. So we think that we have an opportunity to craft that. The holy grail there is to create allogeneic CAR-T cells, and that is our goal. The CTX cells has positive clinical data in stroke disability, has potential in other neurological diseases as well as Huntington's and TBI. It is out-licensed to Fosun Pharma in China, and we're following a pure partnering strategy for CTX. So it is available for licensing in all other territories. Let's go to Page 6, which is the pipeline. Lead indication, as I said, is retinitis pigmentosa with the hRPC program. Pivotal trial to commence in 2022 would be the next step after the ongoing Phase II study. The second program, exosomes, the next milestone here is proof-of-concept data to be yielded from our current research collaborations. We expect that over the next 6 months. And then the third program is the iPSC platform. The next milestone here is to validate the technology via animal proof-of-concept data that we're generating internally. So with that, I'd like to hand over to Michael for the interim results on Page 7.

Thanks, Olav. So Slide 7 just gives a summary of the interim results for the 6 months ended 30th of September last year. And we announced the more detailed interim numbers alongside the completion of the fundraising that Olav mentioned briefly a moment ago. So these numbers reflect a number of steps we took last year to make -- essentially refocus the business primarily on that retinal program that Olav's just summarized, and that's led to a pretty substantial reduction in our overall operating costs. And you can see that reflected in the numbers here. It's about a headline 35% reduction over the prior period last year, and that really enables us to obviously extend the runway that we have and to focus in on delivering clinical data with that retinal program, first and foremost. So you'll see that the operating costs, as I said, have reflected that reduction in the overall cost base that we enacted last year. The result of that is a cash balance of just shy of GBP 10 million, as you see here at the end of September. And of course, since then, we have completed that, placing an open offer. Both the placing element and the open offer element were oversubscribed, and that gave us GBP 17.5 million gross. And that gives us a runway of at least 18 months from where we are now. So it takes us well into the second half of calendar 2022 in terms of our cash runway to enable us really to deliver the milestones that Olav will take you through in a second in terms of data generation and so on across those programs. And with that, I'll hand back to Olav.

