Prescient Therapeutics Limited (PTX) Earnings Call Transcript & Summary

Well, good afternoon, everyone. It's just ticked over 12 noon here on the East Coast. So, we'll start the webcast in about 30 seconds or so. Before we get to it, I'll just run through some housekeeping while people are settling in, starting off with the disclaimer. Any information contained in today's presentation is general in nature and does not consider your personal circumstances; you need to decide for yourself whether it's appropriate for you. The information we're giving you is for educational purposes only. Past performance is not a reliable indicator of future performance. And if you're going to make a decision to invest in PTX, then you should be someone that has got the capabilities to go and do your own reading and make your own informed decisions. So, really excited to be bringing the session to you today. We've got PTX or Prescient's new CEO, providing his first investor and shareholder update. Joining us today is James McDonnell. And so, I welcome new investors and shareholders to the session. James is going to be giving us an update, really focused on the PTX-100, key milestones for Phase II, and a broader update and understanding of the pathway through to commercialization. There's also going to be some comments around OmniCAR and CellPryme and a bit of an update there as well. The session will run for approximately 30 minutes. But if you've got any questions as we go, we'll put them into the chatbox, we'll endeavor to get as many answers to questions as possible. And if we don't get to all of them, we'll provide feedback in later sessions or through direct communication. But look, before we get into the session today, just, I guess, from my perspective and from our team's perspective on why we are so excited about where Prescient is at the moment. They're making significant strides to addressing a critical unmet need for cancer. That represents, for many who receive it, a death sentence, when PTX in their Phase Ib trials, we're able to demonstrate 64% of patients experience a halt or a reverse of the cancer growth, which is amazing and represents great outcomes for people that Prescient are able to provide their therapy to. But as such, they've received strong backing from the FDA, including orphan drug designation and, very importantly, IND. And this is why there's that opportunity for them to turn this Phase IIb into a registration study. They are progressing rapidly towards commercialization and representing one of the fastest commercial pathways for an oncology drug development. Importantly, they're well-funded to execute clinical and commercial strategy with success of the Ib trial being more effective than existing treatments, significantly better duration response and really unmatched from a safety profile perspective. So Phase IIa is now focused on validating these results and demonstrating efficacy and safety. The initial drug market for T-cell lymphoma treatment is approximately 27,000 patients globally, sort of a $2.9 billion market. So they're really well positioned. It's an exciting time for PTX, and they're sitting with one of the most advanced therapies on the ASX. Now just as I hand over to James, a little bit of a background on him. He took over as the CEO of PTX in January, accomplished CEO biopharmaceutical leader, track record of delivering exceptional commercial results, importantly, [indiscernible] oncology and hematology portfolio, which led to a $2.9 billion acquisition and with experience commercializing and marketing pharmaceuticals, he's a great addition to the team and essential to this next phase for Prescient. So, James, you should now have control of the presentation. I'll hand it over to you.

