Thanks for standing by, and welcome to the Syntara Care Opinion Leader Investor Webinar Today, following the company's announcement of positive progress in its skin scarring program. All participants are in a listen-only mode. There will be an initial presentation provided by those on the webinar, after which we will focus on some Q&A. If you would like to submit a question, please do so using the Q&A function within Zoom, and we will get to those at the end. 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 are joined by Professor Ardeshir Bayat, who brings more than 20 years' experience at the forefront of translational dermatological science. To begin, I will hand it over to Gary. Please go ahead. Thanks, Matt. If you could move to the summary slide at the beginning, that'd be great. Welcome, everybody that's taken time to join us out of your busy days this morning. 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 two of the people in the team behind the pipeline that we've generated. That pipeline has reached a stage of maturity where we have a number of clinical studies ongoing at the moment, a lot of them due to readout in the next 12 months. The company has cash that takes us through to the beginning of 2027. It is really looking at a very exciting 12 months for the company. 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. The people joining us on the call this morning, foremost is Professor Bayat. We first got to know Professor Bayat, actually, because we did a Google search about who was most published in scarring. He comes up very—he's top or almost top of the list. It has been a collaboration that has gone on for a few months. We have 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 as those translational studies. As I said, very heavily published. We are really looking forward to hearing from him this morning. I am 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 and a lead in the skin scarring studies as we progressed through the phase 1a study that we're reporting today into the next study, which we're about to start, which we'll talk more about later. I am also joined by Dr. Jarolimek. Wolfgang has been with us for 15 years now. It is true to say that all of our pipeline, as Wolfgang has been behind all of it, going through the research labs here in Frenchs Forest. You have 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. 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. After that, Dr. Wolfgang Jarolimek will talk about the phase 1a healthy volunteer study results that we've had and how we've transitioned from the first-generation compound through to this next generation, SNT-9465, before Dr. Baskar finishes off with going through the protocol of what we're doing next in this study. Next slide, please. I just wanted to pay credit at the beginning to two 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 email exchange with her yesterday. That study is going really well. She's been behind a lot of the clinical studies we've done. Also Professor Mark Fear. Mark unfortunately passed away earlier in this year in an accident, but his presence is felt today. The work that he did in the pre-clinical setting and then leading into the clinical studies will always be remembered. We got some great publications from the collaboration that we had with Mark. Next slide, please. That early work that we did with the Fiona Wood Foundation and the University of Western Australia was with a compound, SNT-6302, Solaria I and Solaria II. This was a topical compound that, like 9465, is a pan-LOX inhibitor. We used it in a three-month study of patients that had relatively old scars. The average age of the scars was 13 years, at 13 years of age. In that study, three 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 three months treatment. We also showed an increased vascularization of the scars and the structure of the scars. Those scars gradually becoming structurally and biologically closer to normal. That study led directly to the compound that we're going to talk about today. We did see some patients, a small number of patients, who had reddening of the skin. Wolfgang will talk a little bit about the background to that and why we decided to move on to 9465. That first study really, really encouraged us to go on, and has led us to where we are today. Next slide. I will hand over to Professor Bayat to talk us through a bit of the background to scarring and about the compound that we have. Professor Bayat. Thank you so much, Gary. It's a pleasure to join you all today. I must say that I've spent the last two and a half 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 three worlds: surgery, laboratory science, and translational medicine. Skin scarring happens to be at the intersection of all three. I've seen the clinical burden firsthand as a plastic surgeon, and then I continued to study the molecular and mechanical biology 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. 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. 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 any scars from burns, trauma, road 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. Despite that scale, there is still no FDA-approved therapy that truly remodels scars or softens the underlying biology. Everything we have today is symptomatic, procedural, or temporary. The problem is large, global, as well as predictable. Therapeutically, the space is still quite wide open. Next slide, please. 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 use the scar mnemonic a short time to make it memorable. S stands for stretch 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. 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 devastating. A refers to atrophic or indented scars. Acne scars are the classic example. 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, thick, 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. What links them is a shared downstream mechanical bottleneck, collagen cross-linking. Regardless of the cause or category, once cross-links accumulate, scars become stiff, persistent, and extremely difficult to treat. This is the common pathway we will be focusing on and targeting. Next slide, please. Scarring is often dismissed as a cosmetic, but for patients, it's rarely just a mark on the 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. 