We're on time, so we'll make a start. Good morning, everybody, and thank you for joining the PYC Therapeutics First Quarter Investor Webinar for 2025. Before we begin, I'd like to start with a big thank you to the team at PYC who are driving a very substantial body of work in the background that is enabling us to realize the outcomes that we're going to speak to you about today as we frame the vision for the organization, the objectives for 2025, and outline the operational roadmap to deliver those outcomes. Before we begin today's call, I have a couple of housekeeping matters. The first one is to let you know that this call is being recorded, and the second one is to read 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, and the company disclaims any obligation or intention to update these statements in the future. With that, I want to walk through the objectives for today. The first one is to introduce the company for those who are new to the story, and the second one is to frame effectively a from- to where are we today in the course of 2025, and where do we hope to be at the end of this year in Q4 2025, and how does that orientate itself within the company's 48-month roadmap with which you are already familiar in relation to the transition to a commercial stage biotechnology company.
Once we've set out the objectives for the year, we're going to go into more detail in each of the programs with a focus on the three clinical stage assets to outline exactly what we're expecting with respect to the path to realization of those objectives. Finally, I'm going to touch on how delivery of the data that we are looking to generate through the course of 2025, specifically in the retinitis pigmentosa type 11 program, is going to create commercial opportunities that will drive optionality for the company in terms of how it builds and extracts value for investors as we progress deeper into that journey. I'll talk for around half an hour, and then we'll open up for a Q&A.
I apologize that we couldn't find a booking window within the auditorium, so today is purely virtual, but if you enter your questions into the chat function on the Zoom, we will endeavor to answer those at the end of the call. Firstly, in terms of an introduction to PYC Therapeutics and for those of you who are newer to the story, the company is a drug discovery and development company who make genetic medicines for patients who have severe unmet needs, and we're going to dig in in a moment to what that looks like, but we do it in a very particular way. We make drugs for patients who have mutations in a single gene or what we call monogenic disorders, and we make drugs that address the root cause, the underlying cause of that disease process.
We are trying to make the class of drug that has got the highest potential impact for patients in that setting. We do it, as I mentioned before, for patients who have no treatment options available to them today, and there's really a galvanizing purpose around the idea that we can have life-changing impact in patients who currently have not just inadequate but actually no treatment options available to them in the current setting. We do that in the context of higher prevalence monogenic diseases. Indications where having that desired patient impact, if we are able to change the life of a patient, we know that will flow directly through to a substantial commercial benefit. These are markets that exceed $1 billion per annum in addressable market size.
The defining feature of the company is the enhanced propensity for success in clinical development of drugs that target single-gene disorders. There's an enormous amount of literature on this. For those of you who've been on the course of the journey with us, we've spoken about this at some length, and we'll talk about it again in the latter parts of the discussion today. A five times higher propensity for success in clinical development associated with drugs that target single-gene diseases. The reason for this is because it is a lot easier to fix something that is broken when you know how it is broken and exactly what you need to do to fix it.
There's an additional dimension to what the company does that gives us even higher conviction in the translational capability of our drug programs in clinical development, and that is that we validate our human genetic medicines in a human mini organ before we even enter clinical development. What we're talking about here is the ability to take a tissue sample from a patient with the target disease, and because this is a genetic disease that is contained within the DNA in every cell in the body, we can take a cell that is not affected by the disease, most often a skin sample from these patients, and we can use the type of cell that we gather through that harvesting process. We can send it backwards to become a stem cell, and a stem cell is a cell that can turn into any other cell type in the body.
We can now use that stem cell and tell it to turn into an eye cell or a kidney cell or a brain cell, whichever is the target organ that is manifesting the disease that we are looking to cure, and we can then see that genetic error manifest in the disease phenotype. What we will look to do here is to determine whether or not the drug is exerting its desired effect and effectively becoming a quantitative cure for this condition by restoring the gene expression that is missing in these patients and correcting that downstream disease phenotype in the organ on a dish or organoid model that we speak about. Very, very powerful recent addition to the preclinical repertoire for assessment of drugs' efficacy profile before we move into clinical development.
I think the really exciting thing about PYC Therapeutics in 2025 is that's all well and good, but really where the rubber meets the road is in demonstrating the translational ability of all of that preclinical work into life-changing impact in patients. We are now in a window where through the course of the next 12-18 months, we are going to see three first-in-class and drugs with disease-modifying potential read out not just on human safety, but to give us an insight on human efficacy as well. A very exciting window for the company. That is what an unmet need looks like, and they say that a picture tells a thousand words, and I think it's really easy to gloss over the idea, yes, we understand unmet needs in patients, but these are diseases that have a really profound impact on the lives of the patients.
These are two polycystic kidneys that have been removed from a patient because they have reached end-stage renal failure, and that patient now needs a renal transplantation. If you think about the life of that patient in the 10 years leading up to that kidney transplantation and also the life of that patient on immunosuppression following on from that kidney transplantation, you will start to understand the magnitude of what we mean by life-changing science. These kidneys weigh 22 kg each as opposed to the normal weight of a kidney that is in the order of 700-800 g.
What we're looking at here is the potential not just to stop disease progression, but based on what we have seen in the animal models and also the ex vivo patient-derived models, is the potential to partially or ideally completely reverse some of these disease processes, at least in those patients who have sufficient plasticity within their tissue to demonstrate that reversal and stop the disease progression in the context of those patients who are later on in the disease course. You can imagine a similar impact in the context of blinding diseases of childhood. The impact on the quality of life of those patients in the context of a disease that is occurring so early in life has recently caused the FDA to come out and say that inherited retinal diseases like RP type 11 represent the single greatest unmet need in ophthalmology today.
