Well, good morning, ladies and gentlemen, and a very warm welcome to the 2024 Annual General Meeting of PYC Therapeutics Limited. There is a quorum present. I'm pleased to declare the meeting open. My name is Alan Tribe. I'm the Chair of the company, and here with me today on my immediate left, I have the CEO, Rohan Hockings. Next to him, Andrew Taylor, our CFO and Joint Company Secretary, and on the far left, Kevin Hart, also Joint Company Secretary. Due to the time differences, our two U.S.-based non-executive directors are not in attendance today, and they send their apologies.
A copy of the notice convening this meeting has already been circulated and sets out the nature and purpose of the resolutions to be considered in the formal part of this meeting, and I propose to take that notice as read.
Voting on all items of business on the agenda will be conducted by a poll, and the results of the poll will be announced to the Australian Stock Exchange later today. But before we move to the formal business of the meeting, I would like to provide some observations about the company and two factors that I consider important to our current and future operations. Then I'll hand you over to PYC's CEO, Rohan Hockings, who will provide a review of the business in 2024 and the future outlook. And following this, we will take questions.
And then we'll go to the formal part of the business and the poll at the very end of that part, and then the closing of the meeting. So firstly, some comments from me.
PYC is an emerging leader in the field of precision RNA therapeutics for patients with genetic diseases caused by haploinsufficiency in the eye, kidney, and central nervous system. The company is developing four first-in-class drug candidates in areas of severe unmet need for the tens of millions of patients affected by these diseases. Two drugs are already in clinical trials in the United States and Australia. They address the blinding eye diseases, retinitis pigmentosa type 11, and autosomal dominant optic atrophy.
Clinical trials in the third program, autosomal dominant polycystic kidney disease, will commence in Australia next year. Furthermore, there is a pipeline of earlier stage programs, the most advanced of which is to develop a treatment for the debilitating childhood disease, Phelan-McDermid syndrome. It is an impressive pipeline of drugs.
The company is developing at a fast pace and is progressing on each of these programs for the patients who need them. You'll hear more about these programs in Rohan's presentation, which follows. The availability of capital and the organization to support operations are both key considerations for an expanding company, and I would like to address both of these points now.
PYC is an efficient, cost-effective organization. For example, in the last fiscal year, the total amount, that is, the total amount spent by the company after government grants received, was AUD 43 million, which equates to about $28 million . The results achieved from this expenditure added significant value to the company's programs and therefore the company itself. It's been an excellent investment of shareholder funds. Further progression of the programs will, of course, require further investment and, in turn, access to additional funding.
The potential sources of that funding are the sale or licensing of one of the company's assets or the issue of additional shares through equity capital markets. I'm pleased to report that interest from third parties in both the company's individual assets and also its shares have improved access to future funding. We have seen an increase in the value of the company's shares over the past year, currently in the order of AUD 0.20 versus AUD 0.07 at this time last year. This has improved the terms upon which future capital could be raised.
The overall market capitalization of the company remains low compared to its U.S. peers, making any capital sourced from equity capital markets relatively expensive by comparison. As each of these funding options is considered, the interests of patients and shareholders remain paramount in determining the best way forward.
In addition to capital, the other key requirements to support growth and development are internal resources and organization. Our team has continued to be strengthened with the recruitment of additional skill sets within the past year, and this will continue. Selecting the right people with the right capability and commitment to the PYC culture is vital. This time next year, PYC will, in all probability, have three drugs in clinical trials, with a fourth headed in that direction. Furthermore, the pipeline of earlier stage programs offers good prospects for more drug developments.
It is an exciting time for both patients and shareholders. And although much has been achieved, we look forward to more success from the hard work and commitment of the PYC team, and I again recognize their achievements and thank them. And lastly, to shareholders, both longstanding and new, we appreciate your support.
It is our goal to achieve an above-average return for your investment by pursuing the worthwhile objective of providing treatments for patients, most of whom have no treatment options available today. Future prospects are excellent. And with that, I'll hand over to Rohan for your presentation. Thank you, Rohan.
Thanks, Alan, and good morning, everyone. Firstly, I'd like to echo Alan's sentiments in terms of the gratitude to the PYC team. There's an awful lot of hard work that has gone into getting the company where it is today, and we're very grateful for that.
From a formatting standpoint, I will open up for Q&A at the end of the presentation, but I'm also very happy to take questions as we go along, so maybe, Andrew, if we can get a microphone out to members of the audience who wish to engage, if you've got a burning question, please feel free to put your hand up, and we'll send a microphone out to you to field that question.
In terms of the objective for today, we are really looking to try and give you a bit more color in relation to where each of the assets are today, in the context of the company's wider ambition as we transition to a commercial stage drug development company over the course of the next 36 months. And so the way that I thought we would do that is by briefly looking back. If you guys cast your minds back to two to three years ago, we stood here talking to you about the company's objective of putting three first-in-class drugs with disease-modifying potential into human trials before the end of 2024.
