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

Thanks for standing by, and welcome to the Syntara Key Opinion Leader Investor Webinar today following the company's announcement of positive progress in its skin scarring program. [Operator Instructions] We estimate that the webinar will last for approximately 45 minutes pending questions. On the webinar from Syntara, we have the CEO, Gary Phillips; Head of Drug Discovery; Dr. Wolfgang Jarolimek; and Chief Medical Officer, Dr. Jana Baskar. They're joined by Professor, Ardeshir Bayat, who brings more than 20 years of experience at the forefront of translational dermatological science. To begin, I'll hand it over to Gary. Please go ahead.

Thanks, Matt. And if you could move to the summary slide at the beginning, it would be great. So welcome, everybody, that's taken time to join us out of your busy days this morning. I really appreciate the time. This is the first update that we've given on our skin scarring program for a while as we've progressed through early-stage studies with one compound and then switched to a next-generation compound, which we really are excited about and we want to talk to you about today and the plans for that going ahead. For those of you who are rather new to Syntara, we are a clinical stage drug developer. The people that are joining me on the call this morning, Dr. Baskar and Dr. Jarolimek are actually 2 of the people in the team behind the pipeline that we've generated. That pipeline has reached a state of maturity where we have a number of clinical studies ongoing at the moment, a lot of them due to read out in the next 12 months. And the company has cash that takes us through to the beginning of 2027. So it is really looking at like a very exciting 12 months for the company. And today, we're going to not spend too much time any time on the blood cancer indications that we've reported most recently in myelofibrosis and myelodysplastic syndrome, we're going to focus on skin scarring. Next slide, please. Next slide, please, Matt. So the people joining us on the call this morning, foremost is Professor Bayat. So we first got to know Professor Bayat actually because we did a Google search about who was most published in scarring. And he comes up very -- he's top or almost top of the list. So it's been a collaboration that's gone on for a few months. We've talked extensively with Professor Bayat, and he brings a wealth of knowledge as a surgeon scientist, which has done a lot of both research work in scarring, but also clinical work in scarring as well those translational studies. And as I said, very heavily published. So we're really looking forward to hearing from him this morning. I'm also joined by Dr. Baskar, our Chief Medical Officer. Jana has been with us for a few years now, having joined us from a CRO and before that, Novartis. Jana is running the clinical studies in myelofibrosis and also the Parkinson's study that we're running at the moment, and has taken a keen interest in a lead in the skin scarring studies as we progressed through the Phase Ia study that we're reporting today into the next study, which we're about to start, which we'll talk more about later. And I'm also joined by Dr. Jarolimek. So Wolfgang has been with us for 15 years now. And it's true to say that all of our pipeline, as Wolfgang has been behind all of it, go through the research labs here in Frenchs Forest. So you've got an opportunity today to ask questions beyond me, which you normally see my face talking at these webinars. Please feel free, Wolfgang and Jana are here to answer your questions about the work that they do. Next slide, please. So what we're going to cover today is the -- I'll go briefly over the history of what we've done in the skin scarring project. Professor Bayat is going to cover off what are the types of scars we see in the clinic and how they're currently treated, what's the unmet need, what else is going on in research in scarring, where does our compound stack up against those in terms of the biological rationale, and also some of the challenges that we're facing in doing skin scarring programs as we go forward. So -- and then after that, Dr. Jarolimek Wolfgang will talk about the Phase Ia healthy volunteer study results that we've had and how we've transitioned from the first-generation compound through to this next-generation 1 9465 before Dr. Baskar finishes off with -- going through the protocol of what we're doing next in this study. Next slide, please. So I just wanted to pay credit at the beginning to 2 of the individuals that were the foundation of the skin scarring project. Professor Fiona Wood, Fiona is still running a study in keloid scars over in Perth at the moment. Very active. That study is 50% recruited. I had an e-mail exchange with her yesterday. That study is going really well. So she's been behind a lot of the clinical studies we've done. And also Professor Mark Fear. Mark, unfortunately passed away earlier in this year in an accident, but his presence is felt today. And the work that he did in the preclinical setting and then leading into the clinical studies will always be remembered. And we've got some great publications from the collaboration that we had with Mark. Next slide, please. So that early work that we did with the Fiona Wood Foundation and the University of Western Australia was with a compound SNT-6302, Solaria 1 and Solaria 2. And this was a topical compound that, like 9465, is a pan-LOX inhibitor. We've used it in a 3-month study of patients that had relatively old scars. The average age of the scars was 13 years. But 13 -- 13 years of age. And in that study, 3 months treatment versus placebo, we showed some pretty stunning results. We showed that there was a 30% reduction in collagen content in the scar tissue after 3 months treatment. And we also showed an increased vascularization of the scars and the structure of the scar. So those scars are gradually becoming structurally and biologically closer to normal. So that study led to -- directly to the compound that we're going to talk about today. We did see some patients, a small number of patients who have reddening of the skin, and Wolfgang will talk a little bit about the background to that and why we decided to move on to 9465. But that first study really, really encouraged us to go on and has led us to where we are today. Next slide. So with that, I will hand over to Professor Bayat to talk us through a bit of the background of scarring and about the compound that we have. Professor Bayat?

