Prescient Therapeutics Limited (PTX) Earnings Call Transcript & Summary

Good day, everyone, and welcome to PTX Investor Briefing. While everyone settles in, we'll do the normal housekeeping. The presentations that Reach hosts are suitable for self-directed investors who've got the experience and capabilities to make their own informed decisions. Any information contained in today's presentation is general in nature and does not consider your personal circumstances. You need to decide yourself whether it's appropriate for you. The information we're giving you is for educational purposes only and past performance is not a reliable indicator of future performance. My name is Patrick Nelson. I'm the MD at Reach. I'll host the session, but we're joined by James McDonnell, the CEO of Prescient Therapeutics to run the presentation now. The format for today is that we've had a couple of recent announcements. So we're going to start off by asking James, some questions about these, and once we've gone through the Q&A, James will then do a quick deck run through. This run through will be similar to the last deck run through that we did. So -- and I imagine we'll take sort of 15 minutes or so. And then when we get to the end of that, we'll get into any broader Q&A that you may have. So expect the session to run for up to 60 minutes. We'll make that available to you. So you can put any questions that you've got into the chatbox. I may hold the question -- some of the questions till the back end of the presentation, but we'll go through everything that's put forward. We're aware that there are some new investors that have joined the call as well as existing shareholders and we've designed the session as such. So by way of a quick introduction, PTX have developed a unique technology which is a platform that can stop some cancers from reproducing. It does this by attacking the biochemical processes referred to as the RAS pathway that are behind up to 22% of all cancers. And while the technology is a platform that can potentially help sufferers of up to 22% of all cancers, PTX first chose to prove the technology on cutaneous T-cell lymphoma, which I will refer to in the presentation today as CTCL. And it's a cancer that is considered by many clinicians to have no viable treatment, therefore, a death sentence. In their Ib clinical trials for CTCL, an astonishing 100% of patients cancer stopped growing or reduced and 0 patients experienced serious adverse effects, which is particularly important as a lot of cures for cancer can be worse than the cancer itself. They chose CTCL because it's an orphan disease with very limited treatment options. The FDA and other regulators are much more likely to support or fast-track orphan diseases, and whilst a rare disease with limited treatment options, it still represents a $1.2 billion market in the U.S. alone. So this strategy of, I guess, attacking an orphan disease first off has been very successful. And the company received a fast-track orphan drug and IND designations from the FDA and recently, the EMA gave them fast track. And they've moved at great pace to now with CTCL being one of the most advanced therapies on the ASX. Now moving into a IIa. There is a potential for IIb to be a registration study. And beyond the results for CTCL now advanced -- and how advanced this therapy is there is -- there are broader applications for this technology. We've been involved with Prescient for a number of years, and we've seen the team move this forward. We're now -- they've now got patients through the Ib and 18 patients recruited in IIa. And it's an amazing to be part of something that is already demonstrating a real meaningful impact on the lives of the people that are incredibly sick and suffering from this terrible disease. The idea that this is to be able to be applied to potentially thousands of people and then potentially across other cancers and have such an amazing and positive impact. It's exciting to be involved in. James McDonnell, who's been at the helm of the company has progressed them from Ib to IIa and is here to talk us through the plans from here. So James, thank you very much for joining us today.

Thanks, Patrick. Good to be here.

And just back from your travels, so we appreciate you being up to dust yourself off for the session this morning. When did you arrive back from Europe?

Just on Saturday. So I actually arrived back from the U.S. I went to Europe and the U.S. to make the most of the trips. So yes, it's been pretty exciting, pretty long trip. So happy to discuss it.

Now you've now got 12 of the 15 targeted sites initiated. Can you give us an update on how things are going? And where does this sit in terms of your plans?

Yes. No, it's going well. We're happy with the sites that are activated. And as we said in the previous 4C, we have 18 enrolled patients and the next 4C is due in not-too-distant future. And I think we'll see some good numbers on that as well. So our expectation of a dose optimization committee meeting at the end -- towards the end of the year is very much on track. So that will be certainly a good piece of information to have.

And the sites in Europe, how are things going over there?

