Good morning, everyone, and welcome to the PYC Therapeutics third quarter investor update. My name is Rohan Hockings, and I'll be your host for this morning. Before we begin today's call, I'd like to make you aware of two things. Firstly, that today's call is being recorded, and secondly, to make the following safe harbor statement, reminding you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in our filings with the Australian Securities Exchange. As such, actual results may differ materially from what we discuss on today's call. We disclaim any obligation or intention to update these statements in the future. So we're going to walk through three different parts of the presentation today. Firstly, we will have a look at the company's vision and where we plan to be as the next twelve months evolve.
And then, what we're going to do is enter into the presentation proper. We're going to have a brief introduction to the company, who we are and what we do, for investors who are new to the journey. We're going to have a look at some of the macro trends within the industry, briefly to touch on the continued strength that we're seeing within the RNA therapeutics domain. And then we're going to look more specifically at the progress of the company in each one of our programs at a very high level, and then we're going to focus specifically on the retinitis pigmentosa type 11 clinical trial and drug development program, because we have reached a very exciting time in that program, and we're going to see two readouts either side of Christmas that are going to have a very material impact on this company's future.
Before we do that, I thought it was worthwhile sharing with you my thoughts on where PYC is heading, and the reason that it's an appropriate time to do that is because three years ago, for those shareholders who've been with us long enough on the journey, we set out a vision to put three first-in-class drugs with disease-modifying potential into human studies, and in a few months' time, we will realize that ambition as our program for polycystic kidney disease enters clinical development, and so, having realized that window in the company's strategy, and implementation thereof, it's now appropriate for us to look forward, not three years this time, because there's so much going on that, the extent of the activities really need to be looked at in detail on much smaller time windows.
And so if we take a bar from where we are today, a cut vertically across our pipeline of programs, and we fast forward twelve months' time, where we hope to be is in a pivotal study in the lead indication. On the back of having demonstrated clear clinical proof of concept, a favorable risk-benefit profile in the lead indication. In addition to that, we will have taken the polycystic kidney disease program into human studies. This is a drug development program that addresses the most prevalent monogenic indication known to man.
We should have in hand initial safety data from the dose escalation study, and we should be very close to seeing proof of concept to define whether or not the extraordinary observation that's been seen in the animal models, that we can actually reverse this disease and not just stop its progression, and thereby have a very fundamental impact on the severe morbidity and accelerated mortality in this indication. Before we start thinking through how we transition into a registrational study in that domain. In our third drug development program, we'll be at a very similar window to where we are today in the RP eleven program. We should have a good handle on both human safety and the initial efficacy signal within autosomal dominant optic atrophy.
The particularly exciting thing about that program is having established proof of concept in a monogenic orphan indication. We know we have potential application of this drug development program in other blinding eye diseases that have an underlying bioenergetic deficit. The way that program works is by increasing the bioenergetics or the fitness of those cells. And we know that the two primary unmet needs in ophthalmology, being geographic atrophy and glaucoma, both have an underlying bioenergetic deficit. So there is excitement in much larger indications in the non-orphan realm. There is also excitement in other smaller indications, where similarly, we have an underlying bioenergetic deficit, like Leber hereditary optic neuropathy. So what we hope to see there is having established safety in the ADOA patient population.
As we move forward internally to look at the efficacy profile in detail in ADOA, we have investigators or clinicians who are interested in driving their own clinical studies in these other indications and progressing directly into a phase II study. In addition to that, there is a fourth program that many of you are aware of that is not yet formalized in our pipeline because we haven't nominated a clinical candidate at this stage of development. We are intending to do that by the end of this year, and so you will see the Phelan-McDermid syndrome program enter translational studies, and we will formalize its adoption into the pipeline at that point in time. It's a very significant undertaking, and a period of transformation will be required to deliver on the magnitude of the aspiration in that context.
Having given you a bit of color on where we're heading as an organization, we'll now step back, try and bring our newer shareholders on board for the journey with respect to who we are and what we do, and then have a look at some of the macro trends that are emerging in the RNA therapeutic space. Literally, on a daily basis, we're seeing developments that are relevant to our domain. The RNA community is going from strength to strength, and it's really emerging as the third major pillar in the pharmaceutical landscape, alongside small molecules and biologics. The stars have very much aligned externally, and we're now in a position internally, as we move to the third part of today's presentation, where we really control our own destiny.