Thanks, Michael. Yes. So let's go to Page 8 for the news flow that we expect to be generated from the funding that we have now added. So yes, it's quite a busy chart, and that's because we expect an excellent news flow over a few of the months ahead. Above the line is the Human Retinal Progenitor cells program and below the line is exosomes and iPSCs. So starting with the RP program, the next step there is to open the first non-U.S. center for the Phase IIa program. As you know, we have centers ongoing in the U.S. We expect to open Oxford University shortly, so in this quarter, and it would be great to get that open. We're also looking at opening a second European site. The extended study, and I'll come back to details on that in a few slides, it has started. It's 9 patients being recruited in that. We expect that recruitment to end early the second quarter this year, and that will yield 3-month data, for most, if not all of those patients in time to be presented at the ASRS meeting, which is in June in Stockholm or maybe virtually, depending. It's the American Society for Retinal Surgeons, and that's one of the big ophthalmology meetings of the year. And it will be a good moment for us to present the 2 million dose data, this extension. Plus, we should have all the first 1 million dose patients, all of them should be at 12 months of efficacy that we will also include in that meeting. The next opportunity to present data is the American Academy of Ophthalmology, very large meeting in the U.S. And by then, we should have 6-month data on all the extended patients, and obviously, 12 months-plus from all the previous patients to update at that meeting. We then, at year-end this year, expect to meet with the FDA to discuss the study design for the Phase III study. I use singular because we expect only one Phase III study to be run. And the design format for the study is quite well-known already, and I'll come back to how that's going to look. And then based on the full Phase IIa data, we have the opportunity to discuss out-licensing deals. Those discussions are ongoing already, but we're not planning to do anything serious on until we have all the data in hand. Below the line is the exosome side. So we expect further pharma collaborations to be signed this quarter. There is -- it's actually more of a bottleneck on our resources rather than the interest out there, so we can pick and choose a little bit on those. Over the next 6 months, we expect proof of clinical -- proof-of-concept data in animal models for the delivery of the different payloads that we are working with right now, so that will be very important to validate that entire approach. Given the positive proof-of-concept data in one collaboration, we would expect that to lead to an out-licensing deal with that party that generated that in the first place. So let's go to the hRPC program in more detail on Page 10. So the first indication, as I mentioned, is retinitis pigmentosa. There are obviously other potential indications here as well. So RP is inherited, degenerative eye disease. The incidence is 1 in 4,000. So that means it's orphan, but it means it's a relatively large orphan disease. There are over 100 different genes that have been identified that mutate, leading to RP. So that means it's not a great area for gene therapy in that every gene mutation is quite small in terms of number of patients. It's very fragmented. Having said that, there is only one treatment available. That is for this specific gene defect for RPE65, which is 1% to 2% of the patients with RP. That product is called Luxturna. It's been launched in Europe as well as the U.S. So patients with all other types of RP, they have declining vision. They will eventually go blind. And they are -- they need therapy and they need help. So a therapy that can deliver efficacy independent of the genetic cause is obviously what's needed here, and we have great expectations to deliver that. Let's go to Page 11, a little bit more specific on our specific approach. So our human retinal progenitor cells differentiate into functional photoreceptors and integrate into retinal layers in animal models. So obviously, the -- that's the whole basis for taking these cells into human clinical trials that we've done. There's a broad potential across different eye diseases, but we're targeting RP first, which is a very attractive indication. We have orphan drug designation in U.S. and Europe, and the FDA has granted those Fast Track designation, which is something that means to get quick response times because they see it as an important potential, this therapy, in an area of large unmet medical need. And we've always noticed that we get very, very quick responses. The manufacturing process is a key part of the uniqueness here. It took us a while to figure out how to get stable, high quality and high quantity production of these cells. And we have important IP around low oxygen culture, which is at the heart of that. We licensed this product from Harvard Schepens Eye Research Institute, which is part of Harvard originally, and we work closely with them as well as UCL currently. I mentioned the cryo formulation earlier. That gives us 9-month shelf life. It's shipped in validated shippers, and so it is becoming very much mainstream. Actually that's the vaccine development for COVID as well, that there's a whole industry on cryo delivery and distribution. The commercial potential is large, obviously, because there's a large patient potential since the mechanism of action is independent of genetic cause. The pricing set by Luxturna is important because it kind of sets some precedence. Luxturna is priced by $850,000 in the U.S. NICE has approved the price at GBP 613,000, so kind of a similar level. And that sounds like a lot, but don't forget that that's a single injection, which is also what we are aiming for, one shot therapy. Let's go to Page 12 and have a look at the clinical program. So Phase I has been completed. We -- has a normal single ascending dose study where we establish safety in various quantities as well as we move from fresh cells to cryopreserved cells in that Phase I study. So that's taken us into a Phase II study with a validated cryopreserved cell. We treated them 10 subjects with established retinitis pigmentosa with a 1 million cell dose. Primary endpoint in all this studies are really safety, but we obviously -- you include visual acuity and other efficacy measures to be able to make