Prescient Therapeutics Limited (PTX) Earnings Call Transcript & Summary

Good day, everyone, and welcome to PTX Shareholder Briefing. While everyone settles in, I'll get through the disclaimer and housekeeping. The opportunities and the sessions that Reach put on, this session is for PTX shareholders only. If you're going to make a decision to invest, you need to look at all the materials and make your own decisions. The information that we're providing is for educational purposes, past performance and not a reliable indicator of future performance and any information contained in today's presentation is general in nature and doesn't consider your personal circumstances. You need to make your own decisions on whether it's appropriate for you. My name is Patrick Nelson, MD at Reach. I'll host the session today, but James McDonnell will be running the presentation. And James, as you will know, is the CEO of Prescient Therapeutics. As shareholders, we know that you're across the story that we've delivered the slide presentation pretty closely to the form that it's in now previously. So we're going to run the session as some questions upfront. Then James will quickly run through the presentation, and then we'll get into any more detailed questions. I'll lead the questions upfront because I've got some questions around the SPP and where the business is at this moment in time. If I don't get to your question at that point in time, I'll get through all of the questions during Q&A. We expect the session to run for sort of 40 minutes, but we've got up to an hour if people have got lots of questions. So yes, a reminder for anyone that hasn't received or requested their SPP forms. They'll be out in the post now. I imagine that we'll probably start seeing them come through maybe today, maybe early next week. But the fastest way to get the forms are actually to just request them. So if you type yes into the chat box, we'll make sure that we send your personalized forms through. And if you need any other details around the offer or any other information, please just speak to one of the advisers at Reach. Now just a quick introduction to Prescient. PTX-100 is one of the most advanced cancer therapies on the ASX. We're targeting CTCL, cutaneous T-cell lymphoma, which is in advanced stage as seen by many clinicians as a death sentence. It's a terrible disease. Patients are constantly itchy, uncomfortable. They suffer from secondary infections. Their sleep is terribly affected. And so it's a horrible disease. PTX-100 had remarkable Phase Ib results that saw 100% of patients record either a halt or reduction of their cancer and even more remarkable with 0 serious adverse effects. So even for those people whose tumors didn't shrink, it has a really positive effect of stopping itchiness, getting their sleep back. Obviously, halting in itself is very, very important. But PTX-100, fast track and orphan drug designations from the FDA. They're now in the IIa study, 28 patients recruited, they need 20 available patients for their first Dose Optimization Committee meeting, which is scheduled and on target to meet later this year. This meeting and data readout is a major milestone for the company as it nears commercialization. And this is already a really rare feat and an amazing milestone for PTX. With fast track designation and beyond there, a potential for IIb to be a registration study, we're at an interesting juncture after investors who have really supported this company for a very long time and now getting to that phase where commercialization can happen and some major inflection points are in front of us. So having a dose as well as a registration study are really those -- start of those real commercialization stages where mid-tier big pharma start to get involved. They're already paying a lot of attention. PTX is perfectly positioned here. Very interesting opportunity. It's been great to be involved in Prescient because of the results that it's delivering for patients, but it's also a very well-run business. It's been very well led by James McDonnell. And they sit there with $9 million in the bank, starting off with an SPP to ensure that they're well capitalized through this IIa and into IIb. So with that said, James, I might ask you a couple of questions upfront about the SPP. I've got the terms up here, and again, for anyone that hasn't got the docs typed in yes. But yes, look, why SPP? We've run these before, but what makes this the right structure at this moment in time?

Yes. I mean it's an important part of our funding model as we progress through our phase program with PTX-100. And we do have a very engaged shareholder base. Thank you. And really, it's an opportunity to provide an 18.8% discount to the 10-day VWAP for shareholders who are engaged and wanting to help support the furthering of PTX and PTX-100 through the significant points which are coming there. With PTX-100, we're running a Phase II program. As you mentioned before there, we have progressed, and we are expecting a Dose Optimization Committee to occur later this year, and that's a significant point in the study. So it's an encouraging time and appropriate time.

Yes. And so where does this raise get you to?

This raise will get us obviously through the DOC and other DOCs. But ultimately, it's defining the dose. If we can get the dose, that will be critical, and then we'll be able to move to the next level. So it will depend on Dose Optimization Committee, but we hope it will get us to a dose.

Yes. Why are you raising money, I guess, now and at this price?

Yes, we're raising money now because we want to maintain our fiscal responsibility. I guess, it's better to raise money when you -- we have money, as they say, and not a distressed business. It's a good discount to the 10-day VWAP. And it's also a significant increase on the last SPP pricing we showed. So it's helpful for us as we progress.