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'd 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. Band scars require years of follow-up, rehab, and repeated procedures. Keloids have recurrence rates that can approach 100% post-surgical excision without adjuvant therapy, driving repeated clinic visits for injections, lasers, etc., often with worse 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 raise expectations for those scars which should look and feel good. Economically, that gives us a large, consistent, replenishing patient base. 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. 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 silicone sheets or 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. Repeated injections thin the skin and 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. In keloids, cutting out the scar alone often makes it come back larger. Surgeons know this well. It's a classic example of anatomical improvement without biological control. Across this whole pathway, you see a common theme: multiple modalities, high recurrence, no durable solution, and everything is off-label. 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. 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. Up to this point, we have covered the burden of scarring, the limitations of current treatments, and the frustrations felt by both patients and clinicians. The natural next question is, what does the field actually need? For patients, their needs are remarkably consistent across geographies and skin types. They want scars that are softer, flatter, and less visible. 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. 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 non-invasive, that integrates easily into routine care, that does more than suppress symptoms. They're looking for something that genuinely alters the extracellular matrix, softens stiffness, improves elasticity, and reduces recurrence. They also want a single modality that can be used across all types of scars: post-surgical, burns, trauma, cosmetic, etc. 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 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 instead of restricting motion, as we want to reestablish matrix turnover, that healthy state where collagen is continually laid down and broken down instead of being frozen in a rigid configuration. 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. Lasers 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-linking. Once locked-driven cross-links are formed, the scar becomes mechanically locked. You can cut it, you can laser it, you can inject it, but the underlying scaffold remains. The biology simply rebuilds on the same rigid template. This is why recurrence is so common. We keep editing the facade while the structural engineering underneath is unchanged. What is missing and what does not yet exist as an approved option is the 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 as therapeutic target. Next slide, please. 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 that can blunt early signaling. Once a scar is mature and stiff, their impact is modest because the collagen scaffold is already formed. We also saw anti-TGF biologics, including the well-known Renova Recombinant TGF-β3 program. Those were ambitious, well-funded trials that ultimately failed 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, radiofrequency microneedling, can create partial remodeling, but the results are equally operator-dependent and often temporary. Many patients drift back toward baseline within months. There are other biologics and cellular approaches in early exploration, but none has yet shown reliable remodeling of established scars. Globally, there is no proved 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 and importantly the skin. It acts as a biological bottleneck that integrates essentially all upstream profibrotic signals, yet it's almost no therapeutic competition. Locks 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. Importantly, pan-LOX inhibitors have already shown evidence of ECM softening and remodeling in humans, which moves us beyond theoretical biology into early clinical traction. Next slide, please. Now let's zoom in. Why do scars become mechanically permanent? The true molecular root cause. The LOX and the LOXL1 through four enzymes sit at this final common pathway of fibrosis. These copper-dependent amine oxidase convert lysine residues on collagen into reactive allysine, which then forms irreversible covalent cross-links. Once mature cross-links accumulate, the tissue becomes stiff, resistant to degradation and remodeling, and almost essentially locks 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 activity is 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 this stiff matrix, which are defining features of pathological scarring. 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 this scar its permanence. As LOX integrates every upstream fibrotic signal into one final mechanical endpoint resulting in stiffness. Next slide, please. Up to this point, we have established that LOX enzymes create the mechanical stiffness that locks scars in place. The next question is, why do we need pan-LOX inhibition rather than targeting just one isoform? In the skin, the LOX family behaves 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 have not shown meaningful remodeling in the skin. The biology simply reroutes around the blockade. A pan-LOX inhibitor, however, prevents this compensation by reducing the total cross-linked formation across all isoforms. We finally allow collagen to become susceptible to natural turnover again. In practical terms, this means scar tissue can soften, vascularity can recover, and matrix will regain some ability to remodel. The value proposition is simple. Targeting a 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. Therefore, pan-LOX releases that mechanical lock and reactivates the turnover. Next slide, please. Clinical development in scarring has historically been difficult for a very specific reason. First, scars are heterogeneous. A thin post-surgical line, a thick hypertrophic scar, and keloid are all biologically different, and trials often mix them together, making