Good morning, everyone, and welcome to the 2025 Annual General Meeting of PYC Therapeutics Limited. My name is Rohan Hockings, and I will be chairing today's meeting on behalf of the Chairman, Mr. Alan Tribe, who is an apology for the meeting. I'd like to introduce you to my fellow board members. Here with me in the room, I have Professor Ian Constable and Mr. Kevin Hart, our Company Secretary. I'll deviate from the script momentarily. Sorry, that's just quite loud, that microphone. Take a step back just to acknowledge the contribution of Mr. Alan Tribe to the company and to thank him for his efforts over the course of the past seven or eight years. When Alan and I set about turning this company around from a cold start back in 2018, Alan was the only one who really had the vision for what PYC could become in that time and the commitment to see that through. We'll talk at the end of today's meeting about the proximity to human efficacy readouts for four first-in-class drugs with disease-modifying potential over the course of the next 24 months, and we would not be in a position to have that opportunity today in the absence of Alan's commitment and contribution to PYC. On behalf of the board and all of the staff, I'd like to acknowledge and to thank Mr. Tribe for his contribution. I'd also like to welcome our two new directors to PYC. Firstly, Professor Ian Constable. Prof has been helping me over the course of the last several years already in the background, but I'm delighted to bring Prof. Constable on board with his depth of knowledge in our scientific programs and also the journey that sits in front of us, the challenges and opportunities for a company like PYC Therapeutics as we seek to move multiple assets into late-stage development. I'm personally very grateful, Prof, that you have joined the board, and very much looking forward to working with you. Although not officially part of today's meeting, Mr. Peter Coleman is our incoming chair from outside of the industry, but with a very deep corporate and commercial capability that is going to be very helpful for the company, particularly in the domains of at-scale M&A and overseas listings as we pass through those human efficacy readouts and the associated commercial optionality that those afford for the company. Also, very much looking forward to working with you going forward, Peter, and welcome to both of you to the board of PYC. For the record, I'm advised that a quorum is present, and I declare the meeting open. The format for today's meeting will be as follows. Firstly, I will attend to the formal business of the meeting, which on conclusion will be followed by a presentation on the company's outlook over the coming 12 months. A copy of the notice convening this meeting has previously been made available to all shareholders and sets out in detail the nature and purpose of the resolutions to be considered at today's meeting. I propose to take the notice as read. The company has received valid proxies from 198 shareholders holding a total of 225,119,341 shares, representing 39% of the issued capital of the company. After each resolution is displayed on the screen, I'll invite questions from the floor. I'll be limiting questions to the motion being considered. Opportunity will be provided for shareholders to ask questions on the resolutions. I would ask that you state your name for the record when you address the meeting. If a question is asked which, in my opinion, does not relate to the motion which is before the meeting, I will rule the question as inadmissible. In my capacity as Chair, all resolutions today will be decided by a poll rather than any vote on a show of hands. Accordingly, the resolutions will be for discussion purposes only. The poll will be taken once we have been through all of the resolutions. Ballot papers were given to eligible shareholders at the time of registration, and I will ask you to complete these. The poll will be taken, results of which will be announced to the market later today. I will further explain the procedure for the poll at that time. Note that each shareholder at the meeting can only vote for his or her personal shareholding at this time. Only proxies lodged with the company up to 48 hours before can be counted in the vote. We will now proceed with the business of the meeting. Agenda item number one is the annual report. The first item on the agenda is consideration of the financial statements, the directors' statement and report, and the auditor's report for the financial year ended 30 June 2025, all of which have been made available to shareholders in accordance with the requirements of the Corporations Act. The company's auditors, PricewaterhouseCoopers, are represented here today by Mr. Adam Thompson. In accordance with the requirements of the Corporations Act, he is available to address appropriate questions or comments from shareholders on this agenda item. Are there any questions or comments in relation to the reports under consideration? There is no requirement for a vote on this item, so we shall proceed with the second item of business. Agenda item number two is resolution number one, the remuneration report. The next item relates to adopting the remuneration report. Further details, including key management personnel, which includes directors, voting prohibitions, and the voting of undirected proxies, are included in the notice of annual general meeting dated 17 October 2025. The remuneration report is 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 take the outcome of the vote into consideration when reviewing remuneration practices and policies of the company. I now refer shareholders to the screen displaying in full and the valid proxy results. Don't have those ones, actually. We've got a blank table. Do you want to come and set the microphone? IT. All right. Results for the proxies for the first resolutions are 4.224 million against 178,000, open 85,000, and abstained 109. So that's 99.88% of the votes are in favor of this resolution. Thanks, Kevin. I now formally move the motion that resolution one be put to the meeting in the form set out in the notice of meeting. Is there any discussion on this resolution? Resolution two relates to the reelection of Mr. Alan Tribe. As announced to the market on 13 November, Mr. Tribe will be stepping down from the board at the conclusion of this meeting and will not be seeking reelection. Accordingly, the resolution has been withdrawn, and any votes cast on resolution two will be