Thanks, Patrick. I appreciate that and welcome investors. So today, we have our Prescient Therapeutics presentation, and you can see we have a major inflection point listed here. And that major inflection point is the Phase IIa started for PTX-100. So if we move through this presentation, there's our disclaimer and safe harbor. I do want to focus on 3 key messages. Firstly, it's about PTX-100. It's a major inflection point with the Phase II initiation. The study has begun. It's encouraging data in an area of unmet need, and PTX-100 is the first in class; therefore, it's up to us to look at the wider application of this class. We have our cell therapy platforms, a low-risk exposure to the cell therapy sector, improving third-party therapies, and agnostic to cell type and targets. And, of course, as Patrick mentioned, we're capitalized to deliver on our milestones. Here's a snapshot of Prescient and what we're about. We're about targeting improved oncology patient outcomes through novel approaches to treat cancer, including targeted and cell therapies. We're led by an experienced team of drug developers and deal makers, and we have a track record. The PTX-100 is a targeted therapy, one of the most advanced on the ASX. It treats cancers with high mortality rates and unmet needs. Our promising Phase Ib results for T-cell lymphoma were 64% response, and so that means patients either had a stable or an improved disease listing. This was over an extended period of time compared to alternatives. From a safety perspective, it was also advantageous compared to other options. As mentioned, the Phase II study in cutaneous T-cell lymphoma is underway. It's underway with an orphan drug designation, which provides market exclusivity, which is important from a commercial perspective. It has regulatory support and a fast-track potential. The T-cell lymphoma market in 8 major markets in 2030 is estimated to be $1.8 billion. The preclinical assets that we have are OmniCAR and CellPryme and the potential to improve CAR-T therapies. So, this is our snapshot of Precient Therapeutics. Now, I mentioned the experienced team. As you can see here, I'm the CEO, newly appointed, and Dr Marissa Lim is the newly appointed Chief Medical Officer, and you can see our directors, along with our Board of Directors. Now we have gained experience through a large number of global companies. Through that experience, we are able to cover preclinical, clinical, regulatory, pre-approval, approval, launch, and commercialization. So it is the team for Prescient. An investment snapshot. So, on Friday, we had a share price of $0.048 or $0.48 and a market cap of $39 million. And you can see there the performance over the 12-month period. So now I'd like to cover an overview of our portfolio, and there are 3 components to our portfolio. Firstly, PDX100 is the first-in-class targeted therapy. Now, for a bit of a science lesson, it inhibits the general transferase. By doing so, it disrupts the RAS family pathway. So, the RAS is important because 22% of human cancers have RAS involvement. By targeting this enzyme, we are able to stop the RAS family pathway from activating. What that means is that we can increase cancer cell death and reduce the growth, survival, and migration of cancer cells. So a very important pathway. Our second asset is CellPryme, and it is enhancing cell therapies in 2 ways. Firstly, CellPryme-M is a manufacturing component. You can seamlessly add this to the manufacturing step. And in the expansion phase, the CAR-T phenotypes you will get will be more memory-based, and this means there's more persistence and more activity. Cell Pryme-A is an adjuvant. Now, this is given to the patient while they're on CAR-T therapies. The tumor microenvironment is a protective factor of the tumor, but CellPryme-A is able to break that down, allowing more access to the CAR-Ts and more activity. Interestingly, we also saw that when you use CellPryme-M and Cell Pryme-A together, you get an enhanced synergistic effect. So, instead of 1 plus 1 equaling 2, we have a 1 plus 1 equaling 3 effect. So, it is a very promising technology. We're currently in discussions with 3 companies reviewing the manufacturing process, and we hope to have further news on that. OmniCAR is our third technology and asset. It's a modular plug-and-play approach to CAR-T. So, traditionally, CAR-Ts have a permanent and single fixed-type approach, and there are approved CAR-Ts in that space. But ideally, we would like to have a plug-and-play approach where you have flexibility, you can target more than one antigen, and you can turn it on and off at times. So, for instance, if you have an AML patient who is neutropenic, you may want to turn off your CAR-T to allow the patient to recover before turning it back on again. OmniCAR can do that. So with Penn University Research and Oxford University Research, which was further enhanced by the CSIRO and Peter MacCallum Cancer Institute last year, we now have an OmniCAR receptor and 2 targets for AML, which we will go through the process of validating and then continuing our discussions with partners. So now I'll continue the discussion about PTX-100. Now, it is a first-in-class targeted therapy. I've mentioned that we have started the Phase II clinical trial in cutaneous T-cell lymphoma. So what is cutaneous T-cell lymphoma? Well, firstly, it's a cancer of the white blood cells, which are typically used in our immune response. But these cells travel and live in the skin, where they divide and are uncontrollable and attack the skin. There are a few types of CTCL that include mycosis Fungoides and Sezary syndrome. Typically, it's rated from a 1 to a 4. And so you have an indolent or more aggressive disease. In our Phase II study, the patient's inclusion criteria is 1b refractory and relapsed. And so those patients are progressing, and they also have limited options. In terms of patients, particularly in the U.S., there's data to show that there are 3,000 new patients per annum in the U.S. and an estimated market size of around $600 million just in CTCL around in 2032. You can also see some pictures here of a patient or patients with CTCL. And you can tell it's quite a dramatic disease. One of the issues we have with this disease is social isolation. Patients have a very poor quality of life. And also, with the attacking of the skin and the pain and the itching, we end up with secondary bacterial infections in an immune suppressed patient, these can be quite dramatic in [indiscernible] and further create social isolation. So you can see that these patients have a challenging quality of life as well as a challenging cancer. So, I had the privilege of traveling with Professor Miles Prince to a T-cell lymphoma forum in San Diego last week. He is very encouraged by the Ib results, and he's very much looking forward to starting the Phase II study. Now, we have a video on our website, which is the Q&A of Professor Miles Prince. And if you haven't had a chance to view this, I highly recommend it. And we do have a snapshot of that Q&A here. So Corey, I'll pass it to you.

