Prescient Therapeutics Limited (PTX) Earnings Call Transcript & Summary

All right. Good day, everyone. Thank you very much for joining us for Prescient or PTX.ASX's Investor Briefing. While everyone settles in, I'll go through the disclaimers and housekeeping. Presentations that Reach hosts are suitable for self-directed investors who have got 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 for yourself whether it's appropriate for you. And we're giving you information for educational purposes. Past performance is not a reliable indicator of future performance. Now my name is Patrick Nelson. I'm the MD at Reach. I'll host the session, but we're joined by James McDonnell, the CEO of Prescient Therapeutics. And today is an update off the back of the recent 4C, which announced the patient enrollment, which is now at 28 patients, global clinical sites expanding as well as the developments with investigators and prospective partners. So we'll go through a few questions first off and then run around the 4Cs and the patient enrollment probably more specifically. And then James will do a quick run-through of the deck, similar to what he's done on other sessions like this and then at the back end, that will go for sort of 15 to 20 minutes. And then we'll go into any more broader Q&A. If you've got a question, put it to the question box. I'll get through the ones are relevant at the start. And then if I don't get to something, all questions will be answered at Q&A at the end of the session. So we have allowed 60 minutes for the session today. I'm not sure we'll need all of that time, but let's just see how we go with Q&A. So look, just to set the scene a little bit, I know that we've got some new investors on the call today as well as existing shareholders. So a quick introduction before I hand over to James. PTX have developed a unique technology which 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. Whilst this technology is a platform solution that can potentially help sufferers of these 22% of all cancers, they've started or chosen to prove their technology with cutaneous T-Cell Lymphoma, CTCL, a cancer that is considered by many clinicians to have no viable treatment, therefore, a death sentence. In their Ib clinical trials for CTCL, an astonishing 100% of patients cancer stopped growing or reduced. 0 patients experienced serious adverse events, which is particularly important as we know a lot of cures for cancer can be worse than the cancer itself. They chose CTCL because it's an orphan disease with very limited treatment options and the FDA and other regulators are much more likely to support or Fast Track orphan diseases. Whilst a rare disease with limited treatment options, it still represents a $1.2 billion market in the U.S. alone. And going down this path has been successful for the company. The company received Orphan Drug and IND designation from the FDA, Fast Track from the FDA and recently, EMA also gave them Fast Track Designation. They've moved at great pace with CTCL being one of the most advanced therapies on the ASX. Moving into IIa, there is a potential for the IIb to be a registration study beyond the results for CTCL and they put their hands on a very advanced therapy. There are -- what's important to note here that this is much broader applications for this technology. So I guess what we're focusing on today is the enrollments and now being in IIa and what that means, I guess, in the immediate term. So James, thank you for joining us today.

Thanks, Patrick, and thanks, everyone else, for joining the call.

Yes. So we've now got sites open in the Australia, U.S. and Italy. And I guess these are the sites that have brought in the 28 patients referenced in the 4C. Is that correct?

That's correct. Yes, we have -- we're pretty happy with the progress. We had 14 -- or actually 16 patients now since the last quarterly update, and that's a very strong outcome for us. And then it is likely that the dose optimization committee meeting will be towards the end of the year.

Okay. So just to that end, so you've had 12 patients. Now after this past quarter, that's now up to 28. So that's a significant escalation. Are you expecting that sort of similar numbers to be able to continue?

We brought some Italian sites on and that boosted the enrollment. But now with a broader number of sites, each of them will be contributing to additional patients. So we're pretty comfortable with how we're tracking in terms of the patient enrollment, and we'll continue to monitor that. It's obviously summertime in the U.S. and Europe. So we keep monitoring some sites on holidays as well.

Yes. And France, there's still work being done to get France open. Is that correct?

Yes. We've submitted some further documentation for that. We have a specific aspect that we have to deal with from a bureaucratic perspective. It's got nothing to do with the actual study itself. It's about how -- well, it's about asking or answering a question from the ethics committee, particular to France and their working environment. And we do have a solution now, and so we've submitted that solution to the ethics committee. So we are progressing in that space.

Okay. So you've got 28 patients now enrolled. Could you just talk about your milestone of having 20 patients dosed? And what needs to happen from where we are now to when the dose committee, optimization committee can meet.

