Percheron Therapeutics Limited (PER) Earnings Call Transcript & Summary

Good morning, everybody. My name is Charmaine Gittleson, and I am the Chair of Percheron Therapeutics Limited. I'd like to take this opportunity to welcome all shareholders and guests to the 2026 Annual General Meeting of Percheron Therapeutics Limited. The meeting is being conducted in person at the offices of Hamilton Locke in Melbourne and virtually through the Lumi online portal. You will see this morning that I am also joined by my fellow Board members, Dr. Gil Price, who is online, and in the room by Dr. James Garner and Dr. Michael Baker. And the other members of the company's personnel with us today is Percheron Therapeutics' Chief Financial Officer, Company Secretary, Deborah Ambrosini. I'd also like to introduce the partner from our auditors for the 2026 financial year, Mr. Alan Finnis of William Buck, who is attending the meeting virtually as required under the provisions of the Corporations Act. This is the Annual General Meeting called by the Board pursuant to the notice of Annual General Meeting that was dispatched to shareholders on the 7th of September 2026. I note that a quorum of shareholders is present as required by the company's constitution, and so I declare the 2026 Annual General Meeting of Percheron Therapeutics open. As in prior years, today's meeting will be presented in 3 parts. Firstly, I will deliver my address, after which Dr. Michael Baker will deliver a management presentation. We will then move on to the more formal part of the meeting where the resolutions put to the members will be voted upon. I intend to vote all undirected proxies appointing me as proxy in my role as Chair in favor of Resolutions 1 to 6 and 8 to 13. All shareholders will be given the opportunity to vote and ask questions at the meeting today. We encourage shareholders to ask general questions related to the company's activities after the management presentation and to reserve questions specifically pertaining to the resolutions for the formal part of the meeting. For those shareholders participating through the online portal, I encourage you to download the Lumi online portal guide from the company's website if you have not already done so. I will now go through the voting instructions. For those of you in the room, you would have received a voting card at the registration desk. Persons entitled to vote at this meeting are all shareholders, corporate representatives, attorneys or members and proxy holders who hold a green voting card. Please ensure you print your name where indicated and sign the voting card. If you require any assistance, please raise your hand and a representative from Boardroom will assist you. When you have finished filling in your voting card, Boardroom will collect them at the end of the discussion of all resolutions, when I have announced that the poll is closed, and all votes will be collected online and in person at that time. Please note any unsigned voting card will be invalid. For those shareholders online, you can submit questions at any time to ask a question, select the messaging tab at the top of the Lumi platform. At the top of that tab, there is a section for you to type your question. And once you have finished typing, please hit the arrow symbol to send. Please be advised that only shareholders holding either a green voting card or a white non-voting card are entitled to ask questions within the room. Please also note that while you can submit questions online from now on, I will not address them until the relevant time in the meeting. Your questions may be moderated if we receive multiple questions on one topic, and they'll be amalgamated together. And finally, due to time constraints, we may run out of time to answer all questions. And if this happens, we will endeavor to answer them during the course -- either during the course or after the meeting. If you are eligible to vote at this meeting on the Lumi platform, a new voting tab will appear. Selecting this tab will bring up a list of resolutions and present you with voting options. And to cast your vote, simply select one of the options. There is no need to hit a submit or enter button as the vote is automatically recorded. I would like to remind you that online attendees who have submitted their proxy prior to today's meeting and who have now logged in as a voting shareholder need to resubmit their vote online. You will have the ability to change your vote up until the time I declare voting closed. Voting today will be conducted by way of a poll on all items of business. I now declare voting open on all items of business and online via Lumi. The voting tab will soon appear on Lumi. Please submit your votes at any time. I will provide you with a warning before I move to close the voting. I propose to take the Notice of Meeting the 2026 Annual General Meeting of Percheron Therapeutics Limited dated 2nd September 2026 as read, and I will now proceed with the items of business. Limited copies of the Notice of Meeting are available if anyone here requires a copy. I'll now move on to my address. I'm very pleased to welcome you on behalf of the Board of Directors to the 2026 Annual General Meeting for Percheron Therapeutics Limited. As I've stated previously, we are holding this meeting in person in Melbourne, and it is also being provided in a virtual format for those who are unable to attend. I'd like the first slide, please, and the -- thank you very much. Okay. This slide depicts the progress that we have made over the last year. And I'll just run through it quickly. On the right-hand side of the slide, activities that occurred in 2025, and on the left, in 2026. So the past year has been a period of very significant transition for the company. As you are aware, we in-licensed a new asset, HMBD-002, which is an oncology drug that has completed a first-in-man study under the jurisdiction of the FDA. It was busy in its Phase I study when it came to us. And as you'll see, in October 2025, a year ago, we released the results from that Phase I study where it depicted that the drug was safe and can be administered to patients with various malignancies. Now I know for many that the time periods between active clinical trials can feel like a hiatus. But in reality, there's a lot behind the scenes, a lot of activity that is required. And in fact, we have completed a great deal of important work and made relevant progress over the past 12 months. To begin with and very importantly, a new batch of drug product was manufactured this year and is now ready for deployment in clinical trials. To those unfamiliar with drug development, a topic such as manufacturing