Syntara Limited (SNT) Earnings Call Transcript & Summary

Good morning, everyone. The clock has just ticked over 11 a.m. now so we will get started on today's call. My name is [ Alfred ]. I'm from Pharmaxis' Investor Relations team. Today, we're joined by CEO, Gary Phillips. As many of you will have seen this morning, there's been some new interim data at least from Pharmaxis' skin scarring trials in collaboration with UWA. We will -- this is one of the trials we get the most amount of questions for. So if anyone does have questions through our presentation, feel free to type them into your Q&A box. If you're on a computer, your Q&A box is on the left-hand side of your screen, and if you are on smart device, it's at the bottom. Once we get through the brief presentation, where Gary will talk through the data, we'll open up to Q&A from those in attendance and anyone that's emailed questions through already. So Gary, I will hand over to you.

Thanks very much, [ Alfred ]. And thank you to all of you who've dialed in coming along to the Internet this morning. It's a relative short notice. As [ Alfred ] said, we put out an announcement earlier this morning releasing interim data from skin scarring study that we're doing in collaboration with the University of Western Australia and Professor Fiona Wood. So I've got a few slides just to frame the results that we're going to talk about and then very happy to take your questions. So for those of you who perhaps aren't familiar, I just need a reminder, Pharmaxis is a clinical-stage development company. We develop small molecule drugs that are either first in class or best in class. We target fibrosis and cancer indications. And we're a global leader in a particular enzyme called lysyl oxidase, which we'll spend most of today talking about. And this -- the results we're seeing today are the result of a multiyear research program. And we've done that leveraging it with a lot of external collaborations, of which the one with Fiona Wood, Mark Fear in UWA is perhaps one of the longest lasting and most productive ones. We have 5 studies that are either recruiting now or will start recruiting next year to lead to real value for shareholders in the company. 5505 is our lead asset, an oral pan-LOX inhibitor that's in a rare bone marrow cancer called myelofibrosis. That's more than 50% recruited now. Liver cancer study with the same drug, which is due to start recruiting in this quarter and 6302, our trial in scarring, which we've got the ongoing study in established scars and another one due to start recruitment at the beginning of next year. And finally, on neuroinflammation drug that we recently had a deal with Parkinson's U.K., who gave us $5 million to do a study in a sleep disorder, which is program or leads to development of Parkinson's. So quite an exciting pipeline, all reached a clinical stage, which is -- gives us many shots on goal at delivering value. So just going on to the lysyl oxidase and just before I dive into the results, just a reminder of the way that these enzymes work and their role in fibrosis or scarring. So the chart that you're seeing on the left-hand side here shows the -- what happens during the process of fibrosis or scarring. So we all have within ourselves to what types of cells in our bodies called fibroblast. And when these -- the body is injured either through a mechanical injury or chemical scarring, metabolism or genetics, then these fibroblasts become activated, and they start producing a substance called collagen. And collagen, when it's cross-linked together into a close-knit mat, gives us the scars that we can see on our skin. It also causes the scarring that we don't see, which is in our organs, which can cause long-term damage. Now the process of that cross-linking is caused by an enzyme called lysyl oxidase, and that's a family of enzymes. In the skin, it's lysyl oxidase itself, pan-lysyl oxidase 1 that are the key enzymes that cause the cross-linking and, therefore, cause the scarring. Now this is a normal process in the body and is a perfectly healthy one. But if you get too much collagen production and too much lysyl oxidase released, then you get excess scarring. That, in turn, leads to a very stiff and hard tissue. And that mechanical stiffness of the tissue in effect, gives mechanical stress that causes feedback loop back to the fibroblast, which will then release more collagen and more LOX. So it's a feedback loop that can get revved up and go into excess. And that's when we see scarring, which can be problematic, both in organs and, in this case, we're talking about on the skin there. 6302 is the drug that we're talking about today. That's given -- it's a pan-LOX inhibitor that's given in a topical form. So it's given in a cream which is applied to the skin. Like a lot of our drugs, these are very recent pans. They're 100% owned by Pharmaxis. They're not licensed in from anybody else. There's no lean on them anywhere, so we don't have to give away any royalties or anything as we develop it. Patent was filed with a priority date of 2019. So this is a product with a long life ahead of it. We've got strong preclinical evidence in models of skin fibrosis and scarring. I'll touch on that in just a minute. And we've already gone through Phase I showing we had a safe and well-tolerated drug when given to healthy volunteers. So scarring, in particular, hypertrophic and keloid scarring are the sort of 2 areas which we've really focused in on. The number of patients who have problematic scars every year is huge. It's 100 million patients that get scarring from elective operations or operations after trauma or burns. And these hypertrophic scars or keloid scars are ones where that scarring process that I talked about do go into overdrive and cause excess scarring that can -- and that's driven after you have the injury. These scars are both a cosmetic problem in that they often stand out, and we've all seen examples of these, I'm sure, on people that we know or even ourselves. But they also cause functional problems as well, depending on where they are. They're often stiff. They're not very pliable. They can restrict movement and cause a lot of harm to patients in terms of their well-being, both from a mental health point of view and a physical health point of view. Now we started our work with UWA several years ago. And in fact, the researchers there, Dr. Mark Fear and Fiona Wood -- Professor Fiona Wood, came to us when they heard that we were developing a LOX inhibitor and said, "Look, we think this enzyme is really important in skin." And they embarked on a series of preclinical work in several skin models, models of skin scarring. And we, quite frankly, had some really great results. And the results of those studies were actually published at the end of last week in Nature Communications, so a high-value journal the first time that this data has been released. And I can just summarize it there with that quote from Mark Fear. So the models are scarring, and there were several that they ran, found that the topical application of our drug reduced collagen deposition. So we talked before about the amount of collagen that was going through and cross-linking and