Major lymphoma for which this PTX-100 trials are directed is universally incurable in patients that have not responded to their initial therapy. So we are in desperate need of a treatment that will allow patients to respond and give them prolonged remissions.

Thanks, Corey. I take it. I'll have the floor again. So, Professor Miles Prince was the initial site for the Ib, and he had some very good results. In fact, he still has an ongoing patient. So he's extremely looking forward to continuing with PTX-100 and his CTCL patients. So, we talked about the PTX-100 Phase Ib study. And so, let's have a quick look at it. And if you look across the top, we have a benchmark, which is what we would expect to see and what we at least need to see before progression. Lymphoma, which is an FDA-approved product and PTX-100 Phase Ib. And down, we see response rates, which are CR and PR, clinical benefit, which is the CRPR plus with an additional stable disease, duration, and serious adverse events. So if you look at response rates, we would be expecting around 30%, and Lymphoma was approved by the FDA at 36%. We had a 45% Phase Ib result. So that's very strong. From a clinical benefit, we see 45% would be considered benchmark. But in fact, we had 64% in Phase Ib. So, 64% of our evaluable patients were able to have stable or improved disease. And that's pretty significant when you consider the aggressive nature of this disease. The duration of response is also listed separately for CTL and PTCL, but we had a 10.7-month duration in the study. So again, far exceeded what we would expect. Additionally, we typically see greater than 30% serious adverse events for approved products. Lymphoma was approved at a 36% adverse event rate, and we've shown 4%. So I want to look at that a little bit more. So these are other products that are approved on the market, and you can see quite significant and adverse event profiles. And so PTX compares very favorably to these approved products. It suits that fragile patient population and is also a really good candidate for combination therapy. In the U.S., at the T-cell Lymphoma Forum, one of the speakers said that CTCL has a very, very active tumor microenvironment. It's almost like playing whack-a-mole where you hit something down and something else pops up here, and then you hit that down and something else pops up here. And so it lends itself to combination therapy. And so PTX, with its favorable safety profile, will be added to the other material, not only a single-agent activity, but combination activity. So what is the rationale for our CTCL Phase II study? Firstly, we have high confidence from our Ib study. There's a greater need for new therapies because there are fewer sponsors in the space. It's likely to recruit faster because there's less competition, and the patient pool is available, and it's likely to be smaller, faster, cheaper, and a better design. From a PTCL or peripheral T-cell lymphoma perspective, we are not leaving this alone. There is a large patient population out there, but it is a very competitive environment. We would typically need a much bigger study with a comparator arm. So, we will use a compending approach for peripheral T-cell lymphoma. And so with further studies, we'll use an investigator-led program, and we'll then use that data to list on compendiums which are in the U.S., which then allows insurers and payers to reference that compendium and offer reimbursement. So that's the PTCL approach. Now we talk about the Phase II study, and here's the scheme of that Phase II study. Firstly, up to 40 patients are in Phase IIa, and that's at 2 doses, and then there will be a dosing optimization committee, which will confirm the dose. Now, this is an open-label study. So, the dosing optimization committee will monitor the progress of patients. If they see a statistical change, enough to define a dose, that will happen before the 40 patients. And then we'll go and seek a meeting with the FDA and a protocol amendment for the Phase IIb. And this is a very, very important point. The Phase IIb protocol amendment provides avenues to discuss and look at where we're going based on the efficacy of unmet need, and this is an opportunity where we can encourage a registrational approach in Phase IIb. You can see it's a multicenter study in Australia, the