With the submission of the regulatory documentation to take the third asset, polycystic kidney disease, into clinical development next month, and with the regulatory response that we're expecting in the first quarter of next year, we'll fulfill that ambition. So now the company's mind turns very much to the future and what the next 36 months holds. As I mentioned before, that is the transition for this organization to that commercial stage biotechnology company. I think the first thing that strikes you about this image is that there's an awful lot going on.
As Alan mentioned before, it's a very broad and deep pipeline. We're going to get into the detail that sits underneath each program very shortly, but I just wanted to draw your attention to a couple of the macro factors affecting the pipeline as a whole as we go forward.
We're going to talk shortly about high-probability assets and why they're so attractive in the industry at the minute. And there are some features that go into each one of these programs that sit off to the left-hand side of what you're looking at here today, decisions that were made by the company five, six, seven years ago in relation to where we wanted to play within the industry that have fundamentally changed the risk profile of these assets.
For those of you who have been on the journey for a while now, you'll know that PYC pursues single-gene diseases, monogenic diseases, diseases with a five-times higher propensity for success in clinical development. You will also know that we validate these human genetic medicines in the context of the human target cell of interest before we get into clinical studies.
This is the trick through the technology that has been made available recently of turning a tissue sample from a patient backwards into a stem cell and then forwards into any cell type in the human body. So we can choose the target cell in which the disease is occurring, and we can create ourselves a model of that cell and that organ from a patient to see whether or not we have a quantitative cure for that condition before we head into clinical development. So these are very high-probability assets in that context.
There's also a lot of interest in the industry at the minute for relatively obvious reasons about assets that can be accelerated through clinical development. You're going to see a quote from another industry figure very shortly on this. These particular drugs for these particular indications are a focus of the U.S.
Regulator right now for the specific purpose of accelerated approval timelines. So that is a very helpful trend for us. And then I think finally, with respect to the industry and our potential pharmaceutical partners that Alan alluded to, we haven't seen the wave of M&A that everybody was expecting to reignite the industry coming out of the downturn over the past few years.
The big pharma players are sitting on a lot of dry powder, but the assets that they are looking for are these specific high-propensity late-stage assets that don't have long before they hit the market. So from a macro standpoint, we're very nicely set up in that context.
And now what we're going to do is have a look at each one of these assets independently after we've had a look at the big picture vision in relation to how things are likely to unfold for the company right now. So I've touched on the first two points there. I think I'm going to just pick up here briefly on the third and the fourth.
There is a lot of industry attention for the third asset, polycystic kidney disease, because of the fact that millions, if not tens of millions of patients worldwide are affected, the severity of the disease process that requires a kidney transplant at the age of 55 in more than half of patients, and the accelerated mortality of those patients alongside the lack of effective treatments.
Just one drug that only 5% of the patient population is currently taking means that this has got an extraordinary amount of interest from the industry as a whole. So as we move into next year, it's very nice to have the ophthalmology programs reading out. We're deeply invested in delivering drugs for those patient communities as well as the Phelan-McDermid patient community, but we're going to see an increasing amount of attention on the polycystic kidney disease program.
And then I think to the point that Alan spoke about before, we are not stopping in terms of the ambition of the company to scale the platform technology. We have consciously made a decision that you're aware of at the Board level to continue to invest in the entirety of our pipeline throughout the downturn.
We have resisted the temptation to go all in on one asset and reallocate resources behind assets that are more advanced, like many of our peer companies, and the reason for that is because not only do we have a lovely portfolio of assets conferring the portfolio theory benefit in terms of the diversity of risk, but we also have the ability to scale into potential upside very quickly on the back of having this rapid-fire sequence of assets that are reading out in human development, and you'll see very soon, in fact, before the end of this year, the nomination of the clinical candidate in Phelan-McDermid syndrome, and we will look to transition that program into what we call IND enabling studies next year as well.
What we won't talk about today are the dimensions that sit below that in relation to the discovery activities of the company, but we continue to have an interest in further scaling of the pipeline in that context as well. This quote was in an article from an industry publication a fortnight ago, and I think it just really resonated with me in relation to the points that we were touching on before. Companies that have programs with high probability of success in the clinic and the opportunity to accelerate quickly through clinical development are in demand right now.
And so to the point that Alan spoke about previously, the company's options with respect to access to capital are diversifying very quickly.
As we move into later stage development, we are creating options from a business development standpoint as well as creating a better understanding on the part of investors in relation to the value of the assets. We're moving much more to a market-backed mindset as the risk is approaching levels that have been substantially diminished as a consequence of the strength of the data in each one of those programs in the clinic, building on those dimensions that we spoke about that took them into the clinic, the high-propensity nature in the context of genetic medicines.