Yes. No, the site is good. I spoke with 2 of the key opinion leaders or 2 of our investigators and Professor Luigi Zinzani, who's a key opinion leader of quite significant notes. And he was very positive. And I think we mentioned that in a recent post, he can see the benefit of PTX-100 as a unique mode of action and providing sort of a backbone with good data and really providing some -- a good treatment option for patients who are really struggling because this is -- a lot of patients are refractory and relapsed to everything that's out there.

Okay. So yes, so professors since Luigi Zinzani. So what role does he play?

He's an investigator within the study. But he is also a significant key opinion leader in this area. He is -- he's kind of like the miles prints of Europe. He's a miles prints of Europe. But he is well respected. He's a key member of the Italian Hematology Society and very strong in lymphoma. And therefore, he's important to have in the study because if you've got these key opinion leaders as part of your investigator pool, it means that there's a lot of respect within the study and very keen, and he's very happy with recruiting patients and moving forward.

Yes. When do you expect the remaining European, I guess, clinical trials to be set up?

Yes. I mean those are the French sites, and we have -- we're dealing with some bureaucracy there. And so -- so that's quite interesting. We will -- we're working as hard as we can to try and get those sites activated. And it's very dependent on the French bureaucracy at this stage, which is in some ways disappointing, but it's the way to go. These sites are pretty keen to get going, but it takes a process.

Yes. And I mean do you need them? Is it like the end of the world if you can't move it forward, do you just concentrate your energy into other areas?

We're very happy with the progress to date. So I don't think it's causing us too many issues at this stage in terms of recruitment speed. It would be nice to have them on board, though.

And in terms of where you're expecting to get in terms of total patients recruited, how do you -- where do you feel it...

We haven't changed in that respect. We say that the dose optimization committee will be meeting towards the end of this year. That means that we will be 10 in each arm that will have had a global response score measured. And so all that's on track. So we are very happy with the progress. And we're pretty confident that the dose optimization committee is -- will be going ahead later this year.

Okay. And so while you are on your travels, you dropped into the conference of BIO '26 conference in San Diego. What do you hope to get out of going to conferences like these?

Well, as I said previously, part of moving forward is we need to look past these studies and how we can commercialize PTX-100 in various territories, whether it's a global deal or looking for options. And the BIO U.S. 2026 is really a condensed environment where everyone is there. And so I had quite a number of meetings with potential partners and both global as well as regional and it's really starting those conversations, creating the environment to actually continue that conversation forward. And they, of course, are very interested in the dose optimization committee and the data that will come from that as well. And so it's about getting them on board and then working through them as we get to that data and then seeing what happens after that.

Okay. So these partners, at what point does this turn into real discussions or a deal getting done? Is it post the -- well, I might pause there. At what point does that happen?

Well, the interest that I had from the partners was they're very, very happy with the story, and they're happy with the Ib, but they just want to see some validation in terms of the interim data from the dose optimization committee, and then it's going to get busy. We may sign some CDAs beforehand, but at this stage, there's a lot of focus around what that data looks like and where they go from there. And so I had some really good conversations with globally capable partners and also regionally capable partners. So when you have that much interest, it's actually quite reassuring.

Now we recently appointed Dr. Rosalind Wilson as your CMO, Chief Medical Officer. She was previously Global Head of Drug Development at Telix Pharmaceuticals, for those who don't know, this is a circa $5 billion Aussie listed company. Can you give us a little bit about her background and I guess why she would join a little company like PTX.

Yes. Well, I mean that's quite encouraging. I mean Dr. Marissa Lim, who's deciding to semi retire. She has -- was very high caliber as well. And I'm excited for her. She's got some plans moving forward for her semiretirement. So I'm happy for her. But to be able to attract someone like Ros really demonstrates the -- what we have here, and it's encouraging. She has significant experience from Roche and from -- she's been previous CEO, all sorts of strength of experience that will help us move forward into -- as we get closer to commercialization. So I think we're -- well, I'm very pleased to have Ros joining us, and she will be a significant addition to the team.

Very good. And there was a video that we -- I think we shared with shareholders recently with you demonstrating the model that the CSIRO had done the 3D print of. So maybe start before we get to looking at the model, what's the purpose? What are you trying to achieve with the work that you're doing with the CSIRO?