disregarded. Resolution three relates to the reelection of Professor Ian Constable. I now refer shareholders to the screen. Kevin, you might have to jump up again. Okay. Shares in favour 224 million, shares against 372,000, open 94,000, abstained at 34,000. That is proxies 99.79% in favour of the resolution. Thank you. I now formally move the motion that resolution three be put to the meeting in the form set out in the notice of meeting. Is there any discussion on this resolution? It is now time to take polls for resolutions one to three, and a representative from Automic Share Registry, Eric Mervin, will act as returning officer. Recent changes to the Corporations Act have changed the law in relation to the obligations of proxies to vote where a poll is called on any resolution. If the proxy is the chair of the meeting at which the resolution is voted on, the proxy must vote on a poll and must vote 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're a proxy holder with open votes, you may vote as you wish. You have been handed a ballot paper for the poll on registration this morning. The resolutions upon which the poll is being taken is to be set out on the ballot paper by you, that is, resolutions one to three. You should record your vote by placing a cross in either the for or against square on the paper. You should also print on the ballot paper your name, if you are a shareholder, or the name of the shareholder whose proxy, representative, or attorney you are. If you hold multiple proxies, please state this and we will complete the information from the proxies. One up three. Yeah. Thanks. Have all persons who intend to vote now voted? Good. It appears as though the voting process has been completed. The results of the poll will be announced to the market later today. That concludes the last item on the agenda. I now open the meeting to all members to ask questions. Does any member have any questions or comments? One, Greg, will you take the... If you just wait for the microphone to come. Yeah, good morning, Greg Wall. In the press recently, you talked about the company that granted support and talking about board renewal. What we've seen is the exit of two very senior people who are experienced in bringing pharma to market in America in particular. We've seen the exit of the major funder today to this business being replaced by a highly respected professor, albeit a very senior professor, 82 plus years of age, and an oil and gas man. Doesn't seem like board renewal to me. Can you comment, please? Yes, I think as I alluded to at the start of the meeting, both Professor Constable and Mr. Coleman bring skill sets that are highly relevant to the company in its journey going forward. We talked about Professor Constable's background, both as a physician with a very deep understanding of the patient interface, but Professor Constable's experience is far broader than that. He has a background in research and has founded several companies that have been on the drug development journey and made their way through to the U.S. market. He also has a very deep understanding of the commercialization journey associated with drug development pathways as a whole. In relation to Mr. Coleman, you're quite right that he comes from outside of industry. I think that is a good thing to have the diversity on the board representation as well. I think the domain skill set that Mr. Coleman brings to the company is, as we spoke about before, the at-scale M&A and the experience with dual-listed entities, and in particular, those that grow up on one market and move across to another market that is potentially closer to their home in the longer run. I think both of our two new appointments bring highly relevant skill sets to the company. I do not think the board renewal process has ended yet, and we may look to further build out the board, particularly through the course of next year, with additional industry-based skill sets that I think will stand the company in very good stead going forward for its journey. Any other questions? How does the board handle Mr. Tribe's not insignificant holding in the company now, given that he has left under those circumstances when he holds 33% of the shares? Look, Alan has been a long-standing supporter of PYC and, as you point out, retains a very large shareholding in the company. I think Alan has got a very clear understanding of the company's trajectory going forward, the gap between the intrinsic valuation that has already been created and the enterprise valuation in the company. I think Alan's interests are very much aligned to the broader shareholder base with respect to the company's need to find a pathway for closing that gap, as well as continuing to build intrinsic value as we move through these critical upcoming human safety and efficacy readouts. I do not see any misalignment there between Alan's longer-term objectives and those of the broader shareholder base in PYC. Any other questions? Anything? Thank you. I you. I suppose I was anticipating an update on how you're progressing with the number of the drugs. Are we still going to do that? Once we've closed the formal part of the meeting, we'll have a presentation in relation to where the company has got to through the course of 2025 and the outlook for 2026, 2027, yes. Yeah, because I'm sort of very keen to understand where the progression is on the various products that you're developing, in particular, kidney, which is the one that really offers the greatest return for shareholders. I'll be very interested in that. Hopefully, we satisfy you through the latter parts of the presentation. Any other questions? No. Ladies and gentlemen, that concludes the business of the meeting. Thank you all for your attendance, and I formally declare the meeting closed. Okay, on to the informal part of the meeting and the presentation of progress on the scientific programs and the company's outlook. I'm going to keep the presentation relatively brief today. We will endeavour to give you a holistic update in relation to each one of the four programs and specifically what 2026 holds for the company in relation to each of those programs going forward. Given the proximity to our recent investor webinar, what I thought we'd do is open up early for Q&A to give you control over the topics of most interest for you, and we can take a little bit more time to elaborate and give some slightly more fulsome answers in relation to those. What I propose to do through the course of this presentation is