a decision about going forward or not. In this study, we have 2 clinical sites in the U.S. One was Mass Eye and Ear and another one in Phoenix. And going forward, we will expand on that, and I'll come back to that in a second. Maybe before we do that, let's have a look at how these cells are delivered on Page 13. So the surgical technique is subretinal injection. We think it's very important to put the cells in the right place. Luxturna is using this delivery technique, so it is already approved. So that's good. It's kind of an off-the-shelf technique. It's not something that's unique to our product. The advantage is that you can place the cells where you want them in the retina or rather underneath the retina so that you can have integration of the cells into the right levels. The cells not only has a potential for connections creating new photoreceptors that are viable, but also sitting there, creating prolonged production of trophic factors that creates a healthier environment in the eye. So the results so far on Page 14. You can see in front of you, the -- before we look at the results, I mean the efficacy in ophthalmology clinical trials is measured by reading letters in a chart. It's called the ETDRS chart. In early phase studies, you measure just one eye, the most affected eye. And then later on in Phase III, both eyes are treated. That's required for FDA approval. The entire chart, if you can read every letter on this chart, you could read 100 letters. 20/20 vision is 85 letters. 20/200 vision is approximately 35 letters. So -- and 20/200 vision is the definition of -- legal definition of blindness for central vision. So there's a 50-letter difference from blindness to perfect vision, just to give you a little bit of a scale of this chart. So clearly every letter counts and if you have a 5- or 10-letter difference, that's very noticeable. The largest selling drug in ophthalmology is EYLEA. That is an anti-VEGF for wet AMD. EYLEA sales were $8 billion in 2019. They have 8 to 10 letter gains in ETDRS and charts in their clinical trials. And that's what we see. We also see 8 to 10 letter gains in the treated eye across the different time points. And just kind of, again, for perspective, obviously, that's a very -- it's a different drug and a different indication so no direct comparison, but it gives you a little bit of perspective what's needed. The -- yes, if you look at the chart here on the treated eye, 8 to 10 letters is kind of where it's hovering around for every time point. Let's have a deeper look at the 12-month data as this will be the Phase III endpoint. And on Page 15, here are the 7 patients that we so far have 12 months data on with a 1 million dose. You can see that there are treated eye gains for all the patients. Some of them are extraordinary. And really, the question in our mind when we look at this is, can we help the patients on the left here to gain even more vision? We have no dose-limiting toxicities, so we can put in a higher dose. There is space for it. And then the question is, can we get even higher? Having said that, a mean of 10 letters is fantastic already, but that doesn't mean that we don't want more. On Page 16 is then the answer to that question, we've decided to expand the study with a higher dose, a 2 million cell dose, to see if we can improve even higher, particularly on the patients kind of on the left on the previous page. So here on Page 16, you can see that we decided to go ahead and line 9 additional subjects. We have escalated dose from 1 million to 2 million cells in these patients. The first 2 patients have been treated already. So this is ongoing. We added a couple of other things here. One is the ability to perform something called microperimetry, which is another efficacy indicator and that's been added into the study. We also modified the surgical technique a bit. We're trying to avoid lifting of viable retina and place the cells more in the periphery of a viable retina. Easier said than done though. Sometimes the [ bloods ] go where they want to go. Again, the primary endpoint is still safety, but the secondary measures, you can see here, is all around different efficacy parameters. We have decided to add more sites, very much kind of a COVID plan so that in case we have centers closed due to restrictions from the pandemic, that we have all the geographies that we have centers. So Oxford is being opened, and we're adding one more center in the U.S. and another one in Continental Europe. On Page 17, we have the therapy landscape for retinitis pigmentosa. So this is RP, ongoing development programs. You can see ourselves at the top. So the 2 companies working in cell therapy, ourselves and jCyte. And all the other companies here are working on gene therapy with the limitations that you have there with relatively small patient pools. Spark's product, Luxturna, has been approved. Spark was acquired for $4.3 billion by Roche in 2019. And Nightstar, I mentioned, was also acquired in 2019 for $800 million. And then there are a couple of other players that you can see listed here. In terms of market caps, you can see there's room to grow for us. The GBP 26 million market cap listed here is a little bit out of date because that was a month ago. So we now double that around GBP 54 million today. But yes, tons of room for us to grow when you look at the other players there. So let's look at the next steps for the RP program on Page 18. So yes, there's a lot of news flow over the next year or so. First, we obviously are continuing to collect long-term data on our 1 million dose subjects. They -- the COVID restrictions are not severe for these patients, RP patients, because they're relatively healthy otherwise, most of them. But some of them have -- are missing appointments and appointments being delayed, et cetera. So -- but we expect to get all those appointments back on track shortly so that we can have the 12 months data on all the patients, and we follow all of them to at least 2 years post treatment. And then the second part on data is to recruit this high dose expansion study. As I said, there are 9 patients that we're targeting for that. We've treated the first one in September, treated the second one in December. So that's ongoing, and we expect to have all those patients treated by early Q2. The presentation of the data I mentioned earlier, so ASRS and American Academy of Ophthalmology are the 2 key conferences this year that we expect to present