signal detection extremely hard. Secondly, our traditional endpoints have not been well suited to fibrosis. Thickness alone, redness, pliability, all of these vary between patients and even within the same scar. Thirdly, scars differ dramatically in age, height, and vascularity. A three-month-old hypertrophic scar behaves differently from a five-year-old keloid. Yet historically, they've been treated as interchangeable. This variability slows recruitment and dilutes treatment effect. Finally, recurrence is common. Even when an intervention seems promising early on, the underlying biology often 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. These challenges historically blocked meaningful drug development. They do not mean scarring is unfixable. They mean that the field has needed a more mechanistically precise target and a more disciplined clinical approach. That is 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 the 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 five to seven 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. Three-dimensional volumetric imaging allows us to measure scar volume, area, height to sub-millimeter accuracy. Elastography gives us a direct readout of stiffness, which is the exact parameter governed by LOX biology. 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, shrinks sample sizes, and accelerates 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 designed to change. Next slide, please. Human data consistently show that LOX is not a theoretical target. It is embedded in real scars. In hypertrophic scars, keloids, burns, and post-surgical scars, we see elevated LOX expression. These biochemical 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 fibroblasts activated, and activated fibroblasts keep stiffening the matrix. Therefore, here comes a LOX strategy where the enzyme that sustains that loop. When we inhibit that LOX enzyme, the picture reverses. Cross-link density falls. In SOLARIA II, we saw around a 30% reduction in collagen. That was a significant effect in structural terms, not just cosmetic smoothing. As collagen turnover resumes, microvasculature starts to reemerge, and tissue oxygenation improves. In other words, restored microvasculature equals restored metabolism. On OCT, scars begin to move back toward a 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. For patients, the benefit is simple. When you reduce cross-link density, scars become softer, thinner, and less stiff. 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 white space. The market is global, steady, and constantly renewing because every surgical procedure produces a scar. There are no approved therapies anywhere that remodel scar tissue, 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 showing 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 atrophic 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. LOX activity sits at the mechanical root 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, imprecise measurements—are now solvable. Modern imaging, quantitative stiffness tools, and split scar designs give us that clean interpatient 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 where 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 some wonderful explanation on the role of this lysyl oxidase in skin scarring. As a biologist so convincingly pointing to the use of pan-Lysyl Oxidase inhibitors, I'm truly delighted to explain the efforts of our chemists and biologists to develop the best-in-class inhibitors. The development of these topical anti-scarring treatments was based on three 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, who 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 helped 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 the animals, but equally in skin structures that we have derived to make sure that we are inhibiting the enzymes 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 we have found bind to the active site of the enzyme and block its activity completely. This process is not reversible, which means that the body needs to make a new protein to recover the activity. They actually have a long-lasting effect. It is a powerful mechanism. It's long-lasting, and it is consistent throughout all the scars because it is, as Professor Bayat mentioned, the last point in the cascade that it is inhibited. Obviously, we have done several other studies to understand the profile of these compounds penetrating the skin as well as what's their metabolism to ensure that they are suitable for preclinical development. The last thing, which is very important as well, is these compounds need to be able to be formulated in a cream. They need to withstand an environment where there's water around for 25 degrees over years and still being stable. All 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 that had all these properties. It was successful in the studies and Professor Bayat and Gary already mentioned these clinical studies. Mechanistically, the inhibition that we have seen ex vivo and 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 confirmed our preclinical work. 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. Where the incidence occurred could be reduced by reducing the frequency of dosing or the amount of SNT-6302 we have given to a certain surface area. Finding at that early stage made us believe that we should actually improve the compound. 