Prescient Therapeutics Limited (PTX) Earnings Call Transcript

Welcome to PTX's investor briefing, while everyone settles in, I'll go through the normal housekeeping. Any presentations that reach hosts are suitable for self-directed investors who have the experience and capabilities to make their own informed decisions. Any information contained in today's presentation is general in nature. It doesn't consider your personal circumstances, and you need to decide whether it's appropriate for you. We're giving you information for educational purposes and past performance is not a reliable indicator of future performance. My name is Patrick Nelson. I'm the MD at Reach. I'll be hosting the session today, but we're joined by James McDonnell, the CEO of Prescient Therapeutics trading under the code PTX on the Australian Stock Exchange. So today's session is off the back of the recent 4C which announced patient enrollments now up to 29 for the IIa trial, global clinical sites are expanding and referenced the Dose Committee -- Dose Optimization Committee review meeting in December. so I might ask James a couple of questions on that front. And then we'll go to Page 10. Now the deck is quite similar or is the same deck as the one that we have run recent sessions on. So just bear that in mind. We -- there are some new investors on the call today. So we'll run through the deck quickly, make sure everyone is on the same page, and then there will be further Q&A. If you've got a question, put it in the chat box at any point in time, and we expect the session to be -- we'll have a few questions now. James will go through the deck probably 15 to 20 minutes, and then we'll be back for Q&A at the end of that. Now -- just to get everyone on the same page, I'll do a short intro before I hand over to James. Prescient have developed a unique technology, which is a platform, and it can stop some cancers from reproducing. It does this by attacking the biochemical processes referred to as the RAS pathway that are behind 22% of all cancers. And whilst this technology is a platform that can potentially help sufferers of up to 22% of all cancers, the Prescient first chose to prove their technology on cutaneous T-cell lymphoma, which is CTCL. And it's a cancer which is considered by many clinicians to have no viable treatment, therefore, a death sentence. And in the Ib trials for CTCL, an astonishing 100% of patients cancer stopped growing or reduced. and 0 patients experience serious adverse events, which is particularly important as a lot of cures to cancers can be -- can have terrible side effects. So they chose to pursue CTCL in the first instance because it's an orphan disease, which has very limited treatment options. The FDA and other regulators are much more likely to support or fast track orphan diseases and support many other ways as well, which is important commercialization stages. And while this is referred to as a rare disease with limited treatment options, it still represents a $1.2 billion market in the U.S. alone. So the company -- the strategy behind going down this pathway has been very successful. The company has received fast track and orphan drug designation and IND designations from the FDA. The EMA also given them Fast Track designation, and they've moved a great pace. The CTCL is now one of the most advanced therapies on the ASX and moving into IIa, there is a potential for IIb to move with the fast track being fast track to be a registration study. And beyond the results for CTCL, there are now -- there are broader applications for this technology as well. So they're interesting spot. So James, thank you very much for joining us today. Before I hand over to go through the main body of the presentation, maybe just a couple of things are in the recent for, how are you today.

Yes. Good. Thanks, Patrick. Great to be here, and thanks, everyone, for joining us today.

Yes. So now I guess this dose optimization meeting in December is a major milestone for the company to get to the point where that meeting is being scheduled or you've got a time line to that meeting. What are the possible outcomes from the DOC meeting?

Yes. I mean it's very good that we now have the likely results in December from DOC. It's a significant inflection point. What the DOC is looking for, it's a dose optimization committee. They're looking for a dose effectively, but they'll also review efficacy and safety. They'll look at the efficacy in different arms and the safety across the whole study. What they're likely to say is, well, the goal is to choose a dose. We're halfway through the study. Could they choose a dose at Away, may or may not. They may choose to go further. But what we'll get is safety information. We'll get some efficacy information. And that's pretty important. We're halfway through the study. It's -- everyone is looking out for that information. So it's an exciting time.

Yes. I mean getting some more results back, I mean, anything that looks like the Ia results, what would that mean?

Yes. I mean the Ib results were well within the range of what we're targeting under our benchmark sort of target product profile. So those are the results that we are after, and that would be a very good win. And so we're looking for those types of results. But this will be the first time we'll get a look at how the study is progressing. It's an interim measure. So yes, it's an exciting time, the first time we'll have looked at it and they give us an idea of where we're going. If we can define a dose that early, that means there's been some really good efficacy data in one particular arm, which helps us then go further in the process.

