PYC Therapeutics Limited (PYC) Earnings Call Transcript & Summary

So welcome, everyone, to the PYC August quarterly call. Just to go over some quick housekeeping first. Sorry, just admitting some more people into the meeting. But if possible, please remain on mute and have your cameras off for the remainder of the call. We're going to do about 30 minutes of a general presentation, an update for PYC for the last quarter. Then we'll hand it over to our senior leadership team who are going to go through a number of questions that you guys have provided online. [Operator Instructions] So with that, I'm going to quickly go through a safe harbor statement. So before we begin today's call, I would like to make the following safe harbor statement, reminding you that today's discussion will contain forward-looking statements that involve risks and uncertainties. These risks and uncertainties are outlined in our filings with the Australian Securities Exchange. As such, actual results may differ materially from what we discuss in today's call. We disclaim any obligation or intention to update these statements in the future. Nothing on this call should be construed as either an offer to sell or solicitation of an offer to buy or sell shares in any jurisdiction. With that, I'd like to hand over to Rohan Hockings who will lead the first section of this call.

Sorry, everyone. I was just saying welcome to the call. And thank you, Kaggen for the intro. If you don't mind, Kaggen, just looking back up 1 page, I'll just introduce the team before we go through. As Kaggen mentioned, 30 minutes of an update on progress and then move across to 30 minutes of Q&A. So I'm joined in our Perth office by our Chief Scientific Officer, Professor Sue Fletcher. And we have joining us from the U.S., our U.S. Chief Executive Officer, Sahm Nasseri; Glenn Noronha, our Chief Development Officer; and Kaggen Ausma, our Chief Business Officer. If you take us through the next page, Kaggen. I know many of you are already quite familiar with PYC's technology, but what we thought we'd do for those who are less familiar with it is just take a very big step back and at a high level, introduce the fact that if you look at the right-hand side of the page here, the class of therapeutic that our company is developing is known as an RNA therapeutic. And our RNA therapeutics have garnered a lot of excitement recently, as many of you will be aware, really because of the attraction of particular features of the class of drug, largely to do with the ability to modulate the behavior of a cell in a very precise way and in a durable way, but without making permanent changes to that cell. And so what we really are seeing now is the emergence of RNA therapeutics is the third major pillar in the pharmaceutical landscape alongside small molecules and biologics. So it's a really nice and strong macro trend towards the class of drug that we are developing. Within the RNA therapeutic class, we are working specifically with a type of RNA therapeutic known as a PMO or a morpholino. And the reasons that we like working with those are they are a particularly safe class of drug within the RNA therapeutic broader modality. They're very durable because of the stability of the backbone chemistry that is used. And they've got a range of other drug-like properties such as solubility, that make them an ideal type of therapy to be working with. The one fundamental challenge of this class of precision medicine is that they can't reach their target very well. And that's a fairly fundamental drawback for precision medicine. The reason for that is they largely get stuck on the outside of the cell, whereas we need them to be on the inside of the cell to be able to interact with their target. And so the solution, as we move across to the left-hand side of the page, is facilitated delivery. And you see more and more companies now moving into the space of the facilitated delivery of RNA therapeutics and specifically morpholinos. For those of you who follow the space, you'll have seen earlier this year the clinical validation of the PPMO modality that was created by Sarepta Therapeutics in the context of a drug on which Sue is the co-inventor. More recently, last week or the week before, I think it was, a company called PepGen who are also using CPPs to deliver the morpholinos raised USD 121 million to take their drug also for Duchenne muscular dystrophy into clinical development. And you see companies like Dyne and Avidity using antibodies or [ target modalities ] to deliver PMOs inside of cells. So it's really an emerging class of therapeutics. And PYC's technology puts us on the forefront of that class. And if you move through to the next page, Kaggen, I think I'm using more than my allotted time. So very quickly, we have 2 platform technologies, as you've seen on the last page. We are combining those across a range of different indications that lend themselves to modulation at the RNA level. As you know, we have a very clear focus on proof of concept of our technology in the eye, in the context of blinding eye diseases. We also have a very deep interest in neurodegenerative conditions, so diseases of the brain and the central nervous system. And then more broadly, we are also looking at the application of our technology and systemic applications and have got some very nice data in small animal models, demonstrating the utility of our technology in that context. So if you move down the page, Kaggen, we're just getting more and more specific here. So if we double-click on our retinal pipeline, in particular, our most advanced programs are our co-lead programs for the treatment of retinitis pigmentosa type 11 and autosomal dominant optic atrophy. I think the insight here is that we are looking to apply our technology in the context of very well-validated genetic targets. If the advantage of our technology are that it's very, very precise and specific in its target engagement and the ability to control the behavior of the cell, we want to do that in the context of targets that we know the modulation of which will rescue a disease process. And so we spend a lot of time thinking through upfront the biological validity of our targets that we are pursuing and in particular, the genetic evidence that sits underneath those targets. So for both PRPF31 and OPA1, the genetic targets in our disease indications that we are pursuing, they are what we call monogenic disorders, which means that it is a mutation in that gene and that gene only that is driving the disease process experienced by those patients, which gives us a very strong propensity for success in clinical development. So with that, Kaggen, I might hand over on the next page to Sahm.

