Morning, ladies and gentlemen. Welcome to the 2022 Annual General Meeting of PYC Therapeutics Limited. My name is Alan Tribe. I'm the Chairman of the company. With me here today, I've got the Chief Executive Officer, Rohan Hockings, the Company Secretary, Kevin Hart, and also in the room we've got our Chief Financial Officer, Andrew Taylor.
Apologies from our two U.S. Board Members. Because of the time differences, I think you'll understand that it's a little difficult for them to attend. I gave them a bit of a leave pass on your behalf, so I hope that's okay. Should there be any questions or issues you wanna raise with them, I'll be happy to take them, and they will be more than happy to respond. There is a quorum present, and I therefore declare the meeting open.
Now, the format of today's meeting will be, firstly, my Chairman's address, and then we will attend to the formal business of the meeting. After that, there will be a presentation by Rohan, who will give an update of the company's progress and the outlook going forward. A copy of the notice of the meeting has been circulated to all shareholders and sets out in detail the nature and purpose of the resolutions to be considered today. I propose to take that notice as read, if all acceptable. Thank you.
No, thanks.
Hello. To my address, first of all, then, PYC is part of a major step change taking place in precision genetic medicine. The pipeline of RNA drugs that we're developing use-
Lost it. Hi. Lost it.
Stop 1.
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 the resolution.
Very good. The valid proxy results. These are the votes that we've got for and against the resolution already. It should be noted that on the remuneration resolution, 0.19 of the votes cast are voting against the resolution. Is there any discussion upon this resolution at all? Any questions? Very well. In my capacity as Chairman, I call for a poll. That poll will be taken once we've completed the formal part of the meeting. Resolution number two, relates to the re-election of me as a director. For purposes of considering this resolution, I'll hand over the chair to my colleague, Rohan Hockings. Thank you. Bye.
Paula, can you just help Carol enable screen share? Thanks, Alan. Agenda item Number three, Resolution two, re-election of Mr. Alan Tribe. I now refer shareholders to the screen displaying the resolution in full and the valid proxy results. I now formally move the motion that Resolution two be put to the meeting in the form set out in the notice of meeting. Is there any discussion on this resolution? A poll on this resolution will be taken once all of the resolutions contained in the notice of meeting have formally been put to the meeting. I hand the chair back to Alan.
Agenda item Number three is resolution-- Sorry, we've just done that. Hang on, let me move on. Agenda item Number four, Resolution three is the approval of a 10% placement capacity and refer shareholders to the screen again displaying the resolution and the proxy results. I now formally move the motion that Resolution three be put to the meeting in the form set out in the notice of the meeting. Is there any discussion on this resolution? No. Very good. In my capacity as chairman, I again call for a poll, and the poll will be taken once the formal part of the meeting has been completed.
That being the end of the items on the agenda, it's now time to take the polls for Resolutions one to three, and a representative from Automic Share Registry, Eric Mervin, will act as the Returning Officer. You've met Eric on the way in. 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've been handed a ballot paper on registration this morning.
The resolution on 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're 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'll complete the information for the proxies. We'll just complete the voting process. Very good. Everybody who wants to vote has voted. Okay. The process, having been completed, I declare the poll closed. The results of the poll will be announced to the stock market later today, as I said earlier.
That concludes the last item on the agenda and the dry part of the meeting. I'll now open the meeting to all members to ask questions, bearing in mind that Rohan will be coming along to make a presentation immediately afterwards. Are there any questions for anybody? Okay. Ladies and gentlemen, that concludes the business of the meeting. Thank you all for your attendance, and I formally declare the meeting closed, and hand the meeting over to my Co-Director, Chief Executive Officer, Rohan Hockings. Thank you.
Thank you, Alan, and welcome everyone. My name is Rohan Hockings. I'm the CEO of PYC. Before we begin, a couple of formalities. I'd like to draw everybody's attention to the forward-looking statements disclaimer that was available at the start of the presentation, and also to let everybody know that the contents of this discussion are being recorded.
There are two primary objectives for the session today that I want to communicate across to you. The first of these is that amidst the contextual backdrop of something of an annus horribilis in the life sciences market generally, PYC, as a company, continues to deliver on the strategy and implementation roadmap that was set out when this board and management team came in place around four and a half years ago now.
