Syntara Limited (SNT) Earnings Call Transcript & Summary

Thank you for standing by, and welcome to today's Syntara investor webinar discussing the announcement earlier around its skin scarring program. [Operator Instructions] From Syntara today, we have the CEO, Gary Phillips. But in addition, we're very pleased to welcome the world-renowned Professor Fiona Wood, known for being both a highly talented plastic and reconstructive surgeon and an expert in skin injuries and burns. As many will know, she was named as Australian of the Year in 2005 for the outstanding impact she made, treating many victims from the Bali bombings. In terms of the format today, we'll first hear from Gary for approximately 10 minutes before we hear from Professor Wood and then take some questions. Gary, I'll hand it over to you first.

Thanks very much, Matt, and thank you all for your time this morning and joining us. This morning is due to be a quick update on our media release we put out earlier. It really talks about the reinvigoration of our skin scarring program and the launch of a new drug into a clinical study that builds on all the work that Syntara have done with the Fiona Wood Foundation and the University of Western Australia over many years, and it's come to fruition today. So just to go to the crux of this and the issue that's still faced globally with scarring of the skin. And I guess this has really come into focus. We now see more than 100 million patients developing scars in the world alone. I don't know who came up with that estimate, but it's a very large number, but one that's quite believable as the rate of elective operations and surgery continues to increase. And there's a particular branch of this scarring, hypertrophic scars and keloids, which we'll talk a little bit about today. And these are disorders which really are driven by fibrosis and they arise after any deep cutaneous injury caused by trauma, burn, surgery. But the mechanisms underlying this haven't really been well established. And I think the work that's been done by Fiona Wood and her team at UWA has really helped us understand a lot more about scar structure, the mechanisms that are going on within a scar and importantly, how we might change the biology with some unique pharmacology approaches to this. These hypertrophic scars and keloids are cosmetically and functionally problematic. Not only are they obviously disfiguring, they can cause lack of function, but also have quite profound impacts on quality of life in patients as well, the patients are carrying these scars. And current standard of care, we'll talk to Fiona Wood about this a little bit later, but there are several different ways of approaching these scars. But I think it's fair to say that there's room for improvement here. And again, the early promise of the preclinical work that we did with the team over in Western Australia showed that a LOX inhibitor, a pan-LOX inhibitor approach given topically to the skin does seem to have a way of modulating critical stages in scar formation and hold out promise for going into clinical studies. So the team together did go in to do a study, and we had an earlier compound called SNT-6302 that went through early-stage healthy volunteer studies and then into a patient study in patients with very mature scars or patients actually that ended up with an average scar age that was, I think, around about 13 years, so very mature scars. And in that study, we learned a lot, and we identified the need for and ideas for further improvements. 6302 did have a good safety profile. We didn't have any serious adverse events, but we did see 2 patients who withdrew because of reversible rash. And we had settled on a dosage which was 3x a week rather than daily in order to help manage that. So there was clearly an opportunity there to improve the tolerability of the program that we had. Having said that, though, we got a very good inhibition of LOX activity in the skin with that drug. We had 66% of reduction of activity of the enzyme that we were targeting compared to baseline and placebo. And that was taken 2 days after the final dose. So we were pretty happy with that. But clearly, the opportunity to maximize LOX inhibition by increasing the dosage from 3x weekly to daily also holds out potential for further improvements in efficacy as well. That study has recently been analyzed with a subset as well with a further group looking at noninvasive imaging. And I think overall, we were really pleased to see the reduction in collagen in those scars and also an improvement in scar vascularization, which really, I think points to this treatment being could be quite transformative for patients with scars and certainly worthy of further development. I think the other thing we learned from that early development was that there was room -- we learned a lot about what kind of study