Hello everybody. It's 12:00 A.M. on this Wednesday when we have our monthly digital meeting in Hamlet BioPharma, our September meeting. I think you can see, you can appreciate around the table here that many of the group members are present in Lund, and we're in a very good mood discussing all sorts of exciting issues. Petr Bouska is with us. Petr, as you know, is the coordinator for the regulatory process in Prague for the phase III trial and also our support for any regulatory issues that we are doing. Not only that, it's really good that you're here, Petr. We may also see the appearance of our U.S. support, he's a medical doctor who is working with us on the U.S. site in Iowa, where we are proceeding towards starting the clinical trial. I'm on, Catharina. Oh, Joel, welcome. This is Dr. Joel Silver. Nice to see you as well. Hello, everyone. To the business of the day, the digital meeting, which will feature two of the very good things that have happened and that we have press released during this month. The first one being the start of the phase III trial in bladder cancer in Prague, and the second one, a very recent press release about BAMLET, where our work has resulted in a publication in a major journal. I have actually chosen to show you excerpts from these two press releases and a little bit of data at the end. We would also like to emphasize that the purpose of these meetings is discussion. Discussion with you. I know there are questions online, different things that we may not be fully aware of. Please feel free to bring any topics, any discussions, or questions that you have into the meeting today, and we will do our best to respond if what we have is in the public arena, as always. The first thing to focus on is the press release from September 17th, the successful patient enrollment in Hamlet BioPharma's phase III bladder cancer trial. You have all been aware of the work that has been going on, and of course, you understand that we are very proud to announce that the clinical phase has now formally started. Patients with non-muscle-invasive bladder cancer are being enrolled and treated according to the study protocol, which is approved by the European and the FDA authorities. I think I will move that one down a bit. Okay. Some more text, some more wording from the press release. This remarkable milestone, as we put it, is reached shortly after the company has communicated the successful approval process with the EMA at the end of June, the successful production of Alpha1H drug at phase III quality in collaboration with the Rechon company in Malmö and internationally, transport to the trial site following the trial site initiation with the clinical team at Motol University Hospital in Prague, which is led, of course, by Professor Babjuk. Especially we want to emphasize how grateful we are for the commitment of the Prague team of bladder cancer experts and for the regulatory support by InClino that Petr Bouska also represents. Maybe with these words, we should stop here and allow you to ask any questions related to the bladder cancer trial that you have or that have been discussed in the different groups that you represent. Please go ahead. What questions do you have? [Non-English content] These are questions that we have not yet got the material to address and that we will be happy to discuss with you and make public. The ambition is, of course, to recruit as quickly and efficiently as possible. The drug is there at the site, and the team is very keen to work with it. But we cannot give you any predictions about the, w hat should I say? The enrollment pace is always up to the individual patients. This follow-up. Yeah. Could a partner deal be in place during 2026? It's not impossible. It's something we are working towards. But of course, we cannot definitely say when the deal will be and how it will be done. But this is definitely our ambition. If you make a deal, could dividends to the shareholders be likely based upon that you work effectively and very cheap? Yes. Of course, the two could be connected, but the thought of the shareholders and dividends and returns to the shareholders is on the table all the time. This is something that we are considering very seriously. Of course, everything depends on the magnitude of the deal. Also, our way of working efficiently is a factor. It is a very positive factor in the discussions with the presumptive partners. They are seeing us as an innovative model for drug development, not least in the cancer field. The fact that an organization of our size can actually take a project through the different phases of clinical trials to phase III, as you know, is not very common, and it is being acknowledged more and more widely. We are very proud about that. We are also hoping to keep a reasonable cost for the phase III trial, which of course depends on the sites that are involved and the number of sites. I am sure you probably are thinking about big phase III trials with a large number of centers and a multicenter type design. Our study has a multicenter type design with a limited number of predicted centers, but we are very aware of different ways of making the process cost-efficient, also in that kind of scenario. This is also something that will be interesting for all of you in the