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

Hello, everybody. Thank you for joining us today for an in-depth exploration of the complex landscape of plaque psoriasis and the innovative use of anti-interleukin-17A/F single-domain antibodies, VHH antibodies for intralesional treatment. I am Amir Reichman, the CEO of Scinai Immunotherapeutics. And together with me is a distinguished panel that will discuss together the significant unmet need in plaque psoriasis treatment and reintroduce us to the innovative approach with anti-interleukin-17 single domain antibody, the unique benefits of local administration, the key stages of development, the uniqueness of single-domain antibodies as such and, of course, the clinical implications for the patients. So a little bit about me. I'm the CEO of Scinai since 2021, located in Israel, here in the headquarters of Scinai in Jerusalem. I served in several global roles in the headquarters of GSK vaccines in Belgium for many years and, prior to that, worked for Novartis in different sites in North America, including Cambridge, Massachusetts and North Carolina, worked also there in different global roles in the biologics, R&D and manufacturing operations. I earned my masters degree in biotechnology engineering from the Ben-Gurion University in Israel and my MBA in Finance and Health Care Management from the Wharton School of the University of Pennsylvania, United States. Together with me here is the Professor Matthias Dobbelstein. Matthias?

Yes. Thanks very much for a kind introduction, and yes, I'm Matthias Dobbelstein. I'm heading the Department of Molecular Oncology here in Göttingen in Germany. I was trained as a medical doctor at Munich, and I then moved to Princeton University to do my postdoctoral stay in tumor virology. After that, I have group-led positions in Marburg, Germany as well as Odense in Denmark and was then appointed full professor here in Göttingen, and I'm also a fellow of the Max Planck Institute of natural sciences here in Göttingen. And couple of years ago, we started this exciting collaboration with my colleague, Dirk Görlich, here in Göttingen at the Max Planck Institute about the development of VHH antibodies, and this also took us to this exciting collaboration with Scinai. And I'm looking forward to talking about this in more detail during this webinar.

Thank you, Matthias. And Professor Michael Schön, please?

Thank you very much, Amir, for having me. My name is Michael Schön. I'm a board-certified dermatologist and immunologist. I reserved my training at the universities of Ulm, Berlin and Düsseldorf in Germany and Harvard Medical School in Boston and has served as a consultant at the University of Magdeburg, Würzburg and now Göttingen. My current position is the Director of the Department of Dermatology, Venerology and Allergology at the University Medical Center of Göttingen, and my primary research interest are chronic inflammation and immune processes governing those diseases.

Quite relevant to the topic today. Thank you very much. It's a pleasure having you, too. Tammy is our distinguished Chief Scientific Officer of Scinai. Tammy, tell us a little bit about yourself a little bit?

Thank you, Amir. I'm the Chief Scientist at Scinai for the last 20 years and immunologist by training. My PhD was at the Weizmann Institute in Israel, and I'm responsible for the preclinical and for the clinical development with a huge experience in vaccine development from Phase I to Phase III and now in immunotherapies.

Thank you, Tammy. So a little bit about Scinai, who is hosting the -- this webinar today, Scinai Immunotherapeutics is a traded company on the NASDAQ under the symbol SCNI. Scinai is a biopharmaceutical company focused on developing inflammation and immunology, I&I, biological products and on providing CDMO services through its Scinai BioServices business unit. Scinai Immunotherapeutics is -- has 2 business units. And the first one is an innovative R&D unit discovering novel VHH antibodies under the research agreement and the exclusive license with the Max Planck Society in Germany and developing those antibodies in its facility in Israel under an exclusive license from the Max Planck and University Medical Center, Göttingen. The second business unit is a drug development service unit, a CDMO, providing services to early-stage biological drug development projects for customers in Israel and now expanding its customer base to Europe and the United States. Our innovative R&D unit is developing, as I've mentioned, VHH antibodies for I&I, and they are derived from alpacas. We will discuss it soon. And those unique features that are coming with these VHH antibodies provide them advantages in manufacturing, costs and efficiencies, cluster drug discovery cycles, superior thermal stability, which translates to longer shelf life and the ability to extend higher storage and transportation temperatures. Our pipeline is composed of antibodies that can treat various diseases, from COVID-19 to psoriasis, asthma, atopic dermatitis and wet macular degeneration. Our next-in-line project is a nanobody, VHH antibody, for the treatment of psoriasis, which will be the topic of this round table discussion. So let's dive in now -- through the introduction of the participants and the topics and the company that is hosting, let's dive to the discussion.