Yes. So we need to understand how PTX-100 interacts with geranylgeranyl transferase-1. By understanding that, it will then give us an idea of where to look going forward, where to look next in terms of what tumor types, but it also satisfies some requirements for an NDA. So completing the application process as we head towards approval. And so it's a dual purpose, but the -- I guess the most exciting component is if we're understanding more about how PTX-100 interacts with geranylgeranyl transferase-1means that we can start looking a little bit further downstream about what's happening after that as well. So this is an area where I would like the team to focus on once the study is rolling and we have an ability to fund some extra work there. But the CSIRO work to date has been quite positive in terms of getting that understanding.

So I think the CTCL, which we know the results in Ib, which are very exciting. The potential application for other cancers or 22% of cancers that have that RAS protein involvement. This work is it to determine what are the best cancers to target?

Yes. It's to provide more information to allow us to sort of think about where -- which tumor types may be more appropriate. There's 170 RAS proteins, we disrupt those -- the process of those proteins. So we don't inhibit the actual protein, but we disrupt the process at which they go to, to signal downstream oncogenic approach factors. So if we can understand a little more about the molecule, it's interaction and where -- what's happening, it should give us some idea about where to go next. We also need to look at -- there's a lot of KRAS activity going on in pancreas at the moment. And so we need to think about the commercial side of it as well. So we'll match up the scientific and understanding the process of PTX-100 well as match up the commercial side of it as well and see where we go next. And that's something we continue to work on. That's basically what we have to do.

And that is that PTX-100 is the potential to be a platform which could be used to go after like you're doing with CTCL to go into other indications, but also be used in partnership with other treatments. Is that right?

Yes. I mean, I've had a lot of discussion about that, and I think Professor Zinzani even mentioned it as well in our conversation that PTX-100 has shown clinical benefit in CTCL. And it does it without any serious adverse events attributed to PTX-100. So that means it's a really good candidate. So we have a unique mode of action and something that's not really causing more fragility to the patients. So there's a lot of encouraging components, and we know that RAS proteins are involved in 22% of all cancers and some say 30%, but 22%, and we disrupt a process within that. So there's opportunity there, and we need to do more work. But not only have we got new tumor types, but we also got the commercial benefit of combination therapies. And I think we talked about that on our page turn, the HDAC inhibitors, the biologics, all are different modes of action or mechanism of action. And so therefore, PTX-100 would sit nicely with them.

You've got the 3D printed model with you. Oh, there we go. Do you want to step us through what that model actually shows us or demonstrates?

Yes. So these -- this is the 3D printed enzyme from the CSIRO. It's got an alpha and beta component. And it's -- I'm not sure you can see in there, there's a little black area, that's actually the molecule of PTX-100. Now that sits in a pocket called the prenylation pocket. And typically, what happens is that you get RAS proteins come into here and then prenyl donating groups come in on this side. They get together and they prenylate and therefore, the RAS protein can go and start signaling downstream effects. But because PTX-100 is sitting in there, they can't get in. And now that's really good. But we also understand that the affinity of that pocket of PTX-100 sitting in their pocket is quite strong. And so normally, a cell when they see something like this happening, they start bombarding, so they'll bombard RAS proteins to get them through, and they'll bombard prenyl donating groups to get them through. But because of the affinity to that pocket, PTX-100, it's really stuck in there and it does disrupt the process. So it's less likely to cause resistance development and those sorts of things. So yes, it's exciting to sort of have a visual of it, but a lot of work has gone into understanding that and a lot of science and physics and AIs and -- but yes, that's what we have. It's pretty...

So a step further to this is the goal is to understand that mechanism of action so that you can then work out what the potential next cancer to target is? Or what's...

There's a couple of things there. We need to understand because those RAS proteins are being trying to get prenylated but they're not. So we need to understand the effect of having unprenylated RAS proteins around. We need to understand what are we inhibiting -- what's prevented from happening downstream and whether that's affecting the tumor environment. So the next step is about, well, with all those unprenylated RAS proteins, is it affecting some way the tumor growth and those sorts of things? And can they not form a tumor or all those sorts of things. So there's a lot going on there. And the more we know about that, the better it will be for us.

And the potential size of market for PTX-100, is that another element to determine from doing this work? Or what are your thoughts there?