Well, thank you so much, Gary. It's a pleasure to join you all today. I must say I've spent the last 2.5 decades trying to understand one deceptively simple question. Why do some wounds heal normally, while others become persistent pathological scars? You could say my career has been split across a few worlds, surgery, laboratory science and translational medicine. And skin scarring happens to be at the intersection of all 3. I've seen the clinical burden firsthand as plastic surgeon and then I continue to study the molecular and mechanobiology of scarring in my own lab and subsequently run many clinical studies in order to understand and gain insight into the mechanisms of scarring and various therapies. So my contribution today is to frame the biological and clinical context for why innovation in scarring is so overdue. And why targeting LOX represents one of the most compelling opportunities I've seen in the field to date. So next slide, please, Matt. Thank you. Let me put the scale of this problem into perspective because it's often underestimated. The 100 million new scars per year quoted here refers only to post surgical scars in the developed world. It does not include the rest of the globe or new scars from burns, trauma, or traffic accidents, obstetric, C-section deliveries, acne, conflict injuries or workplace accidents. When you factor those in, you move from tens of millions to hundreds of millions of new scars every year. This is not a niche cosmetic issue. It is a common, lifelong condition with functional limitation, pain and psychological burden added in. And despite that scale, there is still no FDA-approved therapy that truly remodel scars or softens the underlying biology. Everything we have today is symptomatic, procedural or temporary. The problem is large, global as well as predictable. And therapeutically, this space is still quite wide open. Next slide, please. So before we talk solutions, it's worth recognizing that a scar is not a single entity. It's actually a clinically and commercially important spectrum. I used the SCAR mnemonic, a short term to make it memorable. S stands for stretched scars. These are the widened surgical scars, classic C-section scar that can start off normal, but once they spread, they become highly visible and an aesthetic concern. Now C is for contracture scars, most commonly seen after burns. These aren't just a cosmetic issue as they physically restrict movement, tether the skin and drive a huge amount of reconstructive workload worldwide. Functionally, they can be equally devastated. A refers to atrophic or indented scars. Acne scars are the classic example. And finally, R covers the raised scars, which is where our main focus sits today. Hypertrophic scars remain within the boundaries of the original wound, but are raised, big, red and symptomatic. Keloids, however, also are raised, but are much more aggressive and progressive. They grow beyond the original wound, are recurrent, often symptomatic, painful, itchy and have real psychosocial impact. They're also the most biologically distinct. These phenotypes look very different, and they behave differently. But what links them is a shared downstream mechanical bottleneck, collagen cross-link. Regardless of the cause or category, once cross-links accumulate, scars become stiff, persistent and extremely difficult to treat. This is a common pathway we will be focusing on and targeting. Next slide, please. Scarring is often dismissed as a cosmetic. But for patients, it's really just a mark on their skin. Hypertrophic scars itch, burn, tighten. Those across joints, restrict movement and make everyday activities unbearable. Keloids are painful, disfiguring and socially stigmatizing, and they tend to recur. So patients move through multiple rounds of treatment with very little durable benefit. People describe anxiety, sleep disturbance, social avoidance and loss of confidence. This isn't vanity. It's a visible reminder that affects identity, function and well-being. The useful way to think about it is that scars sit at the intersection of biology and self-perception. That's why willingness to try new technology is extremely high. Very few patients would say, "Oh, I'm really attached to my scar. I like to keep it exactly as it is for the rest of my life." From a clinical and economic perspective, the burden is equally striking. Every surgical list, every burn unit, every trauma service is effectively a scar generation engine. Burn scars require years of follow-up, rehab and repeated procedures. Keloids have recurrence rates that can approach 100% postsurgical excision without adjuvant therapy, driving repeated clinic visits or injections, lasers, et cetera, often with worst scarring each time. At the same time, the aesthetics boom has dramatically increased elective aesthetic procedures. This expands the pool of people who care deeply about scar outcomes and raised expectations for those scars which should look and feel good. Economically, that gives us a large, consistent replenishing patient base, but no disease-modifying therapy, alas. We can compress, inject, laser cut, but we don't yet have a way to change the underlying biology of the scar. So the unmet need is clear. Both patients and physicians are looking for something that finally addresses the mechanisms that keep scars rigid and persistent, rather than just managing symptoms at the surface. In summary, the emotional burden is often greater than the physical one as scars sit at this intersection of identity and biology. Next, please. Our current standard of care, sadly, is a patchwork of partial solutions. Here's the reality of current scar management. The standard of care is fragmented, inconsistent and frankly, outdated. We usually start with the silicon sheets of gels. They are inexpensive and widely recommended, but their effect ranges from limited to negligible in most real-world scenarios. Next is steroid injections. They can temporarily flatten or soften a raised scar, but the relapse rate is extremely high and equally other side effects, especially in keloids. And repeated injection into skin can cause side effects such as lipodermal atrophy. We then move to lasers, which can help with redness or texture, but they're operator dependent, very expensive and not available to all, and still don't modify the underlying biology driving persistence of these lesions. When those fail, we escalate to surgery, but in keloids cutting out the scar alone often makes it come back larger. Surgeons noticed well, it's a classic example of anatomical improvements without biological control. Access -- sorry, across this whole pathway, you see a common theme, multiple modalities, higher recurrence, not durable solution and everything is off the label. And crucially, there is no approved molecular therapy that targets scar biology at the source. None of these therapies touch collagen cross-linking. They don't alter the scaffold. And that is why this field is currently stuck in a very motionless, stiff scenario. We are treating the appearance of the scar, not the mechanism that keeps it rigid and persistent. Next slide, please. After this point, we have covered the burden of scarring, the limitations of current treatments and the frustrations felt by both patients and clinicians. So the natural next question is what does the field actually need? For patients, they need a remarkably consistent across geographies and skin types. They want scars that are softer, flatter and less visible. And they want that improvement without pain, downtime or the risk of making the scar worse. Many have been through repeated cycles of steroids, lasers and surgeries only to relapse. They're tired of the temporary gains. And for patients with darker skin types, long-term safety is essential, particularly avoiding the pigment risk associated with aggressive procedures. Clinicians frame the need through reliability and practicality. They want a treatment that delivers consistent results across all skin types that is noninvasive, that integrates easily into routine care, that does more than suppress symptoms. They're looking for something that genuinely alters the extra cellular matrix, softens stiffness, improves elasticity and reduces recurrence. They also want a single modality that can be used across all types of scars, postsurgical, burns, trauma, cosmetics, et cetera. When you put these perspectives together, the message is very clear. Patients want confidence and meaningful lasting change. Clinicians want consistency and true biological effect. At present, no available therapy achieves both, which is exactly the gap we're aiming to fill. Next slide, please. When we treat scars, the real target is not the surface. It is indeed remodeling, getting that scar tissue to behave more like a normal, elastic skin. Clinically, that means several concrete issues. We want to reduce collagen density, so the tissue is less rope like and bulky. We want to normalize vascularity, moving away from the red hypervascular, early phase and the poorly perfused Ischemic late phase. We want to restore elasticity, so the scar moves with the body into the restricting motion as we want to reestablish a matrix turnover that healthy state or collagen is continually laid down and broken down instead of being frozen in a rigid configuration. So the goal is not simply a scar that photographs a little better. It is a biological and functional correction. Current treatments rarely achieve this because almost all of them act upstream or at the surface. Steroids dampen inflammation for a time, laser change color and texture for a short while, surgery removes bulk, none of these directly address that all important tissue, which is the collagen cross-link. Once LOX-driven cross-links are formed, the scar becomes mechanically unlocked. You can cut it, you can laser it, you can inject it, but the underlying scaffold remains. So the biology simply rebuilds on the same rigid templates. This is why the recurrence is so common. We keep editing the facade, while the structural engineering underneath is unchanged. And what is missing and what does -- not that exists as an approved option is a molecular therapy that targets that cross-linking machinery, softens the ECM and reopens the window for true remodeling. This is the context we're looking at LOX at therapeutic target. Next slide, please. So if you take a step back and look at the competitive landscape in scarring and fibrosis, almost everyone is concentrated at the top of the cascade. We have upstream inhibitors, such as anti-inflammatories, anti-fibroblast agents, immune modulators. They can blunt early signaling. But once the scar is mature and stiff, the impact is modest because the collagen scaffold is already formed. We also saw anti-TGF biologics, including the well-known renewable recombinant TGF-beta 3 program. Those are ambitious, well-funded trials that ultimately fail to deliver durable remodeling. It highlighted that targeting a powerful cytokine upstream does not necessarily shift the biology of a mechanically locked cross-linked matrix. Energy devices, including lasers, where the frequency microneedling can create partial remodeling, but the results are equally operator-dependent and often temporary. Many patients drift back towards baseline within months. There are other biologics internal approaches in early exploration, but not has yet shown reliable remodeling of established scars. And globally, there is no approved molecule with a primary claim of scar remodeling. This is where the white space emerges. LOX enzymes sit at this downstream at the level of the matrix mechanics. Their cross-linking activity represents a final common pathway of fibrosis across organs, including an imported skin. It acts as a biological bottleneck that integrates essentially all upstream probiotic signals, yet almost no therapeutic competition. So lots of inhibition is the only strategy that directly targets matrix stiffness by blocking the cross-linking step we're not simply modulating, but we're altering the physical state of the scar itself. Important pan-LOX inhibitors have already shown evidence of ECM softening and remodeling in humans, which moves us beyond theoretical biology into any clinical traction. Next slide, please. Now let's zoom in why scars become mechanically permanent, the true molecular root cause and the LOX and the LOXL-4 enzymes see that this is common pathway of fibrosis. These copper-dependent amine oxidases convert lysyl residues on collagen into reactive [ aldehyde ], which then forms irreversible covalent cross-links. And once mature cross-links accumulate, the tissue becomes stiff, resistant to degradation and remodeling and almost essentially locked in place. In normal skin, there is a balance between deposition and remodeling. Collagen is laid down, reorganized and cleared. In hypertrophic scars and keloids, this balance is broken down. LOX activities consistently overactive, and the result is not just too much collagen, but too much cross-linking. This mechanical rigidity has biological consequences. We see vascular collapse, reduced perfusion and persistent fibroblast activation as a result of the stiff matrix, which are defining features of pathological scarring. So if the goal is truly to remodel a mature scar, the intervention has to target this cross-linking machinery. Once the matrix has hardened, upstream processes like inflammation and proliferation become secondary. Targeting the LOX family directly addresses the biochemical architecture that gives the scars permanence. So as LOX integrates every upstream fibrotic signal into one final mechanical endpoint resulting in stiffness. Next slide, please. So up to this point, we have established that LOX enzymes create the mechanical stiffness that LOX scars in place. But the next question is why do we need pan-LOX inhibition rather than targeting just one isoform. In the skin LOX family, there is like a compensatory network. If you block one isoform, the others increase activity and maintain collagen cross-linking. This is why selective approaches such as only blocking one of the enzymes has not shown meaningful remodeling in the skin. The biology simply reroutes around the blockade. That pan-LOX inhibitor, however, prevents this compensation by reducing the total cross-link formation across all isoforms. We finally allow collagen to become susceptible to the natural turnover again. In practical terms, this means scar tissue can soften, vascularity can recover and matrix to regain some ability to remodel. So the value proposition is simple. Targeting the single isoform is not enough for meaningful scar remodeling. The skin requires a coordinated pan family inhibition to actually shift the mechanical state of the tissue and therefore, pan-LOX releases that mechanical lock and reactivate the turnover. Next slide, please. Clinical development in scarring has historically been difficult for a very specific reason. First, scars are heterogeneous. A thin postsurgical line, a thick hypertrophic scar and keloids are all biologically different, and trials often mix them together, making signal detection extremely hard. Secondly, our traditional endpoints haven't been well suited to fibrosis, thickness alone, redness, liability, all of these vary between patients and even within the same scar. And third, these scars differ dramatically in age, height and vascularity. A 3-months old hypertrophic scar behaves differently from a 5-year-old keloid. Yet historically, they have been treated as interchangeable. This variability slows recruitment and dilute treatment effect, and final recurrence is common. Even when an intervention seems promising early on, the underlying biology of them reasserts itself months later. If you do a long enough endpoint for the study, you'll find that masking efficacy unless you have the right design and follow-up windows. So these challenges historically block meaningful drug development. But they don't mean scarring is unfixable. They mean that the field has needed a more mechanistically precise target and a more disciplined clinical approach. And that's exactly where a LOX directed strategy combined with rigorous phenotyping and better endpoints can finally shift the trajectory of clinical development in this area. Next slide, please. Historically, one of the biggest barriers in scarring research was a simple fact that we couldn't measure the biology with any precision. For decades, we relied on photographs and subjective scoring systems. That made trials slow, noisy, inconsistent and extremely hard to reproduce. What has changed the field in the last 5 to 7 years is the arrival of modern imaging and biomechanical tools that finally let us quantify what matters. OCT, for example, gives us simultaneous structural vascular information, essentially a real-time biopsy without ever touching a scalpel. 3-dimensional volumetric imaging allows us to measure scar volume area, height to soft millimeter accuracy. And the elastography gives us a direct readout of stiffness, which is the exact parameter governed by LOX biology. And patient-centered tools such as POSAS and PRISM let us integrate symptom burden and quality of life relevance into our endpoints. Most importantly, split scar clinical designs eliminate interpatient variability. Each patient becomes their own control, which dramatically improves signal detection, shrink sample sizes and accelerate proof of mechanism. In short, the tools have finally caught up with the biology. We can now measure stiffness, vascularity, thickness and remodeling with unprecedented precision, which means we can finally evaluate a LOX targeting therapy on the exact outputs as it's desired to change. Next slide, please. So human data consistently showed that LOX is not a theoretical target, it is embedded in real scars. In hypertrophic scars, keloids, burns, and postsurgical scars, we see elevated LOX expression. These biomechemical changes track with what we feel clinically, increased stiffness, higher recurrence rates and poor vascularity, the classic fingerprint of a persistent pathological scar. Mechanobiology links this together. Stiff matrix keeps fibroblast activated and activated fibroblast keeps stiffening the matrix. So therefore, here comes the LOX strategy with the enzyme that sustains that loop. When we inhibit that LOX enzyme, the picture reverses. Cross-linked density falls. In Solaria 2, we saw around a 30% reduction in collagen. That was a significant effect in structural term, not just cosmetic smoothing. As collagen turnovers resume, microvasculature starts to reemerge and tissue oxygenation improves. In other words, restored microvasculature equals restored metabolism. On OCT starts begin to move back to order normal skin phenotype, rather than just looking a bit flatter on the surface. In other words, even established scars retain the capacity for true biological reversal, if you remove the mechanical lock that LOX provides. Next slide, please. So for patients, the benefit is simple. When you reduce cross-link density, scars become softer than unlisted. And symptoms like pain and itch will decrease. That leads to better function and better confidence because the scar is no longer a constant source of discomfort or self consciousness. Addressing the mechanical driver also lowers the risk of recurrence, which is one of the main reasons patients feel defeated by current treatments. The relevance spans post surgical scars, burns, traumatic scars and the rapidly growing cosmetic procedure space where scar expectations are higher than ever. For investors, it is a rare wide space. The market is global, steady and constantly renewing because every surgical procedure produced as a scar. There are no approved therapies, anywhere that remodel scar issue, which means no established competitors and no mechanism crowding. Pan-LOX inhibition is a truly first-in-class approach, and we already have human proof of concept on structural reversal and vascular normalization because LOX biology is consistent across all scar types. This biology with platform expansion across surgical types would include hypertrophic, keloid, burn as well as aesthetic scars. Final slide, please. In summary, scarring remains highly prevalent, clinically significant and deeply underserved. This is a large, predictable, globally replenishing market with no true disease-modifying therapy. Both patients and physicians are asking for the same thing, real remodeling, not temporary suppression or short-lived improvements. We now understand the biology well enough to target stiffness directly rather than just calming inflammation around it. So LOX activity sits at a mechanical route of scar persistence. And its involvement is consistent across scar types. When we inhibit LOX, we see meaningful structural reversal in human studies, showing that even mature scars can remodel once the mechanical lock is released. Importantly, the historical barriers to scar trials, heterogeneity, subjective endpoints and precise measures are now solvable. Modern imaging, quantitative stiffness tools and split scar designs give us that clean inter-patient comparisons and remove much of the execution risk that used to slow this field. Pan-LOX inhibition is therefore uniquely positioned. It directly targets matrix stiffness, has early human data showing real remodeling and representing a true platform that addresses surgical hypertrophic burn, keloid and aesthetic indications. This is one of those rare moments when biology, technology and the unmet need finally align. With that context, it is my pleasure to hand over to Wolfgang, who will introduce SNT-9465, the next-generation pan-LOX inhibitor designed for daily real-world use, built to translate biology into a durable, scalable therapeutic solution. Thank you.