So now we're going to go asset by asset just to try and give you a little bit of color on exactly where we've got to and how things are going to unfold from here. Sometimes internally, I think we forget that we're in it every day and we've got that awareness.
We're trying to bring you on the journey at that high level and frame that in the context of the company's wider ambition, so I think generally everybody knows that we are running two combined phase I/II multiple dose studies here, an open label extension of the single ascending dose study concurrently with a multiple ascending dose study, and so what we are looking to do here is to build out that phase I/II data pack that is giving us important answers in relation to what the design of the registrational study that we're looking to kick off in the middle of next year is going to look like.
You have seen some very encouraging signs on the part of the vast majority, in fact, of the 15 patients for whom data is in the public domain already in relation to those patients who have a progressive and irreversible blinding eye disease having improved vision as compared to where they were before they started the clinical trial. This is very impressive. That is not just compared to baseline, but it is compared to the control contralateral eye that did not receive the treatment as well. We're really trying to isolate the drug-mediated effect in that context.
What we need to do, given that we are seeing movement on two registrational or potentially registrational endpoints, is work out what is our internal view in relation to which one of those endpoints we're going to nominate as our primary endpoint in that registrational study.
We need to think through, should we look at a composite endpoint that combines the two of them or, in fact, a co-primary endpoint? We will need to engage deeply with the clinician community, the KOLs, before using the fast track status to go off and have a conversation with the FDA at the end of the first quarter, start of the second quarter, in relation to what that clinical study design looks like.
I think the very exciting thing here, as we're moving that program into late stage development, you will not see data coming from this program because that will be a masked study. But what we are going to do is we are going to convert the patients in the ongoing phase I/II studies into an open label extension study.
We will continue to provide access to the drug to those patients, and you will continue to generate data for one year, two years' worth of exposure in those patients where we're hoping to see that separation between the treated and the untreated eye spread even further. At a certain point, we will then decide to cross over the contralateral untreated eye and treat that eye as well for the benefit of those patients who are bold enough to enroll themselves in a clinical study. So that's where we've got to in the context of RP11.
In ADOA, you're aware that we have recently started a phase I study in patients in Australia. And I think the immediate focus here is on good execution of the single ascending dose studies. This is directly in patients.
So we are interested in the context of the early efficacy profile of that drug candidate as well. But I think in all reality, in the context, again, of a slowly progressive disease, we are hoping to be as lucky as we have been in RP11 with respect to seeing that visual functional improvement, but there are no guarantees. We'll be looking at different endpoints in this context. And I think at the midway point of next year, as we move into the second half, that's when the data on the efficacy dimensions is going to get really interesting for those patients.
What we are planning on doing concurrently with that, and we have started the body of work that will go in here as well.
Remember, this asset is the one asset in the pipeline that has the potential to treat diseases other than the single-gene disease that we're going after here, optic atrophy. And in particular, there are two very significant unmet needs within ophthalmology, blinding eye diseases in the form of glaucoma and geographic atrophy that are posited to have an underlying bioenergetic basis. And this drug improves the bioenergetics of the cell.
So we know, for instance, already in a mouse model of glaucoma that increasing the expression of the OPA1 gene, which is what this drug does, is protective of the retinal ganglion cells. That is a very good start. But as you know, we place a very high value in this organization on patient-derived models.
Our job now is to think through what is the best recapitulation in the preclinical setting of glaucoma as a disease process and build out the body of evidence that will give us conviction to move directly into a phase II study, having established safety in the ADOA patient population in glaucoma and geographic atrophy, so there's the potential to expand directly into mid-stage clinical studies in very large indications, that asset, and you should be looking for us to release that data in the context of the course of next year as well.
In relation to the third program, we've spoken about the submission of the regulatory documentation in December. Here, we are looking to release the entire preclinical data pack over the course of the remainder of this month.
So you're going to get a very good look at the body of evidence upon which we are basing that transition into clinical development. You have already seen the drug being effective in models derived from kidneys who have end-stage renal failure as a consequence of ADPKD. We were the beneficiaries of a tissue sample from those patients as the kidneys were removed. That saved us the need for generating the kidneys from those patients ourselves through the stem cell approach that we've spoken about previously.
And you see quite a profound and dramatic reduction in the number and the volume of the cells, the cysts in the kidneys of those patients after treatment with the drug. So there's a huge amount of interest here on the part of the clinicians and on the part of patients with that disease indication.
There are no disease-modifying drugs that are approved in polycystic kidney disease. What we would like to see is to build out that data pack with an in vivo data set from animal models showing us that we can achieve very high concentrations of the drug in the kidney.