If we think about the inadequacy of the treatment options for these patients, this journey that PYC is on is really about taking groups of patients who have no treatment options available today and giving them the very best class of drug that is possible, a drug that addresses the underlying cause of the disease and ideally can have a very profound impact in relation to stopping that disease from progression or, as we mentioned, in some cases, even reversing elements of that disease phenotype. From a patient standpoint, these are what we refer to as high-impact medicines. What PYC has done is it has taken its technology and it has applied it in a very careful place. It's not illustrated in this page, but what we specialize in as a company is in subtly increasing gene expression.
Using the RNA modality to compensate for a genetic mutation that is causing there to not be enough of a particular gene expressed in a particular cell type in the body. That is what unifies each one of these four programs that you can see on the page here. The company has progressed three of them through to clinical stage development, have a very high-velocity path forward through to market because of the extent of the unmet need in these patients and the propensity for us to be able to merge the clinical development pathway into combined phase I/II studies and combined phase II/ III studies, effectively running two clinical trials as opposed to the conventional three on that path to market.
What we're looking at here are drugs that have got a very high likelihood of success, very high potential impact in the patient population, and very high velocity through clinical trials on that path to reaching those patients who desperately need the drugs. It's quite a unique place to play within the context of the broader pharmaceutical and drug development landscape, and it's one that has led the company to a very exciting stage where we're now getting clinical safety, clinical efficacy data in relation to these three programs in the course of the next 12-18 months. That's PYC in a nutshell, a drug discovery and development company in the context of single-gene disorders, creating disease-modifying therapies for patients with severe unmet needs. That's what we do as a company.
If we break down our journey, I would refer you back looking at the broader window to the February ASX releases that outline the company's four-year roadmap in the transition to a commercial stage drug development company. What I want to look at here is where are we today in 2025 and where do we hope to be at the end of this year as the first 12 months within that broader 48-month journey. We will, through the course of the presentation, zoom out and have a look really at the first half, the first 24 months of that journey in some detail so we can contextualize you with the information required to understand what's going on, given that we have a lot of milestones coming this year.
We want to give you the framework through which you can interpret all of the data that is about to unfold through the remainder of 2025. The company has recently undertaken a rights issue to raise AUD 145 million, coupled with the AUD 50 million that the company started the year with and some anticipated R&D rebates for the fiscal year that is now nearly complete and the coming fiscal year. That gives us a cash runway somewhere between AUD 200 million-AUD 250 million. We are well capitalized. We have funding for effectively 24 months of the forward part of the roadmap through which we can deliver multiple milestones that have the potential to very much change the position that the company is in. As a consequence, the value creation for shareholders associated with that is extremely high. The company has high propensity science.
The nature of the molecules that we are reading out in clinical development are those that have got the highest propensity for success. We've spoken about that, but that is very much informing our expectations of what we are going to see over the course of the next 12 months or so. We'll dig into that in a little bit further detail. In fact, it is reflected in what we have already seen. In the early clinical data that is coming out of the RP11 program, we are seeing some very encouraging early signs, particularly on the safety tolerability standpoint, but also with respect to improvements in vision in those patients who have received the drug in the treated eye. I think, fortunately, we're in the position that all biotechs would like to be in with respect to immediate catalysts, and we have multiple of them.
It is an incredibly rich period from a milestone standpoint, given that we have these three clinical stage assets that are moving at maximum velocity alongside one another. That does create the need for us to give you the framework to understand exactly what is the objective across each one of them, and that is what we are intending to do today. If we turn our minds forward now to where we hope to be at the end of this year, we have referred back to in the past the Holy Trinity in red. Here, what we are referring to is to have a very strong intellectual property position, protecting the assets which PYC does have in relation to each of its assets, to be targeting markets where the patient impact that we are setting ourselves up to achieve will translate to substantial commercial benefits.
This is the focus on those larger patient populations. If you look at the material that is sourced here, they're talking about indications that affect more than 1,000 patients in the Western world. Those markets tend to land around the $250 million per annum in total addressable market size. PYC is focused on indications that affect more than 5,000 patients in the Western world. We're really about patient impact at scale. These tend to be markets that exceed $1 billion per annum in addressable market size. The third dimension in the Holy Trinity is that excellent clinical efficacy profile. It's giving patients, investors, confidence that we are going to have life-changing impact in that patient population.
Each one of our drugs is set up to do that because of their disease-modifying nature and the data that we've generated in the preclinical setting showing that these are quantitative cures in the case of RP type 11, where we can restore gene expression back above the level seen in patients who are not or individuals who are not affected by the disease process. It comes down now in the RP11 program to taking what is a good data set, an early data set, and demonstrating that that is in fact a great data set.
As we follow a larger number of patients for a longer period of time, what we're hoping to see is a continuation of the improvement, that early improvement that we have seen that is really crystalizing not only that the drug is effective in that setting, but also illustrating for us how we can quantify that efficacy signal to satisfy the various regulators who will be responsible for evaluating the late-stage studies that we are about to transition into when we come to the new drug applications for those respective markets. That is the objective now for RP11 in 2025, to add to the two existing elements of the Holy Trinity with that critical third component, an excellent clinical efficacy profile. We're going to talk very shortly about how we plan on doing that.