can seem almost pedestrian. In fact, this is a complex, high-risk and time-consuming activity. And I speak from personal experience when I say that it can be a critical impediment in a biotech company. The fact that this step has recently been successfully completed is a huge step forward for our program, and it has involved a lot of time from our management team. We have also invested time discussing the optionality and potential uses with clinicians, researchers and possible future partners. With a drug such as HMBD-002 that targets a cell surface receptor that can be expressed by a number of different cell types, there is optionality in terms of which cancers to investigate and how to administer it. And it really is quite complex VISTA receptor that a drug is targeting. And Michael will go into some detail during his presentation to depict the optionality that we have, the positive optionality that we have with this drug. Before we took over the drug, the prior company had done some early work with some researchers, UTSW and Stanford high-quality medical researchers. And that data was published in 2025. Once we took over HMBD-002, we chose to work with the Queensland Institute of Medical Research, QIMR Berghofer, which is one of the leading independent medical research institutes here in Australia. And they performed laboratory work, which was recently presented at the very prestigious ASCO conference. It's the American Society of Cancer and Oncology (sic) [ American Society of Clinical Oncology ]. It was presented earlier this year in June. It's not easy to get a poster presentation or a lecture at ASCO, and we were really pleased that this data was deemed good enough and significant enough to be able to have that presentation. Again, a little bit complex, and Michael will take you through what this all means. But the research demonstrated that VISTA, the target that we are after, is upregulated, so expressed increasingly in patients with triple-negative breast cancer resistant to chemotherapy. These are patients, women who really have virtually no options available to them at this stage. And the marker can also be overexpressed in women who are treated with what's known as PD-1 inhibition, a checkpoint inhibitor, the most famous probably being KEYTRUDA. So those 2 patient groups have this overexpression of VISTA. And this suggests that VISTA may be a relevant target in these patients who become resistant to therapies, and it supports the rationale for further development of the drug. These investigators were very excited by their results. More subtly, but just as importantly, the generous feedback of the clinicians that we have spoken to over this past year has helped us to evolve and develop a clinical trial program for HMBD-002 in a way that I think is profoundly innovative. In August, we announced the next clinical trial. So it's just under a year since we had results of a trial from October last year and now announcing that we're going to be going back into a trial. And that's [indiscernible] in our industry. And the first patient group that we're going to be exploring the drug in are patients with acute myeloid leukemia, or AML. As the name suggests, AML, myeloid leukemia, perhaps it doesn't suggest it to everybody, but myeloid is cells which grow in the bone marrow, and this is a cancer of the bone marrow. These cells that's been discovered express high levels of VISTA as a way of hiding or escaping from the immune system. And the rationale for a clinical trial using an anti-VISTA drug is overwhelming. And we are very pleased to have partnered with the team at Vanderbilt Health in Nashville, Tennessee, who to make this a reality, and they are leaders in this area. The study is a little bit different from what our Percheron shareholders may be used to. It's quite innovative the way that this has been approached. The study is structured as an investigator-sponsored study or an IST. Put simply, this means that the clinical trial site, the university center performs the majority of the work in executing the study. So we don't contract with a third-party contract research organization as one would do when doing a big clinical trial. Academic institutions usually only do this with a sponsor, sponsor being a commercial company, if they are believers in the drug's potential. And the benefit to the sponsor of the company are the cost savings, and that's substantial. In other words, the commitment of this institution allows us to launch a first-class clinical trial without incurring prohibitive financial liabilities [indiscernible] at this stage of our size. I think this is an enterprising and efficient way to move the drug forward. I congratulate the management team on thinking of this, of gaining the acceptance from Stanford and of being able to sign and get an agreement with Stanford -- I'm sorry, with Vanderbilt. They are challenging to get in place with the academic institutions. All of us look forward to seeing the study commence and seeing recruitment in the near future. Can I have the next slide, please? And this next slide really highlights where we are at with the drug. So there are a few really important things that we, the commercial company and you, the shareholder, do want to know and see. The first is, is the drug safe? And yes, the drug is safe. That has been demonstrated. And the U.S. regulator, the FDA, has seen the study and happy with us being able to move forward. Can it reliably be made? Well, yes, and that's not an insignificant achievement. These monoclonal antibodies can be challenging to make, and we have reliably made the batch for the clinical trial. Does it work? Well, we have a lot of data in different preclinical models that suggests, yes, it works. The Phase I study was designed as a safety study. But within that, patients received ongoing doses, and there are patients who were heavily pretreated and really were thought to be almost terminal in their disease who actually had ongoing much longer than expected stable disease or did not progress on their disease. And will clinicians prescribe this? In other words, do they believe in the scientific rationale? And obviously, if it works, would they be interested in this type of approach because they see an unmet clinical need, still an ongoing clinical need. And we've had amazing responses from clinicians really interested in being able to move this forward. So we think we are now in a great place to be able to continue, and Michael will speak to this more. May I have the next slide, please? And one more, please. slides. Yes, just keep clicking. I think we've got a mix up on the slides. I'm sorry. These are your slides, right?

