Prescient Therapeutics Limited (PTX) Earnings Call Transcript & Summary

Welcome, everybody, to this PTX Investor Briefing. While people settle into the session, I'll just quickly provide the disclaimer for today. The presentations that Reach hosts are suitable for self-directed investors with the experience and capability to make their own informed decisions. Any information contained in today's presentation is general in nature, does not consider your personal circumstances and need to consider for yourself if it is appropriate for you. And the information we're giving you is for educational purposes only. Past performance is not a reliable indicator of future performance. Great. Hi, everybody. My name is Christian Riedel. I'm Executive Director here at Reach, and I'll be hosting this session today. I'm joined here, obviously by James McDonnell, CEO of Prescient. Hi, James, good to have you back. And today's session is off the back of Prescient's recent ASX announcement, which was an update on their Dose Optimization Committee meeting, which is now scheduled for December. What we'll do today for the session because we have a mix of existing shareholders and also new people to Prescient. We'll -- I'll ask a few questions to James first about the announcement itself. After that, James will do a quick deck run through, which is mostly targeted at people who are new to the story, and then we'll open up the floor for Q&A. [Operator Instructions]. As I said, some people are new to the story. So I'll just quickly kick off with a short introduction to Prescient. Prescient's lead drug, PTX-100, is one of the most advanced cancer therapies on the ASX. It targets a disease called cutaneous T-cell lymphoma, which at advanced stages is seen by many clinicians as basically a death sentence. It's a truly terrible disease. Patients are constantly itchy. They may suffer from secondary infections, can't sleep, so really affecting the quality of life. And Prescient's results in their previous Phase Ib trial had some remarkable results with 100% of patients recording either a halt or reduction of their cancer. And even more remarkable was the fact that there were 0 serious adverse effects. And then even for those patients whose tumor did not shrink, PTX-100 can have some really positive effects such as reduced itchiness and getting their sleep back, so really things that are relevant to quality of life, and James will obviously talk about that. Since CTCL is seen as a disease of unmet need, PTX has received Fast Track and Orphan Drug Designation from the FDA. And they're now well into their Phase IIa study. 28 patients out of 40 targeted are enrolled. And out of those 28, as just announced, 20 are now evaluable patients, which means that these have received 4 doses. This is a milestone for the company because it triggers the first Dose Optimization Committee meeting, which is now scheduled for December this year. And that meeting and the related data readout could be a major milestone for the company. So really worth paying attention to. Getting to this point is really a rare feat for Prescient or for companies in general. And from here, there is further potential for Prescient, like, for example, the potential for Phase IIb to become a registrational study, which would further shorten the path to market for them if that materializes. These milestones could really represent then the start of a real commercialization stage for the company, and I will ask James some questions around that. And so they're really well positioned for these type of opportunities and at a very interesting stage with $9 million of cash in the bank as they're running through their trials.

So yes, hi again, James. Over to you. Let me just ask a few questions about the recent announcement. So maybe let's start like how big of a milestone is it for you to reach these 20 evaluable patients?

Well, this is a big milestone. We're very focused on the Phase IIa trial for CTCL with PTX-100 and to reach this prespecified halfway point is significant. It represents a strong execution focus from the team and also provides some certainty about the Dose Optimization Committee timing, which is an important milestone for us. It's the first time we'll receive a report from experts relating to the dosing, efficacy, safety and those sort of things and the continuation of the study. So it's a critical time for us, and it's nice to know that it is going to happen because we do have sufficiently evaluable patients in each dosing arm.

And what specifically is that committee looking for when they meet in December?

Yes, they're looking to -- it's a Dose Optimization Committee. So they're looking to find an optimized dose. And so that's their goal. Whether they can do it on 10 evaluable patients in each arm, we don't know yet, but that's what we're hoping to get to. If they decide that they don't have quite enough information, we'll have a continuation to a next point that they choose. So this is all about dose optimization, finding that dose, so we can then go to the next step. But it's also -- they'll be assessing the usual things such as safety and those sorts of things. So it's a critical time, and it's an exciting time to know that we've put in a lot of work to get to this point, and we'll see what happens at that point.

