I have worked with Aptahem for almost 10 years, supporting management with primarily communication and IR activities. The purpose of this webinar is to provide an overview of Aptahem's strategic direction, ongoing preparations for a planned U.S. listing, and recent key regulatory developments. Some practical information: CEO Michael Lindström will start by giving his presentation. After the presentation, we will answer the questions that you send us during the event. You can send your questions via Questions & Answers, which you find to the right on your screen. You will not be able to ask questions verbally. The webinar will be recorded and published on our website and social media channels. With that, I hand over to you, Michael. Thank you so much, Erika, and welcome everyone. As Erika said, I'm Michael Lindström, I'm the CEO of Aptahem, and I'm also a co-founder of the company. Today, I'm going to talk about the horrors of sepsis and how we could approach making a better world for those who actually get struck by sepsis. I will also present a little about the company, the lead candidate that we have for our approach to curing, or at least making better for those who get sepsis, a little forward-moving where we are going, and what we have done also, a little backwards. Let's start with actually the big thing that... Did you switch, by the way, Erika? Or I did it? OK. Sorry about that. OK, sepsis. I just spoke about that. Here is something that we should look very carefully at: 50 million people per year get sepsis. 20% of those die. That is extreme. I will come back to this with further slides ahead of us. It's one of the most frequent causes of death in the world. If we look here, 2020, as I just mentioned, 20% were hit by sepsis and died. That means 20% of those 50 million were hit by this. Sepsis is such a situation that there are no real direct cures. There are a lot of different remedies to treat those who get struck by sepsis, but it's also about the timing, luck, and other things that you will soon see on the next slides coming up. The problem is that it also puts a big burden on society, a socio-economic burden. You can lose a loved one, a working comrade, and also treatment and the longevity, if you have the luck to survive, cost a lot of money. In approximately around terms, $30,000 for a treatment. It could be more depending on the hospitalization. Here we have a few scenarios. We call it the phase of sepsis. If you look to the far left, this is something that could happen. You have a really evil infection that goes septic. That means you start to see tissue breakdown. That's what you see here to the left. That's just the beginning. If you then look at the mid-picture, I will come back to that because it's actually a video which we will soon show you, is the effect. If you are a lucky, unlucky patient for sepsis, it can end up with amputations, or you die, or you manage to survive anyway. What you can see here in the picture of this young woman in the middle is that you can also have severe organ damage and other things. Mostly those lead to death, but you can also go through that without dying. You have severe aftermath of such things. We have an example where you are lucky or you had good treatment, you come in at a good time, and that is the well-known Madonna. She got struck by sepsis, and she managed to pull through. You know, 80% survived. How many are actually surviving in the case of the mid-part here? I would like Erika to just show a short video on that young woman, what she's going through. Please do that. It wasn't obvious that I had something life-threatening that was about to occur. I had what felt like a cold. I thought it was just general end-of-term kind of sickness. I do sometimes worry what could have happened had my housemate not seen that my light was still on and that I was awake in the middle of the night, as when I did end up in A&E, things took a turn for the worse quite rapidly. It's amazing what you've achieved in such a short time. Thank you, Jason. This is life for Lily now, learning how to complete simple tasks as a quadruple amputee after contracting mening. Thank you. We can go back to the presentation, please. Thank you, Erika. Here's an example, as I just mentioned, where you survived, but with a huge handicap to come from that one. You know, this is no secret why they call it the silent death. Where's the presentation? Did it disappear? I can't see the presentation, I'm afraid. Thank you so much. As I just was saying, it's no secret that you call it the silent death. I mean, as she mentioned here, she wasn't aware of what would happen. It can take such an easy thing like poking your nose with a dirty finger and get a bacterial infection there. That can lead to something like an infection of some sort. You get a little fever, this and that. Just out of the blue, you can be hit by a very severe infection response in your body if your immune system is not there to protect you. That's what happened with her. That happened to some other people as well, hence all the deaths we have. With that, let's go on to see why is sepsis not top-ranked? Here we have the World Health Organization again showing the 10 biggest death reasons in the world. If you look to the left, you see 68 million in 2021 died. That's, of course, probably added a little from the COVID situation. Here you see the 10 top causes of death. As you can see, they are relating to 57% of all deaths, which shows us 11 million deaths per year. Putting that in the context of that ischemic heart disease, which