Yes, that's a good question, actually. So what we actually mean 20 -- what we are looking at is 20 evaluable patients. And so we recruit patients, but we don't know if they become evaluable until after the first 2 months where they've gone through some cycles. And so yes, we've enrolled 28 patients. Our goal is to have 20 evaluable patients, 10 in each arm. So there's a -- also we need to ensure that there's 10 in the 500-milligram per meter squared arm and 10 in the 1,000 milligram per meter squared arm. And so we feel we are on track for later this year. Patients go through up to 4 months before they get their PET scan. And this then completes what we call the global response score. The global response score is what we're measuring in terms of objective response rate. So that's the one thing we need, and that happens 4 months after a patient is enrolled. So there's a few time periods in there that we need to consider and the dose optimization committee are monitoring that, and then they need a package to be put together and then they'll review that package.

Yes. So comfortable that it's a calendar 2026 meeting at this stage based on enrollments to date.

Based on enrollments to date and based on where we think it's tracking, yes, I mean as confident as we are. We mentioned in the [ fore ] it will be later this year. And at this stage, I'm pretty sure that is the case. The dose optimization committee will review for safety. They'll review for dose and they'll review for continuation of the study. And so then we'll get some information relating to that after that situation.

Yes. And I guess, the potential things that the dose committee will provide PTS in terms of where you're situated and where to from there. Could you just talk us there?

Yes. We're likely to see a safety. So safety is the most important aspect at this stage. In terms of dosing, we need to -- the dose optimization committee is there to determine also the dose, not just safety. And so having 10 in each arm, it would -- I'm not sure that would be enough to choose a dose. So the likely situation is that they would say that the study will continue on until a point that they -- and I can't sort of see or say what they will decide because they are the deciders. But I suspect they'll want to go to 30 patients, so 15 in each arm and then evaluate at that point. So they'll be hopefully, great with the safety. I'll say from a dose perspective, we need to see more information and then the study will be continuing. And what that package looks like, we'll see at the end.

Yes. And so I guess that means that at what point would a decision be made about a dose that you can take into IIb or going to IIb or whether IIb is a potential...

I mean it's a really important decision about the dose, and it's something that we don't want to cut corners on because that -- if we have enough information to define the dose, we have enough information from data which comes out from the study, we will then have a Type B meeting with the FDA. And that having the best responses in terms of dose and efficacy and those things at the FDA time is the most important thing because that's where we start discussing about the potential for an accelerated pathway. We do have a Fast Track Designation for mycosis fungoides. So that's really what we'll be looking at. So we don't want to shortcut early because we want to have the best potential at the FDA meeting. And so -- and that's what we'll be looking at. If it's a very, very clear dose and efficacy and safety, that will be brilliant.

Have there been any developments? You've been on the road a little bit recently. Are you -- you're getting a little more attention or any -- is the heat rising around potential partnerships or outreach from that perspective to whatever extent you can...

Yes. I mean I had an extensive trip. I went to European Hematology Association and actually had a really good meeting with Professor Zinzani, and I think we've commented that he got some good comments there. I also met with Alessandro Aiuti, who's another investigator in the Italian team there on the Italian site. So -- and that's very important for the cohesion of the study. I met with some companies that are interested in PTX-100. And so they're quite positive. And when we have more information from the Phase IIa, that will be important for those conversations. I then went on to meet with some other companies in Europe. And interesting, I met up with a colleague who is the CEO of another company, and he's just been through a partnering process. And I learned quite some interesting point is from that situation, particularly about pricing. When you're going through and looking at pricing, Donald Trump's most favored nation pricing has changed the way drugs are launched in Europe and associated countries. And so when you're doing partnering agreements, you need to be very clear about who owns the decision for pricing and launching. And that was a very good piece of information I picked up in that situation. And so very happy about that and met with some other companies. And then went on to the U.S. for Bio, which is the largest partnering meeting really held and had extensive meetings with many -- quite a number of companies. They like the first-in-class, the Phase I 43% objective response rate is strong, and they are engaged, and we'll keep engaging them as we progress. And as the Phase IIa progresses to have more information available, we'll progress those discussions. So it was -- yes, I was really happy with that trip, and it's provided some very good information and some very good connections and contacts and establishing the foundation for partnering.

Very good. Now the -- a couple of questions on IIa. So Jamie, I'll come back to that in a moment. Actually, what is the plan to get 40 enrollments in Phase IIa before getting results from dose optimization committee to guide Phase IIb. Now is there appears to be a risk hitting this number before getting results?