future in terms of calculating the total cost of the trial and so on. I have to take this in Swedish [Non-English content] The question is the long-term effects of Alpha1H treatment in mice with bladder cancer. Actually, we have done those studies. Hien Tran, who is not here, has performed those studies with the rest of the group. The protocol is to establish the tumor in the bladder of the mouse. It is a model that we have used a lot. It is very efficient, and the tumor is growing very rapidly, so that within a couple of weeks, the mice need to be sacrificed because of the tumor load. When we treat with Alpha1H in connection with the establishment of the tumor, we can delay the tumor growth significantly. If we repeat the treatment every four weeks, we can actually delay or even remove the tumor development in that time. There is definitely evidence that we can achieve a long-term effect. In the patients, so far as you all know, we have been treating with six instillations during a little bit more than one month. The reason for this is that this is established in bladder cancer circles. BCG is an example where this kind of protocol is used and also other drugs. We are not excluding that Alpha1H could be used more extensively. For example, in a recurrence situation, if we wanted to reduce the risk of recurrences, there are several different protocols where Alpha1H could be given. We are also discussing with the University of Iowa for the CIS study to have repeated treatment in these patient groups. Yes, definitely, this is something that we are thinking about. Yes. How many CIS patients have you treated in earlier studies? It seems like at least two from what I can read. What was the response, and how big part of the tumor disappeared for these patients? Guys, this is impressive. They know everything we have done. I cannot believe it. Yes. There were two patients in the first human study with carcinoma in situ. I hesitate to give you data because the study was not controlled. We did the study to see if we could find any effects on tumor cells, and we ended up finding all these effects on cell shedding and tumor size and so on. It was not a controlled study. All we can suggest is that if we did not have a positive outcome in these two patients, it is not likely that we would have continued with this indication. Nothing that can be quantified in an uncontrolled open study, as you know. Yes. When do you think the phase III will be terminated when it comes to tests at patients? When will it be possible to present results of these tests? Petr, should I start, and then you can see if you want to add anything? Okay. Sure. Our approach is to see that something is happening, something that then could be either expanded into more centers or more patients or tweaked to modify the protocol in some way. We have a protocol that takes the patient to 12 months, and then with the possibility of further controls. But we hope to have some information about the study outcome before then. Would that be fair to say, Petr? Yeah, that is correct. Well, I completely agree with what you just said. The study is designed in a way that it allows us to look at the results on an ongoing basis to see the effects during the course of the trial and to decide on the next steps and the actual design, or the total design, or total number of enrolled patients. Thank you. It is your brainchild, this stepwise clinical trial protocol that has been so fantastic. Thank you. I think I've mentioned it many times, but Petr's approach allowed us, you know, in the phase II study, to first do a placebo control part, then add a dose escalation part, and then add some other testing of different types of protocols that were not continued. So it's very cost-effective. It's part of why our approach has been so cost-effective, I think. I hope that was a response to your question. Have you done market analysis on the price of Alpha1H when it's approved, considering differences in Europe and the U.S.A, cost-effective versus SOC and/or BCG? Yes. We have definitely performed market surveys of different kinds. I think the first one was a health and safety survey that was done when we received the Horizon 2020 grant from the European Union because it was mandatory at that time. At that time, there was also some very preliminary comparisons between a predicted cost for Alpha1H and mitomycin and BCG. Now, these drugs today are largely generic, as you know, and the price of generics is quite low. I think everyone is aware of the fact that introducing a new drug like Alpha1H would require a somewhat higher cost. We have many discussions about ways of reaching the market and ways of making all the drugs attractive at the same time. This is really important. We have not press released all our data on company valuation and the market surveys. They are mainly used internally for negotiations and for the authorities when required. I think a more extensive discussion would be a subject of a separate discussion with you at a suitable time. Yes. Why didn't you choose to do two rounds of instillation in phase III like you did in the extra part of phase II study, the phase II study? I would just say one thing, FDA. There are so many compromises that are made during a long process such as the one we