In the ADOA program, there's a nice opportunity here to do something bigger than the sum of the parts. Not only if we can translate the safety tolerability profile seen for the modality, same target tissue, same modality, same route of administration into the ADOA program and give ourselves line of sight to a second first-in-indication approval in a billion-dollar-plus market, there is substantial additional read-through in relation to the use of the modality in blinding eye disease more generally. If we can demonstrate efficacy, and it'll be an early efficacy signal in the context of the ADOA program, if we can show efficacy in two programs coupled with that very clean safety tolerability profile that we have observed to date, we really are starting to get into a position where we are seeing that we have control over gene expression in the retina.
That opens up an enormous opportunity for the organization in other blinding eye diseases, both within the rare disease monogenic domain, but also encouraging us to consider some of the non-orphan indications that affect larger numbers of patients, such as geographic atrophy and glaucoma in that context. We can have a chat about that later on through the Q&A session. I know there's some interest in expansion opportunities for not just new programs, but actually repurposing of that ADOA drug asset into alternative indications. As we move through those outcomes in the ADOA program, there will be a lot of excitement generated in the second half of this year around the polycystic kidney disease program. The reason for this is because it is a much larger target market affecting a higher percentage of the population.
One in every 1,000 people is affected by polycystic kidney disease. We are right on the cusp of transitioning into clinical development here. In fact, next month, we will plan to move through the first cohort of human dosing in the phase I- A study in PKD. If we can use the early parts of 2025 to demonstrate the safety tolerability profile, there will be a six-week wait as we evaluate the safety tolerability data in that first cohort before a planned dose escalation to a second patient population. As that second patient population moves through its safety review committee meeting a further six weeks later, and assuming no adverse safety tolerability, we will then be splitting and continuing to dose escalate in the healthy volunteers at the same time as starting dose administration at the original starting dose in the PKD patient population.
From there, in the context of the established safety tolerability profile, all eyes will be transitioning to look at the efficacy dimension of that drug program. We might get some early insights on that in 2025, but it'll be a very exciting window through 2026 as we transition from the single ascending dose studies into a multiple dose setting there. We'll talk about that later. Hopefully, you can see from that if we can establish excellent clinical efficacy in the RP11 program, if we can complement that with some early efficacy, just like we saw the evolutionary profile of that data as the first patient cohorts who received a therapeutic concentration of the drug started to give us a hint of those efficacy signal, and then that continued to build out as subsequent cohorts were dosed with the drug candidate.
We're looking to see exactly the same thing in ADOA, and there'll be a complementary effect of that pooled data set for the modality in blinding eye disease in that setting. With that data in hand, we'll very much transition the focus to safety tolerability in PKD. As we move through into the latter parts of the year, the focus there will shift to efficacy in a very large 2026 in terms of the continuation of those milestones. Now, if we look at the bridge, we've had a look at where we are today and where we plan to be in the end of the year, how are we going to get there? I want to just walk through program by program. We'll have a particular focus today on RP11 and PKD.
We'll come back in the second half of the year and talk in more detail around ADOA. The reason for that is there's a little bit more going on in the immediate future in the context of the first and third assets in the pipeline. I want to do them justice by speaking in sufficient detail to give you the color required to fully understand what's happening here. As you know, we have ongoing phase I studies and open label extension of a single ascending dose study, as well as a concurrent multiple ascending dose study in RP11 patients. There are going to be a couple of scientific fora occurring in May at which some of the principal investigators involved in those studies are going to present an update on the data that you have already seen in RP11.
There is a Foundation Fighting Blindness Conference that will immediately precede the Association for Research in Vision and Ophthalmology Conference in the first half of May, at which data is being presented in both of those fora by different PIs. That will give you an opportunity to have a look at how that data set has extended over time as those patients have come back for later follow-up appointments and evaluation in each of those studies. What we are going to do from there is we will extend those studies. The patients are very keen to remain on drug, and the principal investigators are very keen for their patients to remain on drug, which is terrific. That gives us an opportunity to extend that study into a 24-month follow-up window.
What we're looking to assess here is how long can that improvement in the vision continue such that we can get very clear separation from the natural history of this disease process, which is a very slow decline in visual function. To the greater extent that we see continuation of that improvement, that's going to start to help us in a very material way think through the design of the study that's happening down here, the registrational combined phase II/ III study. The more separation we get on the back of the improvement there, the shorter the duration of the registrational study will need to be. That is in particular the piece of the puzzle that we are looking for here.
Concurrently, we will have a meeting with the FDA in the U.S. in the first week of June to align with the FDA in relation to the design of this registrational study. We don't need to fully finalize the design of the registrational study at that time point. What we will continue to do is to use the data that is coming from the open label extension of the phase I/ II, in particular looking at how patients perform in that second 12 months of exposure between month 12 and month 24 to inform the final design of what this registrational study is going to look like. From there, the focus in the latter parts of the year are really going to return to an efficient enrollment of that study. Top down, we're looking at approximately 60-80 patients in that registrational trial.
It's a relatively small study that we're looking at here in that context, so quite manageable. Increasingly, we are finding in our conversations with clinicians around the globe that there are large numbers of RP type 11 patients who are already pre-identified. It'll depend on the final patient stratification criteria that we impose, who are the patients that are going to allow us to see our signal in the earliest and most profound manner possible. That will then inform how many sites we need around the world to ensure that we can enroll those patients very efficiently into that registrational study so that we can get that last second-in milestone as early as we possibly can within that window.