this data. We don't expect to present via press releases beforehand or -- our wish to present data in larger conferences and more meaningful updates rather than send out a press release every time there's another data point coming in. So the next step then for getting approval for marketing is to do a Phase III study. The FDA has clear guidelines on -- it's actually for gene therapy studies in ophthalmology. They've told us that we should use the same guidance for cell therapy. The advantage of this guidance is actually that although the studies will be randomized, it will not be placebo-controlled. The reason for that is that it's not possible to do a placebo injection subretinally. So the way that's handled is that you actually do 3 patient groups. You do a high dose, which is what your intended dose is. There is a low dose or subtherapeutic dose, they call it. And then the third group is observational cohort. So the patients will be randomized into 1 of these 3 groups. If you end up in observational cohort, you obviously know that you're not getting treated. You will have to do all the same measures, and you will then create the comparison arm. But there is no placebo effect in the terms of people trying harder, et cetera, because they know they didn't get the good stuff. So we will obviously have these discussions with the FDA late this year. With that, we'll move on to the exosome program shortly or briefly rather on Page 20. So exosomes are nano-sized vesicles that are excreted by all cells in the body, and they're part of how cells communicate with each other. And so it's basically a natural liposomal delivery system. It's possible to hijack this system, either to use it as a drug delivery system or even as a therapeutic in itself, or as a diagnostic tool. Our current focus is on the drug delivery bit, and we have collaborations ongoing on that. On Page 21, you can see some of the advantages of what we are working on. The first is that we've noticed a favorable distribution across the blood brain barrier. That's one of the biggest hurdles in drug therapy is how to get drugs into the brain efficiently. So we are exploring that now to see if our exosomes can answer that. We've shown ability to load micro RNAs and proteins, we've shown stable and high yields with a clinical-grade product. Obviously, our starting point is a GMP product, which is [ GP ] and CTX. We've been working on this some time and so we have established analytics, and we have seen a free scalable process already established. On Page 22, a little bit more on the collaborations we have ongoing. So the 3 partners we're working with, their names are undisclosed. We would wait on disclosing that until we actually have a licensing deal, which should follow from a positive proof of concept. It's all about -- it's focused on delivering our partners' payload, and they are siRNAs and mRNAs for the moment. And the way this is done is that a partner sends the payload to us. We load it into our exosomes. They pay us for that work so that we can cover our costs. We send them the new construct back to the partner, and they run animal studies in the chosen indication to see if we can knock down the target with an exosome-delivered gene therapy. Now if the animal data comes back positive, we would expect then that our partner would like to take it forward. We own this new contract 50-50, so they would then obviously need to license rights from us to go forward. So in summary, on Page 24, I wanted to share a little bit about what the potential value is in the areas that we're working currently. So if you -- on Page 24, you look at the left-hand side, our partner -- sorry, our competitor, jCyte. So I mentioned there were 2 cell therapy companies working in RP. jCyte is doing something different than what we're doing. What jCyte is doing is that they have a similar cell type, however, they put the cells into the vitreous rather than subretinally. When you put the cells into the vitreous, I mean, it's easier to do and you'll get some trophic effect, but what you will not get is any replacement or any new photoreceptors created. They have announced data, which is very modest. We're talking 3 to 5-letter gains, depending on if you look at net or gross gains. So that was, however, good enough for Santen, which is a large Japanese-based ophthalmology company, to sign licensing deals. So they licensed in -- Santen licensed in jCyte's product for ex-U.S. They received $62 million upfront, $12 million of that was a convertible note and the rest was cash. And I think that shows a pretty substantial interest in the field based on what we think is very modest data. And I would say that the data that we've seen, the 3 to 5 letters, is kind of what we expected to see. Some trophic support will give some effect, but you need to put the cells in the right place to get a much more profound and long-term effect, which is what we're doing. And we see it as a validation of our approach. On the right-hand side is the 2 exosome companies. The largest ones are Codiak in the U.S. and Evox here in the U.K. and in Oxford. Codiak signed 2 deals, and you can see the details here where we have significant deals, both of them and so has Evox. So it shows the interest in the field of exosomes. Codiak has gone public. Actually, they went public in October, and that seems to have gone very well. I think the market cap is about $600 million at the moment. So if you get things right, there is a significant opportunity to benefit, I think would be my conclusion from that. So on Page 25, and that's our last slide before I take questions. I'm sure you agree that there is a major opportunity for -- to create significant value over the next 12 months for our hRPC program. New data coming in, that's going to be presented at significant conferences. The jCyte data support our approach, showing that there is a potential to get much higher efficacy if you put the cells subretinally as we do. The potential of -- on the interest in ophthalmology is underlined by the deal jCyte has signed with Santen. And the exosome program is very much hitting a hot button in terms of research as a very hot field. And I think we have a very good approach there where we are not using a lot of resources as the trials are being financed by the partners. But it remains the upside of having a great benefit if the data is positive. So with that, I'm going to ask the operator to take over here for the Q&A session.

