Syntara Limited (SNT.AX) Earnings Call Transcript & Summary

Thanks for standing by, and welcome to the Syntara 2026 outlook webinar and Q&A. [Operator Instructions] On the webinar from Syntara today, we have CEO, Gary Phillips, and he's joined by Non-Executive Director, Hashan De Silva, whose from KPRX, is also one of Syntara's largest shareholders. To begin, I'll hand it over to Gary. Please go ahead.

Thanks, Matt, and welcome to all of you, and thank you for sparing some time this morning to listen to us. We thought about the year ahead, and I think Syntara stands out amongst its peer group as having a really busy '26 with a pipeline of assets which are going to deliver near constant flow of news as we go through the year. So we thought we'd start the year by actually giving a chance for shareholders to ask questions about that pipeline and for us to go in a bit more granularity about that news flow, what to expect and when as we head through the year. I'm delighted that Hashan has joined me today. Hashan sits on the Board with me at Syntara, so he's well across all of the operational issues of the company and the strategy going forward as well, as Matt said, being one of our largest shareholders as well. So we go back -- Hashan, and I go back a long way to the time when he was in Karst Peak, originally looking at us as an analyst. So he's been on the journey with me as well. And I think having his perspective on the call gives an opportunity for shareholders to ask things from a different point of view as well and hear different opinions about the stock and the news flow that we've got. So just very briefly, I think many of you are familiar with us. We are a clinical stage drug developer. We've got a 43% institutional backing, which is quite unusual with this company with this level of market cap. We've got multiple shots on goal, and all of that comes from our own internal drug discovery group, which is funded a lot by the R&D tax credit from Australia. So it's a really efficient way of building pipeline in a small biotech in Australia, and we've made the most of that. And to the point where we've actually got 5 clinical trials, which are delivering clinical trial data, efficacy and safety data during this 12-month period, so that's an outstanding level of return, getting that number of opportunities to read out within a short period of time as well as that, all of those assets have got pretty long intellectual property on them as well. So they're valuable from a potential partnering commercial perspective because they've got a lot of patent life ahead of them. And on top of all that, not a lot of those trials have been funded by nondilutive cash. So we announced pancreatic cancer grant earlier in the year. That brought us to over $11.5 million in nondilutive grant funding we've been awarded in the last 3 years, which is supporting that news flow and those trials going forward, so a really broad pipeline from a company which is delivering a lot of assets to value inflection points in a short period of time. That's just a reflection on the -- where we are at the moment with the share price. So we're standing at about a $50 million market cap as I said, with that 40% -- just over 40% institutional. So there's smart and health care specialist money invested in Syntara. And we've got a lot of coverage as well. So Canaccord, Bell Potter, Euroz and Evolution Capital all issue coverage reports on the company. As we headed into '26, we had a really strong last quarter. We presented amsulostat, our lead asset at the American Society of Hematology, ASH, in Orlando in December. And that was really the foundation for that asset really building momentum as we entered into this year. On top of that myelofibrosis data presented at ASH, we had the second myelodysplastic syndrome study. It's a related hematological cancer initiated in Australia. So that's the MESSAGE study that goes on with the AZALOX study, which was already started earlier in quarter 4. So both of those studies now recruiting and you'll see in a minute when we're going to expect to get news out of those. We broadened our regulatory interaction by going as well as to the FDA to the European Medicines Agency. They granted us Orphan Drug Designation. That is a slightly different process from the FDA, a very rigorous one where they have to see that the drug is going to add value in the indication that you're asking for before they grant it. So it's not just is this a small group of patients. This is a small group of patients, and we can see from the results of the studies that this drug is potentially going to add a lot of value for patients. And then obviously, that announcement that we were getting granting for a pancreatic cancer study that's going to start later in the year as well. So the lead asset, amsulostat really building momentum. And then backing that up, our pipeline assets, 4728 in a Parkinson's disease patient group who suffer from a sleep disorder, iRBD. We announced that was fully recruited with data expected later this year, also triggered a payment from Parkinson's U.K. of $1.8 million, which we expect to get in this quarter and also the skin scarring program with 9465 progressing into a hypertrophic scar study. And we -- in quarter 4, we had a great webinar for those of you who caught it, those of you who haven't, I strongly recommend it as a good watch with Professor Bayat, really digging into what it is about scarring that makes it problematic for patients, why there's so little in development at the moment, the hope he had for 9465 and the, I think, the very innovative design that we have now going forward. On top of that, we ended the quarter with a cash balance of $12.3 million. That cash balance takes us into 2027, so a strongly funded position with a lot of news flow to come. Now just before we go into the Q&A, just to break down that news flow for you, so in the first half of the year, lead asset, amsulostat, we are in discussion with the FDA to get them to approve our development plan to go forward with the asset in myelofibrosis. That approval of that plan also triggers partnering engagement and potential deals with that asset at that point. So that is the trigger point that we're waiting to see in -- for this lead asset. And those discussions are ongoing now, and we expect feedback from the FDA and announcements in the first half of this year. Those 2 MDS studies, AZALOX in Germany, MESSAGE trial in Australia, the AZALOX study is in high-risk MDS patients. The MESSAGE study is in low-risk MDS space, so 2 different patient groups. The AZALOX study is running a bit ahead. We expect interim safety and efficacy data around the middle of the year and then initiation of the Phase II study on the back of that in the second half of the year. The MESSAGE study, which is running slightly slower, is we expect interim safety and efficacy data in the second half of the year. On top of that, the pancreatic cancer study, which we talked about earlier, trial initiation in the second half. And just a reminder that both of those MDS studies and the pancreatic studies, cancer studies funded by nondilutive cash at this point of their development. Skin scarring program, 2 different assets. The first generation scarring program, 6302, is in the hands of Fiona Wood and the University of Western Australia. In keloid scarring, we're expecting interim safety and efficacy data in that keloid scarring study around the middle of the year. The hypertrophic scarring study is open. It's recruiting. We expect top line safety and efficacy data in the second half of the year with that. So those 2 studies, and in particular, the one in hypertrophic scarring are the ones that really unlock value in the assets. We think this is an enormously powerful study, is going to give us clinical proof of concept and evidence that will allow us to really accelerate that program and potentially opens up immediate partnering as well for that asset. Finally, the study in iRBD Parkinson, as I mentioned just now, that study has completed its recruitment. So we're now on a schedule to release Phase II data. So we will have top line data from that study in quarter 2 this year. So with that, I will finish my presentation, and I'm happy to hand back to Matt to lead us through the Q&A. Matt, back to you.