U.S., and France. And so it's a very comprehensive study but using all the world and international experts in CTCL. Now, I talked about that registrational pathway. And here is the typical registrational pathway from preclinical through to clinical Phase I, II and III marketing and on market. Now, that's typically for a large patient population. But when we look at our small population, there are opportunities to actually condense the clinical trial component, use a confirmatory study approach, and then move forward. Now, this allows shortened time and also saves money. And so this is the point where we will be discussing our Phase IIb as a potential registrational component based on efficacy. And so it is in a pathway. It's defined, and there are steps to actually discuss this with the FDA. So we'll be doing that based on efficacy data. Our goal in Phase IIa is to replicate these data points. And by doing so, it gives us a strong case for a registrational pathway. Now, we have mentioned orphan drug designation. This is a very important designation. It provides 7 years of guaranteed market exclusivity in the U.S. In fact, it's 10 years in Europe, and we're looking into that now. There are higher prices. The sales side is more resilient. Particularly in the U.S., the CAGR for an orphan drug is high with patient growth but also with pricing growth. In the U.S., you're able to increase the prices, unlike most other countries. For our T-cell lymphoma environment, it's a high unmet need and large market opportunity. So you can see the market opportunity is there just in the 8 major markets, and 67% of that is in the U.S. alone. When we refine it down to CTCL in the U.S. alone with 3,000 new patients per annum, almost all relapsing and combination therapy likely, it's a good opportunity in the market space. So, we have some key milestones coming up. And really implementation is going to drive the value in the space. So we have already started the study. The first patient in the dose will be the next key milestone. Fast Track designation will be another key milestone. We are waiting on that in Q2. The U.S. and European site activations and then continuous review of data in Phase IIa. So, later this year, early next year, we are likely to see some data points because it is an open-label study. And, of course, we have OmniCAR validation of the receptor and the targets in AML, and we continue to discuss with CellPryme partnering opportunities. We mentioned in the messaging earlier that PTX100 is a first-in-class. And so we have an obligation really to look beyond T-cell lymphoma. We know that 22% of all cancers have RAS involvement, and we interrupt that RAS family. Here are examples of the type of RAS genes that are involved and the type of cancers that are involved with that RAS gene. So it's up to us to provide a strategy beyond T-cell lymphoma, and we have a number of options available to us. And so there's work to be done. So, summing up PTX100. It is driving a major inflection point. The Phase Ib data was exceptional, with 64% clinical benefit, a good duration of response, and minimal adverse events. That gave us the confidence to move into Phase IIa, and it's already started. There are multiple sites; we're using international experts, and the recruitment will drive the timing of the study. Now, from a regulatory standpoint and milestones, we have orphan designation and IND acceptance and the potential for a Fast Track designation coming soon. We do know that T-cell lymphoma really aligns with the FDA's interest in sponsors and really keen to get drugs for unmet needs in the marketplace, and that gives us hope for the registrational potential for PTX-100 at the Phase IIb stage. And our market size is significant. So we start with 3 key messages, and I'll finish with 3 key messages. The PTX-100 is a major inflection point for Prescient Therapeutics. We have started the study. It's in an encouraging area of unmet need, and PTX-100 is first in class and has a wider application. We have our CellPryme and OmniCAR assets, which will work with third-party therapies, and we're looking at partners and also validating the new OmniCAR constructs. And, of course, $12.1 million in cash, so capitalized to deliver on milestones. So, with that, I'll hand it back to Patrick, and we'll continue with the Q&A.