The 40 evaluable patients would mean 20 in each arm. We have -- the statistician works with the dose optimization committee. So they will be able to make a call on that dose. That is the end of the Phase IIa study, and that is where the dose optimization committee will make a call on the dose. And they'll use the statistics, their own experience because they are clinicians in the study and our CMO will produce -- define a dose at that point and then go to the FDA with dose safety, efficacy information. So [indiscernible] study, so it will happen.

Yes. And I mean, you've been -- since you joined Prescient, your focus has been to channel the resources and the energy of the business into preparing to get you where you are right now. You've set yourself goals throughout this process. I mean you're a fairly conservative person by nature, I know. But to whatever extent, I mean, how satisfied are you that you guys have got the enrollments where they're at and you're at the stage you're at right now?

Yes. I mean the enrollments are a very important part. Obviously, we can control that in terms of making sure everything is implemented and able and sites can recruit patients. we can control the CMC side. So the chemistry manufacturing control is another very important part to have progressing at this time. We have that on track at this stage. The components we don't control are the actual data that will come from the study. But I'm happy that all the things that we have and that are our responsibility to have in place and working are working.

Very good. Look, I think we'll pause there. There is a couple of questions I'll get to because they're taking us in a slightly different direction when after the Page 10. So James, I'll come and talk to you.

