The binding option agreement to acquire the Italian biotech company PinCell. We prepared together a grant application, which we submitted to the Polish government, seeking EUR 12 million of non-dilutive capital to develop the next stage of PC111. Together with me here on this webinar to review this drug are our distinguished panelists. First of all, I'll introduce myself. My name is Amir Reichman. I am the CEO of Scinai Immunotherapeutics. We have with us Dr. Jonathan Sadeh. Jonathan, maybe you introduce yourself. Hi. My name is Jonathan Sadeh. I'm the head of R&D and CMO at Bausch Health All right. Jonathan Sadeh is our scientific advisory board member of Scinai. In addition, we have Professor Michael Schön. Michael, please introduce yourself. Hi everyone. Thanks, Amir. My name is Michael Schön. I'm Professor of Dermatology at the University Medical Center Göttingen in Germany. All right. Michael is as well a scientific advisory member of Scinai. Together with us, two members of the PinCell team, Chairman and CEO, Mr. Tony Amato. Tony? Hi, Amir. Thanks. Welcome, everybody, and welcome the opportunity of being here. I'm a physician, and I'm the CEO and Chairman of PinCell. Last but not least, Professor Carlo Pincelli, the inventor and the brains behind this exciting drug. Carlo? Thank you, Amir. Hi, everyone. Actually, I'm actually CMO of PinCell. I was the founder of the company. I'm a dermatologist by training. I've been Professor of Dermatology at the University of Modena and Reggio Emilia, Italy. Thank you for welcoming us. Perfect. With no further ado, we will move to the agenda of today. Today, we will have an overview of the pemphigus, Stevens-Johnson syndrome, and toxic epidermal necrolysis symptoms. We'll talk about implications, pathomechanisms. We will talk about an overview of the current treatment landscape. Then we will do a deep dive into the PC111 antibody mechanism of action, the achievements to date done by PinCell, the comparison to the current standard of care, safety profile that is expected from PC111, and the evidence to that, and the potential combination with existing drugs, and the development plan that is now facing the two combined teams. Of course, we'll talk also about challenges in conducting rare disease clinical trials. Last but not least, we will also have commercial market considerations that should be very important in considering drug development in general. We will conclude with a panel discussion and a summary. Let's jump into our first question. The question here is to Professor Michael Schön. Question number one, would you please give us an overview of the pemphigus, Stevens-Johnson syndrome, and toxic epidermal necrolysis symptoms, implications for the patient and for the society? Just before you start, a continuation of the question, what are the underlying pathomechanisms of pemphigus and Stevens-Johnson? Please, Michael. Certainly. Thank you, Amir. We're actually dealing with two different groups of diseases here, both of which are medically quite important and for which there is a significant medical need. Both share some similar pathophysiological mechanisms in the end. Let me just say a few words about these groups of diseases. Now, when we talk about pemphigus first, we're talking about a rare but very serious autoimmunological disease of the skin and mucous membranes. Pemphigus vulgaris is the most common form, but there are also others such as pemphigus foliaceus or paraneoplastic pemphigus. Patients affected by pemphigus vulgaris develop painful blisters and erosions on their skin and also mucous membranes in the mouth and genitals, for example, as you can appreciate in these pictures here. These lesions obviously severely impair their ability to eat, to speak, to maintain general personal hygiene, etc. The risk of infection is significantly increased on these large superficial wounds, and patients are therefore at great risk for infections. This is also the reason why the disease often leads to death if left untreated. If left untreated, the mortality rate is roughly 5%-15%. Now, the disease is chronic, which obviously means that new flare-ups can occur throughout the patient's life and must be treated or prevented. In addition, the disease is also quite often resistant to treatment. Now, on this slide, you can appreciate the incidence and prevalence. The incidence of pemphigus is around 0.5-3 cases per 100,000 people per year. There is a peak incidence in middle-aged or older adults at around 40-60 years of age. As the disease is chronic, the prevalence is much higher, of course, than the incidence. It is estimated that 15-30 people per 100,000 suffer from the disease. That means that roughly more than 2 million people are affected worldwide. Certain ethnic groups, for example, in the Mediterranean region, Middle