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. We went out and we looked for the right compound that has this property and we synthesized many more compounds so that we at the end ended up with SNT-9465. SNT-9465 has also other compounds that come from the lab benches that are portrayed in this particular figure that you are currently seeing and has been developed by the chemist here in Frenchs Forest. We have tested its pharmacodynamic and pharmacokinetic properties. We are confident that we have overcome this redness issue that is seen in humans, but at the same time, it maintains important properties that it is an inhibitor, which is very importantly 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. Out of that one came the clinical study that we have conducted in the first in man, and we finished that recently. Besides the additional improvements, we also have now a compound that is also highly water-soluble and can be formulated in the green base as well. Available data today suggests that this drug will produce a strong drug product that can be given once daily. In our single ascending dose trial, we have in each cohort two subjects who have received placebo and six subjects which got always the same dose of the drug. We have taken biopsies before and 24 hours after the cream has been given. The 24 hours obviously mimics the rhythm that the patients would give on a daily dosing regimen. A biopsy is only a three mm 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 is. Most importantly, we do measure the Lysyl Oxidase activity. The difference between the drug-treated biopsy and the biopsy which has been taken before the drug treatment shows us the 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. This correlates with a reduction in Lysyl Oxidase activity. Also, the data from the study, two subjects that were enrolled in the study were carefully analyzed by the Safety Review Board. I am really pleased to report that we have not seen any safety signal of any concern. Therefore, we wanted to progress in the next phase. I am delighted to hand over to my colleague Jana, who will explain the study in a second. Thank you. Thanks, Wolfgang. It's incredibly exciting to share further details about a phase I, first in human integrated patient study for SNT-9465. Next slide, please. The one after. As announced to the market in late July, the phase I a 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 four cohorts, recently concluded. Now, as Wolfgang just mentioned, there was a dose-dependent increase in drug concentration in the skin correlating well with Lysyl Oxidase reduction. The Safety Monitoring Committee was supported with studying the highest dose in the second part of the study, which I will explain in more detail now. 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. We treat one segment with active drug and another with placebo, minimizing interpatient variability. Why sternotomy scars? Hypertrophic sternotomy scars can affect up to 30% of the cardiac surgery patients due to high-tension wounds. They're optimal due to their uniform length, and they're easily accessible, unlike keloid or burn scars, which are variable based on location and etiology, for example. The inclusion criteria that we have in the study are quite specific to ensure consistency. We're looking for scars aged between three to 12 months with a total scar length of at least 15 centimeters. The scars need to be one to two centimeters wide to ensure we have two square-centimeter scar segments to work with. They must have a height of at least two millimeters indicating true hypertrophic scarring. The treatment duration will be for three months. What makes SNT-9465 particularly promising is that it retains all the anti-scarring efficacy featuring a previous compound, which Wolfgang alluded to, 6302, but with an improved tolerability profile, which will make it suitable for daily application and help with patient compliance. Next slide, please. Our trial design has been carefully optimized for both inclusion criteria and endpoints to capture comprehensive data on safety and efficacy. The primary endpoint is safety measured through treatment, emergent, and burst events. Safety is always our first priority in any first-in-human study. 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 raters 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. 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 II 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 means better, more functional tissue. 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 input compared to the previous version that was used in the SOLARIA II study. This multimodal approach gives us a 360-degree view 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 and 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. Thanks, Jana. Next slide. When thinking about the opportunity here, you know we're in a number of different markets with our pipeline. I think the skin scarring opportunity stands out 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. 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. I hope you've also seen the very careful and innovative design of the clinical study that will deliver endpoints 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. I've just shown some pictures there of hypertrophic scars in a number of different places. 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 from the patient, so more likely to produce hypertrophic scars. We think with 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 three-month period. Next slide, please. All of that leads to a really dramatic opportunity in the market. I, you know, we've talked, I think Prof. Bayat talked early 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 silicone sheeting. The hypertrophic and keloid market at the moment is worth globally something in the order of $6 billion. 45% of that comes from silicone gels and sheeting. The market here is enormous for drugs and mechanisms which have very little impact on the scars of these patients and producing long-lasting benefits. 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 wound surgery and burn injuries are all driving this. The increase in awareness of aesthetic treatments, advancements in therapeutic formulations are all contributing to market growth. Topical treatments represent the largest part, the 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 is very attractive. The concept behind 9465 is it 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 three-month period after the treatment, after the scar is initially, the wound is initially healed, and prevent the long-term adverse effects of scarring in these patients. I think a really exciting opportunity here. Next slide, please. 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, two 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. have accelerated this program based on the results we have seen. We do expect to see results in the next year from that study and also from the study which Fiona Wood and her colleagues are undertaking in keloid scarring, which, as I said, is 50% recruited already. It looks like we will see some results of that in the next year too. Finally, but not last, is our Parkinson's Disease study, which is nearing full recruitment. All of the patients that are still remaining to be dosed have been now scheduled. We are optimistic that that study will finish recruitment at the end of the year, beginning of next year. We will see a result from that study in Quarter Two. It is an exciting time for the company and its investors and its shareholders. 