Thank you, Professor Bayat, for the wonderful explanation on the role of lysyl oxidases in skin scarring. As a biologist, it's so convincingly pointing to the use of pan-LOX inhibitors, I'm fully delighted to explain the efforts of our chemists and biologists to develop the best-in-class inhibitors. The development of these topical anti-scarring treatment was based on 3 pillars. First, and most importantly, a deep understanding of the biology. As Gary already mentioned, we have been very fortunate to collaborate with the University of Western Australia since more than a decade, together with Mark Fear who we deeply miss, and Professor Fiona Wood really pushes us to develop drugs to improve the life of patients. Their knowledge in the disease from the patients, but also in the disease models, in vivo and ex vivo, really help us to develop drugs with the right properties that we could develop further into preclinical candidates. All preclinical candidates go through a very thorough cascade of in vivo experiments where we show the effects in animals, but equally in skin structures that they have derived to make sure that we are inhibiting the enzyme and we can measure the effects in the clinic and can translate this data that we are seeing. Second, with our chemists, we have developed extensive knowledge to discover novel mechanism based inhibitors. These compounds that they have found bind to the active side of the enzyme and to block its activity completely. This process is not reversible, which means that the body needs to make a new protein to recover its activity. So they actually have a long-lasting effect. It's a powerful mechanism, it's long-lasting, and it is consistent toward old scars because it is -- as Professor Bayat mentioned, the last point in the cascade that is inhibitor. Obviously, we have done several other studies to understand the profile of this compound penetrating system as well as what's the metabolism to ensure that they are suitable for preclinical development. So last thing which is very important as well as these compounds need to be actually able to be formulated in a cream, so they need to withstand environment where there's water around for 25 degrees over years and still being stable. And all of our compounds that we progress have these properties so they can be distributed worldwide without any issues. SNT-6302 is a compound that we have put first in the clinic for the treatment of skin scarring had all these properties, and it was successful in the studies and Professor Bayat and Gary already mentioned these clinical studies. Mechanistically, it's inhibition that we have seen ex vivo, in vivo translated very well, the concentrations in the skin that we have achieved and the very limited distribution to the body, which we have measured in the clinical trials were as expected for a topical treatment and actually confirm our preclinical work. So we were very confident that we were on the right track. Unfortunately, and only in a very small number of patients, we have seen some redness, which we have not seen preclinically or in any of the other studies. But the incidents occurred could be reduced by reducing the frequency of dosing or the amount of SMT-6302 we have given to a certain surface area, finding at that early stage made us believe that we should actually improve the compound, and we can. The reason why we actually are working in this field is that we actually have a large number of compounds synthesized and we understand very well the chemistry of our compounds. So we went out and we looked for the right compound that has this property and we synthesized many more compounds so that we ended up with SNT-9465. So SNT-9465 as well as other compounds comes from the lab benches that are portraying [indiscernible] that you are currently seeing and has been developed by the chemist here in French Forest. We have tested its pharmacodynamic and pharmacokinetic properties, and we are confident that we have overcome this redness issue that is seen in humans, while at the same time, we maintain the important properties that it is an inhibitor, which is very potently reducing the activity of the lysyl oxidase in the skin. When analyzing all available data, it became evident that we had improved the chemical properties and the metabolic stability of this compound so much that we feel confident that we could put it into all the preclinical safety trials that had to be done. And out of that one came the clinical study that we have conducted in first in man, and we finished that recently. So besides the additional improvements, we also have now a compound that is also highly water soluble and can be formulated in the clean base as well. So available data today suggests that this drug will produce strong drug product that can be given once daily. So in our similar ascending dose trial, we have in each cohort, 2 subjects who have received placebo, and 6 subjects which got always the same dose of the drug. We have taken biopsies before and 24 hours after the cream has been given. And the 24 hours obviously mimics the rhythm that the patients would give on a daily dosing regimen. A biopsy is only a 3-millimeter in diameter, small piece of the skin, not much larger than a sesame seed when prepared for the assays. Out of the skin we can extract the drug and can measure its concentration. So we are sure that the drug has reached the area where the lysyl oxidase actually are. Most importantly, we do measure the lysyl oxidase activity, and the difference between drug-treated biopsy and the biopsy which has been taken before the drug treatment, shows us inhibition that the drug has achieved at a certain concentration. We have seen an increase in the drug concentration which is dose dependent in the skin, and this correlates with a reduction in lysyl oxidase activity. All the data from the study 2 subjects that were enrolled in the study were carefully analyzed by safety review [ bot ] and I'm really pleased to report that they have not seen any safety signal of any concern. Therefore, we wanted to forecast in the next phase, and I'm delighted to hand over to my colleague, Jana, who will explain the study design.