East, India, or Ashkenazi Jews, are relatively more frequently affected. Also, women are also affected more often than men. Now, on the next slide, I would like to say a few words on how pemphigus develops. The immune system of those affected develops antibodies against structural proteins in their own skin. These antibodies are primarily of the immunoglobulin G, the IgG subtype. These antibodies bind to and are directed to a structural protein called Desmoglein- 3, and sometimes also Desmoglein- 1, by the way. Now, these structural proteins are characterized, among other things, by the fact that they mediate the adhesion of epidermal cells to each other. If the pathogenic antibodies bind to these molecules, they can no longer perform their function of holding the skin cells together, and the epidermis can detach over a large area of the body surface. We refer to this as acantholysis, which means the loss of cohesion between the keratinocytes. Now, this leads to blistering detachment of the skin and subsequently to erosions over large areas. Now, on the next slide, I would like to allude to Stevens-Johnson syndrome and toxic epidermal necrolysis. The situation is somewhat different with these two entities. These two diseases are actually at the opposite end of a spectrum of diseases with varying degrees of severity. There are mucocutaneous reaction patterns that can be very serious. Patients usually feel ill and exhausted and sometimes have a cough in the beginning. Painful, erythematous spots can then develop quite rapidly, which can progress very quickly and lead to blisters on the skin and, again, mucous membranes. The skin then peels off over large areas of the body surface. The so-called Nikolsky sign is positive, which means the skin can be moved or detached by applying slight tangential pressure on it. Patients experience severe pain, dry out very easily, and are at extremely high risk of infections or even sepsis. Now, the next slide shows that SJS and TEN are very rare diseases, as mentioned earlier. Because this is a spectrum with varying degrees of severity, there are also overlapping cases. Most patients suffer from Stevens-Johnson syndrome, about 16% roughly from typical TEN. In addition, there are overlaps in about 14% of patients. Now, these diseases are very rare overall but very severe with considerable suffering and a high mortality rate. Women are also slightly more frequently affected. Now, in most cases, the symptoms are triggered by medication. These are therefore drug-induced hypersensitivity reactions. Cytotoxic T cells and released Granulysin play key roles in these reactions. Ultimately, this leads to apoptosis, which is a programmed cell death of keratinocytes, and thus to massive death of epidermal cells with lesions similar to those seen in severe burns. Thank you very much for these insights and for this very interesting presentation and explanation. Another one for you, Michael, what is the current treatment landscape of these diseases, if you could explain to us? Certainly. As to the treatment of pemphigus, currently approved therapies primarily include systemic glucocorticoid steroids, some steroids bearing immunosuppressants such as azathioprine, methotrexate, and rituximab. Rituximab is a chimeric monoclonal antibody that blocks the surface molecule CD20 on B cells, thereby inhibiting antibody production by these B cells. However, both steroids and rituximab may have severe risks and side effects with prolonged use, in particular, some of which can even lead to the death of patients. There is therefore a significant unmet medical need for pemphigus, which is estimated at approximately ITA 1 billion annually given the frequency and chronicity of the disease. More on that later. Now, with respect to SJS/TEN, on the next slide, there is also a significant mortality rate due to the severity of the diseases. This depends heavily on the measures taken early on. Of course, the triggering medication must be discontinued immediately, and patients must receive supportive care, often in an ICU. Systemic immunomodulation has been reported in the literature with varying degrees of success. Ultimately, there are no approved therapies. Overall, it can be said that pemphigus and SJS/TEN have different pathogeneses. However, there are clear similarities and parallels in the final stages of the diseases, in particular the fact that structures of the epidermis are destroyed by similar mechanisms in both disease groups. These molecular mechanisms are therefore common targets for new therapies. Both disease groups are very severe, and there is a significant global medical need for effective and well-tolerated therapies. Thank you very much, Michael, for this explanation. Definitely looks like an area that requires some innovative drugs to be developed. With