have had with the FDA. Even though we have been met positively with the Fast Track and the personal visit and everything else, there is a lot of convention as to how a new drug is allowed to sort of put its mark on the field. There are a number of things that we may have wished that we could do that we haven't been able to do for that reason. I think the freedom with hopefully positive data from this study, our freedom to improvise, Petr, with your help. It's for the benefit of the patient after all. But we were not allowed to add further treatments in this study. Yes. Will you test BAMLET in mouse models of IBD, Crohn's? That's so interesting. We had a discussion yesterday. It's very relevant. The problem is the specificity of these disease models. Our argument yesterday was that we are working both in the infection project and in the cancer project with very clear models. With BAMLET, it was the colon cancer model, where the genetics of the mice mean that the controls have multiple cancers. You can follow the disease, and the treated mice then don't have the same extent, then you can get very significant differences. The IBD models are more tricky. As an immunologist, I'm familiar with them and all the elegant work that has been done there, but it's a bit difficult for us to see that at the moment. We're happy. If anyone has a good model, let us know. Yes. Will the study in Iowa be fully financed by the university, or will Hamlet BioPharma also co-finance this study? The study in Iowa is of very reasonable cost due to the collaborative nature of the study. There is a smaller portion of the cost, which is due to whatever extra is done to the patients because of Alpha1H treatment. There is no expectation that we should pay the full cost. I think Hamlet will contribute to that cost. That's the way. Mm-hmm. Is there any reason not to apply for accelerated approval today based on the phase II data that exists, and that the phase III already has started? That's a very good point. We've been so keen to get the phase III started that we haven't. Actually, Petr, we have discussed it previously, but maybe we should have another look at it. Mm-hmm. We can have a look at it, of course. Yeah. That's one of the options. Joel, are you there? Would you have comments on the accelerated approval? The issue with accelerated approval is you need, I think, a bit more clinical data than we currently have. The way it works is if it looks like the drug can be approved then you can bring it to the market while you're doing the rest of the required research. But I think we're a little bit too early for that. Yeah. We need a little bit of data from the phase III study. But we could be in the, what do you call it? The starting blocks. Y ou said starting blocks? Yeah. [Non-English content] We don't say that in Swedish. What do you say for a runner in a stadium when they have their feet in the blocks? Yeah, starting blocks. Yeah. Sorry? Starting blocks, I think is correct. Okay, good. All right. All right. Are you having partnering discussions regarding the glioblastoma project? How is the tuberculosis project- Tuberculosis project moving forward? Yes. The glioblastoma project is on hold at the moment because we are, you know, our resources and number of scientists is limited. We are on good terms with the British collaborators. The tuberculosis project, we are expecting an update meeting in two weeks with the Korean group, so we will know more then. When can the shareholders expect next clinical milestone regarding Alpha1H? As soon as possible. It is early days and I think we need to make sure that the recruitment. It takes about one month for the patients to be treated with Alpha1H. Then if they are not completely free of tumor, they will undergo surgery. So it is a process where we need a little more time to see the patient response and to appreciate the technicalities of this new study that is not exactly. It is very like the phase II, but it is not exactly like the phase II. Yes. How much more clinical data will there be needed? How many more patients is needed for the accelerated approval application? It is something we cannot say. It depends on the data. If there is strong data, obviously, this can be accelerated. I think-- Should we switch to BAMLET? Have we answered all the questions? I think so. Okeydoke. Oh, no, it's one coming up here. Have you outspoken strategy within the company for how you are going to get in all the money to run all the phase II in parallel with the phase III studies? When in time is this? Yes. This is a key question, isn't it? We are still slightly surprised at our ability to take the project all the way to phase III with the kind of funding. That's because of all you guys who have actually invested, and many of you have been very patient with us and not sold your shares, and we really appreciate that. Now, obviously, there needs to be extra funding added. Partnering is one immediate mechanism for funding, and we also have different international contacts ongoing to discuss other forms of funding. We are optimistic. We are aware of the challenges, but if we were worrying, we would definitely let you know. Yes. Thank you for the question. We can come back to this one many times. The next press release is about BAMLET treatment