Okay. Welcome to this R&D day for Orexo. I'm pleased to be here together with many of my colleagues. I'm also pleased to be here on a day when we were a little nervous arranging this, that there was a lot of stuff happening in the Middle East, and I think today was the 48-hour deadline that Donald Trump set up a few days ago. Now it seems like it's quiet down, maybe a little. Happy to see many of you here and not too disturbed by geopolitics. We are here to talk about Orexo and our R&D portfolio, our AmorphOX technology. I hope you will come with better understanding of what we are aiming at now after we sold Zubsolv, some of the core technologies, but also some of the late-stage projects that we have. My hope is that you go back and see that Orexo have a fantastic technology in our AmorphX technology and have a big area of applications, but also that you see we have some quite exciting late-stage opportunities in our OX-640 project, OX-390, and also IZIPRY even though we won't talk that much about it today. I'm joined today with the entire management team after the Zubsolv divestment. I'm here. We have Frederik, our CFO, and also working, leading the business development team. We have Robert Rönn, who is head of R&D. You will hear from all of them. We have Cecilia Coupland, who is head of operations, but also quality control. We have Ed Kim coming in from the U.S. Ed is Chief Medical Officer, but also the lead of our OX-390 project and working tightly together with BARDA. Then we have Lisa Moore, who is actually, for those of you who have been with us for a while, she's probably a new face, so Lisa has been with Orexo for some time now, but in a different role in our U.S. commercial organization. Lisa has a long experience from strategic marketing and also working with nasal rescue medications, among others, Narcan with Emergent, and Lisa will also have some air time today. Apart from the management team, we also have Lena, that most of you have seen. Lena's working and leading our investor relations work. We have Åsa, who was signing off. Åsa's working with the design and packaging for Orexo and also helping us with presentations like this. Then we have Jonas Sjömark, and Jonas is actually the inventor behind the AmorphOX technology, so the one who knows most about that technology is Jonas. He won't be speaking this much, but he will stay here for lunch, so those of you who want to grill him and get more information, and he's the guy to go to. Our agenda is quite tight, so we're kind of 15-minute slot. I have a clock ticking here, and we will go through. Overall, from my perspective, we'll have some more deep dive into the AmorphOX area and also what we're working with GPIs and vaccines. OX-640, then we come in with Lisa and Cecilia. Cecilia is leading it from a project management and Lisa is working with the commercial part of OX-640, our anaphylaxis treatment. Then we have OX-390, which is a little larger block because Ed will talk about OX-390, the project, but we'll also have a pre-recorded interview with a key opinion leader from the U.S., Mark Smith, that Ed did a few weeks ago. Then Fredrik will come back and talk a little about our financials and in particular with a focus on business development. Why are we here today? We sold, as you know, Zubsolv at New Year's Eve, actually on the thirty-first of December. It gave us $91 million and plus earn-outs. We do expect a decent amount of the earn-outs to be paid out, but that depends on Zubsolv performance in the U.S. In the agreement, which was really rounded up in the last few weeks of December, we had meetings on Christmas Eve, on New Year's Eve. We had to get all the money in on New Year's Eve also, it's a lot of work. In that process also, Dexcel took over the majority of the employees in the U.S. Little more than 30 people left the company to Dexcel more or less overnight. We're moving into our restructuring process, that is going on right now, it's a stepwise restructuring because in the agreement with Dexcel, we have to provide services to keep Zubsolv on the market with uninterrupted supply. For example, Cecilia is heavily involved still with the manufacturing and supply of Zubsolv in the U.S. You will see that we, as we laid off or basically have to lay off people in the U.S., those who didn't go to Dexcel, we have a severance package. We also, as you probably noted a few weeks back, we have a vesting of our long-term incentive program, and that's basically a contractual obligation we have to the employees. If you're a so-called good leaver, you will have an accelerated vesting of part of your program, and that happened a few weeks ago. We have to work with exiting our supplier contracts. We just left our office in the U.S. a few weeks back and have moved to a smaller office in New Jersey. Restructuring of balance sheet. I'll also just, to be transparent, have to point out that, because when you have a product in the U.S., then we have products in the market and supply chain that has been sold by Orexo, so with Orexo codes and names on, and some of that is associated with a rebate. We have to here, even in 2026, we have to pay some rebates in the U.S. to payers, and we're also responsible for returns. That's the way it works in the U.S., when you sell a product, if it's returned to you, then you basically compensate. That makes it a little more complex right now because we are not replenishing that return, and that, of course, is a benefit going to Dexcel. Orexo will have to pay for some returns, and that will take a while. You saw that there was an escrow in the agreement, and that was part of the announcement. That's actually to cover some of these expenses. Then we have our Department of Justice investigation that has been following us for more than five years. We are still seeking a resolution. I would say it's not easy because of the volatility in the Department of Justice in the U.S., but this is a part that we of course now when we have left the commercial field in the U.S. find this should be an opportunity to get that resolved. That leads us into the transformation, and what we're going to talk about today is how we can become the global leader in amorphous powder technology, in particular in nasal, but we see other applications of that also, how we can advance our existing projects to what we call value inflection, and then how we can work with partners to expand the use of amorphous into new technologies. We're not doing this from scratch. We have a long history of developing products. We have had four products that we've taken from idea to product. We have launched products and been part of approval process in more than 25 markets. We have done a lot of partnerships, from in all both development and also commercial partnerships. When it comes to amorphous, we have worked with this for eight years. Robert will come back and talk a little about how we have evolved over the years. We have, in this process, been doing more than 500 batches of different, and we're doing that internally in our own facilities, of products based on AmorphOX. We've had five clinical trials which have all been successful, and we have more than 100 patents associated with the AmorphOX technology. That leads into the platform we have today with what we call, and you will hear this throughout the day, Exploratory. That's today focused on large molecule GLP-1s and particularly semaglutide vaccines. It will come into our own projects where we have OX390, which is in partnership with BARDA. We have OX640, the epinephrine product, and we have IZIPRY that we're expecting to file with FDA later this year. We have our launch products which some of them are in the end of their life cycles, but Zubsolv U.S., as you know, we will still expect to get some earn-outs, but also Zubsolv Europe I think is an interesting phase right now because they have just got approval from EMA for their own manufacturing site, which is enabling them to bring down cost of goods. We had an unfortunate situation with our European supply that the only supplier we had in the U.S. who could supply to Europe, basically decided to leave that space, and if we want to continue, they want to have a significant increase in the cost of manufacturing for Europe. Accord decided to take the investment and build up their own manufacturing facilities in Europe on Subsol, and they just got approved for that, which should enable that to get a little more traction than it has today. The big focus of today is on the amorphous technology. It's a very versatile technology. You will hear a lot about how we're working with the bioavailability, how we can work with stabilizing even complex peptides, proteins, and other biologics, and of course, how we can move from injection to needle-free in drug delivery. We're doing this in three areas, and this is really how we're looking at the business today. We're working with what we call Explore. This is early-stage. This is trying to find new ways of applying the amorphous technology. Where we see the biggest opportunity, and Lisa will talk to that because we did a larger strategy assessment last year, is in the GLP-1 and vaccine space. These are early-stage. This is something that will take some time before, but it's also where we see the biggest benefit of the technology. The explore over time, we hope will evolve into something we call develop. Already today, we have project in the develop phase, and that means projects where Orexo have set up a timeline. We have clinical trials planned, so the entire development program is in place. Today, we have three projects here. The last part is partnering. We're working, and we do that already today, work with companies who see a benefit of the technology applied to the API that they think is interesting to evolve. What we're looking for there are companies who are basically paying for the service, but over time, Orexo will take part of royalties and others based on the patents we have for AmorphOX. Going a little more into the depth, in the explore area, as I said, this is where we're working to really transform the delivery of drugs from injection to nasal delivery. This is where we see new areas where we need to show proof of concept, and that's the feedback we get when we are out talking to companies is, "What is your proof of concept that this really works?" What they want to see is in vivo data, that's animal data. They want to see human data on some areas, and this is where we're working. What you will hear today is how we are expanding. For example, in GLP-1s, we have some good feedback from industry players saying, "Why don't you try to make a tablet out of this?" We actually have some very good ideas for how we believe we can make a much more efficient tablet than what is today with Rybelsus and Wegovy that was just launched by Novo Nordisk. We'll come back to that a little later. We have our development phase, and in the development phase, as I said, this is where we have IZIPRY, OX640 and OX390. What we're looking at the next big milestones in the development of these is for IZIPRY is that we get it into the FDA for approval. As you know, we have been there a couple of times, but now third time is the time, and we're expecting to refile after the summer, which will then allow for an approval early next year. OX640, also what we are looking forward to is actually take the final commercial product, the final commercial dose, and take it into the first human study, and that is planned for later this year. This is again feedback we get both from investors, from in particular in the U.S., but also from industry players is let us see the results in the final formulation, in the final dose, to see that you're actually within what they call the bracketing for the low dose that you need to, and that you don't get too high in the exposure of epinephrine. For OX390, we are now moving. We're doing in vivo studies right now. We're testing this nasally on dogs. We are planning to get or we're getting those results during the summer, which will then enable us to sign the final development program. Ed will talk a little more about that. Then we have our partnering part, where we are basically doing a lot of feasibility studies, and we're doing that with quite a few companies. Small companies, larger companies, some technology companies that we're testing their technology together with our technology to see if it works. A lot of that is actually financed. If not fully financed, then at least the testing of the molecules is financed or conducted by the partner. This is not where I see the biggest potential, but it's a way for us to get coverage of our expenses. The same people working on these projects are the same people we need for our own projects and for the exploratory. Basically getting some cost coverage out of these projects is important and expand the pipeline and of course also for all of these projects we generate new data, new IP, new knowledge. Taking from a timeline perspective, we are basically looking in this year for Zubsolv, then we will have a launch in Europe with the new manufactured product from Accord. IZIPRY to get it filed in the third quarter. OX640, Q4 pivotal trial starts, so we start what we call a nasal allergen challenge study. You'll hear more about that later. OX390, we get the first in vivo data. It's an important milestone. For the GLP-1 studies, we are doing more in vivo studies to show how we can work with both vaccines and with GLP-1s, and we come back to that later. There is a list of milestones coming forward. As you know, for every project, new milestones will emerge as we get more knowledge about the project. We do see there's a quite high pace of activities, at least when you look at it from a pharma perspective. Pharma things take a little longer, but