The second element that we want to get across is, as the company now is making the progress through to completion of the ambition to become a clinical stage multi-asset company, we are looking to the next horizon for PYC. Very much what is involved here is an aspiration to move towards a multiple clinical asset company, pushing more than one program through human safety and efficacy readouts in parallel. We are lifting the vision now to the next stage of the journey for PYC, and that stage is bookended by two very important features from a shareholder perspective.
The first one is that we are operating in the domain that has the highest propensity for success in clinical development of any modality in the facilitated delivery of RNA therapeutics, but also in the context of any target indication in monogenic disorders or disorders that are caused by mutation of a single gene. That's highly relevant from both a shareholder perspective, but also the patient perspective and the impetus to move these therapies through to market.
The second comes at the back end. What PYC focuses on from a strategy perspective is first in class and potentially disease-modifying therapies. We'll come later to the issue of the disease-modifying therapy and why they are so important from a patient perspective. The other key, I think, from a shareholder perspective, is that these are first in class therapies.
We are not looking here when we consider the downstream end of the value chain at the market around how much of the market we are going to take, but how quickly, rather, we are going to take that market. Those two are very important considerations for shareholders. We're going to touch on all of those in a little bit more detail. The basic framework for today's conversation is to give a brief introduction or re-introduction to PYC, depending on where you are in the journey, but cognizant that this will be the first exposure to the company for some shareholders.
The second is to take a step back and look at the journey to date against the strategy and the implementation roadmap that was set out, that I mentioned earlier, by the board and management team when we took control of the company in 2018. Where have we come from, and I think even more importantly now, where are we heading as we move into clinical development and start to turn the focus from the lead program that Alan has spoken about, Retinitis Pigmentosa type 11, to programs two, three, and four, and then we start to consider the next wave of therapies. If those are wave one, what is going to come behind them? What's happening in the macro environment that informs the evolution of our strategy?
How does that inform where we're heading for that next wave of programs that are coming through? We're gonna do all of that despite the investor sentiment being profoundly negative in the context of the tech sector and life sciences generally. There is, in fact, a very strong macro trend in support of RNA therapies. RNA therapies are set to become the third pillar of the pharmaceutical industry, alongside small molecules and biologics. We are actually here in the context of a very supportive macro environment, despite what you've seen in the share price over the course of the last 18 months, and share prices generally, with the index in the U.S. down around 60%.
That's something that is very important for us because it informs why is the company espousing an opportunity to throw out the spinnaker and benefit from the very strong tailwind in the context of the carnage that we're observing in the markets. It's important to reconcile the commercial and the technical paradigm in that context. Firstly, in terms of what the company does, there's a fairly simple statement up there that covers it in its essence.
PYC discovers and develops RNA therapies to change the lives of patients with genetic diseases. There's a little bit more to it when you start to unpick that. We were originally a drug discovery company. We are now a drug discovery and drug development company. We are perfectly happy taking our assets to those patients who have that urgent unmet need that we are looking to address independently.
If there is a commercial and a strategic rationale, ideally a combination of the two, for going in partnership with another party, we are very open to doing so. We get the benefit of creating the intrinsic value for shareholders, and we're going to have a look in a moment at the case study of how that has played out in the context of another genetic medicines company that has decided to go it alone.
Also it's very important for shareholders to understand that the BD window for genetic medicines assets is earlier than the industry standard. You don't necessarily need to wait for the phase II readouts that the industry as a whole look out for. It's very much in the context of first in human studies or phase I/II, where genetic medicines are in their prime from a commercialization perspective.
We're going to have a look at a very recent example of a peer transaction that has occurred in the space. The second element is we are looking here to change the lives of patients with genetic diseases. We don't pick indications where there is not a very severe impact from a quality adjusted life perspective of the patient population.
We're going after the more severe end of the disease spectrum, and that's why it feeds back into the logic of the very rapid uptake that we see in the genetic medicines market for these in-indications. If you think about it from a patient perspective, you go from a paradigm where the standard of care is genetic counseling, to having the potential for a disease modifying therapy that addresses the root cause of your disease.
It's very much a paradigm shift that we are pursuing here. We're not looking in American parlance for the base hit. We are swinging for the fences, and I don't think we have made any secret of that fact throughout the course of the journey. A little bit of a contextual background as to why, with a technology that is pushing the boundaries and the frontiers of science, why do we focus on such small patient populations?