That's what you should be looking for in the first instance, so that at a safe and well-tolerated dose in a non-human primate, we can get enough drug, ideally the same amount of drug that was used in the patient-derived model to engender that reversal or the reduction in the cyst frequency and size in that context so that we can link across how much drug do we get to the target organ when we administer it intravenously to the effect that we're seeing in the human kidney that's come out of that patient.
That becomes a very powerful combination data set in that process. The other dimension, when we have spoken to the interested big pharma companies fielding the inbound interest in the program and acknowledging that we wish to take this asset in clinical development ourselves, so we're not looking to partner the asset at this point in time. But nonetheless, because of the size of the indication, the extent of the unmet need, there is a lot of interest on the part of potential partners here.
The other big question that they have asked us is, can you confirm that you can see biodistribution or does your drug get to the cyst-forming cells? So they are suggesting that over and above distribution within an unaffected kidney, a kidney that is not affected by polycystic kidney disease, they also wish to see drug trafficking to the cyst-forming cells in that context.
That is a critical piece of data that will come out in the context of that preclinical data pack as well. If you can show in the species that is most relevant from a biodistribution standpoint that you have got a lot of the drug in the target organ at a safe and well-tolerated dose, if you can show that within the organ you are reaching the cell types that are affected, both those that are not affected by the disease and also those that are affected by the disease, and you can show in the human kidney model that you can stop propagation of those cysts in the context of treatment with the drug, you have a very, very powerful data pack as you're moving into patients. We have had the pre-IND conversation here with the FDA.
We know that we will be required to start the clinical studies in healthy volunteers. So we're looking at Q2, Q3 next year to progress through the healthy volunteer studies. And in the second half of the year in Q4, we'll be transitioning into patients in a multiple ascending dose study context. And this is where things are going to get very interesting. You know that the protein that we are trying to increase the expression of is ultimately excreted by the kidneys in the urine. So we'll be looking to see whether we can measure an increase in that protein in the urine of patients.
And you know that the ultimate objective here is to stop the growth of the kidney. This is the surrogate anatomical endpoint that the FDA have committed to as a registrational outcome in a phase II study. Because of the unmet need, we don't need to run a phase III with kidney functional improvement until after the drug is approved.
If we can start to show movement either at the individual cyst level or at the level of the totality of the organ, slowing the rate of growth as compared to untreated kidneys or ideally starting to see a reduction in the volume of the kidney size, as has been seen in the animal models of this disease when we can restore the missing protein, that is going to be a very, very critical outcome for the future of this company. It's a largely overshadowed program at this point, but it's a great shame. There's also a beautiful data set emerging in the context of Phelan-McDermid syndrome.
This is a very severe neurodevelopmental disorder where the children are so profoundly affected by the disease that they are nonverbal, don't communicate with their parents. What is driving that is the absence of a scaffolding protein that's sitting in the neurons that enables the neurons to communicate to one another properly. And that scaffolding protein is known as SHANK3. And so there's a critical piece of data coming again in the fourth quarter of this year that will look at the ability of this drug candidate to restore SHANK3 levels back to those seen in unaffected individuals in brain cells from patients who have Phelan-McDermid syndrome.
We haven't actually taken brain from these patients. We've taken a tissue sample, reverse differentiated, and then forward differentiated to the brain cells.
As we spoke about before, this is a very high degree of validation, the desired change in gene expression in the target cell of interest from a human, a very powerful piece of data. This will be complemented by that biodistribution dimension that we just spoke about in the kidney, this time in rat models.
The reason for doing it in rats is because we are the beneficiaries of a large body of work that has been done by big pharmaceutical companies like Biogen and others, linking rats to non-human primates to humans in relation to triangulating between the concentration of drug in the cerebrospinal fluid, the fluid that bathes the brain, the plasma, and the brain tissue itself. You can measure two of them and infer your concentration in the target organ.
And we can read through from the rat to the non-human primate to the humans. We have a very clear clinical development and commercialization path on the back of that. So there's some exciting work coming there too. This will be complemented by some downstream functional assays. So not satisfied with quantitatively having cured the condition, we will also look to see whether we can improve the function of those neurons.
This is ultimately what we want to do to change the lives of the patient with this disease on the two dimensions of the phenotype that are of most interest to them and their families: language and cognition. If we can restore the communication between those neurons by replacing the missing scaffolding protein, this has the potential to have a very profound impact on the lives of these patients.