we think there are some very material events coming forward, in particular in 2027, 2028 with approval of IZIPRY, readout of the OX640 study, potentially moving into in vivo for our exploratory projects. Where are we ending? We are trying to build leadership in AmorphOX drug delivery. When we look across the world, we have not found anyone who's working with a powder formulation that is more sophisticated than what we have. For nasal delivery, we see the AmorphOX platform we have can be applied both nasally and for tablets. We're going to do this to work both on the AmorphOX powder, but we're also working to finance our own projects to value inflection and to expand our partnerships, getting access to more API, more knowledge. These are the pillars that we're working with them as a company. With that, I will invite the first new speakers from the management team with Robert Rönn and Cecilia Coupland. I think Robert will start talking a little about the AmorphOX technology first. Thank you. Thank you, Nikolai. Great to see everyone and, as Nikolai said, my name is Robert Rön, Head of R&D at Orexo. I would like to take you back to the start of AmorphOX, where it all started. This goes back to 2017, and basically began with an unmet medical need in the U.S., particularly in the U.S., and that was for the development of a naloxone rescue product with rapid absorption and high bioavailability in order to combat opioid overdoses that was seen from strong synthetic opioids. We set out an hypothesis at this stage, where we believed that we could meet such requirements by developing a nasal naloxone powder. In this process, we evaluated different formulation principles, and finally, we identified the most suitable principle, which was a spray-dried amorphous composite powder that later has turned into the AmorphOX platform. Obviously, the development of our nasal naloxone powder continued and is now represented by our most advanced product based on AmorphOX, the IZIPRY product. This product actually met the objectives we set out initially. It has rapid absorption and very high bioavailability, especially when we compare it to more traditional liquid-based nasal sprays. Possibly more surprisingly during this development was that the powder that we developed was highly stable, which is not always the case when you're dealing with amorphous materials. Sometime during the development of IZIPRY, we asked ourselves the question, you know, can we formulate other molecules into this technology? The answer to the question was yes. Today, we have formulated successfully numerous other small molecules, including epinephrine, which is the basis of OX640, very sensitive molecule that is turned into a very stable formulation when formulated into the AmorphOX technology. We have further expanded the scope of AmorphOX, where we have formulated successfully peptides of different sizes and even very fragile biological-type molecules like proteins, enzymes, and vaccines. What all started as a product idea actually turned into being a versatile drug delivery platform. Looking into some depth on the structure of what AmorphOX really is. This is a powder that consists of amorphous composite particles. We use a unique combination of a drug in combination with certain excipients. Two core components are a disaccharide and a polymer. We also have the optionality to add other excipients, such as a permeability enhancer, which could be of importance, for example, for nasal drug delivery, but also in other cases. Again, this is an amorphous material, high energy state material. The good thing is that these powders, they dissolve extremely quickly, which helps boost bioavailability in the end and also the speed of onset. This is a monoparticulate powder, and what I mean by that is that all materials are contained within the one and the same particle. We don't have different types of particles in our powder, so all particles are basically identical, which has certain benefits, especially when it comes to commercial manufacturing. We manufacture by spray drying, which is good. It allows us to precisely control the particle size, which is of extreme importance when developing a nasal drug product. Spray drying is also an established, continuous, highly scalable process. As Nikolaj mentioned, we have built a solid patent portfolio around AmorphOX. Today, we have more than 100 patents and patent applications filed globally. This is still evolving. The current protection, it lasts until 2047. In addition to patents, we have also built up and gained a lot of know-how, especially around our manufacturing process. Turning to the differentiating positive attributes of AmorphOX, first of all, it's a versatile technology. As I mentioned, we can formulate anything from small molecules to large vaccines. We can develop products using different administration routes, for example, nasal products, but we're also looking into developing tablets, for example, for oral administration. Again, dosage forms, we can develop products based on different dosage forms. We can use the powder as it is. We can put the powder in a capsule to have it orally swallowable, or we can even make a powder for reconstitution, which could later then be injected. So it's a versatile technology. Secondly, it's a very stable technology. It's a stabilization technology, I would say. This allows us to develop products with long shelf life with more flexible storage conditions. You can store these products at cold temperatures or very high temperatures. In some cases, it could even completely eliminate the need for any kind of cold chain requirements. It provides rapid absorption and high bioavailability. One of the reasons is that we are able to generate a supersaturated state of dissolution at the site of absorption, which helps boost the bioavailability and the speed of onset. When developing nasal products, there is also an opportunity to reach the brain directly from the nose, which is called nose-to-brain delivery. This is always an option when developing nasal products. We can also see a benefit in that in certain instances, we can reduce any type of food effect that you may have. This being a composite powder, as I said, it's not built up of different type of particles, so we cannot have any kind of powder or particle segregation. This is significantly de-risking commercial manufacturing. This segregation of powders can cause huge difficulties in, especially when it comes to commercial manufacturing. This is a good positive thing. We also, thanks to its composite nature, we can co-localize or co-formulate critical formulation components, which can further help increase bioavailability, for example. Looking at the very high level process on how we do when developing products based on AmorphOX, it always starts with an unmet medical need with a target product profile that we would like to meet. At this stage, we have identified a molecule to work with, the API. Once that is identified, we are using the AmorphOX design space to tailor each formulation to meet the particular requirements for that particular API. This is obviously knowledge that we have been building over the last eight years, which makes this process relatively quick, I would say. After having identified an initial formulation candidate that is later optimized through analysis of certain critical parameters, we advance that into the selection of a final formulation. This is then before we have the final commercial product, we need to optimize the manufacturing process. That's kind of the last step before we have reached the final commercial product. With that, I will introduce Cecilia, who will take us through some more depths about the manufacturing process. Thank you, Robert. My name is Cecilia Coupland. I'm Head of Operations. In recent years, the commercial manufacturing setup and data from that has limited the regulatory approval timeline for a lot of commercial products. In our spray drying process, we have great advantages. We talk about a scalable process. What does that mean? It means you can move from lab scales with a few grams up to pilot and commercial scales, up to hundreds of kilos, and you can do that in a reliable way. That is most often not the case with pharmaceutical manufacturing. In early feasibility and exploratory clinical phase, Orexo uses our small lab scale manufacturing in our own facility so that we can produce material for technical trials, but also for early clinical work. This allows us to move quickly through the phase and also work iteratively, which Robin spoke about, which is very important. We then transfer to our CMO, where we have the commercial spray drying process set up, which is easily adapted to new modalities and with the manufacturing design space that works for all the different APIs. This design is using Orexo know-how and have been used to manufacture multiple commercial batches across products successfully. This stable, free-flowing powder that we end up with simplifies downstream manufacturing. That could be filling into capsules or nasal devices. It does so by reducing the risk of segregation, but also reducing the need for further protective measurements, such as protecting for light or oxygen, and that helps us to produce a homogeneous product. One other option we have with this type of powder is that we could use the powder as a powder for reconstitution for injectable products by producing a sterile powder through an aseptic process. That means that this powder can then be filled in vials, and that can be handled and shipped throughout the world without the cold chain requirements. Overall, Orexo's spray drying process is versatile, scalable, commercial process that is designed to fit this platform, and it takes us swiftly and reliably from early feasibility phase to final commercial process ready for regulatory approval. With that, I invite Lisa to start the next section. Thank you, Cecilia. Good morning and welcome. I'm Lisa Moore. I lead Product and Portfolio Strategy here at Orexo, and it's my pleasure to speak with you about AmorphOX today. You've heard Robert and Cecilia talk about the unique attributes of AmorphOX. Cecilia took us through why the manufacturing process is scalable. AmorphOX is going to be the driving force behind our future. It is the engine that will power our future growth. The obvious question is, where do we go next with AmorphOX? How do we ensure rapid adoption by our technology partners? How do we optimize the commercial potential of the technology? I will say that last year, I worked with our team to build a strategic plan for AmorphOX, and we did a lot of deep dives with the team, and it became very apparent that there were certain things that needed to align to ensure success of the next application of AmorphOX. They were including things like reaching a commercial imperative that the manufacturer needed to be having some sort of pressure on revenue generation. It needed to fulfill an unmet need. There needed a problem to be solved. Differentiated enablement, the technology needed to improve the manufacturing of the target asset. The last is that value needed to be generated. It was very clear that to attract a new partner for AmorphOX with a new application, that we needed to de-risk the platform, and that meant moving beyond the initial animal preclinical proof of concept studies and getting into first-in-human studies. How did we do that? How did we determine where we went next? Well, we got an outside firm to help us with a very rigorous, very disciplined, very intentional process where we started with a very long and broad list of AmorphOX use cases. We covered multiple therapeutic areas, infectious disease, oncology, neurology. We looked at multiple modalities, large molecules, small molecules, vaccines, and multiple routes of administration. We were able to then triage those use cases, and we triaged them based on what was feasible in the near term and where there was a good degree of technical fit with AmorphOX. Our external firm also conducted interviews with industry experts, with clinicians in the field, and we landed on a few opportunities that provided the most material opportunity for Orexo and had the greatest unmet need. It was an iterative process. It wasn't one and done. The two use cases that were at the top of our list were GLP-1s and peptides and vaccines. A little bit about the vaccines. Actually, I'll start with a little bit about the GLP-1s. That is our first priority use case. Why GLP-1s? Well, we could develop an intranasal GLP-1 ourselves. It could become our own internal project. We could partner it with someone else, or more likely, we could use it as a door opener to talk to other pharmaceutical companies that are interested in bringing GLP-1s to market or their own incretin or their own multi-agonist. Nevertheless, a GLP-1 intranasal offers a variety of benefits, one of which is it's injectable free. You don't have a needle. It's nasal delivery. It eliminates the cold chain, which is an issue with the injectables today, and it has other, it avoids a lot of the food effects that you see with the current orals. You don't have to worry about degradation in the GI tract, which is what you see with orals today, and sometimes that reduces efficacy. Robert is going to now take you through a little bit more details on the GLP-1, some of the data that we have today, and some exciting new data we have going beyond the nasal formulation. Robert. Thank you, Lisa. If you have followed Orexo for a while, you may be aware that last year we publicly presented also some results from our first generation of nasal semaglutide formulations. Last year, we performed a preclinical proof of concept study in animals, where we compared bioavailability from the amorphous nasal formulations