Thanks, Gary. As you mentioned, we'll move on to the questions. [Operator Instructions] Gary, the first question is, you've now got 3 separate blood cancer studies running in parallel. What have you found -- what have you learned about where amsulostat's clinical sweet spot might ultimately be across risk categories and lines of therapy?

So we've completed studies in myelofibrosis, a number of them now in patients who were not responsive to standard of care, the JAK inhibitors and also those patients who were still on JAK inhibitors but really weren't being well treated. I think the things that we've learned about the sweet spot, first of all, the safety seems to be really robust in a wide range of patients now. We've got patients who have been have come out the other end of ruxolitinib and not been treated on it at all, but 12 months really from end of life and; through the patients who have been 3, 4 years on ruxolitinib and those patients who have just started on ruxolitinib as well. And throughout all of those, we're seeing a really clear picture, which is that the safety seems to be pretty robust. The last study, I think, showed us that time to efficacy was actually a bit quicker than we thought. We extended that last study in suboptimal patients from the 6 months we looked at with the ruxolitinib failures through to a 12-month study because we thought, from a mechanistic point of view, our drug would take a little bit longer to work. And actually, we saw really strong response to symptoms inside 3 months. So that was -- that's really quite interesting in terms of unveiling where the sweet spot for this thing. And I think it's really important from a profile point of view, patients who see benefit early on are much likely to stay on drug are going to stick with the therapy because they immediately feel better. I think in myelodysplastic syndrome, it's a bit too early to tell. The preclinical work that we did with the University of Heidelberg in Germany was in high-risk patients. So if I -- if you ask me to look at those 2 studies, 1 in low and intermediate risk, 1 in high risk, I think the 1 in the high risk is where we've got evidence in the preclinical study that we should see a fairly rapid response in red blood cell -- numbers of red blood cells quite quickly in that study. So -- but we need to wait and see clinical data now whether the preclinical work translates into the clinic in the middle of the year. And in myelofibrosis, I think going back to that finally, I think, suboptimal patients mechanistically, we know now that the amsulostat blocks a pathway that bypasses the JAK inhibitor efficacy. So having patients who are still on a reasonable dose of ruxolitinib, not at the end of their disease and with -- are still on a reasonable dose, we think it's probably that sweet spot that, that question was trying to get to. So yes, I think we've learned a lot in the studies we've got, and I think we've got a clear idea about where to go in the future in myelofibrosis, and in MDS, we need to wait and see.

And then Hashan, what qualities of amsulostat do you think make it attractive as an asset?