No, they were just...

Right. That's where I want to be. So sorry, everybody. I see those slides in my mind. Okay. Right. Our return to the clinic is not only a significant transition in Percheron this year. I want to take a moment to mention our CEO of the past 3 years, Dr. James Garner, who is here in the room, and you'll hear from him shortly. James has stepped into a Non-Executive Director role with us, which I'm really pleased that he has agreed to remain on the Board. I want to take this opportunity today to thank him publicly for his service. James guided the company through an extremely challenging period when our prior drug did not demonstrate clinical efficacy in a trial. There have been a few of these unfortunate occurrences in Australian biotech over the last year. And a number of those CEOs have elected to move on from the organizations they were with, not stay and turn it around, try and turn it around for the shareholders for various reasons that they may have. But James stepped up and he stayed with us. And as you know, small biotech losing an asset can spell the end of a trial of a company -- of a company, the end of a company. But James found a way to successfully navigate forward and keep us here. It was James that worked tirelessly to identify HMBD-002 and negotiated the acquisition, and we're very appreciative. I look forward to continuing to work with James in his new capacity on the Board and the company benefiting from his ongoing involvement. And of course, we wish him all the best in his future endeavors. You will shortly hear from Dr. Michael Baker, who, despite only becoming officially the CEO 2 days ago, has already given the road ahead much thought, and he hits the ground running. I and the other directors are delighted to have him on board, and we look forward to working with him. Michael brings a wealth of experience and a great deal of energy to the company, and I'm confident he'll achieve much in his new role. I'd also like to take this moment to recognize my fellow Non-Executive Director, Gil Price, who has continued to lend understated wisdom to the company over the past year. I want to acknowledge the company's management team, most of whom are here in the room and say thank you because it's your efforts over the past 12 months that will shortly pay dividends. Lastly, but not least, the Annual General Meeting is an opportunity to say thank you to you, the company's shareholders, and for your patience and support throughout the year. Each of us continues to be inspired by your encouragement and the achievements that Percheron will make over the year ahead and indeed the fruits of a shared labor. We have worked hard on your behalf to position the company for a successful year ahead. We do enjoy hearing from you. So please continue reaching out, sharing your thoughts, and I look forward to sharing our progress with you throughout the next 12 months. I am now going to hand over to Dr. Baker to take you through the management presentation.

Thank you, Charmaine. Thank you very much, firstly, to the Board, all Board members for the opportunity to come in and lead Percheron. I take that as a tremendous privilege. I'm certainly looking forward to working through things as the assets progress in development. I thought it'd just be worthwhile giving a small background about myself. For those of you that don't know me, I'm a PhD biochemist originally, did my PhD in Melbourne, Australia, moved to Germany to do postdoctoral studies. Came back to Australia, knowing I wanted to move out into impact. So I commenced an MBA and then moved into the biotech space, helping early-stage assets get from discovery to clinic. Left after finishing my MBA to join a venture capital fund based in Melbourne, Australia. And following that, I was fortunate enough to be recruited in to lead another company called Arovella Therapeutics. During my time there, we took it from about $4 million to $8 million market cap to $200 million at its peak, and learned a lot along the journey. And that will start clinical trials quite soon and hopefully have the impact in patients that we want. But now I'm delighted to be at Percheron. As I said, I think it's a terrific start. James, you've done a brilliant job bringing in a really exciting asset. And so I think the groundwork is laid and looking forward to getting underway and presenting where things are at and how things look to be moving forward. Next slide, please. Now I will make forward-looking statements in this presentation. So please, as always, do note our disclaimer. Next slide. So what better place to start than where my due diligence over this process of coming on board have found some really interesting and I think pertinent investor highlights. We have strong science, number one. I think that's a really important point. And to Charmaine's point, strong science early is what lays the foundation for good data. Good data underpins ultimately what's going to become a good therapeutic. And with HMBD-002, there's no shortage of good science backing this as a leading potential checkpoint inhibitor. And as Charmaine noted, it's got validated clinical safety data from an already completed U.S. FDA IND-enabled study. That's both as a monotherapy, but also in combination with KEYTRUDA, one of the most successful anticancer therapeutics. The way that we look to move forward is by combining this with other anticancer therapeutic modalities. Now that's a really exciting prospect because it means as we partner this with different therapeutics, it opens up a world of possible partnering opportunities, which is quite exciting for the company. To Charmaine's point, I think that was beautifully stated that we have had a lot of interest from investigators globally, and that's always nice when they're very prestigious U.S. institutes. And what that's translated into, obviously, is our first investigator-initiated study, which I'll talk more about in a moment, but that's not the only one. There's other