Scinai Immunotherapeutics Ltd. (SCNI) Earnings Call Transcript & Summary

Into a 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'm 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 Gottingen in Germany.

All right. And Michael is as well a Scientific Advisory Member of Scinai. And together with us, 2 members of the Pincell team, Chairman and CEO, Mr. Tony Amato. Tony?

Amir, thanks. Welcome, everybody. I welcome the opportunity of being here. I'm a physician, and I'm the CEO and Chairman of Pincell.

And 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, patho-mechanisms. We will talk about an overview of the current treatment landscape, and 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 combination -- the potential combination with existing drugs and the development plan that is now facing the 2 combined teams. And of course, we'll talk also about challenges in conducting rare disease clinical trials. And last but not least, we will also have commercial market considerations that should be very important in considering drug development in general. And we will conclude with a panel discussion and a summary.

So let's jump into our first question. And 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. And then just before you start, the continuation of the question, what are the underlying patho-mechanisms of pemphigus and Stevens-Johnson. Please, Mike?

Certainly. Thank you, Amir. We're actually dealing with 2 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. So let me just say a few words about these groups of diseases. Now let me talk about pemphigus first. We're talking about a rare but very serious autoimmunological disease of the skin and mucus 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 mucus 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, et cetera. 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% to 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 to 3 cases per 100,000 people per year. There is a peak incidence in middle-aged or older adults at around 40 to 60 years of age. As the disease is chronic, the prevalence is much higher, of course, than the incidence. It is estimated that 15 to 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, and 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 binds 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. In the pathogen -- 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 2 entities. These 2 diseases are actually at the opposite end of the 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, mucus membranes. The skin then peels off over large areas of the body surface. The so-called Nikolsky's 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 for -- 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 10. And in addition, there are overlaps in about 14% of patients. Now these diseases are very rare overall, but very severe with considerable suffering in the high mortality rate. Women are also slightly more frequently affected. Now in most cases, the symptoms are triggered by medication. So 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 deaths of epidermal cells with lesions similar to those seen in severe burns.

Thank you very much for these insights and for these very interesting written 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 glucocorticosteroids. Some steroid-sparing immunosuppressant 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 1 billion annually given the frequency and chronicity of the disease, but 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. But ultimately, there are no approved therapies. So overall, it can be said that pemphigus and SJS/TEN have different pathogenesis. 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 a similar mechanism 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, it looks like an area that requires some innovative drugs to be developed. And now with that, we will actually shift to Carlo. And 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, the -- today, we were talking -- we will be talking about PC111, that is a fully human monoclonal antibody that target 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 form then bind the receptor and exert a number of activities. 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 bind 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 see -- we should say that patient's sera have very high levels of Fas ligand and at the same time, PVIgG, 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. But 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 ultimate formation of the blister. What is the solution in our view? The solution is PC111 that blocks soluble Fas ligand both in sera and when it is released from keratinocyte by 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 sera of patients with pemphigus. We demonstrated them more than 20 years ago, Fas ligand positive cells are present in the skin of patient with pemphigus, and I should say that is true even before skin detachment. PVIgG, again, the pathogenic autoantibodies induce Fas ligand release from keratinocytes. And also, like I just mentioned, PVIgG causes blister formation through the activation of apoptosis. On the contrary, if you silence Fas ligand, you block the PVIgG-inducing effect. So 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, and we have shown that mice, neonatal mice lacking a soluble Fas ligand gene failed to develop blister, failed to develop acantholysis, as shown by histology and if you see in the pink in the graph below, also by measuring the relative acantholytic area. On the contrary, PVIgG can induce blister formation in mice lacking membrane-bound Fas ligand or in wild-type mice, indicating that only mice lacking soluble Fas ligand failed to develop blister upon injection of the pathogenic autoantibodies. On your right, using -- no, no, sorry, -- on your right, using the same well-established pemphigus mouse model, we inject pathogenic autoantibodies directly from patients to the neonatal mice. And as you can see, we -- this results in a very clear intraepidermal acantholysis. Then if we add anti-Fas ligand neutralizing antibodies 1 or 2 hours after the induction, the acantholysis start to decrease to definitely disappear 3 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, the Fas ligand is highly present in the sera 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. So 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 and sera and PBMC, thereby blocking disease progression.

Thank you very much, Carlo. It was a very insightful explanation on the mechanism of action. I will address now the question to Tony, 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 the chemical physical terms of our lead product, PC111. Again, as Carlos 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 picomolar level. It has shown a very low immunogenicity in a very well validated in-silico platform and has gotten an optimal saleability, 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 nonhuman primates target. 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 valuable 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, and our monoclonal antibody blocked very effectively blister formation also in this setting. This was achieved adult tested doses with an efficacy of at least 90%. So this in vivo data fully confirmed the previous proof-of-concept data obtained with a 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. And indeed, also in this setting, PC111 dose dependently abrogated cell death in human keratinocytes induced by SJS/TEN serum patients. And 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. And 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 and maybe the same answer for SJS/TEN.