Perfect. Thanks very much, Rohan. And just to kind of pick up on where you've come from, really over the last couple of months, we've made some really important progress on, in particular, those lead programs that you mentioned, Rohan, as we kind of move those programs closer to clinical development and as well expand our pipeline and presence in the U.S. What you see on this slide is just a summary of some of the key points of progress over the last months. And first and foremost, the start of our larger animal studies for our VP-001 program for retinitis pigmentosa type 11 is a really significant milestone in the preclinical development journey for this important potential medicine. Data from these studies will provide the critical inputs to the final step of preclinical development for this program, which we are due to commence later this year. And we remain on track, as you see on the slide, for an investigational new drug application with the U.S. FDA in the middle of next year before we then start clinical trials shortly thereafter. We'll go a little bit deeper into this program and in particular, those readouts. You'll hear from Glenn shortly. Second, over the last couple of months, we've also released some really exciting data related to then our co-lead program, VP-002, for another rare inherited eye disease called autosomal dominant optic atrophy. This program has the potential to treat roughly double the number of patients as compared to our VP-001 program, representing what we would estimate to be a multibillion-dollar market opportunity per year at peak, of course, also addressing a really important patient unmet need. Patients with these conditions go progressively blind, often leading to legal blindness by around age 40. So debilitating conditions but also very attractive commercial opportunities. Sue is going to talk a little bit more in depth about this program and some of the important data we released over the last couple of months as we look to push its development hard and fast in parallel with VP-001. At this stage, we anticipate an IND filing for this program, for the VP-002 program, just over 6 months or so after the IND filing for VP-001. The third point on the slide, we actually talked about quite a lot during our last quarterly investor call, which relates to the expansion of application of our PPMO technology outside of the eye. We continue to believe that there is significant potential within the eye for our technology but also outside. And so earlier in the second quarter, we released our first proof-of-concept data applying our technology to the central nervous system, with the goal of unlocking applications of our platforms towards neurodegenerative diseases. These diseases represent a very significant unmet patient need with over 50 million people suffering from a variety of diseases, often with a genetic route, meaning that our technology is particularly amenable to this application. We also estimate the market size for medicines to treat this population is in excess of USD 30 billion per annum, again, representing a very important commercial opportunity for the next therapeutic application of our PPMOs. We won't spend so much time on these data during the call, but feel free to check out the video from our last quarterly call where we went into this in some depth. And then, finally, over the last few months, we've really continued to deepen our presence in the U.S., including announcing our U.S. headquarters in San Diego where we've been selected to join Johnson & Johnson's biotech incubator, JLabs, which is where Kaggen and I are currently calling in from. It's really key for PYC to build a deep base here in the U.S. not only to access the critical drug development expertise to complement our discovery team's expertise in Australia but also to put the company on the map in the biggest life science market in the world. And I've spent a lot of time over the last month engaging externally with prospective investors, banks and business development partners. We've spoken really at this point now with really the top biotech investors in the U.S., more than 50 groups who are well regarded by the key biotech banks, and we've been spending significant time introducing the company and our technology to business development partners, having engaged with more than 20 of those potential pharma companies that may have an interest to partner on our technology going forward. And I'm looking forward to this really translating to value for our shareholders as we map the corporate path forward for the company. If we jump on to the next slide then, Kaggen. You might recall back in February, we shared a set of corporate objectives with you all for 2021. And we shared this specific slide also during our last call as a summary of those objectives. Organized into the buckets of execute, relating to our top priority ocular programs; establish, in terms of building our presence in the United States; and expand, in terms of expansion of our pipeline within and outside of the eye. And I'm pleased to share that we continue to make important progress against these objectives. I've talked already about the commencement starting at the top of the slide here of our larger animal studies for VP-001. This comes off the back of successful manufacturing campaigns for our PPMOs for this program, which we're now scaling up for the first preclinical -- for the final preclinical development steps, sorry, and for the commencement of clinical trials. From an establish standpoint, as I've said, we've made a lot of progress in building the team here in the U.S., both at the Board, management and team levels. And as I've said, we've been building the foundations of our relationship and presence with important stakeholders here in the U.S. And then finally, as I've said, on the expand bucket, we've shared our first set of data in our CNS discovery efforts and look forward to showing more progress over the coming months as we expand application of our technology into important new areas. And then last but not least, if we jump on to the next one, Kaggen. Looking ahead to the remainder of the year, we have a very exciting set of catalysts coming over the coming few months. Starting in blue at the top of this slide, we anticipate sharing data from our larger animal studies for the VP-001 program over the coming few months, a really important catalyst for us as we progress this program to the final step of preclinical development before we enter first-in-human trials. Glenn is going to go into more detail on really what we're looking for with these readouts. In yellow, while we've shared already some of the critical patient-derived data efficacy readouts for our VP-002 program, over the coming months, we anticipate additional readouts from patient-derived in animal models, and these data will really build deeper evidence on the efficacy of our approach and aid in selecting our lead molecules for further preclinical development. Recall that there are synergies also across our ocular programs that we draw on. For example, as we generate larger animal data for VP-001, there are learnings that can then be applied to accelerate development of VP-002 going forward. And then last but not least, on the bottom part of this slide, as we look to continue to grow our pipeline, we anticipate sharing additional data in the second half of this year related to our CNS efforts, including naming our first program for a neurodegenerative condition together with potentially naming additional ocular programs. So a very exciting coming couple of months as we execute on the programs on our plate today but also expand application of our technology into new areas. I think I'm now passing over to you, Sue, to share some additional information about our VP-002 program for autosomal dominant optic atrophy.