Okay. And I mentioned, I alluded quickly to the potential for Phase IIb becoming a registrational study. What is the connection between -- or is there a connection between that meeting in December and the potential for that?

I guess the connection is that the Dose Optimization Committee are tasked with finding a dose. Now if they can do it in December, it means that's great news. It means we'll get to go and have a Type B meeting with the FDA, which we'll discuss the dose, the safety, the outcomes and therefore, work with the FDA to see whether we can interrogate the possibility of running that pivotal program as the next step. We do have Fast Track designation, so that's an acknowledgment by the FDA that this is a clear unmet need and Fast Track designations are designed to get active therapies into the patients as quickly as possible. And so under those sort of parameters, getting to the FDA Type B meeting is critical. The Dose Optimization Committee is there to identify that dose. And if they do it after 10 evaluable patients in each arm, that's great. But we'll have to wait and see what they come up with.

Understood. Final question. There's also a data readout on how these patients have done so far. Where does that sit on the time line? And where is that coming out?

Well, we will receive guidance from the Dose Optimization Committee based on what they've seen in the 2 arms of the study. So it's a 2-arm study with 2 doses. And so once we receive that guidance, we'll be able to issue a report based on that.

Understood. Okay. Great. These are all my questions on the announcement. I'm going to hand over to you, James, now to run through the deck. If anyone has questions also including to this announcement, just again put it into the chat box, and we'll come back after the presentation to ask some more questions to James. James, over to you.