that, we will actually shift to Carlo. We'll ask you, Carlo, could you tell us about the mechanism of action of PC111 and how it is expected to affect these diseases? Please go. Thank you, Amir. Like you mentioned in the beginning, today we were talking we will be talking about PC111, that is a fully human monoclonal antibody that targets soluble Fas ligand specifically. And Fas ligand has been identified as a critical factor in the pathogenesis of pemphigus and also of SJS/TEN. But what is Fas ligand? Fas ligand is a transmembrane protein that can be proteolytically cleaved to its soluble form, the actual target of our drug, as we will see in a minute. Both forms then bind the receptor and exert a number of activities. As As far as pemphigus and SJS/TEN are concerned, we should focus on the fact that they trigger the extrinsic apoptotic pathway, inducing mostly keratinocyte apoptosis and acantholysis with the ultimate formation of the blister. Again, PC111 binds specifically and with high affinity to soluble Fas ligand blocking apoptosis. Next slide, please. This cartoon nicely shows the role of Fas ligand in pemphigus and mostly the role of PC111 in the treatment of pemphigus. First of all, in a nutshell, we should say that patients here have very high levels of Fas ligand. At the same time, PV IgG, the pathogenic autoantibodies Professor Schön was mentioning before, can upregulate Fas ligand and facilitate its release from keratinocytes. In turn, Fas ligand induces apoptosis of keratinocytes. At the same time, by cleaving the adhesion molecules, particularly Desmoglein- 1 and 3, if we talk about pemphigus, it induces acantholysis, that is, the detachment of keratinocytes with the ultimate formation of the blister. What is the solution in our view? The solution is PC111 that blocks soluble Fas ligand both in the serum and when it is released from keratinocyte, thereby blocking blister formation at the keratinocyte local level. Next slide, please. This is a short list of the many evidence we and other labs have demonstrated to validate Fas ligand as the target in pemphigus. First of all, Fas ligand is increased in serum patients with pemphigus. We demonstrated that more than 20 years ago. Fas ligand-positive cells are present in the skin of patients with pemphigus. I should say that is true even before skin detachment. PV IgG, again, the pathogenic autoantibodies, induce Fas ligand release from keratinocytes. Also, like I just mentioned, PV IgG causes blister formation through the activation of apoptosis. On the contrary, if you silence Fas ligand, you block the PV IgG-inducing effect. We can say that we have a potential breakthrough in the treatment of pemphigus by stopping skin blistering and blocking Fas ligand to ameliorate and treat this devastating disease. Next slide, please. This slide shows that and is the actual proof of evidence that only soluble Fas ligand is indispensable for blister formation in pemphigus. We have used a very well-established neonatal pemphigus mouse model. We have shown that mice, neonatal mice, lacking a soluble Fas ligand gene fail to develop blister, fail to develop acantholysis, as shown by histology. If you see in the pink in the graph below, also by measuring the relative acantholytic area. On the contrary, PV IgG can induce blister formation in mice lacking membrane-bound Fas ligand or in wild-type mice, indicating that only mice lacking soluble Fas ligand fail to develop blister upon injection of the pathogenic autoantibodies. On your right, using the same well-established pemphigus mouse model, we inject pathogenic autoantibodies directly from patients to the neonatal mice. As you can see, this results in a very clear intraepidermal acantholysis. If we add anti-Fas ligand neutralizing antibodies one or two hours after the induction, the acantholysis starts to decrease to definitely disappear three hours after the induction using anti-Fas ligand antibody. Next slide, please. Now, if we move to SJS/TEN, we know that from our lab and from a number of studies around the world in different labs, that Fas ligand is highly present in the serum of patients with SJS/TEN, also in keratinocytes, and even in peripheral blood mononuclear cells. Specifically, we know that soluble Fas ligand is elevated in the very early days of the disease to then decline within 9 or 10 days. We believe that PC111, given its rapid mode of action, could be administered intravenously immediately after the diagnosis, block keratinocyte apoptosis, block soluble Fas ligand in serum, and PBMC, thereby blocking disease progression. Thank you very much, Carlo. That was a very insightful explanation on the mechanism of action. I will address now the question to Tony, the Chairman and CEO of PinCell. Tell us, Tony, about the drug development activities already done by PinCell