improved scar appearance without reducing the tissue strength. And that's a really important point in scarring. Obviously, we want to reduce the excess scarring, but we don't, in any way, want to damage the ability of the skin to heal itself. So he said -- he sees this as being a unique way of modulating what's that critical stage in scar formation. And there are very few other treatments available for scars. A lot of them are quite physical in their approach. Surgical revision or laser therapy are very commonly used. Corticosteroid injections into the scar are sometimes used, but they're quite temporary fixes to the thing. So the idea that you could have a pharmacological approach to scarring and actually reduce the scarring process and manage it would be a real breakthrough for these patients. And we've had, as I said before, the clinical evidence from our Phase I in healthy volunteers showed good tolerability and full inhibition of the lysyl oxidase in the skin. So the drug looked promising. The total market here is very large. So depending on which one you're going for, but even the subsegment of keloids and hypertrophic scars is worth several billion dollars per year in treatments that are currently used. So just going on to the study that we're reporting on today. So this is a 3-month, placebo-controlled study. It's being done in adult patients with an established hypertrophic scar. So the scar has to be of 1 to 5 years of duration. So we're not looking for people with new scars. These are people with established scars, have to be over a year old, less than 5 years old. We've tried to restrict the group here to certain types of the scars, have got to be more than 10 centimeters squared, so a significant scarring area. And it excludes patients with acute skin conditions or a history of keloids. We're really focusing on hypertrophic scars in this case. Now the study was split into 2 parts. The first is cohort 1, which we're reporting preliminary data from today. Now that was 8 subjects that were treated for 12 weeks. And the objective there was to confirm what was the level of drug that we could measure in skin and what was the level of inhibition of the lysyl oxidase enzyme in the skin. We could measure it in biopsies taken at those patients' skin after 12 weeks of therapy. That was done to confirm the doses that we saw to be effective in the healthy volunteers that we did in the study before this. So once we have those 8 patients all on active treatment, open-label, unblinded to see, we then progress into cohort 2, and that's 42 patients. Again, they're being treated for 12 weeks with the objective there, again, to confirm PK/PD but also look for safety and efficacy of the dose that we selected in that cohort 1. And primary end points were safety -- are safety. Secondary end points there, some -- several -- lots of different ways of physically in -- assessing the physical and visual appearance of the scars. So that study started to recruit earlier this year. And I'm pleased to say it's progressing really well from a recruitment perspective. So moving on to the results. So the results today are just coming from the first cohort. So that's important to note. The second cohort are patients who are placebo-controlled. So of those 42 patients, 24 of them are -- so 21 of them are going to be on active and 21 on placebo. We've already recruited 24 out of those 42 patients. So the total study is more than 60% recruited and the UWA doing a terrific takeout. They're screening lots of patients all the time. The results from the first cohort of the open label. So these patients were all received a definitive dose of the drug through an -- through a special applicator that was put on to a defined area of skin on a daily basis. So the skin biopsies we got showed excellent skin penetration and a very high inhibition of the lysyl oxidase enzymes as we had predicted. We were able to take those biopsies and then look at the biomarkers of the scarring process. So if we're having an impact on the scar, then what we should see is a reduction in the amount of collagen that's present in the scar and also a reduction in the amount of lysyl oxidase enzymes sitting in the scar as well. And in fact, we see a reduction in both of those measures. So based on the work we've done preclinically in animal models, reducing those 2 biomarkers suggests a drug which will have a disease-modifying effect. So we're all really excited by this process. We also saw some patients experienced some redness and a couple of patients with itchiness at the site of application. That resolved when the treatment was taken away. So as a result of that and the very high inhibition we were seeing of the lysyl oxidase the drug accumulates over a period of 3 months. We've modified the regimen in the cohort 2 reduce the frequency of the dosing. So we've gone from a daily dose to one that's applied 3 times a week. And I'm very pleased to note that we haven't experienced any episodes of revenue or richness at the site, having reduced the drug exposure. But we're still very confident that we're seeing enough inhibition of the enzymes to have a treatment effect on these patients. So Fiona Wood, many of you have -- know of her and have read her articles and know her work. She's noted positive changes in appearance of the scars of the patients that were all on active drug. Also a change in the liability. So if you roll the scar between your finger actually sense a change in the stiffness of the scar and those results now need to be confirmed by the placebo-controlled phase. So this is, I think, a really nicely designed study. We've learned a lot from the first cohort of 8 patients, and that's allowed us to go on confidently with the second cohort. We appear to have resolved the side effect issues that we had with redness and the application site. And we're now -- we now have to wait and see the results so we can see a difference between the patients who are on active and the patients are on placebo. So it's really, really excited by the stage we've reached and the continued collaboration with the group in Perth. So just to finish up. This is -- this one study is part of a number of studies that we'll be reporting in this quarter that we're just entering into now. we will hopefully report the first patient joining the liver cancer study. We expect to have interim data from our myelofibrosis study. That's a big deal. That's 24 patients in open-label study with the first patients that have completed 6 months treatment. We hope to have some data from them to share with the market later in the quarter. And then hopefully fully recruiting that study by the end of the year and some publications still to come on that drug from key opinions and the collaborations we had with them. And then following into next year, we expect to see the top line data from the study that we've talked about interim data today and starting the second study with the group in Perth. The neuroinflammation study should start recruiting. And then later on in the year, we'll see the 5505 reporting and that the 4728 recruiting -- recruitment continuing. So with that, I'll stop, and I'm very happy to take any questions that you have.