to give those who are new to the story a very brief introduction to the company and what we do, to look back on the highlights of 2025, a year in which a great amount has been achieved by the company, but spend most of the time looking forward to what's coming in 2026 and extending that vision to include 2027, specifically as it relates to our Phelan-McDermid Syndrome program as our fourth drug development asset moves into clinical development. We'll then open up for Q&A to ensure that everybody is fully comfortable with where we've got to and where we are heading. For those unfamiliar with the company, PYC makes drugs for patients who have severe genetic diseases and who do not have any treatment options available to them today. We do this in a very particular domain. We serve patients who have diseases that are caused by haploinsufficiency. What this means is that you have two copies of every gene in your body. Patients with a haploinsufficiency have a mutation or a spelling error in one of those two copies of the gene. Consequently, they are expressing half as much of that gene at the protein level in one particular cell type in the body as they need. This is a very well-suited domain for RNA therapeutics, where we can design a drug that goes to the good copy of the gene and tells that gene to make two copies of the protein when it otherwise would have made one. What we are trying to do here is to create what we call quantitative cures for these patients. If you look at a cell that is unaffected by the disease process and you compare that to a cell that is affected by the disease process but has been treated with PYC's RNA therapeutic at the protein level, you should not be able to see any difference between those two cells. The quantitative cures, they're very high-impact drugs because they are what we call disease-modifying drugs. They are addressing the root cause of what is driving that patient's phenotype or the disease manifestation. It's a very elegant approach to disease correction, but it brings you headlong into the Achilles heel of the RNA therapeutics, which is that they don't get inside cells very well, and they are only active on the inside of cells, meaning that we have a delivery challenge. This is where the other half of PYC's technology comes into play. We use a delivery peptide to take that drug inside the cell where it is active, and we use that delivery differentiation to create a competitive advantage over other RNA therapeutics players in the space. There is a very carefully considered and proximate link to the way the disease is manifesting and the use of this specific modality to correct it. We have used those two platforms to create four drug development programs. Three of those drug development programs have entered human testing, and the fourth one is anticipated to do so next year. We are now in the window where we are going to generate human safety and efficacy data for all four programs over the coming 24 months. These are the four patient communities whom we serve. I would like to extend a particular thanks to all of the patients with retinitis pigmentosa type 11, autosomal dominant optic atrophy, and polycystic kidney disease who have volunteered to participate in one of PYC's clinical trials. It is a very brave thing indeed to do to volunteer to help characterize the risk-benefit profile of a drug candidate that has never been evaluated in a human before. On behalf of the entire team at PYC, we extend our gratitude to those patient populations with whom we feel very much part of the journey together. We are very grateful to each of those individuals as well as the healthy volunteers in the case of polycystic kidney disease who have volunteered for those trials. If the potential of each of these programs is fully realized in the clinic and associated with that disease-modifying potential that we spoke about beforehand, there is a very large derivative commercial benefit to changing the lives of those patients. The four indications that you see in front of you today have a collective annual market value of $30 billion. We are playing a very high-stakes game here in relation to genuine innovation, creating therapies for patients who have no treatment options available today, with a view that we make a very profound impact in the treatment landscape because of the extent of the impact that those drugs can have in those patient populations. To give you some color, many of you will be familiar with the acquisition of Avidity Biosciences over the course of the past month by Novartis for $12 billion. Avidity are going after two different rare diseases, two forms of muscular dystrophy, both of which have a prevalence that is very similar to Phelan-McDermid Syndrome. One of the comments, we're going to look at some of the other comments of the Novartis CEO in acquiring that asset, but one of the comments that was made by Vasant Narasimhan at the time was there are two assets within this pipeline that could potentially repay that $12 billion purchase price. I think that's a particularly relevant comparison or transaction for you to be aware of because the acquisition was made on the back of phase one two data, with a further comment from the CEO that we will look at later that suggested had we waited for the phase three readout, we would have had to have paid double for the asset. The human efficacy data that is coming over the course of the next 24 months is what moves the needle from a big pharma standpoint. That is what is going to create the commercial optionality for this company and its path going forward. In addition to the patients, I'd also like to extend a very heartfelt thank you to all of the PYC staff for all of the late nights, early mornings, and weekends committed to those patient populations. It is a very long and arduous journey, one of drug development. It is referred to in the life sciences as a team sport, and it very much is. PYC has an exceptional team who are working very hard to drive impact in these patient populations, and it's through those efforts that we have been able to already achieve quite remarkable outcomes. If we look back on the top three highlights of 2025, for me, those have been the progression of the polycystic kidney disease drug program into human trials. Not only did the asset dose its first subject in the second quarter of this year, but all four cohorts in part A, the healthy volunteer study, have now been successfully dosed. We have also dosed the first cohort in part