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. To start off with one that came through via email. 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. Yeah, we partially alluded to this in my talk in that there is heterogeneity in scar types, particularly raised scar types. In terms of treatment, you really have to look at the age of the scar. This is particularly relevant for scars that are quite mature. These topical gels and creams are not going to be doing anything to change the biology of that scar then. That is why it's important to address the biology before it sets in. When the boat has sailed, there's nothing you can do. That is why it's critical to address that cross-linking of collagen at the earliest opportunity. 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 familial predisposition. Those individuals who have multiple keloids and have a strong familial tendency will have and will likely have had previous treatments which have failed or will likely have a higher recurrence rate. It's very difficult to look at all of the different types as one raised scar entity. You have to take all of those individual features, those endotypic features in mind before treating them. I'm not quite sure where this question was going to go or what the person wanted to get out of the question. Suffice to say that this is a heterogeneous entity. You have to bear that in mind with your treatment plan. Thank you. Thank you. 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? Yeah, sure. The first phase of the study was a single ascending dose. 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 II Study were seen, with the caveat that this is just the one daily dose for now. Thank you. 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? Yeah, absolutely. 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. Prof. Bayat was very much the mastermind behind that. We have seen other studies done that have tried to do the same thing as well. I think there's an example of a historical study that was done in tummy tuck surgery, which again was trying to find a uniform scar across thing. I think also hypertrophic hyalodectomies as well has been another area. I think the sternotomy scar stands out because of the place where it is, the length of it, which really lends itself to using the patient as their own control. Thank you. The next question is, what would a phase IIA/IIB look like? Would it be as specific as hypertrophic sternotomy scars? I think 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 three-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. I think, you know, again, we recognize 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. I think we want to move one step at a time. We'll certainly look to this first study. I think we've given ourselves every chance of showing that this drug works by controlling the patient group very tightly. Hopefully, we'll be able to expand beyond that for the next study once we see the results. Thank you. One for Prof. Bayat is, what has been your experience with other topical agents that have been trialed in skin scarring? For recruitment, what went wrong? Do patients just rely on less expensive treatments such as laser or all laser? Wow, there's a lot packed 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. What they do is typically they act as occlusions. They keep some of the scars hydrated. In time, the scar improves in appearance. However, there is no biologically active component with the silicone itself. It's an inert material that sits on top of the skin. Some of the other actives, you know, anything from onion extract to pixie dust has been sold as a topical. 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. Most of these trials have limited efficacy. Unfortunately, there is none that has truly shown to me that has got a place in managing scars. I think one of the most important things is that 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. If you don't have a mechanism and you don't have evidence behind it, it's a non-starter. You were talking about lasers. Lasers are not an inexpensive way of treating scars. They are expensive. They're operator-dependent. They can be destructive. They have their role. They're particularly useful in certain scenarios as there is a particular role for surgery where adjuvant surgery given with adjuvant treatment is suitable for particular scar types. One that eminently requires surgery is the contracture scar type because unless that's released, that problem will continue. Therefore, a combination of surgery and a topical that works is going to make a huge difference. I hope that addressed the question. Thank you. Another one for you, Professor Bayat, was, can you please set some expectations for what would be clinically meaningful outcomes from this phase 1b trial, specifically focusing on the secondary efficacy endpoints? A meaningful outcome is really to see a significant difference. 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. You couldn't have designed a more objective quantitative study than they have put together now. A good study requires the ideal study design. The design here of sternotomy scars is fantastic. Well done to the team for choosing that. Also, the sort of the next part of this is that we're looking at this linear scar as its own control and then using very objective devices to measure that. Very likely to show meaningful data from this study. There are very few studies that I've come across that have 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. I hope that that was answered your question. Thank you. The next question is, it sounds like the field has significantly advanced in terms of objective measurements and biological endpoints. Have regulators kept up, or will they need persuasion to adopt new endpoints? I think I'll start that maybe, and maybe Professor Bayat would comment. I think there are no approved biological therapies, drug therapies for treating scars and certainly modifying the nature of scars. 