Of the day, onto the stage, Annexin Pharmaceuticals and CEO Anders Haegerstrand. Welcome, Anders. Thank you. Great to be here. I am presenting Annexin Pharmaceuticals. Next slide is over here. Yes. We are based in Stockholm. We are a small company. We are four main people employed. Me, my CMO, CSO, Anna Frostegård, who is also founder, Susan Suchdev, Susanne Andersson. We work with a senior ophthalmologist also based in the U.K. We are working with Annexin. Annexin is an endogenous protein, basically. We all have it in ourselves, called Annexin A5, and it regulates the signaling of a phospholipid on the surface of cells. That phospholipid can actually do a lot of harm, which we are trying to inhibit by using Annexin. We are a clinical stage company. We have done our phase I and phase II-A data from the U.S., which I will not talk through today, much of it. We have a two phase II-A study ongoing in the U.K. and Germany currently, called the NEXUS study. Key activities right now is to finalize the NEXUS study and find a licensing partner for our asset. Alluding to the conversation we just had, we are looking at the U.S. mostly, but also trying to find partners maybe for Asia and Europe. Ophthalmology is our key focus. Annexin could actually do a lot of good things in other diseases as well, but we aimed at focusing on ophthalmology. The normal eye functions like light gets in through the lens and hits a little black spot they call the macula over here. That is where you try to focus when you want to see sharp. The retina is actually quite complicated with 10 or so different layers, with a lot of vasculature in there, and the vasculature is what we are trying to target. If you do a cross-section, which is now actually done also at Specsavers or other opticians, they can actually look at a cross-section of that and looks like that. Healthy volunteers will look very healthy, and they have all the layers into the right. The fovea is the key part where you actually try to focus and see very sharp. You use the other parts as well. That is more for diffuse vision. If you have retinal vein occlusion, which is one of the diseases we are targeting, you get actually a small clot in the vein that tries to get the blood out of the eye. What happens then is that if you have a clot there, you have a backflow problem. You will start producing VEGF and other cytokines, which actually drives inflammation and swelling. If this animation works, you can look at this one. What happens here is that this fluid between the layers of the retina, you can easily understand why you cannot see if the fovea is totally lifted up and totally out of focus. So that is what it looks like. You get inflammation and get bleedings, leakage of fluid, and basically impaired vision is the endpoint. This is how they are treated. They are treated by injecting anti-VEGFs typically, straight into the eye. Like this, repeated on average 5 x per six months in the U.S., maybe a little bit less in Europe. We offer something very different. Annexin is infused via a vein in the hand. We have done five infusions in our phase I and phase IIa study. We are now moving down to three injections or infusions, I should say. Diabetic retinopathy is a vascular disease of the eye as well, driven by the varying fluctuating glucose levels in the blood, which drives inflammation and small thrombi in the eye. You develop pathology over time. If there is about 20 million or so patients with RVO, there is about the same amount of patients that we can treat potentially with Annexin in diabetic retinopathy. It is a slow-developing problem, and millions of people become more or less blind due to diabetic retinopathy. They are treated in a similar way when this end stage happens, when they get abnormal blood vessels and fluid accumulating, by, again, treatment of injections with anti-VEGFs. The difference between Annexin and anti-VEGFs is primarily that when the blood flow is not functioning, it is ischemia. Ischemia drives the production of VEGF. You basically put anti-VEGF into the eye, which soaks up the VEGF, which does good things. You reduce the edema, but you have to repeat it because the problem is not solved. Annexin, on the other hand, is aimed to seal the small capillaries by improving the function of the endothelial cells, and it seems a bit doing quite well in that regard. The NEXUS study, in which we have shown that the patients do get improved blood flow, and it stays for 15 days or longer. This is an ongoing study, so we have not closed the database and looked at the data, but we have a very good interaction with our PI in the U.K. and in Germany. So is this unique data? Absolutely unique data. I hope that this will drive the development forward, that we are probably the only company presenting this kind of data. Also in diabetic retinopathy, this has not been seen before, that patients actually improve perfusion in the eye. Retinal function will follow. It starts quickly. Even if the drug is only given three days or five days and the drug is out of the system in a few hours, they sustain improved blood flow. The patient received. The patient was stable in the disease for a long time. They actually had neuropathic pain, which is the same token in a way. It is a microvascular problem from the peripheral nerves. Patient self-reported that the neuropathic pain was gone, it was two days or so after the Annexin treatment, which is a very good news for the medical professionals, I would say. And very well tolerated. We have treated about 25 patients by now. We have basically seen nothing which is related to the drug in terms of safety and tolerability. This is the kind of image we present to make you feel more comfortable. This will be the black, the darkest part here, which will be the fovea. You do not want to have it really lightening up in yellow or red, but you want it to be small and concentrated. What you see here is a development of more sound, healthy retina. This is where the occlusion sits over here. You see the dark spot here where you have no profusion, and you see profusion coming back