Thanks, Christian. So a safe harbor statement here for forward-looking statements is the usual. So -- and here is a company snapshot. It was as of the 25th -- 24th of August. You can see that we do have $9 million in cash at the end of the financial year, which is our latest reporting time. And we're around the $70 million market cap and progressing well. So there's some highlights that you'll see today. And these highlights are related around PTX-100, which is a drug we've licensed from Yale University. It really disrupts a RAS family pathway, which -- and RAS is implicated in up to 22% of cancers. So therefore, effectively, we're pioneering a drug platform, which can have applications in 1 in 5 cancers. So that's what you'll hear about today. PTX-100 is first-in-class. It's the most clinically advanced GGTase inhibitor that we know of, and it is progressing through this Phase IIa program. So that's encouraging. First-in-class drugs also come with some upside, which we'll discuss as well. We're targeting a rare blood cancer based on our initial responses from our Phase I program. Interestingly, this blood cancer exhibits predominantly in the skin before moving through to the nodes, the viscera and the blood. So it's a very complicated disease, and that's one we'll take you through. We have near-term milestone, which we have just finished discussing relating to the Dose Optimization Committee. This is the first time we'll be looking at data from the Phase IIa program. And so it is a significant point for us. And we continue to create value. We've recently seen a transaction in the CTCL space by another company, which really demonstrates there is commercial value in this environment. And so we are preparing that in terms of continuously speaking with potential partners and creating that dialogue as we progress. So some good things to look forward to as we move forward. But first, let's look about -- let's talk about the mode of action of PTX-100 and where it fits and how it functions. And so -- and this is from the Cancer Foundation. It's -- you can see normal cell growth happens that way. But when you get abnormal cell growth, so there's genetic changes, you get cancerous cell division and therefore, the development of a malignant tumor. And I've added to this slide, the area where RAS family proteins have a role and RAS family proteins work in that sort of the cell division environment. And so when you're thinking about RAS proteins, they are actually present in the normal functioning. So normally, they switch on, you get cell replication and then they switch off, and that's how they are meant to work. When there's a mutation in the RAS family proteins, they don't switch off. And so therefore, you've got a continuous switched on protein, which is activating protumor effects, including proliferation, migration and survival. And you can see here, the RAS family proteins use an enzyme called GGTase to actually do something called prenylation. So they add a lipid group to the protein. And that lipid group allows the RAS family protein to attach to the cell membrane where it can do that switching. So therefore, we've interrogated that a bit, and we can see now with PTX-100 actually plays a role by inhibiting prenylation by GGTase. So PTX-100 fits very nicely in the prenylation pocket of GGTase. And so when RAS family proteins come along to try and get that lipid group attached to, therefore, switch, they're not able to do it. So we disrupt that process. And through that disruption, we create a more antitumor effect. So we effectively try and switch them off. So we've done some work with the CSIRO in terms of AI and physics modeling. And what we discovered was that PTX-100 fits very nicely within that pocket of the -- prenylation pocket of the GGTase enzyme. And so we tested that further with some in vitro work, and we saw using [indiscernible] (00:15:48) that there's really strong binding of PTX-100. And you can tell this by the movement of the line to the right. So you can see the PTX-100 in the central graph there moves to the right. And that indicates a strong binding, and that's exactly what we were hoping to see. And on the third graph, third table there to the right, you can see we are looking at how much anchoring on the cell wall we get. And so Rap1 is a RAS protein. And so we can see there with 4 different cell lines, so those are 4 different tumor types, 4 different tumors there that we reduce the attachment of a RAS protein on the membrane by 40% to 60%, where the control would be at 100%. So that's exactly what we were looking for, and it's very encouraging. So we'll use this information to add to our nonclinical program. So I mentioned first-in-class. And the reason why we mentioned that earlier is because if you're first-in-class, you are able to go and speak to the FDA and other regulatory agencies in terms of designations. And so we have Orphan Drug designation with the -- in the U.S. and in the EU. We also have a designation called Fast Track designation and refractory relapsed mycosis fungoides from the FDA. So this is something I'll discuss further, but it's an encouraging designation to have. When you are first-in-class, you're not really competing against other GGTase inhibitors. You're building strong relationships with clinicians and you're creating data that allows you to start looking and be first mover in other cancer types. So all very helpful when you have a first-in-class situation. Why are we looking at CTCL? So when you're developing a drug, you start looking for a target product profile. And so we're thinking, well, we need a RAS involved. It would be great to have a high unmet need and a reasonably sized market. And we saw with CTCL following our basket Phase I study and then a more directed T-cell lymphoma study that CTCL fits the bill. So there's RAS involvement, it's an orphan disease. It's a very high unmet need and the market opportunity is significant. And you can see here some outcomes from that Phase Ib study of 43% objective response rate with no drug-related adverse events. And I mentioned there from this data, we've received Fast Track designation. So that's very encouraging, and that is the reason why we're here. So CTCL is a challenging disease, as mentioned by Christian earlier. It's actually a disease of the white blood cell, the T cell, which is normally involved in our immune process. But in this instance, these T cells mutate. They actually migrate to the skin where they really replicate uncontrollably, disrupt the skin and eventually end up in your nodes, viscera and the blood. So it's a progressive disease, one which is not very much fun. In terms of quality of life, as Christian said, when you've got skin involvement and a significant degree of skin involvement, you're really struggling with itching, secondary infections, your appearance is actually socially isolating as well, and you're not sleeping and lots of fatigue. So it's not a great disease from a quality of life perspective. We know that the -- typically, we're seeing -- it's a rare disease. So we see about 8 patients