Thank you, Sahm. So I think you will be aware that we've talked about the autosomal dominant optic atrophy previously. It's a genetic disease. It's another haploinsufficiency disease of the eye. And the reason the eye is affected and the other cells in the body are not is because of the very high demand for energy in the eye. So deficiency of OPA1 results in severe progressive blindness. Onset is often from age 5 or at least below the age 10. And some -- there's a reasonable amount of variation in both onset and the rate of progression. But ultimately, the patients tend to lose their sight between 14 and 50 years of age. Primarily affects central vision, which is different to RP11, which starts off affecting peripheral vision. And these patients really have -- they have no therapy. It is a relentlessly progressive disease and, obviously, severely affects their ability to engage in independent living and contribute to society. So we have a disease-modifying therapy that we believe will address all patients of autosomal dominant optic atrophy caused by mutations in this gene, in OPA1. Currently, no approved drugs nor any in clinical development. And we estimate between 9,000 and 16,000 patients have this disease in the Western world. So thank you, Kaggen. Can we have the next slide? So it's caused by mutations in this gene, which primarily affect the retinal ganglion cells. These cells have a very, very high demand for ATP, which is the fuel, the energy supply themselves. And the retinal ganglion cells gradually degenerate and die, and these are the cells that then form the optic nerve. So there's no ability to transmit signal from the retina through to the brain.. So decreased OPA1 levels result in decreased mitochondrial health and the mitochondrial fragment. There's reduced production of ATP, the membrane potential, which is kind of the electrical signal that is critical in these cells, reduce oxygen consumption and an increase in these reactive oxygen species, which are so damaging to cells and apoptosis, which is cell death. And ultimately is, as I said, atrophy of the retinal ganglion cells, loss of these cells damage or loss of the optic nerve and an inability to transmit signals to the brain. So thank you, Kaggen. So with our lead molecule, the team have shown that we can increase the protein levels from the remaining functional healthy copy of this gene in fibroblast. So these are cells from patients with a number of different mutations. So on the left-hand side, we have a look at patient 1. From quite low dosages, we see an increase in the OPA1 protein. And on the right-hand side, we've got pooled data from 3 different patients carrying different mutations, showing that we can still increase the -- we can increase the protein levels from patients with these different mutations. Thanks, Kaggen. So we have our generation 1 PMO. So that's the data on the previous slide, was derived from cells treated with PMO1, and this is just the PMO doesn't have the CPP on it as yet. This is just cells in monolayer culture. So we can increase OPA1 protein, and then we have looked at additional sequences, so in kind of maturing and optimizing the -- optimizing the sequence to perhaps give us a further boost, we show that we can get increased levels of OPA1 protein with these generation 2 PMOs. Thanks, Kaggen. And the most important data is to show that we can -- we need to be able to rescue cells from cell death. So we can rescue patient fibroblasts, remain a challenge between rescuing them from apoptosis. And we showed here from 3 different patients, all of them, that the bars in black are the healthy -- kind of the healthy levels, the healthy