Prescient Therapeutics Limited (PTX.AX) Earnings Call Transcript & Summary

[Audio Gap] We will send through the last investor briefing, which was a page turn when we send through the recording of this at the end of today's session. So if anyone wants to go back and go through and look into more detail the presentation deck and the previous presentations, which goes into a lot more detail, you can do that at your own leisure. But today's session is a bit more of a Q&A format. I imagine it will run for circa 30 minutes depending on how many questions you've got for James. So my name is Patrick Nelson, MD at Reach. I'll host the session, but James McDonnell, the CEO of Prescient will be running the session. So James, thank you very much for joining us today.

Thanks, Patrick.

And now I might just quickly set the scene. So today's updates off the back of another milestone for Prescient securing their EU Orphan Drug Designation for PTX-100. And for those of you that have been following PTX's journey, they've developed a therapy or a technology I should say, the technology, which is first application is for CTCL or cutaneous T cell lymphoma. And it has shown outstanding results for, in particular of a cancer of unmet need. So essentially, it's been described as a death sentence for patients and the CTCL patients going through the 1B trials experienced 100% halt or reversal of their cancer tumor with zero serious adverse effects. And this was updated data because originally, the one to be included was CTCL and PTCL and with just the CTCL focus now going into 2A, these are the results albeit of a small cohort. They offer a lot of optimism for those people that are going to need this therapy. So they're now advancing through 2A trials off the back of the IB results. And they received FDA support with Orphan Drug Designation and Fast Track Designation and they've got the opportunity to look at the 2B turning into a registration study, and that opens up the commercial pathway for PTX-100 to go through into manufacturing or production and marketing of those therapies. So it's a really interesting time. The data around PTX-100 gives us a lot of optimism for the future here. And as such, we've looked at this as a really interesting opportunity for investors, especially if you look at where PTX is trading, we think that there is a really good opportunity here. So the update, James, that came out last week was the European Medicines Agency EMA Orphan Drug Designation.

Maybe if you could step us through what that means for Prescient?

Yes. I mean it's an important development and as we set out PTX-100 to go through the CTCL sort of progression, EMA or European orphan designation provides 10 years data exclusivity. So that's quite a significant period of exclusivity and we know that the European Union there are a number of countries there. So that's really strengthening our commercial offering in terms of PTX-100. So it supports what we've done in the U.S., and now we're repeating this in Europe. So very important. There's also, we're, again, allowed to speak to the agency a little more often in terms of getting protocol assistance and the fees and stuff they waiver at certain times. So it's -- from a progression perspective, it's exclusivity. It helps with commercial strength, but it also helps with engagement with the agency. So a very nice to have and it does make the story quite a lot better.

How the EMA and the FDA come together? Do they come together at all?

They -- it's like the TGA, FDA and EMA are all their own bodies, but they do talk and they do cross-pollinate. And so when we have Fast Track Designation in the U.S. for CTCL, we'll be talking directly to the FDA. But at the same time, we'll be informing the EMA of what's going on because as we progress through the FDA process and we get some results, we identify a dose, we have the potential to go to pivotal, we also want the EMA knowing what's going on at the same time because they may have something, a little tweak at that point could actually speed the whole process up globally. And so you want a slightly more coordinated effort. But from a priority perspective, the FDA takes priority.

Yes. Got it.

For us.

Yes. Maybe if we drop down to have a look at Phase Ib and I'll just jump on to this slide here. So maybe you could just talk us through the Ib results and why this led to a Phase II study on what the FDA is particularly interested in?