Thanks, James. Now, we've got a few questions coming through, and I'd invite anyone who has a question for James to put it into the question box. I think it's Matthew who has asked: Will you be collecting efficacy data during IIa? If so, will you be reporting efficacy performance to the market?

It's a very good question. As I've mentioned, this is an open-label study. And so we are able to see that data, and the dosing optimization committee will evaluate that data. So, there will be opportunities to release the efficacy data along the way. I suspect it will be most likely around that Q4, early Q1 next year, where we will get the first reasonable look at that data.

David has asked patients who were in the Phase Ib trial.

There were up to 25 patients in that trial, and the evaluable patients were 11, and the results, as we've seen, are very promising.

David also asked a comment on whether orphan drug allows 7-year data exclusivity. How much patent life is left on PTX-100?

We will be relying on the orphan drug designation for our exclusivity protection. The patient's life will be running out later this year. Orphan designation is a very good exclusivity vehicle, so we're encouraged by that. We're also looking in Europe, where a 10-year exclusivity in other markets. So it's something we look at as our protection. But I also mentioned that we are first-in-class and looking at wider applications, and part of that strategy will be to strengthen our IP as we move forward.

David asked, is manufacturing of PTX-100 all under control for clinical trials and potentially future market approval?

Yes, we have a very comprehensive CMC department. It's a very valid question. I have seen a number of studies fall over because they did not have GMP-required materials, but we do have this, and we are able to manufacture at a very good level. We will have GMP commercial products in the Phase II study.

Jerry has asked a question about IND. I might just expand on it slightly. And could you explain what it is and why it's important?

Yes. So moving into Phase II, we're really following a defined pathway and the defined points that you need to address along that pathway. And so we submitted our clinical trial to the FDA, and they, through various discussions and there were quite a significant number of discussions- we agree on what that study will look like. Therefore, the FDA gives you an acceptance, which is an IND acceptance of that clinical trial. And now in that acceptance process, we did note that the FDA -- it's actually quite encouraging that we have a IIa and a IIb component within our Phase II clinical trial because that allows that a point of contact at the Phase IIb point where we've defined that optimal dose, we get to go back to the FDA and discuss how that's going to look like. And so we're actually utilizing a defined pathway, but in a very clever way in terms of having that secondary meeting with the FDA to look at our protocol amendment to see what happens at that point. And so that's actually really, really good. With the IND acceptance, the FDA is very engaged in understanding all the ins and outs of the study.

Thank you. John has asked what needs to happen in Phase II so that Phase IIb becomes a registrational study.

Well, it's about replicating our Phase Ib results. And if they are strong enough, if this is, as I mentioned, an FDA area of unmet need, they're very keen to get products to patients with unmet needs. And so the FDA will be inclined to discuss the potential for registration of the Phase IIb based on good efficacy data, but also it is likely where we're waiting to see if we have Fast Track designation, that's another step in the process of this defined pathway. So, there are steps along the pathway. But the IIb is a really good point to discuss that registrational component. But efficacy data will be key, and also the fact that it's an unmet need, it will also be very helpful. And you can see the efficacy data there on the slide. 64% clinical benefit rate. I mean, this is a really good result, and replicating anything near that well above the benchmarks that we quote will be a solid discussion element with the FDA when we talk about protocol amendments in Phase IIb.

So Greg had asked, and maybe sort of at the start of you answering that question. So you may be going back over a little bit of old territory here, but his question was, why are you so confident that the FDA will not ask for a Phase 3 study? I mean, do you want to point to what about the Ib results would lead the FDA to want to see this get fast-tracked?

Yes. I mean, we are waiting for our Fast Track designation; it's an application process. So again, a defined process. The results here, when you look at what a benchmark result would look like and then you look at the Phase 1b results, are significantly improved. So when you have efficacy data, which is very powerful, the FDA is willing to discuss that. And because of the point within our Phase IIa, where we have up to 40 patients in that first round, we're getting solid efficacy data there, we may then discuss what that Phase IIb looks like. Currently, it's defined as 75. It may need to be a little more, but if it's a little more than a registrational component, we're likely to move along that pathway. But it is a negotiation and a discussion. Am I confident? Well, I'm really confident in the data, and how that will play out with the FDA is up to those discussions.

Greg has asked a question about an RAS inhibitor. So what about the RAS inhibitor is so important to the PTX-100?

Well, because we inhibit the general transferase, it stops the RAS Family pathway from activating. And if you have RAS involved and there's quite a number of those proteins, and we will need to do further work there, you can interrupt the oncogenic pathway of the tumor. In doing so, you then will switch it to a cancer cell death and reduce growth survival migration. And so the schema is simplified because the RAS Family is quite complex, that the inhibition with a targeted therapy allows for that disruption. And in that disruption, we see that we can impact an awful lot of cancers. So, 22% of all cancers have a RAS involvement. Now, having said that, I mean, the tumor microenvironment can be quite dynamic as in the case of CTCL and T-cell lymphoma. And so you might need more than one treatment option. And this is where the other benefit, which is unusual to talk about, is a favorable safety profile. But in combination therapies, PTX-100 is not going to add to the further trauma of the patient by the drug itself. It will help with the treatment, and in combination, that's very, very helpful.

A couple of questions on OmniCAR and CellPryme. What are the commercial pathways for both these therapy platforms?