B of the study in polycystic kidney disease patients, and we expect through the efforts of our clinical operations team to have dosed the second cohort in B2 in part B of that study before the end of the year. That will leave us with one final cohort, B3, in the new year before we move through to the very highly anticipated repeat dose studies, the phase one B study in polycystic kidney disease, upon which we all have a very lot riding. The second achievement is in relation to the Phelan-McDermid Syndrome program. You have seen a non-clinical data pack here, and it's interesting that we are getting very excited in relation to preclinical results here due to the elegant and comprehensive nature of the outcomes that we're seeing. Many of you, the familiar faces who were here at the earlier investor webinars, first saw the data that we generated in the patient-derived neurons or brain cells, the brain cells that come from the children with Phelan-McDermid Syndrome. What we were able to show there is the quantitative rescue, the lift from 50% gene expression back to 100% or unaffected levels of the target gene, in this case, SHANK3. We were also able to show that the SHANK3 protein localizes after we have that increased synthesis of the protein, that it localizes to where it needs to be. It is found in the cell in the post-synaptic density where it is responsible for helping the neurons communicate with one another. Many of you will remember that quite remarkable video showing downstream of that, the restoration of the communication between the neurons post-treatment with the drug. On the patient-derived model side, we have some very elegant data. More recently, you've seen how that applies at the level of zooming out to the whole organism in the non-human primate studies. Here to answer the critical questions of when we administer the drug to a living organism, can we, at a safe and well-tolerated dose, achieve enough drug in the target regions of the target organ, in this case, the brain? You've seen those very nice results that have been generated there. Not only that, but we got very fortunate, and the non-human primate was able to show us an efficacy signal. We see target gene or SHANK3 movement in the key regions of the brain that we are then able to link across to the extent of the upregulation in the patient-derived models and the rescue of the phenotype. We have a very, very high degree of conviction now as we move that drug into clinical development that we're going to see the full potential of upregulating wild-type SHANK3 protein in children with Phelan-McDermid Syndrome. That is something very much to look forward to as that asset moves into clinical development next year, and we see the early safety and exploratory efficacy outcomes in 2027. The third achievement of this year has been the establishment of the clinical proof of concept data in retinitis pigmentosa type 11. You have seen this presented very recently at the RANSCO presentation. You're starting to see the longer-term follow-up of those patients who've been enrolled in not just the single ascending dose study and the open label extension of that, but also the multiple ascending dose study. We have now progressed those patients through to an open label extension of the multiple dose study, and we'll be seeing the longer-term 12-month-plus follow-up in relation to those patients through the course of next year, as well as crossing them over to treat the fellow eye once we have that 12-month safety package in the initially treated eye. Extraordinary things by an extraordinary team of people. I do want to call out a couple of the key individuals. Paula, I think your efforts and those of the team, not just in getting the PKD program to where it is today, but all of the thinking in relation to where that program is going, have been quite extraordinary. I think it's not well understood what the implications of a high-velocity clinical development pathway are. We have a very narrow window of time within which to optimize our dose and dose interval for the repeat dose studies, and we need to start preparing very early for the new drug application submission. There is a lot of work that goes into a comprehensive NDA pack that when you have a limited time in clinical development for very good reason, the extent of the unmet need, there are multiple parallel bodies of work that need to be synthesized, and it's quite a sophisticated undertaking. I think the team have done an extraordinary job in that indication. I think Janya Grainok and the PMS team, the generation of that data pack and the excitement that they have been able to generate amongst the key opinion leaders, the pediatric neurologists who really lead the thinking in Phelan-McDermid Syndrome to get them on board and excited about running this clinical trial, particularly because that team have moved further downstream in the drug development journey than they are typically used to. That is a really exciting asset, and as you, I think, are getting the sense, we are very much looking forward to seeing what that can do in clinical development next year. I think Sri has done an outstanding job again with multiple concurrent complex bodies of work, running the clinical trials, engaging with the key opinion leaders over in the U.S., and now preparing for the regulatory meeting with the FDA that is scheduled for the first quarter of next year to align on that registration of study format. What is it going to take to get that drug across the finish line and create the first treatment for these patients with this blinding eye disease of childhood? I mentioned before some of the commentary in relation to the acquisition of Avidity Biosciences by Novartis, and these were the two sentences that really stuck out to me. I think there is a perception amongst the ASX Life Sciences community in particular that you can sit back and wait for phase three outcomes. I am here to tell you today that that is very much not the case because of the different trajectory of precision medicines going after a genetically validated target and the fundamentally altered shape of the risk curve. The phase one two data that we generate in these programs is absolutely critical to driving propensity for these assets to be launched as first in indication and potentially best in indication drugs. That very much changes how the industry looks at these assets, which is where that commercial capability and skill set is really relevant to the organization going