Yes. It's about -- once we understand it more, we can then -- we can select tumor types, we can maybe strengthen our IP, we can do all sorts of things. And so the future is an opportunity there. So with 22% of cancers impacted by RAS proteins, we -- some are seriously impacted others are not so impacted. But there's the resistant tumors and all that sort of -- all those sorts of things that play a role. So I think CTCL, we're progressing really nicely. And once we'll really work on moving forward to see what else we can sort of work on.

Beautiful. All right. I will stop the questions here. We'll just do a quick page turn before I hand over. I'll just mention that on Wednesday, we've got Stuart Roberts, who is -- runs Pitt Street and they've updated their research price guidance target has gone up quite significantly. Off the back of that. And Stuart's a health care biotech analyst, and he's got quite a resume. So worth coming in and getting his perspective on some of these things as well. That will be on Wednesday, if you would like to be invited to that session, just type yes into the chatbox and we'll make sure that you're into that as well. So what we'll do now, James, is let you go through and do a quick page turn on the deck. And if anyone's got any questions on anything, any of the news, anything we've covered so far please put them into the question box or at any point in time, we'll come back for some more questions in a moment. James, I'll let you take the floor.

Thanks, Patrick. Appreciate it. We will flip through this. Here we go. So there was a disclaimer notice there, and this is where we are. This is our focus. We're focused on oncology. We have a therapeutic that has -- can be a trip possible impact on 22% of cancers and therefore, it is creating value for patients and investors. In terms of our proposition. We've talked a lot about PTX-100, and it's a selective inhibition of GGTase-1. It's currently in clinical development, and that's really moving us forward. CTCL is where we decided to move it forward, and we've had some really good Ib results. And in doing so and going through the process, FDA has granted designations, which are very helpful. So some background. So in the cancer process, we see a normal cell. So this comes from the Cancer Foundation, so cell division. And you can see abnormal cell growth is where you get a genetic change and therefore, cell division. And this is where we see that is mediated by RAS family proteins and tumors. And so we're really looking at where we can impact that mediated activity by the RAS family proteins. So PTX-100 has originally come from the Yale University in the U.S. It's the first-in-class and the most advanced in the clinic at this stage for GGTase-1 inhibitor. And we really disrupt the RAS family pathway by impacting the GGTase-1. So just to quickly go through what I mean by that is that typically a RAS family protein, you see there uses GGTase-1 to prenylate and then create a prenylated RAS protein, which basically is an arm on the RAS protein, which allows it to attach to the cell membrane and therefore, signal downstream protumor effects, whether that's proliferation, survival and migration, those are the 3 typical things that it impacts. But with PTX-100 blocking the GGTase-1 activity, you can see that we impact that RAS family protein prenylating and therefore, antitumor effects result. So it's a first-in-class, and there are advantages with that. And we've seen already, we've been able to gain some favorable regulatory designations, both orphan drug and Fast Track Designation and orphan drug at the FDA and orphan drug in the EU. We're not competing with other GGTase-1 inhibitors, and we're able to really gain momentum with key opinion leaders in the space and of course, the first-mover activity is always a nice advantage. So we talk about our process, the way PTX-100 works. And when we consider CTCL therapies and after patients have gone through chemotherapy, they become refractory and relapse and they end up with these types of therapies, either a HDAC inhibitor, looking at tumor gene suppression, the biologics targeting particular antigens on the cell membrane, and there's 2 approved and there's a couple in research and also biologics that carry payloads and LYMPHIR is one of these, which is recently approved in CTCL. So you can see that PTX-100 has completely different mechanism of action, inhibiting the RAS family protein signaling and so disrupting a process. And so by that fact, it means that there's likely to be a really good combination with HDAC inhibitors, but also sequential dosing with biologics. And there will be some really nice combination work to come. So in CTCL, we were looking for a good indication where we had high unmet need, regulatory support, et cetera. And we see that there's RAS family involvement in CTCL. It's orphan disease. So that's very nice for us in terms of our strength of commercial benefit. And obviously, the market is strong. We've got good results with 100% clinical benefit rate shown in our Phase Ib study. And the designations have been very significant. So the Fast Track Designation and orphan drug designation. So that's the strategy, and it's -- the outcome so far have been very positive. We chose CTCL and you saw that it was an orphan designation, orphan disease and with Fast Track Designation means that it's considered a clear unmet need. And this gives you an example of why that is the case. This is 5-year overall survival and staging of the disease underneath. Now if your stage IIb or worse, your 5-year overall survival is diminishing quite significantly. And in fact, if you're in the 4A or B, you've got an 18% 5-year overall survival rate. So not a great picture. But that's only part of the story because then we also have quite significant quality of life issues. You can see here if your skin is impacted, you're really itching, you're causing secondary infections. The appearance is quite challenging. So it's socially isolating and it's really sleep disturbance and fatigue is a big thing. So it's not a great disease, not only from a survival benefit, but also from a quality of life perspective. And so patients are typically refractory and elapsed in this space. So it's a rare type of cancer where the white blood cells, which normally involved in the immune response are actually replicating in the skin and actually causing disruption and destruction of the skin, it will eventually impact also the nose, viscera and blood. So it can progress to quite a severe disease that we saw just previously. So there's a lot of patients who are refractory and lapsed. And we see from a prevalence or an incidence perspective, there's 3,000 new cases per year in the U.S., and that's increasing. So that's about 8 people for 1 million of population. And other populations outside of the U.S., it varies between 6 and 8. So you can see it's