to date. Thank you, Amir. In this slide, you can see the list of the main features in chemical-physical terms of our lead product, PC111. Again, as Carlo was saying, this is a fully human monoclonal antibody with a unique non-immunosuppressive mode of action, as explained in the further slides. It is specific as an antibody for the soluble form of the Fas ligand, and it binds to it with a very high affinity in the pico-molar level. It has shown a very low immunogenicity and is very well validated in silico plasma. And it has gotten an optimal solubility, which supports strongly its administration even by the subcutaneous route. Finally, this antibody does not cross-react with the Fas ligand present in mice and dogs but does recognize very highly the non-human primates' targets. That's why we have planned our toxicology studies in such a species, as you will see later on. Indeed, PC111 is our best candidate for further development, also based on its patent protection and on the orphan and biologics exclusivity and data protection that it boasts. In order to confirm our initial proof of concept data generated with murine anti-Fas ligand antibodies directed versus the murine target, we have generated a viable transgenic mouse producing a human Fas ligand protein, which was achieved by swapping the murine gene with the human one. In the next slide, you will see the applications that we have had using this strain of mice. Not only PC111 was shown to dose-dependently bind the soluble Fas ligand produced in a concanavalin A injected transgenic mice strain, but also, as you can see in this cartoon, we have replicated the gold standard model of pemphigus in our transgenic mice, not in the wild mice as previously done. Our monoclonal antibody blocked very effectively blister formation also in this setting. This was achieved at all tested doses with an efficacy of at least 90%. This in vivo data fully confirmed the previous proof of concept data obtained with the murine antibody, therefore minimizing any translatability issues that may be seen in humans. Next slide, please. Finally, we tested our therapeutic hypothesis also in well-established models of SJS/TEN. Indeed, also in this setting, PC111 dose-dependently abrogated cell death in human keratinocytes induced by SJS/TEN serum of patients. Furthermore, it prevented conjunctivitis, a very important early sign of disease progression in a mouse disease model induced by injecting white blood cells from patients plus a causative drug, also significantly inhibiting apoptosis of the conjunctiva. Thank you very much, Tony, for this question, for this answer to this question. The next question is back to Carlo. Carlo, the question is, how does the expected efficacy of the new drug candidate compare to current standard treatments like corticosteroids or rituximab for pemphigus? Maybe same answer for SJS10. Yeah, thanks, Amir, for the very interesting question. Like Professor Schön mentioned in the very beginning, pemphigus has been always treated with strong immunosuppressors, including, of course, steroids and more recently rituximab. Rituximab has been approved in 2020 as a first-line treatment for pemphigus in combination with steroids. In combination with steroids, we should say that rituximab is a highly effective treatment, as shown both by clinical trials and also in the real-world setting. Yet rituximab presents several limitations, including a median time to achieve remission, which is around six months. The therapeutic effect is most of all transitory. Moreover, according to recent publication and recent data, between 40% and 80% of patients relapse after a period of remission that ranges between 6 and 24 months. Only a small percentage of patients stay free of disease off therapy. This implies that, like we as clinicians experience every day, that patients need to undergo more and more frequent infusions that are associated with severe and strong immunosuppressors and, of course, associated side effects. On the contrary, PC111, with its unique mode of action, which is a non-immunosuppressive mode of action, it acts at the keratinocyte level downstream of the immune system, blocking keratinocyte apoptosis and acantholysis at the keratinocyte level. This non-immunosuppressive mode of action would allow a treatment of pemphigus without the just-mentioned associated side effects. PC111 can potentially replace rituximab. At least it can achieve remission much more rapidly than rituximab without the use of any steroids. By acting as a non-immunosuppressive drug, it would also not avoid the risk of the strong side effects also associated with the other immunosuppressants currently used as adjuvant therapy to rituximab or steroids. Therefore, we believe that PC111, it is the first targeted therapy. It is going to be a disease-modifying