per million in the Western population. And in the States, we see that equates to around 3,000 patients -- new patients per year. And that, we believe, is increasing. Now I've mentioned a couple of -- I've mentioned a couple of times mycosis fungoides. The reason why I mentioned that is because CTCL has 2 main subtypes. One is mycosis fungoides and the other is Sezary syndrome. So it's probably worth looking at that a bit further. And you can see with mycosis fungoides, it's the largest subtype of CTCL, depending where you look between 50% and 70% of cases actually are mycosis fungoides. It's predominantly skin initially and then it progresses more through the nodes, viscera and the blood. The other subtype -- the other secondary main subtype, although it's only 5% of cases is Sezary syndrome. And this is a much more aggressive CTCL where there's more leukemic involvement and there's a lot more blood involvement which creates significant problems. And what do I mean by that? Well, poor outcomes in advanced stages is the headline there. And this is a graph depicting the 5-year overall survival of patients with CTCL. And you can see in the top there, if you're staged at IA to IIA, and you have mycosis fungoides early stage, it's really a quality of life challenge for you. Yes, your prognosis is diminishing, but it's actually more about the quality of life. It's more about having to deal with all those symptoms and the fatigue, et cetera, which creates the problem. As you progress, so you get from -- if you stage from IIb down to IVB, you can see there's a significant progression in terms of your overall survival reduction and from -- right down to 18% at the bottom there. So with advanced stage mycosis fungoides and Sezary syndrome, you're really not just challenged with quality of life concerns, you are challenged with prognosis concerns as well. So it's quite a challenging disease. And we know that existing treatments really have modest efficacy, quite poor safety and tolerability profiles and a lot of patients are refractory and relapsed to those therapies anyway. So -- hence, the reason why the FDA considers this a clear unmet need and has provided the Fast Track designation in mycosis fungoides. So if we look at the different modes of action here with the current therapies. And these are more second-line therapies. Typically, if you're in the early stage, you're getting topical therapies that then progress, you might get a series of chemotherapy. But then you get into the more relevant treatments here, which are second-line treatments. And if you look to the left of the graph, you can see biologics carrying payloads. Those are -- Lymphir is the most recently approved product by the FDA in CTCL. So that's one way of addressing the disease. And if you go across to the other side, you can see Poteligeo and Campath. These are antibodies targeting particular antigens on the cell membrane. And I'll draw you to the IPH4120, which is actually called lacutamab now. And this is an antibody which has some really good results in Sezary syndrome, and they've recently had a transaction done with another company, which I'll discuss in a moment. So you can sort of group these therapies in different areas. And down below there are HDAC inhibitors impacting the tumor gene. So more like an epigenetic approach. And you can see up the middle there RAS family proteins. And you can see that lipid group, the [ geranylgeranyl ] group with the GGTase combines with the RAS family proteins attached to the cell membrane and therefore, creates that on switch and the continuous signaling, which is the problem in this area. So PTX-100 actually impacts the GGTase enzyme and therefore, disrupts the prenylation of RAS family proteins, so they don't get to hold on to the cell membrane and switch. So you can see here that it's -- compared to others, it's a unique mode of action. And with what we've seen in terms of our adverse event profile, it's a very -- it's very comfortable for patients. So there is a possibility for PTX-100 with the right results to be a backbone therapy and second-line therapy. So that's really encouraging for us. So let's think about those results. And we have mentioned PTX-100 and CTCL Phase Ib results. And you can see on the right there in green, those are the results for the evaluable patients that we had in the Phase Ib study, 43% objective response rate and a good -- 100% clinical benefit rate. And you can see down the bottom there, the serious adverse events attributed to PTX-100 is 0. So that's super encouraging when you consider what benchmark we were targeting from a benchmark perspective. And we've listed here as benchmark in clinical development, you'd call it a target product profile. And so the TPP, we were focused about the 30%, the 45% and less than 30% serious adverse events. So that's what we were targeting. When you match that up to approved products in the space for CTCL, Lymphir is the most recently approved by the FDA, 36% objective response rate, but quite significant serious adverse events. And Poteligeo is a significant contributor to the market commercially. You can see a 28% objective response rate and significant serious adverse events as well. Now lacutamab is the investigational product I mentioned there just a few minutes ago. And you can see from Sezary syndrome a 42.9% objective response rate in their Phase II program. And that's super encouraging in this disease area. And mycosis fungoides are far more modest. And so we do know that they have set their first -- their pivotal program coming next with an accelerated component with Sezary syndrome and a confirmatory component with mycosis fungoides. And in doing so, they've also been able to secure a really strong transaction from a company called Sobi, where they have a USD 75 million upfront payment to support the development of their pivotal program, a USD 40 million milestones along the way and then a USD 465 million payment for the program at approval. So -- and following that, double-digit royalties. So really, really encouraging for them to get that deal. It also validates the commercial presence of why we're in this space. So it's a very good commercial opportunity moving forward. So if we move forward, we talk a bit about safety, which is unusual circumstance typically. But you can see here, there's a significant difference between what we've seen in approved products. So none of these are head-to-head studies, but it's purely about what we've seen in the development program. PTX-100 is actually not really impacting the fragility of the patient population. So with a unique mode of action, this really lends itself to a really good combination candidate. And with that unique mode of action and good clinical data could actually perform the -- be a backbone of second-line therapies. So we're progressing in our Phase II program. We've talked about at the beginning of the -- that we are halfway through our Phase IIa program and really looking at a Dose Optimization Committee. So let's look at what that study might -- is actually based on. It's a