discussions ongoing. So looking forward to talking more about those as they mature. Now the way this still works, as Charmaine noted, it's complicated. I think the complexity is a good thing. Why I'm excited about that is it actually looks like it should have potential to work across a range of different cancer types. That is a very good thing for us because it doesn't open up just one market opportunity, it opens up several. And again, I think we've got a fantastic team, both Board level and at management level, experience across certainly antibody drug development, which is exactly where we are, but also regulatory strategy and deal partnering, which is important. Next slide, please. So let's talk quickly about the financials. I think it's always worth stopping at the market cap of the company, currently valued at $7.3 million as of last week. I and I'm sure others, certainly the Board and management do not feel this is an adequate reflection of the value of the assets as they stand today. And just reiterating, we have a Phase I completed monoclonal antibody in the checkpoint space, which is one of the most important treatment modalities for cancer. So my aim, over the next months, years to come, is really to unlock the value of this asset. And the way that comes is by demonstrating data in the form of clever clinical studies like the one we've just announced with Vanderbilt. We're in a good position cash-wise. I've presented there the $4.1 million is the end of June 30. And let me be very clear, we also have just received $700 million -- $700,000 through our R&D tax rebate. And we're also, as part of the formal business, completing the $2.3 million placement. So we are in a good position financially, which is nice, and we have funding to do a lot of work through that investigator-initiated study. Now it's always important, and this is a key aim for me moving forward in the short term, to meet with many of our shareholders. Some I have met with already, and I'm very, very uplifted by the positivity around where we're moving forward and how the company is progressing. So that's great to see. And the idea now is we go out and meet with these investors and also bring on new investors and really importantly, ones that understand the risks and the rewards that come with a biotechnology investment, we want patient strategic investors that will stick with us. Another great point to note there is that we've got directors and management holding quite a lot of the company at 4.7%. I personally, after the formal business of the meeting is concluded, we'll also be a proud Percheron shareholder. So looking forward to that as well. Next slide. So let me just stop here briefly and just talk about why we think checkpoint inhibitors are so important. And again, I'll explain what they are because I think that's always important. It is always complex, but I'd like to try and break this down into simple messages. So please bear with me, and let's go through it. Next slide. And you'll have to click again, please. So on that -- in the top corner there, we've got the little green, what we call a T cell. And through everybody's body, we've got T cells floating around. They're what we call the soldiers of our immune system. The job is to eliminate things that don't belong in our system, bacteria viruses, also cancer cells. Now that little red guy is a nasty cancer cell. What it's learned to do is put markers out on its surface. This one is called PD-L1 in this picture, and it sticks to PD-1 on that T cell and essentially stops it from doing its job. So it won't kill the cancer cells anymore. Click the slide, please. So what clever people have done through decades of research, this doesn't happen overnight, they've come up with clever concepts there called anti-PD-1, and it's that little gray thing binding to the T cell now. And it stops the T cell from being able to be blocked by the cancer cell. And so you actually turn the brakes off the T cells, they come back and they start killing the cancer cells. So we have seen tremendous impacts and successes using this type of approach to cancer treatment. Click one more. Now there are other checkpoints, and this is where VISTA fits in. And what they actually do, there's some pretty nasty names here, myeloid-derived suppressor cells, I prefer to call it MDSC. I think that's a little bit more manageable. And tumor-associated macrophages, TAM or TAM for short. They also have checkpoints. They're a little bit different. And what they do is they actually communicate to the tumor cells in a separate way to continue to grow and at the same time, also turn our immune system off from killing the cancer cells. One more slide. And so what we plan to do is use our monoclonal antibody anti-VISTA to play a role in stopping those other immune cells from helping the tumor cells grow. If we're able to do that successfully, again, what we're able to do is turn back on our immune system, and we shape what we call the tumor microenvironment, so it's far more favorable for killing of the cancer cells. Next slide. Now just to this point, this is -- I can say it all day long that checkpoint inhibitors are terrific cancer cell therapeutics, but data, I think, speaks far more. And what you're looking at here is just 4 of the products, some approved now getting on 15 years ago for Yervoy, 2014 for KEYTRUDA. But as of 2025, they're almost bumping up at $50 billion in sales per annum. So clearly, very successful revenue-wise because they're having such big impacts in treating a range of different cancers and helping cancer patients. Now, a really important point here is that when we develop things like this at all, the currency really is in the form of intellectual property. And for these guys, what we're going to start seeing, and they're already happening, is that patent cliffs are looming. So for a company like Merck, where I think KEYTRUDA contributes almost 50% of their revenue, they're going to have to start to look for other modalities, potentially