And maybe the first question that we would like or the topics that we'd like to address is the disease, the psoriasis disease, and the unmet market need. So Michael, let's start maybe with you. With so many solutions of biologics, monoclonal antibodies and the new JAK inhibitors now, which fragment of the patient's population is still in need?

Well, thanks, Amir. As you know, psoriasis is a chronic systemic disease, which means that it can basically recur throughout life, and the real cure is not yet possible for that disorder. So accordingly, the level of suffering or the burden of disease of those affected is often very high. Around 2% to 3% of the worldwide population are affected, although, of course, there are some regional and ethnic differences. Worldwide, roughly 125 million people have psoriasis. So having that said, in most patients, psoriasis is a mild disease. However, around 1/3 have moderate to severe psoriasis. And for these, we have a number of systemic treatment options these days. As you have already mentioned, there are several biologics. There are roughly a dozen biologics approved for psoriasis on top of that small molecules. However, these molecules or these very successful treatments still leaves some unmet needs with patients suffering from mild to moderate psoriasis, but they still may have a very high disease burn because they may have affection of highly visible or functional important parts of the body or may not respond adequately to currently available treatments. So patients may have lesions on hard-to-treat areas, location, just like the scalp, the genitals, the palms and the soles of the hand and feet and so on. In addition, there are some unfavorable adverse events of corticosteroids for local treatments in use. And all current biologics are basically for systemic treatment, and there is no real option for local treatment of recalcitant lesions. That's basically why there is still an unmet medical need.

Thank you. That's a very enlighting point. It sounds like there is still quite a lot of need in this segment. Let me think and maybe flip the discussion towards the next point, which is the role of cytokines in psoriasis pathogenesis. Again, Michael, this is still for you. What is the role of IL-17, interleukin 17, in the pathogenesis of plaque psoriasis? And follow-on question on that is why is the IL-17 being considered a better target for treatment of psoriasis versus the, for example, TNF-alpha [indiscernible] and IL-23, which seems to be quite successful?

Well, as you mentioned, I mean, there is quite a few cytokines that have been identified as players in the pathophysiological network of psoriasis. Among these, interleukin 17 can be considered a key cytokine because it influences quite a few or many immune cells and immunological functions. So this is, of course, important for many inflammatory diseases, especially for psoriasis in our case. Among other things, IL-17 is regulated by IL-23. This is one of the reasons why IL-23 inhibition is also an important therapeutic principle. However, there is also IL-23 independent reduction of IL-17 so that IL-17 inhibition is perhaps more specific in some respects. TNF inhibition is another principle but is even broader and, therefore, maybe less specific than IL-17.

Amazing. So what you're saying is, yes, indeed, there is a utility in the usage of both the TNF-alpha blockers and to the IL-23. However, there might be some level of IL-17 still escaping the route of IL-23 and, therefore, still generating the psoriatic response. And that's why 17 antibodies developed by the different companies, for example, Cosentyx that we know from Novartis, we have now Bimzelx from UCB, Taltz and Siliq, all are targeting this unique IL-17 [indiscernible] receptor. And basically, whereas he's saying it's much more specific. Is it -- when you say more specific, does it mean that it's -- we should perceive it as being safer than the more broader or targeting antibodies?

Well, safety data from systemic application of all of these drugs indicate that they are all very safe compared to the older conventional systemic treatments, like methotrexate, cyclosporine, acitretin and so on. But having that said, there are certainly some differences because there are some side effects that may occur, such as a slightly increased risk of infection with all of these. And that also applies to IL 17, although, overall, one has to state that treatment with anti-IL-17 therapeutics are very safe, very effective and that's why they have such a broad place in the market so far.