I think that is a paradigm that some people struggle to get their heads around. Whilst rare diseases are individually rare, collectively they are incredibly common. About 7% of the population has one. They tend to be extremely severe in terms of their implications, and they also tend to disproportionately affect the pediatric population or children. The problem historically in the industry has been because these are small patient populations, they are underserved from a therapeutic options perspective. Drug developers have typically decided that these patient populations are too small to make a therapy for.
The industry has made a decision that we don't want an n plus one cancer therapy that changes the life expectancy by a very subtle margin. Nonetheless is an improvement on the standard of care. What we need are treatment options for patients who have none, given there are a very large number of them out there. The way they've done that is by incentivizing drug makers to make medicines for orphan indications or patients with a rare disease.
That helps to explain the commercial paradigm of why payers are willing to accept pricing, median orphan drug pricing of U.S. $150,000 per annum. That's an important contextual piece for the investors in PYC and rare disease companies generally to understand. PYC's focus, and I mentioned it before in the context of the first in class therapy, is very much on those patients who currently have absolutely no treatment options available to them today. The interesting thing here is you get a very good understanding of the competitive landscape based on what's going on in clinical development. If we have understood and designed our clinical trials appropriately, we effectively shut the gate on the competition as we move through the IND.
That is a very clear benchmark that you are likely to be the first person to market in the event that you are successful in clinical development. In the context of a highly uncertain, highly competitive landscape, you actually get a bedrock of certainty as you start to move through the investigational new drug filing. That, for the benefit of everyone who's not so familiar with the clinical trials development process, that is effectively the tickets to start the first in human studies that we are very proximate to in the context of the RP11 program right now.
PYC's technology fundamentally addresses the Achilles heel of precision medicines. There is an existing class of drug, an RNA therapeutic or an antisense oligonucleotide, that is incredibly potent and also very precise. It's an ideal molecule from that perspective. It's got an Achilles heel in the sense that it is not able to reach the space within the body where it is free to engage with its target. It doesn't penetrate cells very well. It's got the perfect properties that you would want in a drug other than the critical weakness that it is not able to reach the target and it is required to, and through which it exerts its effect.
PYC's technology is a drug delivery technology that enables that existing approved class of therapy, firstly, to chaperone to the target cell of interest and secondly, to cross the cell membrane, so it is free to engage with its target on the inside of the cell. This is an important paradigm for investors to understand because there are many naked antisense oligonucleotides already on the market today.
We are taking something that has already made it in the context of some disease paradigms, where a sufficient amount of drug is able to cross the cell membrane and reach its target to exert a therapeutic effect. We unlock a whole new paradigm of, or level of treatments, indications that we can create or potentially create a therapeutic benefit for because we are getting more drug inside the cell.
That is why the strength of that macro trend has been so strong for the RNA therapies generally. We are using that, as I mentioned before, to create this pipeline of first-in-class genetic therapies. The company's strategy, though, goes beyond the drug delivery technology. There are some additional dimensions that it is important to understand in the context of exactly what we are doing in the pipeline.
We've articulated the strategy previously, and we're not going to go into that in depth today beyond the monogenic elements. What we are really looking for, though, in very simple terms, are intracellular protein deficiencies. The two components of that, we're looking intracellular because we, through the delivery technology, get a very broad reach to all of the target cells within a target organ.
We are using that, linking the advantages of the delivery technology to where they are best applied. If you're getting into every cell, go after the hardest indications where you need to get into every cell in order to fix the problem, as opposed to secreted protein deficiencies or other disorders where the cell is making a protein, but it is then excreting them outside of the cell. The second element of that is protein insufficiency disorders.
There are lots of technologies out there that can knock down an aberrant protein, so you can reduce the level of expression of a particular gene in a particular cell. There are many different ways of doing that. There are also an increasing number of ways of introducing a new gene into cells through DNA or gene therapies. We are not choosing to be competitive in that domain right now because we are going after a competitive white space.