combinations in order to extend that revenue growth that they've enjoyed because the moment they come off patent, we see biosimilars coming into the mix, and they'll start to erode pricing and obviously, revenue growth. So we see that this is a really good opportunity to have a checkpoint inhibitor at this point in time, tackling different cancers. Next slide. And I won't go through this, please do so at your own leisure. This is not a slide to go through every deal, line by line. What it highlights here is that we have seen a number of whether it's an acquisition, investments, licensing agreements, with high-profile large pharmaceutical companies often into little guys where they've got a checkpoint inhibitor that may go after a range of different targets. And you can see in many cases here, the upfront values for these transactions are often not less than $100 million or so, sometimes much larger and the milestone payments associated often end up in the billions. Some interesting ones, for example, down the bottom, Gilead acquired Forty Seven. That was some time ago now, but it was a CD47 molecule that was being targeted. It was $4.9 billion upfront, and that was a Phase I/Phase Ib. And if you look at the targets there, we've got things like TIGIT, IL-27, CTLA-4, PD-1. I don't expect anybody to know what those names are, but they are all different checkpoints with different roles in helping the cancer cells evade the immune system. What's really important for Percheron is I don't see VISTA in that list, and that's quite exciting. Next slide, please. So let me tell you why we are excited by VISTA and why we think it is a novel checkpoint that plays an important role in the treatment of a range of different cancer types. Next slide. So what we're looking at here, and again, it might be a little bit small, so please bear with me. This is just a data set from a recent publication. And what it's doing is looking at the amount of VISTA that sits on the surface of various cells in these particular cancer types. So it goes through the whole list, but probably important to note there that when we look at all cancers, it's more than 1/4 of all cancers that have in red high levels of VISTA and probably around the 80% market have median levels of VISTA. So that tells us that there's a lot of cancer types that we may be able to target if we've got a molecule that's successfully blocking VISTA. Click through, please. And I just want to pull this one out. It's a very specific example. It's probably come up over the last 18 months or so. And it looks specifically at one malignancy here, which is glioma, sorry, so nasty brain cancers and often patients have very poor outcomes for these type of malignancies. But it's -- in this publication, it's a very nice walk-through of patients that have high-grade glioma there in red, 82.4% of them will have high levels of VISTA, whereas when it's earlier or lower grade, it's only about just over 30%. In that middle panel there -- so I mentioned some of those other checkpoint names, TIGIT, CTLA-4, PD-1. If you look at the very left of that sort of hurricane plot, in the red, you can see that's VISTA. So VISTA is the highest expressed checkpoint. That's quite fascinating to me, and I'd love to know more about what it's doing in that context. And if you look at the very right panel, we see that if you look at the red, which is high VISTA or the blue line, which is patients with low VISTA, and what we're looking at here, we call these survival curves. So as unfortunately, people die, the curve shifts down, and we're just looking at over time. And you can clearly see that when VISTA is high, patients die much faster. So again, this is a very good example, a very thorough example of why we think VISTA is a wonderful target. Next slide, please. So again, I just want to touch on quickly how do we think it's doing its job. And I will note now that it's still being fully uncovered exactly how VISTA plays a role in different cancer types because it seems like it's got multiple roles. And again, I think that's a good thing for us. So we have a tumor sitting there on the left. What it does, they hijack various components of the cell themselves. They release what are called chemokines or cytokines and think of them as signals. And it starts telling things like what we call regulatory T cells. Again, these MDSCs or these TAMs come into the tumor microenvironment. We're going to basically take you. We're going to use you for our purposes. And if you click through, please. Then what ends up happening is these regulatory T cells, MDSCs and TAMs, they all start to have VISTA on their surface. So they're basically presenting this molecule. And when they've got VISTA on the surface, what they do is they start to release other components that have a negative feedback loop. We get immunosuppression, we get increased blood supply, we get decreased tumor cell killing, and this results in negative outcomes for patients. So next slide -- click, sorry. And that's what we see here. So this is a nice cartoon representation of the tumor microenvironment. So it's basically all these cells now in together forming a barrier. And essentially on the top right, the T cells that we normally would rely on to start attacking and killing the cancer cells, they can't get in and they can't do their job. So if we're able to successfully use HMBD-002, we're talking about breaking apart this tumor microenvironment. And that's really exciting because it means we are able to tackle a range of different cancers where this is an enormous problem. Next slide, please. So again, I can say this to all I like. It's always nice when we've got data, and I think James has done a wonderful job prior of showing these slides. On the vertical axis, we look at tumor volume and on the horizontal, it's time. So we're looking essentially at how do these tumors grow over time in the administration of different therapeutic strategies here. And the first left panel, it's