refractory CTCL patient cohort for mycosis fungoides and Sezary syndrome. Patients have at least failed 2 lines of prior systemic therapy, and we're targeting 40 evaluable patients as a whole. And we're dividing it up into 2 dosing strengths there. You can see 500 milligrams per meter squared and 1,000 milligrams per meter squared. And this is as a result from the FDA Project Optimus where it's no longer considered appropriate to go to the highest effective dose. You've got to find an optimal dose, and this is part of that program. We're running the program in Australia, the U.S., Italy at the moment, and then we are expecting to move into France in the early 2027. So there's a dose optimization committee. The role of the dose optimization committee exactly what it says is find a dose. And so their charter is to start looking at data from the Phase IIa program when there are 10 evaluable patients in each group, and we have reached that point. And so we know now for relative certainty that we will be running a Dose Optimization Committee meeting at the beginning of December as the first milestone in this Phase IIa program. Now when we're looking at what we -- where we're going with the Phase II program, you can see objective response rate is the primary endpoint. Lots of secondary endpoints, including one there, which says mSWAT, which is a CTCL unique measure of skin response, and this is used extensively clinically. So this will be very useful data and other good data there. You can see we'll also be looking at safety and tolerability. And of course, as we mentioned, because of the significant quality of life impact here, we are also evaluating the effects of quality of life. So some really substantial data to come out of the program, and we have now reached a halfway point in allowing the Dose Optimization Committee to have a look. So this is our clinical trial plan. And you can see we've completed a Phase Ib program. We're in the Phase II program, Phase IIa. And typically, we -- you would normally expect to do a IIb, Phase III marketing authorization and a way you go. But as you can see down below, there's Orphan Drug designation and also Fast Track designation for CTCL and mycosis fungoides. So that provides an opportunity. Firstly, Fast Track means that the FDA recognizes there's a clear unmet need, and they would like therapies that are effective to patients sooner. And so that allows us to talk to the FDA more frequently. It allows us to go through a rolling submission and those sorts of things at the application end. But it allows us to actually go to the FDA in a Type B meeting and really discuss what we've seen in the Phase IIa program and whether based on that, based on the level of unmet need in the space, whether we end up with a pivotal program as the next step as opposed to a IIb. And so that's what we'll be aiming for, but it is required subject to FDA agreement and obviously finding the dose is key, looking at efficacy data and safety and those sorts of things. So there's a lot to play here, but with Fast Track designation, there's an ability to have those discussions with the FDA. So we mentioned there's a significant commercial impact here, and this is a third-party research, which demonstrates. In 2034 the expected market size for CTCL is about $1.2 billion in U.S. alone. So we know that there's about 3,000 new patients there per annum, and that's progressing. So let's look a little bit about at that U.S. market at the moment. And this is Poteligeo or it's the drug that's called mogamulizumab, and it has a 28% objective response rate. And you can see here, this drug was actually FDA approved in late 2018. So this data is from 2020 into 2025. And you can see that in that time, the use of mogamulizumab in early-stage and late-stage CTCL in second-line instance is in the yellow line. And you can see the top line there is the total revenue for the CTCL space, and they're pretty much growing at the same rate. And so that tells us that there's clear unmet need in this space that a unique mode of action will be utilized by clinicians. And so therefore, when PTX-100 enters the market with a unique mode of action with relevant data, it will be used effectively and therefore, create its own market share. And also handy is that we've also got some good pricing comparisons. So when we're talking in a market access environment, looking at that pricing component, we've got some good comparisons in the space. So from the U.S. market and it's growing, we'll see a really good opportunity for us. And that's why we've seen a transaction take place with Innate Pharma and Sobi that is up to USD 580 million in valuation plus the double-digit royalties. So that's why we're getting deals like that. So our focus really is about CTCL and getting things done. We've done that well so far, but completing a registration study and looking at commercial opportunities is where we're heading next. Now we mentioned with PTX-100 disrupting the RAS protein approach. There's opportunity in other tumor types. And we saw in our early stage there when we looked at cell lines that there were 3 cell lines there of different tumors. And so that indicates to us that there's a benefit in other tumor types. So we'll probably look at this in a staged fashion. And certainly, an Orphan Drug is the next one. And then as we've strengthened our IP, we'll look at a much bigger cancer opportunity. So we'll be focused on strategic commercial pathways. And we've got some good core competencies, and we'll look to see if there's any complementary assets around as well. So that's kind of the expansion phase, but we're very focused on PTX-100 and our program at this stage. So having said that, there's upcoming milestones, and you can see that the milestone -- the first major milestone coming is the Dose Optimization Committee at 20 evaluable patients. French sites opening, if we -- depending if we get to the 40 evaluable patients, we expect that to be in the first half of 2027 and then the Dose Optimization Committee review of the final amount if needed, will be in the second half of 2027. And then potential Type B meeting once those results are identified and what we can do and heading towards the next phase. So good milestones ahead, very focused on PTX-100, and we -- and yes, it's exciting times. We have a strong management team and a very supportive Board and all with experiences in this space, particularly blood cancers and other cancers. And we really do have a unique value proposition. This is a first-in-class therapy, which we are running through a Phase II program. So we're the first GGTase inhibitor in the clinic. There's a platform opportunity with 22% of cancers have RAS family -- RAS protein implications. We've seen -- we are progressing on the study. We've seen Ib results, which are very encouraging. We've got FDA designations in place, and we are setting up for a really good partnering discussions. So a really good value proposition and really encouraging from a shareholder perspective. So I will hand back to Christian, who's appeared on my screen.