Interesting. And just maybe last follow-on on this one. I know that there are 2 types of isoforms of the IL-17, the A and F. Could you maybe tell us a little bit about the differences in the roles of these cytokines in the pathogenesis of psoriasis and potentially the interesting opportunity with developing antibodies targeting also the F isoform?

Yes, that's an interesting and actually also very specific question. Indeed, IL-17, in order to function, needs to dimerize. That means 2 parts of the molecules need to come together to interact with the receptor and then transmit the relevant signals to the immune cells. Now there are several isoforms of IL-17 that can dimerize. In our case, 2 IL-17A molecules can dimerize, 2 IL-17F molecules can dimerize or there may be heterodimers consisting of 1 IL-17A and 1 IL-17F. And all these 3 different dimers interact with the same type of receptor and can transmit a signal. Now the affinity to this receptor is much higher with IL-17A. On the other hand, in psoriasis, in particular, the concentration of IL-17F is much higher as compared to IL-17A. So having that said, it is very likely that both isoforms play important roles in the pathogenesis and the pathophysiology of psoriasis. So inhibiting both actually makes a lot of sense, and drugs that target both of these isoforms tend to have a more pronounced effect as compared to those inhibiting only IL-17A.

Thank you very much for these insightful answers. Let me move to the next topic, which is the comparison between a single domain VHH antibody and monoclonal antibody, human monoclonal antibody. And the question is to you, Professor Matthias Dobbelstein. What is a VHH single domain antibody? And how is it different than the monoclonal antibody?

Yes. Thanks for this question, Amir. So VHH antibodies are still antibodies, and they are still monoclonal antibodies, much like the monoclonal antibodies that are still being produced using technologies that were developed in the 70s of the last century. However, we decided to take a different approach to make a more compact kind of antibodies, which we call, as others do, the VHH antibodies. So what they really are is still proteins that bind to an antigen. That's what they have in common with just regular antibodies, and they are monoclonal. So there's just one kind of an amino acid sequence within that VHH antibody. That's what they have in common with regular antibodies. However, whereas regular monoclonal antibodies are typically composed of as many as 4 different chains, 4 different proteins that come together, the VHH antibody is just one peptide chain and its overall size is about 10x lower, 10x smaller than what you find with a regular antibody. So what we feel is that, in many cases, small is beautiful. So that this smaller antibody is more compact, it's more robust, it's more stable. Many of these VHH antibodies, you can actually boil to 95 degrees Celsius then cool down, and they still retain their activities. So they are far more stable. In many cases, they are more robust. And the technology that we use to make them allows us to choose from a very wide range of VHH antibodies, allowing us to select those that retain the utmost affinity. So what we get there is also very strong binders to their antigens. So that's how I would describe those VHH antibodies in the first place.

Amazing, amazing. And so what are the advantages or -- and disadvantages of a VHH single domain antibody in comparison to a monoclonal human antibody or IgG antibody?

Yes. I mean, let me start with the advantages. So the advantages of the VHH antibodies are -- yes, just to summarize again. They are robust. They are stable. They are small. And since they have this simple composition, this just one peptide chain, you can also make them at a larger scale and with lower cost of goods to produce them. Moreover, you can also start being a little creative with these VHH antibodies since you can quite easily fuse them to a different protein. So you can, for instance, make a bi or even trispecific VHH antibodies, and you can fuse them to, say, proteins that would alter the half life, the biological half life of the molecule. So yes, you can also be more creative with them as compared to regular antibodies. So that's what I would consider their main advantages. One disadvantage is -- even though you can overcome it. One disadvantage is that if you simply inject such a small VHH antibody into the vein of the patient, it won't stay very long in the blood. It will be eliminated through the kidney because it goes through something that's called the glomerular filter. And that's something that would make these VHH antibodies more suitable for local administration to the skin, to the lung where we want it. But as such, they are less suitable for systemic application. However, if you still want to use it for a systemic application, what you need to do is to fuse them to something that will prolong the half life. So that's also possible. And in that way, you can overcome that disadvantage.