forward. It is these efficacy readouts that are coming within the next 24 months that are going to change the game for PYC. If we look ahead to what is coming, there is a lot here because we are a company that is running multiple programs concurrently. The ones that I specifically want to call your attention to are in the first column. In the polycystic kidney disease program, the efficacy data in the second half of next year, three to six months' worth of drug exposure in the kidney in patients. As that leads through into the first half of 2027, it is really that window, the three-month data plus, that is going to be critical in understanding the propensity for that rapid transition into the registrational study. If we zoom out for a moment and we think about what is the broad objective here, you guys know that there are two studies that are required to see an approval in polycystic kidney disease. There is the currently ongoing combined phase I, I B study, and then there is a single registrational trial, 12-month primary endpoint trial that is directed towards the volume of the kidney. That's the primary endpoint, an accelerated approval pathway. Those patients are then followed for another 12 months to look at what we're ultimately interested in, which is the function of the kidney, the estimated glomerular filtration rate. That is what we mean by a high-velocity or rapid clinical development pathway. What we're looking to do in that I B study is to show in a smaller number of patients, probably 30-40 patients, what we expect to see in the registrational trial that sits thereafter in approximately 200 patients directed towards the NDA, the same endpoint and the same outcomes. It's the volume of the kidneys in the first instance and then downstream to the function of those kidneys that you're going to be looking at next year. This is really going to captivate the interest of the pharmaceutical industry as a whole. Polycystic kidney disease is a very, very important indication. The next one that we are extremely excited about, as I spoke about before, is the exploratory efficacy data that's not coming in 2026. You'll see an IND in the second half of next year to transition to first in human studies, but it will be the 2027 data in the Phelan-McDermid Syndrome patients where we see the full potential of a disease-modifying drug at the RNA level in that patient population. Some very exciting material coming there. In Q1 of next year, we will have the meeting with the FDA where we align on that registrational pathway that we spoke about in our RP11. You will continue to see data generated in that multiple dose study, the extension study that will be running ultimately parallel with the mass registrational trial. You will be looking at the phase one two study to try and glean what is going on in the mass registrational study so that we know when to unmask that study and submit the new drug application. We can go into that in a bit more detail in the Q&A if you'd like to. Finally, in autosomal dominant optic atrophy, we basically need to get this program to where the RP11 program is today. We want to see the impact on the vision of those patients, bearing in mind that it's a very slowly progressive disease with about 12 months or more drug exposure in the retina. We have now dosed our first patient in the multiple ascending dose study. You need to wait until very late next year or the early parts of 2027 to see the meaningful efficacy data in that context, bearing in mind that that's also an open label study. As you've seen already, a very clean safety tolerability profile and some encouraging early efficacy outcomes in that patient population. With that, I'm going to stop and hand over the floor to you. Did we fulfill your expectations in relation to the update on the program? Are there any questions in relation to where the organization is heading? Thanks, Rohan. In relation to the RP11 program, have you worked out which hurdle that you want to overcome? Because in the results, I think it was early this week, there were four that you've kicked goals on. Does that sort of help you determine what your ultimate goal is going to be? Because presumably when you set the program with the FDA, you only get one shot at goal. So you've got to choose your best shot, if I'm right. Yes, I think that's right. Maybe in relation, there might be one minor qualification to the last part of the statement. There potentially is some flexibility in relation to nomination of more than one endpoint on which the FDA will have an interest on the back of the extent of the unmet need in this patient population. Certainly the conversations that we've had with the regulators today to have a look at the totality of the data. That being said, we do have to consider nomination of the primary endpoint in that study. Yes, I think we've got a very good idea in relation to what we are going to propose to the FDA in Q1. We are trying to give the information to investors very much guided by our thinking in that respect. You see the first chart or figure one in that ASX announcement looks at the mean change in low luminance visual acuity. I think to make that relatable for you, you're probably all familiar with going to the doctor's office and reading the letters on the eye chart. These patients are doing that under a low luminance setting. They are turning the lights down and getting the patients to read the eye chart. That is the low luminance visual acuity endpoint, and that is almost certainly going to be the primary endpoint that we nominate. Within the LLVA endpoint, there are a few different ways you can slice and dice it. I think what we will be looking at there is the mean change in LLVA as between the treated arms of the study and the sham control group. If we think about the design of the P3, almost certainly you will have three arms, two treatment arms at the 75 and 30 microgram doses versus a sham control arm. What we are going to be looking at there is exactly that data that you are seeing. To what extent can we see an improvement in the visual acuity of the patients who are receiving the drug, and how does that compare to what we expect to see in the sham control group, which is very similar to the natural history studies or the rate of progression of the disease in the absence of treatment? Not only do we need to see a statistically significant spread of the data between those two groups, but there is also an absolute clinical meaningfulness threshold that the FDA