is top, are 9 million deaths per year. That gives some strange thinking, at least for us at Aptahem and others too, I would guess. I will come to that in the next slide and explain how sepsis actually is hidden in many different sickness conditions. Here we have it. You recognize the list or the 10 biggest, as we had in the previous slide. Here you can see how these are relating to sepsis or can give sepsis. As you see here, there are different reasons. I will not go through everything, but there are always situations with these conditions that may lead to sepsis, as you can see from these different. If I just take a few examples, if you look in the middle, this is with oxygen imbalance when it comes to ischemic heart disease leading to inflammatory response. The body reacts very bad if it doesn't have oxygen enough. That means it can start to damage the tissue. The tissue is dissolved because you need oxygen to keep your tissue as well as your organs in good condition. This is where it all can start. Of course, there are stuff and reasons, and pneumonia is a very common reason. It's a bacterial pneumonia, for example, that also leads to deficiency in oxygen uptake, which leads then to a tissue breakdown. That goes into a spiral where you have tougher and tougher to breathe. That could also extend into a septic condition. There are many different reasons here when it comes to sensitive organs like the lungs, the only open organ in our bodies, but also kidneys, which are extremely sensitive. As I mentioned in the beginning, I will bring this forward to where we are going with the company for the next study. That means patient studies, phase 2. I will come back to that a few slides down. There are many reasons from these top 10 that can lead to a septic condition. That is also something not many people know, but we should be aware about that. What do we have in one in Aptahem? It's our lead candidate. It's an RNA aptamer. An aptamer is an oligo. An oligo is something that is coming more and more in our surrounding world when it comes to treatments. You have heard about AOCs, perhaps, and there's the O in the oligos. Oligos are getting more and more traction into the medical, the therapeutic industry. Back to Aptahem. We have a novel mechanism. What does it mean? Because Aptahem goes into our target protein, in this case, thrombin. It binds on thrombin, which is the driving force mechanism or protein that is signaling at an adverse effect with an inflammatory response in the body. That is massively fallout. Here we can dock on with Aptahem to a very specific point called exosite 2 or the heparin binding motif, which is also called. What's so special with Aptahem when it binds to thrombin is that it only binds to one point, only one place, and that's the exosite 2. Other drugs out there may bind to other places on thrombin. Those usually lead to side effects. The most common side effect, which is other drugs, which usually could be an anticoagulant, leads to a bleeding side effect. Because we don't bind to these other sites, we avoid having these side effects because we keep the blood system, the homeostasis, at a very good level. It doesn't get imbalanced, which happens at the septic condition. Also, downstream from thrombin, we affect signaling on something called the platelet activation. There we have the key to stop the inflammatory response in the body, especially when in sepsis, you have this, what we call cytokine storm. It's a total rolling inflammatory response, and the body cannot really respond to that. The own immune system doesn't know really what to do and gets confused, and then it rolls over. That's what we see we could actually put a hampering to and also regulate. We'll come back to that later. That's about Aptahem, our lead candidate. We have done a lot of investigations with Aptahem. First, we did the preclinical studies, and we did loads of preclinical studies. Being a new kind of modality and also doing things that no one's seen before had us do a lot of preclinical studies. There were comparative studies, there were different models, there was also a lot of benchmarking. I already mentioned something that I will bring forward further down the line here. If we look at this, we've done a lot of sepsis models or sepsis-like models, and we could see how we could improve survival enormously at some settings. We could dampen the inflammatory response, we could counterbalance the coagulation system and homeostasis. We could also stimulate the body's own immune system to get it up to a level, actually above the levels what you would see it could do by itself without the stimulation of Aptahem, which is fantastic. If you look to the left here, you see we have done something called RDS studies. RDS is acute respiratory distress syndrome. It happens when you have a very severe lung infection of some sort. In this case, it was not bacteria we worked with, we worked with a viral. That means we have introduced a virus. We could see how we could improve the situation for those who got Aptahem. In this case, we have a maintained or healthier lung tissue. One of the most important things, and I mentioned it before, is that we could maintain a good oxygen pressure or oxygen delivery to the tissue. That is key in this case. Just to mention something is that within the care today in sepsis, they make sure to try to maintain a good blood pressure, which is not always, of course, possible when all your vascular leaking because of the tissues breaking down. We can stay with that. We could see that we