Very good. And has this got the potential to get you through to a Phase IIb?

It comes back to that Dose Optimization Committee and the outcomes from the Dose Optimization Committee. Finding the dose is really the key to that point, and that would allow us to then progress to our phase -- a Type B-type meeting with the FDA and look at what the Phase IIb or pivotal study could look like. And so I would hope we get to a dose, but that's dependent on data that comes out from the studies.

Yes. So -- I mean, you can maybe step us through these key stages. So what are the next steps from here?

So the next steps from here, the immediate next steps, I guess, will be an enrollment update as we do the 4C and the next 4C. Then there will be -- the Dose Optimization Committee will meet towards the end of the year, we expect, and their report will be a significant report for the study and the progress. After that, there will be DOC meetings, possibly if needed, at 30 evaluable patients and then at what point the DOC committee or the DOC chooses to meet. Once the dose is defined, then it's a Type B meeting and then it's -- we'll interrogate the opportunity to see whether the next study is pivotal.

Very good. So commercialization pathway, I guess, have you had any engagement? What sort of conversations have you been having?

Yes. I mean, recently, I was in Europe and also in the U.S., where we -- in Europe, I had a number of meetings. And in the U.S., I had actually 15 meetings at BIO. There are sort of mid- to strongly funded pharma companies as well as an interesting group of companies who have U.S. and sort of global setups, but they're actually funded by Indian generic companies who are well funded. But they see their model as being challenging because the margins in generics is really not going to grow. And they're looking for branded rare disease products to assist in their organic growth around the world. So interesting mix of companies we talk to. We also talk to regional companies such as to Japan, such as to Europe. Ideally, a global deal would be one that would make more sense.

Yes. And what will -- I guess, we saw that Sobi recently did a deal with Innate on a CTCL drug. I mean, what transpired there?

Yes. So that's a really encouraging transaction actually. What transpired there is innate had completed their Phase II. They have a particularly strong data in Sézary syndrome, which is about 5% of the CTCL subtypes. And they have spoken to the FDA and have a program which has an accelerated component for Sézary syndrome and a confirmatory component. And so that shows that the FDA are looking at dynamic approaches, which I'm also encouraged with. And that allows Sobi to come in with the deal to say, we'll fund with the USD 75 million upfront, a USD 40 million milestone along the way and then a USD 465 million commercialization fee and then double-digit royalties. So CTCL -- it kind of validates being in the space of CTCL because it is commercially attractive.

And is this the kind of deal that you're looking for -- you foresee potentially for Prescient?

Yes. I mean it's a solid deal. Innate Pharma are a different setup to us. They have other programs. And so they probably ran this on a lacutamab-only type approach. PTX-100 is our key asset. And so what comes to the table may look different. But it's certainly a good example of a deal that can be made. And yes, it's encouraging.

And what -- I mean, you've now obviously been talking to these mid-tier, the generics, the big pharma groups and so forth. I mean, what are they looking for before they -- I mean, engagement aside, but before they actually make an investment?

At this stage, they're really keen on the next dose -- on the Dose Optimization Committee. and the report that comes from that. And then the engagement will strengthen based on data and progress along. They will -- as we get to the dose, that will be a very compelling point for them to start engaging and looking at commercial deals. And then certainly, after a Type B meeting with the FDA, there's more information provided. So it ramps up in terms of the likelihood of a commercial deal. We do know that there's a lot of engagement, and we continue to engage and almost prepare the environment as we progress.

Yes. And I guess, how does that compare with, say, Sobi?

Sobi, we're obviously watching the Innate Pharma. They're a mid-tier pharma company, global. And so that's encouraging. Often, we see in rare disease, the companies are mid-tier pharma as opposed to the very big ones because those very big ones need much -- a bigger market size and they have more cash to splash in terms of those other -- like other broader non-orphan environments. So that's kind of where we're at.

I guess, my question is also coming from the perspective -- from a timing perspective. So at what stage -- you've just mentioned that big pharma and so forth come in at this point, we're at this point. How does that compare, I guess, to where Sobi came in and made their investment?

Well, they came in to really -- actually funding model of the phase -- the pivotal study, if you like. So the next phase that we would get to, following successful negotiations with the FDA and then the potential for a pivotal study, that's where they are entering with Innate Pharma. So you can see that it's -- yes, it's a good model to look at and see what actually happened in the CTCL space with a good asset.