rare, but there's definitely patients there. So from a clinical data perspective and why we are currently in our Phase IIa program is because of this data. And firstly, it's important to understand what the benchmark in the disease area is. And so with evaluating the situation, we see that roughly a benchmark is about a 30% response rate, a 45% clinical benefit rate, which is stable disease, PR or CR, some duration there. And interestingly, in this cohort, hopefully, if you can get less than 30% serious adverse events attributed to the drug that's a positive. So that's quite a low bar to get past, I guess. LYMPHIR is the most recently approved FDA product, and you can see a response rate of 36%, so slightly better than the benchmark. But you can see a serious adverse event rate which is at 38%, and that's significant. So when we look at our studies in the Phase I, we see in the overall study, which was T-cell lymphoma. We had some good results. And in fact, 0 serious adverse events attributed to PTX-100. And then when we look at PTX-100 and CTCL only patients, and there were 7 evaluable patients here, we see some very encouraging results with a 43% response. All patients in this cohort received a clinical benefit. So they were -- their disease stabilized or was better and over a reasonable period of time. So when you have this sort of data, you have a good reason to move towards the next step. And so just reiterating the importance of understanding a favorable safety profile. You can see that this is all adverse events, not just serious adverse events, and you can see there's a lot attributed to these drugs. And PTX-100 just down the end here has some diarrhea attributed to it, but not serious. And therefore, it continues to be a really good candidate for combination therapy because it's not impacting the patient's fragility and it's a unique mode of action. So really, really encouraging moving forward, but with the data to date. So as I mentioned, we have moved into Phase II, and there's 2 parts to the Phase II. It's IIa and IIb. And the first IIa component is with 2 prior lines of systemic therapy, will enroll 40 patients. They will be assigned to either 1 of 2 dose arms, so 500 milligrams per meter squared or 1,000, and that will progress with 20 patients in each arm. Now we do have a dose optimization committee here and their charter is to start looking at patients in the Phase IIa when there are 10 patients in each arm. And so the first dose optimization committee meeting will take place when there's 10 in each arm. And as I mentioned previously in our discussions, that will be most likely later this year. So we're quite -- we'd definitely be pretty encouraged by that. And so we're looking forward to that time. The dose optimization committee is there to define the dose, but also check safety, efficacy and those sorts of things. If the dose can be defined, we would then start talking about a Phase IIb from an efficacy perspective, and that will be an encouraging time. But we will actually go to the FDA first before we move there for -- and I will talk about that going forward. It is multinational, we currently have 3 countries, and we're working to get France on board. Our recruitment seems to be progressing pretty well. So I mentioned where we are in terms of the status of CTCL and we've progressed through Phase I. We're in the Phase II phase. We have some really encouraging designations from the FDA orphan plus Fast Track. Fast Track is a very helpful one to have. And this is the standard process depending on the outcome of the Phase IIa in terms of efficacy, safety and dose, we will actually go to the FDA because having Fast Track Designation means that we have an ability to communicate with the FDA on a much more regular basis. And so we will ask for a type B meeting as soon as we can, as soon as we have understanding the data and as soon as we have a dose defined because we would like to really work with the TGA to see the potential for an accelerated approval pathway. They do recognize it's a clear unmet need and there's a potential here. And so that would be the goal, looking at the Phase IIb being a registrational potential and an accelerated approval pathway, but this is subject to the FDA agreement on endpoints, et cetera. So -- but that's why the Phase IIa data is quite significant. And in terms of CTCL, we've mentioned before, $1.2 billion by 2034 is an estimate by third-party research agency. We do know that there's 3,000 new patients per annum and that's increasing. And so yes, it's certainly a healthy market. In terms of that market, we see here an example of a relatively new drug. This is one of the biologics that we referenced earlier. It was launched in the late 2018. So this is from 2020 forward. And you can see the reason that I'm showing this is that you can see the growth from Mogamulizumab has been quite encouraging, but it actually is growing the market pretty much the same rate. So if you have a unique mode of action that clinicians are really encouraged with, you can grow your own market share. And so this is an important component. And we will look at that from a PTX-100 perspective. And so when there's already some therapies out there, there's also some good pricing comparisons to be had. And so all that will work well in terms of our commercialization. So just in summary, we're running our Phase IIa program in CTCL based on the back of some good, some really solid Phase Ib results in CTCL. There's a good market size. We have some designations and the study is progressing well. And Patrick has mentioned this, and we had a discussion about this earlier on. It's about this 22% of cancers having a RAS involvement. And as you can see from our mode and mechanism of action, we actually disrupt the pathway of RAS proteins. And so this disruption is attributed to up to 170 of these RAS proteins. And so we need to -- we are continuing to do more work to understand where our next tumor type where we are likely to have a really good impact on patient outcomes is. And so that's the focus of where we're going next. So as you can see, we've got CTCL already focused, and then our expansion strategy is other tumor types. And so a good one to approach, but we certainly need to tie up the Stage 1 first and then move. We have a very capable and strong management team and Board. Marissa will be leaving us in a few days, but will be replaced by Ros, who's also a very capable CMO. So it's exciting to be able to attract such high-caliber CMOs. And so that's encouraging. And so yes, I start with the slide from the beginning. We have a PTX-100 inhibiting an enzyme which disrupts a pathway, which has potential applications to 22% of cancers. We're seeing some good results from CTCL and Phase Ib, and we're working hard to move that forward. And so -- there we go. And so I'll hand back now to Patrick, and we can pick up questions.