I mean this is a -- I quite like this slide actually. It talks about a benchmark, and the benchmark of what we spoke with clinicians to identify when you start a study, what would you expect in terms of a good result. And so we created the benchmark. Here you can see 30%, 45%. This was Ib study was in T-cell lymphoma. So that's CTCL and PTCL, two sort of classified T-cell lymphomas. And we wanted a serious adverse event less than 30%. So you kind of got to know what you're doing -- what you want to expect before you go into it. And so that was that benchmark and you can see which is a recently approved FDA product had a reasonable response rate. The duration was a little bit less than our benchmarks. And certainly, the adverse events profile were not so great either. So from the Ib study, which was in T-cell lymphoma, we had 11 evaluable patients. And you can see there that the results were clearly above benchmarks in terms of response rate, clinical benefit, the duration and there were no attributable serious -- attributed serious adverse events to PTX-100. Now that was in a combination of PTCL patients and CTCL patients. and PTCL patients are pretty fragile patients, and they are quite challenging, as you can see by the benchmark duration of response time being much less. So that sort of influenced those results. Now we had 1 patient who was in CR and was holding up the closure of the Ib study. And following discussions with Professor Miles we felt that we could move that patient into a compassionate access program where they continue on drug and that allowed us to close the Ib study and sort of do what they call cleaning. So they need to clean the electronic data process and things like that. And in doing so, it allowed us to do a sub-analysis of the CTCL patients only. So there are 7 evaluable patients in the CTCL cohort. And you can see there that we -- the response rate was pretty solid, well above benchmarks. The clinical benefit rate, so that means they either had stable disease or better was 100%, which was really encouraging. And the duration of those responses was out to just over a year and again, no attributable serious events. So what does that mean? So when you look at clinical benefit rate, if you've got a patient, yes, they may have stable disease, but their disease is settling down to the point where they are not scratching, their pain is reduced, they might be sleeping. And so there's real benefit on that, even though the disease is stable. And so that's -- in this CTCL, it's considered very positive, a stable disease approach. So yes, we were reasonably happy with those results. But again, it's in 7 evaluable patients. So you have to be cautious.

Yes. Yes. I mean for the broader cohort also strong results when you...

Yes.

Right? So if you talk about obviously the 43% and 100% clinical benefit rate is an amazing result even for a small sample. Duration result of 12.4 months. Why -- what's significant about the -- why does the duration of response? Why is that so important?

Well, I guess patients are in a progressive environment. So these patients have already failed 3 systemic therapies. And so they've been refractoring or relapsed to a number of other therapies and their disease is progressing. So they're becoming more challenging. So to actually -- to then have a 12-month duration of response PTX-100, that's very significant. And so we know that patients who are in Stage IIb have a medium overall survival of less than 5 years. But if you're in you're really down to 1-year median overall survival. These are -- that's a significant amount of time to either -- to have at least a stable disease or often a better response. So that time means a lot in these patient cohorts.

Yes. And so going into IIa, right, what are you looking for? What do you think leads to a registration study in IIb?

Well, I think we received Fast Track Designation after we went through the IND process for Phase II, and that was on the back of -- there's a clear unmet need and the results that the FDA was seeing. So when you think about what could be beneficial is certainly similar results we sort of -- yes, this is a better slide. We see that for the IIa, if we can identify the dose and really then also have efficacy and safety in that same range, we will be definitely going back to the FDA and saying, there's an opportunity here. With the Fast Track Designation is an expedited pathway. You acknowledge that there's a clear unmet need and you would like to get active therapies to patients sooner. So that is encouraging. It will be down to how the FDA responds to that, and everything is a negotiation. Even the Phase IIa was a bit of a negotiation because you see we've got 2 dosing arms in our Phase IIa. And that there's a program called Project Optimus at the FDA, and that they want to have an optimal dose as opposed to the highest effective dose, which is what used to happen in oncology. So they're still fine-tuning that, and we're fine-tuning that. So we use a Dose Optimization Committee to find an optimal dose based on the efficacy and safety of the IIa and then the opportunity there is there for the IIb and we'll talk to the FDA about that. But fast designation means expedited pathway. And so they're trying to encourage us to beat this up.

Yes. And so what happens when you get to IIb if it's a registration study?

If it's interesting study, it gets very busy for us, but it will be probably busy for us before then. We will engage more steady sites at that point where we're certainly engaging with all the clinicians and all the investigators. But the other flip side of that is on the business side, we will be, obviously, near term from a commercial perspective near term to NDA. And so that becomes a very attractive proposition for companies. And so we'll be discussing business development and those options at that time as well, maybe even sooner than that, depending -- as results come out. This is a study where the Dose Optimization Committee get to have a look after there's 10 patients in each of the dosing arms. So we'll get to know that information, and therefore, we'll -- we always discuss things with partners, potential partners. And so that will be encouraging. And so it's very rare these days to be able to get close to an NDA without very serious commercial discussion.

Yes. Very good. In terms of -- I mean, this slide here, which is sort of the process through Phase II, is there anything to call out here?