Having taken first-in-class molecules into clinical development, having accelerated ourselves ahead of the pack through the decisions that we made four, five, six years ago from a strategy standpoint. Through a good implementation, we really have an opportunity to show the true value of what we have across each one of the programs, so as I mentioned before, there's a lot happening in RP type 11 , and it is quite a complex field, so we're going to walk you through what's happening at a high level and then try and explain in some further detail what to look out for as we deliver the repeat dose data in Q4 across both the Part B extension study in the single ascending dose program, and also in the multiple dose program.
What are the issues that we are grappling with as a company, as we look to transition into that registrational study in the middle of next year? We've had some exciting news this morning in the optic atrophy program, with the FDA designating this a rare pediatric disease program. We will have human safety data imminently. We have announced in the recent past, earlier this month, that we have received regulatory approval to move into clinical development in Australia in that program. So we will see human safety data start to emerge from the early dose cohorts in the single ascending dose study there. In polycystic kidney disease, we will finalize the preclinical development pack and submit an application to the regulator to move into first-in-human studies. In the Phelan-McDermid syndrome program, as I mentioned, we will nominate a clinical candidate.
Stepping back now, as an introduction to PYC Therapeutics and who we are. What we do is we create precision therapies for patients who have severe unmet needs. They have a disease that drives a high level of morbidity or an accelerated mortality, and they don't have any treatment options available to them today. And we do it in a very particular domain. We do it in the space of diseases that are caused by mutations in a single gene. And the reason that we do that, and focus on this small subset of the overarching industry, is because when you know precisely what is going wrong in a target cell, you know precisely what you need to do to fix it. And we see a very good symmetry between the precision medicine modality and these single gene disorders.
What that translates to, if you look at the company's strategy, is a much higher probability of success in clinical development. So for those of you who've been on the journey for a while, you will have heard me speak about this ad nauseam, but it's because it's a very important point. The industry as a whole has around about a 10% success rate in terms of a marketing authorization or launch of a new product when they start a first-in-human study, a phase I clinical trial. It's a very low rate of success as you progress through three phases of clinical evaluation. Drugs targeting monogenic diseases are five times more likely to succeed. It is the single most important decision that you make as a drug developer in relation to the propensity to have patient impact.
Building on that pillar and having made that decision, we try and change the shape of the risk curve even further. Because we are using human precision medicines, we are very interested in evaluating their efficacy in the context of the human genetic background as early as possible, and there is quite an extraordinary new tool available to the industry in recent years, where we can bring phase II risk, human efficacy risk, into the preclinical setting, and we can do that by growing ourselves a mini human organ with the target disease outside of a human. We can take a tissue sample from a patient who has the disease that encodes for the single genetic mutation that we're interested in.
We can turn that cell backwards into a stem cell, and we can turn that stem cell forwards into every cell type that exists in the target organ that we're interested in. This is a very powerful tool, specifically in the domain of human precision medicines in monogenic indications. That is how we change the propensity for success. On the right-hand side, it's about competitive differentiation. So our modality, oligonucleotides or RNA therapies, are very good at gently turning gene expression up. So as a company, we made the strategic decision to go after indications where we don't have enough of a particular target gene being expressed within a certain cell type in the body. You have two copies of every gene in each of you.
If an individual acquires a mutation that loses the function of one copy of that gene, you will end up with half as much protein in the target cell as you need from that specific gene. Our objective is to re-rescue the protein expression levels back to what we call wild type or 100%, baseline levels, so that we rescue the underlying cause of the specific disease that we're going after. This is a very nice place for RNA drugs to play. It's where they are uniquely differentiated, but it leaves us with a fundamental challenge. If you map the issues associated with RNA drugs, 90% of the problems are driven by drug delivery, getting enough of the target cell, sorry, of the drug to the target cell.
Rather than suffering from the same burden as the broader RNA therapeutics field, this is the domain on which we choose to differentiate. We have a facilitated delivery technology, a peptide-based, non-viral delivery technology that acts as a chaperone. It carries the RNA therapeutic to the target cell and across the cell membrane, where the RNA therapeutic can step in and address that single problem that is driving that disease process. Those four pillars form our strategy, and it's upon those four pillars that we have built this pipeline of first-in-class drugs with best-in-class potential, addressing the underlying cause of these indications. We call them rare diseases, but collectively, they address 0.1% of the population, those four indications that you see up on the screen, driven largely by polycystic kidney disease, as I mentioned before, being a very high prevalence indication.
You can see that we have a lot going on in terms of where the assets are at and also where we plan to take them. The nice thing from the company's standpoint is we've really reached the window where the rubber meets the road. We're in the domain now of having human data in hand and looking to unequivocally address this question of the risk-benefit profile of each one of these drug candidates. And you'll see from the deep dive that we go into, that we've got multiple readouts. In fact, each of these three programs is going to read out in the next 12-18 months and provide critical human data in the domain that is the currency of our industry. So that's PYC in a nutshell.