to an oral commercially available reference product, so to an oral tablet. We can see the PK curves up in the right corner, where we have, especially in red and magenta, two of the best performing nasal powder formulations, and we have the oral Rybelsus tablet at the bottom. We saw significantly improved bioavailability after nasal administration of amorphous formulations. This is early still, but it's obviously very encouraging and very promising. Furthermore, we have demonstrated that our nasal semaglutide powder is highly stable. We can see in the bottom right corner, we have a stability graph over six months, and here the powder has been stored at 40 degrees for six months, and we still have 100% of the API left. So there is basically no degradation occurring of the semaglutide API. Since last year when we generated this data, we have had the opportunity to discuss and interact with the experts in the field and with companies who are active in this space. I think today we have received a good understanding of what will be required for us in order to meet or to be able to develop a commercially attractive nasal product. Right now, we are in the process of making the next generation, I would call it, of our nasal semaglutide powders. This is work that is ongoing, and we definitely plan to perform an additional proof of concept study also on this new generation of nasal powder formulations. In addition to looking at GLP-1s after nasal administration, we are currently also exploring if amorphous could add value to oral peptide delivery. This is also something that came up in our discussions with the key experts in the field. Why do we think that amorphous actually could add value to also oral peptide delivery? Well, first of all, again, it's an amorphous material. It can create a supersaturated state of the molecule at the site of absorption. In this case, if you take it orally, it's in the gastrointestinal tract, not in the nasal mucosa, but the principle is basically the same. We know that we have a lot of experience developing tablets, and we know that we can make tablets with suitable disintegration, dissolution properties, which is important for oral peptide delivery. Again, our composite powder allows us to co-localize certain critical formulation components together in the same particle. This could, for example, help in the avoidance of peptide aggregation, which is detrimental for oral bioavailability of these peptides. We can make sure that we get these critical components released at the same time and at the same place, at the site of absorption, again, with the hope of this helping the oral bioavailability. Obviously, the benefits that could come from amorphous in oral peptide delivery is that we could We are aiming for higher bioavailability that would allow us or others to reduce the dose of these rather expensive peptides, which is, of course, a huge benefit. We could reduce the food effect and allow for a product with more flexible and convenient dosing. The stability properties we see with AmorphOX could allow for a product with extended shelf life. Right now, we are in the process. We have started to make our first set of oral tablets based on AmorphOX, so this is work that is ongoing. During this process, we also identified new IP opportunities, so we have filed new IP around this concept as well. We are looking as a next step, that is to perform and test this in animals later this year, in a preclinical proof of concept PK study. That is the immediate next step, and we're very much looking forward to those results. Back to you, Lisa. Thank you, Robert. I'll introduce our second use case, and then I'll turn it back over to Robert. Our second priority use case is vaccines, and we're focusing on respiratory vaccines, specifically infectious disease, and that is where we will start because it's most feasible in the short term. It doesn't mean that we won't go into other areas in the longer term. Why an AmorphOX-formulated vaccine? Well, it is thermostable, and thermostability is extremely important, whether it's powder for reconstitution or whether it's powder for intranasal administration. It eliminates the cold chain, which certainly increases patient access and patient reach around the globe. Even in the developed world, it reduces transportation costs, it reduces storage costs, it reduces distribution costs because you do not need refrigeration. AmorphOX vaccine is stable at room temperature. We also have some preliminary preclinical data, which Robert will go through later, that shows that an AmorphOX-formulated intranasal vaccine induces a strong systemic immune response, IgG, and also local response, IgA in the nose, and that mucosal immunity could help to reduce transmission of disease. I'm gonna turn things back over to Robert, who will take you through some more of our data on formulating vaccines and some of the success that we've shown. Thank you. The data we have generated so far, I would say is very promising and again demonstrates the versatility of AmorphOX. We have successfully been able to formulate three completely different type of vaccines. The first one here is actually the spike protein, the COVID spike protein. This is a protein-based vaccine that we. I think this was the first vaccine example that we generated. We were successful in formulating it. We could demonstrate that the protein actually survived the manufacturing process, and actually, it turned out to be a thermostable powder with this protein being intact and still active after storage, again, at 40 degrees for three months. Forty degrees is. That's very high temperature when you're dealing with a vaccine. The second type of vaccine that we formulated was actually a live attenuated virus, and this is particularly remarkable, the results we were able to generate. These live virus particles, they are extremely fragile. They are usually stored at either minus 60 or minus 80 degrees Celsius. We were able to turn this into a powder that we have data. I can't go into details because this was done in an external collaboration, but we have data that supports the development of a thermostable powder with a live attenuated virus. These results are pretty remarkable, I would say, and shows the stabilization properties of AmorphOX. Thirdly, we have successfully formulated OMV type vaccine, and OMV stands for outer membrane vesicle. This was done in a collaboration with another Swedish company called Abera Bioscience. We used their Abera vaccine platform. We can see the OMV particles that they used, and then they link protein antigens to this to form these vaccine particles. We did a collaboration, a preclinical proof of concept study using their influenza vaccine candidate. We formulated this influenza vaccine into our powder-based platform. We nasally administered this to rats in this case, and it was demonstrated that we got a strong immune response, both a systemic response, as Lisa mentioned, as well as a local immune response. This was very promising data and so far the most progressed vaccine data we have to date. In addition, we have again demonstrated the thermostable properties of AmorphOX. We formulated the OMV particles, these vaccine particles, into the platform. We stored them at 40 degrees for 6 months, and basically, we see no change in the structure or in the build-up of these particles. It's labeled protein integrity here, but basically there is no degradation of these vaccine particles. This is very, very promising. Again, this is early explorative research, but very encouraging. Looking ahead on our efforts in the vaccine space, obviously, we aim to advance our collaboration with Abera. We are planning a next set of animal study, which is hopefully more advanced. We are also aiming at initiating new collaborations, both with industry partners as well as academic partners, and we have actually several discussions that are ongoing at the moment. In the end, the aim is to generate more data, showing the capability of AmorphOX in the vaccine space to hopefully get better traction and be able to close larger partnerships in the future. That actually concludes this session. Then I will give the word back to Lisa Moore, who will introduce OX640. Thank you, Ola. Our presentation now is going to focus on OX-640 or 640, as some of us call it. It is our epinephrine nasal powder that is in development for type 1 allergic reactions, including anaphylaxis. This candidate is critical for the future success of Orexo 3.0, and we think it's going to be one that will contribute considerably to that future. It addresses a rather large market. Around the world, there are over 200 million people that have food allergies. The market is about $3 billion currently. It's projected to grow to $8 billion, $6 billion over the next 8 years by 2033. We strongly believe that OX-640 is well-positioned to become the gold standard in nasal epinephrine. There are three things that I want you to take away from this presentation. The first one is, yes, the epinephrine market is large. It's large, and it's growing, but it's an unsatisfied market. Why is it unsatisfied? It's because the market leader is the auto-injector, which you see right here. It's rather large, and it's bulky. It's not easy to carry around, and there's a lot of needle fear and individuals who hesitate to give an injection when needed. The second thing is a nasal spray has entered the market. A nasal epinephrine spray has entered the market. They're the first to market, and they're seeing commercial traction in the United States and around the world, and that means a lot for OX640's future as well. The third thing is that we intend to provide a better solution for patients and provide differentiation in the eyes of the customer, meaningful differentiation. A little bit about the first nasal spray that's come to market. It hit the U.S. market in the fourth quarter of 2024, and the first year has been very promising, with over $72 million in revenue. Their third quarter revenues were two and a half times their second quarter, which beat analyst expectations. They're also expanding their footprint globally with regulatory approvals in the EU and U.K., Japan, China, Australia, and New Zealand. They launched in Germany six months ago, and within six months they were at 18% market share. It's been well received by the payers. It has a price premium over the nasal spray, which shows that they value that non-clinical attribute of being a non-injectable. Analysts are forecasting that product to be $1 billion in revenue, $0.5 million in the United States and $0.5 million ex-US. There's certainly some parallels that can be made to the naloxone market. Nikolai mentioned at the beginning that I was with Emergent, and I was actually there in 2018 when they acquired Adapt Pharma, the makers of Narcan nasal spray. I was a part of that M&A team, and Adapt had launched Narcan in 2016 as a nasal spray. That injectable had been around for many, many years, since the 1970s. They weren't sure how the market would be transformed, and it was a little slow to start. When Emergent acquired the product by 2019, it added $200 million in top-line revenue to the company, and at peak in 2021, it was over $400 million. It is possible for a nasal spray to come in and transform the market. Granted, the naloxone market is different. The price points of the products are different. The buyers are different. There are some similarities, and we think that the signals are very positive for an epinephrine nasal spray. This is our target. We want to be the best-in-class nasal option for severe allergic reactions. We are aiming to provide a differentiated product profile, and that differentiation needs to be meaningful in the eyes of the customer. We have very good data on our powder. It is very stable at low temperatures and very stable at high temperatures. It's important because at low temperatures, at freezing temperatures, it does not freeze, which is unlike the liquid nasal sprays, which do freeze at freezing temperatures, and they need to thaw out before you actually use them. We're also aiming for a rapid onset and high plasma levels that extend for a long period of time under both normal conditions and allergic rhinitis conditions. We're aiming for a very long shelf life with good stability. We have good data, and we're well-positioned to achieve these things. Here we have some preliminary data. These are preliminary PK data from our dose-finding study and also from our final formulation study. Mind you, this study was done with healthy adults that have seasonal allergies, and the study was done outside of the allergy season, so we were able to test our product with the patient under normal conditions and then with the patient under allergic rhinitis conditions. These are geometric mean concentrations. We measured plasma concentrations of OX640 under normal conditions, which is the red or orange line, I should say. Under allergic conditions, which is the magenta line. In black, we have the manual injection curve, which is the reference product, and the dotted line is an auto-injector curve, which was superimposed. That was not a part of the study. That's a cross-study comparison. As you can see, we have a very sustainable PK profile with clinically relevant plasma levels that stay above the 100 picogram per milliliter threshold, which is typically the measure of effectiveness in anaphylaxis. It's a measure of therapeutic efficacy. We have very rapid absorption, we have high bioavailability, and we have good margin versus the IM. Now, we have not done a competitive head-to-head study versus the nasal competitor, but we have done a cross-study comparison, and under NAC, which is the nasal allergen challenge, we have a superior profile, and we have longer relevant