response to these challenges. And we see untreated cells, we get 100% cell death and the cells are challenged. The treated cells show rescue of -- the rescue of the cell from apoptosis with treatment with the -- at this time with the PPMO. So we're getting this enhanced delivery to these patient fibroblasts. Thanks, Kaggen. And we have also shown that we -- very importantly, we need to be able to deliver our drug to the retinal ganglion cells. And these result in mice using our surrogate reporter, which is SMN, using the surrogate reporter readout, which is actually an exon-skipping oligo, day 7 and day 28, in 3 different doses we've shown. We get a dose-dependent in response in the retina treated with the PPMO. So this is really evaluating the function of the CPP to deliver our PMO to the retinal ganglion cells to the target. It's no good just delivering broadly to the retina, we need to ensure that we can deliver to the retinal ganglion cells. If we have a look on the right-hand side, we've evaluated 3 different PPMOs. Again, using the exon skipping reporter. So this is not a therapeutic PMO, this is just a reporter that showed very importantly that we can actually deliver 2 retinal ganglion cells, which is that layer of cells highlighted with the pink arrow there, showing the little pink dots are actually the readout showing that we have delivered the PMO to these cells and got the oligo effect, which is skipping up excellent setting from this SMN reporter. And the important thing here is we can show, with different CPPs, we get a differential readout in these cells. So we -- the PPMO 1 is our PPMO that we've been using in RP11, but we can see almost a doubling of the delivery with a third PPMO. So we have parallel programs going on. We are refining, maturing and optimizing this PMO sequence to get the very best result but, at the same time, continuing to explore the CPPs to ensure that we get the very best -- ultimately, the best combination of PMO and the CPP because our drugs, as you know, have these 2 very important components. Thanks, Kaggen. So just to summarize. We show that we can upregulate the target OPA1 protein by at least 1.5-fold increase mitochondrial bioenergetics and we didn't actually show the ATP production this time, we showed it last time, I think, in a dose-dependent and mutation agnostic manner.. So different mutations, different patient cells, different mutations, we are getting this consistent upregulation of the protein. As I said, very importantly, we need to be able to protect these patient cells from apoptosis, gained in the mutation agnostic manner. And this is the critical function deficit that's observed in patients with autosomal dominant optic atrophy. And we really are getting levels of rescue close to those observed in healthy cells with no challenge. And we've also shown with our CPP, we can effectively reach the target neural retina cells in vivo and specifically delivered to that retinal ganglion cell there that is very, very important in this disease. And this is compared to alternative approaches using more traditional ASOs, which have limited ability to reach these cells at very much higher doses. And this really -- the benefits from this -- from the positive attributes observed in the profile of these CPPs, the PYC CPPs, is paramount in us being able to move these programs forward. Without being able to deliver our PMOs to the target cells, we really wouldn't be in the game. So this is so critically important and why we are putting so much effort into continually maturing and optimizing both the CPPs and the PMOs. So thank you. I think I hand over to Glenn now. Is that correct, Kaggen?