I wanted to just thank all of the team within PYC Therapeutics who have given me the opportunity to present the progress that the company has made. We have gained a critical momentum at this juncture, and it is an honor for me to present the work that you have done in that context. Stepping back now to look at what's going on within the broader industry and specifically within the domain within which we play, the RNA therapeutics context, we know that we have chosen a very strong link between disease causation and the RNA therapeutic modality. The strategy is right for the reasons that we have just spoken about. What it comes down to now for PYC is high-quality implementation.
We have a lot of balls that we're juggling, and if we manage to deliver each one of those through this critical window, where we're generating those human safety and human efficacy readouts, we're going to situate ourselves in a very good spot. You can see here there is a broader industry appreciation of the appeal of these genetic medicines in the context of single-gene diseases. This is very well understood within the industry now, and there's something else that's happening in the macro that's very important to us, and therefore, to you. The regulator, particularly in the U.S., but more generally, globally as well, has understood the unique value proposition of these genetic therapies in the context of rare disease.
They appreciate all of the dimensions that we have just spoken about, and they are seeking new ways to accelerate the path of these drugs to patient populations who don't have any treatment options available to them. They're getting a lot more flexible in terms of the thinking around what registrational study design could be in relation to supporting drug approvals and specifically accelerated approvals. The concept of running a post-marketing confirmation study in relation to proving out the longer-term benefits of the drug is something that we are very interested in. And as a single sentence, this from a U.S. life sciences investment bank last week, really captures the extent to which RNA therapeutics are expected to feature in the evolution of the clinical landscape in coming years. The time has really come.
Okay, we're now going to look very closely at what's going on within the RP11 program. I'm very happy through the Q&A to give you more color on what's happening in the other programs as well. So we are deferring those conversations for another date. In order to meaningfully engage with the subject matter, we need to spend a bit more time on each one, so we've chosen RP11 for today for the reason that I spoke about before. We are right on the cusp here of delivering critical human efficacy data. I'm very happy, as I said, through Q&A, we can address any questions that you have in relation to the other programs. Where have we got to date?
Winding everybody back to the transition to first-in-human studies at the start of last year, we have undertaken what we call a single ascending dose study. We have administered the drug at a very low level to ensure safety tolerability. It's the first time the modality has been used in a human eye, and we have seen no issues from a safety standpoint, so we have escalated to a second cohort, and then a third, and then a fourth. In doing so, we have crossed the threshold at which we expect, based on the modeling from the preclinical setting, that drug to have reached a therapeutic concentration within the human retina. We have completed dosing in this phase I single ascending dose study.
We have then converted these two patient cohorts into an open-label Part B extension, where those patients are now going to receive multiple doses of the drug, and concurrently, we are running a multiple ascending dose study, and we have completed dosing, initial dosing in this cohort one. Those patients will be coming back for their second dose in September. Once that second dose has established that there are no safety tolerability issues, we will then move to add a second cohort in the multiple dose study, and collectively, these two multiple dose studies will let us look at N of 11 or N of 12 patients who have had sustained exposure to the drug at an anticipated therapeutic concentration, so this is very important for us.
I just want to wind everybody back to the objectives of each one of these studies, because I think that has been lost a little bit in the wash. When we went into the phase I single ascending dose study, we're really primarily interested here in safety tolerability. We need to establish that the modality is safe and well tolerated in humans. There's a secondary objective to see whether it's possible in the context of a slowly progressive and irreversible disease, the opportunity to see an efficacy signal, because in theory, once we have lost cells in the retina, they do not regenerate. So if we stop a very slowly progressive process, it could take a long time to see whether or not the drug is having an impact, because the untreated fellow cohort may not see meaningful disease progression for a substantial window of time.
So what we were very much hoping to see was what has been observed in some other, clinical trials in different forms of inherited retinal dystrophies, that we may actually be lucky enough to see some improvement in some patients. But remembering that in the context of a single dose of drug that needs to be administered on a repeated basis, the extent of the insight that we could gain on that dimension was going to be limited. It's the multiple dose study that is really going to let us assess the robustness of that signal, and also to help us start to understand how do we best quantify it. And that's critically important, because if we look to what sits off the right-hand side of this page, all of this is gearing up towards a registrational study that is kicking off next year.
The more we understand from how patients are manifesting a potential benefit from the treatment, the better we are able to design the registrational study with the input of the regulator around what they would like to see in order to support a marketing authorization for that drug. So they're the different purposes of each one of those studies. What we're going to do now, I'll introduce you to some of the efficacy endpoints in the SAD and the MAD studies. We're going to look back at the results that we've observed to date, and then we're gonna try and provide some context and color for you, both in relation to other entities that have seen results on these dimensions in other forms of retinitis pigmentosa.