I think it has many features that make it quite attractive. If I start at a high level, I think the safety that we've seen now across many different patients in many different stages of the disease, give amsulostat optionality. Whether it can be used early stage or late stage, that's quite unique to a lot of drugs in development in oncology where you see that the safety profile kind of limits the drug's use. Mechanistically, so we're talking about just in myelofibrosis, it's quite unique. A lot of the drugs in development are kind of pseudo anti-inflammatory drugs. And so combining those with other anti-inflammatory drugs, can make it -- can have diminishing returns quite quickly. And then the side effect profile of those drugs mean that you can't really combine them in patients who are otherwise feel well. With amsulostat, theoretically, you combine it with the JAKs that are on market or any of the drugs that are in development, mechanistically should be synergistic. And when you think about that mechanism of action, it is a pipeline in a pill in the sense that it can be used in these blood cancers. It can be used in solid tumors where fibrosis is an issue. It could be used even outside of oncology where fibrosis is a hallmark of disease. One of the things that I've spoken about before is in solid tumors, fibrosis is often key to the tumor spreading. And we've seen now in at least in breast cancer that fibrosis predates the metastasis. So fibrosis is required in order to terraform the liver so that breast cancer can survive in other areas as well. So mechanistically, this is very, very exciting. There are more things that we could explore that I think Syntara can afford to. The other kind of key benefit here is long IP that is also unencumbered by having to pay royalties to anyone else. If you look at some of the other drugs that are on development on -- in the ASX, there might be just have protection from the orphan drug designation. They might have some kind of use patents or manufacturing patent. Amsulostat has a plethora of patents with composition of our patents that extend out decades. And that makes it very attractive to a potential acquirer especially given the optionality of this drug across many disease states that you could do dozens of clinical trials and still have protection well into late 2030 and potentially even into the 2040s.

And what do you think the market is missing about the myelofibrosis clinical data?

I think a few things. I think first, when it comes to safety, well, I think the market is looking at the data maybe in isolation or thinking about how this data can be combined with every -- with other treatments in development or other JAK inhibitors given the safety profile of amsulostat. So I've heard some people focus on spleen size, saying look at the spleen size here, look at the spleen size there. Why isn't amsulostat delivering a similar spleen size to XYZ drug? That needs to be taken into consideration with the safety data, right? So you can reduce the spleen size in these patients really well by a drug called navitoclax, right? But then the patient essentially is suffering in every other aspect of disease. So it's not about just what is the headline results. It's about the headline results in -- associated in hand in hand with the safety data. I think also the market got very confused or very distracted by the FDA feedback by going into a Phase II before we enter Phase III. I mean that is normal drug development, right? That's not -- the FDA is not asking us to do anything different than we would have done otherwise. Now we were shooting for the stars. Maybe we're going straight into Phase III, but the FDA has brought us back to Earth. But from a shareholder's perspective, it's not materially that different, right? So you are funding a Phase II trial, which cost a whole lot less and significantly derisks the asset before you have to raise for a much larger Phase III trial. So from a risk-adjusted IRR perspective, there really isn't that much difference to an investor today than going through into Phase III, I believe. The other aspect that I think that the investors are missing and something I've discussed extensively in the past is that we know now definitively that binding to and inhibiting LOX prevents fibrosis. We've seen that in the topical skin scarring trials, where we saw a 30% reduction of myelofibrosis. Now when I did that podcast a while ago, I said the question left to be answered is does doing that in myelofibrosis cause a modification of disease? And I think we're even closer to answering that because we've got the Phase II data that shows quite a rapid onset of symptomatic relief and then a reduction of spleen size. The results that we saw from the myelofibrosis trial at least from my perspective, KPRX perspective far exceeded what we thought was available -- was possible in this patient subset. And so we are very excited about the future. Another thing that I quickly mentioned in myelofibrosis specifically, the safety profile and the speed of action means that this drug could potentially be used even earlier in the disease course, potentially even as early as pre JAK. And that would make amsulostat the backbone therapy for myelofibrosis where everything else gets added to amsulostat. No other treatment in development can be used in that patient subset because of its side effect profile. And so I think when I look at everything else in development from myelofibrosis, to me, this is the most exciting asset in myelofibrosis development.

One for you again, Gary, which aspects of the future trial strategy do you see as the most critical to get right to support successful late-stage development and the regulatory approval and commercialization, obviously?

Right. So yes, if you're talking about development and regulatory approval and commercialization all in one bucket, I think I've spent a lot of time in the last 12 months talking to multiple potential partners. So the clear feedback we have from them is that we have a really attractive and well differentiated asset for all the reasons that Hashan and I talked about a bit earlier. And what they want to see as well as us is the sort of trigger point to sort of going forward with both the development and potential commercialization, is that clear guidance from the FDA in the first half of this year that will really unlock that value. And I think the thing that we are absolutely focused on now is demonstrating the safety and efficacy of this drug in a controlled trial. We need to absolutely nail and get a very clear baseline of the patients coming into the study. So we understand what their history has been, what their symptom score and spleen size is coming in and then that really clear comparison with those baseline patients going into both a control arm on placebo and the JAK inhibitor and on our drug and a JAK inhibitor combination. Our open-label study had patients treated out for 12 months. And I think -- we saw improvements in patients who had been 3 years on ruxolitinib, sometimes even more. And those patients were still getting more than a 50% improvement in their symptoms and a reduced spleen size, which all of the key opinion leaders when looking at our open-label data, thought was remarkable and could clearly see it was absolutely the drug working. We now need to do that in that controlled trial setting, and that will give the confidence of both the regulator and potential partners that what we have is something which is -- will get through regulatory approval and will bring real benefit to patients.