Perfect.

Thank you, Sue. So from this wealth of early information, we'll -- we are in a -- have a rich choice. We will get to select a lead candidate from the information that we'll continue to optimize. So in the later part of this year, as we progress toward the second half that we've begun of 2021, we'll start to evaluate efficacy as well as safety in both the patient-derived models as well as in animal models. We'll finish the lead selection in the early part of next year. And at that time, we'd have gathered information on tolerability, on efficacy as well as biodistribution. So we'd be able to make a choice between several lead candidates, which Sue has been talking about, and presenting the information that's leading up to their choice that will go into these animal studies. We'll then begin all through 2022, we'll begin our IND-enabling studies, trying to find dose finding for the tolerability, leading up to the GLP toxicity for the lead molecule, with this culminating in the IND filing with the U.S. FDA sometime in the first half of 2023, which then will lead to the beginning of our clinical development program where we'll dose patients in an interventional dose escalation study, which will begin soon after we have filed our IND. If we go to the next slide, Kaggen. So I'm going to focus the rest of the conversation on the first program, which is our lead program, VP-001, which is for the treatment of retinitis pigmentosa type 11. So as everybody knows by now, retinitis pigmentosa type 11 is a disease that is -- falls on the broad classification of a rod cone dystrophy. So rod cone dystrophies have a commonality in terms of their phenotype. They're characterized by night blindness and peripheral vision loss, eventually losing -- leading to loss of central vision. Manifestation is usually between the ages of 10 and 20, and then slowly progressive blindness from peripheral to central blindness within the framework of this disease. There are no approved drugs for this particular disease nor are there any in clinical development currently. There are between 4,000 and 8,000 patients in the Western world, and that includes Australia, the U.S. Canada, the EU 5 as well as Japan in terms of what's viewed as this patient population. And as we mentioned, there's a high unmet need. If we go to the next slide. So I've picked out one of the slides that has been shown previously. What we are showing here is that when we correct this particular problem in a haploinsufficient disease by increasing the production of healthy PRPF31 protein, this is a disease in which you've got a healthy copy and an unhealthy copy, and we're increasing production of the healthy copy of the PRPF31 protein. So if you focus on the left-hand side, you see what a healthy set of RPE cells looks like. In the middle, you see a patient set of RPE cells. And you'll notice that the layer has lost its structure, and it has losses in function as well. The treatment with a single dose of VP-001, our lead candidate, shows the restoration on the right-hand side of the structure looking more like the healthy cells structurally. But when you measure functional measures, I'll mention one, for example, if you look at the electrical resistance between cells, you'll notice that it's normalized. So in the measurements we look at, both structurally and functionally, we're able to show that there's a correction in these functional measurements in addition to the RPE regaining its normal structure. This is actually a really substantial result because the damage to the cells are what lead to blindness eventually because the RPE cells are critical in the visual path in terms of their interaction, the photoreceptors and their ability to maintain structure and then function is critical in these patient slides. We go to the next slide. We have constituted a clinical advisory board that's just come together. Mark Pennesi from Oregon Health Sciences (sic) [ Oregon Health & Science University ]; Jacque Duncan from the University of California at San Francisco; Fred Chen, who's local in Australia at the Lions Eye; and David Birch from Texas Retina. All 4 thought leaders as well as subject matter experts within the inherited retinal disease community are helping us in terms of this particular program, and they'll be guiding our clinical development in terms of both our strategy as well as our execution of these studies that we're going to plan and execute in the near future. If we go to the next slide. We have a number of events that are occurring all through the rest of this year and through next year. This is a busy slide. So I'm going to point out some features. We're looking at rabbits and primates as the 2 larger eyes and larger species that we're evaluating. We're going to get biodistribution information. We're going to get dose-finding toxicity information. These pieces of information will help us to design our GLP tox studies that will begin late this year, early next year. And the idea would be that we will then move this information to design what our human studies are going to look like. We're well underway in our dosing of these rabbits and primates, as Sahm pointed out in the early part of the study. And there are a number of outcomes we'll be looking for during the course of these studies, all to guiding what the human dosing is going to look like and how to support those human studies through the filing of our IND. Okay. I want to summarize what we are looking for in our larger animal studies. We'll be looking for the distribution of the drug within the eye, that we need to reach the back part of the retina. We need to get to the RPE cells. So that will be one of the outcomes we'll be looking for in our biodistribution studies. We'll also be looking to get what are tolerated doses and where we find toxicity in order to guide our first-in-human clinical trial dosing because there will be a way we'll scale those doses and then calculate what the human doses look like. We're looking for what the frequency of dosing is going to look like, what our base case would be, what our upside case would be. And we're looking to see whether we need to dose 3 times a year or twice a year or less frequently than that. And then what we'll also be looking for, and we have some preliminary information to support this, we want to show that we can engage our target and that can we engage in exon skipping in these larger animal eyes, and we have preliminary information that supports this particular outcome. If we go to the next slide. I think I'm passing this back to you, Sahm, at this point.