I got you. Okay. That's very interesting as well. So maybe -- I'm trying here to share -- maybe the moderator can help me -- allow me to share slides. So I wanted to share your slide here about the discovery process of the NanoAbs or the single-domain antibodies. You prepared here a very nice slide that I'd like to share here with everybody. Hope you can see my screen. So that's maybe just to summarize what you just described before. I'll take us through one slide before and basically to demonstrate the differences between the conventional antibody, the IgG, heavy chain only. Do you want anything just to highlight from what you said before looking at this?

You can just compare the size. I mean, if you look at the regular monoclonal antibody that -- what you see here, you have -- I think you have your pointer just there. That's what's derived from humans. You see these 4 chains. And then you just compare it with a single domain antibody, and you can appreciate already that its composition is not only small, it's also simpler and that's why it's easier to work with it.

So basically, not only that you are using the heavy chain only antibody, you are actually cleaving the variable heavy chain part, right, from here -- but if you see...

That's correct. Yes. We are kind of cleaving it or actually what we really do is to just clone the coding region for only this VH1 domain into an expression construct that allows us to make this in bacteria. I should add that this is something that would not be possible without the collaboration with our partners at the Max Planck Institute. You had our colleague on the previous slide, Dirk Görlich, who actually -- who is heading the group who is making these VHH antibodies. But yes, you asked me about how they are made, and I think that's on the -- that's -- yes, that's here on this slide. So what the animals that we need to identify such VHH antibodies in the first place are alpacas, more generally, they are [ camelates ] or camel-like animals, since they have this property that they can make such antibodies that only consist of the heavy chain, as we call it, but not the light chain. And what we do with these animals is to just vaccinate them and draw blood from then. So we treat them very well. It's -- what they get is the same as what most of us got for a COVID vaccination, for instance. That is a vaccination with the antigen. In this case, this was antigens derived from interleukin 17. And a few weeks later, you draw blood from these animals. And that's it. After that, you can send them back to the flock. And with the blood, what you do is you isolate what's called the B cells, the cells that encode antibodies. And from these B-cells, you extract the DNA and you amplify with a technology called polymerase chain reaction. You amplify those regions in the DNA that encode the -- this VH1 domain, the antigen-binding domain of such single chain antibodies. This then goes to bacterial phages, that's viruses that can infect bacteria, and those bacterial phages then make the single-chain antibody and bind to the antigen, in our case, IL-17. And this allows us to select from a library of many as 100 million different VHH antibodies, 10 to the power of 8, 100 million antibodies to select the very best binders. And those we would then transfer to bacteria, express them, meaning that the bacteria would make the VHH antibody that we are desiring. We can sequence it. We can produce it, upscale it and then test their ability to neutralize the antigen, in our case, to neutralize interleukin 17. That's basically how these VHH antibodies are made.

Amazing. So let me maybe go back to the questions I had before, and these are -- how we make them now is clear. So then last question for you, Matthias, is what is then the opportunity using NanoAbs or VHH single-domain antibodies for the treatment of psoriasis?

Yes. I think we can answer this jointly, if you want. But my take of it is that due to the ease of production and due to the robustness of these nanobodies or these VHH antibodies, we have a chance to apply them locally, to apply them not in a systemic fashion, which would shrink the toxicities that are almost inevitable, but rather apply them just where they are needed. And that's on the psoriatic lesion. And that's the major advantage of them as compared to the systemically applied monoclonal antibodies.

Thank you much. And Professor Schön, how do you see -- what got you attracted with this new potential innovative or novel use of VHH single-domain antibodies for the local treatment of psoriasis?

In that case, we will have a chance of really individually targeting single lesions that are recalcitrant to other treatments or difficult to treat and still pathogenesis-oriented therapeutic approach rather than the very broad approach with all the side effects that, for example, topical corticosteroids would have. So that is an exciting and promising development.

Okay. And Tammy, then you're the -- our Chief Scientific Officer for Scinai. So tell us a little bit about the product you are in charge of developing, describe a little bit about the target product profile of Scinai's anti-interleukin-17 single-domain VHH antibody.