[Operator Instructions] First question comes from Christian Glennie from Stifel.

Let's kick off with the expansion phase of the study, if I may. You mentioned a couple of patients treated so far with that 2 million cell dose. Have you now cleared the DSMB reviews of those so you are now free to enroll sort of as you wish across the sites? Or is there some further steps to go on there?

There are some further steps. We had -- the way the study was set up is that we are supposed to have a DSMB after the first and last patients from each cohort. So we had a DSMB after the first patient was treated. So that means you wait 6 weeks, collect the data on that 1 patient and then set up a meeting with that group. They give approval to continue with 2 more patients. As we expected, we treated 1 of those 2 patients. So we need 1 more patient treated before we have the next DSMB. That hopefully will be the last DSMB of the expansion. So 1 more DSMB to go through, and then we should be able to do the next 6 patients relatively rapidly.

Okay. Great. And then in terms of a bit more in terms of what data to expect and how these patients compare. So is there a sense for what sort of baseline vision these patients have? In my understanding, as we talked about before, is that the previous dosing at the 1 million was roughly sort of initial -- in the early cohorts were slightly lower levels of vision with some quite very strong responders there. And then you step through to sort of higher levels at baseline, more modest response in absolute terms, but then the control eye or the untreated eye deteriorated more, and so the delta was retained in terms of the difference between the 2. What sort of level -- are you going back to the original sort of baseline that you saw the very strong responders in? Or are you sticking with those sort of higher levels of vision and trying to boost that level -- that response as you described, I think, with more modest responses on the left-hand side of that chart, as you said?

Yes. I think I mean, in our opinion, we cannot really make a conclusion if patients with very poor levels of vision at the starting point or moderately higher levels of vision at the starting point, and that's really a big -- makes a difference. The -- so yes, I don't think we have the same conclusion. We don't think that low level will mean they gain more. Now they have opportunity to gain more because obviously, they're starting with very few letters of vision. So I don't think we have enough data to say that 1 pool of patients is better or will give better data than the other, which is part of the reason of doing another 9 patients will give us a bigger data set before we go into Phase III to see if we want to define further the population that we have in the Phase III study. The changes for the expansion is this microperimetry requirement. So that will mean that patients will need to be able to focus on a specific point when they're being tested. And not all patients can do that, so it will exclude some patients that otherwise would be included in the study. But this is based on input actually from Professor MacLaren, who obviously is very knowledgeable in the subject after the Nightstar experience. So yes, I think the patient might be a little bit different because of that 1 requirement, but I'm not so sure that, that actually means that it will be either higher or lower on the visual acuity chart. So let's wait and see. My conclusion is probably not quite the same as yours in terms of starting levels.

Okay. Okay. Sounds good. And then, just a follow-up on that point. In terms of -- I think you mentioned you had looked at things like retinal sensitivity in the -- as a secondary, maybe in the previous 1 million dose group, but we've only seen the acuity data so far. But maybe you're talking about slightly different endpoints that you haven't previously measured. Is that the right way to think about it?

Yes, it is -- I mean the microperimetry, we haven't actually been able to measure that before. And that was the key input from Professor MacLaren. He said that, that's one of the key things that they did in their trial for -- because -- for Nightstar. Nightstar actually did not have much improvement at all in visual acuity in the clinical trial for RP, but they were able to show efficacy in microperimetry and that clearly was good enough for $800 million buyout by Biogen. So I think we'll tap into his experience very gladly on that.

Yes. Okay. Great. And then finally, on this data, you flagged the initial data coming at ASRS. You mentioned June, I think, but also at some point in the slide deck there was July. I'm not sure if you can clarify that. And then also, is the concept here really probably that sort of no news is probably good news in the sense that, yes, it's open label, but you want to wait for the full data set to disclose it in full and [indiscernible] is more meaningful. I'm presuming no news is good news in the sense that the people seeing the data are still seeing responses as they would expect as along the lines of what you've seen so far, I think.