There's an awful lot happening in RP type 11, and we're going to talk about the impact of, in particular, that data set and that blue star that we're seeing here, the clinical proof of concept as we look to release more and more data from that ongoing phase I/II study in relation to how those patients are progressing on those two registrational endpoints in particular that we've previously spoken about. Visual acuity as it's assessed by low luminance visual acuity and retinal sensitivity as it's assessed by microperimetry or flashing a light onto the central part of the retina in those patients. We'll talk more about that very shortly. In ADO, sorry, in ADPKD, as I mentioned before, we are looking to transition into dosing the first cohort of healthy volunteers in a phase I- A study next month.
In fact, we are looking to complete dosing of the first cohort within the month of April. That will mean that we go May, June is the window that we would be looking to administer dosing in the second cohort, and you are into Q3 for the safety review committee that is then going to split continued escalation of dosing in those healthy volunteers and the transition into initiating part B of that study, which will involve patients who have polycystic kidney disease. In addition to the safety tolerability data that we'll be generating in both of these individual human populations, we will also be looking at the urinary biomarker of PC1, the protein or the gene that we are looking to increase the expression of is ultimately excreted in the urine.
Even within the healthy volunteers, we can get a proxy or a biomarker indication of whether or not the drug is achieving the desired effect. We will specifically be looking at that in the context of the patient population in addition to imaging of the kidney itself. Looking at the volume of sentinel cysts within the kidney, individual cysts, but also critically looking at the total kidney volume in those patients. That is very much the objective of the follow-on multiple ascending dose studies. Here, what you're looking at is a mirror of the registrational trial format that sits on the right-hand side. We know that the FDA will accept total kidney volume as a biomarker in support of an accelerated approval in the context of a single 12-month registrational study in polycystic kidney disease.
What we are trying to do is to mirror the design of that study in the multiple ascending dose study here. You are seeing patients on drug for 12 months, effectively a smaller patient population than what you would be looking at in the ensuing clinical trial that is directed towards the registration of that drug. We have just articulated that here as well. I just reiterate that point. We will complete the single ascending dose studies through 2025, early parts of 2026. They will be either converted into an open label extension of those single ascending dose studies, which is effectively a multiple ascending dose study.
There will be a concurrent multiple ascending dose study that will also be run to give us a larger pool of patients in which we will be evaluating across the combined studies, the same endpoint at the same time point that we will be looking for in this single registrational phase II/ III, whatever we want to call it, a registrational study that is directed towards supporting new drug application in the context of PKD. Okay, that is the operational roadmap and how we will go from where we are today to where we hope to be by the end of this year. Hopefully, you understand the excitement that is instilled within the organization as we deliver those milestones.
They are significant de-risking milestones that are shedding a substantial amount of light on the propensity of each one of those assets to enter market and the impact that they are going to have in the lives of patients. By the time we have got to that point, I think we're going to get a lot of additional color in the ADOA program through the second half of this year and early parts of 2026. We'll come back and have a chat about that in more detail at the next investor webinar. For today, focus on RP11 and PKD. I wanted to also touch briefly on how the transition into late-stage drug development, a combined phase II/III study later this year in the RP11 program, is creating optionality from a commercial standpoint for the organization as well.
I think it is just worth outlining the three essential ingredients of a business development deal of the nature that PYC is looking to do. For those of you who've been on the journey longer, we have been very clear that we are looking to take our assets to a point in the development pathway at which we can extract a very substantial amount of the value pool. The way that we do that is by translating our internal conviction in the assets into high-quality data that is de-risking the proposition from the counterparty's perspective. Within the ophthalmology domain, particularly, we knew that that was going to require us to move into later-stage development. Particularly as you get a good handle on human efficacy data, now the assets start to become extremely attractive from a business development standpoint.
Beyond just the clinical data, there are a couple of additional ingredients that are required to execute the size of BD transaction that this company would be looking to extract, given the value of each of the assets that has been generated to date. The first one is strategic alignment. You need the counterparty to be interested in the therapeutic area, the modality, and in particular in how the modality is being used within that particular indication to drive that patient impact. It's very important that we get strategic alignment here. We've spoken previously about the migration of the larger pharmaceutical companies towards RNA therapeutics generally and specifically to the use of RNA therapeutics to increase gene expression.
More broadly within the industry, facilitated delivery of RNA therapeutics to overcome the Achilles heel of the modality, which is that we're not getting enough drug inside the target cell. There is really a beautiful alignment of these forces in the context of PYC's development pathway. Increasingly, we are seeing that strategic interest in exactly what we are doing. That needs to be accompanied by a strong scientific hypothesis. Why do we believe that we are going to be able to have a profound impact in the context of these specific patients? It is much easier to divine in the context of single-gene disorders. It comes back again to that genetic validation of the target.
We're going to have a look at that in a fairly cursory fashion because I think that you understand scientific hypotheses don't get any stronger than correcting the gene expression deficit in the context of a single-gene disorder. That is what I referred to beforehand as a quantitative cure. That is addressing the primary driver of the disease process, and at least in theory, the entirety of the phenotype should be stopped at that point, if not reversed in the context of an organ that has residual plasticity. The final point here is differentiated clinical data.
I think for understandable reasons, the better the clinical data, the greater the insight that we can generate into establishment of standard of care, which is again a lot easier for PYC given that there are no approved drugs in the indications that we're targeting in large part with a couple of exceptions that we can touch on in the context of PKD. The differentiation of that clinical data is going to give a very good understanding of the market uptake of these drugs, the extent of the patient impact that we're looking to see. There was just a nice quote very recently here around another pharmaceutical company. We've previously spoken about GSK and their migration towards single-stranded oligonucleotides.