What we are looking to do then is increase the level of gene expression in haploinsufficient diseases where a patient has a mutation in one copy of a gene, where everyone has two copies of the gene in every cell, and you can neither overexpress that protein, so you can't go beyond the level of protein expression afforded by two good functioning copies of the gene, but you also can't have one functioning copy of the gene. It's called the Goldilocks paradigm. We don't want too much gene expression, and we don't want too little either. This is a very, very well-defined domain within the pharmaceutical industry. These drugs are associated, as I mentioned before, with the highest prospect of success in clinical development.
A second element that is critical to understand is because there is no standard of care available to these patients, we have a potentially faster path to market, the prospect of two clinical trials rather than three. We are accelerating through the clinical development pathway. If you have a look at drugs that have gone on this journey before, Nusinersen or Spinraza for spinal muscular atrophy is a very pertinent example.
Where the patient population has no treatment options and a new therapy comes to market, you see a very rapid uptake of that therapy in market. You're looking at an 80% or thereabout peak sales projection hit within 24 months of launch of the drug. In the context of multibillion-dollar markets, that is a very attractive commercial paradigm in which to play. We've spoken previously about the median orphan drug pricing and why that has been a priority for payers. In terms of what PYC has done with its pipeline and where we have chosen to apply our technology, I think everybody is quite familiar now with our RP11 program.
This was the flagship asset that enabled us to get very close now to realization of the horizon that we set for ourselves in terms of becoming a clinical-stage multi-asset company. What you see in the white box is where we anticipate getting that asset to within the course of the next 12 months. I think it's clear to everyone that we have an ambition to initiate a combined phase I/II clinical trial in the RP11 program next year.
What there are increasing levels of excitement within the organization about are what comes next, programs two and three, and what we're looking for in terms of the next wave of the therapies that are in the earlier discovery domain. ADOA is exciting because it's a larger patient population than RP11. It's also exciting because we can leverage a lot of the data from the RP11 program, given the commonality of the target tissue between program one and program two.
We can skip ahead through inference. It still needs to be proven there's no shortcut in the process. We can glean a lot of information from the progress of the RP11 program and the non-clinical data pack that we generated in support of it. Questions like in the large animal studies in rabbits and non-human primates, will this drug molecule traffic to the target cell of interest?
How much will penetrate the cell, and how long will it stick around? Those are questions that we get a lot of insight to on the back of what's happening in the RP11 program. It's more advanced than what it might seem in that context. We're gonna touch on a conversation shortly about an application in the second target tissue. One thing that the U.S. investors are always particularly keen on is the scalability of our platform technology. Fantastic what you're doing in the eye, but can you show me the potential to move to different indications, different organs in the body?
There's some very interesting work going on in another central nervous system rare disease called Angelman syndrome, that has got a very similar pathogenic mechanism in the context of being a protein insufficiency disorder or a disease caused by low levels of expression of a particular gene in neurons that give us a very nice clinical and commercial proof of concept for the naked antisense oligonucleotide. A high degree of conviction that this asset will make it into clinical development because it is the same class of drug by the same route of administration for the same target cell in the context of the same pathogenic mechanism.
It is just the naked antisense oligonucleotide, and you have seen the data that we have generated demonstrating that we can increase the expression of the underlying gene responsible for causing Phelan-McDermid syndrome in the form of SHANK3 to 2.2 times the baseline level. If you think about having two copies of a gene, you're getting 100% protein expression.
If you get a mutation in one, you're losing 50% of that expression. If you can then engender from the good copy of the gene a 2.2-fold increase in the protein expression, you are taking the expression levels of SHANK3 back to what you would see in an unaffected individual. As I mentioned before, the organization will take a breath, have a look at what's going on in the macro environment, and then decide what programs four, five and six are going to be.
Wave two of our clinical development assets. The nice thing here is we are learning the lessons of the clinical development journey, the non-clinical development journey, and how that informs the clinical development journey from each of the assets. Every asset that PYC puts into clinical development will be better than the last.
We are also getting more efficient in the process and building out the capabilities within the organization to share insight about particular parts of the value chain, how they inform what's going on in other domains, and how we integrate as a team to create differentiated assets for these patients. This is the second part of the agenda items that I set out, taking a step back and having a look about where we have come from as an organization since 2018, when Alan and I took our positions on the board and management team respectively.
Importantly, where we're heading from here as we draw the ambition to become a clinical stage company to a close. We spent the early years looking at a platform technology that had some data in support of it, but really was lacking a strategy in relation to how is it going to be applied to make a product. Over the first couple of years with the early development parts, the discovery dimensions of the programs, bringing the two parts of the molecule together.