strengthens metabolic health nutrition as a first step towards commercialization. This is also part of the answer to your previous questions about finding different approaches to financing and partnering. Our new research findings define BAMLET's beneficial effects on metabolism, and the paper has been published in Scientific Reports, which is a journal within the Nature Portfolio. Briefly, the study shows that oral treatment with BAMLET reduces weight gain, blood glucose levels, and adipose tissue growth, and improves intestinal function in several models of obesity and diabetes. The find has also defined biological mechanisms underlying these effects and a scientific basis for using BAMLET to improve metabolic health. I have taken just some of the points from the press release. I hope this doesn't get too long, but just to give you a view of the key points as we appreciate them. The results show that BAMLET reduces weight gain and blood glucose levels compared with placebo in mice with diet-induced obesity. Mice that eat too much fat, if they are treated with BAMLET in the drinking water at the same time, they don't put on weight to the same extent, they don't get diabetes to the same extent, and they don't make this fat in the belly and in different parts of the body, these cushions of fat that you see in the control mice. This is accumulation of visceral and systemic adipose tissue that is also prevented or reduced. What is very interesting here is that it's an orally given substance, BAMLET in the drinking water. This means that the intestine, which is the first organ to come into contact with BAMLET, is a very important target organ. Of course, diabetes is the pancreas with insulin production, and obesity is all the places in the body where the fat sits. What we are saying is that if you treat orally with BAMLET, you actually can reach these different types of disease that represents the response to either too much food or genetic susceptibility. In models of chronic diabetes, intestinal barrier function improved after only three days of oral treatment with BAMLET. This is a very rapid and very strong effect. Everyone around the table here has contributed. We've looked at mechanisms of action where BAMLET actually reduces levels of glucose transporter. This means that either from the food or from the blood, you need transport of glucose into cells. That's what they use to live, and BAMLET is reducing that. The researchers, Sid and Atefeh, also identified effects on systems regulated by adiponectin and leptin. This is science again for you, but these are hormones that are produced in the body to really control adipose tissue. We see very, very potent inhibition of the functions that adiponectin and leptin are responsible for. Ines, you have a comment here. Yeah. [crosstalk] Yeah. A major comment for this press release, that this study is the first to provide a clear picture of BAMLET's effect on several central mechanisms of glucose and fat metabolism that are affected. The combination of oral administration, this effect in several independent disease models, and increased understanding of the mechanism of action provides a very strong foundation for further development of this. Indeed. Yeah. One of the conclusions is that new findings broader BAMLET's potential use. I can read. Maybe we look at this one instead. Yeah. Nutrition and pharmaceutical development therefore do not need to be viewed as alternative paths. The important thing here is that we show effects on health defined by obesity. We show effects on disease defined as diabetes. We also know from previous studies that BAMLET has effects on colon cancer. Nutrition can represent the first commercial step, while the scientific including for the foundation for future pharmaceutical development continues to be built. One can discuss if early commercialization within nutrition can help establish production and other essential steps towards an actual product. The long-term opportunity, which is for pharmaceutical development for metabolic diseases. Nutritional products and more disease-specific products can be developed in parallel. Just a few entertaining images at the end here. You remember that BAMLET is produced from cow's milk, where alpha-lactalbumin is extracted. It's not in cow's milk. It needs to be made from cow's milk. That's very important. A complex with oleic acid is made according to Hien Tran's patent that of course sits with us, and we now say that there are fundamental health effects. Metabolic effects on BAMLET summarized here, effects on body weight and blood glucose levels, glucose transport and uptake. This hormone, the adipose tissue loss and regulation of lipid metabolism. Chronic diabetes, where the gut was brought back to health after three days, and a general effect, restoring metabolic balance in the treated mice. Just one image where you can see the effect of body weight gain. The red here is the control, and the green is the treated, and the black is mice that have only received normal food, not fat food. I think you can appreciate the fact that the BAMLET and the control are very similar, lower weight. The blood glucose levels, the same graph, where the fat-eating mice have high blood glucose levels. BAMLET is reducing, and the controls