Well, I guess it highlights the design -- they're all interrelated actually. The FDA influenced the study design. The results really influence the fact that we go for CTCL. We're nicely into a IIa, IIb design, which I like, some people don't, but I like that because we get a definite inflection point in the mix there and the potential for a IIb registration study. If we can fine-tune the dosing there, it all rolls through. And that's the important thing. So -- and obviously, the patients, I mean patients will benefit from this therapy. We've seen that in terms of our Ib results for CTCL, 100% clinical benefit rate. And that's important. And so when clinicians can see patients benefiting, they also get encouraged. So yes, it's all part of the mix here.

And as far as the recruitment of patients goes.

Yes. I mean that's -- this is a rare disease. And they don't -- they're not around every corner. My team are actively working with clinician sites, we will have by the end of the year, all the U.S. sites that we had planned to open this and we are hopefully about to receive some information from the European or EMEA about allowing us to start the European sites. So we need to have a number of sites open to actually get patient recruitment because it's a rare disease. And patients have also had to fail 2 other systemic therapies. not have had a stem cell transplant. So there's some nuances within that patient recruitment process. But in terms of team awareness and it's very high. And it's not hard to imagine what our focus is there.

Yes. And I think it was mentioned, maybe I pick this up on the webcast at that there is a high instance of CTCL in Japan. Is that a market that you're able to enter?

Well, they also have an orphan designation approach there, too. So it takes some nuance there, and we are looking at that at the moment in terms of how we engage with the Japanese market. We would -- if we move into a IIb registration study, there's a possibility we may or may not -- I would like to add a Japanese component to that because it would be very helpful. but it all depends on negotiation and how we've engaged at that time. But our key market is the U.S. market. So anything that would disrupt the U.S. market approach would have to be well thought of and we're not really aim to get in the way of that. But certainly, the Japanese market is a significant market. They have an orphan designation. So it strengthens our commercial attractiveness but they do have some nuances about doing studies there. So -- and hopefully, they're about to change that actually. So they have changed and they started to get a little more flexible about having patients in Phase III or pivotal studies, global pivotal studies that if you've got 1 or 2 arms from a Japanese site, you can actually get some benefit there. So those are the things that we think about on a regular basis and the discussions we have with various Japanese companies.

Okay. Joseph has asked, how long will it take for the first patient to be dosed in the EU?

Well, the -- so the process is -- there's a 28-day screening. And so once the patient is screened and suitably goes through that, they can be dosed. And so when you have your first site open, which we hope to have before the end of the year, it's probably going to be more of a January, February type scenario. But we do know that we've been discussing with 6 sites in Europe quite extensively. And we've also been going through the European Union process. And so there's been lots of discussion going on there. So we hope that these sites -- well, we anticipate these sites have already identified where those patients are and depending where they are fitting within their clinical program can start the screening of those. So 28 days and then they can be dosed. So it's not like they can turn up tomorrow and you can start the dose the following day. There's quite a lot of process just to follow, but early in the new year.

So from the trials and the patients that are currently in those trials, is there any kind of soft data or any kind of updates that you can provide?

Not at this stage. But yes, I mean, to be honest, it's something I'm looking at and seeing what options there are. But we -- at this stage, the dose optimization committee there is to review it on 10 and 10 each arm. But I mean, it would be nice. That's where we sit at the moment.

And then for anyone that hasn't been in 1 of these sessions before, I guess, just understanding the initial target market for CTCL, what is that?

Yes. I mean in the 8 major markets, there's -- we have some data to show like over $600 million worth of patients -- of target market. But with our Ib, we are actually in T-cell lymphoma, and that's $1.8 billion. And we think in the U.S., particularly, we will run an investigator-led program for PTCL and so we're hoping to gain some leverage in that market as well using the compendium approach. So in market access terms in the U.S., they have FDA approval, but they have compendiums and quite often on a compendium, you have a registered product but with other indications under it, that the clinicians can use to go to the payers and to get reimbursement. So it's a market access nuance but we need an investigator-led study program for that, which is what we'll be looking at.

Okay. And so in the IIa, how many patients do you need to put through the trial?