Here, I think a really elegant distillation of exactly what PYC are doing, using the RNA therapeutic in an off-the-shelf manner, so a mutation-agnostic manner, addressing all patients with the target indications to do something that the first generation of RNA therapeutic drugs did not do. Most of the first generation of RNA therapeutic drugs were directed towards turning gene expression down, knocking down gene expression in the context of a mutant protein or even a wild-type protein that was driving a part of the disease process. Here, we are looking to turn our mind to a different set of diseases that are caused by having insufficient expression of a particular gene.
We are now using the RNA therapeutic to engage with the one remaining good copy of the gene, remembering that you have two copies of every gene in the body, to enhance that translational process or make more protein to compensate for the loss of function mutation in the other copy of the gene. That means no protein is being made from that copy of the gene. It is a very clever way of subtly intervening in cellular processes to correct the underlying cause of the disease. You are increasingly seeing, BioMarin is just one example here, an appreciation of this use of this modality in the context of these specific diseases. There is an enhanced understanding and I think greater competition for assets in this particular space.
A really nice quote from John Maraganore, the founding CEO of Alnylam, another monogenic disease company who's just outlining the extent of the power of the genetic validation of that target. I know I go on about it a lot, but it really is important that we understand here how different targeting a genetically validated target is in the context of the drug development pathway as compared to going after something that we have some evidence for playing a role within the broader disease process, but it's not the primary driver of that specific disease. We have got a very, very strong supportive scientific hypothesis that is built out in an even greater extent through the use of those patient-derived models. Not only can we show that we have quantitative cures for the target indications, but we can actually show the impact on the downstream phenotype there.
A lot of the functional elements that sit between the two have been mirrored in PYC's preclinical data packs supporting the progression of those assets into the clinical trials. It has obviously become less important as we now move through into the clinical setting and are generating that clinical data. The clinical data is going to trump the preclinical data, but it is very, very nice to have the complementarity between the two. The final part, again, we have spoken previously, but there is a shift within the industry at the minute towards companies who are creating clinical data packs that support the establishment of the standard of care. Really here, it is about market share. How much of the market are we going to get?
There is a huge focus and an incredible value gap emerging, a striking delta between those companies that have good clinical data as compared to those that have very good clinical data. Here, the quality premium that we refer to is the relative value of that excellent data set over a good data set. It is particularly amplified in rare disease. It is probably less relevant in the context of PYC because, at least in the context of the RP11 and ADOA program, these are the first drugs ever to have been dosed in a human with that condition. We do not have competitors in that context, but it is still very important for us now to transition our mindset to the absolute impact in the context of the patient. That is where that visual functional improvement that we are seeing in the RP11 patient population is so critical.
We know as we move through to late-stage development that the median enterprise valuation of companies that have these excellent efficacy sets is AUD 4.4 billion. You can see how this very near-term milestone that's coming in Q2 in relation to the RP11 program is fundamentally changing the situation for PYC. That is really driven not just from an intrinsic valuation standpoint that should be reflected in the equity capital markets, but it's also being driven because we have that optionality to now do a licensing deal around a late-stage asset with a compelling efficacy data set. That really does put the company into a different space to where we have been before. With that, I'm just going to wrap up by referring briefly back to the 24-month roadmap that we spoke about.
Again, this fits within that broader 48-month roadmap that is outlined in the February release that outlines how the company plans to transition to a commercial-stage organization, revenue-generating organization. We want to focus very much on the first half of that journey. There is a huge amount going on within PYC right now. We are in the critical window for each one of these drug development programs. There is clinical efficacy data coming very soon. We just want to be very clear. We're focusing very much today on the clinical stage assets, breaking that down, what's going on in each one of these programs.
While we're getting that critical phase I data set, as patie nts move through to 12 months and beyond on drug, we can now see how that improvement in the vision in the treated eye as compared to both the contralateral control eye and the natural history studies is going to inform how we capture that efficacy signal in the context of the registrational study. The data here is very important. It's going to be important in addressing the question of, is the drug having the desired effect? To start to give us an indication in relation to the magnitude of the movement. What we really need to see, though, is those patients progressing from that 12-month time point through to 24 months. We can run that concurrently with the registrational study in the context of very strong conviction that that drug is working.
What we'll do is we will convert that phase I/II study into an open label extension where we are continuing to dose those patients with the drug through months 12 to 24. That then will be used to inform the ultimate design of the registrational study, which will be kicking off in the second half of this year. Extremely exciting time for the RP11 program, and you don't have long to wait. I think we'll get a meaningful insight in relation to how that data set is evolving in the context of those scientific presentations occurring in May. We'll drop down ignoring ADOA because we're going to come back to it in the second half, not because it's not exciting. This is also very exciting, creates a lot of optionality for the company.
I think it's going to be in the second half and the first half of 2026 that we're starting to transition to the efficacy data there. We'll go straight down to the PKD program. Here, if we can demonstrate a clean safety tolerability profile in the next two quarters, we are going to turn our attention as we move into the patient population in PKD onto that efficacy signal Q3, Q4, and you're going to get a very nice insight in relation to movement on the registrational endpoint, total kidney volume through the course of 2026 in the context of an open label study. You'll be getting data updates as we progress, an incredibly exciting time in the context of PKD.
PMS will come back and have a chat too another time because it hasn't yet entered clinical development, but some very exciting stuff happening in that program as well. Okay, with that, I will try and synthesize what we have in the chat function. Hopefully, okay, we've got a designated Q&A function. I will read through the questions, and if there are consistent themes within them, I'll address them together. Otherwise, we'll go through them individually. If you do have a question, please put that into the chat function, and I'll endeavor to address that as we go. There are a couple of questions here. The first one, there are a number of valuations that are a multiple of the current share price. What are the plans to get the market to match this value and also reduce future dilution in any capital raising?