treatment with a rapid onset of action and with a better safety as compared to the current immunosuppressors. Next slide, please. If we talk about Stevens-Johnson toxic epidermal necrolysis, we all know that there are no molecules approved for the disease. There are no current guidelines for the disease. There is no targeted therapy currently under development for SJS/TEN. In addition to withdrawal of the causative drug, hospitalization, and supportive care, a number of drugs have been used and are currently used for the treatment of SJS/TEN, including steroids, cyclosporine, IVIG, and anti-TNF with controversial results. PC111 prevents keratinocyte apoptosis at skin detachment. It blocks soluble Fas ligand that, as we mentioned earlier, is upregulated in the very first days of the disease and would allow a very early therapeutic effect, just blocking the disease at its start, not forgetting that we are talking about an acute and deadly disease. With the non-immunosuppressive mode of action, PC111 would be the first targeted therapy for this devastating disease. If we talk about the safety profile of PC111, first of all, we should mention that given the unique mode of action, we strongly believe that PC111 could be used without combination with systemic steroids. That is why we do not expect any major side effects due to protracted immunosuppression, as we see with rituximab or steroids. In addition, we have preliminary in silico data where we showed that PC111 is associated with a very low immunogenicity. That is why we do not expect a decrease of efficacy in the long term and in the medium term. There would be no need to either prolong treatment or to increase the dosage. You might wonder, and we are concerned, or actually, I should say we were concerned about blocking the entire Fas ligand pathway in the Fas ligand system because this would interfere with T-cell activities and with the risk of developing the so-called lymphoproliferative condition named ALPS. On the contrary, because PC111 specifically blocks only the soluble form of Fas ligand and not the membrane-bound Fas ligand, we will not incur that risk. We also have the in vitro evidence that PC111 does not affect T-cell apoptosis. We will not have any risk of lymphoproliferative autoimmune conditions. All right. Here we are talking about discussing using the new drug candidate, PC111. Carlo, can it be used in combination with existing therapies? What are the potential benefits or risks for each of these diseases? As far as the combination, yes. Let's start with pemphigus. Again, given its unique, rapid, and non-immunosuppressive mode of action, we are confident that PC111 might induce or maintain remission without the use of steroids, like I mentioned before. It certainly can be administered in combination with rituximab, given the very different mode of action, to accelerate its therapeutic effect. Let me remind you that rituximab has a very slow time to achieve remission. Given the different mode of action, they could be combined and accelerate the therapeutic effect. On the other end, talking about SJS/TEN, we know, again, that there is no drug. We certainly think that given the rapid mode of action, PC111 could reinforce the currently used supportive care by rapidly targeting soluble Fas ligand. In other words, if you have patients in front of you with a strong suspect of SJS/TEN, you, of course, hospitalize them. You remove the culprit drug. You put them under supportive care. Very, very early, you have to administer PC111 that would block Fas ligand, thereby blocking the progression of the disease. In reality, I also think that PC111 could be used in combination with all the other drugs that are currently used for SJS/TEN, and in particular, steroids, cyclosporine, and other drugs, being the faster and the more rapid to achieve remission. Thank you very much, Carlo. We'll shift to Tony. Tony, could you please describe to us the next steps and the timeline in the drug development plan of PC111 for pemphigus, SJS, and TEN? Certainly. Thanks, Amir. Actually, we anticipate two parallel development plans for PC111, one using it subcutaneously for the chronic pemphigus condition and another plan by intravenous administration of PC111 in the acute SJS/TEN setting. Following a common set of CMC and toxicokinetic studies to form the IND and CTA package for the two formulations, of course, to be properly discussed with any regulatory authorities, we will start a phase I/II study of around 50 patients with pemphigus with relapsing pemphigus, which, if positive, should be the basis for an accelerated approval of this drug. If all pans out, we expect to obtain an approval in three to four years after the start of this program. After achieving this, a confirmatory study will be carried out for full approval of