Thanks, Wolfgang. It's incredibly exciting to share further details about our Phase I first-in-human integrated patient study for SNT-9465. Next slide, please. And the one after. So as announced to the market in late July, the Phase Ia part of the study, which is a single ascending dose commenced at the linear clinical research site in Perth, Western Australia. This part of the study, which included 4 cohorts recently concluded. Now as Wolfgang just mentioned, there is a dose-dependent increase in drug concentration in the skin, correlating well with lysyl oxidase reduction. Now the Safety Monitoring Committee was supported to start being the highest dose in the second part of the study, which I will explain in more detail now. So as you can see, this is a randomized double-blinded placebo-controlled split scar design involving 20 adult participants with hypertrophic sternotomy scars. The split scar design is particularly elegant because each participant serves as their own control. So we treat one segment with active drug and another with placebo, minimizing inter-patient variability. So why sternotomy scars? While hypertrophic sternotomy scars can affect up to 30% of the cardiac surgery patients due to high tension wounds, they're optimal deep to their uniform length, and they're easily accessible unlike keloids or burn scars, which are variable based on location and etiology, for example. So the inclusion criteria that we have in the study are quite specific to ensure consistency. We're looking for scars age between 3 to 12 months with a total scar length of at least 15 centimeters. The scars need to be 1 to 2 centimeters wide to ensure we have 2 square centimeter scar segments to work with, and they must have a height of at least 2 millimeters, indicating true hypertrophic scarring. The treatment duration will be for 3 months. So what makes SNT-9465 particularly promising is that it retains all the anti-scarring efficacy featuring a previous compound, which Wolfgang alluded to 6302, with an improved tolerability profile which will make it suitable for daily application and help with patient compliance. Next slide, please. So our trial design has been carefully optimized for both inclusion criteria and endpoints to capture comprehensive data on safety and efficacy. The primary endpoint of safety measured through treatment-emergent adverse events. Safety is always our first priority in any first-in-human study, and our secondary endpoints are quite comprehensive. First, we'll be measuring PK and PD to understand the drug behavior in this patient population. For efficacy measures, we're using multiple approaches incorporating objective measures, as Prof. Bayat alluded to. First is scar rating by multiple blinded radars to minimize bias and ensure objectivity. This will be through conventional photography, utilizing the systems and protocols of an imaging CRO that has been successful in delivering studies that conform to regulatory standard. Now this same provider will also support 3D imaging, which is being used to measure actual scar volume changes. Also, there will be optical coherence tomography, OCT. This is the same imaging technology used in the Solaria 2 trial. OCT allows us to look beneath the surface at matrix remodeling and vascularization patterns in real time. Elastography will be performed using a cutometer. This measures skin elasticity, a key indicator of scar quality, more elastic skin needs better -- means better, more functional tissue. And finally POSAS, the patient and observer scar assessment scale which captures both the clinical perspective and importantly, the patient's own experience with their scar. The latest version of this scale will be deployed, which has had extensive patient and international clinical import compared to the previous version that was used in the Solaria 2 study. So this multimodal approach gives us a 360-degree of treatment effects, from molecular mechanisms all the way to patient reported outcomes. By combining objective measurements with subjective assessments, we can build a complete picture of how SNT-9465 performs in treating hypertrophic scars. I'm truly excited in being involved in this program as it unravels. There is a significant unmet clinical need, as Prof. Bayat mentioned, and we have an excellent opportunity to truly make a difference here. I will now pass it on to Gary, who will wrap up the formal part of the presentation with a summary.