Thank you, Amir for this question. So eventually, we're planning to have these VHH antibodies as -- in a pen for injection. When possible, it will be self-injection, and people will use it intralesionally and will have the opportunity to have a biological drug, even though they have a mild disease and, usually, they are eligible to have only corticosteroid therapy and phototherapy. Maybe the other professor can tell more what are the limitations of this therapy. But we know that the most effective one is the biological, and this is what patients really want. We plan to apply this therapy for the mild to moderate patients suffering from lesion located in areas that are -- sorry, that generate high disease burden for them. It can be on the face, on the scalp. These people are even cannot smear corticosteroid or have a phototherapy in these areas, and also the hand, the feet, and they are seeking for a better solution. We will be able to provide them a solution that is not -- doesn't need a daily therapy, unlike this -- the phototherapy and the corticosteroids because we showed in the preclinical studies, at least, that we can give the therapy and see the effect for a long time.

Brilliant. So again, I happen to have a slide here that can help. For me, it's really astonishing to see the percentage of patients suffering from mild psoriasis. And so it goes back to what Professor Schön talked about before about the classification of mild to moderate, et cetera, and we have this slide here that talks about the current plaque psoriasis treatments. I go back to you, Michael Schön. You mentioned before briefly about the corticosteroids and the phototherapy and their potential limitations in treatment. Could you maybe expand on that? Just to explain the need in this patient category.

Certainly. Thinking of corticosteroids, they have a very broad immunosuppressing effect -- immunosuppressive effect, and they're actually in the market for decades now. However, the flip side of that coin is that they have long-term side effects. They make the skin more vulnerable. They lead to skin atrophy. So you cannot just use them for any period of time. Similar limitations apply to phototherapy. Sometimes, it's just practical reasons for patients to not be able to use phototherapy because they have to be applied 20 to 30 times, 3 to 4 times a week. And you cannot do this indefinitely because phototherapy increases, for example, the risk of skin cancer and skin aging. So there still is a need for alternatives. And a pathogenesis-oriented approach, such as the local modulation of key cytokines such as IL-17, promises to be very advantageous to those patients.

Interesting. And so many times, we -- I even have somebody that I know that just recently came back from a treatment of psoriasis, and she was given, in addition to the phototherapy and corticosteroids, some systemic immunosuppressants. I think methotrexate was the one that is kind of all over the world is prescribed. She didn't really like it, but that -- these are kind of generic drugs. What are the limitations in use of these immunosuppressant drugs?

Well, methotrexate certainly is a classical systemic treatment for psoriasis and also associated disorders, such as psoriatic arthritis, again, also for decades. However, it also has a long-term immunosuppressive effect. It can have adverse effects, for example, on liver functions. So you need to watch out for those. In general, however, methotrexate is a systemic treatment that is reasonably well tolerated.

Okay. And so what -- tell us a little bit about the decision-making of a physician. You are a dermatologist in practice, and you see patients, right? You see patients suffering from psoriasis in your clinic and...

Yes.

So tell us a little bit about the line of thinking. Okay, here is a patient that already got corticosteroids, phototherapy, methotrexate. What makes you suggest to a patient, "You know what? You should consider going to the second-line systemic immunomodulators, such as Sotyktu, the JAK inhibitors or even moving to the injectable biologics? Could you maybe talk a little bit about the considerations and how you decide when to apply the -- and recommend this therapeutic agents?

Sure. So there's 2 major fields to be considered. One is the individual situation of the patient. So what is the nature of his or her disease? What is the area of body surface affected? What is the burden of disease? How chronic is the disease? How inflamed are the lesions and so on? What comorbid diseases do we detect, such as cardiovascular diseases, gastrointestinal diseases? Is there arthritis? Are there any other medications that could interfere? So this is a patient individual basis for making this decision. And of course, you also have to make a shared decision with your patients. So what is most feasible for your patient? Would he or she rather take a pill? Would he or she rather have an injection every few weeks or so on? The second area that is important for making the decision is the current approval status of the therapeutics. So is it a first-line treatment? What other costs that is also important in many countries, such as many European countries? And based on all these different factors, you come up with a decision that you make together with your patient and then find the most suitable treatment for him or her.