are even lower. There is a lot of data in this paper that those of you who are interested can share and look at. These are images of BAMLET uptake in the small intestine. To the left, you see intestines taken out of mice, and they are full of red color, Arunima. This is your labeled BAMLET that is being shown to be retained in mice, in the intestine. Mice for 24 and 48 hours, and the control mice to the right here do not have, or they have very little left after 48 hours. The brown color to the right shows a section of the intestine, and brown is stained for BAMLET. We can actually see BAMLET in the intestines of these mice compared to controls where there is very little staining. They are blue, and they look much less complicated. Below, an image where you can see cells taking up BAMLET. The protein, Arunima, these are yours. The protein is green and oleic acid is red, right? You get a yellow color because both are taken up. Brilliant. This is also your image where what we said about effects on glucose uptake and GLUT2 staining. GLUT2 staining is here. You show a lot of GLUT2, and then below where BAMLET treated cells are shown, you see much less of this receptor for glucose. Here you can even see the green, which is glucose uptake in the control and a reduction in the BAMLET treated. This is a project that has very direct and tangible effects on specific endpoints. Atefeh, the modeling here that you see in green is the receptor, and then we have the BAMLET's complex binding to this receptor and even to the glucose binding pocket here to the far right. You have explained in a way why we get inhibition of the glucose levels, which is fantastic. Finally, we have no evidence of toxicity. You have heard this before from the Hamlet family of molecules. Even when given to healthy mice, we have not seen any side effects so far. The development is obvious, of course. The current study is preclinical, and BAMLET has not yet been evaluated as treatment for obesity or diabetes in humans, and this is what we want to do. Further studies will form the basis for the development of both nutrition based and future medical products. Thank you. That was a quick summary. I hope you have questions. Yes. In the CIS studies and even in phase III study, w hich part is there that will be extra to the normal treatment? How many visits and what is done during these treatments? Okay. If you start with, guys, help me if you want to. If you start with the patient groups, the first study is performed in patients with early disease. Okay. This is one scenario. The CIS patients is a completely different scenario. They have very severe disease. They are resistant to all other treatments known. They have been tested with both treatments that are available in Europe and treatments that are only available in the U.S., and are still resistant to those treatments. The approach to treatment is going to be different. It's going to be more intense, potentially, in the CIS, and also more repeats of treatment than we can have in the neoadjuvant group with less severely ill patients. I hope that was a response to your question. How is the status with BAMLET and the agreement with Tetra Pak that was done many years ago? Is it still ongoing, and what is the next step? That's also a good question, and I'm impressed with your memory. There is no termination of the relationship to Tetra Pak, but Tetra Pak has had the grace of transferring the collaboration to another large company or corporation that's interested in nutrition. We have very fruitful discussions that were mediated by Tetra Pak to begin with. Could Linnane Pharma be ready to sell BAMLET entirely to Novo Nordisk or another company that has specialized within this area? Or do Linnane want to be there to develop the project? Help with the development? Yeah, forward. I think Linnane Pharma is interested in the product coming out to the market. Whatever solution was more efficient here would fit both Linnane Pharma and Hamlet BioPharma because of Hamlet BioPharma's licensing agreement. I believe that the organization has a lot of competence that might be useful for a future partner, and that the future partner would select to work with both Hamlet BioPharma and Linnane Pharma until the product has reached a certain state. There is no contract on the table that we can refer to. For BAMLET, do you know what data that will be needed to apply for health benefits within food additives within the European Union? That is the perfect question, and this is actually exactly where we are at this moment to understand the extent of human data that needs to be in the portfolio. As you saw from the text, there is a sort of long-term potential of first doing nutrition and then eventually use some version of BAMLET also for metabolic health in a more therapy-related way. We are just at the point where we are trying to find out the borderlines between those two worlds, and it is a fluid line. We really need experts to decide how soon we can go ahead. Can I make-- Yeah. --some comment? We also think about the big industry in the animal food. Yes. Because we can use it. Also in animal food. Yes. That is the big industry. Yeah. There are so many-- Yeah. --so many opportunities. One thing I forgot to say about Tetra Pak is that we had