Next question, any update on your RP11 program, re: timing FDA discussions, and when we may get more color on endpoint selection in a pivotal? Another one on, can we please discuss Nanoscope's MCO- 010 that is in II-B/III for RP versus PYC's RP11 asset in terms of safety, efficacy, approval time, and competition? Yep, we got an already answer to that one. Anticipate Q2 monthly dosing for 003 and Regulus seeing benefit versus placebo at three months with two weekly dosing. Do you think a single dose of 003 will lead to signals of clinical efficacy? When will we see first multidated both data? Are we likely to see an update on RP11 data with PKD? How are we viewing competitive pressure from Regulus? The recent data reads. Do we foresee recruiting any later stage trials if they're approved early or are you competing for patents?
That's pretty handy. That's a focus on RP11 and PKD, very much aligned to the content of today's discussion. In relation to the first one, look, the idea here is that we release the clinical efficacy data for the three programs that we're developing. We need to ensure that the market understands the value of what is being done here and the impact of those. We will increasingly transition, and I'm encouraging the analysts who are covering us in this space to directly engage with the key opinion leaders, the clinicians, so they can talk through the relevance of the clinical data. This is very much the currency of the realm, right?
If you can demonstrate that you have an asset that is highly likely to enter a commercially attractive market, we should be starting to see that flow through and be recognized into the enterprise valuation of the company. We understand the frustration of shareholders. I think that's why it's in the sense that it hasn't been recognized to date. That is why it is important that the company has that optionality that we spoke about in the context of the BD licensing transactions for those much better commercial terms than what we see in early stage licensing transactions. That gives us the freedom to move into the BD licensing domain in the event that we are not seeing full recognition of the value of the assets in the equity capital markets. I am very confident that we will see that translate.
It really comes down to the company in the short term demonstrating the difference between good and very good or excellent clinical efficacy data. I think if we can put that to bed, you really are going to see a lot more interest driven on both fronts, both BD and licensing and the equity capital markets. That will create a very nice competitive tension for the company in relation to the options and the sourcing of capital. RP11 program timing of the FDA, yes. First week of June in that sense to guide the endpoint selection. Although here, look, I think we've given a pretty strong indication of what we're focusing on. It will be between low luminance visual acuity and microperimetry, probably with a subtle bias towards LLVA as the primary endpoint, but potentially considering microperimetry as an alternative endpoint, possibly at a different time point.
You will see, I think the final answer to that will be dependent on how the patients evolve through months 12 to 24 and the work that we do in terms of understanding the efficacy signal from the phase 1/2 study, which patient population is going to allow us to see that signal earliest on which endpoint and how does that align with the regulators' understanding of what constitutes registrational data. It's the integration of those pieces of information that we are looking to engage the FDA on in that meeting in June. On the Nanoscope data, look, I don't want to go too deeply into the gene agnostic approaches. In the context of retinitis pigmentosa, specifically, patients and clinicians are always going to prefer a disease-modifying approach.
What we've seen in the context of the gene agnostic approaches, particularly those that are directed towards use of retinal ganglion cells to perform the function of photoreceptors and other specialized cell type, it may be helpful in patients who are at the very end stage of the disease. Those who've got extremely limited visual function, we're talking about detection of hand waving in front of the eyes here, but it's not going to be a replacement or a competitor for a disease-modifying drug that is going to be broadly applicable throughout the entire patient population, but that is also going to be addressing the underlying cause of the disease and therefore has the scope for greater impact in that context as well. On the efficacy data for 003, yes, it's very interesting.
I think the other dimension that goes into informing when PYC could expect to see its efficacy signal is the longer half-life of drug in tissue in relation to the PYC approach, knowing that we've got around a 15-day half-life in non-human primate tissue. It is possible that we will start to see movement even at the three-month time point, potentially even in the context of the single-dose studies. That makes what's happening in the latter parts of this year particularly exciting. I really do want to stress that the better evaluation is getting that 12 months of data mirroring what's going on in the registrational trial. I think the one advantage that PYC has got here is that our non-clinical tox studies enable us to go into a 12-month multiple ascending dose study.
Whereas Regulus were limited by what they've done in the non-clinical setting to that three-month evaluation in the repeat dose format, we're looking to extend that beyond, effectively concurrently with Regulus, possibly even ahead of them, given the difficulties in recruiting a phase III versus the smaller multiple ascending dose study for PYC, in that we will be reading out that 12-month data in the open label format, potentially ahead of Regulus. Are we likely to see an update on the RP11 clinical data in the near future? Yes, you are. That's coming within the next six weeks or so, and we'll be directing towards the presentation at those scientific fora. With PKD, how are we viewing competitive pressure from Regulus with their recent data readouts? Look, I haven't actually got fully across the data that came out this morning.
From what I do understand, it's very similar to what has previously been seen in the fixed dose cohort. It sounds like encouraging signs of efficacy in that context, which I think is great broadly for the patient population, for regulators, and also for PYC. If we think through the relativity in the preclinical setting, we've spoken before about the elements on which we see differentiation. We are focused very much here on biodistribution, how much drug is in tissue, on the integration of the PK/PD safety tolerability readout in vivo, in particular in non-human primates, in the efficacy profile of the drug modality that's being used in humans in isolation in the ex vivo models, and in terms of the specificity of the approach, the direct targeting of PKD1. That's what excites us about the PYC data pack.