we ought to do. And the age of the study, age of scar in that first study was perhaps making it difficult for ourselves. It might take longer for those patients to remodeling. So whilst we saw changes in structure of the scar, we didn't see any changes in the physical appearance of the scar as assessed by patients and clinicians at the end of a 3-month treatment. So this time around, we're looking at a trial in patients with younger scars and looking at alternative endpoints as well from what we learned before. So the new drug is 9465, SNT-9465. It's -- we've classified it as a next generation of inhibitor. It's a got a new intellect property behind it. So we've refreshed the IP behind this program as well, which is always helpful. And 6302 clearly gave us proof of concept. But again, those issues with tolerability and trial design meant we felt we can improve on that. So the next generation came from a rapid advancement of the backup compound. Now this is obviously facilitated by the fact that we do have an in-house drug discovery capability in Sydney at Syntara. And it's that team that once we saw the limitations of 6302 immediately flipped and worked on 9465 and brought through forward what we think is a compound, which is what we've already demonstrated in preclinical studies to be optimized versus 6302. So we're quite optimistic that we've got a drug now which can be used in daily use with the potential for both improved tolerability and efficacy. And the study that we aim to start in this next quarter coming is a Phase Ia/b study design. So we'll start off with a single ascending dose in healthy volunteers, where we'll look at 3 different doses of 9465. And in that part of the study, we're really looking at safety, but we're also looking at what level of dosage we need to give to show effective inhibition of the lysyl oxidase enzymes in the skin and monitoring to see whether we're getting any systemic circulation of it. So really checking out the safety of the drug as a whole. We then move into what we call the multiple ascending dose stage of this study, which again is still healthy volunteers. But here, we're using 1 or maybe 2 doses that we select from the single ascending dose phase in those healthy volunteers, again, to check whether we've got tolerability and efficacy in terms of its inhibition of the enzyme, the target inhibition over a longer period. So in this stage, rather than single doses, we're giving these patients the topical treatment for 28 days. And that's the stage where we'll really see whether we have derisked the compound and whether we are seeing improved tolerability, and we're not seeing some of the redness that we saw in a few patients with 6302. Having done that, we move then quickly on to a study in patients with scars. So these will be healthy subjects, but they will have hypertrophic scars. We're looking for patients with scars of less than 24 months in age. So quite a bit younger than the scars we had in the 6302 Solaria 2 study. And we're treating them for 3 months in an open-label study with a dose that we've selected from the previous stage of this study. And endpoints looking at physical and visual skin and scar assessments, again, trying to improve on what we had in Solaria 2, learning from the lessons we had there to try and see that we can get to at least a proof of concept with these few patients to show that we are modifying these scars, and we are making a change within 3 months of treatment, which we think is -- would be -- is both practical for this drug, but also it would be a real benefit to patients. That sort of treatment length is -- would be ideal with the treatment that they can apply topically over a relatively short period of time to change the course of their scarring. The study is due to start in quarter 2, and we expect results in the first half of next year. So as I said before, this really came on the back of a very long-term collaboration we've had with Professor Wood, her team and her foundation and the team at UWA. It's a multiyear preclinical program, which resulted in a publication in Nature Communications. It's a collaboration that's completed already 2 clinical studies in Solaria 1 and Solaria 2 with the previous compound. And now that group is looking at exploring this further using 6302, which is still perfectly valid to try out in clinical studies. It's not the drug that we would take forward commercially, but it is still very useful in terms of trying to understand in other groups of scars other than the hypertrophic scars we're using with 9465. So with that, perhaps I'd open up the discussion now to involve Professor Wood. And Fiona, maybe just ask for your maybe your observations on what we -- the recent findings in Solaria 2, those the advanced imaging thing and the overall thoughts on where we stand with pan-LOX inhibition and scarring.