Yes. No, in terms of -- we need to publish anything that's material quickly or announce quickly to the market. This study is open label, so not necessarily me, but Rick Beckman, our Chief Medical Officer, receives the data on an ongoing basis. So now that we have larger and larger patient numbers, that would mean that any single individual data point is probably immaterial. We had to kind of go out with a press release after the first 3 patients because that was 3 out of 3. We would have preferred to wait until we had all 10 patients treated before we went out with anything, because it's better to give a more holistic view, I think, rather than preceding the market. So it's a long answer to saying we don't expect anything to be material because the patient numbers now are larger, and that gives us the opportunity to collect the data and present it in one coherent way at the conference. Was that an answer to your question?

Yes. Yes, that's right. Only whether it was June or July, I know I can follow up offline, if you want.

I guess Google it. It's -- you're right, it's July, I think. July 24 to the 26.

Our next question comes from Edward Thomason from Nplus1 Singer.

Okay. So I've got a few. I hope you don't mind, but hopefully, they won't be -- it will be quite quick. But just on the theme Christian was talking about, when it comes to the expanded cohorts for the Phase II trials for the retinitis program, are you going to be taking any genetic analysis of the retinitis pigmentosa patients? I know, clearly, with the cell therapy, you're aiming to be a universal solution. But it would be interesting to know if you are investigating some of the genetic profiles of the patients that are in the study.

The answer is, yes, we are collecting the genetic of the patients. And no, we don't expect to be able to see anything from that. Again, because the fragmentation here, we probably will have 1 or 2 patients for each different gene mutation. That's not going to probably tell us much. but we're collecting it.

Okay. That's right. That's quite clear. And then again, another quick one. Just a quick update on the exosome project for the COVID-19 collaboration. What's the status of that?

Yes. So I think we're -- we actually have a meeting this week to decide what our strategy is on exosomes in delivering COVID vaccines. So I think the questions that we're asking ourselves internally is what is the future of vaccination for COVID-19 over the next few years. And I think based on those discussions internally with experts, then we will decide what our plan is. So #1 is, what will the need be in the future for effective delivery of COVID vaccines? And then secondly, will our exosomes be able to solve any problems that are present? And I don't think we know the answer to those -- to all the questions. At least, we don't know them publicly. But it's an internal discussion.

Okay. And then also just an update on in -- with Fosun in China on the expectations, not only for the stroke program and the clinical trial that's ongoing, but also for retinitis pigmentosa and whether the IND is likely to be far this year. Or is that still their intention?

Yes. On China, the -- I don't want to make any future predictions on kind of the specifics on the collaboration in China. But the focus of Fosun from the start has been the CTX program because the stroke indication is such a huge opportunity in China, mainly due to high levels of smoking. So -- and they're still very much committed to taking CTX forward. So that's ongoing. They also have, obviously, the rights to the hRPC program there. And we are in discussions with them about how their efforts can be helpful from a global point of view, not only for China, on that program. But yes, I don't have anything to comment in terms of specifics.

Okay. And then a question more for Michael is with the -- whilst you are obviously talking about license deals for RP, there is talk of a design for a single pivotal trial. And I'm just wanting to get a perspective on the costings for that. The -- it looks -- and probably the rough size as well as patients and the number of trials -- [indiscernible] that need to be included in that trial, if it was a single pivotal trial.

Yes. I mean, we don't have a protocol for that study yet, of course. But I think in very broad terms, in this sort of indication, you're probably looking at less than 100 patients for a pivotal study. And therefore, in cost terms, probably something in the order of maybe around sort of GBP 15, something like that. It's that order of magnitude. So we're not talking hundreds and hundreds of patients, and we're not talking the sort of cost that would be prohibitive for a company like us, because we could certainly do that within the scope of our ability to raise money to do so. So it's that order of magnitude. But again, I sort of hasten to add that we don't have a specific protocol yet for that study. So those estimates obviously come with the usual health warning.