Okay. Great and thank you. Thanks, everyone, for joining. I will go through this, and we'll get back to questions. It looks like there's some engaged questions, which is always a good sign. And so in terms of PTX and our company snapshot, as of Friday, we had $9 million -- just over $9 million in the cash position and the share price is at $0.085. And so you can see it there. So as you may have picked up, our focus is oncology and particularly a therapeutic that targets a Ras pathway and Ras is involved in nearly 1 in 5 cancers, 22%. Sometimes it can be described as a bit higher. And therefore, we're aiming at creating value for patients and investors. So that's our focus. With our PTX-100, it is the most advanced GGTase inhibitor currently in development. And as I mentioned, it is really impacting a biology that's targeting 22% cancers. So far, we've seen some efficacy signals from the Phase Ib study. Patients were receiving clinical benefit, evaluable patients. And we also have worked well to gain key designations such as Fast Track Designation and Orphan Drug Designations. And as we work and get more information and clinical data, this will help our partnering discussions. So we're on track in terms of how things are progressing. So a little background. So some of the mechanics of what we're talking about. So this is a slide from the Cancer Foundation, which we've added a little bit to the cancer cell division section there. So normal cell goes through that to healthy tissue and abnormal cell has a genetic change, it creates a cancer cell division and near of tumor. And you can see that the cell division is mediated -- can be mediated by the Ras family proteins. And so that's where we're targeting and where we're looking at. So PTX-100 has come from Yale University in the U.S., as I mentioned, first-in-class, and it really is impacting an enzyme, which is crucial to the Ras pathway. So GGTase is prenylate Ras proteins that allow them to continue switching. So by inhibiting that prenylation process, we impact the ability to switch and therefore, downstream effects. So to put that into a bit more of a picture, this is the situation where on the pro-tumor effect side there, you'll see that Ras family proteins, and there's about 170 of them, some are more prevalent than others, but they go through a process called prenylation using GGTase. And this enzyme adds a general group to the Ras proteins that allow them to attach to the cell membrane and switch. So the Ras proteins are effectively switches. If the switches on, it's all -- it continues to happen. And therefore, that's where you get these pro-tumor effects. You get the migration, proliferation and cell survival based on those switches being on in an excessive manner. So PTX-100, if we go to the other side, actually sits in the prenylation pocket of the GGTase enzyme. And it physically puts a barrier to Ras proteins and general translation groups getting together. And so therefore, they're not able to attach to the cell membrane and they're not able to continue their switching. So disrupting that process in some way will have an antitumor effect. So we mentioned first-in-class. The reason we mentioned that is patients -- it makes it to be first in class, it's helpful to go and get designations in terms of Orphan Drug Designations and Fast Track Designations, and we have that with mycosis fungoides. It also means that we're not competing with other GGTase inhibitors at the moment. We are the first out there. And we're creating really strong relationships with clinicians. And we're creating more and more data, which allows us to then start looking at other tumor types. So we talked about this mode of action. And I want to really highlight here why the mode of action is quite unique. These are therapies that are actually used in the treatment of refractory and relapsed cutaneous T-Cell Lymphoma. And you can see on the top there, there are a number of antibodies that are targeting antigens on the cell wall and they induce cytotoxicity. On the other side, we've got biologics carrying payloads and they also -- or they cause cell death by targeting the antigen, but also dumping an active payload. And down the bottom there, you see tumor gene suppression. So this is an epigenetic approach where [indiscernible] is inhibited and therefore, gene suppression occurs. But in the middle there, you see the Ras family protein, and you can see the geranylgeranyl group sitting there that they prenylate and you can see that the Ras family protein is able to hold on to the cell membrane and switch and continue that activity. But PTX-100 inhibits the GGTase prenylation process and therefore, puts across -- puts a stop to that process. And so you can see from this situation, a unique mode of action can really work well as a backbone in terms of future treatments such as working with -- in combination with HDAC inhibitors or working in sequentially with the biologics, et cetera. So an interesting dynamic there. So that's something that we'll look forward to. So let's look at PTX-100 and CTCL. So why is the CTCL? Well, when you have an inhibitor of geranylgeranyl transferase-1, which is disrupting the Ras pathway, we'll look for a Ras involved tumor. We need something which is a high unmet need, good regulatory opportunities and also market opportunities as well as competitive -- less than competitive space. So that's why we are at CTCL. ROA is the Ras protein most likely involved in this situation. It's orphan where it's clearly unmet need and the market is reasonable. We've seen from the Ib results that we have an impact and here is the clinical benefit, but the overall response rate or the objective response rate of 43% is also as impressive. And without the serious adverse events related to the drug really sits well. And we have those Fast Track Designations and Orphan Drug Designations, which are helpful from a access and commercial perspective. So CTCL, Patrick mentioned that it's considered a death sentence. And I think Professor Miles Prince, I think referenced that in the earlier comments. But you can see here is the 5-year overall survival graph and the 2 boxes down below are the 2 main subtypes of CTCL mycosis fungoides, early stage and advanced stage and Sezary syndrome. So Sezary syndrome is about 5% of CTCL. Mycosis fungoides is up to 70% of all CTCL. And you can see the 5-year overall survival is not so bad in early stages. But as you stage lower, it becomes quite impacted. And particularly at late stage, 18% 5-year overall survival is not great. So that's only part of the story. The quality of life is also a significant issue in this disease state. When you've got skin is being impacted, you're itching, you've got secondary infections, your parents are socially isolating and you're really struggling with sleep and fatigue. And so it's a real double whammy and very uncomfortable for patients. So what is CTCL? Well, it's actually your white blood cells doing strange things. And they are normally involved in immune function. But in this situation, they've migrated to the skin and they're starting to replicate uncontrollably and destructing the skin. Now as those stages progress, that also starts impacting the nodes and the [ vis ] and the blood. And therefore, if you're impacted on all 4 of those aspects, you're really in a 4 -- staging is 4 quite severely impacted and not great. For current treatments, there are treatments there, but they tend -- most patients tend to be refractory and relapse to 3 therapies. And they also come with some reasonably toxic adverse events. We know that in the U.S., there's 3,000 new patients per annum, and this is increasing. And globally, there's a lot more. From our clinical data, we conducted a Phase I study and then a Phase Ib study that looked at T-Cell Lymphoma and T-Cell Lymphoma involves peripheral T-Cell Lymphoma as well as cutaneous T-Cell Lymphoma. And we looked at those data. And when we look at the data, we see some really good response rates for CTCL compared to our product, which is most recently approved by the FDA and also in terms of serious adverse events attributed to the drug. And so we considered this and we considered the fact that there's 2 main subtypes. So instead of having a general T-Cell Lymphoma study, we moved to a CTCL Phase IIa study. And we talk about those adverse events. You can see here drugs that are used in this space, some quite severe adverse events and PTX-100 has some adverse events, but not severe. And therefore, really makes it a really good partner for combination therapy and also being a unique mode of action. So it's odd to comment about safety, but in this circumstance, it really does show a benefit. So we're running a Phase II study and the Phase II study is separated into a Phase IIa and IIb. The Phase IIa actually will enroll 40 patients. They'll be randomized to 20 in each arm of 500 milligram per meter squared and 1,000 milligram per meter squared arm. The dose optimization committee will meet, as we mentioned, after 10 evaluable patients in each arm, and we'll continue to meet until they can define a dose. And that may be 20 in each arm or it may be 15 in each whatever the dose optimization committee decides. And then we'll look at a Phase IIb. But in the interim period, we'll actually go to the FDA and discuss data that has come from the study outcomes and the dosing and really knowing that we have a Fast Track Designation with mycosis fungoides and CTCL, we'll be aiming for the potential for a registration approach. And this is what we talk about. This is the standard process of going through the Phase II to III to marketing authorization and then on the market. If we can discuss and get an agreement with the FDA about what a registrational study might look like, we would take that opportunity because it is faster to the market, would be very encouraging for partners and will also help us then start looking at other tumor types. So we talked about the addressable market. I mentioned 3,000 new CTCL patients a year in the U.S. [ Delve inside ] is a provider of information and market research organization, and they forecast the CTCL market in the U.S. to be around $1.2 billion in the year 2034. So there's a substantial market to look at in this space. When we're looking at the commercialization and what's happening in the space at the moment, we see here some data from mogamulizumab, which is actually indicated for CTCL in -- has a 28% objective response rate. It's actually better in Sezary syndrome that mycosis fungoides. But you can see here that they have grown the market themselves. And what that means is that if you have a recognized therapy, a unique mode of action, clinicians are willing to give to try patients are refractory and relapsed many therapies, and they are willing to give it a try. And so therefore, you can grow your own market share, you can have a commercial presence in that space. So in summary, we have some interesting CTCL response rates and particularly a very good -- no attributable serious adverse events related to PTX-100, and that sets us up well for a Phase II study. So based on those results, based on the fact that we have Orphan Drug Designation and Fast Track Designation, market size, we're really pushing our Phase IIa and the potential for IIb registration and then looking at other tumor types. So that's pretty much the strategy. And what does it mean to look for those other tumor types? Well, it means we've already done a lot of the preclinical work. We'll do some more preclinical work in other tumor types and then we'll be into -- late Phase I to Phase II. So really accelerating that the potential for other tumor types. And it's likely that we'll target another orphan disease followed by something a bit broader, but those are things that we are looking at in the future. At the moment, our focus is really on the Phase II study and acting that study. And this is the expansion process. It's all about the study and then it's all about other opportunities going forward. This is the team. Dr. Rosalind Wilson or Ross has joined the team now. Very happy to have Ross on board. She comes with some significant experience through her race days and she's previously been a CEO. And so really comes with a solid understanding of what's required as we move forward. And we have a solid team and a solid Board, all really active and able to support us through this process. So we've mentioned this many times. We've got a PTX-100 targets the Ras pathway, which has potential to impact 22% of cancers. We've done some good Ib results. We're doing some really good work with FDA and actively now looking at clinical data and generating that to get us through to a marketing authorization, but also to help us with our partnering situation. So I'll finish on that one, and thank you for your time, and then let's get back to questions.