imposed. They want to see a 15-letter gap, which is quite a substantial gap. It is three lines on the eye chart, delta between the treatment arm and the sham control group. I think you will see something very similar to that come out of the type D meeting with the FDA in Q1. Any other questions? Thank you. On previous occasions, you made mention of a therapy for glaucoma. Yes, you want an update in relation to it. Yeah. The commentary in relation to the potential for creating a drug for glaucoma patients is in repurposing the ADOA program, PYC-001. The rationale here is, although glaucoma is not a single-gene disease, so it's not the domain in which PYC specializes, there is a substantial advantage once you have established safety tolerability profile in a patient population in a phase I study of using drugs that have already established that safety profile in other indications. You can go directly into a phase II study here to look at the efficacy profile of the drug. The concept that we were floating around was the idea of using the ADOA drug in the context of glaucoma to see whether the enhancement of OPA1, the target gene, or increasing the expression of the OPA1 protein could actually help preserve the retinal ganglion cells in patients with glaucoma, the cells that are dying that are compromising the vision of those patients. This is based on data from animal models suggesting that if you increase OPA1 expression, you can actually help those retinal ganglion cells survive. We have an ongoing body of work. Effectively, the bar for us is to build out internal conviction that we can see meaningful rescue of a sufficient number of retinal ganglion cells in an appropriate model of glaucoma preclinically. We are trying to complement those animal models of the disease with patient-derived models. What we have done is formed a collaboration with an academic group who have taken tissue samples from patients with glaucoma and created those patient-derived models with which you are familiar, retinal ganglion cells. We are continuing to evaluate the potential utility of the ADOA drug program in glaucoma. I think for us as an organization, we are very much focused on, in the first instance, the delivery of those four efficacy outcomes in the single-gene diseases because of the much higher propensity for success in the genetically validated targets. In glaucoma, we are still very interested and pursuing that body of work, but you must remember it is a more complex disease process. There are multiple things going on concurrently. The big question is, do we have the conviction that increasing the OPA1 expression is sufficient to meaningfully change the course of disease in those patients? We'll continue to update you as that data comes to hand. All right. From a commercial perspective, you've got a runway of cash, and you've got the objectives you're trying to get to. Unless one of those does come off, then you're in a situation where you're short of cash. How does that fit into those programs versus the cash in the runway? I think firstly, that's the paradigm for all drug development companies that they're facing. I think one thing that is nice about PYC is we're a multi-asset company, and we have uncorrelated risk within the pipeline. So you've got in there three different target organs that we're going after, two delivery technologies, four unique oligos, two unique chemistries. You get a lot of downside protection from a portfolio theory event. I think that's one of the other areas of excitement in relation to the Phelan-McDermid Syndrome program. Remember here, this is the two-prong MOE chemistry that's being used by Spinraza, Nusinersen, the approved drug in spinal muscle atrophy. We've got a lot of downside protection if something goes wrong within the programs. Very much exactly as you describe, we are funded through to fiscal year 2028. We've got quite a long runway from a biotechnology standpoint. You can see within that timeframe, we have got a lot of technical milestones that can drive potential upside. We're very much looking at the same paradigm as you, but perhaps with a different lens, looking at what can we achieve from a technical validation standpoint that's going to drive further increases in the valuation of what we're doing before we would look to extend the runway. As I spoke about before, you get into the realm of commercial optionality very, very quickly as you're moving through the generation of human efficacy data. We know the transactional window for these assets has been delayed in ophthalmology because it's a relatively niche area, and these are smaller indications. It is not a therapeutic area of primary interest to big pharmaceutical companies. When you get into late-stage development, when you've got compelling human safety and a good grip on the human efficacy data, that's going to open the window. Talking to the transactional bankers, it's very clear that post the type D meeting with the FDA, you are now in the window where you have the potential to outlicense those assets. We've, I think, been very clear that that's our preferred pathway going forward. I think it's also really important to know that we need to have the wherewithal and the capability to develop these assets ourselves. The phase III trial that we spoke about beforehand is very manageable in RP11 for a small company like ours. Even the commercial launch is very manageable for a small company like ours. We have the flexibility there. I think what you'll find is, as we're generating data in the polycystic kidney disease program, you're starting to get yourself into the realm of transactions very much like the Novartis acquisition of Avidity Biosciences. If you think through the relative prevalence of the indications that I alluded to in the earlier page, polycystic kidney disease is five times the size of those two muscular dystrophies combined. Very, very important indication from an unmet need standpoint. I think if you're seeing in that multiple dose study a good indication that we are going to reproduce the registrational outcomes in the P3, sitting behind it, we're going to see a fundamentally different company to what you're looking at today. You're right, but I think the downside protection is there, and we're very much looking at the upside opportunity of delivering these technical milestones over the existing funding runway. Hi, Rohan. If the magic moment in the kidney drug is when the kidney starts to reduce in size in a meaningful way, does