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 as saying there's a precedent for them. This will be an ongoing discussion. It is 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 any experience with the FDA or any other regulatory authorities in scarring and endpoints. Yes, I think you touched on a very important point here. This is we are to set precedents here with one of the very first trials that really will meaningfully show efficacy. There is precedence in other fibrotic conditions that are ongoing dialogue with the FDA for other fibrotic disorders. Skin is the one that's the commonest problem worldwide and the least sort of the most unmet need, unfortunately. It will 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. Thank you. 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 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. 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 dwarf anything else that we're looking at. 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. 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 who have disfiguring scars which are causing functional issues and long-term quality of life problems. There may well be a significant market in the cosmetic area as well, 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. I think I'm optimistic that this will be a product that will attract reimbursement for some types of scars. I'm also very confident that whether there is reimbursement or not, there will be a huge private market for this too. Thank you. 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, etc.? I haven't looked into Vitiligo as a comparative indication or the thing there. I'd have to come back to that. 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, I think. I could add to Gary's comments in that there's been a huge interest in hidradenitis suppurativa of late. This may be due to intense lobbying 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 has 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. Of course, hidradenitis suppurativa comes with its own bag of multiple problems, and scarring is one of the biggest issues in that condition as well. That was a very interesting point that you raised. I believe that this is a real evolving field. I think Gary's going to be very busy talking to the FDA with what we will be bringing out soon. Great question. Thank you. What is pharma's interest in this condition, and can you give any examples? I personally have talked to a number of very large companies, including the company that currently owns 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. 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. 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. 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 and which are the markets which those big companies want to focus on. Yeah, there's a high degree. There's not a lot of companies in dermatology. It's a relatively small number. Those that are really, really are interested in what we're doing. Thank you. 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? Yeah, 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 will we manage this in the clinic? The patients will be given a skin marker that they will be provided to even take home, and that will be marked into the two different segments. They'll be trained at the site when they leave the clinic. They will also be attending the clinic at least four times where they'll be doing this under supervision. Now, the actual applicator will be colored separately for each segment. Neither the patient nor the site will know that. They'll be very clear. The site will be educated. I'm personally actually going there to both sides to ensure that all the site staff are well trained on this matter, and therefore they will convey this to the participants as well as to which applicator to use for which segment. Thank you. And just one final question. What other dermatological conditions could this be used in? Professor Bayat, I think that's a great one for you to finish on. The list is long, to be honest with you, because this is such a critically relevant mechanism in many fibrotic processes. If you imagine anything from skin scarring all the way through to conditions which share the same pathology, but they're 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. In fact, there was a very famous Australian who talked extensively about this condition, Fiona Wood, and wrote many good papers on the topic. Any other kinds of fibrotic areas in the skin of, literally any pathology would leave a fibrotic remnant. Our focus is really geared now towards skin scarring post-trauma, but imagine all these other conditions that will have a fibrotic element. The list is very long. The other one I already alluded to was Hidradenitis Suppurativa, which has a particularly prominent fibrotic element to it. Thank you. Thanks to everyone for your patience. There were 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 via the contact details on the Syntara announcements. We'll come back to you that way. I'll hand it back to Gary to provide a closing comment. No, I'd just really like 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. I think it showcased 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. Thanks very much for your patience and time and staying on. It's been a long webinar, but hopefully a really educational one. Thank you very much. Gary, can I just answer one question before we finish off? Somebody asked, "Will three months be long enough to show clinical improvement?" I think it's an important one to answer because the answer is absolutely yes. What people need to understand is that hypertrophic scarring is very different from keloid scarring. For keloid scarring, you need a much longer term because there could be repeated response and recurrence. With this hypertrophic model that we've chosen, I think that the outcome is highly eminently doable in the time period because all the time points of vascularity, elasticity, and restoration would be evident in that time period. If that was a burning question, there's your answer. Thanks very much. Thank you so much. Appreciate it. Thanks, Matt. Thank you all.