Yes. Okay. Very good. What I might do is now pass to you to run through the slides, and then we'll come back for more Q&A. Just someone has asked, Paul, why don't we make SPP renounceable? I mean there's any shortfall on the SPP, we'll place it. I don't know that there will be, but -- based on history. But if there is, that gives us the flexibility to bring the extra capital in that way, but we wanted to give -- certainly, the Board wanted to give shareholders the first look at this and for them to continue the support of the business. And I think the company is, after a long journey, at a really interesting juncture in time as a major inflection point. So we think that it's an interesting time to provide that little bit more support for the company as they move through this next stage. So the terms of use of funds and so forth on the screen here. Importantly, if you just type yes into the chat box, we'll make sure that we get you the docs across. Other than that, James, I will now hand to you to take control of the slides.

Okay. Thanks very much. Let's see here, here's our disclaimer and safe harbor notice for forward-looking statements. And here's our company snapshot, which Patrick mentioned earlier, $9 million in cash, and you can see the progression over the year. So highlights. So we have PTX-100, which we actually had licensed from Yale University. It's a candidate that targets an enzyme, which is very important in a pathway that RAS proteins use. And so we're pioneering a platform, if you like, that has potential to address 1 of 5 cancers because RAS proteins are implicated in about 22% of cancers. PTX-100 is the first-in-class, and it's in the clinic and, as we understand, it's the most clinically advanced of this target -- for this target. We are targeting a rare blood cancer, which interestingly exhibits itself in the skin as CTCL, but it is a blood cancer, and we're doing this, following encouraging data from the Phase Ib. As we've mentioned there, we have a near-term milestone expected later this year, which is the first Dose Optimization Committee review. And of course, we're creating value. We talked about the transaction that took place recently in the CTCL space. We are talking to a significant number of partners in preparation for this opportunity from the study. And so therefore, there is a real opportunity to create value. So I know we have shareholders on board today. So I'll try and go through quickly some of these slides that we've already done. You can see here from the Cancer Council -- Cancer Foundation, a slide. And you can see in the bottom slide where the RAS family proteins sort of have an impact in terms of the cancer cell division and therefore, malignant tumor growth. PTX-100 works by disrupting the RAS family process. So in the slide on the -- in the schema on the left there, you can see the RAS family proteins use GGTase to prenylate and therefore, once prenylated, they can hold on to the cell membrane and start triggering downstream effects such as proliferation, migration and survival. So that's a pro-tumor action and then -- and that occurs. PTX-100 actually engages very closely in the prenylation pocket of the GGTase. So if we look to the right, you can see by impacting the enzyme GGTase, we challenge the RAS family proteins' prenylation approach, so we disrupt it, and therefore, we have an antitumor effect that's taking place. Now we have talked about working with the CSIRO and doing some in vitro work. And here is a slide which is new. And you can see the AI and physics-based modeling demonstrated that PTX-100 does fit nicely within the pocket of prenylation within the GGTase enzyme. In the middle graph, you can see -- shows that there was strong binding in this in vitro work called a CETSA. And you can see the green graph moves to the right, indicating that there is a strong binding to the enzyme, which is very positive. And on the third graph to the right, you can see that Rap1, which is a RAS protein and its prenylation or attachment to the cell membrane is impacted by PTX-100. And you can see it's impacted by 40% to 60% versus control, which would be showing at 100% there. So that validates our mode of action and is very important. And interestingly, those 4 bars in that graph represent 4 different tumor types. And so that gives us an opportunity to see what could happen next. So we mentioned first-in-class, and it does provide advantages, and we've seen our FDA designations and orphan designations. We're not competing with other GTTase inhibitors. And we're really speaking to the key opinion leaders in the space. And this also provides data to extend our first-mover activity in other cancers. So PTX-100 in CTCL, why are we here? Well, when we were looking at our strategy, we were looking for RAS, we were looking for unmet needs, et cetera. And from our Ib work, we realized that CTCL was a very good opportunity. It showed there is RAS involvement. It was an orphan disease. There's a clear unmet need and the market is reasonably strong, and we've seen that validated with the recent transaction by Sobi and Innate. And you can see from the Ib results, we had 43% objective response rate with no drug-related serious adverse events and obtained fast track designation for mycosis fungoides as well as our EU and U.S. orphan drug designation. So CTCL, and Patrick sort of described some of the challenges with CTCL, it's a problem of the white blood cells, the T cells. They migrate to the skin and really impact the skin, eventually impacting the nodes, the viscera and the blood. So a progressive disease of -- which is not great. There are significant quality of life aspects such as the itching, the secondary infections, the social isolation, et cetera, from the skin involvement. We noted it's about 8 in 1 million patients. And in the U.S., there's about 3,000 new patients per annum, and that's increasing. And there is sort of 2 main subtypes of CTCL: mycosis fungoides, which we have a fast track designation, and Sézary syndrome. So mycosis fungoides is the most common CTCL subtype, depending where you read, 50% to 70% of cases. It's originally -- it's sort of -- initially, it's skin-related and then it progresses through to the nodes, viscera and blood. Sézary syndrome is about 5% of cases and it's more of an aggressive form, but it demonstrates in the skin and then more leukemic variation in the blood. So what does that mean from an overall survival perspective? So this is a 5-year overall survival. And you can see there's poor outcomes at advanced stages. So if you look at the top there with the MF early stage, these are patients that are impacted by quality of life in terms of their skin involvement, but their prognosis is yet to deteriorate significantly. And so that's staging from 1A to IIA. Now if you then become more advanced, so your MF advanced stage or Sézary syndrome stage from staging at IIB down to IVB, you can see a quite significant impact on your overall survival down to 18%, 5-year overall survival towards the bottom there. So that's a challenge. So not only are you challenged from a quality of life perspective, but you're challenged from a prognostic situation. So we know that existing therapies have modest efficacy and poor safety and