And we're also going to try and give you the groundwork that you need to interpret and understand the data that is gonna be generated in Q4 of this year and Q1 next year. As a brief recap, retinitis pigmentosa is a blinding eye disease that starts with the loss of night vision, progressively sees patients lose their peripheral vision through their late childhood and early adulthood years, and then and then slowly lose their central vision in the fourth and fifth decades of life until they're legally blind. So it's a long duration, very slowly progressive, but irreversible blinding eye disease. It affects around one in every hundred thousand people, and VP-001, PYC's drug candidate for RP11, is the first drug ever to have made it into human studies in this indication.
So we've spoken a lot about microperimetry, and I thought it was worthwhile spending a little bit of time helping you to understand what microperimetry is. My colleague, George, has very helpfully given you a free visual acuity test by using size eight font on the left-hand side of the image. We'll ignore that for now and have a look at the grid that you're seeing here on the right-hand side of the image and also the color coding on this side. What you're seeing here is the patient's macula in the retina. So there's a very specific anatomical area of the retina that we're interested in.
And the reason that we're interested in it is because it's the part of the retina that has got the densest population of photoreceptors, or the cells in the eye, that turn the light photon that hits the back of the eye into the visual signal that then gets sent to the brain, so this part of the retina has got a critical function in central vision, in color vision, and in your fine visual acuity, so it's absolutely critical from a patient standpoint, and what microperimetry is able to do is take a fixed anatomical benchmark or location from within the eye and then superimpose a grid over the macula, so we've encapsulated this area that is critical to your visual function.
And what we then do is we flash lights onto specific subsections, where you see each one of these individual grid locations onto the retina, and the patient presses a button when they're able to detect that light signal. And what we'll do is we'll give them a light signal at varying intensities, from very bright to very soft. And what we're aiming to quantify is the lowest intensity of the light that that patient can see. So we're really testing the sensitivity of the retina to light in this context. And then what we do is we score that numerically. So in a completely normal eye, an unaffected eye with 100% visual acuity, visual function, you'll see a score of 36 for each one of these individual grid points. And you can see the color coding here falling down all the way to black.
You're seeing that in this patient's side. This patient has RP11 and is enrolled in the current clinical trial. You can see a number of what we call scotomas here, or points within the grid that are not able to detect light at all. And the other thing that you're seeing is a bunch of other areas of the grid that are not performing normally, but have not yet completely lost visual function. And the reason that we're particularly interested in microperimetry is because it's a very sensitive way of detecting early changes in visual function. It's where the RP field are consolidating from an endpoint standpoint. So how do we monitor it over time? So we're looking at a different patient here at baseline, and you can see a very similar thing.
You can see this central region where we have scotomas, black spots that are not functioning at all, and then you can see a lot of mid-range scores around the remainder of the macula, these orange scores, and if you think back up here to the grid reference, they're scores of around fifteen or sixteen that this patient is seeing, and what we've observed, and this was a very exciting finding because it was the first patient in which we saw it, this was the subject of a presentation at a large ophthalmology conference in the U.S. earlier in the year, the evolution of that patient's performance on this dimension over time, and the first thing that strikes you is the scotomatous patch.
Those four, potentially five, if we include this very low performance purple grid loci here, shrinks down to two at week four and then later one at week 16. So that's very encouraging because that's suggesting to us that we're recovering function in areas of the retina that previously were not able to detect a light signal. That's great. The other dimension that is very encouraging is you can see this emergence of yellow dots, more of them. And if you look back to this page, you can see that yellow is a higher score than the orange window. So these loci are also improving in their ability to detect light at lower luminance levels following treatment with the drug. So this is a very encouraging outcome here. There are a couple of different dimensions that help you interpret these results that we are working with.
The first of them is what we call whole grid retinal sensitivity. So if you take all of the scores for all of the grid points in that patient and add them together, you get whole grid sensitivity. If you look at what we call the functional transition points, this is the transition between functional retina on the outside of the scotomas and the scotomas themselves, where we're not seeing any response to the light stimulus. These areas are also of particular interest to us because they're where the disease progresses fastest. So this is generally a slowly progressive disease, where patients are losing about point four of a decibel a year on mean whole grid sensitivity. But in the functional transition points, they're progressing at five times that rate.