Thanks, Kaggen, for unmuting me. Thanks, Sue and Glenn, for walking through our -- and we like to think of them as 2 lead programs because they're really tracking and learning off each other as they progress. Around about 6 months apart in terms of IND filing, but we're on track with VP-001 for mid-next year and for VP-002 just over 6 months after that for IND filing. So if I kind of step back from everything that we've talked about. This year is a really transformative year for the company. It's a very exciting time for PYC. We're truly progressing our science further than ever before and clearly now a multidrug biotech company, which has been a significant evolution for the company over the last 12 or so months. Our technology has broad potential, and we look forward to showcasing that through additional ocular applications, building on the momentum we already have but also as we move into new applications, in particular, in the CNS, which is an important area of new focus for us. And finally, I believe we're bringing the right team together across Australia and the U.S. to create a really one-of-a-kind biotech company with the unwavering goal of unlocking the full potential of our distinctive science. And you heard a little bit from Rohan at the beginning talking about the RNA therapeutic realm. We're really in the right place at the right time. And so we have a tremendous opportunity here to help this great science reach its full potential. I think with that, we wanted to spend the remainder of this call working through some questions that have been asked. So I think I'm going to hand over to you, Kaggen, to help facilitate that section of the conversation.

Fantastic. And thank you very much, Sahm, Glenn, Sue and Rohan. I always say, I think at this point of the call, it's a bit of a privilege for the 5 of us to come and have this conversation with all of you on the call today. It's -- there's a lot of other very, very hard-working scientific staff, support staff, both in Perth and now in San Diego, who sort of support us in getting here. And I think our usual thank you is even more required this time around as we continue to progress even first, further and even faster than we ever have. So I'd like to initially start off with just a thank you to our team. And actually, on that point, I might throw to a question that we've got from the investor exactly on that point to yourself, Rohan, which is, could you explain the changes made in the Perth lab staffing and direction of the research since the last investor call? And I'll just let you unmute.

Thanks, Kaggen. Yes, look, I think we spoke about last time, the significant growth trajectory that we've been on, in particular, in the lab operations staff in Perth as we push closer into clinical development and expand our interest in other ocular indications and then into novel target tissues that Sahm has just spoken about. So we undertook a very significant scaling of the operations with a move from about 25 to 60 staff. I think the change since the last call has been the build-out of the team in the U.S. So Sahm, I do think we're up to about 6 or 7 permanent staff and then a whole bunch of supporting contractors and consultants who sit around the U.S. operations at the minute. And that's really where the change has been since the last investor call.

And to sort of follow that one up actually, and otherwise the perfect segue to Sahm, which is a follow-up to that question there, which is, could you please explain where you would like to see the U.S. operation reach in the next 12 months?

Yes. Thanks, Kaggen. And I'll just check, I'm not muted. Okay, very good. Thanks, Kaggen. So I think if we just kind of step back and ask ourselves why did we set up shop in the U.S., it was really for 2 key reasons. Number one, access to the important drug development expertise to complement our discovery team's expertise in Australia. This is a team sport when you think about drug development. And I kind of think of these 2 pieces as like 2 pieces of the puzzle that neatly fit together to create a full picture. It's critical we bring those 2 components of expertise together in order to efficiently progress the development of our programs into the clinic. I'm pleased with the progress we've made in building the team out in the U.S. We have around 6 staff here as part of PYC in the U.S., as Rohan has mentioned. You've heard from Glenn today. Glenn has been doing a tremendous job leading the development pathway for our medicines in close collaboration with Sue and our team in Australia. I think over the coming 12 months, we'll see the team grow as we get closer to clinical development and as we take on more formal preclinical development programs as the pipeline expands. But we intend to do that in an efficient and staged appropriate manner, that growth in staff, just to manage spend with the capability and resource needs ultimately to progress our programs effectively. So that was kind of reason number one we set up in the U.S., was to access that critical drug development expertise. Reason number two really was then to help put PYC on the map in the largest life science market in the world and specifically thinking about banks, prospective investors and potential business development partners. And we spent a lot of time, as I've mentioned, since the beginning of the year, really engaging with those stakeholders, with the simple goal of finding the right kind of partners that are going to help us unlock the full potential of our science and, in doing so, to help close the value recognition gap. I've often spoken in previous forums that if we compare ourselves to some of our peers in the U.S., in the RNA therapeutic space, often at similar stages of development to PYC, we see an opportunity to increase our value recognition by up to threefold. And so I think part of the other reason to be here is to help close that gap and to find the right kind of partners to help unlock the next chapter of our company. And I anticipate making good progress against that over the coming 12 months. Thanks, Kaggen.