Excellent. Thank you very much for that presentation, Gary. We have had a few questions come in already. So if anyone does want a question -- ask questions, type it into your Q&A box left-hand side of your screen or bottom from a smart device. First question, Gary, comes from [ Ian ]. Of the 4 patients which withdrew, how quickly from commencement was the skin reactions seen typically?

We saw them all within the first month of treatment, which is why we're confident now because we've got a lot of patients in the second cohort that have progressed past that 1-month point. And we don't see any of that redness any longer. So we think it was just a dosage-related issue. And fortunately, we had -- we think we've got quite a wide margin in terms of efficacy with the drug. So it was -- dealing with patients and scared skin is not a straightforward thing. Each patient has a different type of scar, often different type of skin based on their racial background that they have different structures. So it really is a -- I think Fiona Wood has talked about the amount that we've learned from the first 8 patients going through the cohort there and the learnings of that now being applied. And also what we hope to learn from this study will go into the design of the second study, which we'll start with them next year.

Thanks, Gary. Following on from that, just one that came through e-mail. Have any more patients pulled out since those initial 4 pulled out?

No, we -- I have to caveat that slightly in our information and discussion. This is an investigator-led study being run by Fiona Wood in UWA. So our information isn't absolutely current all the time as it would be with a study that was being run directly by Pharmaxis. But to my knowledge, we haven't had any patients withdraw from the second part of the study. So as I say, I think the learnings from the first part have been very useful.

Thanks, Gary. A question from [ John ]. It seems to take a long time to recruit. Can you please comment?

I think actually, this study is recruited pretty quickly. I mean, it started in the first quarter this year, and we're just approaching the fourth quarter now in third quarter. So in 6 months, they have put a lot of patients on to drug and through. I think the -- again, the clinicians are also learning as they go, and they started off with a fairly narrow entry criteria in terms of the patients that they were looking for. And the patients were required to be extremely healthy when they came into the study. And they found actually a lot of patients who have these larger burns actually have quite a lot of comorbidities. So they've modified the protocol slightly. They've widened the thing to allow more patients in. And I know that they're screening a lot of patients each week there. So we're still comfortable based on our information that the study will fully recruit this year.

Just a question from [ Mark ]. How consistent was drug penetration and inhibition of collagen and LOX in each of the 8 patients?

I think from the data we've got, it's -- I mean, this is data from a small number of patients. So it would be wrong of me to over -- give too high a level of confidence to the -- to what we've measured. What I would say is from the data we have, we are confident that we're seeing a very good average level of LOX inhibition over the whole week for, say -- for patients that are receiving it 3 times weekly. It's -- but yes, it's probably too small a data set to go into give precise numbers and variability and that kind of thing at the moment. We -- that will be, obviously, a key report that comes out of the study when we finish the completion of the placebo-controlled part of the study.

Fantastic. All right, Gary. It looks like you've gotten through all the questions that have come through in the Q&A box. So we might wrap it up there. I'll hang on a second. We've had one more. Are there any photos available showing the efficacy of PXS-6302 drug? And if not available, can you comment on the visual change further that was provided by Professor Wood to date?

Yes. I think we don't have photos available at this time. And the reason for that is that these patients have just received active drug. And I think in order to really make a judgment on the impact, we need to see the effect of the drug versus the placebo, so we can see changes. What we're doing here is Professor Wood and her extensive experience in this area, a lot of the patients that she recruited are very well known to her, and she's known them for many years, in fact, having treated them for their often burn injuries at the very beginning. So we're going off -- her assessment at the moment is that this drug is making a difference. We are seeing changes in appearance and the pliability, the stiffness of the scar. But the more hard end points, we'll have to wait until we see the comparison with the placebo-controlled arm, which we expect to have in the first quarter next year.

Fantastic. All right. We might wrap up there, Gary. We know you've got quite a few meetings for the remainder of the day. So if anyone does have any more questions, feel free to email them through, and we'll get a response to you from Gary or someone at Pharmaxis or UWA directly. So Gary, on behalf of the shareholders and attendees today, thank you very much for your time.

Thanks, [ Alfred ].