plasma levels, higher total exposure, and that's under allergic rhinitis conditions. The nasal competitor, when you look at their data, they go up to about 150 very rapidly, and then they rapidly fall quickly below the 100 picogram per milliliter level. We do not believe that nasal congestion will impair our drug's absorption or efficacy. Of course, everything will need to be confirmed with the final commercial dose. This is what it looks like. This is the EpiPen, the auto-injector. You've probably seen them before, and this is our product in terms of size. It's about half the size of the EpiPen. Very small, compact, portable, very easy to use. The device is inside of a storage tube. I know that it's cumbersome because I have a son that has asthma, and he doesn't have food allergies, but he has to carry his albuterol inhaler with him at all times because it's induced by pollen and things like that and exercise. Having to carry something like this around would be very difficult in your pocket or even in the backpack. It's much easier to carry something like this. His Albuterol inhaler is about this size, and you can get him to carry it. If it were this big, it would probably get left behind. This is the last slide that I have before I turn the presentation over to Cecilia. We did our own market research on OX640. We interviewed clinicians, allergists, primary care physicians, patients as well, and their caregivers. What we learned from our study really confirms what we're hearing in the marketplace about the epinephrine market. There is great enthusiasm for non-injectable routes, smaller products, enthusiasm for smaller-sized products, enthusiasm for longer shelf life because the auto-injectors have a shelf life of only about a year, the competitor a little bit longer than that, and we expect ours to be even longer. Temperature stability is also important. There's enthusiasm for a product that's stable at very low temperatures and also stable at very high temperatures. We believe that OX640 is well-positioned to become the gold standard in nasal epinephrine delivery. Now I'll turn the presentation over to Cecilia, who's gonna take us through some of the next steps in development. Early OX640 work was done with earlier formulation, also small-scale manufacturing. Now it's time to scale up manufacturing before our pivotal clinical trials. That goes for both spray drying as well as the fill assembly packing process, which I will talk a bit more about later. The product, including the instruction for use, will be tested in human factor studies in which you have lay users test the product to see that they can understand the instruction and administer the product under really stressful conditions. We're right now waiting for the final FDA feedback on our development program, and after that it's time to move into pivotal phase. Since the first clinical study is a PK/PD study in allergic subjects where you have the induced allergic rhinitis that Lisa talked about before, the nasal allergen challenge, this needs... We need to make sure that these subjects do not have any allergic symptoms before the study, which means you have to run the study during the non-allergy season. In the Northern Hemisphere, that's October to March. That sets the timeline on when we can start the program. For OX640, we've used all the learnings we sometimes painfully gained during the Isepre and AmorphOX development projects to de-risk the product. We know the FDA expect to see final commercial product manufactured on the final commercial lines for reliability studies, but also preferably before the clinical studies. As Isepre and OX640 share lots of the same components, we can use the same manufacturing setup. These manufacturing lines were set up, invested, and inspected by FDA during the Isepre project, which we can now take the benefit from. Running human factor studies is notoriously difficult, and to make people read instruction is even harder. We will start the OX640 human factor work early. For neffy, we initially had some problems, but then we had a successful outcome. The instruction for use for OX640 will be based on the successful version of neffy. One benefit of not being first to market is that the regulatory authorities like FDA and EMA has not only reviewed our development program, but they also looked at other nasal epinephrine products. All that information is taken in when we design the OX640 clinical program. For example, the sustained plasma concentration Lisa talked about, that reduces the risk of us having to do a repeat dose study in a nasal allergen challenge that been asked of other competitors. All that has been taken in when we designed the program. Let's look at the timeline. We're in the middle of scale-up and transfer to all our commercial sites. I already talked about the human factor studies. One further point why it's important to do this early for OX640 is that we have a clinical study in which subjects will need to self-administer the product. For that, you need the final label. You need to do it, the human factors work early. The clinical program, as you see, is divided in two parts. First, you've got the program for the adult dose to make sure that's safe and effective before you move it over to the pediatric study. Data from the adults and children over 30 kilos will be included in the initial filings that are planned for 2028. We will have a supplemental approval for a pediatric dose for younger and lighter children to follow after that. My favorite subject, manufacturing. Besides spray drying, we have a unique FDA-inspected manufacturing capabilities for nasal powder products, which is designed to meet the FDA reliability requirement of 99.999%. That means that the risk of a faulty device reaching the market must be less than one in 100,000. The product with all the components and the manufacturing process is designed to minimize any risk far below that level. That type of reliability is not feasible to prove that by testing the finished product, which you would normally do. We have taken a lot of engineering during the IZIPRY development into making this happen with numerous sensors and control stations throughout all the manufacturing steps where we've identified a risk of a faulty something going wrong. We put a lot of know-how, time, and investment in doing that, and now we have one of the very, very few manufacturing lines in the world that can produce pharmaceutical rescue products that meets this extremely high bar. I'll try to tell you a bit more as an example. This storage tube, which Lisa showed before, it has been designed to protect the product from moisture. The product is sensitive to moisture because it's been designed to dissolve in a very small amount of liquid. Inside this, there's a material molded in that capture any moisture that comes into the tube. Every single unit of this storage tube produced is inspected visually and also leak-tested to make sure no moisture has come in, that it's tight, and then it's shipped to us. When they ship to us, and before you put it on the packing line, and before you add the device, you have to measure. The lid is closed. It could have opened during transport. I would have used some of that moisture budget. You put in the device, you close it, and then you measure again. Is it really closed? You will apply a tamper-evident wrap to that would always show if it's been open when it shouldn't have. This type of rigorous process with double and sometimes triple-check is needed for all aspects of the manufacturing where we've identified a risk. Having this manufacturing in place puts us in a very good position, not only for OX640 or other rescue products, but also in a preferable position to other competitors because they would need to invest a lot of time and money to set up this type of manufacturing. With that, I've concluded this. It's now time for a break. 15-minute break. There's coffee outside, and we'll reconvene in 15 minutes. Thank you. Welcome back from the break. My name is Edward Kim, and I am Orexo's Chief Medical Officer. I'm here to describe for you Orexo's journey into the medical countermeasures arena with OX390. Now, the journey actually began back in 2023. As you recall, we had just filed with the FDA for approval of IZIPRY, a high-dose naloxone rescue product, so we were very much aware of and interested in the opioid overdose marketplace. Now, that same year, the White House, the Biden-Harris administration declared xylazine mixed with fentanyl as an emerging public health threat. This was over and above the opioid public health emergency that had been declared in 2017, several years earlier. The DEA also, in their National Drug Threat Assessment, began to cite that they were detecting xylazine, which is an animal tranquilizer, mind you, in numerous seized samples of illicit opioids. Later that year, the nonprofit foundation of the U.S. Food and Drug Administration held a workshop that was both live and via live stream on mitigating the dangers of human exposure to xylazine. 2023 was a very big year. Xylazine, as you may recall, is a veterinary medicine used as a tranquilizer, and so it gained the nickname on the street as tranq. It's an alpha-2 agonist that does not interact with opioid receptors and therefore is not reversed by naloxone. Over a five-year period in Philadelphia alone, overdose deaths went from 2% to over one out of four deaths in the Philadelphia area in which xylazine was detected. It was definitely an appropriate emerging threat. More importantly, it wasn't localized just to Philadelphia. Now, if you look on the left-hand side, it's a little bit hard to read, but the lower line graph shows the detection of xylazine up through last year in powdered fentanyl, which is the most commonly found form of fentanyl that's seized by the DEA, less so in tablets. By the end of last year, one out of three samples of fentanyl nationwide was testing positive for xylazine. On the right-hand side, you see the regional distribution of xylazine being detected by the Drug Enforcement Administration, and it looks very familiar. This is what fentanyl looked like 10, 12 years ago, starting mostly in Pennsylvania and the Northeast, but then spreading across the nation. Now, 10 or 12 years ago, there were people who said fentanyl is just a sporadic, isolated issue. Now, it's everywhere. We believe that the spread of xylazine in these illicitly manufactured opioid samples is going to mirror the spread of fentanyl, and that eventually it will become a nationwide phenomenon, widely used, widely discovered, and widely prevalent. Okay, xylazine is everywhere. What's the problem? Well, it causes some of those unsightly lesions. It causes people to act like zombies, which many of you have seen video of that on the news. That's not the real problem. The problem here is that the number of fentanyl-involved deaths in which xylazine is being detected nationally is increasing, and increasing quite rapidly. Even in 2023, which is the last data point in this slide, that was the first year, if you recall, that the actual overdose deaths in the U.S. began to decrease. It still continues to rise. Now, we believe the decrease may be due to a number of measures, including the widespread availability of naloxone and nalmefene, which may be saving people's lives. As I mentioned, naloxone and nalmefene don't interact with xylazine and drugs like it. Completely different mechanism of action. It's possible that xylazine-related deaths from opioids will continue to rise even if the overall number of overdose deaths decreases, and that xylazine and drugs like it may actually cause an increasing fraction of deaths due to opioids because there isn't an available antidote. It's kind of a disturbing situation, and it's made even worse by another drug, another animal tranquilizer called medetomidine, which is called, appropriately, Rhino Tranq, like a rhinoceros, big animal, because it's about 200 times more potent than xylazine. Just like fentanyl is about 100 times more potent than morphine and heroin. We're talking about a much more serious threat than what the White House declared three years ago. Now, it has a similar mechanism of action, interacts with the exact same receptor, but just much more potently. In Philadelphia, it was first identified in drug samples by the Department of Health in May 2024. By the end of the year, 90% of the opioid drug samples in Philadelphia had medetomidine, and xylazine was only around 20%-30%. Now, that's in Philadelphia, but you remember that heat map, how things spread. What we anticipate is that this even more potent animal tranquilizer will eventually replace xylazine in the opioid drug market. Again, it's getting very common, and it means that there's a second wave of alpha-2 agonists. That suggests that this is not just something that is gonna come and go. Fentanyl, there were people ten years ago who said, "Well, it's just a fad." They were wrong. We have every reason to believe that this is going to be an enduring problem for which there is currently no solution. One question, because we like to follow the science, is why is this so lethal? Why is this combination so bad? Well, the current animal experiments are using xylazine, but emerging data are suggesting that there's going to be an even greater interest in medetomidine. When you give an opioid, the mu-opioid receptor is interacted with. Fentanyl in rats, if you want to kill 50% of the rats, and this is what they do in laboratory experiments, you can give them about a hundred and thirty milligrams per kilogram, and that will kill about 50% of the rats. Dr. Mark Smith, and we'll hear from him in the prerecorded interview, actually gave a non-lethal dose of xylazine to the same rats, and he found that only 1 milligram per kilogram