In the Phase IIa, it's placed up to 40 patients. But once there's 20 patients 10 on each dosing arm, there's a Dose Optimization Committee that will actually come along and review the data and they'll decide -- so yes. So you can see here the Dose Optimization Committee. So when there's 10 in each of those yellow boxes, 10 patients, they'll look at the data and they'll make a consideration back to us to say, actually, we feel that there's a -- we can identify the optimal dose or we need to get another 10. We need to get another 20 patients, but it's up to 40. So there's a bit of flux around the halfway mark.

And I know you can't leak this. So I'll ask this with respect and disclaimers and so forth. But the results that you've had from Ib, I mean, if we're getting results like that, that's the kind of results that would potentially lead to the decision to be made, then that IIb could then be begun as a registration study. Is that -- is it generally some way correct?

You can't be there. I mean, it would allow us to have a really strong conversation with the FDA.

Yes. The other element here is that at the moment, for those patients, what's the alternative? So to get that therapy to market and if you've got the low adverse effects, a good rate of duration and excellent clinical benefit, the alternative for people at the moment is pretty grim.

Yes. And these patients have already -- or these patients that will have had already 2 systemic lines of therapy. They're typically in stage 2 or 3, some are 4, and so they are progressing. And so as I mentioned earlier, that medium overall survival is not looking great. And so yes, they're looking for opportunities. Interestingly, the clinicians talk about a really active tumor microenvironment, and that's where combination therapies are starting to come through. And that's where PTX-100 only having -- like having serious adverse events attributed to it means that from a combination perspective, it's actually very, very attractive in terms of a combination approach. It's a different mode of action. It's not going to add to the fragility of the patient. It provides an option. And whether they stage it or where they do it at the same time. I mean that's where the nuance will come. But certainly, it's setting itself up for a good single-agent therapy, but a really attractive combination therapy as well.

Yes. And for patients, I mean, as you mentioned, these patients you're getting after they've had a couple of different attempts at cure, or addressing the cancer. I mean if you're able to get this to people at the early stages, can there be, I mean, a better, I guess, reduction of tumor type of response? Is that a view that getting it earlier helps? Or is it another factor?

Typically, you need the data to demonstrate that. But normally, you see drugs that are sort of approved in second and third line. And you see over the time they creep forward in their first line to hitting closer up. And so -- and yes, it will be about how the clinicians consider the attributes. And when you saw them fail with high 30s as serious adverse events and a short duration of response, maybe you would consider having something with a longer duration of response, less serious adverse events going ahead of that. But it's up to the clinicians. But in this study, it is after 2 previous lines of systemic therapy. And so our results will be based on that. And so that's all we can say at this stage from a data perspective.

Yes. There was a question with Joseph. I'll make a comment at the start, and then I'll hand over to you, but is Joseph question was is still positive about trials. It certainly was on Ib. We haven't spoken to him on IIa, and we might interview him at some point in time. But James, I'll let you answer that.

Yes. No, he's very positive about this. He's our lead investigator in Phase IIa. He has been recruiting patients. He continues to be an advocate here. And he's a clinician, he wants what's best for his patients. And he's the lead investigator on the study. So I'm not going to talk for him, but I can just point to the fact that, yes, he's part of this definitely.

I've kind of got through most of my questions, but I thought it'd probably be good to click through this slide as a reminder to people on where we're at and what it means with Fast Track Designation and shortening the registration pathway. So maybe I'll let you, James, talk through this slide.

Yes. So this slide is labeled PTX-100 CTCL status quo. This is a classic drug development process. And in the green is where we are at. We are in the Phase II component, dose finding type studies. But if you look at our FDA engagement, you can see we have orphan designation, they provide acceptance for our Phase II study. And then early this year, we had Fast Track Designation. So that really shows a positive intent and Fast Track Designation is an expedited pathway in the FDA process. So that means that you get to speak regularly with the FDA. You can also do a staged NDA submission, if you choose to. But it's really about the FDA acknowledging that there's a clear unmet need and they want to get active therapies to patients as soon as possible once they go through the process. And so I was pretty comfortable with that. And so what that means is that you can shorten that registration pathway. And so based on data, having the right dose and discussions with the FDA you can go through the standard process or they may choose to look at more of an accelerated process. And that would mean that the Phase IIb would be more of a pivotal study moving towards marketing authorization if it was positive. And so that's the benefit there, and so yes, it's an exciting time. And now that we've got orphan designation in Europe, that also strengthens our commercial position. So you can see we're mirroring a few things here. We'll look for Fast Track Designation also in the EMEA and those sorts of things. There's a defined process that we're following, and it's nice to tick the boxes as we go.