We are incredibly excited to transition into clinical development and start getting a readout in those healthy volunteers very, very soon in the next fortnight or so, and then in the later parts of this year as we move into the patient population. It remains to be seen, but extremely important that we create treatment options for patients, as you have seen from the images that we shared through the course of this. Do we have any companies inquiring about the potential of purchasing RP11? Yes, of course. We have maintained a continuous dialogue with a number of counterparties, both from a global and regional standpoint. Really here, it's about generating data that enables us to enter into the transaction that we would like to enter into.
I think we've been very clear that that was always likely to be a later stage transaction in the context of the ophthalmology program specifically, but more generally within PYC's pipeline. We are looking to take drugs deep into clinical development or possibly even all the way through to launching in market. What the key here is, is it's that excellent clinical efficacy data drives the counterparty to understanding the value of the terms that are expected on the PYC side. I think we've given some very nice indications here. We're looking very much at the Johnson & Johnson MeiraGTx transaction. If you think we will now have a data set that is emerging that is larger from a number of patients' standpoint and also from a durability as compared to what MeiraGTx had at the time that they did that deal.
That will be the other dimension to look for as the additional data comes to hand from patients. You know that the safety tolerability profile is a lot cleaner for an intravitreal RNA therapy than it is for a subretinal DNA therapy, very, very much cleaner. If we can also complement that with outperformance on the efficacy side, you are really starting to get yourself a very compelling proposition from an in-licensing standpoint. I think the good thing there is each of the counterparties know as that data comes to hand, there are other people who are in the room. There is a very definite competitive tension in that process as well. In a recent orphan research report, at least 14 other diseases were listed as being potential targets if current programs are successful.
Glaucoma was not mentioned, but we've previously said it's a possible future target if current programs are successful. Is this still the case? Yes, it is. That's what I was alluding to with respect to the ADOA program. We want to wait for the efficacy data in that program first, get ourselves compelling evidence that increasing the expression of the OPA1 protein and the downstream benefits on mitochondrial function are yielding an impact in the setting of ADOA.
The idea there is that you could use the same approach, increasing OPA1 expression and improving mitochondrial health to decrease the sensitivity of the retinal ganglion cells to the secondary pressures like the raised intraocular pressure that drive the cell death in the setting of diseases like glaucoma and also geographic atrophy in the context of the retinal pigment epithelial cells to move directly into a phase II study given that the safety tolerability profile of the drug has already been established in the ADOA patient population. We are still working on this in the background. It's just, it's an awful lot for investors to get their head around with respect to the existing pipeline. We are going to focus very much in the next 12, 18, 24 months on the clinical data in the existing programs.
Know that we continue to work on alternative applications for the existing pipeline, additional targets, additional modalities. The discovery team are very active and making some very nice progress, but we are all about that clinical data for the next 18 months. If we can show efficacy there, the focus needs to be there. We need to get this translated into the enterprise valuation. That will then create a very different organization to what we're seeing today, a huge organizational transformation even between Q1 and Q4 of this year. Mentioning a webinar about PKD, Big Pharma looking for a partial stage in the trial that they cannot get past. I've forgotten what it is, but when will you know this? The data here really breaks down into three.
There is the safety tolerability dimension demonstrating that we have no serious adverse events in the healthy volunteers first and the patients that's coming through the course of this year. You are looking for that biomarker that we spoke about, remembering that what we want to do with the drug is to increase PC1 protein expression in the kidney and knowing that when the kidney has finished using the PC1 protein, it's ultimately excreted in the urine. We are measuring for that protein in the urine at baseline and after exposure to the drug, hoping to see an increase in that PC1 protein. That is the biomarker. We go one step further downstream to the total kidney volume or individual cyst volume within the kidney. That is the registrational surrogate anatomical endpoint here that we are looking at. Timing of the biomarker, you will see that this year, hopefully.
In the event that we see a clear efficacy profile of the drug, we would expect to see urinary PC1 moving potentially in the healthy volunteers, certainly in the patients. As we move into later parts of this year and throughout the course of 2026, you're going to see the impact on total kidney volume. The disappointing phase III readout on OPA1 drug have any relevance to the design of the proposed PYC phase III trials? Look, I think the short answer is no. In that context, it's a different drug modality for a very different indication. It doesn't have any impact on our proposed plans for the P3. It'll be very much focused, as we've spoken about, on those endpoints upon which we're seeing that early movement.
For PYC, it's all about how does that phase I/II data follow through at the later time points with a larger N. That's what's going to inform the design of that P3 study alongside a conversation with the regulator around what their expectations are to support new drug approval. In relation to the difference in value share price, are you proactively engaging with institutional investors to gain buy-side support, which still looks very thin on the ASX? Yes, of course, we are engaging continuously with institutional investors both in Australia and also in the United States. Most recently, we were on the road talking to institutional investors a fortnight ago. We again maintain a continuous dialogue with the investment community. I don't think you'll typically see the institutional investors sitting in markets. I'm not sure that the buy-side is necessarily a good indication of the interest there.
Certainly from the conversations that we are having, we have got very strong levels of engagement with the institutional investor base. I think a lot of the higher quality investors in this space in Australia are gravitating towards the story. There is a strong level of understanding amongst institutional investors around what we're doing. I think the story has become a lot easier for them to digest as we've moved to become a clinical stage company. Particularly now as we're moving through to become a late stage clinical company this year, there will be a keen interest in the release of the RP11 data coming in Q2. Also what's going on in ADOA in the latter parts of this year and also in relation to PKD.