that mean you measure it before you start and then you measure it at 12 months? Is there any point in measuring it in the middle at six months to get a clue? Is that the plan? Yes. Yes, that's right. In the single ascending dose studies, firstly, you're quite correct. The patients are screened and have an MRI at baseline to assess the volume of the kidney. In the single ascending dose studies, those patients are having an MRI at three months and four months to look at the follow-up delta. We also, as we move through to the multiple dose studies, have regularly planned MRIs of those patients to give us that continuing feed of data in that respect. That's the very nice thing about a truly objective endpoint, the size of the kidney. There's nothing complicating it there. We'll have those images processed in multiple different dimensions, not just the size, but looking at individual cyst volume, the amount of residual renal parenchyma that's present within the kidneys. We will be having a look at all of those metrics continually through the course of next year, which is why that data gets so exciting, because you are looking at it at three, six, nine, and twelve months as we are seeing patients who are receiving continual exposure to the drug candidate in the repeat dose format in the same manner as what we expect to take forward in the pivotal. You are looking at identical outcomes in a smaller patient population. Still substantial, 30-40 patients. Did you have any online? Online. I think two of them you have already addressed. Effectively, they are about the potential for accelerated approval across the different programs. I think you have already talked about the trial design for RP11 and the pathway for PKD. There is a third question, which is any positive leads from the AI program into future drugs or diseases? Sure. The AI program being the Google collaboration here? Yeah. Okay. For everybody's background awareness, we entered into a collaboration with Google Cloud to see whether we could use Google's investment in the three-dimensional modeling of proteins, technology known as AlphaFold, to design a ligand or a binder that could specifically engage with that particular protein. The idea here is that you're trying to concentrate—it's the drug delivery challenge—you're trying to concentrate your drug in a particular cell type that is expressing that protein. If we can find a receptor binding domain or a ligand to engage with it, we can append the drug onto the receptor targeting motif and get more drug inside the particular target cell. This has become an enormous area of interest to the field as a whole. The more drug that is in the target cell, the lower the dose at which you need to administer in order to achieve efficacy. Therefore, the lower the propensity for toxicity or side effect profile. We are struggling to put together all of the different elements that are required in order to successfully navigate that challenge. In particular, it is the fidelity of the in-silico or in-the-computer docking simulation between the ligand and the protein that is causing us a challenge. We remain very, very interested in that field. You can clearly see if you are across what is going on in the space, everybody is heading into this domain. We have got some more work to do there. At the minute, it is a secondary focus for us because we are very much focused on those clinical readouts. I think as we think through the evolution of the company to programs five, six, seven, eight, it remains an area of active exploration for PYC. On the potential deal parameters for the RP11 drug in 2026? Look, deal parameters, you guys get the same information that I get. I potentially get a little bit more because I'm privy to the conversations with the bankers, but I don't think there's anything in those conversations that would surprise you. If you look at the recent transaction between Eli Lilly and MeiraGTx, I think for LCA4, it's another inherited retinal dystrophy that is very rare. The potential patient population is about 10%-20% the size of RP11. They got $75 million upfront. I believe it was $300 million- $400 million in milestones, and they'll retain a royalty that's typically in the low teens, tiered royalties between 10% and 20%. I think that, I mean, if you scale for the prevalence, possibly in a non-linear format, that's around the ballpark that you'd be looking at based on the peer transactions, somewhere in that $100 million- $200 million US dollar upfront, $300 million- $500 million in milestones, and a 10%-15% royalty would be what we would consider to be the peer transactional value in that context. Now, it always depends because there are factors that influence higher quality terms. Obviously, the later stage we move, the greater the terms that we would expect in relation to the licensing of that asset. Any additional data that we can generate from those open-label extension studies that is giving us higher conviction that we can reach that stat sig and the 15-letter threshold between the treated arm and the natural history of the disease would give us a greater expectation in relation to what we would want to see back. Now, there is potential scope for trading off at-risk money from the front end to farm into a larger royalty at the back end, but I think that gives you a decent color in relation to where our expectations would be on an outlicensing of RP11. The last question that we have here is, I think, seeking some assurance about the tenure of Rohan Hockings into the future. On the back of the recent events, I have made a commitment to see the organization through 2027. In relation to the human efficacy data that we have on the screen, I'm very, very excited about the potential for patient impact here and would love to be a part of the journey as we see those results come to hand. I think what goes beyond that is going to be dictated by what we as an organization look like on the back end of that process. There is no reason why I would want to step out at that point, but I think shareholders do need to understand the magnitude of change that is going to come for PYC over the course of the next 24 months in the event that we're successful. We have an enormous amount as we sit down as a new board to grapple with in relation to the longer-term future of our organization. Very much dedicated to PYC, to its staff, very enthused about the potential for patient impact. We are at the critical juncture in relation to realization of the outcomes that are