Yes, beautiful. Just going back to the slide where we had the results -- Slide 19. So for the patients that we talk about clinical benefit, but were 100%. So what sort of benefits are they practically getting?

Yes. So these are -- if you've got a stable disease, I mean, we've had some patients who say that they reduce the itch. This is where it comes really much slides towards the quarter of life side of it. So there's less itching, they're more able to sleep. And so the quality of life improves because of that. And as we know that with PTX-100, we're not really adding adverse events to their regime. And so that's very helpful. So things like -- you can see here the skin, typically, anything that's involved in the skin, particularly in such big amounts of skin, it's always going to be itching. And so the problem with itching is that you introduce bacteria, you rupture the skin. There are a couple of diseases where you end up with skin flaking all over your house. It's actually -- it's not great. And so if you can stabilize that situation, reduce itching and really improve some quality of life aspects, that on it's own is really encouraging.

Lisa -- sorry, Lisa, you had earlier question. How many patients now enrolled?

Well, we're using the 4C to indicate the patient enrollment in terms of getting close to the 10 in each arm and the 4C will come out in July. I can say at the moment, that we are encouraged and the dose optimization committee meeting will be -- will hold at the at the end of the year. So recruitment is based on that. So...

In the last 4C, the numbers were?

we had 18 in the last 4C. And so yes, recruitment is...

And the 40-patient threshold. So Chris had asked a question around this, and I know that you won't be able to really answer it. But that threshold, do you need to get to that before we go to the dose optimization committee?