So if you wanna see an early signal of whether your drug is working, this is the window in where to look at it. So that's why we're interested in these functional transition points, and then we're obviously interested in scotomas, because any domain in which we can recover function that's previously been lost, especially within the macula and especially within the central region, is likely to have an impact on that patient's visual function that changes their life. And so these are three different ways of cutting the same data that we are going to be looking at in more detail, and I think it is important for you to understand why we move between the different endpoints within microperimetry. And we'll talk a little bit more about that in a moment. The other dimension to this is coming from the back end of the process.
Which of these measures is the regulator comfortable with in order to support an approval for the drug? And it's the integration of what we're seeing with what the regulator is comfortable with that is the challenge facing the company as we move through to that registrational study. Our co-company secretary nearly fell off his chair when I said I was gonna present this page, but I promised him that you would be able to follow me with it, so it's over to you guys to deliver on that promise. There are two ways that the regulator will accept us, demonstrating efficacy that is meaningful for the patient in a bid to support a marketing authorization for the drug. The first one is to change the slope or the gradient of disease progression across the whole grid sensitivity.
So if we can see a delta between the treated and the untreated patients in the context of that point four loss per annum, setting the baseline in terms of the decibels over the whole grid, that is an acceptable endpoint. The challenge with it is it's a thirty-six-month trial at this point. It's a longer duration trial than what we would otherwise like to do. The regulator has shown some flexibility here, and they have suggested that if a sponsor can specify five or more points on that grid that move by seven decibels or more, that is also an acceptable endpoint, and that creates optionality for us to shorten the duration of the clinical trial if we're capable of doing that, so it's very attractive.
But the challenge that you see here is, it's hard to know which one of these loci are going to light up in yellow. They are the ones that are moving by the seven decibels or more. So we've got to look at the data set across multiple patients with sustained exposure of the drug in the retina and understand whether we want to make a commitment to the pre-specification pathway and a shorter clinical trial or adopt a mean whole grid sensitivity and look at the change in slope of the gradient. There is a third other option at play, where we can sit with the regulator and work out some combination of this endpoint and others, or some other stratification, like looking at the functional transition point.
So it's the whole situation is in flux, and it's not fixed or resolved yet how we are going to address that problem until we have seen the data from the multiple dose study and had the conversation with the regulator. Hopefully, that made sense to you all. We're happy to address any questions that you may have afterwards. Now, what have we seen, and how does that compare with what others have seen in the context of gene therapies for retinitis pigmentosa? Firstly, a word of caution. It is always difficult to compare data across clinical trials. It is particularly difficult to do that in the context of two different genetic mutations driving the disease processes here. So these are two different diseases, but they both fit within the umbrella term of retinitis pigmentosa, so they're very proximate.
They have the same phenotype or manifestation of the disease in the patient, but they're caused by mutations in different underlying genes. The other thing to call out is these two benchmarks that we're looking at here are nominally one-and-done treatments. They are what we call an AAV gene therapy or a DNA therapy. So within genetic medicines, we have the DNA group, and we have the RNA group. The RNA group require repeat dosing and have a route of administration advantage that we'll go into shortly over the DNA therapies. The DNA therapies are nominally one and done. They use a viral vector to introduce a new copy of the missing gene. You cannot have repeat exposure to that viral vector.
What we see here, firstly, to orientate you, the red line that you're seeing is the decline in sensitivity over the whole grid in a retinitis pigmentosa patient over time. So this is the minus point four decibels per annum that we see. If we follow that out for thirty-six months, we see three times point four or one point two decibels of loss over that thirty-six-month window. So this is the benchmark gradient against which the FDA are looking to see the delta, the change in slope. And if you have a look at now what you're seeing in this turquoise line, is the mean sensitivity of the retina in patients who've received VP-001. This is the treated eye that we're looking at here. And so you can see here a change in the slope of the gradient, and it's very encouraging.
but we know that in some of these patients, the extent of VP-001 in the retina will be starting to taper, 'cause we're following this out to three and four months, and we're anticipating a three or four-month dosing interval. We may not, in the 30-microgram dose cohort in particular, have pushed high enough up into the therapeutic range in that single-dose study. so it's very super encouraging to have seen a clean safety tolerability profile. It's very encouraging to have seen visual functional improvement in these patients.
We now need more of the same data. To the extent that we can compare across outcomes, the reason that these benchmarks are relevant for you is that this MeiraGTx asset was acquired by Johnson & Johnson, and I have referred you previously to a transaction in December 2023, where J&J picked up the 20% of MeiraGTx, and this particular asset that they did not own, or I think it was $435 million, with about a third of that paid up front in a phase I/II study at the end of the phase I/II. Beacon Therapeutics is another commercially successful enterprise that has recently raised $250 million on the back of the outcomes that they have seen.