Yes. Thanks, Amir, for the very interesting question. Like Professor Schön mentioned in the very beginning, pemphigus has 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 medium time to achieve remission, which is around 6 months. The therapeutic effect is most of all transitory on -- moreover, the -- 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 and only a small percentage of patients stay free of disease of 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 immune suppressors 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. And this non-immunosuppressive mode of action would allow 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. And by acting as a non-immunosuppressive drug, it is also not -- we would avoid the risk of the strong side effects also associated with the other new immune suppressants currently use as adjuvant therapy to rituximab or steroids. Therefore, we believe that PC111 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 immune suppressors. Next slide, please. If we talk about Stevens-Johnson and toxic epidermal necrolysis, we all know that there are no molecules approved for the disease. There is no current guidelines for the disease. There is no targeted therapy currently under development for SJS/TEN. In addition to withdrawal of the causative drag, hospitalization and supportive care, a number of drugs have been used and are currently used for the treatment of SJS/TEN, including steroid, cyclosporine, IVIG and anti-TNF with controversial results. PC111 prevents keratinocyte apoptosis, skin detachments. 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 this start, not forgetting that we are talking about an acute and deadly disease. So with the non-immunosuppressive mode of action, PC111 will be the first target therapy for this devastating disease. If you talk about 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. So that is why we do not expect any major side effects due to protracted immune suppression as we with rituximab or steroids. In addition, we have preliminary data, in-silico data where we showed that PC111 has very low -- is associated with a very low immunogenicity, that is why we do not expect a decrease efficacy in the long term and in the medium term. So there is -- 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-Fas ligand pathway in the Fas-Fas ligand system, but because this would interfere with T cell activities and with the risk of developing this 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've done -- we won't incur in that risk. And we also have the in vitro evidence that PC111 does not affect T cell apoptosis. So we won't have any risk of lymphoproliferative autoimmune conditions.

All right. So here, we are talking about -- discussing about the using of the new drug candidate PC111. Carlo, can it be used in combination with existing therapies? And 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 and maintain remission without the use of steroids like I mentioned before, but 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. So given the different mode of action, they could be combined and accelerate the therapeutic effect. On the other hand, talking about SJS/TEN, we know again that there's 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 patience in front of you with a strong suspect of SJS/TEN, you, of course, hospitalize them, you remove the culprit drug, you put him under supportive care. But very, very early, you have to administer PC111 that would block Fas ligand, thereby blocking the progression of the disease. But it is -- 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, steroid, 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 time line in the drug development plan of PC111 for pemphigus, SJS and TEN?

Certainly. Thanks, Amir. Actually, we anticipate 2 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 CDA package for the 2 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 3 to 4 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 2-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 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? And 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 SJS/TEN have to involve sites with adequate patients availability in order to meet the time lines 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 advocacies, 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 2 diseases.

Thank you very much. I will shift now to a little bit into the commercial side of things, Tony. We'll stay with you now. And 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 5 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% to 80% after repeated therapy. Why are we focusing on them? Because they are the ones that greater need for an innovative, non-immunosuppressive treatments 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.

The PC111 approved 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 Western World and 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. And 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. Yes. So let's talk about the positioning of this drug. Maybe we switch to how it will be positioned in the market given these 2 -- 3 diseases, tony?

Yes. Certainly. Well, 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? And 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. Well, at this stage, we have developed several scenarios to price PC111 in the target countries present in our business plan, and we have used experienced consulting firms to advise us on this. For pemphigus, a few percentage premiums over the U.S. market price of rituximab have been used as a reference with a range of different percent 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 $0.5 billion 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 $0.5 billion with an upside way over the $1 billion mark.

Amazing. Thank you very much. This sounds really exciting. I'll switch here to Jonathan 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 sublicensing agreements?

Yes. Thanks, Amir. This is really exciting to hear. And 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 a bit. In the past, companies were really focused on the big indications, looking for just some incremental benefits in each disease and showing some improvement in. But going for big diseases because of the big commercial opportunities there, I think now companies are seeing that you can actually go for smaller indications, but achieve a much bigger effect size, actually transformational effect 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. And 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 small opportunity like this is much easier and less expensive for them. So there is a lot of interest in these smaller indications with a big effect size. So 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?

Yes. 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 and TEN really not a lot of or not any approved therapies. And so doing trials, when you're doing a trial with head-to-head against the standard of care in pemphigus may be looking at comparison to rituximab or steroids and in Stevens-Johnson, TEN, really, again, 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. And last question to you, Jonathan. What specific safety consideration should be addressed during the development, particularly given that the drug is non-immunosuppressive?

Yes. I think this is going to be a really important differentiator for this drug. The safety profile, as was described before, 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. So having a target having a drug that is not immunosuppressive and does not -- 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 in 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 the 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.