So the first Phase IIa is about the dose is also -- and therefore, it will be -- whether there's a change between the 2 arms, there will be efficacy, safety and probably not duration. But the dose optimization committee has the ability to say, well, actually, we have enough information now, we don't need to go to 40, and we will go -- we will meet with the FDA at that Type B meeting and really discuss the nuts and bolts of what's happening next. But they can go up to 40 patients. So it's like -- I can't project the future, but the dose optimization committee have the ability to make a call earlier if needed. Yes.

And Chris has asked, could you give an indication of some of the other major cancer types that make up the 22% of cancers that are linked to RAS pathway? And how many patients of these are diagnosed each year? Well, yes.

Well, I mean I can give you some idea -- I mean there are multiple RAS proteins. And at the moment, it's very topical. KRAS at the moment is very topical. There's been a KRAS inhibitor targeting a particular mutation in the U.S., which is doing very well. And so that's mainly in pancreatic cancer, which has mainly KRAS involvement. But we're talking about lung, colon, breast, like a lot of cancers do have RAS involvement, but it's the degree of RAS involvement as well. And so it's the timing of when you approach inhibiting the RAS pathway. So there's lots of things to talk about, but most like some really big solid tumors have RAS involvement, head and neck cancers have HRAS and NRAS. And so there's quite a lot of unmet need in that space as well. So we need to look at that. So that's why we need to do the CSIRO work to find out what's happening, all these prenylated RAS proteins, what's happening there, what's happening to progression of the tumors because we're inhibiting migration, proliferation and survival. So what's going on there and where can that be applied? So to be honest, it's understanding a little more and then looking at the tumor types and the degree of RAS involvement. So I couldn't say how many patients because 22% is a lot, and it's impacting solid tumors and hematologic tumors as well.

Thank you. Michelle has asked, the treatment of PTCL has been guided as a potential development strategy. Does the current Phase II trial allow for protocol changes to include a parallel trial cohort without the need for a separate IND approval? And how would the trial regime differ to better target the aggressiveness of PTCL.

That's a great question. We -- our goal here is to actually utilize the dose that we get from the Phase IIa and then run some investigator-led programs for PTCL. As you mentioned, PTCL is very aggressive and patients are very challenged and the clinicians that I've been speaking to are really thinking that that's a straight-up combination approach. That's a problem for us when we're developing PTX-100, so single activity in this process. So that's why we're choosing CTCL, but we will use an investigator-led program to look at the PTCL. So it's a great question, and it's an exciting part of that, but we will -- we won't use an IND approach, will actually use more of an investigator-led approach where it might be a CTN or might be -- we might get Professor Zinzani to do something. All those sorts of things will take place. But we need to keep the CTCL claim.

Got it. Anthony asked a question about government rebates. Given that as the trials go on, things get more expensive, do the rebates increase?

Yes. I mean I think it's a 43% R&D tax incentive, but it's based on what's happened in Australia. So as we progress further and further in the study, we have more happening outside of Australia as well. So it's a balance, and so it's very helpful in Phase I and early work and things like that, but it becomes -- you need an overseas finding to work with overseas environment such as our study being in the U.S. initially and soon to be France. So there's some dynamic at play there, but there are still rebates, but you have to have specific things in place.

Very good. James asked, how much information or range of information, best case, worst case from the dose optimization we released to the market after the first 20 patients have been assessed.

That's a great question. In fact, I was asked it last week and on multiple occasions, and that's something that I are working with our clinical team to actually get a clear answer on that. I don't want to speculate, but certainly, it's likely to be efficacy and safety and some dose. But I'm taking that on notice because it's something that we need to define, and we'll have a list of that.

And how long do you need to assess from the time you receive the data? And do you anticipate -- and I guess when do you anticipate you'll receive data this year or what do you think the release date will be?

Yes. I think we -- I mean, it's all dependent on recruitment. And so when we have a patient -- when we have 10 in each arm, when that patient is enrolled, we have 4 months to wait before we get a global response score from them. And so once we have 20 global response scores to 10 in each arm, we can compile that data and run a dose optimization committee meeting. Now that information at that point will be made available. Now I'm expecting that -- yes, that will be this year.

Anthony has asked what is the market size in Europe?