Yes. And in terms of this -- what does this mean for the types of partners that you would be having discussions with? And who would those partners be?

Well, I mean, we have been talking to a number of partners. These are large, midsized and other companies that are parented by large generic companies in the U.S. as well. So there's quite a mix of them. There's also a European-based on. But they're all at the moment, all the discussions there, well, let's see what comes out of the interim readout, which is coming up. And so this is what's coming. So we will gear up to the next state of partnering discussions, and that's when it gets a little more serious and where we can start getting an idea of who and if you like.

Yes. What -- like what are the types of partners that you -- I mean, I know you've been having some discussions. What types of groups you're talking to?

Yes. I mean these are companies that have got -- they're already commercializing products. The mid-tier pharmas are significantly large global companies. A global company is ideal for us. They certainly have presence in the U.S. and then Europe and other places in Japan. So we're looking at those probably mid-tier companies for an orphan disease, which has got orphan protection, there's a good commercial benefit there. And so that's who we're talking to. We -- once we get information, we're looking at partnering going forward for our registration approach and then future commercialization. Recent deals with Sobi and Innate Pharma demonstrate this real value in the CTCL space, and that's what these companies will be looking for.

Yes. So I mean, the Sobi deal you just mentioned with Innate, what was that deal?

Yes. I mean it was -- Innate Pharma had a product called lacutamab. It's quite -- it's got very good results in Sezary syndrome, which is 5% of the CTCL patient population. They are moving towards their pivotal study program. They signed a deal with Sobi, which allows a USD 75 million upfront payment and then USD 505 million milestone payments along the way to registration and then double-digit royalties. And so that really validates the CTCL space. Now we have Fast Track designation in mycosis fungoes, which is 50% to 60% of the subtypes in CTCL. So you can see there's some quite -- there will be quite an interest in that space.

Yes. And what -- you mentioned the 5% of the patient population, what -- PTX-100, what percentage of patient population are you?

Well, at the moment, with our Fast Track designation in mycosis fungoides, this is the largest patient population in CTCL. So up to 70% of patients have mycosis fungoides, whether it's moderate to or advanced. And so it's a dominant subtype to have response and really good responses there would be very helpful as we progress forward.

So potentially 14x or circa that the size of the lacutamab.

Yes, I'm not sure the simple modification works, but it would be nice if it was 14x.

I'm not extending that to the size of the deal. But just for context, right?

There's many more patients that are suitable for mycosis fungoides targeted therapy.

Yes. And then sort of at what stage is it -- from where you are today, right, a dose and accelerated pathway to market is that's when those sorts of deals sort of start to occur. Is that correct?

Yes. I mean if you look at that deal as a clear example of what's happening today, that deal was signed as the Innate Pharma has finished their Phase II program and had worked with the FDA to get an accelerated program, and that's the pivotal accelerated process. They signed that deal, and that deal is funding that whole program. It's also set out what potential is in terms of registration and things like that. So we're in the Phase II program stage, and we results -- solid results in the Phase II program would lead us into nearing that phase.

Yes. It's an exciting time. It's quite rare and unique that a company is at the point that P and bring new people looking at this, I would have a look at that. You can reflect on also the valuation and the potential upside of PRCI at the moment. But just moving on, 29 patients now enrolled in IIa. I mean, overall, how do you feel about where enrollments are at versus what your expectations would have been at the start of the IIa setting the IIa trial in motion?

Yes. Actually, we're doing quite well because we still haven't implemented the French site, and we're actually on target for where we thought we were with the French site. So we're happy with that. 29 patients enrolled. We've got 20 evaluable patients we have now set aside for the DOC patients in screening. I think it's progressing as such. The recent time -- the recent quarter was actually summertime in Europe and the U.S. That's typically a slower time for activity in clinical research. And so it's good to be through that phase and then getting back to normal. So yes, very happy with the progress.

It slowed down a little bit last quarter. But do you feel like in December, when you -- by the time the DOC meets, is there -- I'm not looking for a forward-looking statement here, but like is there a world where we could be in that meeting with 40 enrolled patients?

I couldn't say. I mean we are progressing towards that. We are hoping that we can get those patients enrolled, whether there's 40 at that time, based on our current enrollment, it may not be possible. But I mean, at the moment, these -- the clinicians find patients, they come and they -- it's a little bit hard to predict sometimes. But we're happy with the progress. And the data at the DOC, we'll get some interesting outcomes.