HMBD-002 on its own in a colon cancer model. And we can see the black line, we don't see much tumor cell apprehension at all. So they're growing very, very quickly. The pink is now with HMBD-002, we see lower tumor volume. Next panel, this is now important. This is to Charmaine's point before, this is in combination with PD-1. So KEYTRUDA, which is on track to be the most successful drug of all time. And when we look at the blue line in that second panel, that's the combination. The tumors are almost now non-existent. Again, fast forward to the third panel. Now we're looking at a different checkpoint inhibitor, another one that does -- it's a multibillion-dollar product. In the black line, and we can see the same, we've just enormously blocked tumor growth. So these combination approaches appear to be very compelling. And that last one here which is actually a completely different modality. It's radiotherapy, which is one of the more well-known treatments we use for a range of different cancers. In the gray line, we see radiotherapy alone. In the maroon line, we see radiotherapy plus VISTA or in this case, HMBD-002. You also see a reduction in tumor volume and tumor growth. So this is, again, really exciting and an approach that we will look to take forward in how do we combine HMBD-002 with what other therapeutics. Next slide. So again, importantly, it's always nice to be in a position where you are in a space that's relatively untapped. That's where we sit with our VISTA targeted monoclonal antibody HMBD-002. I won't go through all these other groups line by line. Suffice to say that they've either stopped working on their assets due to safety issues or [indiscernible] issues. And we sit in a nice position where, again, there's just one little important feature there for our monoclonal antibody, which we refer to as isotype. We have an IgG1, which is in green. The others -- sorry, we have IgG4. The others have IgG1. On balance, we expect an IgG4 monoclonal antibody to be safer because it doesn't lead to what we call cytokine release syndrome because of the way that it functions. I won't go into detail how that works, but it's a really important factor that differentiates us from all of the other groups targeting VISTA at the moment. And it's just us and TuHURA at the moment that have studies ongoing, fascinating both looking to start clinical trials in AML in the short term. So really excited to see the data, obviously, from our investigator-initiated study that should start soon. Next slide, please. So again, I think we've done a very good job already of talking about where the development sits to date, but I'd like to just run through that so people have a chance to get up to speed. Next slide. And as Charmaine has already pointed out, and I just want to highlight this again, we were very, very fortunate to have an asset that's completed Phase I because Phase I is often the choke point for many therapeutics. They may have terrific anticancer activity, but if they're not safe enough, they'll never move forward. It's an impossibility and our regulators won't let you do that. So what we've got here is a snapshot of some of the safety data that we're able to garner from the Phase I clinical trial, which finished towards the end of last year. And again, we were able to see that it's got a fantastic safety profile for an anticancer therapeutic. There was only very few treatment-related adverse events with greater than grade 3 severity, which is excellent. And one of those was a DLT, which -- grade 3 hepatitis, which was able to be reversed with steroids and one that we think is related to PD-1 inhibition. But importantly, for us, we didn't see any additional side effects by putting KEYTRUDA and our HMBD-002 together, which is quite nice. So we didn't potentiate the toxicity of the PD-1 antibody. Next slide. Now naturally, when you are completing a Phase I study, as I said, safety is always the primary endpoint. That's what matters most. You are looking for efficacy. And this is always an important consideration, but I will make 2 very important points. One very important point here is that when you're starting a study like this, a, there's different tumor types involved, but you're also starting with patients that have really, as Charmaine pointed out, very little opportunity and very little expectation of long-term survival because they have failed so many lines of therapy. In fact, I think one of the patients in the trial had failed 13 levels -- 13 lines of therapy before coming on to the study. Now what we saw was some very encouraging data here. Tumors don't shrink on their own. They typically grow the other way. And so what we're able to see in the ultimate column there is the differential in tumor prior to dosing with HMBD-002 and post. And you can clearly see some of them had reasonable levels of tumor reduction, 17% there at the top, 6%, low for the middle one, but it's stable disease out to 30 weeks, which is quite impressive again for these patients that are quite ill. The second last patient had what we refer to as almost a partial response. So 30% is the cutoff there. So again, a reasonable level of tumor shrinkage and same for the last at 13%. So we've got a molecule that's clearly very safe or a therapeutic that's safe. We're starting to get good signs of efficacy. Now we're thinking about how do we take this forward. Next slide, please. So the strategy moving forward -- and next slide again. I'll just discuss that now. And this is a lovely overview of a therapeutic as it's being developed, what we need to do. Just some really important points here actually. So preclinical validation, IND-enabling toxicology and the Phase I clinical trial, you'll notice all have ticks. Just to make the point here that, that's almost a decade of work, tens of millions of dollars that we do not have to do again, which is fantastic. So that work has already been done. We've got a great safety profile. And as Charmaine pointed out a moment