The next question is for you again, Gary. What's the optionality the company has around partnering and how that might mitigate cash requirements for Phase IIb and then beyond?

Yes. So I think Hashan already mentioned that we had looked to do -- maybe go take this straight to a Phase III. And we're going to go through a 2-step process rather than a 1 step. So to we're going to do the Phase IIb. The partnering after a Phase IIb is almost the same as partnering after a Phase III. You're delivering safety and efficacy data in a controlled setting, so the value of the asset after the Phase IIb is still really, really, really strong. So I think when we talk about partnering at this point, I'd say we remain very open and flexible on deal structures. We're not trying to force this into one particular size hole. We've got a really strong pipeline. So any deal on amsulostat doesn't necessarily look like a company acquisition. It looks more like a, in broad terms, it looks more like a licensing deal with significant cash upfront that give value for the development that the company has done to this point. So I think you could see at this point, the Board, including Hashan, has given me a clear direction that we want to see optionality going into the first half of this year. So we want to explore what might be available from a partnering perspective, and we want to explore what might be possible in terms of raising the cash to do the Phase IIb. So I can imagine regional deals that trade territory rights for cash to support the study as well as a global licensing deal and probably everything in between as well. So it's -- yes, at this point in time, we've put ourselves in a really good position. We've got efficacy and safety data, which I think, as I've mentioned before, is compelling despite the fact that it doesn't have a control group. We're about to get that feedback from the FDA in the first half of this year in terms of agreement on the study design going forward. And then we'll see. We'll see what happens out. But yes, the next few months are going to be really critical for the company and the drug, and we will maintain open dialogues with all interested parties at this point.

And Hashan, with your day-to-day roles with KPRX, you're obviously looking across the market. So how have you seen big pharma's appetite for M&A and licensing changing over the last couple of years? And what sort of deals are getting done?

Yes. So there's been quite an interesting evolution, particularly from the market to 2020, 2021, where we saw a lot of deals focused on platforms or kind of very early-stage deals looking at kind of groundbreaking technology that might generate more than one lead candidate. That has kind of done a complete 180, and we're seeing the deal focus really go to assets that are derisked, that are late stage and with big pharma willing to pay up for those assets rather than take the risk of going early. In myelofibrosis, in particular, we've seen that in the last 2, 3 years with essentially most assets that enter -- that will finish a randomized controlled trial being acquired, that has positive trial data from a randomized controlled trial. And I think that's really been driven by the fact that the patent cliff has come right now at 2026, 2027, is really where the patent cliff falls. And we haven't seen big pharma launch anything outside the GLP-1s, launch anything blockbuster. And so we're seeing a much more activity. JPMorgan this year, the big health care conference, most of the conversation was around the patent cliff and finding assets that can generate revenue within 2 to 3 years. And I think that's been a big big shift that we -- that was not the focus of discussion kind of 5, 6 years ago. On the kind of wider market as well, since 2021, really, we've been in a one-word trend for biotech, right? The -- it was down and to the right, where the XBI was testing new lows every year. 2026 feels different. We saw the IPO markets kind of opening in the U.S. towards end of last year and big deals, big IPOs, big secondaries getting done and the secondary market, secondary liquidity for biotech in particular really coming back. There's definitely more optimism out in the market this year than I think there's been in the last kind of at least 4 years. And so we're quite optimistic that 2026 is the turning point for this -- where 2025 was the lows and 2026 is when the market starts to recover for biotech and med tech.

Yes, it's probably worth adding to that, Matt. In terms of Hashan's comments on patent cliff, ruxolitinib, the $4.5 billion drug, of which probably $1.5 billion is in myelofibrosis, is off patent in 2028. So that's going to shake up the myelofibrosis market significantly at that point with -- yes, makes amsulostat really attractive going into that particular market with that dynamic going on.

Great. And then just changing track, so amsulostat for pancreatic cancer and the recent announcement there, you alluded to, Gary, obviously, a tough indication for drug development. What specifically gives you confidence that amsulostat's mechanism could translate into clinical -- clinically meaningful benefit there?