Thanks, Jana. Next slide. So when thinking about the opportunity here, we're in a number of different markets with our pipeline. I think the skin scarring opportunity stands at as being one of the largest that we're addressing and certainly the most numerous patients. I think Prof. Bayat made a very telling point about the fact that this is a market which renews itself over and over again and every single surgery that goes on does produce a scar of some type. I think also you've heard very clearly the challenges in clinical development and looking at scars where scars vary between patients and also within patients. But I hope you've also seen a very careful and innovative design of the clinical study that will deliver end points, which allow us to assess the commercial value of SNT-9465 at the end of this double-blind, placebo-controlled study. Of course, it all starts with the patients. And I've just shown some pictures there of hypertrophic scars in a number of different places. Now we have chosen to use sternotomy scars because we think this is a reproducible scar in the same portion of the skin, always under tension with -- from the patients, so more likely to produce hypertrophic scars. And we think with it, the patient group that we have, we stand a very good chance of showing what the drug can do in changing the biology of the scar and the appearance of the scar, functionality of the scar within a 3-month period. Next slide, please. And all of that leads to a really dramatic opportunity in the market. And we've talked -- I think Prof. Bayat talked earlier on about the use of standard of care in these patients and how it leads to short-term results or minimal results. One of the first things we talked about was actually -- just as an example, was silicon sheeting. The hypertrophic and keloid market at the moment is worth globally something in the order of $6 billion. And 45% of that comes from silicon gels and sheeting. So the market here is enormous for drug switch and mechanisms, which have very little impact on the scars of these patients and producing long-lasting benefits. So this is an area which, because of probably the increase in aesthetic surgeries as well, a segment which is expanding the fastest of all the scars. This is the segment which is growing more quickly. Traumatic wounds surgery and burnings are all driving this, the increase in awareness of aesthetic treatments, advancements in therapeutic formulations are all contributing to market growth. But topical treatments represent the largest part -- segment within this area. I think because if you're a patient, the idea that you could -- not have to go back into a clinic and receive microneedling or laser therapy with an operator there. It's very attractive. The concept behind 9465 is that will become a tube of cream that can be given to every single patient who undertakes an operation who is at risk of a scar, to apply for a 3-month period after the treatment, after the scars as initially -- the wound has initially healed and prevent the long-term adverse effects of scarring in these patients. So I think a really exciting opportunity. Next slide, please. So with that, I'll just conclude and just note for those of you that are investors in Syntara, those of you who are thinking about an investment in Syntara, that news flow for the next 12 months covers our pan-LOX inhibitors oral in myelofibrosis and myelodysplastic syndrome, 2 different hematology-based cancers. The topical pan-LOX inhibitor, which you've heard about the study, which is going to undertake starting now. It's actually ahead of schedule. We've accelerated this program based on the results we've seen. We do expect to see results in the next year from that study. And also from the study, which Fiona Wood is and her colleagues are undertaking in keloids scarring, which, as I said, is 50% recruited already, and looks like we will see some results of that in the next year, too. And finally, but not last, is our Parkinson's disease study, which is nearing full recruitment of all the patients that are still remaining to be dosed have been now scheduled. So we're optimistic that, that study will finish recruitment at the end of the year, beginning of next year, and we will see a result from that study in quarter 2. So an exciting time for the company and its investors and their shareholders, and we look forward to updating you on this in the months to come. I'll now hand it back to Matt for any questions that there are.