could maintain a good blood pressure. We've seen in all our studies that we have been maintaining in these study models. Key to keep a healthy tissue or healthy organs. We did these thrombosis models where we compare to different anticoagulants out there or antithrombotic agents. What was significant for these studies, all kinds of different ones, and I will show you on a slide further down, is that in comparison or benchmark testing, we could see that we do not have this bleeding side effect, and we also have a very pronounced antithrombotic effect. That means if it's overclotting the system, that could lead to a stop in the vascular, we could reduce those, we could also stop further clotting. Both reducing the thrombosis and also reducing and stopping them. That's quite a very strong feature without the common side effect. If we go over to the right side, we also did a first-in-man study, which we called the phase 1 study. That was done with our Dutch collaborators. That felt very good out of safety, and we could see no side effects there. During that study, a very specific thing happened that one of the healthy volunteers actually came in and had a moderate viral infection. That's not supposed to be a healthy individual, but in this case, this person slipped through. Anyway, the positive thing here is that we could see Aptahem have an effect within eight hours, doing exactly what we have seen in our other models at beforehand and during preclinical studies, which was a very good and encouraging result for us. Even if it just was one, it just followed the same pathway and way in the human as we've seen from the preclinical studies. Very encouraging indeed. That has, of course, helped us now when we have put up the preliminary phase 2 study program. I will come back to that a little later. Talking about that, I think we go on to the next one. I just talk about that. What will we do in phase 2 studies? We have did an extremely due diligent investigation on this, given the results we had in preclinic and the encouraging result we had in phase 1 study, together with our medical experts and other experts in the field. We're homing in here on sickness situations. If we relate to the first slides that you look at and the 10 biggest, here we have some of them, maybe more to the point indications. Of this indication, you can see kidney, you could see pulmonary, I mean from the lungs, and so forth. Different situations that emanate from what you've seen from these top 10 few slides before this one. This, of course, has to go through regulatory authorities before we can see what is doable or not and present our study protocols that we have then produced as a study protocol for these phase 2 studies. It remains to be seen. All these ones are in the field of leading to sepsis or it could happen during sepsis, so they're all relevant. Again, I ask you to think about these top 10 that we just spoke about a few slides about. Also in this one, just for a regulatory standpoint of things when it comes to the authorities, is that there are both orphan indications here as regular indications. What we are looking here is to have as speedy as possible a forward-moving study to save time and money. We, of course, want to reach the market as soon as possible. That will also be a very important part when you judge what to choose and what to go forward with in phase 2 studies next to come. With that said, coming back to the industry, where are we? Do we have big sales? Yes, we have enormous sales, and not to us, but in this field of drugs used in sepsis. If we start looking at the left side, you see here the global market for aptamers. I will say this will be updated soon because it's really increasing. As I said, aptamers are part of the oligo industry. This is very important to remember that this is really booming at the moment. Anyway, if you look at the right side, these are one of the benchmark drugs that we tested against: heparin, bivalirudin, and rivaroxaban, very well known. Please note this, the mid one, bivalirudin. We did a benchmark testing against that. You can see how much money it generates per year. Of course, gaining interest to take this all the way to market, you need to have some kind of market potential. There definitely is. Coming back to bivalirudin, we did benchmarking, and we could see that our drug was absolutely superior to this one in those tests we did, and also without the side effects because bivalirudin has side effects. This is something we will not talk about today. Please remember that so far, we have not seen any side effects with aptamer. That's a good start for the next step we're going to take with phase 2 studies. Anyway, I just talk about phase 2, and you see that on the far right. This is a little overview of what we have done and where we are going. I just talked about preclinical before. A lot of preclinical studies we have done, and it resulted in a few very strong publications and collaborations around the world. We've done the phase 1 with that interesting results that we didn't plan, of course. Now we have started planning to take ourselves to the U.S. Why are we doing that? We see there an opportunity to be valued, as we would love to be, and also tap into the bioindustry there, the regulatory industry, and the big need for new remedies. The U.S. is right now flagging up quite a lot for doing something good in this way. One of these things, or two of these things, you see below in the smaller mid rings, they're FDA pre-check and the CNPV pilot program. I will not talk so much about