As you know, we've had a very clear focus in the course of the last 24 months on creating a molecule that is ready for the clinic. As that asset progresses into first-in-human studies, we are now turning our vision and aspiration to scaling our technology of multiple assets, moving through first-in-human safety and then efficacy signals. Led by the RP11 program, but as fast followers in ADOA and Phelan-McDermid syndrome.
As I mentioned before, that's exciting, not just because we're going to generate data in humans for the first time, but because this opens the traditional window of business development opportunity for genetic medicines assets. This is a lovely review article that was published last month. The reference is at the bottom of the page here, you can go and have a look at it independently. As I mentioned before, it's another disease that likely you've never heard of, Angelman syndrome.
This is a disease of neurons in the central nervous system. What's important here is not so much what's going on in the context of Angelman syndrome or a CNS indication specifically, but much more to give you some color on the strength of that macro trend towards RNA therapies. The excitement here that you see in the context of the antisense oligonucleotide modality.
Short strands of genetic code that can alter protein expression in the brain. Looking to do exactly what we are trying to do here, increase the expression of the target gene. Why this is so important is because it's an advancement in the accessory pathway or supportive therapies that were previously being investigated. Our drugs don't look to address one element of the patient's phenotype or the way a patient experiences a particular disease process.
Our drugs aim to address the root cause of what is driving that disease process. For patients, this is increasingly what they are demanding. As they observe this revolution in genetic medicines, this is where the patients want to be. There's a particularly pertinent comment from a research scientist whose child has Angelman syndrome in this article, suggesting that the patients deserve a potentially disease-modifying treatment in this context.
It's a very similar message that we are hearing when we talk to the patient advocacy groups and the clinicians in the different indications that we are targeting. This is a nice illustration of a genetic medicine that has just gone through its IND submission process. If you look at the sentence down the bottom, first IND clearance was received last month. This is an article from October, so last month as well. A phase I/II trial is being planned, but the timeline has not been set. What you're seeing here is a pharmaceutical company that is not known for playing in genetic rare disease space, moving into this domain through an acquisition of this company.
You can see that the total quantum there, expressed in U.S. dollars, is roughly equivalent, depending on the exchange rate of the day, to around AUD 1 billion. The patient population, with the indication that they are targeting here, is roughly 20,000 patients in the Western world. It's very similar to the ADOA program that sits second in PYC's pipeline and is expected to have around 16,000 patients in the Western world.
This is the part that I think the Australian market struggles to understand, and I think is part of the reason that Alan spoke about beforehand around the disconnect between valuations of the precision medicine companies in the U.S. and what we see on the Australian market. We're going to look shortly at a group that has gone on the journey without the support of a third-party partner.
Before we do that, I think it's important as we look at their evolution as a company, their progression through clinical development and what happened to their market cap as they went on that journey to set out what PYC hopes to achieve in the coming 12-month window. We are looking to initiate a combined phase I/II clinical trial in RP 11, as I'm sure you're aware. We are hoping that we get very close to completion of part one of that study and the single ascending dose protocol that will be utilized as we move into first-in-human studies. We are looking to progress our second asset in ADOA into IND-enabling studies as a fast follower into clinical development.
We're also looking to move into the critical non-clinical readouts that will inform progression of our Phelan-McDermid syndrome program. Here we are looking at the potential for efficacy of that molecule in the context of cellular material that comes from patients with Phelan-McDermid syndrome. This is the best context in which to assess the propensity of success for genetic medicines in the context of the human genetic background.
Also, relevantly, animal models to look at the broader physiology of the application of that drug in a living system. I mentioned before, we continue to invest both in the RNA therapeutic design parts of our platform technology and also in our drug delivery. This is the company that decided to go all the way in rare disease itself. I think it's familiar to many of you because the molecule, molecules plural, that underpin the success of Sarepta Therapeutics were invented here in Western Australia.