So they provide helpful context for you when interpreting the data, subject to the caveat that I mentioned at the start of this discussion. So what's similar and what's different across these different forms of RP? Well, firstly, they are both retinitis pigmentosa. The difference here is that whereas RP11 is caused by a mutation in PRPF31, X-linked RP is caused by mutations in the RPGR gene, so it's a different underlying causative gene. The big challenge for the AAV gene therapies is they have an unattractive route of administration. A needle needs to go all the way through the eye, and they need to be placed underneath the retina. So they are tearing the retina off the posterior globe in order to place the drug underneath the retina. They can only reach about 20% of the retina as a consequence of that.
So it's quite a traumatic route of administration. It comes with risks of procedure-related and also treatment-related serious adverse events. Very fortunately for PYC, and this is a critical feature of the data to date, we have seen no treatment emergent serious adverse events in any patient. So it's very encouraging from a safety and tolerability standpoint. We also have the ability to be repeat dosed, and here, because we are administering the drug into the center of the eye, the drug is going to distribute to the entirety of the retina. So we are also on the lookout, in addition to the endpoints that the AAV gene therapy companies are looking at, are there other endpoints that might be relevant to us that are not relevant to them because we are treating the whole retina.
So there's dimensions that we need to consider that those guys are not looking at. Are there other endpoints that we might start to introduce into the conversation? The answer is yes. Microperimetry is a lead indicator of changes in what we call low luminance visual acuity, or the ability to read the Snellen chart, the box with the letters on it, under low light settings. And low luminance visual acuity correlates very well with patients' functional impact of the retinitis pigmentosa in their lives and is, in turn, a lead indicator of visual acuity under normal light settings, which is a very slow indicator to move, particularly in these conditions, which is why we're not using the visual acuity itself as the endpoint in the study.
Given there is that correlation between microperimetry improvements and low luminance visual acuity, what we are expecting to see is that LLVA starts to move in these patients as we give them repeat dosing of the drug. And what that's going to do is that should give us, in the event we're fortunate enough to see it, flexibility with respect to the primary endpoint in the registrational study. So hopefully you can appreciate there's an enormous amount going on. As a company, we need to look at the data that is coming in Q4 and Q1 very, very carefully, and we need to glean the registrational study design from the data that we're looking at here. The early results are particularly encouraging. We're heading in the right direction.
I think also to put it in context for you in terms of the response rate, if we look at companies like MeiraGTx, I think their response rate was around 22% at 6 months, rising to about 50% at 12 months. Okay, so to see the percentage, this is very early for PYC. It's a small patient population, but if we're seeing exactly what we're seeing to date in more patients and spread out in the context of repeat dosing, we will go into that registrational study in a very good place indeed. With that, we stop. See whether my promise to the company secretary held true, whether you followed, whether you have any questions or would like clarity around what's happening there or in any other part of the company's activities.
We'll open it up to the room firstly, and then, Andrew, if you can facilitate the online questions, that would be very helpful.
Accepting that the dose is small to date, are you seeing any hint of not only preventing further degradation in sight, but any sense of reversal?
Yes. Yes, we are, and yes, we are seeing it. So if you look at this horizontal line, this is data that is benchmarked to the patient's performance at baseline. So firstly, you saw it in the images that we saw here, right? You're seeing points within the retina that previously were not able to respond to light. They are now able to detect a light signal. That's encouraging. You're seeing points within the retina that could respond to light at lower luminance intensities, so they are enhancing their visual function as well. If you look at the data now across all patients, this is the baseline level indexed back to all of the patients in the study. How were they all performing when they first came in for the screening assessment?
And so this lift in the gradient, if we were seeing just stopping a progression, what you would expect to see is the X-axis.... the treated group just sticking and tracking at the zero line. You're not seeing that, you're seeing an improvement. That's a bit bizarre in a progressive disease where the retinal cells are gone once they're lost. The theory here is that you have some cells in the retina that are so sick that they are not helping process the visual signal, but they're not yet dead. And if you can reach those cells and rescue them, you can actually see an improvement initially. Initially, there will be a ceiling effect. We do expect this to stop at a certain point and for this to flatline.
So we'll see a visual functional improvement, which is very helpful in terms of the registrational clinical study, and then a flatlining as the untreated eye or the control group, in this instance, continue to decline in terms of their visual function. If we see that, we'll be very happy. It's worthwhile, I think, shareholders, there were a number of questions that came in around why do we sometimes see the contralateral, the untreated eye, improving in its sensitivity on microperimetry as well? If you look at the Beacon and MeiraGTx data in more detail, you'll see that happening in their studies as well. So you'll see an improvement in the contralateral eye that is not as significant as in the treated eye, but around the three- to four-month mark, it starts to taper and go back below the zero line at that point in time.