them here. I will have a slide later about those. These are incitaments to actually accelerate development in the U.S. and speed up drugs to the market and so forth. We just also did an IPA expansion. I will come back to that soon as well. Right now, the most important is that we're building a case to comply with U.S. needs to make an introduction to the U.S. stock market with Aptahem. By that, hopefully, be valued, as I just mentioned at the beginning, in a way so we can raise the capital to run the phase 2 studies and also expand our program because we have a lot of ideas and fantastic indications in many other ways that I can't disclose today. That's something we would like to expand on and build a company from there. With that said, short, I will not go through everything. I just mentioned these different FDA incitaments. Again, they are to speed up things, to make shorter time with the regulatory so you can get into your testing and also go to the market faster. The one to the left is the FDA pre-check program. It's about manufacturing. U.S. wants to secure manufacturing in the country. As such, they have now released this possibility to apply for speedier treatment of your manufacturing. This is two strong things to watch for Aptahem because with our incitament to going to the U.S., there have been a first round of announcements who got these pre-checks. We were not in it, but it also will continue. It's not stopped there. We are still hopeful that it will happen something in front of us. Of course, we will report that when we know where we are with these programs. I mentioned the patent. On the side of this, my co-founder, Dr. Luiza Jedlina, who is the lead of this program and the development of Aptahem and brought it forward today, has during quite some time now investigated and looked at the mechanism, looked at our results, did a lot of partnering, not partnering, but collaboration studies, and have found that we could see an even broader application for Aptahem, which we now want to secure the protection of. Hence, we did a U.S. provisional patent application earlier this autumn to secure some other indications. One of these, a few of these you see here, neurodegenerative diseases like Alzheimer's, for example, viral infections, cancer, fibrotic diseases. There is a lot of where we can see that the mechanism and the target of Aptahem would have a great and big impact on these different disease indications. This is broadening the previous patent in the patent family of Aptahem, patent family two, where we have then a use patent and indications of Aptahem. This is just to secure a few more indications, which is really interesting and that we are working hard on moving forward on. This will be very exciting to come. We do think so. We're talking about the U.S. Just to see where could we be given what we are doing and what we are heading for sepsis and the candidate we have, here's a few examples of U.S.-listed companies. I think the interesting part is actually what you see on the far right side, their market caps. These are, of course, market caps that we are not today. I come back to what I said before, Aptahem undervalued? Yes, we would say so. We think so. It remains to be seen, of course, but we are working hard on creating a good and compliant bag of company goodies to bring forward to U.S. investors and do that step into the U.S. market and being listed in the U.S. That's what we have to look for. A little about the team. This is the management and board. I just mentioned Dr. Luiza Jedlina there. She has been key and instrumental in bringing us forward when it comes to technology. Ola here, our financial guy, has been with us since the beginning, actually. Penelin, very seasoned and skilled MD, done a lot of things when it comes to clinical studies, been a good collaborator with our CSO, Dr. Luiza Jedlina, going forward with the synopsis, the planned study package for phase 2. Thomas Rupp below, he's a world-leading expert in oligos in the aptamer world. He's been really key for us to take us where we are today. We would say we are leading in manufacturing that type of oligonucleotides or RNA aptamers that we have. We also have a seasoned board that you can see to the right. I'm there right now. We are, of course, looking at skilled people all the time. We are a small semi-virtual company, and we have a lot of collaborations. We have consultants that we tap in from time to time. Our network is extremely wide, and it goes global to tap into. Looking forward, it will be really exciting to continue working with these fine individuals. As a final slide, current focus, I've been talking about it a little, but I will give some more information. Right now, talking about financial, and that's moving towards the U.S. and the compliance with the U.S. needs that comes to auditing. We are right now changing our system to what is called IFRS accounting standards. That is an ongoing thing, and we have come some distance. We are almost there, I would say so. We are also doing this to prepare our U.S. auditor, which is mandatory to be compliant with the U.S. investor interest and analytic diligence that will be done on us. Operational, yes, we are on the field working on partnership and so forth and keeping ourselves visual out there. We just came back from BioJapan, intense trip. We had a lot of follow-ups, took some good time to deliver the material to them, and we have really nice interest. Something I will need to come back to later, of course, if it turns out to be more hot, so to say. I'm going