It's a bit different there. It's also timing, but we have 10 years data exclusivity. It's more in the $400 million type range and things like that. So it's a bit different. And it's also -- there's multiple countries involved. So it's a staging of those countries. One thing I learned while I was away was that usually, you would start with Germany and European Union to get the best price. But now that's maybe not the case. And so there's some dynamic changing in that space. And the most favored nation pricing from the U.S. is impacting the way Europe is looking at the way they fund medication. So to be honest, I think -- but when we get to market, the European Union will be funding more at a higher level of these drugs because of the impact of the most favored nation pricing aspects in the U.S. So it's a really good play. It's a good question, but it's -- there's a lot to go there.

Got it. James asked a question regarding data. Do you receive that as you go? Or do you get it all at once?

Well, the team will receive it. Obviously, they received the recruitment and the clinical team will pick up the GRS scores as they progress. But it's an interim situation. So we will wait on the dose optimization committee to make a call on what it looks like. It's-- and so that will happen later this year. So the clinical team get to look at it and see what's going on. But it's just progressive and at the moment because there's a 4-month delay between the patients enrolled and when we get the global response score, there's always a lag there. So -- but they will collect that data for the dose optimization committee.

Very good. And Lisa, any Phase I patients still taking PTX-100?

Yes, that's a good question. Actually, we -- if you remember, we had to move 1 patient who was in complete response from the Ib study into compassionate access and then to allow us to close the study. That patient continues on therapy. So yes, that's a CR that's over 2.5 years.

Fantastic. Okay. So Michelle, I missed a couple of your questions here. Sorry, I'm just going back down. Can you speak a little bit about the significance of P27 as a biomarker for PTX-100 and our patent in breast cancer, the biomarker has a potential to increase, the drugs clinical utility and commercial value provided ongoing studies confirm its predictive role.

Yes. I mean, the patent in breast expires in 2030. So from a commercial standpoint, it may not be too strong. In terms of biomarkers, it's -- we are looking at biomarkers, but yes, I would probably need the science guys to really answer this question. But at the moment, it's important from a commercial standpoint, sometimes it's really good to have a biomarker, sometimes it's not. And so there's a lot going on in that space. And it sounds like you're quite involved and familiar with that space Michelle. So I could certainly connect you with Lewis, our Director of R&D to cover that a little more.

Yes. Beautiful. Thank you. All right. Okay. So anyone that has a request has typed yes into the chat. We'll make sure you are automatically booked into Wednesday session with Pitt Street. So what you need to do is tie yes, in the chatbox. It's a couple of people that have said, please include me. Just to make it easy for the Pitt team that will then pick this up, just type yes into the chat box and you'll be booked in. And look, the I'm going to talk about the research piece right now, James. But I'll just make a couple of comments that we're going to be looking into in terms of on what basis they are looking at and valuing the company. And look, they've dropped there risk discount on PTX based on how things are moving forward. They've increased the share total equity from 70 to 83 on PTX-100 share and reduced some of the other areas. And these are sort of where the energy has flowed from the business and this I guess the market will determine value and people buying shares on market, not research reports, but just interesting to see on how Pitt Street are looking at it and how Stuart's looking at it and why he thinks that there is an improved investment case for PTX. So come on to that session. You can ask Stuart all your questions there, and we'll run through. I've got some questions for him that, that will be on Wednesday at what time? 1:00, 1:00 p.m., sorry, I should know the answer to that. I'll be in Singapore then, so I'm on a different time zone, but at 1 p.m. on Wednesday is the time. So yes, like I see quite a lot of people have typed yes into it. But James, thank you very much for the update. Thank you. And I know you've done a great job today given the bit jet lagged even better again. So well done there. Anyone leaving the session today, please provide feedback. If we haven't answered the question, just highlight it with again, we'll chase an answer for you and follow up directly. And yes, but thank you, great audience in attendance today and some very, very good questions. So thank you all for your participation. James, thank you. I'll leave the last word with you.

Thanks, Patrick, and I'll reiterate that, too. The questions are great, and it shows that we have really engaged investors in PTX and understanding PTX-100. So that's really encouraging. So I'd like to thank you and ask for your continued support because it's an exciting time. So thanks very much.

Thanks, James. Thanks, everyone. Cheers.