I have miraculously appeared. Thanks, James. Thanks for the presentation. That was very helpful. Look, we are -- I think we're focusing today on this announcement and on your progress through Phase II. You alluded quite a few times on this Sobi/Innate deal and their drug, lacutamab. And just a few questions on that. I mean you mentioned Sezary syndrome is only 5% of the cases. Is that -- and you mentioned some really big dollar numbers related to that deal. Is that -- what does that tell us? Like is it so remarkable because it's like it's a lot of money, over USD 500 million in any case, that is for a company that only addresses 5% of the cases that you are addressing? Like if you could unpack that a little bit for us.

Yes. I mean they have the accelerated component in Sezary syndrome, which is only 5% of the actual cohort. They do have some activity in mycosis fungoides, but very modest. And so they have got a significant deal there. We have Fast Track designation in mycosis fungoides. So we've kind of got the Fast Track in the larger cohort of patients. And so, I guess, the Sobi deal was a really good indicator that there's value in this space in terms of partnering. And -- but each deal has its own nuances. I mean, Innate Pharma have other assets, so they've managed it this way. We will manage a partnering program in probably a different way. But we do know that there's clear value here and that companies will be able to see this as a comparative environment and think, well, there's more here than what we've seen. So it's super good to have this transaction completed. It validates where we are and really validates the value in the program that we have. And as I've mentioned before, we're also looking at -- when we get an opportunity, we'll look at other tumor types. So looking to expand our program and reach that. So there's lots of nuances here, but we do know that there's real value, and that's important.