Thanks, Gary, and to everyone who's participated there. As you've alluded to, we'll jump into the questions and get through as many as we can. So to start off with, one that came through via e-mail. Since separate pharmaceutical solutions are being developed for hypertrophic scars and keloid scars, why would one pharmaceutical solution be unable to treat both scar types?

Professor Bayat, maybe you could address that question in terms of different types of treatments for different types of scars?

Well, we partially alluded to this in my talk in that there is heterogeneity in scar types, particularly raised scar types. And in terms of treatment, you really have to look at the age of the scar. And this is particularly relevant for scars that are quite mature, and these topical gels and creams are not going to be doing anything to change the biology of that scar. And that's why it's important to address the biology before it sets in. When the boat has sailed, there's nothing you can do. And that's why it's critical to address that cross-linking of collagen as -- at the earliest opportunity. And the other thing that becomes important is in keloids, particularly, there are not only different types of keloid in terms of sites, but also the element of familiar predisposition. So those individuals who have multiple keloids and have a strong familial tendency will have -- will likely have had previous treatments, which have failed or will likely have a higher occurrence rates. And it's very difficult to look at all of the different types as one raised scar entity. So you have to take all of those individual features, those endotypic features in mind before treating that. So I'm not quite sure where this question was going to go, what the person wanted to get out of the question. But suffice to say that this is a heterogeneous entity. And you have to bear that in mind with your treatment plan.

And the next question I have is, can you please comment on 9465's tolerability outcomes in healthy volunteers, including redness and rashes compared to the first gen product?