Thank you very much, Gary. I think it's really interesting because like you said, Solaria 2, we went for mature scars, understanding that the scar and the extracellular matrix, the framework of the scar turns over and work that we've done prior to that demonstrated that, yes, it isn't immutable. It is clearly when you have a scar as a child, it changes and grows. And so targeting that turnover with a 3-month application, 6 weeks to 12 weeks and following it out, it really gave us insight into what was possible. And the Solaria 2 wasn't really aiming at what a difference, we're looking at safety, of course. But we saw a difference. We saw what really is very obvious in this imaging. This is OCT, optical coherence tomography, which looks inside the skin without histology, without actually taking parts of the skin. So we can see this from this image, there's quite a difference in the blood vessel pattern. And we've worked a lot with the bioengineers in this technology. And so we understand what the normal pattern of vasculature is in the skin. And as we have been pursuing this plan to unscar the scar for many years, we can see that this LOX inhibition has driven the vascularization pattern into a more normal skin pattern. So that was really, really good to see. And one of the things anecdotally is some of the patients that we treated with very old scars have continued to improve, which I think is really interesting. We changed the extracellular matrix framework. And secondarily, the goal was to change the phenotype of the cell within that framework into a regenerative phenotype as opposed to a fibrotic scar phenotype. And certainly, it would appear that maybe we have done that in some people and trying to understand that is why we're pushing forward with this because it certainly has given us more concrete results than any other methodology. I mean, you do use laser silicon pressure, a whole raft of things, as Gary said. But this is something that really targets -- goes to the heart of the underlying problem. The change in the framework, the extracellular matrix changes the cell functionality that drives scarring. So all this work over all these years has really gotten down into the core problem and actually treating the core problem. So when we look and change the lens on to keloid scars, that's the hardest problem we have. Keloid scarring is much more florid, much -- is different genetically and when we -- and epigenetically to hypertrophic scarring and is very resistant to treatment. And so we're really looking forward to seeing how this kind of technology and pharmacology can -- will it actually do the same in that keloid space, changing that framework such that as the framework turns over, which is continuous, we're changing that framework by the LOX inhibition, can we change the cell functionality? So I think it's really exciting. I think it's the -- over my years, it's the one thing that is actually focused on, as I say, solving the core problem.

Thanks, Fiona. And if you look at a hypertrophic scar and a keloid scar, how would you tell what the difference was if somebody was just looking at that, how would they know they've got a keloid scar versus a hypertrophic one?

I think sometimes that's very difficult, and that sometimes leads to the sort of the mismatch in the literature. A hypertrophic scar will get better with time. Symptoms are often similar with itch and pain, but a keloid scar doesn't get better with time. It continues to expand beyond the zone of injury. And so the history is really key in this, understanding what the original insult was, understanding the path that scar has taken to the point where you're taking that history, which is really important. And then because the examination is sometimes difficult to see. I think our work now demonstrates that if we access tissue, we can see the difference epigenetically. But without that, sometimes to distinguish it is really, really challenging. And so the keloids that we'll be treating will be well and truly established keloids in this trial so that we don't mud -- like muddy the waters by introducing the hypertrophic scar group that we know will respond because of our previous work. So we are taking -- so the history, the -- following the patients, making sure that they don't improve over time and then introducing them into the scar -- into the study.

Do you think the endpoints in a keloid scar study might be a bit different from the ones that we're using for the hypertrophic scars? Or are you looking for something a bit different from them?

I think you're looking for scar improvement, absolutely. So yes, there is a similarity. But how is that measured? Volume is much greater in the keloid scars often. And so the volumetric analysis is -- I think, lends itself to the keloid scars. And that also lends itself to actually putting something concrete around it in terms of the numerical outcome. But there'll be a lot of things that are similar. And absolutely, the patient appreciation of any improvement is fundamental because the POSAS scars, the patient assessment scars -- systems, I should say, questionnaires will be the same across both.

Yes. Okay. Thank you very much. Matt, I think at this point, we perhaps open it up for any questions.

Yes. Thanks very much, Gary. [Operator Instructions]. The first one, Gary, reads, considering this is an improved version of the original skin scarring drug, is there scope to have this drug progress quickly? Or is that limited by the lack of clinical development of the original drug?