soon after vanexin has been doing the job. You see also a functional measurement over there, which is basically the lead time between a light impulse to the retina and electrical signals. It goes much faster. This is a diabetic retinopathy patient, where you actually want to strive to see better profusion, and you also want to see the little tiny spot. The fovea is irregular in the first place. You see it kind of shrinking and getting smaller and nicer, more like a normal fovea. These are the kind of effects we are keen to see, and we get them. Obviously, this is an ongoing trial. We have analysis on an ongoing, continuous basis. We want to confirm the signals. We have started to treat patients for 3 days, I mentioned that. We are also using now, starting with an anti-VEGF and then giving vanexin. Previously, we treated with only vanexin, but now we are starting doing one anti-VEGF and then vanexin. That is kind of the plan for the phase II-B trial, to be able to recruit more patients faster and also to offer them standard of care. vanexin used to be called ANXV, for those who have heard it before. We have gotten an INN for vanexin from the WHO, and we are expected to get confirmed by end of this year. We have a lot of discussions ongoing internally on how to approach FDA. FDA actually launched a new guideline or draft guideline for proving efficacy in clinical trials in June, and it is kind of out for discussion now, and this is a very important document for us to think about how we do the phase II/B and the phase III. We will hopefully meet with the FDA before end of the year. Again, licensing is a key thing. We are talking to many of the usual suspects. Yes, there is a focus on the U.S., but we also talk to European and Asian players. Broadening the program to include diabetic retinopathy is gaining some interest also because some companies are kind of focused on diabetic retinopathy and other eye diseases and not necessarily RVO. The last image. We do have a very differentiated mechanism of action. It is upstream of VEGF and other cytokines. If we use vanexin, these other cytokines will not be produced. That is the whole idea. Also using the intravenous infusion route is unique for us. I would rather prefer having something intravenous than getting something into the eye. I think you can probably agree with me. Some ophthalmologists might prefer to deliver things into the eye because that is what they are most used to, and they make money out of it. That is a challenge. But I think in the long run, if our effects will stay, it will be a good thing to get intravenous infusion rather than an infusion to the eye. Of course, the idea is to reduce the burden of the treatment, reduce the need for anti-VEGF injections to the eye, because if we improve blood flow, there will be no need for these other drugs, in theory. We have to prove it, of course, in larger trials. Huge markets, yes, I mentioned these are probably addressable number of patients in the world is 20 million or so with RVO. With diabetic retinopathy, the later stages is also roughly about 20 million patients. These are huge markets. The price for an anti-VEGF is roughly $2,000, and they get them repeatedly. So the cost for anti-VEGFs in the U.S. currently is about $15,000 per annum. That was what I intended to say. Thank you very much for your attention. Thank you, Anders. If anyone has a question in the room, just raise your hand and use the microphone. If not, I will start from here. Sorry. I have a very quick question. Yeah, no, absolutely. Rather you than me. Go ahead. Is it reversible? Sorry? Is it reversible? What is reversible? If I take the medicine, Yeah does my eyesight heals, or will it just not progress worse? That's a good question. I think these are different. RVO is kind of a sudden onset. It doesn't progress necessarily. It can progress depending on how long you wait to treat. I would say that ideally, we've kind of flushed away the clot, which is the dream scenario. And we have some patients which that seems to be almost true. We cannot see it on the images, but they're just cured, and it hasn't come back for years. Some other patients will still need an anti-VEGF. If they improve profusion, the question becomes, will you have another kind of small clot again, so it gets worse again? But I think in RVO, there's a pretty good chance that they get as good as they can with vanexin and maybe one or two anti-VEGFs, and then they should be flat because there's no cause of re occlusion. Diabetic retinopathy is a chronic disease, right? It develops very slowly. They become worse and worse and worse. I think we will consider or think that we will probably need to treat. Look at the data. One of the patients, it seems to be kind of stable for 120 days. The profusion stays 60 - 90 days improved. How that plays out in terms of the worsening of the patient, we don't know yet. We have to have more patients. We only have three diabetic retinopathy patients. We have six RVO patients in this study, and we have another 15 in the previous study. We know more about retinal vein occlusion. I think in diabetes, we'll probably have repeated treatment cycles, maybe one every third month or so. I think of that as a price one is willing to pay if blindness is maybe at the end of the road. Final question then. It's a question here about what sort of reaction you have had from specialists working within this area. Well, we have seen extremely and not-paid-for experts on the stage say, "Wow, this is eureka. This is actually the holy grail in vascular pathology of the eye." That's really good news. Technologies are new. The images you saw is a new machine coming out of China, which is kind of slowly gaining approval or experience. Some of the U.S. hadn't seen this kind of machine-type data before, so it's very impressive. This is new. It takes time to convince people about this new technology and to show how this improved profusion relates to a better clinical outcome. That is where we stand right now, and we hope this next study will prove that. Okay. Thank you so much, Anders. Thank you.