Well, we're -- I guess, first thing to say it's a free shot for us, right? So we didn't have to make an investment decision on this because the MRFF, the Australian government grant for this to the Garvan Institute has made this possible. So for Syntara shareholders, this is a free shot, which is great. The preclinical work that we did with the Garvan over a number of years, which resulted in a Nature Cancer publication in 2023, was an outstanding piece of work. It really showed that when you add amsulostat to standard of care chemotherapy, what you see is amsulostat breaking down the fibrotic nature of the pancreatic cancer tumor, reducing intratumoral pressure by doing that, which allows in the body's own killer cells, T cells, to go in there and attack the cancer as well as chemotherapy. And the result of that was the tumors shrunk. You've got longer survival. It was really a wonderful piece of preclinical work. So this trial is looking at translating that. I think the trial design itself is really, really helpful in that as you mentioned at the outset, the clinical development in pancreatic cancer is notoriously difficult because patients tend to be diagnosed quite late. Often, they've metastasized before they come in, and they haven't got very long to live. So if you're going to address the fibrotic nature of the tumor, the question you have is how long do these patients have, how much can we change the nature of the tumor, how much benefit can it bring as the disease is progressing rapidly in the background. So I think the great thing about this study is that they've got a huge amount of experience in imaging and genetics within the Garvan Institute and the Kinghorn. So they will be looking at each individual patient that comes in. They'll be looking at what specifically does the treatment at a micro level within the tumor. So even if these patients are still progressing for whatever reason, we will learn a lot about the combination of amsulostat and what it does with chemotherapy on a cellular and mechanistic level with these patients, which will allow the treatment regimen to evolve and to pick the right patients where we can bring benefits. So I think it's a free shot for the company, but I think the study design is brilliant, and I'm really looking forward to seeing that translation of what was a tremendous bit of preclinical work into the clinic.

And we've frequently described the pipeline as being multiple shots on goal. So how do you internally decide what programs deserve to the incremental capital versus being partnered or even paused?

Well, you can see from our record, I think it's an easy question to answer. Amsulostat is our first priority, absolutely. It's already got clinical proof of concept. It's already got lots of interest from potential partners, and there's ongoing regulatory dialogue with already a clear pathway forward to commercialization. So that really -- that asset has all that you would look for in a biotech company to say that is an investable asset, which deserves to be prioritized and accelerated as fast as possible. Beneath that, the scarring program that we have, which came out of the overall look at fibrosis, and it was a long development co-development with the Fiona Wood Foundation and UWA. That's been a really cost-effective program to develop in conjunction with the Fiona Wood Foundation. But it's now on track to get proof of concept by the end of this year. It's a relatively small study but extremely innovative, I think. So it's funded. It hasn't cost us a lot of money. It hasn't distracted at all away from amsulostat, and I think the trial design is right. We just need now to wait and see that the bed has been placed. The trial is funded. The commercial potential in scarring is huge, and we've got a lot of interest partnering in coming when people see what we're doing. And all they're waiting to see actually is can you change a scar. And I think this study, we will see very clearly now whether the -- whether we're going to get that photograph on this, there's a before and after, what a scar looks like before and what it looks like after 3 months with this drug. So it has a bit of investment but hasn't attracted away from amsulostat. And then there's 4728, which is absolutely a free shot. It's fully funded by Parkinson's U.K. If it doesn't come off, it doesn't impact us at all. But if it's positive, then it's a huge upside for shareholders. And we'll again seek probably to use partners or nondilutive cash to advance it. So I don't see 4728 being a distraction. It's ongoing. The study has been paid for. And now we're just waiting to see what the result is.

And then for you, Hashan, if you look at Syntara's portfolio as a whole, as Gary has just spoken to, which program do you think is misunderstood by the market? And why do you think that disconnection might exist?

If I take a step back from an asset perspective but look at the whole portfolio, I think what the market is -- well, what Syntara's suffering from is almost a conglomerate effect that you see in the likes of -- give an example of Berkshire Hathaway and um of the parts is worth more than the whole. Where it's difficult with Syntara given how many programs are being run to -- unless you do this for a living, to look at each of the assets and come up with the probability to assess and the value for each of the assets. And when you try to kind of back solve Syntara's valuation at a $42 million-ish EV, $40 million EV versus all of the programs that they got running, randomized controlled trial in Parkinson's, a randomized controlled trial in skin scarring, a Phase II trial in pancreatic cancer, Phase IIb trial about to start in myelofibrosis, it doesn't make any sense, right? Like you got single-asset companies which arguably have the same, if not a lower probability of success as one of Syntara's programs having a substantially higher valuation than the company as a whole. So I think investors need to take a step back and look at all the shots on goal that Syntara has and to kind of -- to back Gary and the team on the back a little bit, how that's been done so capital efficiently, right? So 4728 is a randomized controlled trial in a very difficult disease to treat, to recruit, a trial to run that is being fully funded by third-party money. I mean I can't think of a single example of an ASX-listed biotech that is doing that or that has done that in the past. And that's just 1 of 2 randomized controlled trials that are being run and being funded that doesn't take away from the lead asset. I mean that's quite amazing, really. In terms of the asset that is misunderstood the most, I still think that is amsulostat, right? The people don't understand -- I think what people are missing is that the safety profile makes amsulostat -- or gives amsulostat so much optionality to be used in all the way from first line, all the way to end-stage patients. The mechanism of action is not disease specific. It's not specific to myelofibrosis, right? So this works in myelofibrosis, it will derisk its potential in myelodysplastic and on the hem-onc but also derisk its ability to work in other kind of solid tumors. And it is one of the rare drugs that I've seen in Australia that is a pipeline in a pill, right? So if we had access to unlimited capital, we could be running dozens of Phase II trials in amsulostat. Obviously, that's not the world we live in. And I think that kind of concept of the safety profile, the mechanism of action makes this drug so unique and so versatile that it makes it a very attractive partner -- a very attractive drug to a partner once we approved it in a randomized control setting.