Yes. Now we had a question saying with the 20 patients now available in dose optimization committee meeting in December, can you clarify whether the shareholders will receive actual efficacy data, including objective response rates for each dose cohort or simply a committee's recommendation?

We'll receive a report from the DOC and the Board will review that report and then that information should be made available. I don't know what's going to be in it, but I do know that they'll be looking at efficacy in both arms. They'll be looking at safety and they'll also be looking at compartment. So this is a CTCL, it's cutaneous. So they'll be looking at the skin, they'll be looking at the blood, the nose and the viscera, those results as well. So there could be quite a lot of data. I think they're also going to have quality of life information there. And as you know, CTCL is quite challenging for patients. And so it will also be quite interesting to see the quality of life information.

Yes. Okay. Good. The follow-on to that question was if the committee recommends recruiting additional patients before selecting dose, will management disclose whether that decision reflects insufficient efficacy, comparable efficacy between doses or simply the need for more statistical confidence?

mean we'll take the advice of the DOC and follow that. I mean it could be any of those options. So it is -- the DOC are the experts and we'll take their advice.

Yes. Okay. The recent raise $6 million boost your funding. Can you talk us through some of the milestones that funding sees you through?

Yes, absolutely. So I mean we -- as of the 1st of October, there's around $11.8 million. We're expecting[ 3.44 ] coming up in the from our R&D tax incentives. So there's about $15 million in the pie, and that will get us significantly well through the milestones in the Phase IIa program. And as we work through that and understanding what that looks like. So we're comfortable where we sit. And DOC in December is our biggest milestone. We'll look at other milestones as we get to the end of that. There could be a wage set could be. It all depends on what comes out of December, and that will help dictate what the new milestones are.

Good. Dave has asked, do we know the date in December yet?

Not exactly. No. So the -- but it definitely will be because we have I know.

I know you don't necessarily know the exact nature of this, but after that, how quickly will the market be informed of whatever is going to be released?

Well, my understanding is that, that would be a material finding. And so we are obligated to make that known to the market as soon as -- so as you have. Yes.

Okay. Very good. All right. Let's pause there, and we'll be back for more questions. If anyone's got any questions, put them in as they occur, you will handle them all during the Q&A which should be in the next 15 to 20 minutes. Thanks. Back to you, James.