Just like in polycystic kidney disease, in animal models of Phelan-McDermid syndrome, if you address the underlying cause of the disease, you can actually not just stop the disease from progressing, but actually partially ameliorate or reverse the disease phenotype. It's a very exciting prospect for these patients. [audio distortion]
Yes, that's right. Yeah. Very late. So late December, we're looking at release of that information. Probably not ideal from a market perspective, but that's when it's coming. And I think it gives you a very good read through the next 12 months. The rat should be predictive of what's coming in the non-human primate from a tox standpoint. If you're going to see an issue, it should be visible in the rat studies. So it gives you very high conviction that you now have that fourth asset with disease-modifying potential with a very clear path into the clinic.
And the other thing that we should point out here, unlike ophthalmology, where it was always very clear that we were going to have to generate human data ourselves because it's a relatively niche area from a big pharma standpoint until you hit mid-stage, late-stage clinical development, there is a lot of interest in central nervous system drugs from a very early developmental stage, very early. So if we cast our minds forward to the end of next year, it will give you a sense of the scale of the activity and the nature of the change that's going to occur in this organization between now and then.
We will be in a late-stage study with a first-in-class drug that addresses the underlying cause of an irreversible and progressive blinding eye disease that robs patients of half of their quality of life.
Equally excitingly, you will have an extension study where you're looking at 18-24 months of data in patients who have received exposure to that drug candidate. We know already that it is safe and well-tolerated. We know already that patients' visual function and functional vision is improving after having received single and multiple doses of the drug. The great hope here is that we can continue to see that trajectory diverge. One caveat here, there will be a ceiling effect for the visual functional improvement that you're seeing.
There'll be a limited number of cells in the retina that can be recovered before the effect starts to plateau, and at that point, you transition from vision improvement to maintenance of vision, which actually, if you talk to the patients, is a satisfactory outcome for those guys.
They just don't want to lose any more vision than what they have today. In ADOA, you'll be looking at the open label efficacy readouts in the context of a second monogenic indication where patients have no treatment options available today. You will also have in hand the outcome of the patient-derived models that will tell us whether or not we're going into an investigator-led phase II study in the context of these other major unmet needs within ophthalmology. In ADPKD, you're going to be in the very exciting window of looking at the human data in patients.
You're going to be reading very deeply into each one of the data sets that are released on those two biomarkers that we spoke about and that anatomical surrogate endpoint, looking for any sign of an early change in those patients on the dimensions of reversibility around that very elegant integration of the preclinical data pack. It's going to be an incredibly exciting time in that program, and you will be basically where we are today in the polycystic kidney disease program in the context of the Phelan-McDermid syndrome.
This is, as Alan mentioned before, an extraordinarily broad and rich pipeline for any company, really, but certainly for an Australian biotechnology company.
It's built very much on the strategic link and the decisions that were made by the organization six, seven years ago that the RNA therapies would be a very good way of addressing what we call a haploinsufficiency or having lost one of the two copies of the gene expressing half as much protein as we need to.
We made a bet that the RNA therapy would be the best way of addressing that indication and that the reason that patients had no treatment options was that no other modality was capable of rescuing the gene expression that is missing without risking overexpressing the gene, which will also induce a disease phenotype in these patients. You are dosage sensitive to these genes. This was a very good strategic bet by the company.
We then further differentiated on the back of understanding that the Achilles heel of the RNA drugs was their delivery profile. So we have sought to overcome that through the use of the non-viral delivery technology that is able to get 100 times as much drug into the target cell as the naked RNA therapy itself. And we are seeing that start to pay benefits already in not just the safety, but also the efficacy profile of the drug candidates in the clinic.
The company is in a very robust position with significant scalability of upside into disease indications that are affecting high single-digit, if not double-digit millions of patients worldwide. So we are in a very good place right now. We will continue to update you on the further discovery efforts in relation to pipeline expansion as they come to hand.
I think you're going to find an increasing focus just given the scale of the clinical safety, clinical efficacy readouts. These are the currency of the biotechnology industry. You'll see an enormous focus on the very rich series of readouts that you have that are articulated on this page. I think, again, applause to the team in relation to the quality of execution through this year. If you look at the roadmap that we set out at the beginning of this year and cast your mind back further two, three years ago, we've very much achieved what we've set out to do.
There have been some marginal delays just in terms of frontline execution issues in one of the programs, but we are largely exactly where we expected to be.
If we can continue to do that and deliver on the potential of this company through to the second half of next year and the AGM, we're going to be in a very strong position indeed. Maybe if we would just wait, David, would you mind?
Yeah. Is it possible? You mentioned that the ADOA program could split out into a glaucoma and a geographic atrophy. Is that possible that we could end up with six by the end of next year, or is it the following year really that that would come through?
I think if you think about the logistics of getting a study like that up and running, and it's likely to be an investigator-led study in the first instance, we'd like to see data coming back from possibly a single site or clinician who's interested in taking the drug into that indication.
It's more likely that you get the conviction in the data to go into that indication next year and you see patients enrolled and treated in the following year. But remember there, you're going directly into the P2 study because you have established the safety profile of the drug by the same route of administration for the same target tissue in the ADOA patient population. So you're really looking at efficacy in that context.