And then, Matt, just to add to that, my discussions with potential partners for amsulostat. And when we talked to earlier about what does the licensing deal look like, well, it looks like one where you also get value not just from the lead indication of myelofibrosis but where you also get value from myelodysplastic syndrome and potentially solid tumors as well. We will be looking to make sure that the sort of valuation does take advantage of all those things that Hashan talked about and the optionality that a pharma company with deep pockets would be able to access almost immediately. So yes, it's -- it very much drives our thinking in terms of how you -- to try and get value from the broad range of indications that not only is it being developed in but also it could extend to.

It's only been touched on briefly so far, but the topic of fibrosis programs, Gary, are structurally different from the oncology assets. So how does that change your thinking around development speed, partnering time lines and ultimate ownership of that?

So yes, I think we talked about this a bit earlier, but I think we've got a really innovative and efficient way to get to clinical proof of concept now with this program. It went through several iterations. We talk a lot of it -- we talked to a lot of surgeons, plastic surgeons, dermatologists globally and also companies globally about what they wanted to see in this area. There aren't any drugs approved for scar modification from -- that have a pharmacological direct action on the scar. Professor Bayat in his webinar talked about unlocking the scar by breaking down the scaffolding, the fibrosis interlinks between the collagen fibers in order to change the scar structure. So we've now got that, and we've managed to get -- we think, to get clinical proof of concept out of a Phase I study. So that study, which is ongoing now, the patients act as their own control. They'll get placebo and active looking at the scar. We will take tissue samples from that, so we'll be able to see structurally what's going on with the scar. We've got several different and again, quite innovative instruments, which will look at the flexibility of the scar, the volume of the scar. We'll have really high-quality photography as well with independent and blinded ranking of the scars at the end of it. So we've done all of that with a Phase I study in Australia, which is the most cost-effective way of getting through to something like that. So it's going to be fast. We hope it gives a definitive answer to the question of whether pan-LOX inhibition modifies the scarring process. Once we have that, then there are many routes forward open to us. This could be a company its own right. A skin scarring program like this is -- if you look at what the value of , I think at the moment, the global market for -- in skin scarring modification, there's more than $1 billion being spent on silicon products, which have no real tangible effect on scarring longer term. So having the first drug, which can pharmacologically change the structure of a scar and modify -- change the scarring process, it's -- it will open up a lot of possibilities for us that include, yes, company-specific ones, investments and partnering as well.

And there was a couple of questions across the board that came in around 4728, so just wondering what the next steps are there, what it might look like if the results are positive from the current trial and the likely funding options going forward?

Well, as you know, that study is in patients that have a sleep disorder who are a very high probability of developing Parkinson's disease or other neurodegenerative diseases in the future. So there's 2 bits of inbound interest in the asset from pharma companies. One is from sleep companies. And we're seeing an emergence of interest in sleep as an indication. Narcolepsy, all other kind of sleep disorders are beginning to see more investment going into them, and therefore, that's driving more research and more partnering activity. So we've got interest from companies that are focused on sleep, saying, look, if you can produce some changes in the quality of life of these patients from -- in a sleep score point of view, then that's of interest. We've also got interest from companies that are really focusing Parkinson's and other neurodegenerative diseases that would look very much at the PET scanning that we've got of these patients' brains and looking at whether we're reducing inflammation in these areas of the brain because, again, that would be novel. It would be the -- something that would be a clear indicator that you might had a slow progression or stop progression of these diseases as they go forward. So there are 2 different ways. And we know also from a global thing, and Hashan noted this as well, is that the uptick in deal values and interest in CNS has risen rapidly in the last 2 years. So there's money going back into CNS at the moment. So we've got partnering potential here if the data looks positive. But also, I want to pay respect here to the philanthropic organizations in Parkinson's who made this study possible, Parkinson's U.K., in particular, through their virtual biotech organization within their group. This is -- this was the biggest investment that, that group had made, and it was the most advanced one. They've not invested in a Phase II study, blinded Phase II study before. The Michael J. Fox Foundation, which also were very interested in what we were doing, are paying a very close watching brief on this as well. And these organizations work together to advance treatments which are going to be helpful for Parkinson's. So I think we will also get a lot of inbound interest from those philanthropic organizations as well as this study, which they have funded, comes up positive in quarter 2 this year.