Thanks, Patrick. All right. Well, thanks for joining, everyone, and I'll take us through our deck today. So there's the disclaimer safe harbor for forward-looking statements. And the highlights. I mean, these are the 6 main highlights to take away today. We have PTX-100, which is a lead candidate from the Yale University, so very prestigious it's pioneering need a drug in an area of -- that hasn't been worked on before and has potential to address 1 of 5 cancers. So we disrupt the RAS pathway. It's the first GGTase inhibitor in the clinic. And so we're not competing with other GGTase inhibitors around. And in we're targeting a blood cancer, which ironically comes out of the skin. But from our Ib results that showed promising and it was very promising, and that's what has led us to this program. the near-term milestone, as we've just been discussing, is the Dose Optimization Committee review, which we -- the Phase I will take place, and we'll have that in December, which is a very important time for the study. And of course, our goal is to create value, value for patients, but also value for our shareholders and partners. As we progress and we've already found that with the recent deal that there's clear value in the space. So a quick background. This is from the cancer foundation, but you can see a normal sale growth in the normal sale growth. What I'm added here is where the RAS family play a role, and that's in that in that cell replication phase there, you can see and forward -- moving forward to other new tumors. and so here is our mechanism of action, if you like. If you have a RAS family protein, it uses GGTase to actually prenylate and that prenylation goes on to the downstream at rail Row and those sort of RAS proteins downstream, which create the tumor effects. If you use -- by adding PTX-100, it addresses the pocket of prenylation and prevent relation happening. And so therefore, the RAS value proteins are unable to prenylateand they can't change the cell member I mean create their next wave of activity. And so therefore, it disrupts that tumor activity. So an antitumor effect. So that's effectively and simply how it works. And we recently checked how it works by validating through a CSIRO program. And through AI and Piolin, we found out where it fits within the GGTase enzyme and it fits very nicely. The set sale, which is the middle graph there shows that if you move the graph to the right, it shows that it's really attaching a nicely in the good affinity to the actual place where we want it to be. And then the last graph there on the left is demonstrating that there's a reduction in the amount of prenylated RAP 1 proteins attached to the cell membrane. And these are in different cell lines. The first you sell lines, the solid tumor and the last 2 as levies. You can see that we understand what it does and we can see through this invite that it is actually doing that. So that's very helpful. So moving forward, we are first in class, and I mentioned before that we're not competing with other GGTase-1 inhibitors, which is really important. We're creating the space, and we're really getting the clinicians on board in terms of our GGTase-1 inhibitor and potentially extending that to other cancer types. So in CTCL, we ran our phase 1 program and then a Phase Ib program looking for an asset or an indication that had RAS involvement and has a clear unmet need and we could work with from a regulatory standpoint and there was value in it. We've settled on CTCL from the 1B results, is RAS, there's orphan disease. There appears to be very good results and the market size is significant from -- as we've just been -- shown from a third-party market research company. So all the right things are replacing. We also now have the FDA designations of Fast Track for mycoisfungoides as well as the Orphan Designations from U.S. and Europe. So we've set the platform, if you like, for CTCL. So CTCL In itself is actually not a very nice disease. It's the T cells of the white blood cells really attacking the skin and these T cells migrate and they really cause problems with the skin and then they start affecting the nodes, the viscera and the blood. So all pretty nasty stuff. There's significant quality of life issues with pruritus and itching and lack of sleep, and it's really quite disturbing, if you like. We know that there's 3,000 new patients per annum in the U.S. And there's 2 main forms of CTCL mycosis fungoides and Sezary syndrome. Now mycosis fungoides is the largest subtype, up to 70% of patients are classified as mycosis fungoides, typically, a lot more skin involved and then they start progressing through each of those nodes in blood. Then the Sezary syndrome, which is a more aggressive type of CTCL, it's about 5% of the patient population, much more skin bar, but also more blood involved and so a little more tricky to manage. So when we look at the overall survival of CTCL, this is the 5-year overall survival, you can see there's clear areas here, the early phase mycosis fungoides stage where they're really challenged by the quality of life and issues associated with that. And then as you get to more advanced stage Sezary Cidery syndrome, you're not only charged with the quality of life, you also challenge with the survival and it gets down to quite significant poor survival there of 18% 5-year overall survival. So not a great one. And you can see that current therapies are modest in their efficacy. There's a clear need for new therapies and then hence, the fact that PTX-100 has Fast Track designation for mycosis fungoides. So the right thing to choose. Now we have -- there are therapies in this space. But as I've mentioned before, they're modest in terms of their approach. On the left there, you can see sort of like antibodies carrying payloads. On the right, you can see different antibodies timing, different antigens on the cell wall down the bottom, you've got HDAC inhibitors, which are really playing with epigenetics. And right up the middle there, you can see how RAS proteins trigger they're downstream triggering. And then if you group them all up, you can see that there's clear there's clear groups there. And then PTX-100 really takes out that middle area there of the RAS protein. So it prevents a prenylation -- so therefore, the rest family protein is not able to get their general group attached and therefore, they can't attach and signal downstream. So that's clear. A good result there means that we've got a unique mode of action, which is not copied by others. And so it will be very good in terms of mono and also combination approaches. No, we moved into the Phase II program because of the Phase Ib sub-analysis. And you can see in the green on the right there, the response rates, objective response rate. And right down in the bottom, we see the attributed to PTX-100 zero. So it's getting responses without causing further issues to the patient. Now if we go right across to the left, we