Okay. And then sorry, last question and broadly to Michael is, we've given -- clearly, R&D expenditure with the expanded trial is going to be higher this year. But what about on the admin side? Clearly, there's been some quite significant cost savings. And do we expect those cost savings to continue or similar reductions for this year? Or are we now probably seen those cost savings coming through that have been completed and gone through?

Yes. I mean, for the half year numbers, you're probably looking at a relatively complete picture in terms of the steps that we took. I think you may see a slight further reduction because, of course, some of those actions took place during the course of that 6-month period we've just reported on. So the full periods' worth of costs aren't reflected necessarily in those numbers. But I wouldn't expect there to be a material further reduction in the second half of the year. It will be perhaps a relatively minor reduction. But the important thing is that we don't see our G&A cost base escalating in any way from here. I think we can get the job done based on a cost base that has been reduced. And certainly from a G&A perspective, we can keep relatively constant.

Our next question comes from Samir Devani from Rx Securities.

I've just got a couple actually. I'm just wondering, in terms of the orphan drug exclusivity, whether you've had any dialogue with the FDA as to what they deem as [ frameless ], i.e. if jCyte gets approval of their product, will that block the launch of your product? That's the first question. And then just one on the dosing. I note that jCyte's using up to 6 million cells in their studies. If you see an improvement at the 2 million, would you be minded to add a third dose expansion cohort?

Thank you for your questions. Very good questions. It gives me the opportunity to maybe expand a little bit on jCyte and the differences and the similarities between the 2 companies and the 2 approaches, so thank you for giving me that opportunity. First, on the orphan drug question that you had, there -- although jCyte has a similar cell type to us, it is different. They are -- without going into too much details on how it's different, but it is a different -- there are differences in the cell. The second thing is that the mechanism action is different between the 2 approaches, and there's a lot of discussion actually between from an industry level with the FDA around orphan that mechanism of action should be taken into account. Route of administration actually isn't a difference for orphan drugs. So -- but mechanism action is something that probably should be a difference. And it is clear that we have a different mechanism action between the 2 entities. So we don't expect any negatives from a jCyte approval. We do, if anything, maybe there will be a positive because, again, it shows that using cell therapy in ophthalmology is a good thing. So we're okay with that. We're not worried about the orphan drug point of view. The 6 million dose for jCyte, so intravitreal administration, there's obviously room for lots of drug there. It's a very large area to put yourselves into and they can kind of go anywhere in the vitreous. You probably need quite a high dose in the vitreous to get some trophic effects from that. And I think they've seen pretty clearly that a higher dose is better. The -- I haven't presented their data here to you. But to summarize it quickly, so they have a study in 80 patients or actually 79 patients that was presented out of the 84 that they treated. They have 3 doses -- sorry, 3 arms. One was a sham surgery because with intravitreal, you can actually do a sham injection. It's basically an empty cannula that you just press against the eyeball and the people think they got the injection. And then they have 2 doses, one with 3 million cells and the one is 6 million cells. And the change from baseline in the treated eye for those 3 groups was the sham had 2.6 letters improvement, 3 million had 1.3. So actually 3 million doses worse than placebo. And the treated 6 million was 5.95, so 6 letters. So they have got 6 letters out of the 6 million, which is 3.5 treatment-free letters better than the placebo. So pretty low numbers, pretty modest efficacy. They did -- despite having 84 patients, they did not hit any other endpoints, primary endpoint nor secondary endpoints. So basically, it seems to have a very modest effect. Exactly what we expected. We expected some trophic effect from putting the cells into the vitreous, but we did not expect anything profound because it's just too far away from the site of the action, which is the retina. So for us, it's very -- I think it's validating. Cells have some effect, but they need to be put in the right place. That will be our conclusion. The other important difference within ourselves and jCyte is the formulation. They have not been able to create a cryopreserved formulation, so they use fresh cells. And that means that in their clinical trials, patients have to go to where their manufacturing is. So the patients are treated in California, close to where they manufacture the cells. Now that's okay for a clinical trial, but it will be very difficult commercially. So I think hats off to them for having signed a very significant deal with Santen based on a data set that we think is modest. Sorry for the long answer.

Our next question comes from Max Herrmann from Stifel.