killed them. He was able, in his experiment, to weaponize fentanyl, as if it's not bad enough, making it 100 times more lethal by giving a non-lethal dose of xylazine. We believe that this has its effect, and there are other labs suggesting that what it does is it reduces the respiratory drive. It increases opioid-induced respiratory depression, which is how people die from opioid overdoses. You take enough, you stop breathing. Xylazine and drugs like it appear to magnify that effect. What's interesting is that anesthesiologists who use dexmedetomidine for human sedation are the first ones to recognize that a targeted alpha-2 antagonist is necessary. These clinicians and clinical experts who understand sedation, understand anesthesia in humans are the ones who began identifying atipamezole as a potential solution. That's exactly where Orexo is sitting right now. What we anticipate is that atipamezole, using the same manufacturing line, using the same AmorphOX technology, is a potential solution because the AmorphOX powder provides that rapid absorption and high bioavailability, temperature stability. Powders do not freeze, therefore, you can actually get the nose-to-brain transmission rapidly. You don't have to wait for something to thaw out. We all know that in the winter here, everything freezes, and in areas of the U.S., everything freezes too. Let's talk a little bit about atipamezole. It is a new chemical entity for humans, even though it's been used since 1996 as an antidote in animals for xylazine and medetomidine. One reason why it's been de-risked is not just because it's been a veterinary product for 30 years, but actually the manufacturer, Orion Corporation in Finland, did extensive preclinical studies to enable the local health authorities to authorize human experimentation, human clinical trials, first in human studies. It was actually studied pretty extensively in the 1980s and 1990s to reverse sedation due to the anesthesia medicine dexmedetomidine, and it was found to be quite effective and really well-tolerated as an intravenous dose in an operating room setting. The reason why they discontinued development was because the anesthesiologist said, "People wake up from dexmedetomidine quick enough. We don't need to give them an antidote." There was no safety signal, but there was a very clear efficacy signal that the pharmacological effects of a potent alpha-2 agonist could be reversed very quickly and very safely. Right now, we're disclosing to you for the first time that in May 2024, we actually had a meeting with the FDA, a pre-IND meeting to discuss with them this problem and begin to map out a development pathway to approval. The FDA at that point agreed that the unmet need due to xylazine adulteration in the illicit opioid supply was quite high and that atipamezole had the potential to meet that need. As a result of that, we engaged with BARDA, the Biomedical Advanced Research and Development Authority, which is within the Department of Health and Human Services, which is also where the Food and Drug Administration is located in the U.S. federal government. You're aware that in September, we announced that we had been awarded a contract for the base period of 18 months to enable the pre-IND preclinical studies that would enable our first in human clinical trials, as Nikolai said, potentially in 2028. It's a cost-sharing contract where BARDA not only provides their technical expertise, but they're also paying for the vast majority of the developmental expenses, including internal salary expenses for anyone working on this project. There are 4 additional option periods leading up to submission and approval of this drug in the United States. The total value of that project is up to $50 million that BARDA would pay to Orexo. The work started at the end of last year. Where we are today is we've completed some in vitro studies. We actually conducted a number of these at-risk while we were still in contract negotiations to identify four formulations that we've begun our in vivo PK study to demonstrate proof of concept with intranasal absorption and bioavailability. As Nikolai said, we should have the results of that later this quarter. Actually, next quarter. This quarter ends next week. Second quarter. We're planning our non-clinical program that will be needed for our first in human PK study. To that end, we actually are in the process of submitting a request for a meeting with the FDA on further guidance to confirm that preclinical program. With that's where we are at this point. I want you to hear a pre-recorded in-Interview with Doctor Mark Smith, who's actually done some of the cutting-edge research to help us understand the threat, the lethality, and the complexities from a basic scientist point of view and why this has public health implications. Thank you, Doctor Smith, for joining me. I'm really interested in hearing more about this alpha-2 agonist opioid adulteration problem that I'm reading about a lot in the news. To start off, what can you say about how this is evolving and how this is starting to occur more in the opioid adulterated supply? Ed, first of all, let me say that I'm very happy to be here. Yes, you are correct, this is a very, very important issue. Just in regard to your question, I mean, this is a relatively recent phenomenon. Just, you know, this just kind of sprang up within the past five or six years. Of course, it kind of began with kind of the replacement of heroin with this illicitly manufactured fentanyl. Then not long after, there was this influx of xylazine. Now, originally, this influx of xylazine started within the Philadelphia area and kind of the northeast corridor, but then it kind of quickly spread westward to the Midwest and finally, really kind of throughout the United States. Now, of course, the major problem, at least initially, was xylazine. Recent DEA seizures, CDC information regarding toxicology screens from overdose victims. They're describing kind of a lessening in the prevalence of xylazine and kind of a new drug coming along replacing xylazine. The new drug is medetomidine. It is very, very pharmacologically similar to xylazine. It's an alpha-2 adrenergic receptor agonist. Right now this is kind of localized to a few regions. Philadelphia, Pittsburgh, Chicago are all reporting kind of very high prevalence rates. Again, we're seeing kind of the slow and steady spread with medetomidine slowly but surely starting to replace xylazine in the supply. In fact, most overdose-related deaths and, you know, even non-lethal overdoses typically report that there are some adulterants within the fentanyl. You see the alpha-2 adrenergic agonist, and they are most prominent. Of course, there are other types of drugs such as benzodiazepines, methamphetamine, and other drugs in these seizures as well. The alpha-2 agonists seem to affect blood pressure, heart rate, and add their own bit of respiratory suppression. In your research in animal models, what are you seeing and what are you seeing coming out of other labs that are studying these sorts of mixed overdoses in animal studies? Ed, that is an excellent question. We are examining that currently in my laboratory, and a lot of my colleagues are addressing this question as well. I've just pulled up a slide here, and what I want to emphasize here is that this represents a combination of fentanyl and xylazine. This was a mouse lethality study. This used several laboratory mice. We used males and females. Just to kind of give you one take-home point, we're seeing similar effects in both sexes. What you're looking at here is a dose effect curve of fentanyl, and this is what you see in the purple circles. What you're looking at here is lethality. Notice that fentanyl has a very, very steep dose effect curve. Within only half a log unit, you go from having non-lethality to complete lethality. It's a very, very steep dose effect curve. You reach a threshold, and then most individuals, you know, die very, very quickly. Now, what you see in the purple triangles is doses of fentanyl in combination with a single dose of xylazine. Now, the dose of xylazine we selected was 100 milligrams per kilogram. Now, this is a relatively high dose of xylazine, but what I wanna emphasize, this is 100% non-lethal. In other words, although the animals are highly sedated, none of the animals died when we gave them 100 milligrams per kilogram xylazine. But notice, if this non-lethal dose of xylazine is on board, fentanyl is much, much more potent at producing lethality, and this is represented by increasing lethality at much, much lower doses. Now, you can determine a lethal dose 50, an LD50. This is a common term used both in science and in the clinic to describe the dose that's estimated to produce lethality in 50% of the individuals. When xylazine is on board, potency of fentanyl to produce lethality is increased by 100-fold. In other words, doses of fentanyl are 100 times more potent at producing this toxicity if xylazine is on board. Looks at fentanyl in combination with medetomidine. We're not looking at lethality in the study. We're looking more at the mechanism by which this toxicity is produced. We're looking at respiratory rate, we're looking at heart rate, we're looking at oxygen saturation, and we are looking at pulse distention. This is a measure of hemodynamics. It's a measure of how well blood is perfusing to the various tissues. What we're seeing is either additive or synergistic interactions between these two drugs. Whereas, you know, at doses that only produce small decreases in heart rate and respiratory rate when these drugs are given by themselves, you see very large decreases in heart rate and respiration when these drugs are given in combination. Although our data are still preliminary, one of the most interesting findings that we're finding is that in regards to the hemodynamic issue, in regards to pulse distention, you know, blood transfusion to the tissues, you know, at moderate doses, these drugs are not producing any effects on that measure. In combination, you're seeing significant decreases in pulse distention, and this really has real-world implications. Because, you know, sometimes you can rescue an individual who has had this drug combination by giving naloxone, and they start breathing again. However, they are still heavily sedated, and they're still purple, because of these, peripheral vasoconstriction and not an adequate, blood supply is getting to the body's tissue. That represents a real problem with this drug combination and the use of our traditional rescue medication, naloxone, in treating these victims. Wow. That sounds like it's just a really difficult pharmacologic situation, that the alpha-2 agonist, xylazine and medetomidine, are likely to increase the lethality of fentanyl, but naloxone alone doesn't seem to reverse all of those effects. Because naloxone only interacts with the opioid receptors, how is this going to complicate these mixed overdose scenarios in the real world? What this kind of translates to, and I'm talking about first responders, those individuals that encounter a potential overdose victim, there's a very standard thing they do. They pull out the naloxone, they pull out the Narcan, and give that immediately. Well, first of all, you don't see the typical response. Now, if it's a kind of just a straight opioid overdose victim, those individuals can be up and, you know, talking to you 60 seconds later. They're typically very, very agitated because you really, really messed with their high. They're probably going through some mild withdrawal syndrome. They are breathing normally again, oxygen saturation is high, and again, this happens within minutes of naloxone Narcan administration. Now, that is not the case with these drugs. One of the principal hypotheses is that the cartels are adding these drugs in order to prolong the effects of fentanyl. Another reason that these drugs are being used is because they are readily available. Both of these drugs are used in veterinary medicine. They're readily available and they're relatively cheap as well. Emerging adulteration of opioids with alpha-2 agonists both has an immediate risk whereby people could die before they're even brought to the hospital. If they are successfully revived by an alpha-2 antagonist as well as naloxone, there may be some ongoing complications related to a withdrawal syndrome, so that this, again, further complicates this opioid epidemic that is really ravaging the United States. That is exactly correct. You know, the one thing I wanna do emphasize, you know, I don't work in medicine, but I've talked to a lot of emergency room physicians, and they say, "You know, if we can get an overdose victim here in the emergency department alive, we can take care of them." Once a person is in the emergency room, there are the resources there to take care of them and get them out, typically within 24-48 hours, even in the most severe cases. The problem, the big problem arises, particularly with this drug combination, they never, ever have that chance to get all the way to the emergency department before suffering that lethal overdose. Again, thanks so much for your time. You've really made it very clear that this ongoing adulteration that's growing is complicating the opioid epidemic. It's making it worse. It appears to be by design, and that an antidote to add to the armamentarium of first responders seems to be necessary. Yes, you're exactly right. Ed, thank you very much for having this discussion with me, and thank you for the important work that you're doing in this area. Okay. Now I want to invite, Fredrik to come up and talk to us about the corporate strategy regarding business development. Thank you, Ed. I'm Fredrik Järrsten. I'm CFO at Orexo, three and a half years now. Let's