the drug in another set of 100 patients, possibly including also a cohort of naive first-line patients. For SJS/TEN, a similar two-staged approach will be used also in this indication with an accelerated approval sought in 20 patients, followed by a full approval in another 50 patients or so. For both indications, sample sizes have been estimated based on comparable drugs. The financing of this program, of the whole program, will require around EUR 55 million spread across several go-no-go decision points to minimize the financial risks associated with these development programs. Thank you very much, Tony. Let's talk a little bit about the challenges in running clinical trials for such rare diseases. How do you plan to overcome them for each of these indications? Sure. As for all rare disease trials, also the studies that we have planned for PC111 in pemphigus and SJS10 have to involve sites with adequate patient availability in order to meet the timelines set in our development plan. Identifying these sites is therefore crucial and will be accomplished with the support of several parties: our scientific advisory board, scientific societies, patient advocacy, but also trialist networks, most of which we have already contacted, and they are very happy to participate in our development programs. Steering committees will be created from these pools of experts to help design the most appropriate and practical study protocols in these two diseases. Thank you very much. I would shift now a little bit into the commercial side of things, Tony. We'll stay with you now. Could you please describe to us the market size for pemphigus and SJS/TEN? Certainly. In this slide, you can see the situation for pemphigus and the prevalence of this disease, as also mentioned by Professor Schön before, as identified in the relevant geographical areas that we have included in our business plan, along with its addressable patient population. There are around 164,000 patients in the five target countries that we have presented, where China is a sizable chunk. Without China, the addressable population would be of around 90,000 patients. We are going to focus our initial development on the second-line relapsing refractory patients, who are at least 35% of the naive patients treated initially and amount to 75%-80% after repeated therapy. Why are we focusing on them? Because they are the ones at greater need for an innovative non-immunosuppressive treatment for all the reasons that you heard before. In all, we estimate that there are around 30,000 patients in the target population that we can tackle. Perfect. If PC111 proved effective as a drug in this disease, we expect to grab the majority of such a patient population. In this slide, you can—if you go to the next—okay, thank you. In this slide, you can see the same market analysis for the naive SJS/TEN patients, whose incidence is larger in the Western world. Therefore, the addressable population for this indication does not change that much if one excludes East Asian countries. The addressable population is around 15,000 patients, as we have estimated. Also, in this indication, should we be able to prove effective with PC111 in halting the progression of the disease, we expect to reach a majority of patients at the triage sites that normally manage them. Super. Very good. Thank you very much. Yeah. Let's talk about the positioning of this drug. Maybe we will switch to how it will be positioned in the market given these two or three diseases, Tony. Yes, certainly. In pemphigus, PC111 can certainly be positioned in first-line naive patients, either alone or in combination with rituximab due to their complementary mode of actions and steroid-sparing effect. However, much better, we see the initial major role of PC111 in relapsing refractory patients since, as I said, they are those in demand of fast-acting non-immunosuppressive and disease-modifying agents. Conversely, PC111 ought to be used in all patients with a confirmed diagnosis of SJS/TEN as soon as possible after such a diagnosis in order to stop their progression towards more severe forms of the disease. Thank you very much, Tony. The next one is, again, a question here to you about the pricing. Tony, how do you expect the new drug candidate to be priced for these diseases? What are the potential revenues that we investors that listen to us or partners that listen to us can expect to have from sales of PC111? Yes. At this stage, we have developed several scenarios to price PC111 in the target countries present in our business plan. We have used experienced consulting firms to advise us on this. For pemphigus, a few% premiums over the U.S. market price of rituximab have been used as a reference, with a range of different% scenarios of such prices to be applied in the rest of the world. The potential