They were licensed from the University of Western Australia in 2013, and they were co-invented by Steve Wilton and Sue Fletcher, who many of you know is the PYC CSO. Things really started to get interesting for Sarepta around about 2016 as they moved into human studies. You can see that the company went from an approximate $100 million market cap at the time of licensing that lead asset to a peak valuation of $20 billion on the U.S. market. It's come back somewhat to $ 10 billion now. It highlights what the journey looks like for those people who decide not to sell their assets and to push forward to market themselves. I think a very interesting reference case on many levels for investors in PYC and something that we are certainly hoping to replicate.
I'm gonna stop there. That should outline for you both where we have come from and also where we are planning to head to as an organization. I will open the floor to questions. For people who are online, if you'd like to submit questions into the chat forum, Paula and Carol, if you can relay them to me, that would be helpful. Any questions from anyone in the room to kick things off? Carol? Just press and hold it. Keep pressing hold it. That's okay. If you.
My name is Michael McDonald. Further to the question, of course, is, and work's been fantastic and progress is great. We all know what the macroeconomics are of the markets. They accept all of that. You say in one of your slides there, 2023, 2024 is when you enter the transactional window for genetic medicines, phase I to II, and I understand all of that. The point is, it's in terms of the runway of where the markets are to where you want to be, and I accept that they're disjointed and not connected. How do you get to that point with the money you've got? Can you get to that point?
Which point specifically are you-
Well, to the point of getting to a transactional window with the money you've got in the bank and the R&D rebates.
I think that that's the point of the Eli Lilly Akouos deal, right? Is to illustrate for a company that has just submitted their IND, so it's literally within a hair's breadth of where we see ourselves in the RP11 program right now, that you're seeing those sorts of dollars farmed out from one company to another in the pursuit of those assets. I think it's very clear, yes, we can.
We are in the window for those assets. If you look at some of the other peer transactions for genetic medicines that sit earlier in the development pathway, I think Stoke and Acadia here for the SYNGAP1 asset is a very good example. That is not an acquisition like the Eli Lilly Akouos deal is. That's rather a licensing deal. Different. They didn't sell the farm, right?
They've sold an interest in the asset. $60 million upfront, $900 million of milestones, and a retained 50% royalty on the asset. Very attractive commercial terms for a program that is in pre-clinical development. It's well and truly several years earlier than the assets that we're looking at in the pipeline. Yes, I take your point. It's a very difficult macro environment.
I think from a shareholder perspective, what you don't want to see is a large diluted capital raising, right? As a board, as an organization, we're acutely sensitive to that. We've got skin in the game. We're working very hard to explore other options of value creation, firstly, and I think we've got those within reach, and value recognition in parallel.
Is there still any plan to list on the Nasdaq?
The contextual background here is that when you wind back 24- months, we were in the context of a very different macro environment to what we're in now. The company was looking at the disconnect between the valuations of peer companies on the ASX versus those on the Nasdaq. We had a series of conversations with U.S. life sciences investors to facilitate a transition between the exchanges.
This is something that we explored in some depth, and unfortunately, the macroeconomic environment changed very quickly and consequently changed the plans for the company. I think we were very clear in communicating on the advice of the bankers in the U.S. we were treated internally, and we were looking to do three things to change the valuation paradigm of the company before we re-explored the Nasdaq listing.
The first thing that we needed to do was to establish a safe and tolerated dose of the lead molecule in non-human primates. You saw that in the dose range finding studies in the non-GLP context in late 2021. The second one that they suggested we needed to do was demonstrate that we can engage the regulator and agree on a protocol for a pathway to first-in-human studies through a pre-IND meeting.
That was done earlier this year. The final piece of the puzzle there, the third milestone, was to become a clinical-stage company and submit an IND in support of the lead program and transition through into first-in-human studies. We are very close to that juncture right now, and I think that is the platform to reconsider the potential for a Nasdaq listing.
Personally, I think the better time to go to the Nasdaq rather than the immediate future is when we are more advanced through the third horizon that we put on the page. If you can have a near-term pathway to three clinical efficacy readouts in the context of first-in-class and potentially disease-modifying assets, I think you have a very strong platform for retaining the interest of U.S. investors, something that makes sure they don't get cold or bored with the story. Having said that, given that we are looking at that as a 24-month paradigm, we would need to start the planning process now for a transition between the exchanges. I think the short answer is, it's certainly something that we would consider, but it's not on the immediate horizon.