Jana, would you like to take that?

Yes, sure. So the first phase of the study was a single ascending dose. So these healthy volunteers were either given the active for one dose or the placebo cream, but no redness or any of the points that we observed in the Solaria 2 study was seen with the caveat that, that is just the one daily dose for now.

The next question I have is, given there hasn't been much success in skin scarring trials is the idea of addressing hypertrophic sternotomy scars in particular to reduce heterogeneity?

Jana, do you want to take that?

Yes, that's -- absolutely. The -- having a linear surgical scar, knowing where the location is and also the prevalence of a scar like that was what was really quite appealing and Prof. Bayat was very much the mastermind behind that.

We have seen other studies that have tried to do the same thing as well. So I think there's an example of the historical study was done in tummy tuck surgery, which again, was trying to find a uniform scar across thing. And I think also thyroidectomies as well. It's been another area. But I think the sternotomy scar stands out because of the place where it is, the length of it, which really lends itself to using this -- the patient as their own control.

The next question is what would a Phase IIa/IIb look like? Would it be as specific as hypertrophic sternotomy scars?

I think that we'll -- I mean, this is very much trying to make sure that we control the scar as tightly as possible so that we really see what the outcome of a 3-month treatment is. I think we'll learn a lot from that. The patient group we use in the next study will depend a little bit on the level of efficacy we see within this patient group and how quickly those results emerge. Clearly, you'd like to expand it beyond just sternotomy scars, if you can, so you can show in other types of scars. But I think -- again, we are recognized that the history of trials in skin scarring is littered with people that move beyond a controlled setting too quickly and lose efficacy by doing that. And I think we want to move one step at a time. So we'll certainly look to this first study. I think it's -- we've given ourselves every chance of showing that this drug works by controlling the patient group very tightly. And hopefully, we'll be able to expand beyond that for the next study once we see the results.

One for Prof. Bayat is what has been your experience with other topical agents that have been trialed in skin scarring? And for recruitment, what went wrong to patients just rely on less expensive treatments such as laser or laser?

Well, that's a -- there's a lot of fact in that question. First of all, the topicals that are out there range from useless silicones, as was alluded to, that have no real biological effect. And what they do is typically, they act as a occlusives, and they keep the -- some of the scars hydrated. And in time, the scar improves in appearance. And however, there is no biologically active component with the silicon itself. And in that material, that's just on top of the skin. Some of the other actives, anything from onion extract to pixie dust has been sold as a topical. And the problem with a lot of these things is that without the science and the evidence, you're really sort of creating a kind of a scenario where it's very difficult to prove efficacy and show truly what the mechanism of action is in order to prove these endpoints. And most of these trials have a limited efficacy. And unfortunately, there is none that just truly shown to me that has got a place in managing scars. And of course, I think one of the most important thing is when you talk about a scar, you have to talk about the type of scar that you're looking at and the endpoints that you will be measuring as part of that study. And if you don't have a mechanism and you don't have evidence behind it, well, it's a nonstarter. Then you were talking about lasers. Lasers are not an inexpensive way of treating scars. They are expensive. They're operating dependent, and they can be -- they are destructive. But they have their role and they're particularly useful in some scenarios. And as there is a particular role for surgery, where adjuvant surgery given with adjuvant treatment is suitable for particular scar types. And one that is eminently requires surgery is the contracture scar type because unless that's released, that problem will continue. And therefore, a combination of surgery and the topical that works is going to make a huge difference. I hope that address the question.

And another one for you, Professor Bayat was, can you please set some expectations for what would be clinically meaningful outcomes from this Phase Ib trial, specifically focusing on the secondary efficacy endpoints?

Well, a meaningful outcome is really to see a significant difference. And if you look at the length that Syntara has taken in designing this study and the devices that are used for objectively quantifying the outcome, it's very likely going to show if there is a meaningful difference here. And you couldn't have designed a more objective, quantitative study than they have put together now. So a good study requires the ideal study design. So the design here of sternotomy scars is fantastic, well done to the team for choosing that. And also the sort of -- the next part of this is that we're looking at this linear scar has its own control and then using very objective devices to measure that. So very likely to show meaningful data from this study. There are very few studies that have come across that has such a thorough plan, which involves not only the design of the study, but relevant devices that then links up with the biology and the mechanism of action of the drug. So I hope that, that was -- addressed your question.

The next question is, it sounds like the field is significantly advanced in terms of objective measurements and biological endpoints. Have regulators kept up? Or will they need persuasion to adopt new endpoints?

One thing I'll start that, maybe -- and maybe Professor Bayat would comment. I think the -- there are no approved biological therapies, drug therapies for treating scars and certainly modifying the nature of scar. So the discussion with the regulators is breaking new ground. We know at the moment that there are no sort of endpoints that they would point to us saying there's a precedent for them. So this will be an ongoing discussion. And it's also important why the endpoints in this study have to be very clear objective and ones that will stand up to regulatory scrutiny. I don't know whether Professor Bayat, you've had an experience with the FDA or any other regulatory authorities in scarring and end points?

Yes. I think you touched on a very important point here. And this is -- we are to set precedents here with one of the very first trials that really will meaningfully show efficacy. And there is precedence in other fibrotic conditions that are ongoing dialogue with the FDA for other fibrotic disorders. But skin is the one that's the commonest problem worldwide and the least -- sort of the most unmet need, unfortunately. So it'd be a very exciting time as we progress with the Syntara study and continue with a very careful ongoing dialogue with the FDA to ensure this goes through the right regulatory approval process.

The next question is, what does the pricing and reimbursement structures look like for a topical agent in scarring?