tolerability. Lots of patients are refractory and relapsed. And of course, we have that fast track designation in the mycosis fungoides refractory and relapsed environment. So here's mode of action. So typically, patients have topical therapies, then they may get a session of chemotherapy, but then you get these second-line approaches and in the refractory and relapsed environment, either in early stage or late stage. So if you look at the left there, you can see Lymphir and is one example of a biologic that carries a payload. There's a couple of them there. If you look to the right, you can see Poteligeo and Campath and the next one there is actually lacutamab, which we've discussed in terms of the deal recently done in its phase -- about to start Phase III and another investigational drug there. So they are targeting antigens on the cell membrane and then HDAC inhibitors, which are lower. So you can see that we can break these into groups. And you can see that the RAS family proteins play a role in the middle there where they attach that geranylgeranyl group, they hold to the cell membrane and then they start triggering. And that's the problem. They stay on, whereas PTX-100 comes in and disrupts that process. And so it really reduces migration survival and proliferation. So that's how the mode of action works compared to others. So you can see there's opportunity for combination approaches there because we are different. So if we look at our Phase Ib sub-analysis on CTCL and to the right there in the green is the performance of PTX-100, 43% objective response rate and down the bottom is 0 adverse events attributed to PTX-100. So if we go then to the left, we see a benchmark, which is effectively what we would consider the target product profile, or TPP. So we're looking for something around 30% clinical benefit there, some duration and less than 30% serious adverse events, which is quite high, but that's actually pretty helpful in this space. So Lymphir, which we mentioned earlier, is recently approved at 36% objective response rate, but high serious adverse events. And the same is Poteligeo , the 28% objective response rate and 41% adverse events -- serious adverse events. Now lacutamab is the drug that's entering into Phase III, which has just done a significant transaction. And you can see why they've done that transaction. There's -- in the 5% cohort of Sézary syndrome, they have an objective response rate of 42.9% and the serious adverse event rate is actually -- it's not so bad. So that's encouraging that even with 5% of CTCL cohort, they can really make an impact with the deal that they've done with Sobi. So we mentioned -- we seem to mention a lot about safety, and you can see that adverse events continue to -- are looking very strong for PTX-100 and favorable, if you like. And so that will be helpful when we have our unique mode of action and the potential for candidates for combination. So very helpful to have that as well. So we have mentioned our Phase II program, and this is the first part of it, the Phase IIa. And you can see refractory and relapsed CTCL patients have at least failed 2 previous lines of systemic therapy, and we'll be enrolling 20 patients in 2 dosing arms, which is following the Project Optimus from the FDA involvement. So at the point of 10 evaluable patients in each of these dosing arms, the Dose Optimization Committee will start looking at data in an effort to identify a dose. And so they will continue to do that until a dose is identified. And you can see the endpoints for this study and the Phase II program are objective response rate. There's a number of secondary endpoints. And the first one there, which is skin responses very specific to CTCL, which is called the mSWAT. And of course, safety and tolerability will be key. And because there's so much quality of life involvement with this disease, we are evaluating quality of life as well. It's a study which is conducted around the world, and we will hope to initiate the French sites in the first half of 2027. So this is where we are with our clinical program. We've completed Ib, we're ongoing in IIa. And in a standard approach, the expected clinical path would be that IIb, Phase III, marketing authorization on the market. But as you can see below, we have orphan drug, but also fast track designation in CTCL, mycosis fungoides refractory and relapsed. So following information from the Phase IIa, the potential pathway when we go to our Type B meeting with the FDA could be a pivotal program followed by marketing authorization. But of course, this requires agreement with the FDA on endpoints and patient numbers, et cetera. But we will certainly be interrogating that opportunity with the FDA in our Type B meeting at the appropriate time. So we talked about -- briefly about the addressable market. We see here from DelveInsight, a research organization, estimating about USD 1.2 billion per year in 2034 is the market size with 3,000 new patients in the U.S. increasing. So this is U.S. data alone. And so that really does show opportunity, and we've seen from the transaction with Sobi that it's considered commercially important. Just speaking on the commercial side, this is mogamulizumab, which is Poteligeo. It was approved in 2018. And so you can see here, this graph is from 2020. I put this graph here because these are actual sales in this space for early stage and late-stage CTCL. And I put this here because you can see the yellow line grows and the top line, which is the total market, almost grows at the same rate. And so this demonstrates that there are very clear unmet needs in this patient population and clinicians when they have a unique mode of action, they have enough CTCL patients who are refractory and relapsed and needing something else that they will use as treatments. And so this will provide us -- this gives us an indication that we can grow our own market share, and there will be pricing comparisons in the space. So our strategy is very CTCL-centric, and you can see from a transaction that's recently done, that makes good sense. And then we'll look at expansion approaches such as new indications, perhaps orphan first and then progressing -- improving IP perhaps in further cancer types, looking at commercial opportunities and leveraging our core competencies and really reviewing other complementary assets that may be available to us. So we have some milestones for PTX-100. And I guess the most significant one is the DOC meeting with 20 evaluable patients. And that is probably a significant -- is the most significant point going forward. And we'll continue to have those meetings, and we'll look at enrollment and really trying to get to the point where we have a dose and can go to that FDA Type B meeting. So this is the team, and we've seen the team and a really supportive Board, and I'm really encouraged with the Board, and we are progressing. So we really do have a good value proposition. It's a first-in-class GTTase inhibitor, good opportunity in terms of cancer involvement. And then we're showing good Ib results. FDA, we've got the designations and with clinical data, the future partnering discussions are very relevant at this stage. So I think that brings us to the end. So I will hand back to...