So that's unusual, surprising in some senses, but it's not unprecedented. Any other questions in the room? Don't think so. Andrew, do you want to... Do we have any questions from online that you want to ask?
Yes. Appears the cohort three and four rolled into the extension study at the existing dosing levels. How are we dealing with cohort one and two participants for the extension study?
Yeah. It's a good point. So anyone from cohort one and two who meet the eligibility criteria for the Part B extension study will be rolled in at the 30 microgram dose level. So only the patients who received 75 micrograms in cohort four of the SAD will be eligible to convert to 75 micrograms in the MAD. Oh, sorry, in the Part B extension of the SAD, not the MAD.
In terms of the registrational study, do we have a view on participant numbers, dosing, et cetera?
Yes, I think top-down, we do. We, we're not going to know until we've seen the definitive data from the multiple dose patients. We obviously then need to engage the regulator in relation to what the endpoints are that we're going to use. We'll then need to engage biostatisticians to inform the powering of the study. But top-down, we're looking, I think, somewhere in the order of 50 to 70 patients. And in terms of the dosing, that will depend on what we see in the back of the multiple ascending dose study. If we continue to see what we're seeing in the single ascending dose study patients, we're going to be very happy indeed with converting the 30 and the 75 microgram dose cohorts.
But remember, it's open to us to continue to escalate the dosing, on the back of the safety tolerability profile that we've seen.
Does the quality of the data we've seen out of VP-001 program change our views at all on partnering, or going alone on the asset?
I certainly think it changes the views on terms of the partnering, and will continue to do so through the multiple dose studies. In terms of whether it changes our appetite for doing it, it's going to create optionality for the company in the very near future, on the back of a continued strengthening of the dataset through the multiple dose patients, and that optionality will be very helpful. We'll have the choice then of considering a licensing transaction in lieu of going back to the capital markets. Which one is more attractive will depend on valuation of the company at the time, and the terms and the nature of the partner who we are engaging with around the asset.
Another question around the RP11 trial, around how the regulator might feel about our tighter patient selection in the current trial, how that would be utilized in the registrational trial, and would that have any impact on the label regarding approval?
Yeah, I think a good question. So the issue here from the sponsor or company standpoint is that we are interested in the patient population who have the ability to show us our signal sooner rather than later. We would like to see the impact in patients, and therefore, we are trying to recruit patients who have the scope to show us that impact early. In the context of a monogenic disease, where the drug is affecting the underlying cause of the disorder, that's very unlikely to have any implications for the label. It's not that the drug is not going to work in patients who are at a later stage, it's that they will be too slow to show us our signal, given it's a very slowly progressive loss of the central vision that ultimately leads to legal blindness.
It's the peripheral vision and the night vision, it's the earliest stage patients who are moving faster on that particular dimension. That's why we are biasing towards them.
Another one on the trial. If we're dosing 50-70 people through the trial, does that mean significant foregone revenue due to those patients not being eligible for the drug?
No, I don't think so. It's a relatively small percentage of the total patient population with RP type 11, and we would certainly be interested in those. I'm sure those patients will want to continue on the drug after the launch of the marketing authorization.
In terms of, there seems to be a prospect of decreasing the time for the registrational study, what is the best we could hope for, or is there a range around that, the length of that?
Difficult to answer at this point. We really need to see the multiple dose data before we can give you any commitment there. The range that you could be looking at is anywhere between the 12 and 36-month window that we spoke about, depending on which endpoint we choose. That's it? Oh, yeah, Brian.
Do you have an update on the Google AI project you announced earlier this year?
nothing material to report at this point in relation to that project. So for those who are new here, we, just before the end of last year, maybe just in January, right over the New Year window, we entered into a collaboration with Google Cloud, looking to see whether or not we could, engender cell type-specific uptake. Google have done a very nice body of work using computing power to model the three-dimensional structure of proteins. Proteins sit on the surface of cells as receptors. If you can engage with a particular target protein, you've got the scope of exploiting the presence of that protein on a particular cell type, and not on others, to concentrate your drug within that target cell type.
And so what we're looking to do here is use that three-dimensional model and the new power of computing to see whether we can find binders to that protein. We've got a body of work to do before we can talk to you about results or the impact of that work. It's too early in the scope of what we're doing to be able to say anything.
One on the PYC-001 program, do we continue to investigate additional indications for phase II trials with that drug candidate?