The second question, which is probably you're going to say no, not yet, but do you have areas that you can tell us that the discovery programs are looking at? Like, is it?
Look, I think we can shed some light on it. What we would be looking to do there is to leverage the validity of the delivery technology that we have established in existing programs.
And there's a particular attraction to these tissues that we've spoken about beforehand, non-dividing in the case of the eye, individual cell layer deep in certain instances. And if you look at the distinctive nature of the delivery technology, we're able to reach every cell in the context of the retina. We've got hopefully going to show a distinctive biodistribution profile in the non-human primate kidney very soon. You see a lot of interest in that space. Three or four companies have been seeded in the U.S. in the course of the past month for RNA drugs in kidney disease.
So we, like others, are very much interested in expanding and leveraging the delivery technology in that indication. And then there are some particular attractions of precision medicines for the central nervous system as well.
So the same three target tissues, but we may well look to change the nature of the indications that we're going after, or possibly even in the more distant future, the nature of the modality that we're using in that context.
Last one from me, RP11. The pictures look fantastic. Are the patients actually saying, "I can see better," or is it just all in statistical data that you can?
I think the first thing to note there is that we are quite removed from the patients. So we have the sponsor and then the principal investigator and then the patient. And it's important that we are not having a direct interface with the patient.
But what I can tell you from feedback from some of the principal investigators in the study is that we have got multiple patients who are reporting visual functional improvement in the treated eye after having received the drug, which is important to the clinicians. It's driving a real sense of motivation, which is part of the reason why the execution has been so efficient. There are a lot of patients waiting to get into clinical trial now.
Can I move the topic over to the kidney drug, please, Rohan? Looking at that slide, the NDA stage 2028 feels like it's a year or two earlier than what our earlier slides on this was, because for some reason I had 2030 in mind.
I also picked up on a comment that you said at this stage you're not interested in doing any sort of deal on the kidney drug, but it's obviously a very large potential drug in terms of the market, the distribution, all that sort of stuff, and we've got a share price, which I think we all think and hope is trading at 20% of what it would be with our peers if we're in America. Why wouldn't you look at effectively farming out half of the kidney drug to a major international company who's in the farming terms of being basically that they fund this expensive stage?
You're a joint venture partner and you've got instant distribution and marketing of the drug, as compared with having to raise money at a price where the cost of capital is ridiculous compared to peers.
So I think on the first part of the question, we do often run two timelines. There's my timeline and the team's timeline. So possibly the team are at 2030 for product launch of the drug, but I haven't seen that one in the public domain, Tony. So I don't think we're moving here in relation to when the NDA is likely to be submitted in that program. In relation to the second part of the question, we know that we can't launch that drug. The indication affects one in every 1,000 people. The scale of the sales and distribution channel that would be required is beyond us.
Certainly in our current state, I'm not sure what the chair's aspirations are by the time we get to that point. But I think in all likelihood, you will see us outlicense that candidate.
But if you think about the quality of the data pack that we've got and the conviction in the asset going into clinical development, if you can change the view of the counterparty in relation to the value of the asset because you firstly establish the safety tolerability profile of this drug.
Secondly, you see movement on a biomarker endpoint in relation to it. But ideally, if we could see in this multiple ascending dose study in patients, if you see movement on the registrational endpoint, height-adjusted total kidney volume, we are going to have added an extraordinary amount of value on the part of our shareholders in the process of having undergone what is a relatively inexpensive clinical development program to get there. So the ideal time from our standpoint is after we have seen some efficacy data in the context of that program.
But we will certainly continue to engage in conversations with those interested parties as events unfold, and we will look at the terms of any proposal that is coming our way, particularly in relation to any party who does, as you say, bring something other than raw capital.
Rohan, just two questions. One, last year you mentioned about the artificial intelligence, the arrangements you had. Can you just give us a bit of an update on where we are with that sort of program?
Yeah, so the collaboration with Google in that context is directed towards delivery to specific cells in the body, whereas we don't need that for any of the existing programs. This was looking at enabling the next generation of what we're doing. So it's a longer lead time body of work. It's ongoing. I think we're directionally heading in the right space.
I think we're grappling with a lot of the issues that the wider field is in the context of the use of AI in drug discovery, drug development. So it's not easy going by any stretch, but I think what we're going to see there is that we extend the duration of the collaboration with Google to give us a bit more time to see whether or not we can yield an outcome that is directly relevant for where we're heading in terms of our discovery activity.
So then, just from my memory, when was that arrangement with Google?
It's a 12-month contract. So it would otherwise have expired at the end of this year. But there's certainly an inclination at this point on the path of both parties to extend that to give us additional time to undertake the magnitude of the challenge.