Suddenly there's a forest of hands. My name is Derek Parkin. In your presentation, you alluded to the fact that whilst you intend to continue on your, on a singular basis on your own, that you would be open to some sort of involvement with third parties should the occasion arise. Could you give me insights as to how you could see that playing out if it played out, sort of hypothetically?
Yes. There are a number of different ways that it could happen, as we've alluded to here as well. One is that we start to communicate the story more effectively to the exchange on which we listed, and we build the intrinsic valuation in a similar fashion to Sarepta, and we get that bottom left to top right share price tracking that they saw in going the journey alone.
I think there's one domain we need to get better at communicating the story. We've had the conversation previously. What I think needs to happen now is we need to get an independent third-party analyst initiating coverage on the story, and I think we've made some headway in that regard. That's one. Two, we could consider going down the Akouos route and selling the farm. Sell everything.
If the offer is sufficiently compelling, then we are obliged to have a look at it, although I think it's clear that that's not our preferred option. That leaves on the table what I think we would have a preference for in the context of a commercial transaction is a licensing deal. There are different ways a licensing deal can be cut.
Either someone can farm in very much in the manner that Acadia Pharmaceuticals did with Stoke asset that we spoke about previously, or I think a particular interest to us is a regional licensing deal, where you look at a particular geography or group of geographies for out-licensing of a particular asset, and you bring a partner on board who brings something to the table in terms of access to those markets and helps to create value. It's not a zero-sum game in the negotiation.
In relation to your RP11 application with the IND. Once you've lodged that, how long do you then expect to hear back from the FDA as to yes, approval to then go into clinic? Is that a regulated period? Because Christmas, New Year, I wasn't quite sure whether it would drag on a bit longer. Any idea of once you announce that you've lodged the IND, how long before we would expect to hear back from the FDA?
It's a 30-day response window, it doesn't change in the context of-- It's 30 days. It's not defined in the terms of business days. I think Tony had a question as well. Not yet.
Rohan, I was just wondering about the market for the RP 11. If everything went smoothly in terms of the human trials, what would be the earliest period that you could see a product out in the market?
Yeah, I think we should have a session where we give a definitive answer to that question in terms of the clinical plan, and we will in time. I can give you some high-level indications that what we are currently planning on are two consecutive 24-month studies. A follow-up period in the multiple dosing part of the combined phase I/II, 20 months, and then the same again in the context of a pivotal trial. There are opportunities to shorten the aggregate pathway on the back of the potential to overlap those studies, as we've seen with some of our peers in the context of retinal diseases.
That, that should give you some indication as to how we're thinking about that. We'll save the definitive answer for another time. Yeah. Yeah, I think a very nice reference has come up recently that I'd encourage all shareholders to have a look at in the context of PepGen, another company that is pursuing the PPMO modality for rare disease. Very much doing the same thing as what PYC does. Those guys have a cell-penetrating peptide, very similar to PYC's technology.
They are using Sarepta's exon 51 as the oligo that they are taking forward. They've got some different questions in relation to the commercial strategy. What they have been able to show, I guess the premise there is that they are going to outcompete Sarepta's PPMO on potency because they've got a potent peptide. Some nice triangulation for validation for what PYC is doing. That company established first in human safety data, I think two or three months ago now, about eight weeks ago.
They saw their share price move from $5 immediately prior to that announcement to $15 post. So you can see that's in the context of a higher market capitalization being a U.S.-listed company. You can see that the two broad milestones that we've got in front of us in this program are establishing human safety and establishing human efficacy.
You've got all of the contextual features of the genetic medicines that we've spoken about that inform just the abstract likelihood of success within these indications. Really the rubber meets the road in the context of the specific program. It's as you move through those two milestones in the human studies that you start to see value accrued.
Another big area of focus for PYC, obviously, we're obliged, the first-in-human phase I/II combined study is primarily directed towards that safety readout. You can also use it to glean some indication as to the efficacy of the molecule. The key thing for us there is to be considering how we can use the phase I/II study to give us an early insight on the likely efficacy of that investigation drug candidate. I think we've spoken in depth before about how that might play out.
You give an update on the U.S. operation and the roles they're currently performing.
Yes. You may have seen that we have expanded our footprint in the U.S. within the state of California to include a San Francisco office as well as our San Diego office. The reason that we have done that and the way that that fits within our organizational structure and informs the roles that those two different groups are playing, we've got a pre-clinical research group in San Francisco.