have benchmark and drug discovery, you can also call that the target product profile. So what we would expect and what we would be aiming for to progress the asset. You can see down the middle, 2 approved FDA-approved CTCL products ones Life, which is an antibody carrying a payload and the other is Poteligeo, which is an antibody targeting a particular antigen on the cell wall. You can see around the objective response rate benchmarks but quite poor on the approaches. So there's room for potential new lacutamab assets in the space. Now lacutamab is the product which we've been discussing in terms of that's recently done the deal. This is an antibody tiding a particular antigen on the cell wall. In terms of Sezary syndrome, you can see there that there's a very solid response rate of 42.9%. And then Phase II program, mycosis fungoides is quite modest. And so hence, they have now a pivotal program, which has accelerated surgery syndrome component and then convert component. Now this is the per program that they've recently signed their deal with Sobi, which allows for USD 75 million upfront and then $505 million ongoing milestones as the product gets to registration and then double-digit royalties. So that's a pretty nice deal, demonstrates its value in the space, and that validates our movement in CTCL. Now I mentioned a couple of times about the safety profile. And you can see the difference between these profiles. PTX-100 is in Phase II program. So still work still going through the programs, but these are the products you can see are quite -- have quite significant adverse events. And so very helpful. And this means that with a unique mode of action, moderate or favorable adverse event profile, it's really good for a combination and really not really challenging the patient for adverse events, but more providing a unique mode of action. So that's actually pretty favorable. So we've talked about a Phase II program, and we've talked about a Phase IIa. We're moving up to the dose optimization committee time. What does this mean? Well, we started the Phase II program. The Phase II program is Phase IIa, which is the dose optimization part where there's 40 valuable patients who -- patients who are refractory and relapsed to mycosis fungoides, the Sezary syndrome, they've received 2 prior lines of systemic therapy, at least some of them, I know -- I believe some of them have more. And we see that the randomized to 2 dosing arms. And so the dose utilization committee is there to define a dose based on these dose optimization arms in the study. After 10 evaluable patients in each arm, the Dose Optimization Committee can start looking, and this actually has occurred now and they -- once they get the GRS and all the things sorted out, the Dose Optimization Committee will meet in December and provide a report for us. determining the next steps in the study in terms of efficacy, safety and also quality of life. Interestingly, I know that clinicians are very interested in the MSA, which is the skin response which is what they typically use clinically. This is a cutaneous disease. And so -- they do want to see the results from the mSWAT outside of just all the GRS or the global response score. So there's going to be quite a lot of data to sift through, but there's a lot of interest in this. So where are we heading? So we're in this phase, you can see the ongoing component there in the phase IIa, which is what we're up to, aiming to find a dose for the future program currently expected to be a 2b and Phase III marketing authorization on the market. However, we do know that we have Fast Track designation and Orphan Designation. We have an ability to communicate with the because of that Fast Track designation. And so there's a potential clinical path which involves more of a pivotal program as the next step and moving to a marketing authorization on the market. Now this is -- this is similar to what lacutamab are now embarking on. And so you can see that the FDA are open to these types of arrangements. It will be based on the dose, the efficacy, patient population and maybe the design of that pivotal program. So there's a bit to discuss, but there is potential there. Now as Patrick said, the market is significant in the U.S. alone, $1.2 billionas we've gained from third-party research, and there's 3,000 new patients per annum, and that's increasing in the U.S. So definitely a good addressable market and typically, we would go first. And when we're looking at that market, and we can see that mogamulizumab entered that market in late 2018. You can see here from 2020, 2025, that their market share grew, it actually grew the whole market. And so that tells me that when there's a clear unmet need, you've got a unique mode of action, clinicians are going to use your product that's approved in CTCL. Now the use of mogamulizumab is actually used in early phase and advanced phase which has surprised me when I looked at the data, it means that clinicians are really struggling not only in the advanced stage of CTCL. They're also struggling in the early phase. So patients, even with the quality of life issues are having problems and refractory and relapse to other therapies. And so is there a clear need for new therapies. So our strategy is pretty clear. We're CTCL centric at the moment. We need to demonstrate the efficacy and safety move through the program to a registrational approach and partnering approach for commercial benefits. And then we're also looking at other indications because inhibiting the RAS family pathway disrupts potential other tumor types, and we know that RAS in the bottom 22% of all cancers. And so we'll look at that in terms of perhaps an another orphan disease first and then something a bit broader as we strengthen our IP and looking at other commercial approaches and reviewing complementary assets as we move forward with gaps in our pipeline. So there's keen milestones here. I mean the clear one is the dose optimization committee in December. This will be a key driver to -- for us as we move forward. And then as we progressed through that study, we will be an FDA Type B meeting to determine the next steps in terms of pivotal programs or Phase IIa -- IIbs and things like that. So lots to be done, but the clear inflection point will be December. So we've had a strong management team here and a very supportive Board as we progress and they continue to support us and that will be part of receiving the package from the DOC in December. So we have a great value proposition in terms of PTX-100, it's first-in-class, its potential to address a large number of cancers. We're seeing good results. We've got FDA support from the designations in terms of Fast Track designation in mycosis fungoides as well as Orphan Designations. And developing this data will also provide really solid partnering discussions as we progress. So with that, I'll thank you and hand back to Patrick and take further questions.