Yeah. Yes, we do, is the short answer to that question. So, the idea here, again, for everyone, is that we are progressing PYC-001 in the context of patients who have a condition called autosomal dominant optic atrophy, and these patients have a mutation in the OPA1 gene that causes them to not have enough of a mitochondrial protein, so the drug in that setting addresses the specific underlying cause of that disease. There are other blinding eye diseases that have got a bioenergetic deficit or a deficit of the mitochondrial function, and so the idea here, question is: Is PYC-001 going to have application in those other diseases? There is already a pre-existing body of literature suggesting that it might.
In particular, in glaucoma, there are mouse models of the disease wherein if we increase the expression of OPA1, we protect the retinal ganglion cells from apoptosis or programmed cell death. And so the idea then is whether or not we want to go in and explore the application of PYC-001 in those indications. What we are trying to do here is to look at the preclinical assessments that we could do that would push our conviction even further. This is going to be a trade-off, right? We're giving away the single gene disorder, probability of success, to go after the larger patient population, leveraging the fact that we've already established safety in humans, going straight into a phase II study.
What we need to know is, are there any other preclinical tests that could give us further conviction in addition to the literature and the work that others have already done? In particular, what we'll be looking for here is patient-derived models. Again, so tissue samples from patients with glaucoma, with geographic atrophy, turning those into retinal ganglion cells or retinal pigment epithelial cells in the two different disease indications, and seeing whether we can simulate the disease process, and whether PYC-001 has an impact in rescuing that disease. And if it does, that will then support the expansion of those indications. What I can say at this point is there is a lot of interest on the part of the clinicians to lead investigator-led trials in those other indications.
Are the endpoints locked in at the start of their pivotal trial, or are they able to be updated midway? And how likely is the FDA to agree on a blended endpoint?
Well, how likely the FDA is to agree on a particular endpoint is up to the FDA, so we'll engage them in conversation around that. But where I think we get a lot of comfort is in relation to the guidance they've already given in relation to the endpoints that we're interested in. So we know, the extent of the improvement on LLVA that they'll be interested in. We know what they're looking for on microperimetry. That comes back to the two alternative options that we've already framed. Whether we can have another, a further conversation with them using the Fast Track designation that we have for RP type 11 or VP-001, that remains to be seen.
What we want to do before we have that conversation with the FDA is have a very good look at the multiple dose data and understand what we think is a reasonable request to the FDA in relation to that registrational study design. You can change endpoints through the course of the study, but we would certainly prefer not to. So we would like to agree on what is going to be the registrational design for that patient population before we initiate that pivotal study. So you can see we've got a lot of work to do between now and the middle of next year when that study kicks off.
And do you envision a case where the MAD or SAD participants would be included in the registrational study?
I think it's unlikely. I think we'll be using treatment-naive patients in the registrational study, but we'll be looking to provide continued access to the drug for patients who have volunteered to participate in the SAD and the MAD, so that they can remain on the drug in parallel to the registrational study.
Do we expect to treat these patients for the remainder of their life, or is the treatments a specified number of doses?
No, because RNA is turned over, and this is a disease-modifying drug that is acting on the RNA, these patients will need to be on the drug for the remainder of their lives. The attractive thing here is if you think about other drugs where patients need to remain on them for the remainder of their lives, in particular in the ocular space, like Eylea and Lucentis, the real problem that patients have is they don't like the dosing frequency. Two to four weekly is too frequent for them. So that's the nice thing about the RNA therapies, is they've got a much longer half-life within the retina, so they stick around for a longer period. This would typically involve a patient coming in once every quarter to see their ophthalmologist and have the drug administered. It's a very simple, straightforward, several-minute outpatient procedure.
We'll give a moment for any other questions online. Any other questions within the room? No. Look, hopefully, that's given you some color on, firstly, where the data that we've generated to date stands, and secondly, what to look for as we move through to this critical window in the RP type 11 program. We're going to find out an awful lot in the very near future in relation to the prospect for patient impact of that drug. It's really been a five, six, seven-year journey to get to this point, so there's a huge amount of excitement within the RP11 program itself. It obviously has massive implications, not just for the RP11 patient community, but also for PYC's pipeline more generally.
And if you think about it, that is going to signal the opening of this eighteen-month window that we've been speaking about in relation to delivering human safety and efficacy data in first-in-class drug programs for these areas of major unmet patient needs over the remaining over the next eighteen months. So it's an incredibly exciting window for the company. There's a huge amount going on internally. It's a timeframe within which we just need good, solid execution, and hopefully, as we went through that evolution of the vision statement, you can see even within a window of twelve months, there is such a fundamental change coming to this company. In the event that we can successfully deliver what we have set out over the next twelve months, it's gonna be a very exciting time for patients, for shareholders alike.