Thank you very much, Sahm. So switch a bit to the science. I think we've got another great question here. This time, I'll throw this one to you, Sue, around -- or how is PYC thinking about the OPA1 program? Are there animal models that you'll be able to use? Or will it rely on patient-derived models much like PYC's lead program, VP-001?

Thanks, Kaggen. So the answer is yes to both. On all research of this type, there is no perfect animal model for human disease. It doesn't matter which model you look at, none of them are perfect. So what we do is we take the best we can from each of the models we have available. It's very, very important to use patient-derived models because this allows us to evaluate our drug against different disease-causing mutations. And we are fortunate with OPA1 in that it's ubiquitously expressed. So we find it in every cell. So we can do a lot of our preliminary discovery in skin fibroblasts, which are plentiful, they grow easily, they're not costly to use. So we do initial discovery in those cells. But in terms of rescuing retinal ganglion cells, which is [ our end ], we actually need to look at that target cell ideally from patients. So that's where we use the models that are derived from the induced pluripotent stem cells that are differentiated into retinal ganglion cells, and we can then look at the biology of those cells when they are being treated with our drugs. So very, very important, that will allow us to show we can actually rescue the bioenergetics. We can look at oxygen consumption. We can use some very high tech and very nice systems to evaluate the cell biology. We also do need to look at animal models because we then need to see that our drug in its final combination or the couple of lead combinations of the CPP and the PMO traffic through the vitreous, get to the retina, distribute across the retina, and exerting effect in the retinal ganglion cells. So we can use healthy mice to look at the distribution of our drug and delivery. And we are fortunate in that we've shown in mouse cells that we can actually upregulate OPA1 in healthy cells. We can actually get a little bit of an uplift in protein production. So that is very, very useful. And we are fortunate in this case that our lead molecules, a couple of our lead molecules, work across human cells and mouse cells. That's very, very -- that's very, very useful. There are models available for this disease, and that is something that we will look at. But we do know that the drug is likely to work in mice. We can then use mouse models, they're actually overseas models, but at the time, we have a fantastic collaboration with some researchers in the U.K. And in fact, those experiments in patient-derived retinal ganglion cells are underway. They already had the IPCs, and they have the protocol to differentiate these cells. So we've shipped our drug over to our collaborators in the U.K., and those experiments are underway in patient-derived retinal ganglion cell models. Sorry, bit of a long-winded answer.

I'm going to ask a quick follow-up to make it even longer, Sue. Because I guess for our lead program, we've been incredibly fortunate with the help of Fred Chen and his ocular tissue engineering lab to help us with RP11. And then you mentioned our collaborators there in the U.K. It would be great to explain who exactly these collaborators are and how excited we are to work with them.

So Patrick, you've all known, is a lead expert in OPA1. He's a clinician. He sees a lot of patients. And his long-term collaborator, Mike Cheetham, is the academic side of that collaboration. He is a researcher who has been developing these models, collecting patient cells, reprogramming these cells to induced pluripotent stem cells and differentiating them into the [ iPSCs ]. So they've already had all of these models and processes and assays in place, which is fantastic for us. It was just a case of us shipping over some of our lead molecules for them to test in their patient cells. So we are very eagerly awaiting those results. And we are following on. We have additional patient models from Australian patients, and those are in progress. But it is a very long procedure during the reprogramming and then the differentiation into the retinal ganglion cells. So that work is under the way here as well but a bit further behind the U.K. So we will have a number of different models from a number of different patients with different mutations to evaluate our lead molecules. And from those, we will be able to select a lead candidate or a couple of candidates to take forward.

Fantastic. Switching tune a little bit then to further down the pathway to the clinic. I was thinking, Glenn, we've got one question here as well around when we're next planning to engage the FDA for our lead program, VP-001.

We're intending to speak to the FDA likely toward the end of this year in terms of our engagement on our lead program.