With CellPryme, the pathway is partnership and certainly a channel partner or like for the CellPryme-M and then moving into a partnership arrangement for CellPryme-A. Hopefully, we can get a partner to do the lot, but that will take some discussion at this stage. We're quite focused on the CellPryme-M manufacturing side at this stage. But that does have potential. As you can see, the synergistic effect does create some positivity, and improving CAR-T therapies that are in the market at the moment is an important factor. And so, if you can improve that efficacy, partners are looking. So, with OmniCAR, we had a disruption last year, and we need to go through the validation of the OmniCAR receptor and 2 AML targets. And once that happens, it gives us confidence to work with partners to look at how we progress that asset. Now, CAR-T environments are quite dynamic. And so we will continue to look at the strategy there, but OmniCAR being modular, adaptable, and tunable is really suited to moving forward.

Beautiful. Stephen had a sort of follow-up to probably the answer to that question is: Is there any time line that you're comfortable talking about? And what are your confidence levels around CellPryme and OmniCAR?

Well, CellPryme, we are in discussions at the moment. And so I'm pretty confident about the CellPryme-M partner and channel partner, particularly. We need to validate the new OmniCar receptor in AML, but we continue to talk with companies in the space. We haven't turned it off, but we do need the validation to move forward specifically. So, OmniCAR will probably be later. CellPryme-M, particularly a channel partner, is probably a more nearer term.

In terms of the registration study, what would be the sort of timing for that, I guess, Phase IIb?

I mean, it's challenging to actually talk about that at the moment because if we're going for a protocol amendment, it will depend on what that Phase IIb looks like. We can see from Phase IIa that it's up to a 2-year time period, and that's for the 40 patients, and we may not need to get to 40 patients. So there's up to 2, so it can change. And depending on the kicking-off moment of Phase IIb, the size of Phase IIb, and what that looks like, we will determine the time period going forward. So, at this stage, it's a bit hard to speculate what that might be. But the good thing is that we get an opportunity to discuss the IIb protocol amendment, and that's the key in that space.

Edwin has asked how close the similarity patient to patient at entry in Phase II in order to assess outcomes.

I'm not quite sure there. So the Phase IIb entry requirement or Phase IIa entry requirement is, I just haven't quite got the grasp of that question. So the Phase IIa, they are refractory relapsed second-line CTCL patients at least 1b and above. And so there is a defined point there, and they will then be split and randomized into those 2 dosing arms. And so we will take out the indolent disease and be more in the more aggressive disease as we progress with the Phase II study. I'm not quite sure I've answered that question, but I'm happy to follow up if needed.

Edwin, if you need any more information, just reach out, and we'll come back to you with an answer. Let me have a look. Ed said thank you. All right. Very good. So now there were quite a few questions coming through. So I might not have gotten through everyone. Let me have a quick scan through. All right. Cole noted that I would pass that feedback on to the company, probably before James's time. So I'll just give him that feedback. All right. Well, I think we've gotten through all of the questions that have come through. And I think, James, congratulations on the first shareholder and investor update. I think you did an excellent job. So if anyone's got further questions, as always, reach out. There will be more updates, interviews, and other information getting put through by PTX and the team. There was a question regarding -- all right, here we go. David asked around the cash runway. So we've got $12.1 million in cash; how far along does that cash get us, and what is your estimate on that?

Yes, it's a good question. We do have enough to get through various milestones, but we have said in the past that we will need to raise more capital before we get to the end of the Phase 2 study. We continue to monitor our liquidity and how that tracks. There are a number of variables associated with how that is determined. At the appropriate time, we'll be coming back to the market to indicate the sort of capital-raising components. But one of the key drivers is actually the recruitment rate in the Phase II study. So, it's something to look out for.

All right. Well, with that said, we'll call the session to a halt. Thank you very much, James. Thank you to the shareholders and new investors who turned up to the session. We greatly appreciate your taking the time. James, I'll leave the last word with you.

Thanks, Patrick. I appreciate it. I'd like to thank our investors for being part of the journey with Prescient Therapeutics. As you can see, we've got a lot of activities coming at a major inflection point with Phase IIa. I look forward to your continued support as we implement our plans and create further value. And thanks for joining today.

Thank you very much. Thanks, everyone. Cheers. I will note, as you leave the session, that there's an opportunity to provide feedback. We'd appreciate any feedback. Please fill in the survey. Thanks, and have a great day.