Very good. And I think people are just starting to cotton on to where PTX is up to and where they're at and the opportunity here. So I think it's going to be interesting times ahead for shareholders. That's my view. Philip has asked, do Stage IIa patients continue to IIb?

They'll continue on therapy, yes. So they'll continue until they progress. And so they stay on therapy. So IIb, they'll be new patients but they're still getting the drug unless -- yes, at the moment, it's a single arm, but maybe the IIb might be -- they might add a comparator arm at 3:1 ratio or something like that. There might be some nuance in that. But patients in the IIa are on therapy on PTX-100 and they'll continue on their therapy until they progress or they just keep going.

Yes. And so just to go back to the end of Phase II, right, if you do a registration study at IIb, all right, that market authorization period. Is that -- is there a time line to that? Or does it just sort of happen as part of the process and you complete and you received your authorization? Have you got a comment on that?

That's another process and NDA has called out a new drug application NDA. With our fast-track designation, we have an ability to do a rolling NDA. So we may choose things that we feel we're not going to change going forward to actually submit it early, and that means the FDA get a chance to look at it ahead of time and that shortens the approval times down. So we will submit. The key data is the outcomes of the pivotal study. The FDA review it. They give you what's known as a PDUFA date, and that is the date that says whether you have an approval or not. Now that can be up to their discretion. It can be a year, it can be more, but with the rolling NDA, we hope to -- that might be a bit faster, but it depends on the data, but there's a clear process, and I'd love to be in that process. happy to be in a process like that.

Yes. Lots of news, value-creating news on the pathway to that point, right? So George has asked -- I might just -- George, I'll take liberty of reframing this question slightly. So maybe make a comment on where you're funded to, to what point you're funded to?

We're funded to milestones within the Phase IIa. So we would like to -- we definitely find it to data. And that will allow us to look at partnering options, ways of capital raising and things like that. So it's -- yes, it's not an expensive process.

To tell us where we're at, potentially getting some feedback from the FDA by that point.

We would still be in the Phase IIa process. So it would depend if the Dose Optimization Committee had come back to us and said we have a dose, we might get some feedback, but I'm not sure how the timing of that, it's all about recruitment. And so I'm a bit hazy on the timeline because it comes down to how many patients we get in over a period of time. And rates of these can be peaks and troughs and so...

So would there be data readouts, I guess, is where we're leading to? What news will we have between now and then?

We'll have data readouts.

We have a good understanding of whether we're lining up with similar data to say Ib, for example. Yes?

Well, yes, I mean, there will be a data readout on -- yes, on the data. It would be -- yes, I can't -- I mean I know what I would like it to be, but it's certainly -- it comes down to the data. And that's the essence of clinical development. We're highly reliant on data. and speculating on data has been known to be difficult for some people.

Yes. So I guess in terms of this milestone chart here, is there anything to call out in particular?

Well, you can see this process involved in this chart. We already have Orphan Drug Designation in Europe. The first site will be key, and we're really excited about getting to that point. One thing in there is a mode of action. So this is something we haven't talked about today is, it's like we want to look a little more about how we work and -- because that will help us fine-tune where our next potential tumors are that are more likely to respond to PTX-100. And so PTX-100 and CTCL, we're in Phase II. So it's obviously going pretty well. But we would like to expand the opportunity with PTX-100 in terms of other tumor types that may benefit from PTX-100 and so the more we know about the mode of action, and that's what we're working on at the moment, will help us direct to us to other tumor types. And again, that helps those patients that again helps our story in terms of commercial benefit and those sorts of things. So there's a lot -- there's 3 letters there, but there's a lot in that.

Yes. And to that end, I mean, your RAS inhibitor, maybe you could just say a few words on why you think that the PTX-100 so far has been successful in doing what it's doing and why that could be replicated in other tumors?