If I can just add to that as well, Matt, there was a very insightful question that was put to us just now through the Q&A about what the BI trial that they did in NASH can provide, some read-throughs or some learnings for its use in iRBD. I'll just hit a couple before I hand back to Gary. I think I want to harp on the safety again, right? So we've got a safe compound that is now being trialed in pre-disease effectively. It's gone in patients with Parkinson's, some patients with a sleep disorder that can -- that gives -- that might develop into Parkinson's later. And the safety profile means we can dose these patients even before they're symptomatic to hopefully prevent disease. And that goes back to what I was saying with amsulostat. The other thing -- the other key insight that I have from that trial is that we know that the drug cross the blood-brain barrier. We know that it binds to and inhibits MAOB. And so we have a pretty good idea of the pharmacokinetics of the drug. Another question that we need to have answered is, does that mechanism of action cause a reduction in the microglial activation. But yes, Gary, keen to hear your thoughts on that question as well because I thought that was quite an insightful question.

Yes. No, I think actually true. And I think when we were talking to Parkinson's U.K. originally about the study, the thing that attracted them about this was just how well developed this drug was. Boehringer despite the fact that they handed it back because they didn't feel in the -- in a NASH setting, which is very, very competitive, that they felt that it had the right competitive profile for them to invest what would have been probably north of $0.5 billion in clinical development. It came back to us and they said, look, we think the drug is safe. It's just not got the right profile. And of course, when you now look at it, they did all of the studies that you need to do to go into Phase III. They did all the GM -- they developed a better manufacturing process. They had -- we purchased GMP material from Boehringer back that now is being used in this study. So Boehringer paid us, I think, over $80 million, we got out of it from the sale of them. They handed it back -- we got it back with not having to pay them anything, but it came back having -- with them having invested probably, yes, $100 million, $200 million in actually getting it forward to this point. So this is a really advanced asset, which if we show efficacy is a really attractive one for pharma again to step in and pick up for all those philanthropic organizations to drive through to something will benefit patients.

The next question is for you, Hashan, and stepping back from Syntara specifically, how do you see the current biotech market bifurcating between assets that get funded and those that don't? And what characteristics do you think investors and pharma are prioritizing right now?

Yes. So like I said before, I think the focus has really shifted to drugs that are on market that have a clear mechanism of action -- sorry, not on market, sorry, drugs that are in the clinic with a clear differentiated mechanism of action. Me-toos aren't getting funded like they were in 2020, 2021. And it's much harder to raise capital for preclinical-stage companies. And so the focus really has been to -- okay, so if this drug is that Phase I, Phase II, what is the mechanistic rationale for this drug working in this disease state? And what is the path to market and how do we get it to market? We've already seen that translating in Australia now, actually, we're even very early on in 2026, where we saw a company, I believe, it was yesterday, raise north of AUD 500 million for a drug entering the Phase II trial, with a very clear mechanistic rationale about why that drug will work in that disease state. And the big investors were U.S. health care institutional investors. 10 years ago, that would have been unheard of in Australia, raising that kind of much money on the ASX, particularly from U.S. investors. And so I think Syntara's assets, I'm so excited, in particular, but also the scarring assets sit at that sweet spot where we've got substantial safety data. We've got early mechanistic data. We've got -- with amsulostat, we will have a clear part to market in this half and their clinical stage assets. And in amsulostat's case, it's a pipeline in a pill. So I really think that amsulostat is -- or Syntara is where the market is today to be able to really kind of capitalize and exploit the assets that they have.

And one for you both, I think, is are you seeing a shift in how big pharma values these clinical stage assets. For example, is there more emphasis on durability or biomarker clarity or regulatory alignment? Just some thoughts on that?

Yes, perhaps I'll just go first. I'm not seeing a huge shift there. I think that there -- perhaps there has been a little bit of a change in they're looking for things, which have a broader applicability. So the days when you had sort of really niche drugs that might go forward in one small area are still there. But I think that the -- probably with some of what we've seen with the GLP-1s is you can pick them up and then they go into several different indications. They're broadening them out, and they're getting differentiation between similar stage molecules of similar assets by taking them on different clinical development paths. And I think that is a real advantage for amsulostat in that it could go a number of different ways. And the -- this is why I said at the outset that when we talk to companies, we're not being restrictive in what we might consider because the value proposition for amsulostat is different depending on which company you talk to and what their particular strategic priorities are. So we'll keep that open. But I think you're seeing that broadly that this idea of of having optionality and more of a platform approach is really attractive for pharma at the moment.