And the second question on the kidney disease, and you sort of mentioned it earlier with this other company raising capital for kidney, is there anyone else chasing your particular, the polycystic kidney disease indication in the market that you're aware of, or you are the only people chasing that at the moment?
There's a company called Borealis Biosciences who've been formed. I think that's the company. There's three of them that have been formed very recently in this indication. But I think if that serves me right, that's the Chinook crew who have reconvened at Borealis. They have expressed an interest specifically in polycystic kidney disease. They are a very early stage discovery company, so literally have just been formed. They need to solve the delivery challenge and the gene modulation challenge before they can get anywhere proximate to where we've got to.
So that's the nice thing about putting drugs that address the underlying cause of the disease into the clinic first is that it really gives you clarity that you are going to be a category leader in the event that you get to market. The dependency for PYC is much less on what other people are doing. It's much more on what our clinical data looks like going forward. So very definitely. And it's a great thing for patients as well. We need a lot of people looking at that indication.
We've had a bunch of conversations in the U.S. recently where polycystic kidney disease is articulated as one of the great unmet needs in medicine, primary driver of chronic kidney disease, enormous impact on patient lives, those individuals affected by it and the families around them. So that's a good thing.
We're very happy to have competition in that context, but lovely for us to be opening clinical development and getting ourselves not first because we obviously have Regulus with the microRNA targeting approach, but we're very clear on the differentiation of the positioning of our asset as compared to theirs. And we're very much looking forward to seeing what the data holds for us.
Okay. Thanks very much, everybody. I'll hand back to Alan for... Oh, okay. You're going to read some out, Andrew? Maybe if you can just take them thematically so we don't spend too long.
A question around your use of the Rare Pediatric Disease Designation going forward.
So this one refers to a Rare Pediatric Disease Designation that we received for the ADOA program earlier this year. What happens there associated with acquisition of the designation from the FDA is that when we submit our New Drug Application, there's a commitment on the part of the regulator to shorten the turnaround time. So they usually have up to 10 months. They commit to turning it around within six.
The added benefit is not only do you get an accelerated review of your own drug application, but in the event the drug is approved, you also receive a transferable voucher that can be sold to another company to be used for an accelerated review of any type of drug, even one that doesn't affect an orphan pediatric population. So the question relates to the use of that particular voucher. Firstly, I should say we are going to apply for the same designationP in the context of the RP11 asset.
So we don't have any need to use it in the context of the more advanced program in the event that the FDA agrees with us and we receive the designation for that program. That will give us two vouchers to look at the use of. Phelan-McDermid syndrome is also an indication that affects children. The one indication in the pipeline that doesn't is polycystic kidney disease. So the question there is whether we would look at using the voucher in the context of our own program or pairing it with the program or looking to sell the assets in the context of approval in those indications. We'll cross that bridge when we come to it.
And just a question around org. Are we still conducting R&D in Perth with the scientific staff? And what is the staffing of the U.S. office like?
Yeah, so very definitely. I mean, we continue to conduct our drug discovery activities in an enhanced capacity. So we're continuing to grow within the Perth side, looking at those other indications and potentially other modalities that we spoke about through the course of the presentation. In terms of the U.S. organization, we're growing there too. And really the driver here is less about expanding the activities other than the fact that just the natural progression of the assets deeper into clinical development requires more U.S. expertise.
And so we're now moving into the context of a global phase III study that is going to have a very specific bias towards the U.S. because we have a large captive RP11 population in that context. But we need more resources to assist in terms of the magnitude of the activity that we've got on foot.
Alan mentioned it, alluded to the capital efficiency of the organization. This is obviously a fantastic thing, but we have many, many balls that we are juggling now, and we need to evolve as an organization to fulfill the very different nature and scale of the activities that we're currently undertaking as compared to what this year looked like. So we will continue to grow and revisit the design of the organizational structure to ensure we are stage appropriate. That's it? Okay, perfect. Thank you. I will hand back to you, Alan.
Thank you, Rohan, for that excellent presentation. So now we will proceed with the formal business of the meeting as set out in the notice. First of all, proxies. The company has received valid proxies from 127 shareholders totaling 997 million odd shares, which represents 21% of the issued capital of the company.
After each resolution is displayed here on the screen, I will invite questions from the floor, and I'll limit questions to the motion being considered. Once we've been through all the resolutions, a poll will be taken. Ballot papers have already been distributed to eligible shareholders at the time of registration, and I'll ask you to complete these after all the resolutions have been considered. Poll results will be announced to the Australian Stock Exchange later today. And just to note that each shareholder can only vote for his or her personal shareholding at this time.