from down and up, of course. Communication with prospective U.S. investors. We have an ongoing dialogue or dialogues, we would say, with different investors. They are, of course, dependent on that we deliver on the compliance needs when it comes to the auditing. That's key in this whole thing. This is why we're working so hard with that. We also have a legal counsel and advisors for going to the U.S. that have done it several times more than just this time and have great experience doing this. All in all, we are full head focused on the U.S., but we're also working on our current dialogues and partnership as well as investors' side of things. We feel very strengthened, and we had very good feedback lately, as I just said. BioJapan was one of those, and we hope that will continue now in BioEurope. I will come back to you guys as we move forward and deliver those milestones we need to deliver on, especially to be compliant to go to the U.S. with Aptahem. With that, I thank you very much for your attention. I leave back the floor to Erika for the questions and answers. Yes, I can see that we have a question coming in. Let me see if I share or I will click on the. I can answer. I see it actually from here. Here we go. Yeah, there you go. Yeah, there it is. Why is the U.S. listing a better alternative than raising capital in Sweden or the EU? We have been around now for more than 11 years, and we see that the financial climate for us and also the valuation we have here is not going to do it for us when it comes to the capital need for making phase 2. We also see that the U.S. is very vibrant right now and wants to make a lot of things happen. I just explained for you these different programs that have been announced and that we have been part of applying to. We do believe we can reach a better valuation in the US. There is a very healthy climate when it comes to investment in the bio area, pharma bio area. We also recently, as I read in the beginning of this year, managed to get those networks and contacts that lead us to serious investors and dialogues. We have been talking to them and so forth. That is where we are today. There are a lot of different things going into big forward-moving action from our side of things. OK, thank you. Next question. Based on your review of the number of deaths caused by sepsis, do you sense an increased awareness of the problem with unsuccessful sepsis? The number of deaths, I mean, this is nothing new for us in the business, of course. Maybe for the common guy on the street, maybe it's not so in the knowledge. We see an increase all the time. We see that there come new candidates in the making, in the process of going towards market for different development paths. There are new modalities, like we have our RNA aptamers, that may open up these doors. We are very confident about our own drug. There are others out there that see a possibility perhaps to find some kind of a cure, remedy, whatever you would call it, at least to take down these death tolls that we see from sepsis. Also, there's a lot of work with awareness about sepsis. There are forums, there are incitaments. Before, it seems like the total impossible to deal with this. There have been so many failures through the years. With these new modalities, there is good hope to do something. Of course, other things are developing during this time. We and other companies focus on finding a remedy for sepsis that helps. Still, it actually is an increase in the death tolls, what we can see from the numbers. There's definitely a need for a remedy here. The awareness among us that develop candidates towards sepsis is increasing. That's a good thing, I think so. Thank you. Over to the next question. Are there any risks associated with the U.S. listing? How are you working to manage them if they exist? There's always risks involved in anything you do until you can conclude and say, how did it go? We try to de-risk this as much as possible, of course. With the networks and the people we are now associating ourselves with when it comes to the legal side of things, also auditing side of things, advisor side of things, and also the contact we had and discussion or dialogues we had with potential investors, for us, it's a possibility. Nothing is given until it happens. That could be things out of our own control or the ones we would like to work with out of control that make this not happen. We do not hope so, of course. We have a very good pathway right now how to do this. If everything holds up, it should hopefully pan out as we plan to do. This is something that I will tell the market wherever we take these milestone steps, as I mentioned before, and tell where we are going and how we're doing with that one. OK, thank you. Here is another question on the same topic. How will you manage to be listed on the U.S. Stock Exchange? This is something that we are working on, of course. With our advisors and the legals that we are working with right now, which have a vast experience in doing this, that is something we have to come back to how we will do it and what we will do it. They've done it several times with companies from Europe and especially Scandinavia as well. The small details will pan out when we go forward and we tap off these milestones I've been mentioning before. That's all I can say right now. Thank you. The next question. How do you view the U.S. FDA's role in supporting new RNA-based therapies compared to the European authorities? Is the U.S. FDA more open to such drug candidates? I don't know really how to answer that