Yes. We know that there's 22% of RAS mutations occur in cancer -- 22% of cancers have a RAS mutation. Now RAS is a group of proteins, which is let's call a super family, we actually inhibit an enzyme, which disrupts prenylation, so it disrupts the protein adhering to the cell wall and therefore triggering downstream oncogenic pathways. So that's a whole lot of stuff there. But we need to know more about what that downstream effect is, and that will help us direct what we can do for other tumor types. And so it's -- I'm not -- I'm a pharmacist, I'm not a scientist, but it gets pretty complex some of those discussions but I'm glad we've got smart people on to it. So -- but yes, there's an opportunity to look at a little more detail where we may pay a better effect on other tumors and whether that tumor type is an orphan drug -- orphan disease, whether it's more than orphan disease, what we need to do to commercially benefit from that and those sorts of things. So it's quite a story in that.

Yes. And that turns you from being -- from moving a therapy through to more of a platform -- being seen as more of a platform. And in terms of how that who that's attractive to. What do you think that the big pharma or whoever the type of groups are looking for, they're looking for the success of PTX-100 and they look back and see what the other applications are will they be looking for you to start to move some other therapies forward?

Well, yes, I mean, it all depends on other companies sort of strategies, but companies are looking at their pipelines and seeing gaps. And so they'll see PTX-100 fitting into their pipeline perhaps at a certain point. And then they'll see that there's future opportunity so there might be additional benefit for their earlier pipeline. So we might actually fit 2 holes -- fill 2 holes in their pipeline as it goes forward. So that's also pretty interesting and -- but again, it's about what the company's strategy is. I know some companies that they're only looking currently at products that are about to go through the NDA process. And so they're going to pay a premium for that, but they decided to wait for them. And others are going much earlier. I mean the trends are a little bit all over the place at the moment. As companies start changing their strategies, some drop out of cell therapies and they need to fill up with more molecule therapies and things like that. So it's a forever changing environment. And so that's why our engagement is continuous in terms of that business development process because it may be that you're talking to 1 company and the strategy changes and then you'll suddenly become their next favorite thing. So it's about continuous engagement.

Beautiful. All right. Thank you. All right. Now we've got a session with Stuart Roberts from Pitt Street, who wrote research on Prescient it would be like 4 or 5 months ago now and he's updated that research. Having a look at, I think, how IIa is running and also having a look at the updated data or with the clean data. So he said he'll be able to answer probably more directly some of the questions that you might want to get his opinion on. Obviously, it's not James' opinion, but it's pretty interesting, it's pretty across the story. So that's this Thursday at 1:00 p.m. 1:00 p.m. this Thursday. So if you want to come on to that session type PTX into the chat box and we'll send you an invite. We'll send via be e-mailing an invite probably out to everyone that's on this list and we'll include it in case you missed it. But if you like us you can type PTX in there now. And George's comment was thanks for the update. It's exciting to see Prescient's drug in clinical trial. Would it be reasonable to us for a two sentence summary of what's upcoming for CellPryme and OmniCAR?

Yes. As you can tell, our focus is very much PTX-100 and OmniCAR will be something we'll look at in terms of a partnering opportunity and CellPryme we continue to work in terms of the CellPryme-M and we haven't quite figured out how to deal with CellPryme-A at this stage. But they're there, but I have encouraged the team to focus on PTX-100 and really get that going because that's where the value infection is going to be, and we can work on those cell therapy options after that. So that's just being honest.

Yes. Absolutely. All right, James, thank you very much for the update, and I look forward to meeting back here with you again when we next see some news flow through. And I'm pleased with you leading the session today. We decided to run today as a Q&A because we've done so many page turns during their share purchase plan that we thought it would be good to bring a slightly different format. So you can give us some feedback on that. And we'll take that on board for what we do next. But thank you for all the people who are following PTX and the story and a lot of people turned up to the session today. So we're try to see that engagement. James, congratulations on what you've been able to achieve.

Thanks, Sorry, I missed that last word.

I'll leave the last word with you.

Okay. Again, I just want to say thank you as well. I mean this is -- we are traveling on a journey. The journey is going well at this stage, and I am really pleased that people are here listening to it and engaging and thanks for supporting us. And we'll continue to update you and continue on the journey. So yes, it's exciting times. Thank you.

Thanks, James, and a reminder that if you want to come to the session, we will -- anyone that's typed PTX, and I know it says for updates on news and cycle, but anyone that types PTX in the chat box will get you along to hear Stuart speak on Thursday at 1:00 p.m., otherwise look out for the e-mail that we send across on that as well. Thank you, everyone. Have a wonderful day. Thank you, Cheers.