Okay. Very well. So this is very insightful. Thank you, everybody, for that. Let me maybe suggest that we move to the next topic. Tammy, this one is for you and for Professor Matthias Dobbelstein. The topic is drug development and drug development stages. So tell us a little bit about the various stages of drug development required to prove that a drug is effective and safe for use so that the clinical trials can commence, whoever wants to go first, tammy or?

Maybe I start because we of -- I can describe is the more basic part of the development. It's not enough to just select some VHH antibodies that happen to bind, in our case, IL-17. We took great care that it would, first of all, bind not just to the IL-17A, but also to IL-17F, which were the 2 different kinds of interleukin 17 that Michael has been talking about before. So we selected a VHH antibody that binds both of them and not only binds them, but it neutralizes. So the first step was then to make sure that it really interferes with the activity of these interleukins and that it prevents them from binding to their receptor. So that was the first part. Then it was important to look at the stability of this VHH antibody, as mentioned before. You can actually boil it and still retain the activity, which makes it much easier later on to produce it, to store it. So that's something that we had to make sure. And thirdly, the -- we had to make sure that it produces in large amounts so that we could also make sure that, ultimately, we would be able to make kilogram amounts of this. And that also turned out to be possible. And I think that's now the point where I hand over to Tammy, who took care of the VHH antibodies from this point.

Yes. So talking generally about the drug development, we have the in-vitro and then ex-vivo and in-vivo study that showed the efficacy and the safety and the potential of the drug to be a real drug. So Matthias mentioned the neutralization, the high affinity, the stability of the VHH antibody that was already shown in the work done in his own lab and the Max Planck institute by Professor Görlich. And then we receive these VHH antibodies and presented the ex-vivo and the in-vivo study. In the ex-vivo study, we use human skin samples that psoriasis was induced in them. And then just wanted to show that it really works, that the local administration is effective in treating the disease. We -- at that time, we had...

Sorry. Let me maybe jump into your words, apologies. Maybe before delving into the specific activities done by Scinai, maybe I found on the -- very interesting, we have on our Internet website kind of a Gantt that explains the horizon of -- or the Gantt chart that, high level, describes the drug development. So before going into what we did in Scinai, maybe just walk through the different stages that are required for the development of the drug before it can go into the clinic. I would say clinic is already -- yes, clinical trials is stage #8 here on the graph.

Okay, very well. So every drug begins with a bright idea of the inventor, and this is the molecular clone selection. In our case, it was the VHH antibodies that were identified and selected according to Scinai's request for a collaborator to find an antibody for IL-17A and F. Next, in lab scale, you have to show that the molecule really works, that it is being able to produce, that you have a strain that is effective and you have to develop all the analytical essay to confirm that what you produce is really what you initially plan to have. And then this is described also in the CMC section. You have to develop the upstream, the downstream to upscale it and make sure that it still have the same characteristics that were initially developed in the small scale. When you have the molecule, then you go to the preclinical evaluation, which I just mentioned, the in-vitro, ex-vivo and in-vivo studies. And then the last stage of the preclinical is the toxicology confirmation. You make sure that your drug don't cause any adverse event, doesn't damage any tissue in the -- still, in an animal model that is relevant. And when everything is positive and then you have to present your data to the regulator and you get permission to go for a clinical trial. The regulator is really very strict in their requirement. You have to show that it is both effective, that you're not just using people to -- something that is not going to be of advantage for them and then tech transfer, where needed. In our case, we plan to have the manufacturing of the VHH antibodies in our own facility. And then you initiate the clinical trials, Phase I, Phase II and Phase III. I think it is an opportunity for us to tell that we met with the Paul-Ehrlich-Institute scientific advice earlier this year, and they allowed us to skip the healthy volunteers stage, which is usually mandatory, and to go directly to patient and see already in the first trial that our drug is both safe and, hopefully, effective.