peak revenues that one can expect for PC111 have been estimated in the vicinity of $ 500 million, with an upside of over $ 1 billion. A similar approach has been used also for SJS/TEN, having, in this case, the life-saving potential of our monoclonal antibody as a reference consideration. Also, in this case, the potential peak revenues are in the order of $ 500 million with an upside way over the $1 billion mark. Amazing. Thank you very much. This sounds really exciting. I'll switch here to Dr. Sadeh. Jonathan, could you please talk to us about the opportunities for collaborations and partnerships with pharma companies? From your experience, what criteria do pharma companies consider when entering into partnerships or sub-licensing agreements? Yeah. Thanks, Amir. This is really exciting to hear. I think, as somebody who's been in big pharma and various pharmaceutical companies over the past few decades, I see a lot of potential for this drug for a few reasons. I think the world or what pharma companies are looking for in the past few years has changed. In the past, companies were really focused on the big indications, looking for just some incremental benefits in each disease and showing some improvement, but going for big diseases because of the big commercial opportunities. I think now companies are seeing that you can actually go for smaller indications but achieve a much bigger effect size, actually transformational effect, as has been described here, and see a lot of advantages to that, both on the development side, regulatory, and commercial side. If you look at just the development that was just described, if you're looking at a really big effect size, you're looking at much smaller studies, less expensive, faster, and certainly, there's a lot of regulatory advantages regulators give you when you're showing such transformational efficacy, certainly with rare diseases. On the commercial side, I think people or companies are realizing that there is a really large commercial opportunity given that you can actually charge a much higher price, and the footprint that you need to actually commercialize a smaller drug or a smaller opportunity like this is much easier and less expensive for them. There is a lot of interest in these smaller indications with a big effect size. I see a lot of interest within medium-sized to large pharmaceutical companies in a drug like this. Thank you very much, Jonathan. What factors do you think should be taken into account to ensure the drug becomes first-line therapy in the treatment regime? Yeah. No, it's really important to get this drug to be first-line. I think, as Tony was describing, the development plan is certainly aligned with that. When the standard of care is really somewhat controversial, there are some therapies, certainly for pemphigus, but for Stevens-Johnson's and TEN, really not a lot of or not any approved therapies. Doing trials, when you're doing a trial head-to-head against the standard of care in pemphigus, maybe looking at comparison to rituximab or steroids, and in Stevens-Johnson's, TEN, really against supportive care, if you do that in the pivotal trials, the drug will be approved as a first-line therapy, and certainly, I expect it to be used in that way. Interesting. Thank you very much. Last question to you, Jonathan. What specific safety considerations should be addressed during the development, particularly given that the drug is non-immunosuppressive? Yeah. I think this is going to be a really important differentiator for this drug, the safety profile, as was described before. The standard of care for these patients or what is being commonly used out there is all these drugs that are severely immunosuppressive, steroids being a big offender, but all these other therapies, TNF inhibitors, rituximab, all these drugs that are significantly immunosuppressive, so cause a lot of complications, infections, which is a big deal in this patient population. Having a target, having a drug that is not immunosuppressive and is not associated with all these infections that are the main reason these patients suffer from morbidity and mortality along the lines will be really important. Showing that you have less infections, less complications along the way when you do these pivotal trials, head-to-head trials, I think is going to be a really important differentiator and a main reason why people will be using this first-line. Thank you, everybody, for the very interesting discussion. Thank you to our distinguished guests for the insightful explanations. I'm very excited about our deal and about the potential of the development of PC111. Thank you, everybody, to those that registered and attended our webinar. More questions and answers can be found on our website at scinai.com. Thank you very much, and have a nice evening.