a very fruitful collaboration with them and ended up, this has been mentioned before, so it is not proprietary. We ended up, I think, with 300 L of BAMLET. The scale-up of BAMLET for production and testing for the different parameters that you need, sterility and if it can be heated or if it can be in different environments and so on. All this work has been done. Yeah. In terms of those properties, BAMLET is ready to go. Yes. Are there any thoughts for using BAMLET as a drug candidate for colon cancer? Of course, there are. This would need, I think, a serious commercial partner that would take on the BAMLET molecule for these purposes. As you know, our favorite molecule, Alpha1H, is not suitable for oral delivery or for these types of diseases, so there is no competition in any way here that we can see. Yes. Have you looked for other changes in non-high fat diet? That is, physiological changes, et cetera, in-- Yes. Great question. --in the treated [RS] control? I think I-- Yeah. These are such great questions. Do you know what we have tested? We have tested mice that are called leptin deficient mice, so they lack the hormone leptin that is required to regulate fat metabolism. As a result, they grow extremely obese. In these mice, it is also possible to see effects of BAMLET, provided that we come in early before. They become so grossly obese that it is hard for anything to treat them. But if we come in early during their development of the disease, we can actually have a significant effect even in that context. So not only food related. No effect. Yes, Sid? No effect in the mice that received normal diet. Yes. Sid is mentioning that in mice that receive a normal diet and are treated with BAMLET, there are no adverse effects. There is a little bit of metabolic response, very weak, but it suggests that BAMLET is somehow targeting. You should say this, but it is targeting disease-associated changes with glucose and obesity, something that has to do with the disease. That is what you saw, right? Mm-hmm. Yes. You have earlier said that it was too hard to manufacture BAMLET for pharmaceuticals. Can you repeat why you put that track down and focus on food additives? Is there new potential to do pharmaceuticals with BAMLET with the new discoveries? I mean, never say never, but that situation hasn't changed. What was produced on a large scale with the help of Tetra Pak's trial facility was a BAMLET that consists of highly purified protein that is commercially available, that could be used as a raw material in a product. Our technology developed by Hien Tran for making BAMLET in an efficient way. We can be sure that there are raw materials for BAMLET production for a non-drug application, right? What will be required for BAMLET to be produced and developed into a drug is a later question. What is fantastic from these studies is that we can see in mice that we can treat disease. If there were a solution to this production problem, that could be. But also that's why the person who helped us write the press release said that while we are hoping for a solution for the nutrition field or metabolism field in a non-drug related way, there could also be discoveries in the future, but we don't have them yet. Yeah. Yeah. Where do I sign up to become a BAMLET test pilot? We're all with you. We can establish a list. Just send us your names, and we will put you on the list. We would gladly test it ourselves, yeah. I think that's about it. That was the last word. That was the last question-- Yeah. --as far as I can see. That was a wonderful discussion. Thank you, everybody, for all the questions, and happy faces around the table. Petr, any last words from your end? Maybe just shortly to the current achievements in the phase III. Yeah. My impression is that the team of [Prof. Marek] has really confirmed their commitment for the phase III with enrolling another one patient in this week. Yeah. Even if it's hard to estimate when we will deliver next clinical milestones-- Yeah. --I think it all looks very positive and promising from my end. Thank you. That's so great. Joel, do you have any comment here? I just wanted to point out in terms of the CIS, the carcinoma in situ-- Yeah. --that the reason this study is being done is because the researcher at University of Iowa, who's very prominent in this field, and his research interest is in treating CIS refractory to BCG, which is the standard treatment. I sent him the papers on Hamlet, on Alpha1H, that were publicly available, and based on the mechanism of action, he got really excited about its potential for carcinoma in situ. Because carcinoma in situ, while it's aggressive, forms only a thin layer on the inside of the bladder, and the cell-shedding properties of Alpha1H, he felt were potentially an effective way to scrub the bladder clean of all the cancer cells. This really came from him, and he's one of the world's great experts in this. I think it's important to keep that in mind. Mm-hmm. Thank you so much. That's a generous comment. We have good news regarding our paper on the mechanism of cell detachment that we will share with you in the near future as well. It's all happening. Great. Okay, everybody. Great discussion. Thanks, Joel and Petr, for your contributions as well. Yeah. Bye-bye. Bye-bye. Bye.