briefly go through how business development can support Orexo's business model post transformation. I'll talk about the platform logic, AmorphOX platform from a business development perspective, the capital strategy associated with that, and our revenue scale through licensing partnerships and milestone economics. Emphasizing what Nikolaj previously said on the strategic transformation following the divestment of Subsol. That gave us financial flexibility to really enabling a shift to a platform and development driven model. Meaning that we focus our investments on the three pillars that Nikolaj also explained. Exploring AmorphOX technology, developing the proprietary projects to value inflection point, and building partnerships leveraging the AmorphOX technology. Now, business development has an important operating role in this. Through market insights, i.e., business intelligence, efforts, steering our R&D priorities toward opportunities which we then deem to have the highest probability of commercial success. Through partnerships where BD will source, qualify, and negotiate partnership structures, revenue from up-fronts, milestones, and royalties, also cost-sharing. Through funding, BD helps out through transactions of both business and corporate development perspective. The end state is that we strive for capital efficient business, scalable revenue streams from technology, partnerships, and milestones resulting in value creation. Continuing on transactions. Orexo has a long and proven track record, partnering track record. Material financial impact, providing financing for development efforts. On the right-hand side on the slide, we list partnerships and funding from transactions, on licensing rights, royalty streams, government funding, and most recently, obviously, the sale of Subsys asset. We think, and we believe we have the track record and credibility of closing partnerships deals, and we know how to structure them and to deliver on commitments, and then obviously how to reinvest this funding into the next development phase. Coming back to our three focus areas and how they diversify Orexo's risk-reward profile. In the graph, Orexo cost share on the X-axis and the profit share on the Y-axis, starting from the lower left end with partner AmorphOX area. The partner bears the most of the development cost. Our profit share comes via royalties at commercialization. Moving to focus area, explore AmorphOX technology in the middle of the graph. That means new transformative areas with potential. We drive initiatives to proof of concept data, and then we partner with reduced risk. In the top right-hand corner, we develop proprietary projects, and we build value to clear inflection point. That could be pivotal data, that could be regulatory approvals, and then we partner. We may also retain a potential role in commercialization when strategically sound. The message is, we believe that our portfolio design diversifies risk return. We talked about value inflection, and partnering at value inflection is a main source of financing for Orexo. We look here at the respective value inflection in each focus area in the explore phase. That is where we have the strong proof of concept data, which then could facilitate a licensing, partnering project where the partners share development costs, and we can structure an agreement with partner paying royalties and milestones. Now in the development focus area in the middle there, the inflection point for IZIPRY is FDA approval. For OX-640, it's clinical data from pivotal trials. For OX390, it's clinical data from humans. Reaching these inflection points, we will strive to sign partnering agreements structured with payments of upfront milestones and royalties. Looking more specifically on our investment focus in relation to R&D costs. The graph to the left that shows the R&D cost level moves upwards exponentially from the early exploratory phase through the clinical phase, and then the significant R&D cost level in our pivotal phase set with the projects of OX640 and IZIPRY. This is underlined also in the graph to the right, showing the allocation of R&D investments to these three focus areas that we talked about. Development area with OX640 and IZIPRY corresponds to approximately 85% of R&D costs in 2026-2028. OX640 also constitutes a main part of those R&D costs, approximately SEK 210 million in development external R&D costs in 2026-2028. That is in order to get to finished developed product. Worth to note also is that we have a fully financed budget for 2026, including development according to plan for each of these product development projects. Now this is, though, not considering any activity outside our control, like any development in the DOJ case. Business development is the main source of R&D funding from closing transactions and finding partnerships. Components of that are the Zubsolv divestment, including earn-outs. We have the BARDA research grant. We have ongoing royalties from products, Zubsolv ex-US agreement, the Abstral and Edluar products. Then we have prospective future milestones, royalties from development programs, as well as partner-funded R&D for AmorphOX-enabled projects. These funding sources have and will be instrumental for Orexo for R&D financing. We will also mention that opportunities for long-term financing through the capital markets are continuously evaluated, as should be. That is depending on company's performance and market conditions. Now, that was short and sweet, and that marks the end of the presentations, and I will now invite Nikolaj to come up for closing remarks and Q&A. Thank you. Is my microphone on? Okay. Thank you. I hope that you share our enthusiasm about the breadth and the innovation that we have in our AmorphOX technology and the platform. I hope that you see that we have some quite late-stage projects in IZIPRY and OX640, where we have an attractive risk/reward balance. The risk in the projects are very controllable because of the work we have done with IZIPRY and for OX640. The clinical data we have already from the first studies are very promising, and that also mean that when we're going into now the last pivotal stage of, for example, OX640, it's done with controlled and manageable risk. When we come to the OX390 project, I will say here, if it's not clear, we are the only company that we know of that is working on an overdose treatment for tranq. There's no other company that we're aware of. There are some academic groups that are looking into this, but what the feedback we get from the market, from FDA and others is they want it to be a nasal spray because you want it to be administered at the place of overdose. The work we are doing there is actually something that is. We are on the forefront of something that unfortunately can turn out to be very serious for the U.S. When it comes to our AmorphOX technology and the projects that we are working on, we did talk a little about our GLP-1s and how we, based on feedback and interactions with industry players, we are seeing how we can optimize or should optimize our nasal administration to reach commercially attractive levels. Also our opportunity to move into an oral formulation which can actually improve the bioavailability of the existing tablets on the market. Those of you who have been following that, it's kind of the Wegovy tablet from Novo Nordisk is doing very well. If you're looking at the actual efficacy and the amount of product that is needed to reach therapeutic level, it's very high. If we can improve that, we think that's a big value, both in terms of functionality, but of course also we have patent and patent applications which reach well into the forties. Where are we as a company? As I said before in the start, the slide has been up before. We are looking to build an engine around our amorphous drug delivery technology and become a global leader in this. That means that we want to drive the leadership in amorphous drug delivery technologies, working with some of our early-stage projects, testing new exploratory areas to document and show how we can work, building partnerships with companies. We do work with companies right now in partnerships around the AmorphOX platform, but as you've seen, we haven't done press releases because a lot of these are in the feasibility stage, but also on some of these exploratory projects, we're working with a knowledge transfer. We basically share what we have, and they share what they have in terms of know-how, and then we're working together to see if there are foundations for a more advanced partnership. We also have to advance our projects. I think this is where we have a lot of value short-term. If you look at the neffy market, for example, it was a little slow start last year, but then it took off more in the second half. All indications from the U.S., expectations from those close to the market is very promising and high. For us to come into clinical trials, I think, is important. Or the final dose in a clinical trial is important. That's feedback we also hear. Driving our projects to inflection point is something that is of high priority at the company. As Fredrik just went into, this is where most of the money goes also. We want to expand. We would like, and Fredrik used internally to talk about AmorphOX, a little like Intel Inside, to see that our amorphous technology is used by other companies to advance their projects. We believe that we have some unique properties around the platform that could be valuable for other companies. Again, most companies we're speaking to want to see more than just a PowerPoint. They want to see real data. In particular, in biologics, this is what we need to generate. Lisa talked about the studies we have done in the U.S., where we were out talking to a lot of industry players and the need to go through proof of concept, which involved in vivo data and probably in vivo all the way up to human data for some projects. This is where we're focusing at right now. I think we have some exciting time ahead of us. We have a fantastic technology, and now the challenge for us is just to ensure that we bring this out and get that converted into revenue-generating partnerships and long-term value creation. With that, I would like to open up for questions and answers. You're welcome to ask questions to the full management team here. We will have a microphone, but are there any questions, and please. To begin with just a assurance that AmorphOX is the focus. No adventures outside of that area. Yeah. Right now, this is the only place we're investing our R&D efforts is in projects based on AmorphOX. There's no other ventures at the moment. Okay. This is a nasal application. It is in no way a respiratory tract product. It's all about the nasal mucosa. I see Robert is ready to give a comment. Yeah. Is it working? It says on. I will try again. Yes, the AmorphOX nasal products, they stay at the nasal mucosa. Thanks to the manufacturing process and our technology, we can make the particles of the correct size, so they don't enter into the respiratory or the lungs. They actually stay at the nasal mucosa, and we have generated a lot of data showing that we get basically nothing, no particles in the lungs, which is of importance, especially from a toxicology perspective. A question about the semaglutide area. What you have is a very quick absorption, which is simultaneously a good thing and a bad thing because sometimes the side effects are higher when you have this spike. On the competitive landscape, you have other companies that have these delayed release options, which is, I mean, if you can give it once a month, once a quarter, that is a very good thing. You're not at all in, of course, not at all in that area. I think that on the last one, we don't have a depot formulation, but our AmorphOX technology could be used in a depot formulation. We are looking with other company who have technologies for depot formulation that could be combined with AmorphOX. It's early stage, but we are looking into this. It's a typical combination where you see the properties of AmorphOX and the properties of other products, and they see there could be advantages of the AmorphOX technology in a depot formulation. We don't have a depot formulation, and we won't be the lead of that, such a project. Our technology could be part of that. I also think there's always is there. If you go for monthly or you're going for quarterly, I know there's another very successful Swedish company who's working on this together with Eli Lilly. I think it's interesting if you talk to a lot of the people who are on semaglutide and others, they don't like the injections. The injection is actually something that people would like to avoid. Right now you do see that the Wegovy tablet, it's early days, but they were at least internally at Novo Nordisk, they're talking about it as one of the best launches they have ever had. That's clearly a drive towards something that is more convenient. It's. If you take a nasal delivery and you could take one nasal dose per week, I would personally prefer that over a large injection. That's, I think, a personal convenience factor. There's definitely competition. It's a very big market. We know about 25% of the population has a needle phobia to the extent that they avoid taking products. There's definitely those who would not take a depo formulation even though it's convenient. I think you have other aspects around the side effects. If you have something that is in there for a quarter, then of course it's a little hard to take out if you have issues with side effects on the product. I think for us, the work we're doing with semaglutide is a perfect model substance because it exists in tablets. They have done some good work going from Rybelsus to Wegovy. There's a