Thanks, James. A few questions coming through. Joe has asked, what is the initial target market?

The initial target market is the U.S. market. Interestingly, when I was in Europe, usually, you go to the U.S., you then look at Japan and then you launch in Germany. That's no longer the case because of the changing processes in the most favored nation pricing. And so the European market is a little bit up in the air on how we approach that, but we know of the issues associated because you don't want to impact the U.S. market. So it's target market is the U.S. and then the rest.

Okay. And that is a $1.2 billion U.S. market for CTCL?

Yes. In 2034, that's what it's estimated to be. It is substantial. And then the reason why it's substantial, it's a rare disease, but patients are really trolling through the therapies. And even when we look at mogamulizumab, which is sort of indicated for refractory relapsed severe disease, you can see it creeping into earlier phase refractory relapsed environment. So early stage. So really, the market is quite broad in both early and late-stage treatment options.

Now there's a few questions regarding the -- I'm not bringing this slide up, but there was a few questions regarding platform and what the work you've done to date means. So I might wrap that into sort of for future indications of other cancers, what does that mean in terms of where you start the journey? Does it mean you can potentially come in a Phase Ib or IIa? Could you give us what that means?

When you're developing a drug, you've got to do a lot of early work in terms of the mode of action and understanding the PK and the pharmacodynamics of the drug. We're already working through that with our first indication. We then will do a little bit of preclinical work to -- in different cell lines, which represent different tumor types. We know that, for instance, pancreatic cancer has a lot of KRas involvement, 94%, but it's really heavily targeted at this stage, but there are other cancers that in the gut, in the lungs, head and neck. And so because the Ras pathway is involved, it will be about fine-tuning where we're looking at and then we'll take that forward. So it's -- it will be much more targeted because we know we'll gain a lot more information from the CTCL environment, and therefore, we'll be able to start later in the phase development.