No, I think the advantage we've got having already had 6302 in the clinic is that that's effectively derisked this next program. So we can move quickly and more confidently with this one. So we can see from our preclinical test that this drug is at least as potent as 6302 in inhibiting lysyl oxidase enzymes. So we don't believe we're going to be surprised when we put it into the Phase I study. And on top of that, from all the work we've done with the tissue exposure tests preclinically, we believe that we've resolved the tolerability, some of the redness we've got. I mean it's quite interesting talking to surgeons and dermatologists about treatments that they put on skin. And we had a few patients that got redness around the area when we applied 6302. And a lot of them said to us, look, we get redness and itching with a lot of treatments we put on the skin. Don't worry too much about it. But I think we looked at this and felt we could make an improvement. And we think that from a regulatory perspective, it puts an easier path forward for this drug. And also with eventual partnering of the drug with a pharma company to take this globally, also it removes a potential flag in development. So in short, I think we are able to move much more quickly because of the evidence we've already got with 6302. And this first healthy volunteer studies, I think, will validate what we've got, and then we can move quickly from that point.

Thanks, Gary. One for you, Professor Wood. In your experience, have you seen any other drugs, be that topical or oral that have improved scarring in a clinical trial? And if not, what does that mean for Syntara's drug?

I think trials in scarring are challenging, absolutely. But yes, the traditional things that we use, such as laser and steroid, we can demonstrate a difference. And so certainly, as we start -- as we go forwards, we can measure against the standard of care because the standard of care is exactly that. The problem with it is it's not good enough. So the steroids and traditional therapies, particularly in chemo scars have a very high incidence of recurrence. So that's what we're seeking to deal with. And by not just changing the inflammation around the scar, which is what most of the other things do, but in changing the core driver of what drives that into a scar, as I said, the framework of the skin. Once that is changed into a dense collagen network, then the cells within that behave differently. And so despite the other drugs that we use, that doesn't change the core problem. What we do here does. So I think that's the key difference.

Thank you. Next question is, can you provide further comment on the similarities and difference between 9465 and the first-gen compound? Any comments on mechanism of action are welcomed?

Yes. So from a mechanism of action, it's identical. So we -- our program around lysyl oxidase has delivered us one drug, which is in Phase II, looking at hematological cancers like myelofibrosis and myelodysplastic syndrome. That early drug in skin scarring, which is applied topically. So we understand the space really well. We understand the chemistry around it. So when we sought to improve the tolerability of 6302, we had some good ideas very early on about which elements of the structure of the compound that we could change that would improve the way that the body reacted to it, but without impacting on the efficacy of the drug in binding to the active sites on the enzyme and removing it from circulation. So from that point of view, the 9465, we believe is as potent as 6302 in terms of its inhibition of the target, which is excellent. But at the same time, the improvements in the way it's tolerated by the skin will mean it can be used on a daily basis and therefore, keep that inhibition level high all the time, which gives the opportunity perhaps to get an even more efficacious drug than 6302. And we shouldn't forget that 6302 did work. It did change -- fundamentally change the structure of the scar, and we've seen the slides just now on the vascularization. It was a really successful trial that we ran, and we're trying to build on that now.

Thanks, Gary. And would you eventually look to go head-to-head versus topical corticosteroids or silicon gels?

I think one of the things we've learned in our discussions with not only Fiona, but with plastic surgeons globally is that the standard of care in different parts of the world is quite different. So I think what you're going to see -- and also skin types are also quite different region by region. So you would find that Asian skin types are quite different from the average skin types you will find in European population and then also in African skin types as well. So we are looking at a study beyond this, which then explores versus the standard of care in the regions where it's being used and in the skin types in the regions where it's used as well. So our aim as a company is to develop this drug and get it to the point where we have clear evidence that it changes the course of scarring. And then we will probably look for a global partner that is able to exploit this and look at it in multiple jurisdictions using -- as Fiona said, skin scarring trials can be challenging, but to take on that because the commercial opportunity at this and the benefit for patients is enormous.