So Tammy, maybe now I'll jump into slides that describe what you just started to explain before about the specific attempts conducted in the development of those unique single-domain VHH antibodies developed between Max Planck and UMG and pursuing the drug development pathway, their development to become one day potentially a therapeutic drug. So what do we see here on this graph and slide, please?

This is the ex-vivo study that we conducted also earlier this year. In this study, we take human skin samples and grow them in a dish. We then treat the skin, which is a psoriatic skin, with the current standard of care, with betamethasone and with secukinumab, the monoclonal antibody, against IL-17A and also with 2 different doses of our own VHH antibodies, which is given once and also daily for 3 days. We then evaluated the IL-17A concentration in the medium, which is mimicking the concentration in the blood, and we can see here that the untreated healthy skin have very low concentration of IL-17. In a psoriatic skin, we have a very high level of these cytokines. And then we can look at the different treatments. Both betamethasone and secukinumab significantly reduced the content of IL-17 in the medium -- or in the blood. But when we treated with our own VHH antibody, we'll see that the level of IL-17 was even lower than that of this standard therapies, and this was very encouraging for us. It was especially important for us to still -- even one dose was sufficient to reduce the IL-17 levels. We know that the VHH antibody remains in the skin for a limited time. And we still see, after 3 days, that the IL-17 levels remain very low and significantly lower than those shown in the other treatment. In this study, we...

Sorry, sorry. Just -- we apologize. It's so exciting, but we also have some time limitations here. And I really want to see maybe some explanation on the recent exciting in-vivo study that you managed. So let me push forward to this area, please?

When having these exciting ex-vivo studies, we move forward to the next proof-of-concept study in animals. I'm saying animal, but actually, the study was not -- was done in SCID mice that were transplanted with human skin. Being a SCID mice mean that they do not have an immune system that can reject the human skin, and you can actually see the piece of skin from a human transplanted on the back of this mice and having appearance of the psoriasis, which is induced by injecting of white blood cells into these skin transplants. Next, we have the treatment session, and we have, for 3 weeks, treated the animals or the human skin and grafts with either negative control, which is an irrelevant VHH antibodies, or with the standard of care, the secukinumab and betamethasone or with our own VHH antibodies. Here, we used quite a low dose that was given either every day or once a week or just once. The objective of the study was to make sure that we understand the mechanism of action of this VHH antibodies. At that time, we didn't know if we have to have a continuous exposure of the body of the dermis to the VHH antibodies or maybe it is sufficient to have it just once a week and will still cause the blocking of the psoriatic cascades. And we got very clear replies to these questions. I think that the next slide shows how it really looks. In the bottom of the slide, we can see a negative control on the left side. We can see the scales. I think Matthias or Michael can tell exactly what we really see here and how it is related to [ flock ] size. But anyone that knows how psoriasis looks, this is the way it is. When looking at the samples treated with secukinumab and also with our VHH antibodies administered once a week, we can see that the scale disappear. The skin looks healthy, clean and like a normal one. We also look at the histopathologic. I'll go back to the previous one. We also looked at histopathological sections of this skin, and we see the IL-17 and IL-17A and IL-17F expression in this sample in the red, squares on the left with the vehicle, we see that there is IL-17A and IL-17F in the negative control in the vehicle sample, but not in those treated with the various treatment for the IL-17A. It's very nice to see that for the IL-17F, we do see the IL-17F in the samples treated with Cosentyx, which is specific only to the A. Whereas in the sample treated with our VHH antibody, we can see that both IL-17A and IL-17F are not there. We then look for different psoriasis markers that I will not go into the exact detail what each and every one of them is doing in the psoriasis. But generally, there are markers that are relevant to inflammation, to keratinocytes. And we feel that in all these samples, there is no significant difference between the sample treated with the VHH antibodies, which is on the right side, and the standard therapies, the secukinumab and the betamethasone. So this is very encouraging. It is also important to tell that we treated the human skin samples for 3 times. Sorry. We treated the animals for a limited time. We know that at the end of this time, the VHH antibody already disappears from the skin. And still, we could see 2 weeks later that there is an effect, and the markers are very low. The skin looks much better. And we proved the concept that local administration of biological drug can solve the burden caused by psoriasis.