question because we have only worked with the European regulatories. They are very understandable and understand this field of modalities. The U.S. FDA, we haven't weathered yet. We just see that there is something happening in the U.S. and there is an openness for these kinds of modalities. Before we actually knock on the U.S. FDA door, it's too early to say where they are concerning this because there are so many other factors playing a role of actually introducing something or getting something approved for clinical studies in the U.S. Hence what I've just shown before, the authorities' programs that they have put out for people to apply. There is a go in the U.S. side, and that may just open up for a wider and understandable way. In Europe, we had very good regulatory treatment and understanding from the authorities. There were no issues, actually. Too early to say too much about this. Next question. You have applied to both the FDA's Pre-Cert and CNPV programs. Are they interdependent? What could these initiatives specifically mean for a faster and more efficient development of Aptahem? I spoke about that in my presentation. It's the U.S. FDA that has given this out. I think the divider between those programs is one is to get a faster regulatory approval, which otherwise could take up to a year or more. Sometimes they want to shorten that time so you get out and do your study. What that means in terms of easier approval or a less diligent view on things, I don't know at this point. The other one is about the manufacturing. I mentioned that as well, that the manufacturing, they want to secure manufacturing in the U.S. to secure the supply of drugs for their U.S. citizens. These are the two differences between those programs. Yes, faster is one, securing is another. Faster through, see, does it bear to the market? Also, can we manufacture and secure a drug in our own country? That's what it's all about. Thank you. Here's another question. What are you doing to drum up the attention about Aptahem among potentially interested companies? This is one way of doing it, of course, and we'll share this later. We are out on the field and choose wisely the events we are going to. We know that Asia and Japan in particular are very interested in these modalities. Hence, we go to BioJapan and meet with companies there. Now we go to BioEurope, which is one of the bigger events in the world. Next year, we are looking towards going to JPMorgan in the U.S. at the beginning of the year. We try to spread into when it comes to partnering and investments or investor events to reach out there personally, of course. We have our feeds on Instagram, and not Instagram, but LinkedIn and Facebook and so forth. We go to different network situations, parties, and so forth where there is a good mix of investors and potential partners, of course. Yeah, we try to be out there and move because you have to be seen to be known. Next question. What type of partnership, big pharma, academic institutions, other biotech, is most attractive to you right now? All, or do you have a certain focus? We have said for a long time that the partnership would be most necessary for us to bring this lovely candidate to the market. I mean, we don't have the personnel. We don't have the experience to do the later stages of clinical development and market approvals and so forth. A partnership that's most truly a big pharma, but it could also be a big biotech or whatever that has the means financially, but also knowledge side of things to bring such a candidate through to the market. That's, of course, what we want to see on the market for the patients. That is the most attractive. Of course, we're looking at academic institutions to further develop and understand our candidate if there's more to understand. There's always something to understand, of course. To give a short answer from this long answer so far is that we need a strong partnership to bring it all the way to the market and know what they're doing. It's very costly, but it also needs a lot of knowledge and backup. That's what we're looking at. Here is the new question. Let's say five years down the road, what is Aptahem's long-term vision? Yeah, yeah. You're allowed to dream a little vision. Of course, I would say that we are close to getting through the last parts of clinical investigation on Aptahem and see the light in the tunnel. We have more pipelines going on, we have other candidates that we haven't developed yet with very interesting potential properties that we would like to develop and look at other indications, of course, when it comes to our fantastic drug candidate that's our lead candidate. We're prosperous and maybe not having one, but more than one collaboration, partnership, or license setup, or whatever would mean a collab in a sense of working with someone else, bringing it forward. A steady flow of new ideas and also maybe expand with other aptamers in front of us. We have learned a lot through this year. That's my vision at the moment. Thank you very much, Michael. I cannot see that there are any more questions. If no one has anything more to ask, Michael, I would like to say thank you for attending this webinar. As I said in the beginning, we will publish this on our website and social media channels, LinkedIn and Facebook, in a few days. You are welcome to attend it again. You are always welcome to contact us via email, info@aptahem.com, and you find the details on our website, aptahem.com. With that, I would like to say thank you very much for today. Thank you, everyone.