Thank you. Is there scope for the skin scarring division and SNT-9465 to be spun off into another company or a JV?

I think I've said before, I think that the skin scarring in its own is a huge opportunity. And the way that the company is structured to take these things forward, we'll make a call on that when we get to the time when we've got a drug that we know has worked. But certainly, there is an opportunity here. I think a lot of the investors in Syntara are focused on the work that we're doing in oncology and myelofibrosis and myelodysplastic syndrome. And there may well be an advantage in having a different set of investors, which would be particularly attuned and want to see the skin scarring program go forward. So we could always do that at a later point. But I think the important thing is from the existing funds we have, we can take 9465 and get it to the point where maybe that opportunity exists.

Thank you. And as a new compound, what is the IP/patent life on it from here?

Yes, the patent is fresh. So it was only -- we have a very clear policy on patents within the company. We only go and file our patents once we're ready to go into Phase I. So this was a very recent filing on behalf. So the patent will go well into the 2040s.

Thank you. And just a couple more quick ones before we wrap up. Recruitment challenges were mentioned for 6302. Might this new trial face similar recruitment challenges?

No, I think this will be similar to, I think, Solaria 1, the healthy volunteers. We're using contract research organizations, one of the same one that actually we worked with Professor Wood in Solaria 1 based in Perth, but also another one based in another territory as well to make sure that we don't experience those things. And we've done feasibility as well. We're looking for 10 patients with hypertrophic scars of the healthy volunteer one, and we're pretty confident we can recruit that in a fairly short period of time.

And last question is you mentioned partnering with large pharma, Gary. At what clinical stage would you consider doing that?

I think probably -- well, let's see what the results of this one look like to see how convincing there are. But I think beyond this one, you would want to do a larger Phase II study once you've got this initial study showing safety and some signs of efficacy under your belt, which would effectively derisk the compound and then there would be a really good investment case for going into a much larger Phase II study against a standard of care to demonstrate what you can do in those studies.

Thanks, Gary. I'll just throw it back to you. I know you've got a couple of slides just to finish off on.

Okay. Sorry, just adjusting my screen a minute. Yes. So just to wrap up. First of all, I'd like to thank Fiona Wood for sharing her time and her expertise with us this morning. It's always -- it's good. I think the relationship, the collaboration that we've had is a great example of industry and academia working together on translational science and clinical medicine for the benefit of patients. And it's been an absolute delight for the 2 groups, and we're delighted it's going to keep going and that we can keep supporting the group to look at other kinds of scars like keloids as well. Just to finish off, I mean, just a reminder that the company is well funded to take these studies through. The cash we have on balance as a pro forma at the end of December was over $20 million. That takes us through to the middle of '26 in terms of the burn rate that we expect and funding this study as well as the studies in myelodysplastic syndrome and myelofibrosis. That list of studies is just here, and it's quite a lengthy list now. And again, a biotechnology company in Australia with a market cap of around about $120 million with this number of assets in Phase II -- Phase I, Phase II studies due to deliver data within the next 18-month period, we think that the opportunities are stacking up. I think Syntara shareholders can look forward to a really good news flow going forward, not only from myelofibrosis and MDS, but now we're hearing about the hypertrophic scarring, the keloid scarring that will be done under the aegis of Professor Wood and her team over in Perth. And then also the IRBD and Parkinson's disease study, which is recruiting, and we expect data by the end of this year. Thank you very much, Matt. Thank you for everybody joining today.

Thanks, Gary, and thanks again, Professor Wood and to everyone for joining. If you have any other questions please feel free to send them in on the details on the company's announcements. Thanks again.

Thank you very much.

Thank you. Thank you.