Is it possible to have total delta improvement for microperimetry for a phase III endpoint instead of the FDA asking for preselected vision points? Yes, it is. There are alternate ways that you can use the microperimetry assessment to support a new drug application. The FDA have been quite clear on this. We could look at one endpoint, which is looking at what we call mean whole grid sensitivity of the macula. Here, you're adding up the numbers or the score for each one of the 68 points in the grid and looking at how that's evolving. That is effectively doing what you're suggesting here.
It's the total evaluation of the macula as a whole as compared to the alternative approach, which is pre-specifying the loci on the grid that are going to move by seven decibels or more in their sensitivity, which is the alternate way of doing it. I think the downside to using the whole grid sensitivity is that the expectation on the part of the FDA is that you're following those patients for 36 months. You must conduct the assessment every four months in the course of that 36-month evaluation. What we're currently looking to do is to see whether there is an endpoint and movement on that endpoint in the phase I/II study that would afford us a shorter duration of the phase 2/3. Whether or not we can truncate that 36-month time period to 24, possibly even 18 months.
I think 24 months is a reasonable benchmark there. That's where the pre-specification attraction sits or the potential to move across to the low luminance visual acuity signal. What's happening in the U.S.A. with Trump causing any concern? I'm inclined to plead the Fifth Amendment in response to answering that one. I think there is some destabilization generally that is causing some concern. I think you have seen a lot of negative leads off the Nasdaq recently reflecting that concern. I think there is uncertainty in relation to the impact of the administration on the FDA. What markets don't like is uncertainty. The greater degree of clarity that we get in relation to what changes are being made and how are they going to impact the sector as a whole, I think that will be a good thing for the industry as we move towards certainty there.
Why do analysts only give value to treatments for Australia, U.S.A., EU? Surely the rest of the world market would be also large. The answer to that is Japan as well is a very important market for rare disease drugs. It comes down to a combination of patient populations. I think Australia is probably less relevant in that context. It's really the U.S.A., EU5, and Japan who are the primary drivers of valuation. It's because these drugs are very expensive. Orphan drugs attract median pricing of in the order of $170,000 per patient per annum. Here we need a healthcare system that pays for the drugs rather than the patient. You cannot expect a patient to pay at that level for a drug.
The focus on the rare disease markets in particular is because these are the markets that are capable of supporting orphan drug pricing, which then drives a lot of continued innovation throughout not just the expansion of that drug into other markets at later time points, particularly when it comes off patent going to the rest of the world, but also innovation in relation to the use of different modalities that start in rare disease, but very much like what we spoke about with the ADOA program. Could that transition to a non-orphan indication later, the use of that innovation technology, much like what we saw with the COVID vaccination? Can we use these very, very highly innovative medicines in the context of broader applications once the cost of their development comes down and as we identify larger patient populations who will benefit from them?
That's the reason that we focus very much on those particular markets for the early parts of the rare disease development pathway. Increasingly, you're seeing China and other large patient populations play a role in relation to the consideration of the value of these particular drugs. Any other questions that anybody would like to ask? Oh yeah, sorry. Do we have a set date for the end of phase II meeting? IE still H1. Yes, we do. Still H1. I believe that the meeting is scheduled for the 6th of June. It's certainly in the first half of June and it is within the first half of this year. Anything else that's front of mind? No? Very good. Look, a very exciting time for the organization. You're going to see an incredibly rich vein of news flow coming in support of these critical milestones.
We tend to think of it as a binary outcome in the context of open label studies. It is not. We see data from individual patients, individual patient cohorts, much like what you have seen with the RP11 program. We are expecting that to occur in both ADOA and polycystic kidney disease. That is going to drive a lot of communication touch points for you in relation to how each one of those programs is progressing through the course of this year and next year. The very, very exciting part from our standpoint is as we generate that risk-benefit profile and we start to look from the safety tolerability to the efficacy dimension, things are getting very, very exciting with respect to building that conviction that we are going to have a successful pathway to a new drug launch in each one of these indications.
We are really in what they call the turning of the cards in industry. The point where you can get your teeth into the data and very much understand the value and the impact that these are going to have in the lives of patients that will flow through to commercial value. The task now for the organization is to get that value recognized. We are doing the groundwork to get people to understand the implications of the coming readouts with respect to the enterprise valuation.
In the event that we don't see the fundamental rerate that would be required to bring us close to that median enterprise valuation of rare disease companies who have what PYC has, we have got the optionality to move into the commercial realm at the individual asset level to give us the optionality from the upfront funding associated with those is such a substantial amount that it would drive massive impact, I think not just in the equity capital markets with respect to forcing value recognition, but also continued development of the pipeline to value crystallization points in some of the larger programs such as polycystic kidney disease and later Phelan- McDermid syndrome. We are in a very fortunate position from an optionality standpoint that comes from the diversity of the pipeline that we've built. What is really important is that we maintain very, very clean execution.
It is critically important that we deliver these milestones on time now because we are so close to those fundamental rerate events that we can really change the course of this company in the course of the next 12 months. It is an extremely exciting time and we very much look forward to updating you on the continued progress in that journey. That will start within a fortnight's time as we move into dosing the first subjects in the polycystic kidney disease program. From there, we will be looking after completion of the cohort very shortly thereafter to updating you on the RP11 program. A very exciting Q2 and we will welcome you back to the investor webinar to describe the progress that we have made in that context.
Thank you all very much for your ongoing interest and support of the company and we will speak to you again very shortly.