Yes, it's a good question. I mean, when you look at the podcast and the webinars, the big pharma has been talking about precision medicine and smart clinical trial design for 10-plus years. Has that -- have we really seen that translate into how they do M&A? I don't. I mean, to Gary's point, I think it's all about the data. They're looking later stage. They're looking at what the data is and their confidence in the ability to get this to market as soon as possible. And this whole kind of -- I think we all want to be focused on precision medicine and personalized medicine, but that shift has been more gradual than I think maybe people expected it to be 10 to 20 years ago.

Just coming back to the skin scarring. A question's come through, Gary, was is the company strategy to license skin scarring treatment or take it all the way to market. I think you touched on it a bit before, but if you can just retouch on it.

Yes. I think we keep our options open. I think if that study comes back and shows that the drug really does make a difference to the way that these hypertrophic scars evolve against a placebo, then we will have a surf of interest in terms of companies that want to. I can't tell you how many companies I've talked to who have been searching around and looking for something that works in scarring. They haven't found anything. And they keep on going back to us and say, please let us know when you've got some result, please let us know when you've got something that works. So I think that level of interest inbound makes immediate partnering possible. But it also suggests that there's enormous value for shareholders in hanging on and developing it as well. So we'll see how that trial goes and look and see what happens yes.

And you touched on the patients who stayed on treatment of amsulostat. And someone's asked for those patients after the end of the suboptimal study, are they still continuing on treatment.

Yes. As far as I know, yes, which again is just a testament to what Hashan emphasized earlier, that the safety of the compound, right? So these are patients who, on average, were on ruxolitinib for 3 years in a disease which is -- has a 5-year life expectancy from when they start on a JAK inhibitor. So this was really good to see those patients that reached 12 months staying on, still getting benefit. Symptom scores were, across the board, almost 50% or more improved and smaller spleens as well. So great to see those patients staying on, and we were delighted that all of them decided to do that. It just spoke volumes. We look at the data, obviously, and we dive in and we spend hours pouring over the data, but at the end of the day, patients saying, please keep giving it to me is the acid test for all drugs.

And just one final one, again, that I'll throw to you both is how important do you see it right now for an emerging biotech to show optionality across various indications rather just a single hero asset?

I think that's one to ask the investors, Matt. I think different investors have different profiles, and there are those that want that black-and-white situation leading up to that, getting a clear answer. And there are those that I think will value what we have, which is one lead asset with a very defined time line already with positive Phase II clinical data, which has been substantially derisked because of that and at the same time, a lot of other news flow, which can add value going on in the background as well, which they're not having to invest in. So I think it depends on your investment profile as to whether you like that or not. But I think -- I hope that we appeal to a broad section of the market. And as the news flow start to emerge this year, more people will see the value in Syntara and the fact that there's a long way to go now this year upwards, I hope.

Yes. So that question, Matt, is -- I'll frame it differently. It's where is your marginal dollar better spend. It's really a capital allocation question, right? So if you got $100, where should that be spent? Should that all $100 be spent on 1 asset or should it be -- or have you maxed out, so if you have more capital than you can spend on that 1 asset, you can spend on others? Syntara actually, it doesn't it doesn't matter now because the other assets are being funded with non-dilutive capital essentially from grant funding. So Syntara can still stay laser focused on amsulostat and getting that product developed and through the market, whereas the optionality is being given now thanks to wonderful groups like Parkinson's U.K., UWA grant funding from the MRFF. It gives us free shots on goal. I mean, like Gary mentioned, 4728 trial results that will come out this half, that is just -- that's a free kick on goal. And if it works wonderful for Syntara and wonderful for the patients, but it hasn't taken away from the focus of the capital availability of Syntara. And I mean I personally have never seen that for a biotech company, and that's where I think the pipeline really comes into its own.

Right. Excellent questions and answers from you both. Gary, I might just throw it back to you to provide a concluding comment.

Yes. Well, I hope that you all found this interesting. As I said at the outset, it was designed to give a bit more granularity on the news flow that's to come and what's going to drive value, what potential is there and when it's going to happen. We'll keep you updated as we go through. But the team and I are really excited about the year ahead. We have made our choices. All of the programs now are well advanced and with studies recruiting or already recruited and coming to conclusion, I think -- I hope that for those of you that are not currently investors, you put us on your watch list. And for those who are the already investors, think about your position because I think at the current prices, Syntara still makes a lot of sense as an investment at the moment, given what else is going on in the market as a whole. And thanks very much for your time.

Thank you, everyone.

Thanks, Gary and Hashan and thanks, everyone, for joining.

Thank you.