going to move the needle. I am super excited to work with our new board and chart that course together. Any other questions? No, I do not think so. Look, I think the synthesis is very positive for PYC. We have been through a tumultuous window. I think we have largely put that behind us and are very much focused on the future now. In relation to each of the four drug development programs, we are in one of those unique windows where they are all going well together. Drug development is usually a process of problem-solving. Touch wood, we happen to be at a juncture where all of the programs are showing an enormous amount of propensity concurrently. I am not sure that any of us thought that all four of them would be looking like they are progressing into late-stage studies without a hiccup or a drama. I am sure there will be twists and turns to come. As we stand here today, I think the excitement amongst the team in relation to those who are driving forward all four of the assets in the pipeline is stronger today than it has ever been. What we now need to do is, to the point before, we need to find a way of having the value recognized within those assets and evolve our organizational future on the back of the certainty that that will afford us into where we are going in the longer term. I think we have a lot of thinking to do there, but it is all exciting. A great range of options. I think if we chart that course well, we put ourselves in a very, very strong position going forward, and hopefully we drive a substantial return for all of our shareholders in the process. Two more? Two more that just popped through. Yeah. Maybe we'll call it at that. Okay. One is asking about your shareholding in PYC, and the other is asking if there's a chance that the FDA might agree to 10 letters instead of 15. In relation to my shareholding in PYC, it's a matter of public record that I don't have one today. I'd very much like to acquire one. I'll be working with Peter as he comes on board to find a window in which I'm not in blackout so that I can go into market and buy some. Very keen to be part of the journey in that respect. Also with Peter to incentivize the broader staff base from an employee share option plan. We have a huge body of work in front of us, and I think it is entirely appropriate that our staff are rewarded for the outcomes that we are looking to generate here. That is the first one. In relation to the second and the propensity for the regulator to lower the bar, look, it is a matter for the regulator primarily. Talking to the IRD specialists, I think there is a clear recognition that a 15-letter improvement, in the words of one of the IRD physicians, requires a monster of a drug to get there. It is a very high bar on visual acuity, and we see very few drugs realizing that outcome. We will engage with the FDA in a conversation in relation to what else might we be able to look at in relation to, and we touched on it before, the other ways that we can use both the LLVA endpoint, looking at the proportion of patients who are achieving that outcome. Focus on the best responders rather than the median responders. Also to look at exactly what the FDA described they will look at with respect to the totality of the data. In particular, and this is why we continue to list microperimetry, the assessment of the retinal sensitivity to light. If we see directional alignment of all of the endpoints, which we have done in the phase one, two study to date, is that sufficient in the context of an unmet need to warrant the approval of the drug, even in the context of a requirement to conduct a real-world evidence or a phase four post-marketing study in that context? It is an area of active exploration, but I'm cognizant of the fact that the regulator's opinion in this regard carries a lot more weight than mine. We will have to wait and see what the outcome of the type D meeting is. I think the general sentiment within the FDA is favorable, as everybody is aware. There is a push for genetic medicines where we have a very strong mechanistic understanding of what is driving the disease and how a disease-modifying drug is addressing the root cause of it to contemplate alternative pathways for approval. We are seeing that evolve in real time in the FDA. We will continue to work with the FDA through the various designations that we have achieved there: fast-track designation, rare pediatric disease, and orphan drug designation, hopefully in the future, breakthrough therapy designation as well, to have a conversation in relation to what is required to get this drug to patients with RP11. I cannot give a more concrete answer than that, I am afraid. One final opportunity for those in the room. Otherwise, we will consider you all fully abreast of progress in each of the four programs. No? Thank you very much for your ongoing support of the organization. I do think the team have worked exceptionally hard to put you in a position where you are going to see the outcomes in patients over the course of the next 24 months. We are quite a unique beast in the sense that you have four programs that are going to do that concurrently. It is an incredibly exciting time for us and for the patient communities whom we serve. We are very grateful for the support of all of the clinical staff, particularly the clinicians who are seeing these patients who I think have understood why these drugs offer something to these patients that no other drugs do. The momentum that we have been able to build on the back of that has then rolled through to very efficient execution of the clinical trials. That puts us in a position where we are extremely proximate to seeing the currency of the realm, human safety and human efficacy data. If we start to see compelling data in that regard, I think we're going to be in a good position. It has been complicated by the variability of the endpoint assessment and the very slowly progressive nature of these blinding eye diseases, which is a good thing for patients. That makes our life a little bit harder. It will become more black and white as we move through to polycystic kidney disease because of the objectivity of those endpoints that we've spoken about. In particular, in Phelan-McDermott syndrome, language and cognition improvements, if we see similar outcomes to what we've seen with the other RNA drugs for neurodevelopmental disorders, it's going to be a very, very exciting time. Thank you all, and we look forward to updating you on the journey through 2026.