That's a really good question. I think that the -- when we've kind of looked at this and modeled it, I think, obviously, some of this depends on the outcomes that we get. You could use laser therapy as a sort of pricing guideline if you do see long-term benefits to the scar. But I think I wouldn't get too hung up on that particular issue at the moment. I think the sheer volume of subjects that there are with scars, the volumes here are dwarf, anything else that we're looking at. So I think this is a market that would be driven by -- if you have any cream, which is effective, which can be given to patients after surgery, then it will be used, and it doesn't need to be a high-priced treatment in order to generate enormous huge revenues in this area. I think also -- we should also bear in mind that there may well be markets where reimbursement is relatively easy to achieve with patients without disfiguring scars, which are causing functional issues and long-term quality of life problems. There may well be a significant market in the cosmetic areas while longer term, where perhaps the reimbursement authorities wouldn't be willing to pay for it. But there's a huge private market. We've seen the -- for example -- just as one example, the amount of BOTOX which is used worldwide for improving appearance and other products coming to the market. So I think -- I'm optimistic that this will be a product that will attract reimbursement for some types of scars. But I'm also very confident that whether there is reimbursement or not, there will be a huge private market for this too.

I'm conscious of time, so I'll just try and do a few more before wrapping up. Next one is as it relates to trials and markets, is there any comparison to vitiligo that can be made as it relates to the reimbursement and how the FDA would view scars, et cetera?

I haven't looked into vitiligo as a comparative indication or the thing there. So I'd have to come back to that. So likewise, the discussions we've had with the FDA have been really focused around endpoints in scars of the hypertrophic and keloid nature and what kind of endpoints they would support in this area, which is quite different from vitiligo thing.

Well, I could add to Gary's comments in that there's been a huge interest in hidradenitis suppurativa of late, and this may be due to intense lowering in the U.S. for looking at an orphan condition, which in terms of numbers, is a lot less of a problem than keloids, but it's suddenly become very much the darling of the NIH as well as not only the funding bodies but also pharma, which are now looking into addressing this. And of course, hidradenitis suppurativa comes with its own -- multiple problems, and scarring is one of the biggest issues in that condition as well. So that was a very interesting point that you raised, and I believe that this is a real evolving field. And I think Gary is going to be very busy talking to the FDA with what we will be bringing out soon. So a great question.

What is pharma's interest in this condition? And can you give any examples?

We've -- I personally have talked to a number of very large companies, including the company that currently has BOTOX that has an aesthetics division, several other dermatology companies. They're all intensely interested in the approach that we're taking and the fact that this is a first-in-class drug in this area. All of them recognize the clinical development challenges going forward. And this trial is specifically designed that we would generate data that would answer the questions that we have from those potential partners down the track. So I think with this sort of before and after scenario showing the patients as their own controls, gives us a really great opportunity to show that this drug does work. And then the design of the clinical trials going forward in the markets that we go into, will, in some way, be driven by the level of interest we get in which of the markets which those big companies want to focus on. But yes, there's a high -- there's not a lot of companies in dermatology. It's a relatively small number. But those are really, really interested in what we're doing.

Would the patient administer the drug and placebo in a different section of the scar? And how would the CRO ensure compliance of application in the correct segment?

Yes. This is an excellent question, and we've grappled with this. I think the importance of the intra participant control has been well conveyed by both Prof. Bayat and Gary, but how we manage this in the clinic. So the patients will be given a skin marker that they will be provided to even take home, and that will be marked into the 2 different segments. So they will be trained at the site when they leave the clinic. They will also be attending the clinic at least 4 times where they will be doing this under supervision. Now the actual applicator will be colored separately for each segment, neither the patient or the site will know that. So they'll be very clear. The site will be educated. I'm personally actually going there to both sites to ensure that all the site staff that are all trained on this matter, and therefore, they will convey this to the participants as well as to which applicator to use for which segment.

And just one final question. What other dermatological conditions could this be used in?

Professor Bayat, I think it's a great one for you to finish off.

Well, the list is long, to be honest with you, because this is such a critically relevant mechanism in many fibrotic processes. And if you imagine anything from skin scarring, all the way through to conditions, which share the same pathology, but not as a result of trauma to the skin such as Dupuytren's disease is a very common fibrotic process that affects Northern European Caucasians. And in fact, it was a very famous Australian who talked extensively about this condition, [ Chap ] called Hueston and who wrote many good papers on the topic. So any other kinds of fibrotic areas in the skin. Well, literally, any pathology releases would leave a fibrotic remnant -- so would leave a fibrotic remnant. So our focus is really geared now towards scarring, post trauma, but imagine all these other conditions that would have the fibrotic element. So the list is very long. And the other one I already alluded to was hidradenitis suppurativa, which has a very particularly prominent fibrotic element to it.

Thanks to everyone for your patience. There was a lot of questions and a lot of good questions. So we really appreciate that. If you do have any others, please feel free to reach out to myself or the team for the contact details on the Syntara announcements. And we'll come back to you that way. But I'll hand it back to Gary to provide a closing comment.

No, I'd just really want to thank Professor Bayat for sharing his knowledge and experience with us this morning. It's been great to have that available to investors and shareholders here to understand what we're doing. We're really looking forward to the next 12 months when this program will come to fruition. We really think we've nailed the clinical trial design, and we've listened to the opinion leaders, pharma companies, regulators alike to deliver what we have. And I think it showcases the team here's ability to rapidly twist on earlier clinical trial results and produce a molecule, which we think now can go all the way to market. And thanks so much for your patience and time and staying on what's been a long webinar, but hopefully, a really educational one. Thank you very much.

So Gary, can I just answer one question before we finish up. Somebody asked will 3 months be long enough to show clinical improvement? And I think it's an important one to answer this one because the answer is absolutely yes. Because what people need to understand is that hypertrophic scarring is very different from keloid scarring. For keloid scarring, you need a long -- much longer term because there could be a repeated response on recurrence, whereas with this hypertrophic model that we've chosen, I think that the outcome is highly imminently doable in the time period because all the time points of vascularity, elasticity and restoration would be evident in that time period. So I think -- if that is a very good question, that is your answer.

Thanks very much.

Thank you so much. Appreciate it.

Thanks, Matt.

Thank you all.