ago, the manufacturing process is developed. We've got multiple batches at significant scale. So we're in a terrific position of being able to make this drug. Now we have to decide on how we're going to take it forward. So as Charmaine pointed out, typically, we might consider going into Phase II. And I think strategically, we feel that there's an opportunity here, as I said before, good data underpins a good therapeutic, that we will partner this with different groups in different ways to find the best possible Phase II clinical study to run. Click, please. So the way we do that, as I said, we're going to define that through a series of ways, and I'll talk about those more in the next slide. But clearly, one of those already is investigator-initiated studies, which we've already kicked off. And we're pretty open to the types of modalities that we'll test in combination. Naturally, checkpoint inhibitors are a good idea, but there are other therapies that we think have scientific sense as well. And one more click. And as I said, we're in a wonderful position at the moment of having is the manufacturing of material, the HMBD-002. I think it's very close to being released, Valentina. And once that happens, we've got enough material certainly to support the investigator-initiated studies, which is terrific. So again, there's a lot to be excited about. And I think the most important point is there's a very short pathway to data, which is great. Next slide. So just to talk more about how do we intend or how we analyze what are the best combination approaches for HMBD-002. As I said, investigator-initiated studies is a very elegant way of doing it. And it's importantly for the company, it's cost effective. So we have a very nice pathway to get data that's meaningful that may shape whether or not we begin a particular Phase II study that's been company sponsored. And again, the Vanderbilt example is a terrific example. We will combine that with venetoclax, and I'll talk about that more in a moment and chemotherapy. And as I said, there are other conversations ongoing. Now what I'd like to do is also we'll start to work with other groups that may have assets that have already been in Phase I but they have interest in combining them with our HMBD-002. And we can assess these combinations very cost effectively and quickly in animal models. If we see good outcomes, great, we can consider pursuing that and starting Phase I study because both have been shown to be safe already. If we don't see good data, we don't need to progress. If we're not seeing good data in animal models, there's not much point in moving forward. So again, a nice pathway to finding what are the optimal therapies to partner with. And again, nice ways of generating more data for the company. Now the third at the bottom there is we'll continue to review aggressively different technologies from all over the globe. This is something that I enjoy doing. I think it's very important for the company overall. And what we're able to do in that situation is find technologies that we think will be synergistic with HMBD-002. We can enter into option agreements with these groups. And if we get promising data under those option agreements, we can license those so they become essentially our assets. And the focus there would be on products that are very cytotoxic, so they directly kill the cancer cells, but also biologics as well. Next slide. So how are we looking at it in terms of what are the best combination strategies? Well, checkpoint inhibitors, I think, is a very sensible place to start. We know that VISTA plays a different role as we've seen from other checkpoint inhibitors. But we also know that when people fail PD-1, CTLA-4s that we see increased levels of VISTA in those situations. So it seems like it's a very robust mechanism for cancer cells to evade the immune system. So we'd like to test it with those. And naturally, preclinical data that I showed earlier has supported the combination of different checkpoint inhibitors with HMBD-002. And as I said, this is really important, patent cliffs, all those things, meaningful revenue streams from previous checkpoint inhibitors, we think opens up a terrific amount of commercial opportunity for the company. Now in the middle there, we've got radiotherapy, which is a very well-known treatment that many people use for many different tumor types. And what it's well appreciated to do is actually bring in these cells that we don't want these TAMs and MDSCs into the tumor microenvironment. So again, a lot of the cases there, they will be VISTA high. So we know that, that's a very good opportunity to target. And again, preclinical data has already supported this approach. And the last there is somewhat new. So we'd be looking at other modalities like oncolytic viruses, antibody drug conjugates, even something called photodynamic therapy, where we expect those to have direct cancer cell killing properties, but then they also elicit an immune response. And again, if we're able to shape the tumor microenvironment with HMBD-002, we'd expect there to be positive benefits with those combinations as well. Next slide. So in terms of -- now, again, Charmaine alluded to it before, what are the most promising tumor types to target. Now this is something that we don't have a shortage of actually. There's a lot of different malignancies where VISTA looks to play an important role. So I won't go through them all in detail, but AML, I'll talk about in a moment. But certainly, as Charmaine pointed out, triple-negative breast cancer seems to play a role in reverting those immunosuppressive TAMs and MDSCs, but also then helping the T cells to get in if we're able to block it. Late-stage glioma, I talked about a moment ago, where it's the highest checkpoint expressed, and it is prognostic for survival for those patients. And non-small lung cell carcinoma is also another interesting target. It is highly expressed on those cells that we know will help the tumors. The data