Okay. Thank you very much, Tammy, for giving this review of that. Maybe tell us a little bit more now, between the 3 of you, what do we see as potential future use of -- or future plans for -- maybe start with you, Tammy. What are the future plans for Scinai with regards to the development -- further development of these NanoAbs targeting interleukin 17A/F for the treatment of mild to moderate psoriasis?

In the study that I just presented, we look for the efficacy 2 weeks after the last administration. But having the nice results, we would like to push it further and see maybe we can see efficacy for a longer period of time. So now we are going to repeat this same study and also evaluate a higher dose of the VHH antibodies and follow the skin samples on this mice for 2 months. We will then know what is the duration of the effect and how far we can expect to see the healing of these therapies. Next, we'll have to do the toxicology, which is mandatory before going to clinical trial. And by the end of next year, we are going to be ready and maybe even initiate the first-in-human trial. This is going to be a really exciting milestone for our team.

Absolutely. Maybe just on the next part. Before -- so I have 2 last questions. One is for you, Professor Schön. One of the things people ask me is how do you know that patients will tolerate the pain that might be associated with the intradermal injection of VHH antibodies. What do you think Scinai needs to do to mitigate this risk? And is this risk massive? Or do you think that there is a motivation from the psoriatic -- from those patients suffering from these psoriatic lesions located in specific areas that will say, okay, if it's only a little bit of a pain, it's nothing? What's the -- what do you think is going to be the patient thinking or sentiment towards such a solution?

You're mute again.

Yes. You're right, unmuted. The question of acceptance by the patients is certainly a very important one, and I certainly agree that it will take a lot of research to minimize the local pain. But having that said, my assumption would be that very fine needles that reach only the uppermost layers of the dermis, which is the connective tissue within the skin, just underneath the epidermis, will go along with very little, if any, pain. So my expectation would be that, if we could manage that, the acceptance will be very high among the patients, especially since you can come up with a means to specifically treat individual lesions that are not otherwise accessible in these patients. So my expectation, with all due caution, of course, would be that the acceptance will be there.

Okay. And maybe next and last one is for you, Matthias Dobbelstein. Tell us, you are -- together with Professor Görlich, you are also responsible on development of the future pipeline that is under the -- covered in the research collaboration agreement between Max Planck, UMG and Scinai. Tell us a little bit more about the future things that are upcoming in the pipe.

Yes. I mean, we are in the process and we have actually developed VHH antibodies against additional cytokines that also act as mediators of inflammation. So the idea is always to dampen excessive inflammation that would otherwise cause disease. So those include VHH antibodies to cytokines called interleukin 4, interleukin 13, TSLP. Those are examples of new targets that we actually have developed VHH antibodies against. And the hope is that this will also broaden the range of indications, the range of diseases that can be treated in that way. One obvious target would be atopic dermatitis, if you talk about skin diseases. But something less obvious that seems very attractive to me, too, is to try and treat lung diseases with that. What we have recently published, actually, is the VHH antibody to SARS-COVID-2, to the virus that causes COVID-19. And we would put this VHH antibody into an aerosol, into small droplets, and those droplets would then be inhaled by animals. And we achieved protection of hamsters against COVID-19 in that way. Now the dream is that we would do the same thing with VHH antibodies targeting cytokines, targeting interleukins. And this would then be a way to treat diseases like asthma, for instance, because again, you dampen the inflammatory reaction that you would otherwise observe in the lung. So on top of treating skin diseases, I think treating lung diseases by inhaled VHH antibodies, that's another strong prospective that I see for the future developments.

Exciting. So I think with that, we will adjourn for today. And I would like to thank everybody for coming and participating and contributing your amazing know-how, experience and insights. So thank you, Matthias. Thank you, Michael. Thank you, Tammy. For additional information, please do not hesitate to go to our website, which is www.scinai.com. There, you can find lots of information. You can also contact us through [email protected]. And that's it. With that, we here from Jerusalem, I -- it is Amir Reichman, CEO of Scinai Immunotherapeutics, thank you very much.