Yes, [indiscernible]. Thank you. So I know there have been a few questions around the SPP. So we'll get into those and then get your broader questions. So in regards to those people that have requested the docs, I mean, you will get them in the mail. If you have -- don't have an e-mail address scheduled as your prioritized way of communicating, the safest way is simply to request them, and then we can ensure that they get e-mailed across to you so that you have them on hand when you need them. Now [ Eric ], I guess, there was a question around share price, and it's always hard for a CEO to talk in open forums about share prices. But in regards to previous prices where share prices are trading at higher levels than where we are now, in the time that James has been here, I think the share price has lifted up, and that's been off the back of the program that's been run. I can't really talk about where things were some years earlier. I mean CAR-T was on the boil back then, and I think that, that had an impact on where we were positioned. At the moment, we're at a major inflection point. And could the share price be trading higher? Yes, possibly with the data that's out there at the moment, that could be the case. But it is where it is. And I think the exciting thing for investors at this moment in time will be a dose IIb registration study or even just moving into IIb. The continued data around recruitment, I think, is also quite material and it demonstrates the support. And if we can get similar results that we've had in the last studies, I think it looks -- both things look very, very interesting. Looking at the Sobi deal and other deals that have been done in this space, when we get to that next phase, I mean, yes, there is -- it's biotech. This is -- that significant upside that you can achieve at that point in time means 4, 6, 8, 10, 15 kind of those numbers aren't as relevant. So look, I get where your question is coming from, [ Eric ]. I don't think there's too much that can be said looking back in time for James to make a comment on, but that would be my thoughts on the matter. All right. So James, a question from Paul. It seems that potential dealmakers who may offer a licensing deal are taking a real hard call wait-and-see approach with PTX-100. Is this normal for this industry?

It is. It's interesting that it has evolved over the time. So it used to be that pharma used to go really early in Phase I, but then there was too much risk involved, and they moved right up to Phase III. So -- and now it's creeping back more into Phase II and so -- depending on the asset. So it does move around a bit, but it is -- at the moment, we're seeing -- I think the Sobi deal is a good representation of where typically we're seeing activity happen, which is that progression in late Phase II to sort of next stage.