So the first item on the agenda is the Annual Report. It's to consider the financial statements, the Directors' statement and report, and the auditor's report for the financial year ended 30th June 2024, all of which have been made available to shareholders in accordance with the requirements of the Corporations Act.
We have some copies here today as well. Company's auditors, PricewaterhouseCoopers, are represented here today by Adam Thompson in accordance with the requirements of the Corporations Act. And Adam is available to address appropriate questions or comments from shareholders on this agenda item. So are there any questions or comments in relation to the reports under consideration? Adam gets off lightly yet again. Well done. So there's no requirement for a vote on this item. So we'll proceed to the second item of business, which is the Remuneration Report.
Further details, including key management personnel, which includes directors, voting prohibitions, and voting of undirected proxies, are included in the notice of the Annual General Meeting. The Remuneration Report is as set out in the Annual report. In accordance with legislation, the vote on the resolution is advisory only and does not bind the directors of the company.
However, the board will, of course, seriously take the outcome of the vote into consideration when reviewing remuneration practices and policies of the company. So now we'll refer shareholders to the screen, which displays the resolution in full and the valid proxy results. I now formally move that the resolution be put to the meeting in the form set out in the notice. Is there any discussion on this resolution? Thank you. Well, you'll get a chance to vote on this resolution at the closing of this business. Now, re-election of one of our U.S.-based non-executive directors, Jason Haddock.
Jason has been a member of the board for three years and has a background in finance and operational experience in the biopharmaceutical industry in a variety of finance, strategic, commercial, and business development capacities.
He has held CFO and COO roles for business units in Asia Pacific, Europe, and the United States. As I mentioned earlier, due to time differences, he is unable to attend today and has tendered his apologies for his absence. I now refer shareholders to the screen displaying the resolution in full and the proxy results, which are strongly in favor of his re-election. Are there any questions? I move the motion. So are there any questions? Thank you very well. We'll get a chance to vote on that again. Resolution three is the consolidation of securities.
So the next item relates to the consolidation of shares and unlisted options in the company on a 10-to-1 ratio. If approved by shareholders, the number of shares on issue will be reduced on the basis that for every 10 shares currently held, they will be consolidated into one share.
Similarly, the number of options on issue will be consolidated on the same basis of 10 for one, and the exercise price of the options will be amended in the inverse proportion to the consolidation. That is, the exercise price will increase by a factor of 10, so basically, we're reducing everything by 10, and the reason for this is some of the considerations are that the company has a relatively large number of shares on issue compared to its peers. We have 4.6 odd billion shares on issue, which people in the United States have difficulty wrapping their brain around.
The consolidation is expected to reduce the level of volatility in the share price and a more consistent valuation of the company and assist in the positioning of the company's long-term growth by making an investment in PYC more attractive to institutional and other shareholders.
So just a symptom of the fact that the company is growing and maturing. I now refer shareholders to the screen displaying the resolution in full and the valid proxy results, again reflecting strong support for the resolution. I now formally move that resolution three be put to the meeting in the form set out in the notice. Is there any discussion on this resolution? Very well. Well, you're going to get a chance to vote through poll on that resolution also. So it's now time to take the polls for resolutions one to three, and a representative from the share registry will act as the returning officer.
Recent changes to the Corporations Act have changed the law in relation to the obligations of proxies who vote where a poll is called on a resolution. If the proxy is the chair of the meeting at which the resolution is voted on, the proxy must vote on a poll as directed. If the proxy is not the chair of the meeting, the proxy need not vote on the poll. But if the proxy does so, the proxy must vote as directed. If you are a proxy holder with open votes, you may vote as you wish. So you've been handed a ballot paper for the poll on registration this morning, and they're now being collected.
The resolution upon which the poll is being taken is set out in the notice paper, and I think we're well advanced in the process. Has everybody had a chance to vote? One gentleman over here. Third row. No, no. No. Okay. Thank you. Well, that closes the formal part of the business today.
Just before we close the meeting, there's just one thing I'd like to share with you going off agenda a bit here. Last weekend, one of our lead scientists presented in Amsterdam at a conference of patients who suffer from autosomal dominant optic atrophy, one of our drugs. She reported back that it had gone extremely well. The patients were highly motivated to obviously embrace any trials and future treatment. I was impressed by her closing comments, and I'll just share those with you because I think it speaks to what I might refer to as the culture and dedication of the group here.
Speaking directly with patients reminded me why we do this work: to make a real difference in people's lives. Hearing their stories and hopes connects the science I work on to its human impact. It's about more than developing a drug.
It's about being part of their healing journey and seeing the true purpose behind every challenge we overcome. I think that speaks largely of the sentiment and motivation that drives PYC forward. It's an amazing team of people. And with that, ladies and gentlemen, I'll close the meeting, and thank you again for your attendance, and look forward to seeing you same time next year. Thank you.