is varied in prognosis, and this is some of the nuances of understanding how VISTA does its role exactly. But what's clear is it looks like it will contribute to resistance within that tumor microenvironment. So again, it looks like another promising target. Next slide, please. So I'll just finish here by talking about the AML IST that we've just announced only recently. Next slide. And again, for those of you that don't know AML, it's a nasty disease. Again, as Charmaine pointed out, it comes from the myeloid compartment. So these cells typically start off as stem cells in the bone marrow. They move into myeloid stem cells and myeloid blasts, and then go off and turn into the cells that they should and get out of the bone marrow into the bloodstream and play their role. And what happens on the left there is those myeloid stem cells or blasts actually have mutations that then block them from turning off their growing pathway. So they just essentially grow uncontrolled. They crowd out the bone marrow and the blood and you end up with pretty nasty side effects that we can see up there like fatigue, bruising, bleeding, infection. And ultimately, if left untreated, patients will succumb to the disease. So it is prevalent, more than 20,000 patients per annum in the U.S., often males over the age of 60. And the 5-year survival rate, depending on age and health status is anywhere between 10% to 35%. So it is an important cancer to be looking at targeting. There's a range of different treatment opportunities. Standard of care is pre-intense chemo. And while that does work in a number of patients, a number of -- or 50% of those responders will ultimately relapse. And there are other treatment opportunities if patients do relapse. One of them is venetoclax. And this is actually a molecule that was discovered at WEHI in Melbourne, Australia, and that's one of the molecules that we're going to combine with in this investigator-initiated study. Stem cell transplants are also an option. Next slide, please. So why VISTA? Why do we think it's relevant? And I'd just like to just quickly walk through this because it is very important. On the left panel in the left square, this is healthy donor. What we're looking at here in the red and blue is how much VISTA is on the surface of these cells that we would like to block. And in a healthy donor, you can see that the red and the blue overlap and what that's telling us is there's more or less no VISTA on those cells. If you look at a patient to the right of that, that has AML, so the red is what we call the control group. There's no VISTA on those cells, but the shift to the right in that blue peak indicates they've got a tremendous amount of VISTA on their surface. So the logic for us is very clear. We put HMBD-002 into these patients, and we can block those tumor cells. Now why that matters is in that middle panel there, again, there's a curve looking at the probability of survival of patients here. And if you have the red curve that's high VISTA and if you have the blue curve that's low VISTA, clearly, over time, high VISTA contributes to a much higher frequency or probability of death. And in the very last column there, we know that, again, this is looking at tumor volume on the vertical axis and time on the horizontal control antibody, we don't see any reduction in tumor growth over time. In the blue line, we clearly see that by adding an anti-VISTA antibody, we're able to bring that tumor growth right down. So a very relevant target. Next slide, please. And the study, as I said, it's an absolute delight to be working with Vanderbilt on this particular study. It will be conducted in 2 stages. The first, we will actually look and find the optimal dose of HMBD-002 when it's given in combination with azacitidine and venetoclax. And then we move into Stage 2 once we've got that dose. And we're expecting to enroll anywhere between 30 to 40 patients. And for the patient groups, while we will have relapsed/refractory high-risk AML MDS patients, potentially for Stage 2, we'd like to be able to enroll newly diagnosed AML patients. So again, some of these details are being worked out with the FDA, and we'll be able to speak more about that protocol as and when we have feedback. Next slide. So I'll just finish here with the catalyst, I think, for some of the things that we've got ongoing. And I think you can probably get a sense there's quite a lot happening in the company, which is terrific. And we do see that there's a significant number of important events to transpire, which have meaningful news flow, which is important. We've already ticked a couple off there, released the drug substance for HMBD-002. I have commenced. We will release the drug product formally quite soon. So that's going to be used in the investigator-initiated studies. Naturally, we'll get feedback from the FDA in the form of the IND is safe to proceed letter, which is great. And as I said, we will hopefully be in a position to announce some additional partnerships we'll be looking to make in the near future. And then on to calendar year '27, and expect the first patient to be dosed first half 2027 in the IST study with Vanderbilt, we should be looking to get initial clinical data. We'll work with various people and groups that we need to and be able to package that data up and present it when it's ready. And as I said, we're looking to form partnerships with other groups to test combination studies with HMBD-002 and also we'll continue to have a focus on looking to in-license technologies that we think to be synergistic with HMBD-002. So lots of exciting things to happen, lots of opportunities for good news flow for the company, which is terrific. And with that, I will stop and just say thank you again very much for all of those in the room. Thank you to everybody online, and happy to answer any questions that may pertain to the company, Charmaine, before we move into the formal business.

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