These are people from industry who have got the knowledge to help us take our discovery operations and move the hit sequences that we are getting in the oligonucleotide space and also the peptides very efficiently through to the minimum viable product that is required to progress the IND-enabling studies, and then to flesh out the information in support of those investigational drug candidates required to push them forward into the clinic.
That's the role of the San Francisco team. The current role of the San Diego team is more in translational development. This is where your focus is very much on regulatory engagement and in particular demonstrating the non-clinical safety profile of the molecule. As the company progresses downstream into the clinical environment, designing the clinical protocols themselves.
They, if you think about it, you've got then discovery in Perth, Western Australia, spreading into pre-clinical research that is still occurring in Perth, Western Australia, but in particular with guidance from the San Francisco office. Further downstream of that, you've got translational development, which refers largely to the IND-enabling stage, expanding downstream into clinical development as the company pushes assets forward into first-in-human studies. Last chance for another 12 months or at least a quarter. Nothing.
I think the last thing then that remains for me to do is to thank the team at PYC. It has been a, again, a very challenging 12 months. Like Alan, I feel privileged to work for this organization and with a group of people who are so committed to, firstly, changing people's lives, but secondly, doing something very different from Australia.
We don't have genetic medicines companies that are fully integrated and willing to pursue the entirety of the value chain in Australia at large, as a general statement, and certainly not within Western Australia. Not only are we swinging from the fences with respect to the impact that we are hoping to have in patient lives, looking to really push the frontiers of science, but we're doing it in a way that other people have chosen not to do it.
In large part for very good reason, because we don't have the infrastructure around the company that gives us the support that we need. We are trying to blaze a trail in that context. We have got a large number of benefits that help us in a very significant way. First and foremost amongst them, the federal government's R&D Tax Incentive. There are many reasons why Australia is a very good environment in which to do this. The most important reason, I think, though, is the quality of the people and the commitment from those people that we get within this organization.
Having a multi-jurisdictional company that operates across two very different time zones but is integrated in terms of what it's doing is a challenge. We get an enormous amount from a lot of people within our team in terms of the commitment to do this. This is hard. We are fighting to create shareholder value and to do something extraordinary for patients on that journey. I'm deeply indebted to Alan as chair of the organization, Paula, and the much larger PYC team who sit behind all of the work that has gone into getting those assets to where they are today. We are very excited about what is about to happen.
I think to the question that came earlier, there's a lot that we've got in the near term in terms of milestones that we can deliver that should, if we are successful, change the valuation of our company. We're very hopeful for what is coming in the next 12 months, but we certainly owe a debt of gratitude to our scientific team.
We have one more online. Assuming you receive IND approval, will you require further funds to enable progression to human clinical trials?
A simple answer to that is no. We're certainly well-funded to initiate those in human studies. What it will require is a transfer of funds from the PYC parent entity to the Vision subsidiary. We'll look to recapitalize Vision Pharma in that context, but we don't require any additional funds to initiate those first-in-human studies.
A brief recap, if you look at the last 4C, we had AUD 21 million in the bank, but with a note that we're anticipating another approximately AUD 10 million from the R&D rebate. I've been informed this morning that we've received half of that through Vision Pharma, which is very helpful. We expect PYC to get its share very soon as well. Remember, we are now nearly halfway through another financial year.
We had a significant period of costs in Q3, in particular, as we look to complete the GLP tox studies and also incur a lot of the setup costs associated with the clinical trial. Getting all of the equipment and the infrastructure set up at the clinical trial sites, those expenses were largely incurred in Q3 as well. We're hoping for a little bit of respite on the run rate burn at the same time, which should give you some guidance as to exactly the forecast period. Very good. Well, thank you very much, everyone. It's been a long journey. It's been a painful journey. I'm sure it will continue to have its twists and turns as drug discovery and drug development does tend to do.
It's a very exciting journey, and I think we are getting very, very close to having an impact in the lives of people who need us to continue the work that we are doing. We're certainly very closely connected to the patient community. I get emails almost every day from patients with RP11 or ADOA encouraging us to continue to push through. There are many other indications that we can make a difference with our technology for, and we're very much looking forward to doing so. Thank you again for your patience and your interest in our story, and we look forward to keeping you updated as we progress.