lot of data existing out there, and we can easily access the active ingredient. We see there's an opportunity, of course, to work with semaglutide. Looking at how the market evolves, now there's a lot of generics coming in in some markets, so we'll see how that works on cost, on prices and others. It's also an opening for other companies working with other peptides because we can now compare. We have a good indication or so on a quite complex peptide, what is the uptake through the nose, and you can deliver it through the nose. It could be a starting block to work on other projects. If we look at some of the large players right now, I don't think Novo Nordisk is thinking that much about semaglutide. Of course, they want Wegovy and others, but they have a pipeline of other assets that they are looking at. Of course, that could be a place for our technology, and likewise with Eli Lilly, Pfizer, Boehringer Ingelheim also working on these projects. We see this as a door opener, but could also be a project that we decide to drive depending on the data that we generate. Lastly, on the commercialization issue, I do understand that in the beginning you will try to partner rather early. I listened to an established biosimilar company the other day. They took the substance all the way and then partnered and got about 40% royalty rather than the 10+. Is that something that you will consider later on? It's an excellent point. I think this is one of the issues we have been running into is some of the partnering opportunities we have had, for example, for six forty, you're giving away a lot of value because we feel that the risk is very low. If you're going in with a partnership too early, your royalty rates are very low. If you're coming in late, you have opportunities to come with much more attractive deals. I also listened at an event with, I would say, a U.S. banker who came in and said the worst time of doing a partnership deal is before you have shown pivotal data from your clinical trials, because that's when you get the highest uptake in value is when you have that last phase data. This biosimilar company, I think, is a good example of that. If you can take 40% really depends on the price point because that's a lot of profit that is going out of the company. I think there is a value inflection that is coming in the last stages of the project. For OX640, I think there's a lot of value for us to take it one step further. If you take for a GLP-1 vaccine, it is maybe a better example. It's very expensive to take this into any larger studies. For Rexulti to drive that through the process is nearly impossible. We don't have any vaccine technology either. It depends a little project by project. We need to look at the expenses. You have an excellent point in terms of the value lift up in the last phases if you get it all the way to approval. Claus. Maybe I could continue then on the same issue, at least, almost. Are you considering partnering OX640 in different geographies? I mean, the strategy here. Those of you, and I recognize a lot of you, who followed us for a while, and to be very transparent, we were very close to have a deal which unfortunately transpired into some highly confidential. Because of market events and change of management and others, we didn't get there, which could have been a good deal for us. We still have dialogues with regional players today. We would like to see someone who can take a bigger chunk rather than have to slice it down. We were also a little concerned about what happens in the U.S. with the pricing. You want to be sure that you don't undermine the prices in the U.S. If in this space, we believe about 80% of the value is created in the U.S. If you're going in with a when you look at partnering, you want to see what happens with the Donald Trump's pricing cap if you actually set a price cap by having a partner in Europe. Now it looks like that if you have a partner product, you can actually that doesn't include into. It's only if you commercialize the product in both geographies, you're under that kind of pricing cap that he wants to impose on Medicaid and Medicare in the U.S. That is an important aspect and that was quite uncertain for a while. I think right now we have to be opportunistic and look at what is the interest. If we can get good regional players, some of these leading epinephrine products. Even in Europe, you have some different leading players in different markets. I think that's quite important, someone who have a good footprint into the market. That is more important than looking at whether it's global or regional. I would say it's much easier for us to manage a large global partnership. Mm. If we can do attractive region by region, that is also an opportunity. Yeah. Especially it seems to be quite attractive pricing in Europe and Japan. It is. That is interesting because that's some of the feedback we got from a European player is to say, "But the prices is going to be set like the injectables." Now with the markets that have come out, the prices is actually quite attractive. Now they have started in the higher priced markets, but at least according to ALK-Abelló, where they have gained reimbursement in Europe, it's at a premium to the injectables, which is good. Just wondering if you have any comments about how you view a potential launch of epinephrine film. I know it's a complete response letter for now, but do you have any comments? Lisa, will you take it? Yes. Anaphylm, as you know, got a CRL. Mm-hmm. They're working feverishly to address the concerns. It was primarily human factors that they need to repeat and change some of their packaging. They expect to resubmit by the third quarter, I believe, of this year, and they'll likely get a fairly quick response. By the beginning of next year they'll be on the market. I think the film is a good thing for the non-injectable market. We anticipate that the market will eventually be majority non-injectables that around the world will see the nasal spray and the film take a stronghold over the injectables. I would say the film, it's for me, and we could probably make a sublingual formulation of our product also if we want to. The one thing, if you look at the people with an allergic shock, a lot of them starts to swallow a lot. You also have a quite high degree of saliva that you produce. For those who have such a severe reaction, to actually place a film and that you're certain that the film is delivering the effect is, I think is a challenge from a pure safety perspective. With a nasal spray, this is like the injectables. You're certain that you give it. There are people I've spoken to a lot of people who have allergies, that those who feel the allergic reaction comes, and it builds up over time. You have a window which is maybe on quite a few minutes that you can do it. Therefore to have the film and have that in your wallet or something is probably relatively convenient if you can do it yourself. I think when it gets to a situation where you need someone external to do it in a rescue setting, that I think is a little more difficult if someone is very swollen. Some of the pictures I've seen of people with allergic shocks, I can't really imagine that you should put your finger in and try to place that and be certain that you give the effect. It must be much easier to give a nasal spray. I think it's probably going to be a combination for some people. You have one when it's easy to transport, and then you have others in other settings. Thank you. Maybe I can leave the mic to somebody else if you maybe. Thanks very much for taking my question. I guess the first one is really just on more scientific interest on the BARDA collaboration, and whether you can just talk about whether there's any animal data on atipamezole actually reversing, helping to reverse the respiratory depression or not at this point. Ed. Yes. We've been in contact with some of Dr. Smith's other colleagues and researched the literature. The science does suggest that atipamezole does block the respiratory depression that is created by xylazine, and that naloxone alone doesn't do it. When they're given in combination, atipamezole alone doesn't. When you give one and then the other and block both mechanisms, that's actually the most successful. Okay. 'Cause you showed some quite nice animal data about the impact of the lacing with xylazine, but nobody's done the experiment where you give a laced fentanyl to rats and then inject with or apply the alpha antagonist followed by the naloxone to show that it reverses. Well, there was an early study done around 2023, 2024 that was recently published, and they did exactly that. They actually pre-treated the animals with atipamezole, and they found that it actually blocked the respiratory- Okay. That's very critical, right? Because the patient's coming to you under severe respiratory depression. They're not going to be pre-treated with something that blocks. Scientifically, how is the alpha-2 antagonist in somebody who's already under respiratory depression going to reverse that blockade? Right. Some of those experiments are actually being conducted, and they're just coming out now. Atipamezole in some of these animal models has been demonstrated to block or to reverse the respiratory depression. Okay. Thanks very much. Then second question to you, I guess to Fredrik. You talked on your slide about partnering for IZIPRY after FDA approval, and I'm wondering why after. I would have thought that a partner would. You'd want a partner on board ahead of approval so they can prepare for the launch. Maybe a few comments as to why you put after approval there. Well, I guess we're putting that there because, as Nikolai talked about and me as well, the value inflection point is in need of an approval. That's, I guess, the short answer. Of course, we are looking for partners even before that. I think because we have had this is the third time. We had first, it wasn't accepted for filing because we had issues with our manufacturing setup. Second time, they were asking for more stability data on the final product. And I think that has created an uncertainty around the product. The kind of uncertainty, where are we with the manufacturing process and to get that sign-off, we think would be valuable. I would hope, and that's our aim, is that we would find interested companies who are maybe ready and the dialogue. All of these partnering discussions are often taking 3-6 months. To have a dialogue starting relatively soon and to identify potential partners. We have been in discussions with some companies. The plan has always been until we sold Zubsolv was that we should launch it ourselves. This is a little unique, new situation for us. We have to build up that pipeline and, of course, if someone wants to sign it up before, we will do that if that's on an attractive term. I think the most important here is that we get a partner. I would also say IZIPRY has two values. One is the monetary value, but it also would be the first product approved on AmorphOX. It would be the first time we have our entire manufacturing chain. As Cecilia presented, it's exactly the same manufacturing we're setting up for OX640 and for OX390. To take away the risk of that regulatory review of the manufacturing process is incredibly important. Just looking at the rescue, I would say without having the exact statistics, but probably 80% of the complete response letters in rescue medications is not due to failed effect, it is due to manufacturing. To take that one out of the equation, I think is incredibly important for all of our projects. We have some excipients that we're using in OX124 for the nasal administration that is also present in our other formulations. Having that approved again for nasal administration could be an advantage both in the U.S., but actually also in Europe, that we can point to the excipients have now been approved for nasal administration by a large regulatory agency. That's a secondary effect of the IZIPRY planning. If someone knocks on my door tomorrow or tonight, then we will start partnering discussions immediately. I think the more realistic is probably that the big value point, whether that has been negotiated before or after, will be at approval. I don't think people would pay us a lot of upfront before the product has been approved. I guess also that it's a completely de-risked project, obviously, with approval. Mm-hmm. which is obviously of importance for potential. Just one final question. Now that you're focusing on AmorphOX, can you talk a little bit about you previously said to us you've had a number of feasibility deals in place. Is the plan now to give us a few more KPIs around how many partner, you know, feasibility projects you have so that we can see how that pipeline builds? Are you restructuring how you do your BD in terms of trying to proliferate a platform which clearly has a lot more uses than you alone can handle? No. We are looking at Fredrik. We took that slide out here, but we're talking about industrialized business development. Maybe you will say. No. First of all, it's a team effort at Orexo. It's obviously a team effort at Orexo. Obviously, I'm heading up the business development team, but that includes obviously a lot of our colleagues. I mean, we have from the research side Scientific Director Jonas obviously always participating. Lisa from the U.S. perspective on the marketing strategy perspective, and Cecilia looking at the supply and CFO perspective. Besides having dedicated people working at business development. Then we approach this from an industrial perspective. You know, the ordinary way of creating a funnel of a pipeline and then moving towards next phase, et cetera. That's clearly an element in everything we do. Yes, we have the capacity to handle the funnel. It takes a lot of effort to go out and source the opportunities. We do that continuously. Jonas is traveling the world in on these all these conferences. The short answer to your first question, right now, we don't have a KPI. We do have internal measures, but before we're ready to go with them, we want to see them materialize. We are reviewing our business development efforts. We are actually in the recruitment process of new people to come in who have a little more of the development background, a little more science background. We did have business development in the U.S., which we have decided to move back to Sweden, partly because that we see it's an opportunity for us to increase the skill set and get closer to this science base, but of also an expense question, of course. We are working, but maybe we'll come with a KPI. I will bring that with me, but right now I don't have a KPI I can give you. There was a question from Joakim. Yeah. Thank you. Microphone. You have to push it. No, no. Okay. Congratulations to the sale of Zubsolv. Thank you. That was very great news. You asked Flax the question regarding Dexcel Pharma that ICPRI, it looks to me that they were also interesting on that product. I mean, in my view, you already have a potential partner here. Are you still having contact with Dexcel Pharma, and do you see them as a partner already in this kind of drug-related area? Are they interesting to grow in the U.S. with these products since it's a severe situation? We're speaking to Dexcel all the time. We right now have several people in the U.S. still. In the end game in the U.S. we will be five people, but I think in the U.S. right now we're about 10 people still working. The other five are all working for Dexcel. We have a day-to-day relationship with Dexcel. OX124 was part of that process. The Zubsolv process was. We got, as I've said before, some unsolicited questions whether we would sell Zubsolv after we settled the case with Sun Pharmaceuticals. Based on that we said, "Why don't we make this a competitive process?" We started that last summer. In that process we have been through quite a few companies. We had 5 companies in due diligence, more than 2,000 questions asked to the company, and we ended up with Dexcel winning the most attractive offer. In that process, we included OX-124 and OX-125, which is the nalmefene product that we have a little on the side. Dexcel were looking at products on the market. That was one very important aspect for them. When OX-124 gets approved, will Dexcel be a company we will talk to? Absolutely. I think that is an opportunity. There were other companies in that process that were also looking at OX-124. But part of it was for them to move into opioid, so it kind of was more of a package deal. To be very transparent, here is Dexcel offered more money for Zubsolv alone than the other one offered for the combination. In that way, it was more attractive. Of that, of course, opens up for discussion with some of those companies. When you get an approved product, are you interested? There's an opportunity and OX124 was in the data room. There have been questions asked, but Dexcel was very transparent with us that we are just looking for approved products generating revenues right now. We'll see. It depends probably a little on how Zubsolv is moving also. Okay, my second question is, if you're looking back in 2025, you were keen on success for a close deal with the OX640, but in Q4 you came up with a headline delayed OX640 and at the shareholder perspective you can see clearly that has put a lot of pressure on the share. What do you think can be some kind of game changer triggers during this year? For me right now when I listen to this presentation, it looks like everything is a little bit delayed, but you have a very interesting pipeline ahead. I think in the shareholder perspective, many would like to see evidence of AmorphOX that you really can make money out of the platform. I think there's. Right now the OX640 is at least according to the project we have had even last year, we are spot on on the timelines. Earlier, there could have been some other timelines, but the real critical study we have right now is the nasal allergen challenge study. As Cecilia explained, that needs to be out of season for pollen and allergens. We can only do that in Q4. We need to start it in Q4 and then into Q3. If it's in the northern hemisphere, and we have been looking at southern hemisphere options, but it's not really. It's not that easy to get same quality and something that would be acceptable to FDA. That one is kind of an annual. On the other projects, I think we are. It's been a balancing act and all of you who've been following us also know about our economic situation. We haven't really had the economic headroom to just push ahead on all of the projects, even though we think there are opportunities. Now we have headroom to actually do some investments into the projects. Should we have just gone on and done a clinical trial last year, then we would have been breaching our covenants on the corporate bond to be very transparent. We ended up, I think, in Q3, we were about SEK 28 million away from that covenant. That's about the cost of a clinical trial. There's been a financial barrier to do this, but I think now we have the financial means to actually push ahead. I think what are some of the main value triggers? I think something that did create some value was the GLP-1 when we talked about the nasal spray. I know that maybe created a little unrealistic expectations that we were ready to go into humans, but we took that data and been out speaking to companies and said, "What data are you really looking for this to be interesting?" They did come back with we need to increase the bioavailability in particular, because we are comparing to Rybelsus and Wegovy tablets, which are the ones that are out now have a higher bioavailability. We're comparing with a tougher competitor, you can say, from a commercial perspective. If we can do something in the tablet, I think if, depending on where we are, it's, as anything, it's biology. Let's see where we are with that in vivo data coming during the summer. I think the start of the OX640 project is important, coming in, that we can say we actually started the study, we are ready to run. We have set up the commercialization, and we meet that timeline of that Q4 IZIPRY that we actually file it, in the autumn, I think is another important milestone, means that our stability data is coming out positive. Of course, if there are partnering opportunities, as we are talking to companies all the time, we are doing some feasibility study. Again, a little rich from experience and also you, Joakim, have been good at pointing out that we should maybe keep a little lower profile until we're certain. Some of the feasibility studies we are running right now, let's see if we get positive data and they are willing to take the next step. Because that's a learning we have had also, is that some companies going into feasibility, their R&D department think this is great and we did actually present for the first time, I think we were a little more explicit about it. We worked with a virus-like particles, right? Something Live engineered particles. Live engineered parent particles. That was with a partnership where we met all of the R&D departments, basically what they were setting as criteria. It comes into business, and then it's for a more broader partnership, and then suddenly there are a lot of other parameters. Do we have money to run a clinical development programs? What is the manufacturing price? How much have we invested into manufacturing? That's a learning that we have, is we have a lot of interest from R&D, but now we need to convert that into the next step. Some of the small companies we're working with there, of course, we're working straight with the CEO, so that is something that's opportunities, but that's a little longer process before it will create real value. I can promise you we will come up with a press release whenever it's something material. Some companies seem to not be afraid of exposing their name. I mean, you just mentioned Sobi before, and then you reply with no. Bohlin, it was done. It's their decision. Yeah. I mean, for me it would be. From a shareholder's perspective, it would be great if, at a very early stage, there is a company that is willing to invest in testing a product. Mm-hmm. You can mention the name. It's the big pharma. It shows really that, yes, they are very keen on the AmorphOX platform to develop, to test new drugs. I Is that your ambition? If they expose their name. I mean, if you have a big- If they're willing. If they're willing. It's not all that are willing. We are in discussions with some larger pharma companies, which is very early stage. They just want to see how our platform works and some. It's more broad for them to see, let's understand how the platform works, and they don't want us to expose the name. That's one of the first thing that was in the discussions because they think it's too early. Then there are other companies who are more willing and of course we will. I think we have to look at it time by time assessment. I will also say it's. I'm a little afraid to go out and say, "Well, now we're working with this global big pharma companies," and it's early stage and then I can see our share price is going through the roof and we can't disclose too much. It kind of fades out a little like Sobi did, because Sobi, we did meet all of the endpoints in the Sobi relationship. Sobi reorganized, the person we talked to disappeared. Another person came in who disappeared. When they looked at their portfolio, and Sobi have done great, I think. In one way they have prioritized other assets at the moment. Again, we actually met all of the endpoints that were set up from their R&D department. Okay. I just want to establish the scientific situation between your nasal approach and the oral films. When I first heard of these oral films some 15, 20 years ago, I took for granted that the film dissolved in the mouth, the product went through the mucosa directly into the bloodstream. Then a couple of years ago, I listened to a competitor with an epinephrine oral film, and he claimed, which would not be in his interest, that, "No, no, just a small part of the substance goes through the mucosa into the bloodstream. The absolutely most of the substance is swallowed, passes the gastrointestinal tract." If that is really the case, then the nasal approach is really superior to any oral film, at least time-wise. What are the facts here? Great question. I will try to answer to my best capacity. Looking at the oral epinephrine film that is available soon, the Aquestive film that actually consists of a prodrug of the epinephrine molecule. That's the first thing, because epinephrine itself doesn't really pass the oral mucosa. They have a prodrug. If you look at the dose, you can see that. Yes, there is only a small portion of the drug in their film that is actually absorbed. Because their dose, if I don't remember incorrectly, it's 13 or 12 milligrams they have. We have 1 or 2 milligram in the nose, and we reach the same plasma levels, basically. The bioavailability of their film is significantly lower, and that is because you have only partial uptake in the oral cavity. A lot of it is being swallowed and, basically destroyed, during first-pass metabolism. They do get quite rapid absorption of the small amount that they get absorbed over the oral mucosa, and they have demonstrated quite rapid exposure, and conversion of this epinephrine prodrug into the active epinephrine form, which takes place by enzymes in the bloodstream. You should be able to outcompete them time-wise. Time-wise and also this is interesting, and it also, to me, demonstrates that they have a lot of exposure in the oral tract because they see a lot of, for example, nausea and vomiting as side effects, which is also another indication that you get a lot of epinephrine into the gastrointestinal tract, and these are side effects that we do not see after nasal administration. Right. I can take it. The problem is recorded, Mats, so. What? It's recorded, so. Okay. Can you hear me? Yeah. Sorry for my bad voice. I wanted to ask you, Robert, we're talking about this. When we're talking about rescue medications, you do have to be predictive dosing. What I mean is what you give is what you get. Is that really possible if you're using an oral film? I mean, I can't really comment that much about the data that is available on Aquestive. Obviously, this is an ultimate decision of the FDA if they think that the variability that Aquestive sees in their clinical studies is- Yeah Acceptable or not. I mean, that's in the end, that's FDA decision. Yeah ... is this product safe and effective? Mm. Uh, so. I think there's no doubt they must have a quite wide variability among individuals. Yeah I think in particular if it was used in real-life settings. Yeah There must be a big difference. I know some of you probably have other meetings and lunches prepared, so we do have lunch for those of you who are interested at the tables. The management team will spread around and you're more than welcome to come and grab us and ask additional questions. Out of respect for those of you who have other engagements, I know there's someone who needs to go to an airplane also. If there's one last question, I can take that right now. Someone who's really burning to ask, otherwise come forward and ask us the question during the lunch break. Lena, and it's okay. We're all done. Lunches are served. Yes. You need to go in that direction and then to the left, and then you have the dinner room or lunchroom. Yeah. Thank you very much for being here. Thank you.